This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organization, or the World Health Organization.

Environmental Health Criteria 231

First draft prepared by Dr Zoltán Adamis, József Fodor National Center for Public Health, National Institute of Chemical Safety, Budapest, Hungary; and Dr Richard B. Williams, US Environmental Protection Agency, Washington, DC, and Regional Office for the Americas of the World Health Organization

Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organization, and the World Health Organization, and produced within the framework of the Inter-Organization Programme for the Sound Management of Chemicals.

World Health Organization Geneva, 2005

The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour Organization (ILO), and the World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for assessment of the risk to human health and the environment from exposure to chemicals, through international peer review processes, as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals.

The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO, the United Nations Industrial Development Organization, the United Nations Institute for Training and Research, and the Organisation for Economic Cooperation and Development (Participating Organizations), following recommendations made by the 1992 UN Conference on Environment and Development to strengthen cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment.

WHO Library Cataloguing-in-Publication Data

Bentonite, kaolin, and selected clay minerals.

(Environmental health criteria ; 231)

1.Bentonite - toxicity 2.Kaolin - toxicity 3.Aluminum silicates - toxicity 4.Environmental exposure 5.Risk assessment I.International Programme for Chemical Safety II.Series

ISBN 92 4 157231 0       (LC/NLM classification: QV 65)

ISSN 0250-863X

©World Health Organization 2005

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ENVIRONMENTAL HEALTH CRITERIA FOR
BENTONITE, KAOLIN, AND SELECTED CLAY MINERALS

NOTE TO READERS OF THE CRITERIA MONOGRAPHS

Every effort has been made to present information in the criteria monographs as accurately as possible without unduly delaying their publication. In the interest of all users of the Environmental Health Criteria monographs, readers are requested to communicate any errors that may have occurred to the Director of the International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland, in order that they may be included in corrigenda.

Environmental Health Criteria

PREAMBLE

Objectives

In 1973 the WHO Environmental Health Criteria Programme was initiated with the following objectives:

1. to assess information on the relationship between exposure to environmental pollutants and human health, and to provide guidelines for setting exposure limits;
2. to identify new or potential pollutants;
3. to identify gaps in knowledge concerning the health effects of pollutants;
4. to promote the harmonization of toxicological and epidemiological methods in order to have internationally comparable results.

The first Environmental Health Criteria (EHC) monograph, on mercury, was published in 1976, and since that time an ever-increasing number of assessments of chemicals and of physical effects have been produced. In addition, many EHC monographs have been devoted to evaluating toxicological methodology, e.g., for genetic, neurotoxic, teratogenic and nephrotoxic effects. Other publications have been concerned with epidemiological guidelines, evaluation of short-term tests for carcinogens, biomarkers, effects on the elderly and so forth.

Since its inauguration the EHC Programme has widened its scope, and the importance of environmental effects, in addition to health effects, has been increasingly emphasized in the total evaluation of chemicals.

The original impetus for the Programme came from World Health Assembly resolutions and the recommendations of the 1972 UN Conference on the Human Environment. Subsequently the work became an integral part of the International Programme on Chemical Safety (IPCS), a cooperative programme of UNEP, ILO and WHO. In this manner, with the strong support of the new partners, the importance of occupational health and environmental effects was fully recognized. The EHC monographs have become widely established, used and recognized throughout the world.

The recommendations of the 1992 UN Conference on Environment and Development and the subsequent establishment of the Intergovernmental Forum on Chemical Safety with the priorities for action in the six programme areas of Chapter 19, Agenda 21, all lend further weight to the need for EHC assessments of the risks of chemicals.

Scope

The criteria monographs are intended to provide critical reviews on the effect on human health and the environment of chemicals and of combinations of chemicals and physical and biological agents. As such, they include and review studies that are of direct relevance for the evaluation. However, they do not describe every study carried out. Worldwide data are used and are quoted from original studies, not from abstracts or reviews. Both published and unpublished reports are considered, and it is incumbent on the authors to assess all the articles cited in the references. Preference is always given to published data. Unpublished data are used only when relevant published data are absent or when they are pivotal to the risk assessment. A detailed policy statement is available that describes the procedures used for unpublished proprietary data so that this information can be used in the evaluation without compromising its confidential nature (WHO (1990) Revised Guidelines for the Preparation of Environmental Health Criteria Monographs. PCS/90.69, Geneva, World Health Organization).

In the evaluation of human health risks, sound human data, whenever available, are preferred to animal data. Animal and in vitro studies provide support and are used mainly to supply evidence missing from human studies. It is mandatory that research on human subjects is conducted in full accord with ethical principles, including the provisions of the Helsinki Declaration.

The EHC monographs are intended to assist national and international authorities in making risk assessments and subsequent risk management decisions. They represent a thorough evaluation of risks and are not, in any sense, recommendations for regulation or standard setting. These latter are the exclusive purview of national and regional governments.

Content

The layout of EHC monographs for chemicals is outlined below.

• Summary — a review of the salient facts and the risk evaluation of the chemical
• Identity — physical and chemical properties, analytical methods
• Sources of exposure
• Environmental transport, distribution and transformation
• Environmental levels and human exposure
• Kinetics and metabolism in laboratory animals and humans
• Effects on laboratory mammals and in vitro test systems
• Effects on humans
• Effects on other organisms in the laboratory and field
• Evaluation of human health risks and effects on the environment
• Conclusions and recommendations for protection of human health and the environment
• Further research
• Previous evaluations by international bodies, e.g., IARC, JECFA, JMPR

Selection of chemicals

Since the inception of the EHC Programme, the IPCS has organized meetings of scientists to establish lists of priority chemicals for subsequent evaluation. Such meetings have been held in Ispra, Italy, 1980; Oxford, United Kingdom, 1984; Berlin, Germany, 1987; and North Carolina, USA, 1995. The selection of chemicals has been based on the following criteria: the existence of scientific evidence that the substance presents a hazard to human health and/or the environment; the possible use, persistence, accumulation or degradation of the substance shows that there may be significant human or environmental exposure; the size and nature of populations at risk (both human and other species) and risks for environment; international concern, i.e., the substance is of major interest to several countries; adequate data on the hazards are available.

If an EHC monograph is proposed for a chemical not on the priority list, the IPCS Secretariat consults with the Cooperating Organizations and all the Participating Institutions before embarking on the preparation of the monograph.

Procedures

The order of procedures that result in the publication of an EHC monograph is shown in the flow chart on p. xii. A designated staff member of IPCS, responsible for the scientific quality of the document, serves as Responsible Officer (RO). The IPCS Editor is responsible for layout and language. The first draft, prepared by consultants or, more usually, staff from an IPCS Participating Institution, is based on extensive literature searches from reference databases such as Medline and Toxline.

The draft document, when received by the RO, may require an initial review by a small panel of experts to determine its scientific quality and objectivity. Once the RO finds the document acceptas a first draft, it is distributed, in its unedited form, to well over 150 EHC contact points throughout the world who are asked to comment on its completeness and accuracy and, where necessary, provide additional material. The contact points, usually designated by governments, may be Participating Institutions, IPCS Focal Points or individual scientists known for their particular expertise. Generally some four months are allowed before the comments are considered by the RO and author(s). A second draft incorporating comments received and approved by the Director, IPCS, is then distributed to Task Group members, who carry out the peer review, at least six weeks before their meeting.

The Task Group members serve as individual scientists, not as representatives of any organization, government or industry. Their function is to evaluate the accuracy, significance and relevance of the information in the document and to assess the health and environmental risks from exposure to the chemical. A summary and recommendations for further research and improved safety aspects are also required. The composition of the Task Group is dictated by the range of expertise required for the subject of the meeting and by the need for a balanced geographical distribution.

EHC PREPARATION FLOW CHART

The three cooperating organizations of the IPCS recognize the important role played by nongovernmental organizations. Representatives from relevant national and international associations may be invited to join the Task Group as observers. Although observers may provide a valuable contribution to the process, they can speak only at the invitation of the Chairperson. Observers do not participate in the final evaluation of the chemical; this is the sole responsibility of the Task Group members. When the Task Group considers it to be appropriate, it may meet in camera.

All individuals who as authors, consultants or advisers participate in the preparation of the EHC monograph must, in addition to serving in their personal capacity as scientists, inform the RO if at any time a conflict of interest, whether actual or potential, could be perceived in their work. They are required to sign a conflict of interest statement. Such a procedure ensures the transparency and probity of the process.

When the Task Group has completed its review and the RO is satisfied as to the scientific correctness and completeness of the document, it then goes for language editing, reference checking and preparation of camera-ready copy. After approval by the Director, IPCS, the monograph is submitted to the WHO Office of Publications for printing. At this time a copy of the final draft is sent to the Chairperson and Rapporteur of the Task Group to check for any errors.

It is accepted that the following criteria should initiate the updating of an EHC monograph: new data are available that would substantially change the evaluation; there is public concern for health or environmental effects of the agent because of greater exposure; an appreciable time period has elapsed since the last evaluation.

All Participating Institutions are informed, through the EHC progress report, of the authors and institutions proposed for the drafting of the documents. A comprehensive file of all comments received on drafts of each EHC monograph is maintained and is available on request. The Chairpersons of Task Groups are briefed before each meeting on their role and responsibility in ensuring that these rules are followed.

WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR BENTONITE, KAOLIN, AND SELECTED CLAY MINERALS

A WHO Task Group on Environmental Health Criteria for Bentonite, Kaolin, and Selected Clay Minerals met at Bradford University, Bradford, United Kingdom, from 18 to 22 October 2004. The meeting was opened by Professor Jeffrey Lucas on behalf of the University of Bradford and Dr A. Aitio, Programme for the Promotion of Chemical Safety, WHO, on behalf of the IPCS and its three cooperative organizations (UNEP/ILO/WHO). The Task Group reviewed and revised the draft monograph and made an evaluation of the risks for human health and the environment from exposure to bentonite, kaolin, and other clays.

The first draft was prepared by Dr Zoltán Adamis from the József Fodor National Center for Public Health, National Institute of Chemical Safety, Budapest, Hungary, and Dr Richard B. Williams from the US Environmental Protection Agency, Washington, DC, and Regional Office for the Americas of the World Health Organization. The second draft was also prepared by the same authors in collaboration with the secretariat, which incorporated comments received following the circulation of the first draft to the IPCS contact points for Environmental Health Criteria monographs.

Dr A. Aitio was responsible for the overall scientific content of the monograph.

The efforts of all who helped in the preparation and finalization of the monograph are gratefully acknowledged.

Risk assessment activities of the International Programme on Chemical Safety are supported financially by the Department of Health and Department for Environment, Food & Rural Affairs, United Kingdom, Environmental Protection Agency, Food and Drug Administration, and National Institute of Environmental Health Sciences, USA, European Commission, German Federal Ministry of Environment, Nature Conservation and Nuclear Safety, Health Canada, Japanese Ministry of Health, Labour and Welfare, and Swiss Agency for Environment, Forests and Landscape.

Task Group Members

Dr Zoltán Adamis, József Fodor National Center for Public Health, National Institute of Chemical Safety, Budapest, Hungary

Prof. Diana Anderson, University of Bradford, Bradford, United Kingdom

Dr Richard L. Attanoos, Llandough Hospital, Cardiff, United Kingdom

Dr Tapan Chakrabarti, National Environmental Engineering Research Institute, Nehru Marg, India

Dr Rogene Henderson (Co-chair), Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA

Dr F. Javier Huertas, CSIC Estacion Experimental del Zaidin, Granada, Spain

Prof. Gunnar Nordberg (Co-chair), Umeå University, Umeå, Sweden

Prof. Salah A. Soliman, Alexandria University, Alexandria, Egypt

Prof. Helena Taskinen (Rapporteur), Finnish Institute of Occupational Health, Helsinki, Finland

Dr Richard B. Williams, formerly US Environmental Protection

Agency, Washington, DC, and Regional Office for the Americas

of the World Health Organization

Secretariat

Dr Antero Aitio, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland

Ms Pearl Harlley, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland

ACRONYMS AND ABBREVIATIONS

Bentonite is a rock formed of highly colloidal and plastic clays composed mainly of montmorillonite, a clay mineral of the smectite group, and is produced by in situ devitrification of volcanic ash. In addition to montmorillonite, bentonite may contain feldspar, cristobalite, and crystalline quartz. The special properties of bentonite are an ability to form thixotrophic gels with water, an ability to absorb large quantities of water, and a high cation exchange capacity. The properties of bentonite are derived from the crystal structure of the smectite group, which is an octahedral alumina sheet between two tetrahedral silica sheets. Variations in interstitial water and exchangeable cations in the interlayer space affect the properties of bentonite and thus the commercial uses of the different types of bentonite. By extension, the term bentonite is applied commercially to any clay with similar properties. Fuller’s earth is often a bentonite.

Kaolin or china clay is a mixture of different minerals. Its main component is kaolinite; in addition, it frequently contains quartz, mica, feldspar, illite, and montmorillonite. Kaolinite is made up of tiny sheets of triclinic crystals with pseudohexagonal morphology. It is formed by rock weathering. It has some cation exchange capacity.

The main components of common clay and shale are illite and chlorite. Illite is also a component of ball clays. Illite closely resembles micas, but it has less substitution of aluminium for silicon and/or partial replacement of potassium ions between the unit layers by other cations, such as hydrogen, magnesium, and calcium.

Quantitative measurement of airborne dust containing aluminosilicates is most commonly gravimetric. The methods used for the identification and quantification of aluminosilicates include X-ray diffraction, electron microscopy, energy-dispersive X-ray analysis, differential thermal analysis, electron diffraction, and infrared spectroscopy.

Montmorillonite is ubiquitous at low concentrations in soil, in the sediment load of natural waters, and in airborne dust. Biodegradation and bioaccumulation in the food-chain appear minimal, if they occur at all, and abiotic degradation of bentonite into other minerals takes place only on a geological time scale.

Major uses of bentonite include binding foundry sand in moulds; absorbing grease, oil, and animal wastes; pelletizing taconite iron ore; and improving the properties of drilling muds. Speciality uses include serving as an ingredient in ceramics; waterproofing and sealing in civil engineering projects, such as landfill sites and nuclear waste repositories; serving as a filler, stabilizer, or extender in adhesives, paints, cosmetics, and medicines, as a carrier in pesticides and fertilizers, and as a bonding agent in animal feeds; clarifying wine and vegetable oil; and purifying wastewater. The uses of montmorillonite-type Fuller’s earth overlap those of bentonite.

Use of kaolin dates back to the third century BC in China. Today it is mined and used in significant quantities for numerous industrial uses. Its most important use is in paper production, where it is used as a coating material. In addition, it is used in great quantities in the paint, rubber, plastic, ceramic, chemical, pharmaceutical, and cosmetics industries.

Common clay and shale, of which illite is often a major component, are used mainly in the manufacture of extruded and other bricks, portland and other cements, concrete blocks and structural concrete, and refractories. Highway surfacing, ceramic tiles, and ceramics and glass are other important uses.

