FAO/PL:1967/M/11/1
WHO/Food Add./68.30
1967 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD
THE MONOGRAPHS
The content of this document is the result of the deliberations of the
Joint Meeting of the FAO Working Party of Experts and the WHO Expert
Committee on Pesticide Residues, which met in Rome, 4 - 11 December,
1967. (FAO/WHO, 1968)
FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS
WORLD HEALTH ORGANIZATION
Rome, 1968
This document contains summaries of data considered by the Joint
Meeting of the FAO Working Party of Experts and the WHO Expert
Committee on Pesticide Residues in arriving at recommendations for
acceptable daily intakes, tolerances and methods of analysis.
A summary Report of the Joint Meeting (FAO/WHO, 1968) has also been
published which contains general considerations, including the
principles adopted for the evaluations and a summary of the results of
evaluations of a number of pesticide residues.
CONTENTS
Introduction
Note to the reader
The Monographs
Aldrin
Carbaryl
Carbon disulfide
Carbon tetrachloride
Chlordane
DDT
Demeton
Demeton-S-methyl sulfoxide - see oxydemeton-methyl
Diazinon
Dichlorvos
Dieldrin
Dimethoate
Diphenyl
Endosulfan
Ethylene dibromide
Ethylene dichloride
Ferbam
Heptachlor
Hydrogen phosphide
Lindane
Malathion
Mancozeb
Maneb
Methyl bromide
MGK 264
Nabam
Organomercury compounds
Oxydemeton-methyl
Parathion
Piperonyl butoxide
Pyrethrins
Thiram
Zineb
Ziram
Appendix I - Glossary
INTRODUCTION
A Joint Meeting of the FAO Working Party of Experts on Pesticide
Residues and the WHO Expert Committee on Pesticide Residues was held
in Rome in December 1967. The general considerations, including the
principles adopted for the evaluations and a summary of the results of
evaluations on a number of pesticide residues will appear in a
publication entitled "Report of the 1967 Joint Meeting of the FAO
Working Party of Experts on Pesticide Residues and the WHO Expert
Committee on Pesticide Residues" (FAO/WHO, 1968). Additional
information, including previously unpublished summaries of data
considered by the Joint Meeting in arriving at recommendations for
acceptable daily intakes, tolerances and methods of analysis, is to be
found in this document.
Many of the compounds considered at this meeting have been previously
evaluated in earlier publications. If only a limited amount of
additional data on these compounds has become available in the
intervening years, only this latter data is summarized in the
pertinent monograph and reference is made to the previously published
evaluation which should also be consulted by the reader who wishes to
obtain a complete evaluation of the compound. If a large amount of
data has become available since the previously published evaluation,
or if the compound was first considered by the Joint Meeting in 1967,
the pertinent monograph is reproduced in its entirety.
As much relevant information as possible has been included in the
monographs. Wherever possible this has been obtained from the
published literature, but other sources of information have also been
used. Early and complete publication of the results of research in
this field is very important, particularly of that part which could
form the basis for estimation of acceptable daily intakes and
appropriate tolerances.
Publication allows the research to be scrutinized and criticised by
scientists from disciplines not necessarily represented at the
meeting. Data contained in unpublished reports, because they may
include more detail than published work, are often acceptable.
However, such reports must be complete and non-confidential and
indicate authorship.
As indicated in the Report of the 1967 Joint Meeting, the terms used
in previous reports were reviewed. Those employed in the current
Report and these monographs were carefully studied and, where
necessary, redefined and explained in the accompanying glossary
(Appendix 1). The Joint Meeting wished to emphasize, however, that the
agreed definitions are solely for convenience in clarifying the
present monographs which are specifically concerned with the hazards
to consumers arising from the use of pesticides in the production and
protection of food.
GENERAL COMMENTS
Organochlorine insecticides
The organochlorine insecticides have been proved to be very effective
and they have been used extensively with very beneficial effects.
Their acute toxicities are much lower than many other pesticides.
However, many of them have been shown to be persistent in the animal
and human body. In addition, even at relatively low doses they have
effects on the liver. The toxicological significance of the induction
of liver enzymes and of the associated morphological changes are
difficult to evaluate. It was therefore recommended that further
studies on this matter be undertaken.
