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LINDANE

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Indentification numbers
      1.4.1 CAS
      1.4.2 Other numbers
   1.5 Main Brand Names/Trade Names
   1.6 Main Manufacturers/ Main Importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the Substance:
   3.2 Chemical Structure
   3.3 Physical Properties
      3.3.1 Colour
      3.3.2 State/Form
      3.3.3 Description
   3.4 Hazardous Characteristics
4. USES
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description of use
   4.2 High risk circumstance of poisoning
      4.2.1 Agricultural uses:
      4.2.2 Application to cattle with bare hands.
      4.2.3 Eating contaminated food.
      4.2.4 Improper use in direct application to scalp or skin, especially in young children.
   4.3 Occupationally exposed population
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
      6.5.1 Inhalation exposure
      6.5.2 Oral exposure
7. TOXICOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   8.1 Methods
   8.2 Toxic concentrations
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systemic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic Nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatologic
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Other
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analysis and other investigations.
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
   10.3 Life supportive procedure and symptomatic/specific treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDTIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), ADDRESS(ES), DATE(S)

International Programme on Chemical Safety

Poisons Information Monograph 859

Chemical

1. NAME

1.1 Substance

Lindane

1.2 Group

Organo-chlorine insecticides

1.3 Synonyms

Gamma-hexachlorobenzene,

1-alpha,2-alpha,3-beta,4-alpha,5-alpha,6-beta-hexachlorocyclohexane, gamma-hexachlorocyclohexane,

1, 2, 3, 4, 5, 6,-hexachlorocyclohexane, gamma-isomer.

Gamma-benzene hexachloride, Lindane, gamma-BHC, ENT 7, 796, Gammahexane, Hexachloran, Gamma-hexacloran, Gamma-hexachlorane.

1.4 Indentification numbers

1.4.1 CAS

58-89-9

1.4.2 Other numbers

NIOSH/ RTECS RH: GV 49 00000

UN 2761

EC 602 -043-00-6

1.5 Main Brand Names/Trade Names

Lindane 1% (Martindale); Lorexane (Care. UK) Cream - Lindane 1%, Shampoo - Lindane 2%; Quellada (Stafford-Miller. UK) Lotion - Lindane 1%, Shampoo (Application PC).

Aphtiria (Debat. Fr); Atan (Switz); Desantin (Fin.Port); Élentol (Aguettant. Fr.); Gambex (Continental Ethicals, S. Afr.); Gamene (USA); Gamma-Col (ICI Plant Protection, UK); Gammasan (ICI Plant Protection, UK); GBH (Rorer, Canad.); Hexicid (Denm.:NAF.Norw.); Inexit (Boehringer IngelheimUK); Jacutin (Hermal. Ger., Neth.; Hermal. Norw.; Hermal. Swed.; Hermal, Switz.); Kwell (Reed & Carnrick, Canad.; Greece, Stafford-Miller, Switz.); Lencid (Belg.); Liceonil (Wilson Pakistan)Lindacol (Boehringer Ingelheim, UK; Shell Chemicals, UK) Nexa Lotte (Boehringer Ingelheim, UK); Quellada (Stafford-Miller, Austral.; Stafford-Miller, S. Afr.; Stafford-Miller, UK); Scabecid (Stiefel, Fr.); Scabene (Stiefel, USA); Skabex (S. Afr.); Yacutin (Igoda, Spain).

The following names have been used for multi-ingredient preparatons containing Lindane- Esoderm (Napp. Uk); Gammalex (ICI Plant Protection, UK); Mergamma (ICI Plant Protection, UK); Sentry (Union Carbide, UK).