In view of the widespread distribution of bentonite in nature and its use in an enormous variety of consumer products, general population exposure to low concentrations is ubiquitous.

There is limited information on occupational exposure to bentonite dust in mines, processing plants, and user industries. The highest reported values for total dust and respirable dust concentrations were, respectively, 1430 and 34.9 mg/m³, although most values were below 10 mg/m³ for total dust and below 5 mg/m³ for respirable dust.

Kaolin is a natural component of the soil and occurs widely in ambient air. Kaolin mining and refining involve considerable exposure, and significant exposure is also expected in paper, rubber, and plastic production. Quantitative information on occupational exposure is available for a few countries and industries only. Respirable dust concentrations in kaolin mining and processing are usually below 5 mg/m³.

No information was available on the kinetics or metabolism of montmorillonite, kaolinite, or illite as they occur in most occupational settings.

Deposition and kinetics of radiolabelled fused montmorillonite after inhalation exposure have been studied in mice, rats, dogs, and humans. Deposition in the nasopharynx increases with particle size and is lower in dogs than in rodents. Tracheobronchial deposition was low and independent of animal species and particle size. Pulmonary deposition was considerably higher in dogs than in rodents and decreased with increasing particle size.

The removal of particles from the lungs took place by solubilization in situ and by physical clearance. In dogs, the main mechanism of clearance was solubilization; in rodents, the mechanism of removal was mainly physical transportation. The clearance by mechanical removal was slow, especially in dogs: the half-time was initially 140 days and increased to 6900 days by day 200 post-exposure.

In humans, there was a rapid initial clearance of 8% and 40% of aluminosilicate particles that were, respectively, 1.9 and 6.1 µm in aerodynamic diameter from the lung region over 6 days. Thereafter, 4% and 11% of the two particle sizes were removed following a halftime of 20 days, and the rest with half-times of 330 and 420 days.

Ultrafine particles (<100 nm) have a high deposition in the nasal area; they can penetrate the alveolar/capillary barrier.

An important determinant of the toxicity of clays is the content of quartz. The presence of quartz in the clays studied hampers reliable independent estimation of the fibrogenicity of other components of clays.

Single intratracheal injection into rodents of bentonite and montmorillonite with low content of quartz produced dose- and particle size-dependent cytotoxic effects, as well as transient local inflammation, the signs of which included oedema and, consequently, increased lung weight. Single intratracheal exposures of rats to bentonite produced storage foci in the lungs 3–12 months later. After intratracheal exposure of rats to bentonite with a high quartz content, fibrosis was also observed. Bentonite increased the susceptibility of mice to pulmonary infection.

There are limited data on the effects of multiple exposures of experimental animals to montmorillonite or bentonite. Mice maintained on diets containing 10% or 25% bentonite but otherwise adequate to support normal growth displayed slightly reduced growth rates, whereas mice maintained on a similar diet with 50% bentonite showed minimal growth and developed fatty livers and eventually fibrosis of the liver and benign hepatomas (see below).

In vitro studies of the effects of bentonite on a variety of mammalian cell types usually indicated a high degree of cytotoxicity. Concentrations below 1.0 mg/ml of bentonite and montmorillonite particles less than 5 µm in diameter caused membrane damage and even cell lysis, as well as functional changes in several types of cells. The velocity and degree of lysis of sheep erythrocytes were dose dependent.

Kaolin instilled intratracheally produces storage foci, foreign body reaction, and diffuse exudative reaction. After high doses of kaolin (containing 8–65% quartz), fibrosis has been described in some studies, whereas at lower kaolin doses, no fibrosis has been observed in the few available studies.

Information is very limited on the toxicity of illite and non-existent on the toxicity of other components of other commercially important clays. Intratracheally instilled illite with unknown quartz content induced alveolar proteinosis, increased lung weight, and caused collagen synthesis. Illite had limited cytotoxicity towards peritoneal macrophages and was haemolytic in vitro.

No adequate studies are available on the carcinogenicity of bentonite. In an inhalation study and in a study using intrapleural injection, kaolin did not induce tumours in rats. No studies are available on the genotoxicity of clays.

Single, very limited studies did not demonstrate developmental toxicity in rats after oral exposure to bentonite or kaolin.

General population exposure to low concentrations of montmorillonite and kaolinite, the main components of bentonite and kaolin, respectively, and other clay minerals is ubiquitous. There is no information on the possible effects of such low-level exposure.

Long-term occupational exposures to bentonite dust may cause structural and functional damage to the lungs. However, available data are inadequate to conclusively establish a dose–response relationship or even a cause-and-effect relationship due to limited information on period and intensity of exposure and to confounding factors, such as exposure to silica and tobacco smoke.

Long-term exposure to kaolin causes the development of radiologically diagnosed pneumoconiosis in an exposure-related fashion. Clear-cut deterioration of respiratory function and related symptoms have been reported only in cases with prominent radiological findings. The composition of the clay — i.e., quantity and quality of minerals other than kaolinite — is an important determinant of the effects.

Bentonite, kaolin, and other clays often contain quartz, and exposure to quartz is causally related to silicosis and lung cancer. Statistically significant increases in the incidence of or mortality from chronic bronchitis and pulmonary emphysema have been reported after exposure to quartz.

Bentonite and kaolin have low toxicity to aquatic species, a large number of which have been tested.

From the limited data available from studies on bentonite-exposed persons, retained montmorillonite appears to effect only mild nonspecific tissue changes, which are similar to those that have been described in the spectrum of changes of the "small airways mineral dust disease" (nodular peribronchiolar dust accumulations containing refractile material [montmorillonite] in association with limited interstitial fibrosis). In some of the studies, radiological abnormalities have also been reported.

There exist no reported cases of marked diffuse/nodular pulmonary tissue fibrotic reaction to montmorillonite in the absence of free silica. No quantitative estimates of the potency of bentonite to cause adverse pulmonary effects can be derived.

Long-term exposure to kaolin may lead to a relatively benign pneumoconiosis, known as kaolinosis. Deterioration of lung function has been observed only in cases with prominent radiological alterations. Based on data from china clay workers in the United Kingdom, it can be very roughly estimated that kaolin is at least an order of magnitude less potent than quartz.

Bentonite, kaolin, and other clays often contain quartz, which is known to cause silicosis and lung cancer.

No report on local or systemic adverse effects has been identified from the extensive use of bentonite or kaolin in cosmetics.

The biological effects of clay minerals are influenced by their mineral composition and particle size. The decreasing rank order of the potencies of quartz, kaolinite, and montmorillonite to produce lung damage is consistent with their known relative active surface areas and surface chemistry.

Bentonite and kaolin have low toxicity towards aquatic organisms.

Clay is a widely distributed, abundant mineral resource of major industrial importance for an enormous variety of uses (Ampian, 1985). In both value and amount of annual production, it is one of the leading minerals worldwide. In common with many geological terms, the term "clay" is ambiguous and has multiple meanings: a group of fine-grained minerals — i.e., the clay minerals; a particle size (smaller than silt); and a type of rock — i.e., a sedimentary deposit of fine-grained material usually composed largely of clay minerals (Patterson & Murray, 1983; Bates & Jackson, 1987). In the latter definition, clay also includes fine-grained deposits of non-aluminosilicates such as shale and some argillaceous soils.

This Environmental Health Criteria (EHC) monograph deals with the health hazards associated with bentonite, kaolin, and common clay, which are commercially important clay products, as well as the related phyllosilicate minerals montmorillonite, kaolinite, and illite. Fibrous clay minerals, such as sepiolite, attapulgite, and zeolites, are not discussed. For a recent assessment of the health effects of zeolites, see IARC (1997a). As bentonite, kaolin, and common clay may contain varying amounts of silica, a short summary is presented of recent assessments of quartz (IARC, 1997b; IPCS, 2000).

Recently, there has been an increased interest in the toxicity of airborne fine (0.1–2.5 µm) and ultrafine (<0.1 µm) particles. Epidemiological studies have indicated an increase in morbidity and mortality associated with an increase in airborne particulate matter, particularly in the ultrafine size range (Pekkanen et al., 1997; Stölzel et al., 2003). There is little information on how much of total airborne particulate matter is clay dust and what fraction of airborne clay dusts is in the fine or ultrafine mode.

2.2.1 Bentonite

The term "bentonite" is ambiguous. As defined by geologists, it is a rock formed of highly colloidal and plastic clays composed mainly of montmorillonite, a clay mineral of the smectite group (Fig. 1), and is produced by in situ devitrification of volcanic ash (Parker, 1988). The transformation of ash to bentonite apparently takes place only in water (certainly seawater, probably alkaline lakes, and possibly other fresh water) during or after deposition (Grim, 1968; Patterson & Murray, 1983). Bentonite was named after Fort Benton (Wyoming, USA), the locality where it was first found. In addition to montmorillonite, bentonite may also contain feldspar, biotite, kaolinite, illite, cristobalite, pyroxene, zircon, and crystalline quartz (Parkes, 1982).

By extension, the term bentonite is applied commercially to any plastic, colloidal, and swelling clay regardless of its geological origin. Such clays are ordinarily composed largely of minerals of the montmorillonite group.

Bentonite is a rock or a clay base industrial material. It is therefore a mixture of minerals. No "molecular" formula can be given.

The Chemical Abstracts Service (CAS) registry number for bentonite is 1302-78-9.

Synonyms and trade names used to designate bentonite include Albagel Premium USP 4444, Bentonite magma, Bentonite 2073, Bentopharm, CI 77004, E558, HI-Gel, HI-Jel, Imvite I.G.B.A., Magbond, mineral sopa, Montmorillonite, Panther creek bentonite, soap clay, Southern bentonite, taylorite, Tixoton, Veegum HS, Volclay, Volclay Bentonite BC, and Wilkinite (CIREP, 2003; RTECS, 2003a).

The term "montmorillonite" is also ambiguous and is used both for a group of related clay minerals and for a specific member of that group (Bates & Jackson, 1987). For the former use, smectite is more appropriate (a group of clay minerals that includes montmorillonite, saponite, sauconite, beidellite, nontronite, etc.) (Fig. 1).

Fig. 1. Classification of silicates (Bailey, 1980b; Rieder et al., 1998). Minerals that can be frequently found in bentonite or kaolin are in bold; the main components are in large typeface. Illite is a component of common soil and sediments and is classified as a mica.

The basic crystal structure of smectites is an octahedral alumina sheet between two tetrahedral silica sheets. Atoms in these sheets common to both layers are oxygens. These three-layer units are stacked one above another with oxygens in neighbouring layers adjacent to each other. This produces a weak bond, allowing water and other polar molecules to enter between layers and induce an expansion of the mineral structure. In the tetrahedral coordination, silicon may be substituted by aluminium and possibly phosphorus; in the octahedral coordination, aluminium may be substituted by magnesium, iron, lithium, chromium, zinc, or nickel. Differences in the substitutions within the lattice in terms of position and elemental composition give rise to the various montmorillonite clay minerals: montmorillonite, nontronite, saponite, hectorite, sauconite, beidellite, volkhonskoite, pimelite, and griffithite.

The molecular formula for montmorillonite is usually given as (M⁺_x·nH₂O) (Al_2–yMg_x)Si₄O₁₀(OH)₂, where M⁺ = Na⁺, K⁺, Mg²⁺, or Ca²⁺ (Brindley & Brown, 1980). Ideally, x = 0.33. The CAS registry number for montmorillonite is 1318-93-0.

Fuller’s earth is loosely defined by its properties and commercial use and not by its mineralogy and molecular structure (Grim, 1968; Patterson & Murray, 1983; Ampian, 1985; Bates & Jackson, 1987; Hosterman & Patterson, 1992). The term is derived from the initial usage of certain clays in bleaching, degreasing, and fulling (shrinking) woollen fabrics. Grim (1968) defines Fuller’s earth as "any natural earthy material which will decolorize mineral or vegetable oils to a sufficient extent to be of economic importance." The term encompasses not only some bentonites but also some kaolinites and some silts with minimal clay content. In the USA, the term Fuller’s earth is used to mean palygorskite, a fibrous magnesium–aluminium silicate mineral close to sepiolite (IARC, 1997c). Data on production and other aspects of Fuller’s earth often do not distinguish between bentonite and non-bentonite types.

2.2.2 Kaolin

The name "kaolin" is derived from the word Kau-Ling, or high ridge, the name given to a hill near Jau-chau Fu, China, where kaolin was first mined (Sepulveda et al., 1983). Kaolin, commonly referred to as china clay, is a clay that contains 10–95% of the mineral kaolinite and usually consists mainly of kaolinite (85–95%). In addition to kaolinite, kaolin usually contains quartz and mica and also, less frequently, feldspar, illite, montmorillonite, ilmenite, anastase, haematite, bauxite, zircon, rutile, kyanite, silliminate, graphite, attapulgite, and halloysite. Some clays used for purposes similar to those for which kaolin is used may contain substantial amounts of quartz: "kaolin-like" clays used in South African pottery contained 23–58% quartz and, as the other major constituent, 20–36% kaolinite (Rees et al., 1992).

The CAS registry number for kaolin is 1332-58-7.

Synonyms and trade names for kaolin include Altowhites, Argilla, Bentone, Bolbus alba, China clay, CI 77004, Emathlite, Fitrol, Fitrol desiccite 25, Glomax, Hydrite, Kaopaous, Kaophills-2, Kolite, Lang-ford, McNamee, Parclay, Pigment white 19, Porcelain clay, Snow tex, terra alba, and white bole (CIREP, 2003; RTECS, 2003b).

The structure of kaolinite is a tetrahedral silica sheet alternating with an octahedral alumina sheet. These sheets are arranged so that the tips of the silica tetrahedrons and the adjacent layers of the octahedral sheet form a common layer (Grim, 1968). In the layer common to the octahedral and tetrahedral groups, two-thirds of the oxygen atoms are shared by the silicon and aluminium, and then they become O instead of OH. The charges within the structural unit are balanced. Analyses of many samples of kaolinite minerals have shown that there is very little substitution in the lattice (Grim, 1968). The molecular formula that is common for the kaolinite group (kaolinite, nacrite, dickite) is Al₂Si₂O₅(OH)₄ (Grim, 1968).

The CAS registry number for kaolinite is 1318-74-7.

2.2.3 Other clays

In addition to bentonite (and Fuller’s earth) and kaolin, the main types of commercial clays are ball clay, common clay and shale, and fire clay. Ball clay consists primarily of kaolinite, with minor amounts of illite, chlorite, smectite minerals, quartz, and organic materials. Common clay and shale contain illite and chlorite as major components, while fire clay comprises mainly kaolinite, halloysite, and/or diaspore (Virta, 2002).