Organophosphorus insecticides
On the other hand, some of the organophosphorus insecticides have
relatively high acute toxicities and their improper transportation and
use has resulted in numerous cases of intoxication and death. Although
these matters are outside the terms of reference of the WHO Expert
Committee on Pesticide Residues, the FAO Working Party of Experts on
Pesticide Residues wished to emphasize that both acute and chronic
toxicity hazards should be taken into consideration when selecting
pesticides for agricultural use.
Fumigants
Much work has been done during recent years on the mechanisms by which
fumigants are retained by foodstuffs and the chemical and physical
reactions which occur during and after sorption. This is valuable in
both assessing the toxicological importance of any residues in food
and in devising methods for their measurement. However, the Joint
Meeting of the FAO Committee on Pesticides in Agriculture and the WHO
Expert Committee on Pesticide Residues (FAO/WHO, 1965) pointed out
that relatively little information is available on residues of parent
fumigant substances in individual commodities and that the possible
chemical reactions between fumigants and, for example, amino acids or
vitamins, have not been fully investigated.
METHODS OF RESIDUE ANALYSIS
1. General Remarks
The meeting has considered the analytical methods available for the
determination of residues of the various pesticides studied. By way of
guidance only, a single method of analysis (which may be a
multidetection procedure) has, where possible, been suggested for each
pesticide in each monograph. This is not to say that methods which are
not suggested for these compounds are unsuitable. In the following
paragraphs guiding suggestions on the limitations and means of
achieving adequate sensitivity for the tolerances and practical
residue limits in this compendium of monographs are given. Special
review articles on residue analysis are published from time to time in
Residue Reviews (Gunther, 1962 to date).
2. Multidetection Systems of Analysis
Many modern chromatographic methods of residue analysis are highly
sensitive and specific. When properly conducted the system permits the
analyst in a single analytical operation to detect and measure any of
a large number of different residues in a sample. It is particularly
emphasized that to do this successfully, it is very necessary for the
extraction and cleanup processes to be properly designed and for the
operational techniques of layer and gas chromatography to be well
understood and controlled.
The multidetection systems of analysis comprise paper chromatography,
layer chromatography and gas-liquid chromatography. Thin-layer and
loose-layer chromatography are themselves essentially simple
techniques useful for the cleanup of extracts in residue analysis.
They can also be used in some cases to separate, identify and measure
individual residues. Gas-liquid chromatography in an excellent method
for the separation and measurement of individual residues, by using
suitable detectors, it is capable of a very high degree of
sensitivity. These features can be further developed when gas-liquid
and thin-layer chromatography are suitably combined in a single system
of analysis, so providing confirmation of the identity of the
residues. Paper chromatography also is a simple and useful
confirmatory method. Other confirmatory methods include the use of two
or more different gas-liquid chromatographic columns, two independent
detector systems, micro-infrared spectrophotometry and
microcoulometry.
When using highly sensitive electron capture gas-liquid
chromatographic techniques, the detector system must function and be
controlled correctly. It must not give erroneous responses arising
from poor geometric design or incorrectly applied voltage, or from the
use of unsuitable operating conditions such as the wrong choice of
carrier gas, flow-rate or column materials. Column temperature also is
very important since pyrolytic changes can occur and, if not properly
recognized, can lead to erroneous conclusions. Even when such methods
are properly used, some pesticides such as toxaphene, if present in
extracts, may cause difficulty. Toxaphene is a complex mixture of a
large number of similar substances and gives a general and perhaps
variable 'background' response which is not readily amenable to
precise measurement.
Provided all of the above considerations are thoroughly understood, it
is possible for the residue analyst to use sensitive gas-liquid
chromatographic detectors which are virtually specific for phosphorus,
halogen, or sulphur compounds. In some cases the sensitivity may be
adjusted to extend to, or to exclude, other types of residue such as
the triazine or pyrethroid compounds. However, while in skilled hands
the multidetection methods are capable of giving highly accurate
results, they are less easy to specify in operational detail than are
most chemical analytical methods. With gas-liquid chromatography, this
is due in part to various factors which affect the behaviour of a
set-up of apparatus. These factors include the column length and
support material, the amount and nature of the liquid phase, the
column and injection temperatures, the detector design and the voltage
applied to it, the nature and flow rate of the gas phase and the
previous use history of the column system as a whole. Some of these
factors are affected by the design and model of the gas chromatograph.