Syn: Aalindan, Aficide, Agrisol G-20, Agrocide , Agrocide 2, Agrocide 6 G, Agrocide 7, Agrocide 111, Agrocide WP, Agronexit, Ameisenmittel Merck, Ameisentod, Aparasin, Aphtiria, Aplidal, Arbitex, BBH, Ben-Hex, Bentox 10, benzene Hexachloride-Gamma Isomer, gamma Benzene Hexachloride, Bexol, BHC, Gamma-BHC, Calanex, Chloresene, Codechine, DBH, Detmol-Extrakt, Detox 25, Devoran, Dol Granule, Drill Tox-Spezial Aglukon, Ent 7, 796, Entomoxan, Forlin, Gamacid, Gamaphex, Gammahexa, Gammahexane Gammalin, Gammalin 20, Gammaterr, Gammex, Gammexane, Gammopaz, Gexane, HCCH, HCH, Gamma-HCH (ISO), Heclotox, Hexachlorane, Gamma-hexachlorane Gamma-Hexachlorocyclobenze, Gamma- hexachlorocyclohexane, 1, 2, 3, 4, 5, 6- Hexachlorocyclohexane, Gamma Isomer, Gamma 1, 2, 3, 4, 5, 6 - Hexachlorocyclohexane, 1 alpha, 2 alpha, 3 beta, 4 alpha, 5 alpha, 6 beta- Hexachlorocyclohexane (CAS), Hexaklor, Hexatox, Hexaverm, Hexicide, Hexcyclan, HGI Hortex, Isotox, Jactin, Kokotine, Kwell, Lendine, Lentox, Lidenal, Lindafor, Lindafor 90, Lindagam, Lindamul 20, Lindane, Lindane(DOT), Gamma- Lindane, Lindatox, Lindosep, Lintox, Lorexane, Malaoxon, Milbol 49, Mszycol, NCI-C00204, Neo-Scabicidol, Nexen FB, Nexit, Nexit, Nexit-Stark, Nexit-Staub, Nexol-E. Nicochlora, Nicochloran, Novigam, Omnitox, Ovadziak, Owadziak, Pedraczak, Pelanzol, Prodactic, Quellada, Sang Gamma, Silvanol, Spritz-Rapidin, Spreuhpflanzol, Streunex, Tap 85, Tri-6, Viton, 666

1.6 Main Manufacturers/ Main Importers

Shell Chemicals, ICI Plant Protection, Boehringer Ingelheim, Stafford-Miller, Union Carbide.

2. SUMMARY

2.1 Main risks and target organs

In severe acute cases, stimulation of the central nervous system (CNS) may result in convulsion, cardiovascular collapse, rhabdomyolysis, renal insufficiency, respiratory and metabolic acidosis and death.

2.2 Summary of clinical effects

Nausea, occasionally vomiting, headache, dizziness, excitability, tremor, convulsion, respiratory and metabolic acidosis, increased irritability leading to cardiac dysrythmias, rhabdomyolysis, renal insufficiency and death.

2.3 Diagnosis

Diagnosis is based on the history of exposure and clinical presentation. Persistence of neurological and gastrointestinal disturbances might confirm the diagnosis. Blood levels may only be useful in order to confirm exposure and demonstrate the elimination of the chemical.

2.4 First-aid measures and management principles

Emesis is contraindicated because convulsions may occur soon.

Do not give milk, fat or oils.

Do not administer adrenergic amines, which may increase myocardial irritability.

Control convulsions with appropriate drug regimen (see Convulsions Treatment Guide).

Maintain a clear airway.

Aspirate secretions from airway.

Perform cardio-respiratory resuscitation.

In case of eye contact, irrigate eyes immediately with water or saline.

In case of skin contact, wash skin with copious amount of soap and water.

In case of ingestion, gastric lavage may be indicated; in severe cases, precede endotracheal intubation with a cuffed tube.

Administer activated charcoal.

Cathartics (not mineral oils) may be administered.

Monitor fluid and electrolyte balance.

Monitor acid-base balance.

3. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the Substance:

Synthetic

3.2 Chemical Structure

Chemical name: gamma - hexachlorocyclohexane

Structural formula

Molecular formula: C6H 6Cl6

Molecular weight: 290.83

Structural name: gamma 1,2,3,4,5,6 hexachlorocyclohexane

cis/trans relationship of Cl constituents = 1,2,4,5/3,6

3.3 Physical Properties

3.3.1 Colour

white, crystalline

3.3.2 State/Form

solid

3.3.3 Description

slightly musty odour

Melting Point

112.5C

Vapour Pressure

9.4 10-6 mmHg at 20C

Density

1.85

Solubility:

Insoluble in water at 20C (10 mg-litre),moderately soluble in ethanol, ether, benzene acetone, slightly soluble in mineral oils.

Stability:

Stable to light, air, heat, carbon dioxide and strong acids. Dechlorination in the presence of alkali or on prolonged exposure to heat. Trichlorobenzenes and hydrochloric acid are formed.

3.4 Hazardous Characteristics

Corrosivity:

Corrosive to aluminium

Flammability:

Not flammable

Hazardous combustion products:

on contact with hot surfaces or flames decomposes forming toxic fumes (phosgene, hydrogen chloride, CO).

n-octanol water partition coefficient:

log Pow = 3.61-3.72

(The Merck Index, 1996; ICSC 1993)

4. USES

4.1 Uses

4.1.1 Uses

4.1.2 Description of use

Lindane is a broad-spectrum insecticide, which has been used since 1949 for agricultural as well as non-agricultural purposes. Approximately 80% of the total production is used in agriculture(Demozay & Marechal, 1972), mostly for seed and soil treatment. Wood and timber protection is the major non agricultural use. Its use in being banned in various countries (Weinhold, 2001). It has been banned by the European Union countries for plant protection and California has banned lindane-based products used to treat lice and scabies. In Europe, lindane usage was reduced by two-third between 1970 and 1996 (Breivik, 1999).