Illite is a name for a group of mica-like clay minerals proposed by R.E. Grim, R.H. Bray, and W.F. Bradley in 1937 to honour the US state of Illinois, a source of illite and a state that had supported research on clay (Grim, 1968; Bates & Jackson, 1987). Illite clay minerals show substantially no expanding lattice characteristics and are characterized by intense 1.0-nm 001 and 0.33-nm 003 peaks that are not modified by glycerol or ethylene glycol solvation, potassium saturation, or heating to 550 °C (Fanning et al., 1989). Grim (1968) stated that illite includes both trioctahedral (biotite) and dioctahedral (muscovite) types of crystallization. The US Geological Survey report entitled A Laboratory Manual for X-Ray Powder Diffraction, however, limits illite to minerals with a dioctahedral, muscovite structure (USGS, 2001). Velde (1995) separated mica-like minerals such as illite from true micas on the basis that the former have almost exclusively potassium as the interlayer ion and a charge imbalance always slightly less than 1.0 per unit cell. (This value for the charge imbalance is much below the 1.3–1.5 given by Grim [1968].) In addition, true micas usually have a greater grain size than the mica-like clay minerals (i.e., >2 µm) and commonly are found in rocks that have been subjected to elevated temperatures.

The Association Internationale Pour l’Étude des Argiles Nomenclature Committee (Rieder et al., 1998) defines illite as a serial name for dioctahedral interlayer-deficient mica with composition K_0.65(Al₂)(Si_3.35Al_0.65)O₁₀(OH)₂. The aluminium in octahedral positions can be partially substituted by Mg²⁺, Fe²⁺, and Fe³⁺.

The CAS registry number of illite is 1217-36-03 (Grim, 1968). Synonyms of illite include hydromica, illidromica, and glimmerton.

The chemical composition of illite deposits from Malaysia is summarized in Fan & Aw (1989) and from the USA and Germany in Grim (1968) and Gaudette et al. (1966). The water content of Malaysian illite ranged from 19% to 26%, and that of the illites described by Grim (1968), from 6% to 12%. The density of illite is 2.6–2.9 g/cm³ (Grim, 1968; Tamás, 1982). Gaudette et al. (1966) mentioned that illites from Illinois, Oklahoma, and Wisconsin, USA, were light green or light to dark grey clays. Illite mined in Füzérradvány, Hungary, is described as greasy, clay-like, and of high plasticity (Tamás, 1982). Its colour is determined by its iron content and may be white, yellow, lilac, or reddish brown.

2.3.1 Bentonite

Bentonite feels greasy and soap-like to the touch (Bates & Jackson, 1987). Freshly exposed bentonite is white to pale green or blue and, with exposure, darkens in time to yellow, red, or brown (Parker, 1988). The special properties of bentonite are an ability to form thixotrophic gels with water, an ability to absorb large quantities of water with an accompanying increase in volume of as much as 12–15 times its dry bulk, and a high cation exchange capacity.

Substitutions of silicon by cations produce an excess of negative charges in the lattice, which is balanced by cations (Na⁺, K⁺, Mg²⁺, Ca²⁺) in the interlayer space. These cations are exchangeable due to their loose binding and, together with broken bonds (approximately 20% of exchange capacity), give montmorillonite a rather high (about 100 meq/100 g) cation exchange capacity, which is little affected by particle size. This cation exchange capacity allows the mineral to bind not only inorganic cations such as caesium but also organic cations such as the herbicides diquat, paraquat (Weber et al., 1965), and s-triazines (Weber, 1970), and even bio-organic particles such as rheoviruses (Lipson & Stotzky, 1983) and proteins (Potter & Stollerman, 1961), which appear to act as cations. Variation in exchangeable cations affects the maximum amount of water uptake and swelling. These are greatest with sodium and least with potassium and magnesium.

Interstitial water held in the clay mineral lattice is an additional major factor controlling the plastic, bonding, compaction, suspension, and other properties of montmorillonite-group clay minerals. Within each crystal, the water layer appears to be an integral number of molecules in thickness. Physical characteristics of bentonite are affected by whether the montmorillonite composing it has water layers of uniform thickness or whether it is a mixture of hydrates with water layers of more than one thickness. Loss of absorbed water from between the silicate sheets takes place at relatively low temperatures (100–200 °C). Loss of structural water (i.e., the hydroxyls) begins at 450–500 °C and is complete at 600–750 °C. Further heating to 800–900 °C disintegrates the crystal lattice and produces a variety of phases, such as mullite, cristobalite, and cordierite, depending on initial composition and structure. The ability of montmorillonite to rapidly take up water and expand is lost after heating to a critical temperature, which ranges from 105 to 390 °C, depending on the composition of the exchangeable cations. The ability to take up water affects the utilization and commercial value of bentonite (Grim, 1968; Parker, 1988).

Montmorillonite clay minerals occur as minute particles, which, under electron microscopy, appear as aggregates of irregular or hexagonal flakes or, less commonly, of thin laths (Grim, 1968). Differences in substitution affect and in some cases control morphology.

2.3.2 Kaolin

Kaolinite, the main constituent of kaolin, is formed by rock weathering. It is white, greyish-white, or slightly coloured. It is made up of tiny, thin, pseudohexagonal, flexible sheets of triclinic crystal with a diameter of 0.2–12 µm. It has a density of 2.1–2.6 g/cm³. The cation exchange capacity of kaolinite is considerably less than that of montmorillonite, in the order of 2–10 meq/100 g, depending on the particle size, but the rate of the exchange reaction is rapid, almost instantaneous (Grim, 1968). Kaolinite adsorbs small molecular substances such as lecithin, quinoline, paraquat, and diquat, but also proteins, polyacrylonitrile, bacteria, and viruses (McLaren et al., 1958; Mortensen, 1961; Weber et al., 1965; Steel & Anderson, 1972; Wallace et al., 1975; Adamis & Timár, 1980; Schiffenbauer & Stotzky, 1982; Lipson & Stotzky, 1983). The adsorbed material can be easily removed from the particles because adsorption is limited to the surface of the particles (planes, edges), unlike the case with montmorillonite, where the adsorbed molecules are also bound between the layers (Weber et al., 1965).

Upon heating, kaolinite starts to lose water at approximately 400 °C, and the dehydration approaches completeness at approximately 525 °C (Grim, 1968). The dehydration depends on the particle size and crystallinity.

2.3.3 Other clays

Illite, together with chlorite, is the main component of common clay and shale. It is also an important impurity in limestone, which can affect the properties and thus the value of the stone for construction and other purposes (Carr et al., 1994). Despite the widespread occurrence of illite in nature, large deposits of high purity are quite rare (as discussed in section 3.2.1.3).

Illite usually occurs as very small (0.1–2 µm), poorly defined flakes commonly grouped into irregular aggregates. Lath-shaped and ribbon-shaped illite particles up to 30 µm in length and 0.1–0.3 µm in width have also been described (Srodon & Eberl, 1984), but their existence is controversial. Velde (1985) stated unqualifiedly that these so-called filamentous illites are mixed-layer structures. Srodon & Eberl (1984), however, drawing on the same references plus their own data, concluded that these filaments in some cases are mixed-layer structures but in other cases are composed only of illite, and they further supported their view with scanning electron microscopic photographs of lath-shaped crystals of what they identified as illite.

The special properties of illite are derived from its molecular structure. The balancing cation is mainly or entirely potassium, and charge deficiency from substitutions is at least twice that of smectites (i.e., 1.3–1.5 per unit cell layer) and is mainly in the silica sheet and close to the surface of the unit layer rather than in the octahedral layer as in smectites (Grim, 1968). These differences from smectites produce a structure in which interlayer balancing cations are not easily exchanged and the unit layers are relatively fixed in position and do not permit polar ions such as water to readily enter between them and produce expansion.

Illite reacts with both inorganic and organic ions and has a cation exchange capacity of 10–40 meq/100 g, a value intermediate between those of montmorillonite and kaolinite (Grim, 1968). Ion exchange capacity is reduced by heating. The potassium in the interlayer space is "fixed" to a considerable degree, making it not readily available to plants, a matter of importance in soil science and agriculture. A portion of the interlayer potassium, however, can be slowly leached, leading to the degradation of the illite. Such degradation, however, can be reversed by the addition of potassium. Wilken & Wirth (1986) stated that fithian illite from Illinois, USA, adsorbed hexachlorobenzene suspended in distilled water with a sorption partition coefficient of 2200–2600 and that more than half of this adsorbed hexachlorobenzene could be desorbed by further contact with distilled water. However, the fithian illite used in the experiment had a composition of 30% quartz, 19% feldspar, 11% kaolinite, 1% organic carbon, and 40% illite, making it impossible to know how much of the measured adsorption could be ascribed to illite.

The dehydration and other changes in illite with heating have been studied by several investigators, with inconsistent results (Grim, 1968). Some of the inconsistency in findings may result from differences in the period at which samples were held at a given temperature, since dehydration is a function of both time and temperature (Roy, 1949). It is also probable that small differences in particle size, crystal structure, and molecular composition among samples of what were ostensibly the same mineral contributed to the inconsistencies. Dehydration takes place either smoothly or in steps between about 100 and 800 or 850 °C for both biotite and muscovite illites. Loss of structure by the various illite minerals occurs between about 850 and 1000 °C.

2.3.4 Surface chemistry

Chemical properties of the surfaces of silicates and, in particular, clay minerals are strongly dependent on their mineral structure. The basic unit of montmorillonite crystals is an extended layer composed of an octahedral alumina sheet (O) between two tetrahedral silica sheets (T), forming a TOT unit (Bailey, 1980a). The stacks of TOT layers produce the montmorillonite crystals. Isomorphic substitutions in the octahedral sheet (few tetrahedral substitutions are observed in montmorillonite) create an excess of negative structural charge that is delocalized in the lattice. Cations located between two consecutive layers contribute to compensate the structural charge and to keep the layers bound. These cations can easily be exchanged, since they are retained by electrostatic attractions. The surface area associated with the basal surfaces of the extended TOT units is known as the interlayer surface when it corresponds to consecutive layers or as the external surface when it corresponds to the external basal surfaces of a crystal. The external and interlayer surface area represents approximately 95% of the total surface area of montmorillonite. On the other hand, the periodic structure of the montmorillonite crystals is interrupted at the edges, where the broken bonds compensate their charge by the specific adsorption of protons and water molecules (Schindler & Stumm, 1987; Stumm & Wollast, 1990; Stumm, 1997). This interruption of the periodic structure confers to the edge surface an amphoteric character — i.e.,a pH-dependent surface charge and the capacity to react specifically with cations, anions, and molecules (organic and inorganic), forming chemical bonds.

The kaolinite layers are formed only by a tetrahedral sheet of silica and an octahedral sheet of alumina, which contain almost no isomorphic substitutions (Bailey, 1980a). Hydroxyls of the octahedral sheet bind to oxygens of the tetrahedral sheet of the consecutive layer in the kaolinite crystal. The structural charge of the crystal is nonexistent, and no molecules or cations are present in the interlayer space. The surface area of the kaolinite is thus reduced to external surface area and to edge surface area. The edge surface area is similar in nature and properties to the one observed in montmorillonite and represents approximately 20% of the total surface area. However, two types of external surfaces are defined for kaolinite: one associated with the outermost tetrahedral sheet and the other associated with the outermost octahedral sheet. The reactivity of the external octahedral sheet is due to the hydroxyl groups present, which i) can produce a pH-dependent surface charge by protonation and deprotonation reactions and ii) can react specifically with other molecules (Huertas et al., 1998).

Quartz is the most relevant accessory mineral in bentonite and kaolin. Its structure is a tridimensional framework of silicate tetrahedra arranged sharing corners. In contrast with montmorillonite and kaolinite, quartz surface area is defined only as an external surface. Broken bonds, which compensate charge by adsorption of protons or water molecules, are found in all the crystal phases.

The "active" surface area is close to 100% in quartz, 20% in kaolinite, and 5% in montmorillonite. This may be related to the observed toxicity of these materials (see chapter 6).

2.3.5 Trace elements in clays

Knowledge of mechanisms controlling the distribution of trace elements in clays is scarce and contradictory, in spite of the many investigations carried out on the geochemical behaviour of some trace elements used in geological reconstruction as "geochemical indicators" (Fiore et al., 2003). It is well known that clays contain trace elements that literature indicate as toxic and/or micronutrients (i.e., antimony, arsenic, cadmium, cobalt, copper, lead, mercury, nickel, selenium, tellurium, thallium, zinc) whose concentrations are widely variable, depending on their geological history. These trace elements may be in the clay (or accessory) mineral structure as well as adsorbed on clay particles, which play the most important role in controlling their distribution and abundance. Chemical elements in crystalline positions are usually "locked," whereas those adsorbed may be mobilized and transferred to leaching solutions.

For information on the leaching and bioavailability of clay components, see chapter 5.

2.4.1 Quantitative measurement of dust

Inhaled dust appears to be the major mode of human exposure to aluminosilicates, and a general review of methodology for dust sampling and analysis is presented in Degueldre (1983). Quantitative methods for the measurement of total dust and respirable dust are described in the NIOSH Manual of Analytical Methods (Eller & Cassinelli, 1994), in Part 40 of the US government’s Code of Federal Regulations (US EPA, 1996a), and in Mine Safety and Health Administration Handbook No. PH90-IV-4 (US Department of Labor, 1990). All of these methods are gravimetric and measure the weight of dust collected on a filter from a known volume of air.

Although the basic principles behind these methods are simple, accurate and precise results demand sensitive equipment and attention to detail. The National Institute for Occupational Safety and Health (NIOSH) method for total dust requires an appropriate sampler with a polyvinyl chloride or equivalent filter with a pore size of 2–5 µm, a pump with a well characterized, uniform rate of air flow of 1.5–2.0 litres/min, and a microbalance capable of weighing to 0.01 mg, as well as a vacuum desiccator, a static neutralizer, and a chamber with constant temperature and humidity for storing the filters. Guidance for optimizing performance of the 10-mm cyclone sampler is provided by Bartley & Breuer (1982). Briant & Moss (1984) recommended use of a conducting, graphite-filled nylon cyclone to avoid developing an electrostatic charge on the cyclone, which may reduce the measured value for respirable dust below the actual value. Significant errors can also be introduced by air leakage in the filter assembly, the accumulation of static electrical charge on the filter, and many other factors.

Another quantitative measurement of dusts is the determination of particle number. The toxicity of particles has been shown to be related more to surface than to mass. The smaller the particle, the larger the surface area to mass ratio.

2.4.2 Identification of phyllosilicates

There is no single or simple procedure for the positive identification of montmorillonite-group or other aluminosilicates or for their quantification in dust and other samples. The application of several methods may be necessary for even approximate identification and rough quantification. These methods include X-ray diffraction, electron microscopy, energy-dispersive X-ray analysis, differential thermal analysis, and infrared spectroscopy. In the past, chemical methods based on differences in resistance of various clay minerals to chemical attack, the so-called "rational methods of analysis," were used.

