General properties: Technical-grade hexaehlorocyclohexane (HCH) consists of 65-70% alpha-HCH, 7-10% beta-HCH, 14-15% gamma-HCH, and approximately 10% of other isomers and compounds. Lindane contains and gt; 99% gamma-HCH. It is a solid, with a low vapour pressure, and is poorly soluble in water but very soluble in organic solvents, such as acetone, and in aromatic and chlorinated solvents. The n-octanol/water partition coefficient (log Pow) is 3.2-3.7. Environmental transport, distribution and transformation: Lindane is strongly adsorbed on soils that contain a large amount of organic matter; furthermore, it can move downward through the soil with water from rainfall or artificial irrigation. Volatilizalion appears to be an important route of its dissipation under the high-temperature conditions of tropical regions. Lindane undergoes rapid degradation (dechlorination) in the presence of ultra-violet irradiation, to form pentachlorocyclohexenes (PCCHs) and tetrachlorocyclohexenes (TCCHs). When lindane undergoes environmental degradation under humid or submerged conditions and in field conditions, its half-life varies from a few days to three years, depending on type of soil, climate, depth of application and other factors. In agricultural soils common in Europe, its half-time is 40 70 days. The biodegradation of lindane is much faster in unsterilized than in sterilized soils. Anaerobic conditions are the most favourable for its microbial metabolization. Lindane present in water is degraded mostly by microorganisms in sediments to form the same degradation products. Limited amounts of lindane and gamma-PCCHs are taken up by and translocated into plants, especially in soils with a high content of organic matter. Residues are found mainly in the roots of plants, and little, if any, is translocated into stems, leaves or fruits. Rapid bioconcentration takes place in microorganisms, invertebrates, fish, birds and humans, but biotransformation and elimination are relatively rapid when exposure is discontinued. In aquatic organisms, uptake from water is more important than uptake from food. The bioconcentration factors in aquatic organisms under laboratory conditions ranged from approximately 10 up to 6000; under field conditions, the bioconcentration factors ranged from 10 to 2600. Effects on organisms in the environment: Lindane is not very toxic for bacteria, algae, or protozoa: I mg/litre was generally the no-observed effect level (NOEL). Its action on fungi is variable, with NOELs varying from 1 to 30 mg/litre depending on the species. It is moderately toxic for invertebrates and fish, the L(E)C50 values for these organisms being 20-90,ug/litre. In short-term and long-term studies with three species of fish, the NOEL was 9 ug/litre; no effect on reproduction was seen with levels of 2.1-23.4 ug/litre. The LC50 values for both freshwater and marine crustacea varied between 1 and 1100 ug/litre. Reproduction in Daphnia magna was depressed in a dose-dependent fashion; the NOEL was in the range 11-19 ug/litre. Reproduction of molluscs was not adversely effected by a dose of 1 mg/litre. The LD50 for honey-bees was 0.56 ug/bee. Acute oral LD50 values for a number of bird species were between 100 and 1000 mg/kg body weight. In short-term studies with birds, doses of 4-10 mg/kg diet had no effect, even on egg-shell quality. Laying ducks treated with doses of lindane up to 20 mg/kg body weight, however, had decreased egg production. Bats exposed to wood shavings that initially contained 10 866 mg/m2 lindane, resulting from application at the recommended rate, all died within 17 days. No data were available on effects on populations and ecosystems. Effects on experimental animals and in vitro: The acute oral toxicity of lindane is moderate: the LD50 for mice and rats is in the range 60-250 mg/kg body weight, depending on the vehicle used. The dermal LD50 for rats is approximately 900 mg/kg body weight. Toxicity was manifested by signs of central nervous system stimulation. Lindane does not irritate or sensitize the skin; it is slightly irritating to the eye. In a 90-day study in rats, the NOEL was 10 mg/kg diet (equivalent to 0.5 mg/kg body weight). At 50 and 250 mg/kg diet, the weights of the liver, kidneys, and thyroid were increased; at 250 mg/kg diet, an increase was seen in liver enzyme activity. This increase in enzyme activity accelerates the breakdown of both lindane and other compounds. In another 90-day study in rats, 4 mg/kg diet (equivalent to 0.2 mg/kg body weight) was considered to be the no-observed-adverse-effect level (NOAEL); renal and hepatic toxicity were observed at concentrations of 20 mg/kg diet and higher. A short-term toxicity study in mice was considered to be inadequate to establish a NOEL. Administration of lindane to dogs at 15 mg/kg in the diet (equivalent to 0.6 mg/kg body weight) for 63 weeks had no toxic effect. In