Lindane is also used against ectoparasites in veterinary and pharmaceutical products(IPCS, 1991; Ulmann, 1972)

As a pharmaceutical preparation, lindane is an insecticide, larvicide and acaricide. It is used topically in concentrations of 1% for treatment of scabies in selected patients. (Martindale, 1996). It is administered differently in the treatment of scabies and pediculosis. In US, Canada and other countries, lindane is generally not used to treat young children and has been voluntarily withdrawn from the market. Comparative studies revealed that lindane may be slightly less effective than permethrine for the treatment of scabies and pediculosis (Roos, 2001, Elgart, 1996). In a study comparing malathion 0,5 %, lindane 1 % and Nix(R) (permethrine) in a well controlled population of a tropical field station in Panama (Meinking, 2001), lindane shampoo was shown to be the slowest-acting pediculicide and the least effective ovicide.

It is also used for the control of disease vectors including mosquitoes, lice and fleas. (Ulmann, 1972). In the the agricultural area, it is mainly used for the treatment of seeds and soils. Wood and timber protection are major non-agricultural use. (IPCS, 1991).

4.2 High risk circumstance of poisoning

4.2.1 Agricultural uses:

During the filling of tanks, dilution and spraying without adequate personal protection equipment.

4.2.2 Application to cattle with bare hands.

4.2.3 Eating contaminated food.

4.2.4 Improper use in direct application to scalp or skin, especially in young children.

4.3 Occupationally exposed population

5. ROUTES OF EXPOSURE

5.1 Oral

Lindane is rapidly absorbed after ingestion.

5.2 Inhalation

A harmful contamination of the air can be reached very quickly on evaporation of lindane at 20C.

Studies done in various levels of exposure groups either at home (by use of vaporizers) or at work (production plants) showed that mean blood lindane levels increase in a rather orderly manner accorded to estimated exposure intensity. (Milby et. al, 1968)

5.3 Dermal

Lindane is readily absorbed through skin.(Feldmann & Maibach, 1970, 1974). Children have been reported to develope acute toxicity after total body application of 1% lindane (Kwell, Kwellada). A single application of lindane to nineteen geriatric inpatients because of an outbreak of scabies, resulted in seizure in three of them (Tenenbein, 1990). An HIV-seropositive patient also suffered from tonic-clonic seizure after a sigle application of 1% lindane lotion in a hospital ward (Solomon et. al, 1995).Surprisingly, immediate washing to prevent absorption seemed to increase absorption instead of reducing it. (Lange et. al, 1981). Comparative percutaneous absorption of permethrine 5 % cream and 1 % lindane for the treatment of scabies was studied and showed permethrine to be at least 40 times less likely to cause toxic effects (Frantz et. al, 1996).

5.4 Eye

No data available.

5.5 Parenteral

No data available.

5.6 Other

No data available.

6. KINETICS

6.1 Absorption by route of exposure

Lindane, either as a pharmaceutical or a pesticide, is easily absorbed by ingestion. (Davies, 1983; Jaeger, 1984, Kurt, 1986, Munk & Nantel, 1977). It is also well absorbed following skin application. (Lange et. al, 1981; Ginsburg, 1977; Rasmussen, 1981). It may also be absorbed by inhalation especially in workers or in home use of vaporizing devices. (Angerer et. al, 1983; Milby et. al, 1968).

6.2 Distribution by route of exposure

Lindane is almost insoluble in water but highly soluble in lipids. It has been detected in blood and adipose tissue of the general population in various regions of the world. The distribution of lindane is related to the proportion of fatty tissue of various organs. The adipose tissue is followed by brain, kidney,, muscle, lungs, heart, spleen, liver, and blood. (USPHS, 1989).

After ingestion lindane is rapidly absorbed and distributed. In rats, after oral administration over 10 days, 35% of the administered dose was deposited in the fatty tissue. After a single oral dose, the fat/blood ratio ranged 145-206 and the brain/blood ratio 4-6.5 (IPCS, 1991).

6.3 Biological half-life by route of exposure

In man, after acute exposure, shows a short serum half-life before redistribution to fat and other tissue storage sites (Sunder Ram Rao et. al, 1988). In one clinical case they describe, a peak serum lindane level of 1.3 ?g/ml was measured 12 hours after ingestion. It has decreased to 0.8 ?g/ml 36 hours after ingestion. A review of the literature (Aks et. al, 1995) shows an initial rapid half-life phase after acute ingestion (distributive) and a delayed elimination phase. The latter phase is comparable to the half-lives found in cases of toxicity due to dermal absorption. (ATSDR, 1994).