X-ray powder diffraction analysis is the basic technique for clay mineral analysis (Moore & Reynolds, 1989). After preliminary removal of sand, clay is separated from silt by centrifugation or sedimentation from suspensions. X-ray diffraction patterns are obtained for air-dried samples and, in the case of oriented aggregates, also for samples treated with ethylene glycol vapour or heated to 350 and 550 °C. Diffraction patterns are compared with standards (Grim, 1968; Thorez, 1975; Brindley & Brown, 1980; JCPDS, 1981) for identification of minerals. Comparisons are complicated, however, by variations in diffraction patterns arising from differences in amounts of absorbed water, by the presence of imperfections in the crystal lattice structure of the minerals, and by mixed-layer structures formed by interstratification of minerals within a single particle (Grim, 1968). Approximate quantification of mineral abundance in samples containing several minerals is possible, although subject to a variety of complications and errors (Starkey et al., 1984; Salt, 1985).

Transmission electron microscopy is valuable for identifying aluminosilicates with a distinctive morphology (Starkey et al., 1984). Particles dispersed on a plastic film can be observed directly by transmission microscopy or shadowed to increase contrast by evaporating a heavy metal onto specimens prior to examination. Grim (1968) and Starkey et al. (1984) provide an entry into the extensive literature on this subject. Many aluminosilicates (e.g., montmorillonite, which occurs as broad mosaic sheets decomposing into minute flakes) lack a distinctive morphology and cannot be identified by this technique.

Energy-dispersive X-ray analysis (EDXA) — also referred to as energy-dispersive X-ray microanalysis, X-ray microanalysis, electron microscopic microanalysis, and energy-dispersive X-ray spectrometry — and electron diffraction may permit the rapid identification of individual clay mineral particles (Sahle et al., 1990; Lee, 1993) and have been applied particularly to the identification of inhaled particles sampled via bronchoalveolar lavage or from lung specimens (Johnson et al., 1986; Costabel et al., 1990; Monsó et al., 1991, 1997; Chariot et al., 1992; Bernstein et al., 1994; Dufresne et al., 1994). EDXA requires a scanning or transmission electron microscope equipped with an energy-dispersive X-ray spectrometer and appropriate mathematical tools for analysing the resulting spectra. EDXA identifies and quantifies elements above atomic number 8. Since the basic classification of clay minerals is based on structural formula and the atomic composition is similar for many different clay minerals, EDXA cannot provide secure identification except by comparison with standards previously identified by other means. Application of EDXA without appropriate standards is likely to generate significant errors (Newbury et al., 1995). In practice, EDXA is ordinarily combined with conventional transmission electron microscopy to first visualize a particle. Probe size is then adjusted downward so that only the selected particle is analysed. The best results are obtained by operating the microanalysis in scanning transmission mode.

Differential thermal analysis (DTA) is based on temperature differences between the sample and a thermally inert material during heating or cooling and is most useful for mineral identification in samples composed mainly or entirely of a single clay mineral (Grim & Rowland, 1944; Mackenzie, 1970; Smykatz-Kloss, 1974). The sample and a control, a thermally inert material (e.g., aluminium oxide), are heated in separate crucibles in a well regulated furnace. During heating, the change in temperature of the clay sample will be modified by endothermic and exothermic reactions. Identification is done by comparing the temperature difference trace with standard curves (Grim & Rowland, 1944; Mackenzie, 1970; Smykatz-Kloss, 1974). DTA is not without difficulties, since results are influenced by furnace atmosphere, heat conductance of sample and crucible, type of thermocouple, rate of heating, grain size of sample, and many other factors (Smykatz-Kloss, 1974). Identification of component minerals in mixtures and quantification of mixtures by use of DTA are difficult and often may be impossible due to overlapping DTA curves (Grim, 1947; Smykatz-Kloss, 1974).

Many aluminosilicates can be identified by distinctive infrared absorption spectra. Absorption is normally measured over a range of frequencies (Grim, 1968), and the resulting spectrum compared with published standards (Van der Marel & Beutelspacher, 1976; Ferraro, 1982). Satisfactory measurements require appropriate mounting of specimens and minimizing of scattering and reflection. The latter is accomplished by using particles smaller than the minimum wavelength (Grim, 1968).

Montmorillonite can be distinguished from beidellite, nontronite, and saponite by its irreversible collapse of the structure after Li saturation and heat treatment. Li migration to the octahedral charge converts montmorillonite to a non-expandable structure upon treatment with water, glycol, or ethylene glycol. The procedure is known as the Greene-Kelly test (Greene-Kelly, 1955). Other smectites, such as beidellite and saponite, should expand to give the characteristic 1.77-nm reflection upon solvation with ethylene glycol.

3.1.1 Bentonite

Bentonite derived from ash falls tends to be in beds of uniform thickness (from a few millimetres to 15 m) and extensive over large areas (Parker, 1988). Bentonite from ash falls and other sources occurs worldwide in strata spanning a broad range of ages, but is most abundant in Cretaceous or younger rocks.

Bentonite is a widely distributed material. Accordingly, its major component, montmorillonite, occurs abundantly as dust at and near surface deposits of bentonite and is dispersed widely by air and moving water. Montmorillonite is thus ubiquitous in low concentrations worldwide in soil, in the sediment load of natural waters, and in airborne dust. Biodegradation appears minimal, if it occurs at all, and there is no evidence of or reason to suspect accumulation in the food-chain. Abiotic degradation of bentonite into other minerals takes place only on a geological time scale (Parker, 1988).

3.1.2 Kaolin

Kaolin and the clay mineral kaolinite are natural components of the soil and occur widely in ambient air as floating dust. Kaolinite is formed mainly by decomposition of feldspars (potassium feldspars), granite, and aluminium silicates. It is also not uncommon to find kaolin deposited together with other minerals (illite, bentonite). The process of kaolin formation is called kaolinization (Grim, 1968).

Kaolinite formation occurs in three ways:

• crumbling and transformation of rocks due to the effects of climatic factors (Zettlitz type);
• transformation of rocks due to hydrothermal effects (Cornwall type); and
• formation by climatic and hydrothermal effects (mixed type).

The type of clay mineral formed during the decay of rocks containing aluminium silicates is influenced by the climate, the aluminium/silicon ratio, and pH. Conditions conducive for kaolinite formation are strong dissolution of Ca²⁺, Mg²⁺, and K⁺ ions and the presence of H⁺ ions (pH 4–5) (Parker, 1988).

Kaolinite quarries can be categorized according to the geohistorical age of the parent rock:

• Precambrian (Ukraine, Spain, Czech and Slovak republics)
• Postcambrian (Cornwall, England, and Ural Mountains, Russia)
• Palaeovolcanite (Meissen, Germany)
• Neovolcanite (Tokaj Mountain, Hungary).

Kaolinite can also be categorized according to whether it remained at the place of formation or was transported (Parkes, 1982; Kuzvart, 1984):

• primary: lateritic types formed mainly under tropical climatic conditions (South America, Africa, Australia); and
• secondary: transported by different forces, water, wind (Georgia, USA).

Owing to the different ways in which kaolin can form, several kinds of minerals may occur in natural kaolins. For example, the kaolin of Cornwall, England, contains 10–40% kaolinite; the rest is made of quartz, mica, and feldspar. The kaolin of Georgia, USA, contains 85– 95% kaolinite, as well as quartz, muscovite, and feldspar (Patterson & Murray, 1975).

3.1.3 Other clays

Illite is widely distributed in nature, abundant, and often the dominant clay mineral in soil, terrestrial deposits, sedimentary rocks, freshwater sediments, and most deep-sea clays (Grim, 1968). It is also an important impurity in limestone, affecting the properties and thus the value of the stone for construction and other purposes (Carr et al., 1994). Despite the widespread occurrence of illite in nature, large deposits of high purity are quite rare.

Illite, together with smectites, is formed by weathering of acid igneous rock containing considerable quantities of potassium and magnesium under conditions that permit the potash and magnesia to remain in the weathering environment after breakdown of the parent material (Grim, 1968). Deer et al. (1975) and Srodon & Eberl (1984) identified many potential sources of illite, including weathering of silicates (primarily feldspar), alteration of other clay minerals, and degradation of muscovite. Righi & Meunier (1995) concluded that illite can also be degraded by weathering into illite–montmorillonite (smectite) mixed-layer minerals.

3.2.1 Production levels and sources

3.2.1.1 Bentonite

Bentonite (Table 1) and bentonite Fuller’s earth (Table 2) are mined worldwide. The USA is the major producer of bentonite Fuller’s earth (Table 2). Approximately 90% of world bentonite production is concentrated in 13 countries: the USA, Greece, the Commonwealth of Independent States, Turkey, Germany, Italy, Japan, Mexico, Ukraine, Bulgaria, Czech Republic, South Africa, and Australia (Table 1). The USA, Greece, and the Commonwealth of Independent States account for roughly 55% of the annual world production of 10 million tonnes. Wyoming produces the bulk of bentonite mined in the USA (Ampian, 1985). In 2002, the bulk of US production was used domestically, and only a small fraction, 11%, was exported worldwide (Virta, 2002). In addition to the mining of natural deposits, small amounts of bentonite, mainly hectorite, are produced synthetically in both Europe and the USA for use as a catalyst.

Table 1. Bentonite production in selected countries^a–d

Table 2. World bentonite Fuller's earth production^a,b

Most bentonite is mined by stripping methods from open pits after removing any overburden, although underground methods are used in a few places, such as the Combe Hay district in the United Kingdom (Patterson & Murray, 1983). Since deposits are often not uniform in composition, bentonite from a single pit may be separated into several stockpiles, which subsequently are blended to obtain the desired composition. Bentonite is usually processed by breaking large pieces into smaller fragments, drying at low to moderate temperatures to remove water and other volatiles without altering the molecular structure of the bentonite, and grinding to the desired size. The desired size is generally 200 mesh (US standard sieve size) or finer, which is equivalent to particle diameters of less than 70 µm. A coarser granular material is also produced for kitty litter applications. Processing may also include beneficiation, which may involve removing sand and other impurities as well as modifying the type of exchangeable ions in the crystal lattice. Some of the calcium bentonite produced in Texas, USA, is, for example, treated with sodium hydroxide to replace calcium with sodium in the montmorillonite and make the resulting product more suitable for use in drilling mud (Hosterman & Patterson, 1992). An organic-clad bentonite is produced for speciality purposes (paint, speciality greases, etc.) by replacing the inorganic exchangeable cations in the montmorillonite with an alkyl ammonium organic cation and is marketed under trade names such as Bentone and Nikkagel.

3.2.1.2 Kaolin

Large quantities of kaolin are mined and traded internationally. Virta (2002) lists 55 countries with a production of more than 1000 tonnes per year. Production figures for each country that produced >0.1% (>43 000 tonnes) of the estimated world production of kaolin in 2002 are given in Table 3. The People’s Republic of China was estimated to produce 1.9, 2, and 2.12 million tonnes in 2000, 2001, and 2002 (Lines, 2003). The estimated annual production capacity of kaolin in China was 3.2–3.4 million tonnes in 2002–2003, out of which washed kaolin was only 700 000 tonnes (Ma & Tang, 2002; Moore, 2003).

Table 3. Kaolin production in selected countries^a,b

Kaolin is usually removed from the mines in large moist lumps, and the initial process of refining involves chiefly a change in the physical state. Two main methods have been used for the refining of the natural clay: the air flotation or dry process, and the wet process. In the dry process, the clay is dried, pulverized, and then carried by currents of hot air into classifying chambers, from which it emerges as a stream of finely powdered kaolin. This process, which generates huge amounts of dust, was generally used prior to 1940 and has now been largely replaced by the wet process. In this process, the crude clay is mixed with water and vigorously agitated, and the individual kaolin particles are thus separated from each other and suspended in water. Water is then removed using different procedures (Edenfield, 1960).

Because of the varying composition of raw kaolin and different uses, raw kaolin generally requires processing (flotation, sedimentation, baking, etc.) to acquire characteristics suited to specific industrial uses.

3.2.1.3 Other clays

Illite is often an important or dominant component of common clay (Murray, 1994). Common clay is produced worldwide and is a major industrial mineral. In the USA, common clay and shale are produced in 41 states. In 2002, this production was 23 million tonnes and had a value of $148 million (Virta, 2002).

Illite occurs in commercially valuable purity and quantity in Malaysia (Bidor area of Perak), the USA (Illinois), the United Kingdom (South Wales), and Hungary (Tokaj Mountain in the north-eastern part of the country) (Grim, 1968; Fan & Aw, 1989). The most valuable ore is pure white and contains minimal iron. The commercial utility and thus the value of illite deposits may be reduced by lack of homogeneity in mineral content. There is no information on the annual production of relatively pure illite worldwide or by country.

3.2.2 Uses

3.2.2.1 Bentonite

Bentonite has many applications to a broad range of industrial and other activities. Usage of domestic production in the USA in 1995, 1999, and 2002 is summarized in Table 4. Major domestic uses, which include binding foundry sand (i.e., in moulds for castings), absorbing grease, oil, and animal wastes, pelletizing taconite iron ore, and improving the properties of many drilling muds, were 79% of the total. Most of the bentonite (79%) exported from the USA was used in foundry sand and drilling mud. Speciality uses of bentonite include serving as an ingredient for ceramics; waterproofing and sealing in civil engineering projects (e.g., blocking seepage loss from landfill sites, nuclear waste repositories, irrigation ditches, treatment ponds, and the like); serving as a filler, stabilizer, or extender in adhesives, paints, cosmetics, medicines, and other products, as a carrier in pesticides and fertilizers, and as a bonding agent in animal feeds; clarifying wine and vegetable oil; and purifying wastewater (Patterson & Murray, 1983; Kuzvart, 1984; Hosterman & Patterson, 1992; Hanchar et al., 2004). Small amounts of bentonite are also used as a catalyst in the refining of petroleum.

Table 4. Usage of bentonite produced in the USA^a

The use of sodium bentonite in hazardous waste containment utilizes a number of its special properties (Jepson, 1984). Its swelling ability makes it an effective soil sealant, since, by swelling within the interstices of the soil with which it is mixed, bentonite plugs the voids in the soil, creating a barrier of very low permeability. Swelling ability is aided by the possibility of a very small average particle size, allowing bentonite to plug even the smallest of voids. The high cation exchange capacity enhances the retention of wastes, especially heavy metals. In addition, a mixture of sodium bentonite and soil forms a tough, flexible mastic that is highly durable and not easily ruptured.

The ability of bentonite to bind cationic metals and certain pesticides has been applied experimentally to detoxifying victims of paraquat poisoning (Meredith & Vale, 1987) and to reducing the transfer of radiocaesium to milk and other animal-derived foods (Giese, 1989; Unsworth et al., 1989). Although effective in reducing the mortality of experimentally poisoned rats, there was no evidence that lavage with bentonite decreased human mortality following accidental ingestion of paraquat. Inclusion of bentonite in the diet of cattle reduced the transfer of radiocaesium into milk, but bentonite proved far less effective than cyanoferrates such as Prussian blue and thus was not the treatment of choice. In addition to these examples, there is an extensive literature documenting the ability of bentonite to adsorb these and other toxics. None of this research, however, appears to have led to major new uses for bentonite.