For this reason the monographs do not contain detailed specifications
of such methods; although in appropriate cases general statements of
the nature and capabilities of the methods are given. For general
guidance to these methods and their capability and limitations, see
Cook and Williams (1965) and Williams and Cook (1967); and for thin
layer chromatography, Abbott and Thomson (1965).
Bioassay methods are recognized as being useful for research purposes
and an screening tests for the presence of pesticide residues and in
conjunction with other confirmatory procedures. As they are
non-specific, however, their uses are limited.
3. Methods for Residues of Organochlorine Pesticides
Methods of organochlorine residue analysis have been reviewed by
Beynon and Elgar (1966); thin layer chromatographic methods have been
reviewed by Abbott et al (1964 and 1965). Until a few years ago, the
only methods available for the detection and determination of
organochlorine pesticide residues were insensitive and lacked
specificity. With the development of modern quantitative
chromatographic methods it has become possible to isolate and detect
the principal organochlorine pesticides, together with a number of
their decomposition products, in sub-microgram quantities. Indeed the
most sensitive gas chromatographic methods now enable the skilled
residue analyst to measure down to a picogram (one million millionth
of a gram) of pesticide in favourable cases. An efficient cleanup
stage is essential in all quantitative chromatographic methods;
layer chromatography itself is a valuable cleanup technique. Some of
the important considerations when using these methods are indicated in
section (2) on 'Multidetection Systems'. For the most effective use of
a gas chromatograph for the organochlorine compounds the samples
should be cleaned up well enough so that the pen of the chart recorder
returns to very near the baseline within one minute of the sample
injection. In the absence of residues of toxaphene the pen should
return to the baseline between many of the individual eluting
compounds, such as lindane, aldrin, heptachlor, etc. The injection of
only one uncleaned extract may cause conversion of p,p'-DDT to a
series of compounds which elute earlier than p,p'-DDT and may even
appear to be heptachlor. If an essentially straight baseline to the
chart record is not obtained, sensitivities may be one-half or less of
the values indicated in the individual monographs for organochlorine
compounds. An extended account of the application of gas-liquid
chromatographic methods of residue analysis to organochlorine
pesticides has been compiled for the U.S. Food and Drug Administration
by Berry, et al (1967).
4. Methods of Analysis for Organophosphorus Compounds
Methods of organophosphorus pesticide residue analysis have been
reviewed by Abbott and Egan (1967). Generally, the wet chemical
methods for the organophosphorus pesticide chemicals are limited to
residues of about 0.1-0.2 ppm or above, and some are not useful in
determining oxygen analogs or other metabolic products.
The procedure outlined by Barry, et al (1967) for the organochlorines
will detect and measure a number of the parent organophosphorus
compounds such as parathion, methyl parathion, diazinon, malathion and
ethion. The development of multidetection schemes for residues of the
organophosphorus pesticides (which include the significant metabolic
products) for use for monitoring food products of unknown spray
history is very important. However, the development of such schemes
for the organophosphorus pesticides has proved to be considerably more
difficult than for the organochlorine pesticides. The organophosphorus
compounds have a much wider spectrum of polarities and have a much
greater propensity to convert to more polar yet toxic residues. Thin
layer and paper chromatography have been utilized for some time in
studying methods of analysis. Since the development of detectors for
gas chromatography which are highly sensitive and selective for
phosphorus compounds (Giuffrida (1964); Hartmann (1966); Brody and
Chaney (1966)), there has been considerable work in gas chromatography
on these compounds. (For a review of both subjects see Williams and
Cook (1967)).
Even though much work has been done, no single procedure of
extraction, cleanup and determinative step has emerged which has been
proved to yield both quantitative recovery and qualitative separation
of a number of the parent compounds in food, especially total diets.
However, some schemes appear very promising and it is expected that
the supporting data will become available in the near future. One of
the schemes is the extraction of Watts and Storherr (1965) and the
column cleanup of Storherr et al (1964). The column, consists of 14 g
of an absorbent mix containing 1 part Norit S G Extra (acid washed in
lab), 2 parts hydrated MgO (Mills), and 4 Parts celite. The column is
eluted with 300 mls of 25 per cent ethylacetate in benzene. This is
concentrated to a small volume and aliquots are chromatographed either
by gas or thin layer. The KCI thermionic detector to utilized
following chromatography on (1) 10 per cent DC 200 on Gas Chrom Q-ABS
or (2) 2 per cent diethylene glycol succinate on the same support. A
number of organophosphorus pesticide chemicals and some of their
oxygen analogs have been added to blank kale samples and analyzed by
the above procedure. Demeton-S-sulfoxide, demeton-S-sulfone and
phorate-S-sulfone have been shown to be extracted, etc., by the same
procedure, but the purity of the sample was not high enough to judge
efficiency of the process.