6.4 Metabolism

As most organochlorines, lindane is slowly metabolised through four possible reactions.

Liver transformation produces a large number of metabolites which are still imperfectly identified. It is metabolised through cytochrome P-450 dependent enzymes. Nowadays more than 80 lindane metabolites of different chemical structure and relevance are known. (Macholz & Kujawa, 1985).

One can conclude that the essential steps of the metabolism of lindane are known today. (IPCS , 1991). Lindane also induces hepatic mixed function oxidase systems, increasing its own metabolism (Van Ert & Sullivan, 1992).

6.5 Elimination and excretion

6.5.1 Inhalation exposure

Humans excrete gamma-HCH and its metabolites in urine, milk, and semen(Angerer et. al, 1981). Chromatographic analysis of urinefrom humans occupationally exposed to HCH showed the presence of chlorinated phenols and all isomers of di-, tri-, and tetrachlorophenol (Angerer et. al, 1981; Balikova et. al,1988).

6.5.2 Oral exposure

Excretion of gamma-HCH and its metabolites in laboratory animals has been well documented. Data indicate that its major route of elimination is via the urine following intermediate and chronic oral feeding in mice. Very little is eliminated in exhaled air and in feces following acute, intermediate, and chronic oral administration in rodents. (ATSDR, 1994).

Very little gamma-HCH is excreted unaltered. Various phenylmercapturic acid derivatives have been detected in urine of rats, formed by the conjugation of gamma-HCH metabolites with glutathione subsequent to dechlorinations and dehydrochlorinations. In vitro investigations using rat liver cells showed gamma-HCH and alpha-HCH are readily conjugated. gamma-HCH derivatives are not only excreted in the form of glucronides and sulfate conjugates, but also into glutathione derivatives. (ATSDR, 1994).

7. TOXICOLOGY

7.1 Mode of action

Lindane exerts its toxicity mainly by stimulation of the central nervous system.(Joy, 1982).

A direct effect on striated muscle (rhabdomyolysis) has been demonstrated in humans(Munk & Nantel, 1977). At high doses, it may also affect vascular endothelial lining (disseminated intravascular coagulation)(Sunder Ram Rao et. al, 1988; West, 1967).

In the nervous system, gamma-HCH is thought to interfere with the gamma-aminobutyric acid (GABA) system by interacting with the GABA-A receptor-chloride channel complex at the picrotoxin binding site. Thus the seizures caused by gamma-HCH can be antagonized by GABA-A mimetics. Other suggestive data concerning mechanisms by which HCH causes neurological effects in animals includes enhanced synaptic activity, altered GABA functional activity, and inhibition of Na+-K+-ATPase. (ATSDR, 1994, Ratra et. al, 2001).

In the liver, gamma-HCH is thought to act by interfering with hepatic oxidative capacity and glutathione metabolism. Another possible mechanism for hepatic toxicity is the increased lipid metabolism. Inhibition of Mg2+ATPase activity has been observed in rat liver tissue, suggesting an ATPase enzyme sensitivity to the action of gamma-HCH. The researchers suggested that some toxic effects appearing in mammals as a result of gamma-HCH exposure may arise from its influence on this ATPase activity. (ATSDR, 1994).

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

The fatal dose in adult is approximately 10 to 30 g; doses of 1.6 and 45 g are capable of producing seizures in young children and adults, respectively. Death have been associated with serum lindane concentration of 1.3 mcg/mL (Kurt et al, 1986).

Serum lindane concentration up to 0.60 mcg/mL have resulted in seizure, acidosis, muscle weakness, acute renal failure, myoglobinuria and hypertension.

7.2.1.2 Children

Ingestion involving 150 - 450 mg of lindane have been shown to be responsible for several symptoms including headache, dizziness, nausea, lethargy and sometimes followed by seizures (Kurt et a, 1986).

Muscle tone and posturing may appear after 1 or 2 days dermal exposure of lindane. Seizures can also occur with such exposure. Few applications of lindane may pose some risk of toxicity (see section 11.1: Illustrative Cases)

Sub-chronic dermal and oral exposure combined have resulted in vomiting and seizures (Lee et al., 1976; Wheeler, 1977).