The chemical composition of bentonite affects its usage (Patterson & Murray, 1983; Kuzvart, 1984; Hosterman & Patterson, 1992). High-swelling bentonite, in which sodium is usually the dominant exchangeable ion, is preferred for drilling muds, pelletizing iron ore, and sealing and waterproofing, whereas low-swelling calcium bentonite is preferred for filtering, clarifying, and absorbing and for serving as a filler, stabilizer, extender, carrier, bonding agent, or catalyst. Both types are used as a foundry sand bond. Sodium bentonites provide good dry strength in moulds, whereas calcium bentonites provide good "green" (condition prior to drying) strength.

Bentonite is used in a large number of different cosmetic products, such as paste masks, skin care and cleansing preparations, eyeliners, foundations, and others. In 1998, bentonite was reported to be used in 78 different cosmetics in the USA, usually at concentrations between 1% and 10%, but reaching 80% in some paste masks (CIREP, 2003). Bentonite has been approved for use as a "Generally regarded as safe" (GRAS) food additive in the USA (US FDA, 2004).

The uses of montmorillonite-type Fuller’s earth overlap those of bentonite (Hosterman & Patterson, 1992) (Table 5). Major uses include serving as an adsorbent for oil, grease, and animal waste and as a carrier for pesticides and fertilizers. Minor uses are filtering, clarifying, and decolorizing and serving as filler in paints, adhesives, and pharmaceuticals.

Table 5. Fuller's earth sold or used by producers in the USA, by use^a

3.2.2.2 Kaolin

In China, east of King-te-Chen city, kaolin was used for making porcelain in the third century BC.

In Europe, kaolin was used for making earthenware in about 5000 BC, but the method of making porcelain was unknown until about 1710. After that time, porcelain production spread first to Europe and then to the whole world (Kuzvart, 1984).

Like bentonite and common clay, kaolin is an important industrial mineral that has an enormous variety of uses. Uses of kaolin mined in the USA for the years 1995, 1999, and 2002 are summarized in Table 6. In all three years, about two-thirds of the total production was used domestically and the remainder exported. Use of kaolin as a coating for paper accounted for almost half of the total domestic consumption and for roughly 80% of the exported kaolin. Widespread use of kaolin-coated papers in the manufacture of cigarettes (Wynder & Hoffman, 1967) may expose smokers to kaolinite particles by inhalation. Other important uses of kaolin were as a filler in the production of paint, paper, and rubber, as a component of fibreglass and mineral wool, as a landfill liner, and as a catalyst in oil and gas refining. The usage historically associated with kaolin, manufacture of porcelain and chinaware, accounted for less than 1% of the domestic consumption in the USA. In China, 80–85% of the total production in 2003 was used for ceramics, 5% for paper, 3% for rubber, and 2% for paint. In India, 290 000 tonnes were used for ceramics, 84 000 tonnes for paints, 68 000 tonnes for paper/paperboard, 29 000 tonnes for detergents, and 27 500 tonnes for rubber (Moore, 2003).

Table 6. Kaolin sold or used by producers in the USA, by use^a

Kaolinite has a number of properties relevant to medicine. It is an excellent adsorbent and will adsorb not only lipids and proteins (Wallace et al., 1975; Adamis & Timár, 1980) but also viruses and bacteria (Steel & Anderson, 1972; Schiffenbauer & Stotzky, 1982; Lipson & Stotzky, 1983). It can be used to induce aggregation of platelets (Cronberg & Caen, 1971), to initiate coagulation of plasma by activation of factor XII (Walsh, 1972), and to remove non-specific haemaglutinin inhibitors from serum (Haukenes & Aasen, 1972; Inouye & Kono, 1972). Kaolin is used in medical therapy as a local and gastrointestinal adsorbent (Kaopectate, bolus alba).

Kaolin is used in a large number of different cosmetic products, such as eyeshadows, blushers, face powders, "powders," mascaras, foundations, makeup bases, and others. In 1998, kaolin was reported to be used in 509 different cosmetics in the USA, usually at concentrations between 5% and 30%, but reaching 84% in some paste masks (CIREP, 2003). Medical, pharmaceutical, and cosmetic uses, however, accounted for roughly 0.01% of the total US consumption of kaolin (Table 6).

3.2.2.3 Other clays

Common clay and shale, of which illite is often a major component, are used mainly in the manufacture of extruded and other bricks, portland and other cements, concrete blocks and structural concrete, and refractories. Highway surfacing, ceramic tiles, and ceramics and glass are other important uses (Virta, 2002; see Table 7). The relatively pure illite mined in Hungary, Malaysia, and the USA has a variety of uses. The illite produced in Malaysia is mainly exported to Japan, where it is mostly used to coat welding rods because of its fluxing properties. It is also used as a filler in sponge rubber and latex foam (Fan & Aw, 1989). Illite increases the plasticity and workability of the porcelain mass and produces a superior end product by filling the gaps in the kaolin crystals. Use in cosmetics requires a light coloured illite with minimal iron. Fan & Aw (1988) suggested that illite could also serve as a less expensive substitute for feldspar in ceramics.

Table 7. Common clay and shale sold or used by producers in the USA, by use^a,b

4.1.1 Bentonite

Bentonite is widely distributed in natural materials that commonly occur as fine particles readily dispersed by air circulation and moving water. Bentonite is also widely used in an enormous variety of consumer products. Accordingly, general population exposure to low concentrations of bentonite must be widespread, if not universal. However, while Churg (1983) identified small amounts of kaolinite and illite in the lungs of a group of subjects drawn from the general population (see section 4.1.2), he did not detect montmorillonite. Similarly, while Dumortier et al. (1989) reported illite and kaolinite as ubiquitous in bronchoalveolar lavage (see section 4.1.2), they did not identify any particle as bentonite.

4.1.2 Kaolin and other clays

Kaolin and other clays are natural components of the soil and occur widely in ambient air as floating dust. Accordingly, exposure of the general population to them must be universal, albeit at low concentrations. In the vicinity of mines and industrial projects, kaolinite is likely to be present at high concentrations in air; no data are available, however.

The occurrence of mineral fibres in lung specimens from 20 persons who had no occupational dust exposure was determined on autopsy. Thirteen different minerals, among which were kaolinite and illite, were identified in the lungs of patients; 71% of the particles were fibres. There was no correlation between the number or type of fibres and age, sex, or smoking (Churg, 1983).

In a further study, Churg & Wiggs (1985) studied the relationship between mineral particles (and fibres) in the lungs (from autopsy) and lung cancer in men without occupational mineral exposure. The average number of mineral particles in the lungs of cancer patients was 525 × 10⁶/g dry lung, and in the referents, 261 × 10⁶/g dry lung. Kaolinite, talc, mica, feldspar, and crystalline quartz comprised the majority of particles in both groups. Approximately 90% of the particles were smaller than 2 µm, and 60% were smaller than 1 µm.

Dumortier et al. (1989) similarly reported kaolinite, illite, and mica in most of 51 subjects sampled via bronchoalveolar lavage. These subjects were all occupationally exposed to various industrial dusts, but not including kaolin or other clays to any great extent. The presence of illite in human lungs is also not a recent phenomenon, since it was found in the lungs of a 5300-year-old male human cadaver that had been well preserved by glacial ice (Pabst & Hofer, 1998).

Paoletti et al. (1987) identified 17 different mineral types in the lung parenchyma of 10 deceased subjects resident in an urban area and with no occupational dust exposure. Approximately 70% of the minerals consisted of phyllosilicates, in particular micas (10 cases), clays (kaolin and pyrophyllite, 10 cases), and chlorites (6 cases).

Samples of nine brands of tobacco and alveolar macrophages from cigarette smokers contained particles identified as kaolinite by energy-dispersive X-ray spectrometry (Brody & Craighead, 1975).

Kaolinite and mica particles were identified in the macrophages of the bronchoalveolar lavage fluid of 18 and 12, respectively, of the total of 22 patients for whom pulmonary lavage was performed. The frequency of these particles was higher among smokers and ex-smokers than among non-smokers (Johnson et al., 1986).

Mastin et al. (1986) determined the inorganic particles in the lungs of persons not occupationally exposed. Quartz, talc, and kaolinite could be detected in the lungs of practically all subjects (number of lungs examined: 48).

Kalliomäki et al. (1989) detected several different mineral types in the lungs from 11 unselected autopsy cases, including quartz, feldspar, kaolinite, and mica, reflecting the Finnish bedrock. Kaolinite particles constituted 10 ± 5% of the mineral particles in the lungs. More mineral particles were found in the lungs of non-smokers, but the differences were not statistically significant. Similarly, Yamada and co-workers (1997) also detected (fibrous) talc, mica, silica, chlorite, and kaolinite particles in the lungs of female lung cancer patients and referents from urban and rural areas in Japan.

Occupational exposure to clay dusts has been studied in many industries. However, numerical figures are usually given on total dust or respirable dust only, without analysis of the components of the dust. When information is given on individual components, it is mostly on silica. Exposure to silica in different trades has recently been extensively summarized (IARC, 1997b; IPCS, 2000) and will not be reviewed here. Clay particles have been detected in the lung tissue of bronchoalveolar lavage fluid of various worker groups (Churg, 1983; Churg & Wiggs, 1985; Johnson et al., 1986; Wagner et al., 1986; Dumortier et al., 1989; Dufresne et al., 1994; Gibbs & Pooley, 1994; Sébastien et al., 1994; Monsó et al., 1997). Exposure to clay dusts can also occur in small, family-run pottery shops — and may be considerably higher than in large workshops. Such exposure will not be considered in this review because of a lack of available information.

4.2.1 Bentonite

The information on occupational exposure to bentonite dust in mines, processing plants, and user industries (foundries) is summarized in Table 8. These data reveal a wide range of values for both total and respirable bentonite dust and indicate that very high total dust concentrations can be present in industrial settings involving both the production and utilization of bentonite. The highest values for total dust concentrations were reported by Melkonjan et al. (1981) in their study of bentonite mining and processing in Bulgaria. Only one of the eight types of locations they sampled, inside dump truck cabs during loading, had values consistently below 10 mg/m³. Their highest reported values, 1150 and 1430 mg/m³, and highest averages, 504 and 749 mg/m³, obtained in the vicinity of packing and loading operations, reveal an extraordinary level of dustiness. These highest values are more than an order of magnitude greater than the highest values reported in any of the other studies summarized in Table 8. In the 1970s in foundries in Germany (Orth & Nisi, 1980), the dust concentrations in air were mostly below older observations for bentonite plants in the USA (McNally & Trostler, 1941; Phibbs et al., 1971), as well as far below contemporary observations from bentonite plants and mines in Bulgaria (Melkonjan et al., 1981). In general, however, these data for total dust concentrations represent too limited a sampling to detect much in the way of regional, temporal, or other trends. Orth & Nisi (1980), however, concluded that their study of two German iron foundries demonstrated that change from the older, partially mechanized methods to modern, fully automatic, boxless moulding resulted in a reduction in dustiness. This may be true; however, in view of their problems in measurement methodology, the small differences between the two foundries in average dustiness, and the fact that only one foundry of each type was sampled, the conclusion seems premature.

Table 8. Occupational exposure to bentonite dust

Values for respirable bentonite dust are generally far below those for total bentonite dust (Table 8). However, values as high as 33.9 mg/m³ have been reported in a foundry (Turkish Ministry of Labor & Social Security, personal communication, 1999). None of the observations from the two German foundries (Orth & Nisi, 1980) and only 1 of the 251 recent observations from the USA (US Mine Safety and Health Administration, personal communication, 1999) exceeded 5 mg/m³, whereas the Turkish data for respirable dust in foundries suggest that this value is exceeded more frequently. Silica, which is widely viewed as the major hazard in many industrial dusts (Phibbs et al., 1971; Oudiz et al., 1983; Oxman et al., 1993), was a significant component of bentonite dust, especially in foundries.

4.2.2 Kaolin

Stobbe et al. (1986) analysed mine dusts of West Virginia, USA. Respirable dust samples collected in three locations in the mines contained 64% illite, 21% calcite, 8.5% kaolinite, and 6.7% quartz on average.

Processing of china clay involves considerable exposure (Tables 9 and 10). Exposure was especially significant before the 1960s (Sheers, 1964). Following drying, nearly all work stages were carried out in high dust concentrations (conveyor belts, bagging, storage in bulk). At present, ventilation is much more effective, and closed technologies are also widely used.

Table 9. Dust exposure in the koalin industry

Table 10. Dust exposure in brick, pipe, and tile industries

^a Unless otherwise noted.;

^f Median (range).

Lesser et al. (1978) analysed the free silica content of the airborne dust from a kaolin mill in Georgia and another from South Carolina and noted that while in most of the (total dust) samples free silica was not detectable, in some specimens (three baggers and a bulk loader) quartz was present at approximately 1%. They also said that in all but one of the plants, some baggers and loaders were exposed to about 1% free silica (no numbers provided).

Significant exposure is expected also in paper, rubber, and plastic production. When producing insulator materials, quartzite and feldspar exposure may occur (Parkes, 1982). Sahle et al. (1990) carried out measurements of airborne dust in a Swedish paper mill. Total dust exposure at the plant was generally less than 3 mg/m³. The respirable fraction of the total dust varied from 15% to 70%. The inorganic dust was 36% of the total dust, and 10–15% of the total fibres were inorganic. The respirable dust at the plant contained kaolinite fibres, wollastonite, talc and other silicates, and cellulose fibres.

Dust conditions in power stations were studied in Poland by Wojtczak et al. (1989). In 14 power stations, average respirable dust and total dust concentrations ranged from 0.45 to 6.95 mg/m³ and from 1.55 to 85.0 mg/m³, respectively. The mean content of free crystalline quartz was less than 10%. At the workplace where ash dust was also encountered, the presence of respirable fibre at concentrations below 0.2 fibre/cm³ was measured. Alpha-quartz and mullite were found in all ash samples. Occasionally, kaolinite and orthoclase were also found. Only at 5 power stations out of 14 was the mean respirable dust concentration below 1 mg/m³.

In ceramic factories, workers are exposed to mixed dust. Analysis of the workplace respirable dust of five Hungarian ceramic factories demonstrated the presence of kaolinite (19–69%) and crystalline quartz (7–30%). X-ray amorphous material amounted to 7–76%, nearly half of which was amorphous silica (Adamis & Krass, 1991).