a two-year study of the toxicity of this compound in dogs, in which a large number of parameters were measured, no treatment-related abnormality was apparent at doses of 50 mg/kg diet (equivalent to 2 mg/kg body weight) and lower. In the group given 100 mg/kg diet, however, levels of alkaline phosphatase were increased; and with 200 mg/kg diet, abnormalities in electroencephalogram tracings indicative of non-specific neuronal irritation were observed. In rats exposed by inhalation to lindane at 0.02 4.54 mg/m3 for 6 h/day for 3 months, the highest dose induced increases in hepatic cytochrome P450 values; the NOAEL was found to be 0.6 mg/m3. In two long-term studies in rats, carried out many years ago, doses of 10 1600 mg/kg diet were tested. In one of these studies, 50 mg/kg diet (equivalent to 2.5 mg/kg body weight) was found to be the NOAEL. At 100 mg/kg diet, an increase in liver weight, hepatocellular hypertrophy, fatty degeneration, and necrosis were found. In the other study, 25 mg/kg diet (equivalent to 1.25 mg/kg body weight) had no effect, but hepatocellular hypertrophy and fatty degeneration were seen with 50 mg/kg diet. Lindane has been investigated for its effects on all aspects of reproduction (in rats over three generations) and for its embryotoxicity and teratogenicity after oral, subcutaneous and intraperitoneal administration in mice, rats, dogs, and pigs. It had no teratogenic effect after oral or parenteral administration (extra ribs were regarded as variations). Fetotoxic and/or maternal toxic effects were observed with doses of 10 mg/kg body weight and above given by oral gavage; S mg/kg body weight is considered to be the NOAEL. Lindane had no effect on reproduction or maturation in the three-generation study in rats at doses of up to 100 mg/kg diet; but with 50 mg/kg diet, morphological changes in the liver indicating enzyme induction occurred in the offspring of the third generation. The NOEL in this test was 25 mg/kg diet (equivalent to 1.25 mg/kg body weight). The NOEL for neurotoxicity in a 22-day study in rats was 2.5 mg/kg body weight. The mutagenicity of lindane has been studied adequately. In extensive investigations of its ability to induce gene mutations in bacteria and in mammalian cells, and for its capacity lo induce sex-linked recessive lethal mutations in Drosophila melanogaster, negative results were obtained consistently. Lindane also gave negative results in tests for chromosomal damage and sister chromatid exchange in mammalian cells in vitro and in vivo. The results of assays for DNA damage in bacteria and for covalent binding lo DNA in the liver of rats and mice in vivo following oral administration were also negative. In the very few studies in which positive results were obtained, either the study design was invalid or the purity of the compound tested was not reported. Overall, however, lindane appears to have no mutagenic potential. Studies to define the carcinogenic potential of lindane have been carried out in mice and rats using dose levels of up to 600 mg/kg diet in mice and up to 1600 mg/kg diet in rats. Hyperplastic nodules and/or hepatocellular adenomas were found in mice given doses of 160 mg/kg die or more; in some studies, the dose levels exceeded the maximum tolerated dose. Two studies in mice with dose levels of up to 160 mg/kg diel and one in rats with 640 mg/kg diet showed no increase in the incidence of tumours. The results of studies on initiation-promotion of carcinogenicity, on the mode of action, and on mutagenicity indicate that the tumorigenic response observed with gamma-HCH in mice is mediated by a nongenetic mechanism. Effects on humans Several cases of fatal poisoning and of non-fatal illness caused by lindane have been reported, which were either accidental, intentional (suicide), or due to gross neglect of safety precautions or improper uses of medical products containing lindane. Symptoms included nausea, restlessness, headache, vomiting, tremor, ataxia, tonic-clonic convulsions and/ or changes in the electroencephalographic pattern. These effects were reversible after discontinuation of exposure or symptomatic treatment. Notwithstanding extensive use over 40 years, very few cases of poisoning in the occupational setting have been reported. In workers exposed for long periods during either manufacture or application of lindane, the only sign found was increased activity of drug-metabolizing enzymes in the liver. There is no evidence for the relationship suggested in some publications between exposure lo lindane and the occurrence of blood dyscrasias. A few acute and short-term studies in humans indicate that a dose of approximately 1.0 mg/kg body weight does not induce poisoning; however, a dose of 15-17 mg/kg body weight resulted in severe toxic symptoms. Approximately 10% of a dermally applied dose is absorbed, although more passes through damaged skin.