Jaeger et. al (1984) reported the following cases (adult and children) of a lindane-solvent mixture:

AGE

AMT OF MIXTURE

SYMPTOMS

ONSET

(yrs)

(g)

 

 

21

100

Vomiting

30 min

 

 

Refractory

 

 

 

Seizures

90 min

 

 

Rhabdomyolysis

 

42

100

Seizures

30 min

 

 

Coma

 

 

 

Pulmonary oedema

 

4

10

Vomiting

30 min

 

 

Seizures

 

3.5

10

Vomiting

 

 

 

Agitation

 

 

 

Seizures

2 hr

3

5-10

Vomiting

15 min

 

 

Seizures

 

7.2.2 Relevant animal data

The acute oral toxicity (LD50) of lindane in different species, depending on the vehicle used, ranges from 56 to 480 mg/kg body weight. Preparations in oil were more toxic than aqueous solutions or suspensions. The ranges for rats and mice were similar(88-270 and 56-246 mg/kg, respectively). The dermal LD50 for rats is approximately 900 mg/kg body weight, but smaller amounts (60 mg/kg as a 1% cream) caused convulsions, anorexia, and deaths in weanling rabbits. No skin irritation or sensitization was observed, and eye irritation was slight.

Although older, long-term studies in the rat suggest a no-observed-adverse-effect level of 25 mg/kg diet, contemporary short-term studies in rats indicate that this level is 10 mg/kg diet, equivalent to 0.75 mg/kg body weight on the basis of increased hepatic, renal, and thyroid weights, increased cytochrome P-450 activity and histopathological findings in liver and kidneys.

7.2.3 Relevant in vitro data

No data available.

7.2.4 Workplace standards

- TLV-TWA: 0.5 mg/m3 (ACGIH, 1995)

- PEL-TWA: 0.5 mg/m3, (skin designation) (OSHA, 1992)

7.2.5 Acceptable daily intake

FAO/WHO, 1978: 0,008 mg/kg body weight, based upon a no observed adverse effect level (NOAEL) of 0,33 mg/kg/day in an 18 weeks study in the rat diet (IRIS, 1997).

The lowest observed adverse effect level (LOAEL) of 1.55 mg/kg/day has been established based on the hypertrophy of the liver and degenerative lesions of the renal tubules (IRIS, 1997). The current RfD for lindane is 3 10-4 mg/kg/day (U.S. EPA, 1998) based on a NOAEL of 0.33 mg/kg/day for liver and kidney toxicity in rats exposed for 12 weeks and an uncertainty factor of 1000 (for use of a subchronic study, to account for interspecies variation and to protect sensitive human subpopulations) (Teuschler et al, 1999).

7.3 Carcinogenicity

Possible carcinogen in human (class 2B) (IARC, 1991)

7.4 Teratogenicity

Large doses studies in animals revealed no evidence of fetal toxicity (ATSDR, 1994).

7.5 Mutagenicity

Negative findings were found in studies on the induction of gene mutation using both Salmonella Typhimurium and Escherichia Coli strains of bacteria (ATSDR, 1994).

7.6 Interactions

Lindane may have additive effects with malathion rather than a synergystic effect after skin application to guinea pigs (Dikshith et al, 1978)

Lindane will interact with other substances which are capable of inducing hepatic enzymes (eg. phenobarbital) (ATSDR, 1994).

Lindane preparations are sometimes marketed in solutions of organic solvents. This combination increases the risk of chemical pneumonitis. Pulmonary oedema has been described after the ingestion of such a preparation (Jaeger et al, 1984).

8. TOXICOLOGICAL ANALYSIS AND
BIOMEDICAL INVESTIGATIONS

(To be reviewed by the analytical group)

8.1 Methods

Gas chromatographic procedures using electron-capture detectors are available for the quantification of lindane in serum and other biological materials. HPLC and GC/MS techniques are also used in specialized laboratories.

8.2 Toxic concentrations

In a study in workers exposed to lindane, (Milby, 1968) showed blood levels of 0.3 ng/mL (ppb) in controls; 0.46 ng/mL in home vaporizer exposure and between 0.3 ppb (limit of detection) to 30.6 ng/mL according to the increasing level of exposure. In an adult who ingested contaminated broccoli and who developed severe convulsions, rhabdomyolysis and renal insufficiency, the serum level of lindane was shown to be 600 ng/mL (Munk & Nantel, 1977).

After the ingestion of one cup (250 mL) of Kwell (1% lindane) an adult male developed convulsions and aspirated while vomiting. With the administration of cholestyramine his lindane blood concentration decreased from 1.3 ?g/mL the first day to 0.11 ?g/mL the fifth day. He died nine days post ingestion. (Kurt et al, 1986).