For guthion, oxygen analog of guthion, and Ruelene (R), the succinate
column must be used and dimethoate and its oxygen analog are much
better chromatographed on the succinate column.
5. Methods of Fumigant Residue Analysis
Earlier methods of analysis for residues of unchanged fumigants mainly
involved classical chemical techniques; they are time-consuming to
perform and are neither very specific nor very sensitive.
The possibility of using gas-liquid chromatography for the detection
and determination of unchanged fumigants has been investigated in
recent years. Such analytical methods are in general far more
sensitive than the earlier classical methods, as well as being more
specific. Of the fumigants, carbon tetrachloride has the greatest
electron capture affinity, a sensitivity some 200 times greater than
that for ethylene dichloride. For this reason, small amounts of carbon
tetrachloride will tend to mask moderate amounts of other halogenated
fumigants when these methods are used. It should, however, be quite
possible to perfect rapid multidetection systems for unchanged
fumigant residues by such methods and it is important to do this. In
the meantime, recommendations for alternative methods are made.
Note to the reader
Any comments on evaluations for tolerances should be addressed to :
Crop Protection Branch
Plant Production and Protection Division
Food and Agriculture Organization
Rome, Italy
Any comments on evaluations for acceptable daily intakes should be
addressed to :
Food Additives Unit
World Health Organization
Geneva, Switzerland
REFERENCES
Abbott, D.C., Egan, E., and Thomson, J. (1964) Thin layer
chromatography of organochlorine pesticides. J. Chromatography 16,
481-487.
Abbott, D.C. and Thomson, J. (1965) The application of thin layer
chromatographic techniques to the analysis of pesticide residues.
Residue Reviews 11, 1-59.
Abbott, D.C. and Egan, H. (1967) Organophosphorus pesticides residue
analysis: a review. Analyst 92, 475-492.
Barry, H.C., Hundley, J. and Johnson, L.V. (1967) Pesticide Analytical
Manual, Vol. 1., (Revised 1967) U.S. Food and Drug Adm., Washington,
D.C.
Beynon, I. and Elgar, K.E. (1966) Organochlorine pesticide residue
analysis: a review. Analyst 91, 143-175.
Brody, S.S. and Chaney, J.E. (1966) The application of a specific
detector for phosphorus and sulfur compounds - Sensitive to
subnanogram quantities. J. Gas Chromatography 4, 42-46.
Cook, J.W. and Williams, S. (1965) Pesticide Residues. Anal. Chem.
37, 131R-142R
FAO/WHO. (1965) Evaluation of the toxicity of pesticide residues in
food. FAO Mtg. Rept. PL/1965/10; WHO/Food Add./26.65.
FAO/WHO. (1968) Report of the 1967 Joint Meeting of the FAO Working
Party and WHO Expert Committee on Pesticide Residues. FAO Mtg. Rept.
No. PL:1967/M/11; WHO Technical Report Series No. 391.
Giuffrida, L. (1964) A flame ionization detector highly selective and
sensitive to phosphorus - A sodium thermionic detector. J. Assoc. Off.
Agr. Chem. 47, 293-300.
Gunther, F.A. (1962-present) Residue Reviews. Springer Verlag,
Berlin-Heidelberg-New York
Hartmann, C.H. (1966) Phosphorus detector for pesticide analysis.
Bull.Envir. Contam. Toxicol. 1, 159-168.
Storherr, R.W., Getz, M.E., Watts, R.R., Friedman, S.J., Erwin, F.,
Giuffrida, L., and Ives, R. (1964) Identification and analysis of five
organophosphorus pesticides: Recoveries from crops fortified at
different levels. J. Assoc. Off. Agr. Chem. 47, 1087-1093.
Watts, R.R. and Storherr, R.W. (1965) Rapid extraction method for
crops. J. Assoc. Off. Agr. Chem. 48, 1158-1160.
Williams, S and Cook, J.W. (1967) Pesticide Residues. Anal. Chem.
39, 142R-157R.