4.2.3 Other clays

There is some relevant information on exposure to illite dust in coal mining and in the manufacture of bricks, but none concerning the mining and processing of relatively pure deposits of illite. Wiecek et al. (1983), in their study of six brick manufacturing plants in Poland, reported illite in workplace floating dust prior to the firing of the bricks. In a sample of 27 dusts from European coal mines, illite was present in most and comprised as much as 55% of the fine material (particles <1.65 µm in mean geometric diameter) in one sample group (Bruch & Rosmanith, 1985). Illite comprised 11% of the total dust and 46% of the mineral dust (i.e., excluding coal dust) in a sample from a coal mine in Saar, Germany, and was also present in the lungs of most and possibly all of a sample of 13 Saar coal miners (Leiteritz et al., 1967). Stobbe et al. (1986) reported that in dust samples collected in nine locations in a bituminous coal mine in West Virginia, USA, illite represented 49–80% of the mineral dust and averaged 64%. In another study of a West Virginia coal mine, illite ranged from 3 to 89% of the mineral dust and averaged 52% (Grayson & Peng, 1986). In addition, observations in Dumortier et al. (1989) discussed above in section 4.1.2 indicated that even in industrial workers not specifically exposed to clay mineral dusts, illite can form a significant fraction of the particles retained by the lungs.

Data from the various studies summarized above suggest that workers in some occupations are frequently exposed to illite particles, which may comprise a large or major portion of certain industrial workplace dusts.

Clays are not distinct chemicals, but are complex mixtures with usually a large component of specific clay minerals, such as montmorillonite, kaolinite, or illite. No information was available on the kinetics or metabolism of montmorillonite, kaolinite, or illite as they occur in most occupational settings. However, Snipes and co-workers (1983a, 1983b) and Bailey et al. (1982) studied the kinetics of fused aluminosilicate particles, prepared from montmorillonite by heating, in mice, rats, dogs, and humans after inhalation exposure. The method consisted of exchange by radiolabel (⁸⁵Sr, ⁸⁸Y, or ¹³⁴Cs) of cations normally present in montmorillonite clay, aerosolization, and heating at 1100 °C to yield spherical particles in which the radiolabel was incorporated in the lattice and very resistant to leaching. The polydisperse aerosol could then be segregated to different monodisperse fractions as needed and the specific fractions resuspended in an aqueous medium and administered to the experimental animals or human volunteers by inhalation.

The initial deposition of particles in the nasopharynx was lower in dogs than in mice or rats and increased with increasing activity median aerodynamic diameter (AMAD) (Table 11), whereas the tracheobronchial deposition was low and independent of animal species and particle size. The pulmonary deposition was remarkably higher in dogs than in mice and rats and decreased with increasing particle size; the change with size was especially marked in rats and mice.

The removal of particles from the lungs took place by solubilization in situ (leading to label distribution in the blood and carcass and excretion in the urine) and by physical clearance. For dogs, the overall clearance was slow, and the major mechanism of removal was solubilization. Rats and mice removed the label from the lungs rapidly, and the mechanism was mainly mechanical removal. The mechanical removal in rats and mice was mostly via the gastrointestinal tract, while in dogs it was mainly to the lung-associated lymph nodes. The mechanical clearance was independent of the particle size, while solubilization was faster for smaller particles. The initial half-time for the mechanical clearance was 140 days for dogs, which increased by 200 days post-exposure to 6900 days. In rats and mice, the initial halftime for mechanical clearance was 35 days and increased to 690 days in rats and 460 days in mice by approximately 500 days post-exposure.

Table 11. Deposition of ¹³⁴Cs-labelled aluminosilicate particles in dogs, rats, and mice after inhalation exposure^a

Radiolabel from fused aluminosilicate particles, instilled in the apical lung lobe in dogs, was transferred mainly to the lateral tracheobronchial lymph nodes; after instillation to the cardiac or diaphragmatic lung lobes, radiolabel was mainly in the middle tracheobronchial lymph nodes (Snipes et al., 1983b). More recent studies indicate that ultrafine particles (<100 nm) have a high deposition in the nasal area of rats (Gerde et al., 1991) and humans (Cheng et al., 1988). Ultrafine particles can penetrate the alveolar/capillary barrier (Nemmar et al., 2004).

After inhalation exposure of seven volunteers to monodisperse fused aluminosilicate particles (1.9 or 6.1 µm aerodynamic diameter), there was a rapid initial clearance from the lung region of 8% and 40% of the two particle sizes, respectively, over 6 days, which was considered to represent deposition in the conducting airways. Of the remaining activity, 4% of the smaller and 11% of the larger particles cleared initially with a half-time of about 20 days, and the rest with half-times of 330 and 420 days. Taking into account the in situ dissolution (estimated to be 0.001 and 0.0005/day for the two particle sizes), the mechanical clearance half-time during the slow clearance stage is approximately 600 days and is independent of the particle size.

Two limited studies have addressed the leaching and bioavailability of metals from clays (Mascolo et al., 2004; Wiles et al., 2004). No significant differences were observed in the contents of aluminium, antimony, barium, bromine, caesium, calcium, cerium, chromium, cobalt, copper, dysprosium, europium, hafnium, iron, lanthanum, lutetium, magnesium, manganese, neodymium, nickel, samarium, scandium, selenium, sodium, strontium, sulfur, tantalum, tellurium, terbium, thorium, titanium, uranium, vanadium, ytterbium, zinc, or zirconium in the brain, kidney, liver, or tibia from pregnant SD rats dosed with 2% sodium montmorillonite or calcium montmorillonite clay compared with animals fed the basal diet. The main element components of the clays were aluminium (10%), iron (3%), and magnesium (0.5%) (as well as sodium in the sodium montmorillonite, 1%), with small amounts (usually less than 0.1%) of barium, caesium, manganese, strontium, zinc, and zirconium. The authors concluded that at this dietary level, the clays did not liberate significant amounts of trace elements (Wiles et al., 2004). Another study suggested that when rats were given 450 mg/kg of body weight of (three different varieties of) bentonite by gastric lavage for 6 days, contents of arsenic, cadmium, mercury, selenium, stibium, and tellurium in different organs were higher than in animals given normal diet (Mascolo et al., 2004). Because of limited reporting, the results are difficult to interpret.

Clays are not distinct chemicals, but are complex mixtures with usually a large component of specific clay minerals, such as montmorillonite, kaolinite, or illite. They may also contain entities with well characterized adverse effects on health, such as quartz. In studies on the effects of clays or clay minerals on laboratory animals and even in in vitro tests, it is often not known what it was precisely that was studied and the impurities present in the material used. Thus, the results must be interpreted carefully. In this chapter, an effort is made to describe the material studied, but many of the studies, especially the older ones, give few details.

6.1.1 Bentonite

Data on single exposures of experimental animals to bentonite via intratracheal and intradermal administration, summarized in Table 12, indicate a variety of harmful effects. Bentonite has also been administered to animals by the intravenous and intramuscular routes (Boros & Warren, 1970, 1973), but these studies were not destined for, and cannot be used for, the assessment of health risks from bentonite.

Table 12. Effects of single exposure to bentonite (montmorillonite) in mammals

Intratracheal injection of moderate amounts (0.16–0.27 g/kg of body weight) of finely powdered (where specified, mean diameter <5 µm) bentonite into rodents evoked responses indicative of cytotoxic effects, as well as rapid and/or long-lasting irritation of or damage to the lungs. Gross effects on the lungs of rats administered 0.19 g/kg of body weight included inflammation and oedema within 12 h, bronchopneumonia by day 1, and a doubling of wet weight by day 3, followed by a gradual decline to a value still significantly above the initial weight by day 90 (Tátrai et al., 1983). The histology of the inflammation included large numbers of neutrophil leukocytes plus some macrophages and lymphocytes at 12 h, mainly eosinophil and necrobiotic leukocytes by day 1, and collapse of the reticular network by day 3. Some bentonite particles were held within the macrophages and leukocytes at day 3.

Changes in gross morphology and histology were accompanied by changes in the chemistry of lung lavage fluid. These included elevated levels of phospholipid (Adamis et al., 1985) and acid phosphatase (Adamis et al., 1985; Tátrai et al., 1985) by day 3. The increase in phospholipid was not, however, accompanied by any change in the relative abundance of phospholipid fractions (Adamis et al., 1986). Phospholipid was still somewhat elevated 3 months after exposure (Adamis et al., 1985, 1986). Tátrai et al. (1985) reported acid phosphatase back to baseline level at 1 and 12 months after exposure, whereas Adamis et al. (1985) found it still elevated at day 30. Hydroxyproline was slightly elevated 3 months after exposure (Adamis et al., 1986).

The effects of smaller intratracheal doses of bentonite on rats are uncertain. Adamis & Krass (1991) reported that 0.027 g/kg of body weight had no effect on protein or lactate dehydrogenase (LDH) in lavage from the lung 15–60 days after dosage, whereas Sykes et al. (1982), also using lavage from the lungs, noted a variety of effects indicating irritation and damage immediately following doses of 0.012 and 0.0012 g/kg of body weight. These effects included large and rapid increases in soluble protein, LDH, and polymorphonuclear leukocytes, with peaks at day 1 or day 2 followed by a decline to somewhat above baseline by day 7. Alveolar macrophages were increased by day 7. The findings in these two studies need not be contradictory, since the observations of Sykes et al. (1982) permit the possibility that elevated values for LDH and protein were present following dosage in the experiment of Adamis & Krass (1991), but declined back to baseline prior to their first sample on day 15.

The changes in gross morphology, white cell abundances, and biochemistry described above appear to form a generally coherent picture. Swelling and oedema stem from changes at the cellular level. Henderson et al. (1978a, 1978b) found increased LDH and protein in the lavage-sensitive indicators of lung damage that preceded visible mechanical damage and impairment of gas exchange. Increased LDH was ascribed to damage to cell membranes and leakage from lung cells, whereas increased protein was ascribed to increased vascular permeability. The latter conclusion is supported by analyses by Sykes et al. (1982), which reported serum albumin as the major constituent of the recovered protein. The increases in polymorphonuclear leukocytes may be triggered by phagocytosis of bentonite particles by alveolar macrophages (Terashima et al., 1997).

Single intratracheal exposures of rats to bentonite produced storage foci in the lungs 3–12 months later (Timár et al., 1979, 1980; Tátrai et al., 1983; Ungváry et al., 1983); even 12 months after exposure, fibrosis had not progressed beyond Belt-King grade 1 (Tátrai et al., 1985). Macroscopically, the foci were visible in fixed material as greyish-white masses up to the size of a "pin prick or a poppy seed" — i.e., approximately 1 mm (Timár et al., 1966). The structure of these storage foci was described in detail by Timár et al. (1966) using slides stained with haematoxylin-eosin, Van Gieson’s solution, and Foot’s silver impregnation. Timár et al. (1966: 5–6) reported that "The foci contained large cells with foamy protoplasm, and [with] nuclei often located at the edge of the cells. In the foam cells no lipids could be demonstrated by Sudan staining. PAS [para-aminosalicylic acid] reaction was intensely positive, showing that substances of carbohydrate nature are accumulated in the foci. In polarized light a great mass of intracellularly located doubly refractive fine grainy substance was to be seen. This characteristic alteration was to be observed in the lungs of the animals killed the 40th day after the application of the dust, and the microscopic findings in the tissues had not changed essentially up to the end of the experiment [365 days]. In the foci, sometimes a poorly developed reticular network of loose structure occurred too, but collagen fibres did not develop. The silver impregnated preparations showed in the area of the foci the precipitation of a greyish-black homogeneous substance between the fibres."

By ultrastructural analysis, Ungváry et al. (1983) augmented the above description, noting that whereas the cytoplasm of the peripheral cells of the foci was foamy, the closely packed cells of the centre with dislocated nuclei, which formed the bulk of the foci, had dark, granulated cytoplasm. No cell division was observed among cells of the foci 3 or 10 months after exposure. The cytoplasm of the dark, electron-dense cells contained a small number of mitochondria and occasionally other organelles plus a large amount of lamellar electron-dense material very similar in appearance to high phospholipid-containing breakdown products of intracellular origin. This material, however, by means of X-ray microanalysis, was demonstrated to be bentonite, which was swollen, presumably due to its montmorillonite content in direct contact with the cellular fluid. "The width of the electron dense and electronlucent layers depends on the degree of the swelling; the crystalline and the swollen ends of bentonite are spread out like cards" (Ungváry et al., 1983: 213). Cells of the foci with light foamy cytoplasm also contained bentonite, but in much smaller amounts. Both the above findings and the enzyme histochemical information on the foci (Ungváry et al., 1983) suggested that the metabolism of the foci is low. Ungváry et al. (1983) concluded that clearance of bentonite stored in foci from the lung is relatively slow and reflects the fact that cells of the foci are designed for long-term storage. The authors speculated that absence of toxic effects in the storage cells indicated that these cells have modified the surface characteristics of bentonite and coated the particles with protective molecules absorbed onto the bentonite.

Timár et al. (1966) provided evidence that the above cytotoxic responses leading to storage foci stem from montmorillonite and not from quartz or other impurities in the bentonite by comparing the effects of four mixed dusts containing varying proportions of montmorillonite, quartz, cristobalite, and other minerals. The composition of these dusts, essentially synthetic bentonites, is summarized in footnote d of Table 12. Dusts containing 55–98% montmorillonite and i) no quartz or cristobalite, ii) 30% quartz, or iii) 15% quartz and 30% cristobalite induced storage foci and no progressive fibrosis in rats following intratracheal administration. Only the dust with 15% montmorillonite and 65% quartz induced fibrosis. The authors ascribed the failure of the dust containing 30% quartz to produce productive fibrosis to a protective effect of the 55% montmorillonite, which they suggested may coat the surface of the quartz particles and thus inhibit the normal cytotoxic effects of the quartz. They further suggested a similar protective effect of montmorillonite against the cytotoxic effects of cristobalite. Havrankova & Skoda (1993) also reported that bentonite exerted a protective effect on rats against the toxicity of quartz dust. Observations by Schreider et al. (1985) supported the importance of molecular properties (crystalline structure and possibly exchangeable cations) in regulating the toxic effects of montmorillonite. They reported that an intratracheal dose (0.15 g/kg of body weight) of montmorillonite, washed to remove organic matter and biologically active cations and heated to 750 °C to collapse the crystal lattice and inactivate any traces of silica, induced not only increased pulmonary alveolar macrophages but also gross lesions in the lung and mild fibrosis at 90 days. This mild fibrosis, however, was not defined in terms of Belt-King grades.

In addition to directly damaging the lung, bentonite had a potential, even at low doses, for increasing susceptibility to pulmonary infection. Hatch et al. (1985) followed single intratracheal injections of 5, 0.5, or 0.05 mg/kg of body weight into mice with aerosolized Group C Streptococcus sp. (Table 12). The lowest dose did not significantly elevate mortality from Streptococcus infection over controls, whereas the highest dose produced 85% excess mortality and the intermediate dose 43% excess mortality over controls. Earlier studies by Hatch et al. (1981) demonstrated a close correlation between the effects on susceptibility to infection following dosing by sustained inhalation and by administering the same amount of test substance in a single intratracheal injection.