In one case of death by disseminated intravascular coagulation (Sunder Ram Rao et al, 1988) observed the following lindane serum levels:

TIME AFTER INGESTION
(hours)

SERUM LINDANE
?g/mL

12

1.30

30

0.93

36

0.80

48

0.31

A 16 year old mentally retarded boy ingested a 392 bottle of 1% lindane. He developed status epilepticus but survived after treatment. His lindane serum levels went from 206 ng/mL to 7.5 ng/mL 18 hours after ingestion. (Davies, 1983).

In topical application to healthy volunteers and scabies patients,(Lange, 1981) showed serum concentration of lindane between 1.8 ng/mL (background) and 8.0 ng/mL in normal volunteers. Scabies showed values ranging between 39 and 425 ng/mL.

In his studies on workers exposed to lindane, (Czegledi-Janko, 1970) showed that in 15 of 17 individuals EEG changes could be recorded at lindane blood concentrations of 20 ng/mL.

9. CLINICAL EFFECTS

9.1 Acute poisoning

The route of absorption (ingestion, inhalation, skin exposure or a combination of these) has little influence on the clinical effects of lindane except for the delay in the appearance of the signs and symptoms.

9.1.1 Ingestion

Nausea, vomiting, hypersalivation, and occasionnally diarhoea may occur. However, convulsions may occur without any previous signs or symptoms (Munk & Nantel, 1977; Jaeger et al, 1984).

9.1.2 Inhalation

There are no reported cases of acute poisoning by lindane through inhalation in the literature. However, it is well absorbed by this route (Milby et al, 1968).

9.1.3 Skin exposure

Convulsions may be the first sign of toxicity after dermal application of lindane in an improper way (Tenenbein, 1991; Rasmussen, 1981).

9.1.4 Eye contact

Lindane is irritant to the eyes.

9.1.5 Parenteral exposure

No data available.

9.1.6 Other

9.2 Chronic poisoning

9.2.1 Ingestion

No data available.

9.2.2 Inhalation

No data available.

9.2.3 Skin exposure

No data available.

9.2.4 Eye contact

No data available.

9.2.5 Parenteral exposure

No data available.

9.2.6 Other

No data avaiable.

9.3 Course, prognosis, cause of death

Mild to moderate exposure may lead to one or a few episodes of convulsions without any other clinical effects and sequelae.

In more severe cases, the complications are related to the severity and duration of the convulsions. Death generally occurs because of disseminated intravascular coagulation (Sunder Ram Rao et al, 1988), brain edema and cardiac arrest. Rhabdomyolysis and renal failure are not generally fatal (Munk & Nantel, 1977; Jaeger et al, 1984; Kurt et al, 1986).

9.4 Systemic description of clinical effects

9.4.1 Cardiovascular

Protracted convulsions may be followed by collapsus and cardiac arrest (Kurt et al, 1986; Davies at al, 1983).

9.4.2 Respiratory

Respiratory depression may be secondary to protracted convulsions (Kurt et al, 1986, Davies at al,1983). Ingestion of mixtures of lindane with hydrocarbon based solvent favour the occurrence of broncho-aspiration pneumonitis (Jaeger et al, 1984).

9.4.3 Neurological

9.4.3.1 CNS

Convulsions, confusion, unconsciousness, and coma represent the main toxic effect of lindane poisoning (Munk & Nantel, 1977, Davies et al, 1983, Kurt et al, 1986, Jaeger et al, 1984, Fisher, 1994). Long-term psychological and neurological complications have been described after a case of severe lindane poisoning (Hall & Hall, 1999).

9.4.3.2 Peripheral nervous system

Paresthesia, hyperreflexia, numbness of extremities have been reported (Jaeger et al, 1984, Davies et al, 1983).

9.4.3.3 Autonomic Nervous system

No data available.

9.4.3.4 Skeletal and smooth muscle

Rhabdomyolysis has been described in a few cases. Electromicroscopy studies suggest a direct effect on muscles.(Munk & Nantel, 1977, Kurt et al, 1986, Jaeger et al, 1984).

9.4.4 Gastrointestinal

Nausea and vomiting, diarrhea have been described.

9.4.5 Hepatic

One case of elevated liver enzymes after acute exposure has been described (IPCS, 1989).

9.4.6 Urinary

9.4.6.1 Renal

Renal insufficiency may occur as a consequence of rhabdomyolysis (Munk & Nantel, 1977, Jaeger et al, 1984, Kurt et al, 1986).

9.4.6.2 Other

No data available.

9.4.7 Endocrine and reproductive systems

Lindane, like other organochlorine insecticides, may have an impact on the course of pregnancies (i.e miscarriages) in certain cases (Gerhard et al, 1998, Konje et al, 1992).

9.4.8 Dermatologic

Concentrated formulation may be irritant to the skin.

9.4.9 Eye, ears, nose, throat: local effects

Irritation may occur.

9.4.10 Haematological

One case of aplastic anemia has been reported after prolonged use of lindane (Rauch et al, 1990).

One case of intravascular coagulation has been reported (Sunder Ram Rao et al, 1988).

Several anecdotal cases of either pancytopenia or aplastic anaemias have been described in patients after repeated exposure by local applications. (IPCS, 1989, Samuels & Milby, 1971 Rauch et al, 1990).

9.4.11 Immunological

No data available.

9.4.12 Metabolic

9.4.12.1 Acid base disturbances

Acidosis may occur secondary to convulsions.

9.4.12.2 Fluid and electrolyte disturbances

No specific fluid and electrolyte disturbances have been reported.

9.4.12.3 Other

No data available.

9.4.13 Allergic reactions

No data available.

9.4.14 Other clinical effects

No data available.

9.4.15 Special risks

No data available.

10. MANAGEMENT

10.1 General principles

In case of ingestion, do not induce vomiting and do not give milk, fat or oils by mouth.

Open and maintain at least one intravenous route.

Control the convulsions (see Convulsion Treatment Guide).

Administer activated charcoal.

Maintain clear airways.

Monitor CPK levels and myoglobinuria.

Atropine and adrenaline should be avoided in case of ECGchanges.

10.2 Relevant laboratory analysis and other investigations.

10.2.1 Sample collection

When feasible, blood should be drawn for either whole blood or serum quantification of lindane. Gastric content may also help in the confirmation of oral ingestion.

In cases of severe convulsions with its complications, organochlorine poisoning should be suspected along with other causes.

10.2.2 Biomedical analysis

Acid-base balance should be monitored if convulsions occurred. Levels of creatinine phosphokinase (CPK) should be controlled for 24-48 hours following severe cases.

Myoglobinuria and renal function should be monitored in the CPK level rises.

10.2.3 Toxicological analysis

Blood or serum lindane levels can be measured using GLC methods. However these laboratory results are seldom necessary for the diagnosis and management of such cases unless we are faced with a severe case of poisoning without any background information.

10.3 Life supportive procedure and symptomatic/specific treatment

Make a proper assessment of airway, breathing, circulation andneurological status of the patient.

Control convulsions using appropriate drug regimen.

Oxygen, intravenous dextrose and thiamine should also be given.

Lidocaine (1mg/kg bw as intravenous infusion followed by 2 - 4 mg/min as continuous infusion) may be indicated in the case of myocardial dysrrhythmias.

Monitor vital signs including ECG changes.

Protect airway in case of convulsions.

10.4 Decontamination

In case of skin contact: Remove and discard contaminated clothing. Wash skin with (soap and)copious amount of water for several minutes.

In case of ingestion, do not induce emesis.

Perform gastric lavage in case of ingestion.

Administer activated charcoal 50 - 100 g and cathartic that has been shown to reduce absorption of lindane.

10.5 Elimination

Enhanced elimination procedures of already absorbed lindane is not indicated.

10.6 Antidote treatment

10.6.1 Adults

No specific antidote available.

10.6.2 Children

No specific antidote available.

10.7 Management discussion

The toxicity of lindane on the haematological system is still open for debate.

Since lindane is present in measurable amounts in the blood, fat and human milk of a large segment of the population, along with PCBs and many other organochlorinated insecticides, interactions and long term effects of these contaminants on human health still need to be studied.

11. ILLUSTRATIVE CASES

(should be added by the author)

11.1 Case reports from literature

ORAL EXPOSURE - Children

A 16 year old boy survived a 392 g ingestion after treatment of apnea and status epilepticus (Ellenhorn, 1997). Seizures occurred in three elderly patients after a single application of lindane lotion 1 % (Tenenbein, 1991).

A 4 year old was given 1 tablespoonful of 1% lindane three times (450 mg) in one day. His symptoms were initial lethargy followed by a seizure(Kurt et al, 1986).

An 8 year old developed vomiting after one tablespoonful of 1% (150 mg) lindane (Kurt et al, 1986).

Three cases of acute toxicity after inadvertent oral administration of lindane in three siblings have been reported (Nordt & Chew(Kurt et al, 1986).

ORAL EXPOSURE - Adult

A 32-year-old female with a history of systemic lupus and seizure disorder controlled with phenytoin accidentally ingested 10-25 ml of a lindane 1% solution. Five minutes later, she vomited and 30 minutes after ingestion she was withnessed to have a generalized seizure of 1-2 minutes duration. (Brunett et. al, 1991).