The mechanism by which bentonite increases susceptibility is unknown. Oberson et al. (1993), however, postulated that enzyme inhibition by bentonite may be a factor, based on their in vitro observation that a low concentration of bentonite can totally suppress the activity of human leukocyte elastase, an enzyme important in the destruction of microorganisms phagocytized by neutrophils.

In most experiments, bentonite also displayed local toxic effects after intra- or subdermal injection (Table 12). Subdermal injection of 10 mg/kg of body weight as 5% bentonite gel into the plantar of rats produced pronounced oedema within an hour (Marek, 1981; Marek & Blaha, 1982). The swelling continued to enlarge for a week and then slowly regressed, but it was still evident 6 weeks after injection. The oedema was accompanied by marked increases in macrophages and polymorphonuclear leukocytes, which peaked at 30 h. The leukocytes declined back to the baseline after 4 weeks, whereas the macrophages were still elevated at 6 weeks. Subdermally implanting 440 mg of sterile montmorillonite per kg of body weight into incisions in the backs of rats produced marked inflammation accompanied by the development of foreign body granulomata and collagen synthesis (Cohen et al., 1976). Incisions with montmorillonite failed to close during the 8-day duration of the experiment.

The granulomatous inflammation resulting from a moderate intradermal injection of relatively coarse (diameter 79–90 µm) bentonite into the skin of guinea-pigs was followed by Browett et al. (1980) both visually and with light and electron microscopy. The injection induced a chronic inflammatory response with ulceration and maximum induration at 7–10 days. By day 2, there was vascular dilation and some infiltration of monocytes and polymorphonuclear leukocytes. The macrophage infiltration rapidly increased in density and by the termination of observations, day 30, had become mainly multinuclear cells, had phagocytized most of the bentonite particles, and had evolved into a loose, disorganized mass. This mass was walled off from adjoining tissues by active fibrosis, which also subdivided the cells into clumps.

In a limited experiment involving two guinea-pigs and subdermal injection of bentonite Fuller’s earth, the bentonite was found encapsulated as a compact mass beneath the skin at autopsy (Campbell & Gloyne, 1942). However, no adverse reaction to the injected bentonite was reported. McNally & Trostler (1941) also reported no adverse reactions following intraperitoneal injection of an unspecified dose of bentonite Fuller’s earth into flank muscles of rabbits, other than adhesions in one animal.

As in the case of the lungs, montmorillonite also increased the susceptibility of subdermal tissue to infection (Rodeheaver et al., 1974). A dose of 0.01 g of sterile montmorillonite per kg of body weight in each of two experimental wounds in guinea-pigs 5 min after a subinfective dose of Staphylococcus aureus established infections in 80–100% of the incisions. Three separate experiments, which were run using montmorillonite saturated with calcium, magnesium, or potassium, yielded similar results. Almost none of the control incisions that received only S. aureus became infected.

6.1.2 Kaolin

6.1.2.1 Intratracheal administration

In the landmark paper in which intratracheal instillation as a means of studying the effects of dust on lungs was described, no collagen production was detected in the lung of a guinea-pig 336 days after the administration (whereas fibrosis was observed after similar injection of quartz) (Kettle & Hilton, 1932). Similarly, intratracheal instillation of kaolin from South Wales or untreated or ignited Cornish kaolin did not induce fibrosis in rats (King et al., 1948) (Table 13).

Table 13. Effects of intratracheal instillation of kaolin and illite on the respiratory tract

^a Where available.

^d MMAD = mass median aerodynamic diameter.

After the instillation of a single dose of commercial acid-washed kaolin containing 8% hydrated free silica and 12% mica, grade 2–3 fibrosis was observed in rats after 8 months (grade 1 = minimal reticulin fibrosis, grade 4 = maximal fibrosis, as induced by quartz) (Belt & King, 1945) (Table 13).

Following intratracheal dust treatment in rats, the histological reaction was found to depend on the composition of the dust (Tímár et al., 1966). Foreign body reaction as an effect of kaolinite was observed in all cases where the crystalline quartz content of the dust was less than or equal to 30%. The sample containing 65% quartz and 35% kaolinite caused progressive fibrosis. In addition to the composition, particle size also played a role in the development of the tissue reaction. Kaolin samples containing particles less than 2 µm caused storage foci (Tímár et al., 1979), while the kaolin samples containing bigger particles (particle size between 2 and 5 µm) caused mainly storage foci but also, to a smaller extent, foreign body reaction (Table 13).

Goldstein & Rendall (1969) observed cellular reaction with minimal fibrosis: some loose reticulin with either no collagen in some animals or a few collagen fibres in other rats 4 months after an intratracheal instillation of kaolin (Table 13).

Martin et al. (1977) observed an increase in the collagen content in the lungs of rats 3 months after an intratracheal instillation of non-specified kaolin; the reaction was considerably weaker than after a similar treatment with quartz (Table 13).

Sahu et al. (1978) described the development of grade 2 fibrosis in mice after 7 months of exposure to non-specified kaolin (Table 13).

Rosmanith et al. (1989) compared the fibrogenicity of four kaolinite samples with that of quartz in rats using intratracheal instillation. The fibrogenicity of kaolinites, as measured by the increase in hydroxyproline content in relation to the amount of dust retained, was approximately 1/10 that of quartz, but the inflammatory reaction was considerably less (Table 13).

No significant LDH, protein, or phospholipid leakage to the supernate fraction was observed in bronchoalveolar fluid 15–60 days after an intratracheal instillation of kaolin to rats. In this system, effects of quartz became apparent towards the end of the observation period (Adamis & Krass, 1991) (Table 13).

6.1.2.2 Parenteral administration

Policard & Collet (1954) demonstrated the development of reticulin fibres in rats 1–3 months after intraperitoneal administration of kaolin (90% <2 µm in diameter). The dust sample contained 1.2% free silica, an amount that the authors considered not to cause the effects observed.

Intraperitoneal administration of kaolinite (<3 µm or ~10 µm particle size; no quartz detectable with X-ray analysis) was fibrogenic in mice; the smaller particle size was just as active as quartz and led to fibrosis in 35 days, whereas fibrosis became evident only after 200 days for the larger size particles (Rüttner et al., 1952).

Intraperitoneally instilled kaolin and kaolin baked for 1 h at 900 or 1200 °C caused marked fibrosis. The degree of the reaction was only slightly smaller than that caused by quartz (Schmidt & Lüchtrath, 1958).

In a study of a large number of organic and inorganic particulates, kaolin (composition not specified, particle size 0.25–25 µm) injected intraperitoneally into rats produced a granulomatous reaction at 1 and 3 months, but no fibrosis. In vitro, it had low toxicity: it killed less than 2% of peritoneal macrophages and approximately 4% of alveolar macrophages (Styles & Wilson, 1973). For the group of some 20 particulate materials, the authors considered that there was a good correlation between toxicity to macrophages and fibrogenicity after intraperitoneal injection.

6.1.3 Other clays

Three and 12 months after an intratracheal instillation of illite clay with unknown quartz content, alveolar proteinosis and increased lung weight and collagen synthesis were observed in rat lungs (Table 13).

6.2.1 Bentonite

A case of profound hypochromic anaemia and mild hypokalaemia has been reported in a cat that habitually consumed large amounts of cat litter stated to contain 99% bentonite. The clinical status was dramatically improved by a transfusion and intravenous hydration. A similar episode was seen in the same cat a month later, when the use of the same litter material was resumed (Hornfeldt & Westfall, 1996). The causality is uncertain, as anaemia causes pica in cats (McDonough, 1997).

Bentonite has also been administered to animals using intravenous and intramuscular routes (Boros & Warren, 1970, 1973), but these studies were not destined for, and cannot be used for, the assessment of health risks from bentonite.

No long-term studies on the effects of bentonite in experimental animals using inhalation exposure are available.

In a study by Wilson (1953b, 1954), the reports of which provide only limited details, mice were fed bentonite (undefined) at 10, 25, and 50% of their diet (Table 14). The total numbers of mice in different treatment groups were not given, but of the 12 mice given 50% bentonite that survived 200 days or more, 11 developed tumours that the authors call "benign hepatomas" (without histological description). Eight of these mice had also been given thorotrast (known to be a liver carcinogen in mice, rats, and humans; IARC, 2001) before starting the diet study. Nine animals of the control group survived more than 200 days, and one developed hepatoma. In historical controls, no hepatomas were observed in 18 animals that had been given thorotrast and had lived >215 days; nor were hepatomas detected in 24 non-treated mice that had survived 484–575 days. Nine animals given low-protein, choline-deficient diet also survived more than 200 days, and three developed hepatomas. Development of hepatomas in these strains of mice on low-protein, choline-deficient diet had also been reported by the authors in an earlier study (Wilson, 1951).

Table 14. Effects of repeated exposure to clays in experimental animals

^a Inbred strains maintained in the author's laboratory for investigation of physiology and pathology of mouse liver.

Mice maintained on the diet with 50% bentonite also showed minimal growth and developed fatty livers and fibrosis of the liver (Table 14). Mice maintained on diets containing 10 or 25% bentonite displayed slightly reduced growth rates and no hepatic tumours (Wilson, 1953b, 1954).

In a separate, 60-day study (Wilson, 1953a), the addition of choline or casein to the 50% bentonite diet was reported to partially prevent the development of fatty liver and cirrhosis and permitted an improved but still subnormal growth rate. The author concluded that bentonite binds choline and other nutrients so that they cannot be absorbed into the body, and this deficiency then induces liver damage and hepatomas (Wilson, 1951, 1953a, 1953b, 1954). Because of the mixed exposure, limited numbers of animals, and limited reporting, these studies cannot be used to assess the carcinogenicity of bentonite.

6.2.2 Kaolin

Carleton (1924) studied the effects of kaolin (see Table 14) by inhalation in guinea-pigs. Until 3 months after the exposure, mild alveolar proliferation only was observed. Thereafter, patchy bronchopneumonia occurred, with massive eosinophil infiltration. By 6 months, plaque formation and capillary bronchitis were observed.

Wagner and co-workers (1987) studied the carcinogenicity of palygorskite and attapulgite in an inhalation study and used "coating grade" kaolin as a negative control: 20 male and 20 female Fischer rats were exposed by inhalation (10 mg/m³, 91.4% of the particles <4.6 µm in diameter) for 6 h/day, 5 days/week, until they died. However, at 3, 6, and 12 months, four rats were killed from each group for ancillary studies (leaving only 28 animals for the carcinogenicity study). At the end of the study, full autopsy and microscopic analysis of the lungs, liver, kidney, spleen, and other organs were performed. In two kaolin-exposed rats, bronchoalveolar hyperplasia but no benign or malignant tumours of the lungs or pleura were observed. However, the number of tumours in the positive control group (crocidolite treatment at the same exposure level) was also low (one adenocarcinoma only). The mean fibrosis grading in the rats at interim sacrifices and at the end of the experiment was between 2.1 and 2.8 on a scale of 1–8 (1 being normal; 2, dust in macrophages; 3, early interstitial reaction; 4, first signs of fibrosis; 5, 6, 7, increasing fibrosis; 8, severe fibrosis).

As another part of the study on the carcinogenicity of mineral fibres, Wagner et al. (1987) injected a single dose (amount not given) of kaolin intrapleurally into 20 male and 20 female Fischer rats and followed the animals until moribund or dead (survival of animals in different groups not given). None of the kaolin-treated rats developed mesothelioma, whereas 34 of 40 of those given crocidolite did.

Mossman & Craighead (1982) treated cultured tracheas from hamsters with Georgia kaolin (composition not indicated; diameter 3–5 µm) and kaolin coated with 3-methylcholanthrene, implanted the tracheas after 4 weeks into syngeneic hamsters, and followed the animals until moribund at 105–110 weeks. Animals treated with kaolin did not develop tumours, but a high incidence of pulmonary tumours, often fatal, was observed in animals treated with kaolin coated with 3-methylcholanthrene. Animals treated with 3-methylcholanthrene-coated haematite or carbon particles also developed a similar spectrum of tumours (carcinomas, sarcomas, undifferentiated tumours).

No information was available on the genotoxicity of clays or clay minerals. Information on quartz has been summarized by IARC (1997) and IPCS (2001). Quartz did not test positively in standard bacterial mutagenesis assays. Results of genotoxicity studies of quartz conflict, and a direct genotoxic effect for quartz has not been confirmed or ruled out (IPCS, 2001).

In a study that provided limited details, Sprague-Dawley rats were administered calcium or sodium montmorillonite orally on pregnancy days 1–15. No effects were observed on the litter weight, implantation rates, or resorptions (Wiles et al., 2004) (Table 15).

Table 15. Developmental effects of bentonite (montmorillonite) in rats

Thirty-six Sprague-Dawley rats were fed a control diet, 20% kaolin (air-floated Georgia kaolin) diet, and iron-supplemented 20% kaolin diet 37–117 days before mating and during pregnancy (Patterson & Staszak, 1977). Dams receiving kaolin diet developed anaemia, whereas anaemia was not observed in dams receiving iron supplementation. The birth weight of the pups of the dams receiving kaolin was 9% smaller than that of the control dams (P < 0.01); again, iron supplementation prevented this decrease. There was no effect on the litter size or macroscopic malformations (Table 15).

6.5.1 Kaolin and microbes and microbe-derived factors

In the study described in section 6.1.1 on bentonite (see Table 12), Hatch et al. (1985) also studied the effect of kaolin on infection resistance in mice. Intratracheal instillation of 100 µg kaolin (not further defined) caused a slightly (40%) and statistically not significantly increased mortality upon challenge by exposure to aerosolized group C streptococci by inhalation.

Intratracheal instillation of kaolin "prepared to the specification of the Society of Leather Trades" with atypical mycobacteria (not Mycobacterium tuberculosis) induced fibrotic reaction in the lungs of guinea-pigs (Byers & King, 1959). No control experiment with kaolin alone was performed.

Attygalle et al. (1954) studied the combined effects of dust samples characterized as mainly crystalline, to a small extent amorphous, aluminium silicate containing 77% kaolinite, 12% mica, and 8% quartz together with autoclaved M. tuberculosis. Kaolin samples alone did not cause macroscopic changes in rats or guinea-pigs.

Microscopically, a diffuse exudative reaction developed with giant cells containing dust particles after 30 days. The cells were prone to form groups. Noduli, however, were not found. Fine reticulin fibres were found in the cells. The lesions showed no progress and, after 500 days, were still of minimal grade 1. An avirulent strain (BCG) alone also produced a network of fine reticulin fibres, but no progressive fibrosis. In contrast, kaolin and BCG together produced, after 180–270 days, reactions of grade 2–3, with thickening of the alveolar walls and collagen fibre bundles. Thereafter, the lesions showed regression and, after 500 days, were of grade 1 only (reticulin fibre network with mononuclear cells).