A 35 year old ate lindane-contaminated broccoli. Thirty minutes later he had a seizure. Subsequently, acidosis, muscle weakness, acute renal failure, myoglobinuria, hypertension and anemia developed. Serum lindane concentration was 0.60 mcg/mL (Munk & Nantel, 1977).

A 16 year old took an unknown amount of 1% lindane. Seizures, coma and respiratory depression developed at an unknown time afterwards. The serum concentration of lindane was 0.206 mcg/mL (Davies, 1983).

A 43 year old woman ingested about 240 mL of 20% lindane. Shortly after ingestion bradycardia, hypotension, seizures, coma and metabolic acidosis developed. At 8 hours post-ingestion DIC was noted. Subsequently rhabdomyolysis, myoglobinuria and acute renal failure developed, resulting in death 11 days after admission (Rao et al., 1988).

A 41 year old took two ounces of 1% (100 mg) lindane orally accidentally. He received ipecac but had a seizure when vomiting. He eventually died of adult respiratory distress syndrome and severe anoxia. His peak serum lindane concentration was 1.3 mcg/mL (Kurt et al, 1986).

A 39 year old ingested three tablespoon of 1% (450 mg) lindane over one day. Her symptoms were headache, dizziness and nausea(Kurt et al, 1986).

A 16 year old mentally retarded boy ingested a 392 bottle of 1% lindane. He developed status epilepticus but survived after treatment. His lindane serum levels went from 206 ng/mL to 7.5 ng/mL 18 hours after ingestion. (Davies et al, 1983).

DERMAL EXPOSURE - Children

An 18-month-old boy was treated prophylactically for scabies by an application of lindane lotion from neck to toes one night followed by washing off the next morning. The following night, lindane was again applicated but the morning bath was forgotten. About 12 hours later, he had a generalized seizure lasting 30 minutes. (Telch, 1982).

A 4 month old had one total body application of 1% lindane. Twenty-four hours later he was found to have increased muscle tone and posturing indicating a possible seizure. Serum lindane concentration 46 hours after the application was 0.10 mcg/mL (Pramanik, 1979).

A 2 month old was found dead. In retrospect, it as determined that a total body application of 1% lindane had been used once 24 hours prior to this. Post mortem serum lindane concentrations were 0.033 mcg/mL. It is doubtful whether this case represents lindane toxicity (Davies, 1983).

An eleven year-old child who had been treated on a constant dose of dextroamphetamine for over one year for Attention Deficit Hyperactivity Disorder (ADHD) with good tolerance, experienced several seizures following the use of lindane for head lice (Cox, 2000).

MIXED ORAL AND DERMAL EXPOSURE - Children

A 13 month old received total body applications of 1% lindane daily for 2 weeks. She was given approximately 50 mg of lindane orally following which she had a seizure (Lee et al., 1976).

A 1 year old was given 14 daily total applications of 1% lindane followed by accidental oral administration of 5 ml of 1% lindane. This resulted in vomiting. A focal seizure occurred 12 hours later followed by coma and hypotonia (Wheeler, 1977).

12. ADDTIONAL INFORMATION

12.1 Specific preventive measures

No data available.

12.2 Other

No data available.

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14. AUTHOR(S), REVIEWER(S), ADDRESS(ES), DATE(S)

Author:

Dr A.J. Nantel
Institut national de santé publique du Québec

Peer Review:

Sjazewski, Turk, Groszek, Adamis, Lubomirov, Besbelli
13th. November 1996 Erfurt

Reviewed by author:

august 2001

Peer Review Update:

Awang R; Besbelli N, Caldas, LQA;
17th. September 2001, Edinburgh



    See Also:
       Toxicological Abbreviations
       Lindane (EHC 124, 1991)
       Lindane (HSG 54, 1991)
       Lindane (ICSC)
       Lindane (FAO Meeting Report PL/1965/10/1)
       Lindane (FAO/PL:1967/M/11/1)
       Lindane (JMPR Evaluations 2002 Part II Toxicological)
       Lindane (FAO/PL:1968/M/9/1)
       Lindane (FAO/PL:1969/M/17/1)
       Lindane (WHO Pesticide Residues Series 3)
       Lindane (WHO Pesticide Residues Series 4)
       Lindane (WHO Pesticide Residues Series 5)
       Lindane (Pesticide residues in food: 1977 evaluations)
       Lindane (Pesticide residues in food: 1978 evaluations)
       Lindane (Pesticide residues in food: 1979 evaluations)
       Lindane (Pesticide residues in food: 1989 evaluations Part II Toxicology)
       Lindane (Pesticide residues in food: 1997 evaluations Part II Toxicological & Environmental)
.