Similarly, when kaolin (75 mg, not specified qualitatively) was injected into guinea-pigs intratracheally together with Candida albi-cans, thick reticulin fibres and collagenous fibrosis ensued; acute inflammatory reaction followed by formation of thick reticulin fibres were observed after kaolin alone (Zaidi et al., 1981).

6.5.2 Kaolin and quartz

Schmidt & Lüchtrath (1958) studied the effects of intratracheal administration of a 2:3 mixture of kaolin and quartz. Kaolin alone did not cause significant reaction in the lung. The mixture of kaolin and quartz caused significant changes in the lung; after 9 months, the fibrosis was grade 5. (Using pure quartz, the development of silicosis was somewhat quicker, but after 9 months, the difference compared with the kaolin–quartz mixture was insignificant.)

6.6.1 Bentonite

Experimental protocols in the studies summarized in Table 16 appear fairly uniform; cell suspensions were incubated with bentonite or montmorillonite for (where specified) 30 min to 24 h, and the cells were tested for physical integrity or functional ability. Cell types included rat peritoneal macrophages, rabbit and rat alveolar macrophages, a macrophage-like cell line, other white cells, human and other erythrocytes, rodent neural cells, hamster tracheal epithelial cells, and human umbilical vein endothelial cells. The results usually indicated a high degree of cytotoxicity. Concentrations below 1.0 mg/ml of bentonite and montmorillonite particles less than 5 µm in diameter caused lysis of human neutrophils, many types of erythrocytes, mouse embryo neuronal cells, and human umbilical vein endothelial cells. The velocity and degree of lysis of sheep erythrocytes were dose dependent. Using cow erythrocytes and montmorillonite, Oscarson et al. (1986) found that particles 0.2–2.0 µm in diameter were most active and that particles greater than 2.0 µm in diameter showed little or no haemolytic activity. The ability of low concentrations of these particles to lyse mammalian cells, although widespread, was not universal, since Murphy et al. (1993a, 1993b) reported no lysis of neuroblastoma cells or oligodendroglial cells incubated in 0.1 mg montmorillonite or bentonite/ml for 18 or 24 h.

Table 16. Effects of exposure to bentonite in vitro

^a Dose recalculated as necessary to mg/ml.

^p 0.1, 0.3, 1,3, and 10 mg/ml.

Lytic activity appeared to stem from surface properties of the particles, since it was blocked by heating montmorillonite and bentonite to over 500 °C, which altered surface characteristics (Mányai et al., 1969), or by pretreatment of montmorillonite with 10% albumin, which coated the particles and thus altered surface characteristics (Dougherty et al., 1985). Mányai et al. (1969) also reported that the haemolytic activity of bentonite and montmorillonite was proportional to the surface areas of the mineral powder.

Other indications of damage to the physical integrity of cells from montmorillonite or bentonite particles were a dose-dependent loss of ⁵¹Cr from hamster tracheal epithelial cells (Woodworth et al., 1982), a dose-dependent loss of fatty acids from human umbilical vein endothelial cells (Murphy et al., 1993b), and elevated loss of beta-glucur-onidase from rat alveolar macrophages (Vallyathan et al., 1988). Montmorillonite also caused a dose-dependent loss of chromate from artificial liposomes (Woodworth et al., 1982) and suppressed the activity of the enzyme human elastase.

Loss of LDH from cells is a sensitive measure of damage to cell membranes. Several authors, however, reported less loss of LDH to the supernatant in cell cultures incubated with bentonite or montmorillonite than in the controls (Table 16). Dougherty et al. (1985) explained this paradox by demonstrating that although LDH was greatly diminished in quantity in cells incubated with montmorillonite, LDH lost from cells was largely adsorbed on the montmorillonite particles and thus did not appear in the supernatant. Pretreatment of the montmorillonite with 1% human albumin blocked this adsorption without affecting lysis. These observations may also explain the low value of another enzyme used to measure cell membrane damage, beta-N-acetylglucosaminidase, in the supernatant from suspensions of rat alveolar macrophages incubated with bentonite (Vallyathan et al., 1988).

In addition to the lytic and membrane damage effects described above, bentonite and montmorillonite also usually exerted other cytotoxic effects. Oberson et al. (1993) noted that montmorillonite particles totally suppressed hydrolysis of elastin by human leukocyte elastase. Adamis and his co-workers (Adamis & Timár, 1976, 1978, 1980; Adamis et al., 1985; Adamis & Krass, 1991) found that bentonite particles were highly cytotoxic to rat peritoneal macrophages as measured by a decrease in 2,3,5-triphenyltetrazolium chloride (TTC) reduction activity (Table 16). Hatch et al. (1985) reported that incubation of rabbit alveolar macrophages with bentonite greatly lowered the viability of the cells as well as cellular ATP. Murphy et al. (1993b) similarly found that montmorillonite significantly decreased the viability of neuroblastoma cells (assessed by trypan blue exclusion), but surprisingly that bentonite had no effect on these cells as measured by this test. The particle size of both minerals, mainly 1–2 µm diameter, was appropriate to produce adverse effects; the composition of the minerals, however, was not specified.

Functional effects of montmorillonite particles on mammalian cells were also reported. Neuroblastoma cells (with differentiation induced by exposure to dimethylsulfoxide) briefly exposed to up to 1.0 mg/ml had their resting potentials depolarized and lost the ability to maintain action potentials in response to stimulation (Banin & Meiri, 1990). Human leukocytes incubated with sterile, magnesium-saturated montmorillonite at a concentration of 5.3 mg/ml lost all capacity to phagocytize Staphylococcus aureus and Pseudomonas aeruginosa (Haury et al., 1977). Exposure of hamster tracheal epithelial cells to montmorillonite, however, did not prevent these cells from phagocytizing the clay particles (Woodworth et al., 1982).

6.6.2 Kaolin

6.6.2.1 Haemolysis

Different kaolin samples were found to have a significant haemolysing effect on red cells (Table 17). Mányai et al. (1970) investigated a water-washed Hungarian kaolin sample. The non-heat-treated samples had a haemolytic effect. The sample pretreated by heating at 200 or 350 °C for 90 min had a somewhat stronger haemolytic effect on the red cells than the original sample.

Table 17. Toxicity of kaolin and illite clay in vitro

The heat treatment caused the loss of water adsorbed to the surface. Samples pretreated by heating at 500 or 650 °C lost the structurally bound water, and the haemolytic activity was practically abolished. Undoubtedly, the presence of hydroxyl groups is important with respect to the interaction between the red cell and the crystal. Heat treatment of kaolin at 800 or 950 °C resulted in the loss of the crystal structure and the formation of mullite and cristobalite and restoration of haemolytic activity. Mányai et al. (1970) established that the haemolytic activity of the kaolin samples is determined by the crystal structure and hydration of the surface. Studies by Adamis & Krass (1991) showed that the haemolytic activities of kaolin samples coming from different sources and used in the ceramic industry were significantly different. Narang et al. (1977) found that the haemolytic activity of the kaolin sample increased with the amount of silicic acid that could be dissolved from the particles.

Oscarson et al. (1981) determined the haemolytic activity of montmorillonite, kaolinite, quartz, and several fibrous silicates. Montmorillonite had the highest haemolytic activity, followed in decreasing order by quartz, palygorskite, chrysotile, and kaolinite. Polyvinyl-pyridine-N-oxide inhibited the haemolysis caused by montmorillonite and kaolinite. If the incubation medium contained sucrose instead of physiological saline, no haemolysis was observed with the dusts. These results indicate that the hydrogen bonding and ionic interactions are important in the haemolytic action of the silicate surface on the erythrocyte membrane.

Robertson et al. (1982) studied the effect of nitrous oxide on the cytotoxicity of dusts. Kaolinite adsorbed nitrous oxide; although the adsorption was small, it caused a significant decrease in the cytotoxicity of the dust.

6.6.2.2 Macrophage studies

Styles & Wilson (1973) studied the effect of a large number of mineral dusts and polymers on the alveolar and peritoneal macrophages of rat. The kaolin sample did not damage the macrophages. Five out of six kaolin samples decreased TTC reduction by peritoneal macrophages, but only one of them also induced a release of LDH to the medium (Adamis & Timar, 1976, 1986; Timar et al., 1979, 1980; Adamis et al., 1986; Adamis & Krass, 1991) (Table 17). The surface cationic groups may play a role in the cytotoxic effect of aluminium silicates (kaolin, illite, bentonite). This is suggested by the observed decrease in the cytotoxic effect of aluminium silicate by adsorption of paraquat cations (Adamis & Tímár, 1976). The cytotoxic effect increases with increasing adsorption capacity of the kaolin sample (Adamis & Timár, 1980; Adamis et al., 1985). This relationship has also been observed in connection with methylene blue, paraquat cation, serum protein, serum lipid, and serum phospholipid adsorption. After dry grinding the kaolin sample in an oscillating mill for 32 h, the adsorption and, at the same time, the macrophage cytotoxic effect decreased (Juhasz et al., 1978). The above indicates the importance of the nature of the crystal surface and the magnitude of the adsorption capacity on the sample’s cytotoxicity.

Quartz, asbestos, and kaolinite increased the elastase secretion of peritoneal macrophages. The increase, however, was not as great as that observed after phagocytosis of latex particles. With alveolar macrophages, a difference was also found between the inert latex and the dust samples. This difference probably reflects the cytotoxicity of the dust. Kaolinite has a cytotoxic effect on both peritoneal and alveolar macrophages (White & Kuhn, 1980).

Davies (1983) and Davies et al. (1984) studied the cytotoxicity of Cornwall (United Kingdom) and Georgian (USA) kaolinite on mouse peritoneal macrophages. The Cornwall sample contained 98% kaolinite and 2% mica, and 98% of the particles were smaller than 5 µm in diameter; the Georgia kaolin contained 99% kaolinite and no quartz, mica, or feldspar. Both caused cytoplasmic LDH liberation from macrophages, and the cytotoxicity was apparently caused by kaolinite, not the other dust components. After polyvinylpyridine-N-oxide adsorption, the cytotoxic effect of kaolinite specimens from Cornwall decreased significantly (Davies & Preece, 1983; Davies et al., 1984). Davies et al. (1984) concluded that the amorphous silica-rich gel coating the kaolinite particles was probably responsible for the cytotoxic effect of kaolinite. The flake-like morphology of kaolinite is unlikely to play a role.

Low et al. (1980), studying rabbit alveolar macrophage cells, found that the presence of kaolinite inhibited the incorporation of amino acids into proteins through the non-competitive inhibition of amino acid transport.

Brown et al. (1980) compared different macrophage experimental systems. Kaolin proved to be cytotoxic; after thermal treatment (calcined kaolin), however, the damaging effect decreased significantly.

6.6.2.3 Other tissue cultures and in vitro systems

Gormley et al. (1979) studied the cytotoxicity of 30 respirable mine dust specimens with varying compositions from the United Kingdom using a macrophage-like P388 D1 cell line. Positive correlation was found between cytotoxicity and the kaolin and mica (combined) content of dusts containing >90% coal, but not in dusts containing less coal. In the study described in Table 16 on bentonite, Gormley & Addison (1983) studied the cytotoxicity of two standard kaolinites, KGa-1 and KGa-2, with particle sizes of 3.2 and 3.9 µm, which do not contain quartz or cristobalite. They showed very little effect on cell viability at 20 µg/ml; even at 80 µg/ml, the cell viability remained at 60% or more.

Kaolinite treated with hydrochloric acid did not increase the liberation of LDH from macrophages. The activity of quartz samples was considerably increased by treatment with hydrochloric acid (Kriegseis et al., 1987).

Bruch & Rosmanith (1985) found that mixed dusts containing kaolinite, illite, and quartz inhibit TTC reduction and induce liberation of LDH from guinea-pig alveolar macrophages; no apparent relationship emerged between the toxicity and dust composition.

6.6.3 Other clays

Illite inhibited TTC reduction but caused only a small LDH release from peritoneal macrophages and was haemolytic to human erythrocytes in vitro (Table 17).

6.6.4 Relationships between in vivo and in vitro studies

Tímár et al. (1980) did not find any direct relationship between the in vitro cytotoxicity of mineral dusts and their in vivo fibrogenicity. Mixed dusts containing 10–30% quartz that were inert in in vitro experiments were found to cause fibrosis in vivo after a long exposure time. Le Bouffant et al. (1980) reached the same conclusion based on in vitro (haemolysis, macrophage) and in vivo animal experiments (lung weight, collagen content after 3 and 12 months). On the other hand, of several particulate organic and inorganic materials, asbestos and polyurethane foam dust were the most toxic to alveolar and peritoneal macrophages and induced the most pronounced fibrosis in rat peritoneum; most of the materials studied neither were cytotoxic in vitro nor caused peritoneal fibrosis (Styles & Wilson, 1973).

Quartz dust induces cellular inflammation in vivo. Short-term experimental studies of rats have found that intratracheal instillation of quartz particles leads to the formation of discrete silicotic nodules in rats, mice, and hamsters. Inhalation of aerosolized quartz particles impairs alveolar macrophage clearance functions and leads to progressive lesions and pneumonitis. Oxidative stress (i.e., increased formation of hydroxyl radicals, reactive oxygen species, or reactive nitrogen species) has been observed in rats after intratracheal instillation or inhalation of quartz. Many experimental in vitro studies have found that the surface characteristics of the crystalline silica particle influence its fibrogenic activity and a number of features related to its cytotoxicity. Although many potential contributory mechanisms have been described in the literature, the mechanisms responsible for cellular damage by quartz particles are complex and not completely understood.

Long-term inhalation studies of rats and mice have shown that quartz particles produce cellular proliferation, nodule formation, suppressed immune function, and alveolar proteinosis. Experimental studies of rats reported the occurrence of adenocarcinomas and squamous cell carcinomas after the inhalation or intratracheal instillation of quartz. Pulmonary tumours were not observed in experiments with hamsters or mice. Adequate dose–response data (e.g., no-adverse-effect or lowest-adverse-effect levels) for rats or other rodents are not available because few multiple-dose carcinogenicity studies have been performed.

Quartz did not test positively in standard bacterial mutagenesis assays. Results of genotoxicity studies of quartz conflict, and a direct genotoxic effect for quartz has not been confirmed or ruled out.

In experimental studies of particles, results may vary depending on the test material, particle size of the material, concentration administered, and species tested. The experiments with quartz particles involved specimens from various sources, using various doses, particle sizes, and species, which could have affected the observations.

Data on the reproductive and developmental effects of quartz in laboratory animals are not available.

General population exposure to low concentrations of clay minerals is universal (see section 4.1). However, no studies are available on the health effects of clays in the general population.

There are important limitations in the data on the health effects of clays in humans. Most studies are case reports or case series (bentonite) or cross-sectional in design (kaolin). Smoking data are not available in most of the studies. In many studies, exposure characterization, both qualitatively and quantitatively, is incomplete.

7.2.1 Bentonite

Data on the effects of occupational exposure to bentonite are summarized in Table 18.

Table 18. Case reports and case series on effects of occupational exposure to bentonite^a