NA Lindane (1,2,3,4,5,6Hexachlorocyclyhexane) [factsheet]

1,2,3,4,5,6-HEXACHLOROCYCLYHEXANE (all stereo isomers)

(LINDANE)

Please Note: The main source of information for this fact sheet is the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for a -, g -, and d -, Hexachloro-cyclohexane and EPA's Integrated Risk Information System (IRIS), which contains information on oral chronic toxicity and the RfD. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure

* The most probable route of lindane exposure in humans is oral ingestion of food containing the insecticide. (1)

* Lindane may be released to the air during its formulation, from wind erosion of contaminated soil, or from release from hazardous waste sites. (1)

* Lindane has been detected in groundwater and surface water samples collected near hazardous waste sites; however, the chemical has only very rarely been detected in drinking water supplies. (1)

* Lindane has been listed as a pollutant of concern to EPA's Great Waters Program due to its persistence in the environment, potential to bioaccumulate, and toxicity to humans and the environment. (2)

Assessing Personal Exposure

* Lindane can be measured in the blood, urine, and semen of exposed individuals by gas chromatography. (1)

Health Hazard Information

Acute Effects:

* Acute inhalation exposure to lindane in humans has resulted in irritation of the nose and throat, effects on the blood (anemia), and skin effects (elevated itchy patches of skin). (1,3)

* The major effects noted from oral exposure to lindane in humans are effects on the nervous system, such as seizures and convulsions. Effects on the cardiovascular, gastrointestinal, and musculoskeletal systems have also been reported. (1,3)

* Oral studies in animals have reported effects on the liver, kidney, immune, and nervous systems from acute lindane exposure. (1,3)

* Acute (short-term) animal tests, such as the LD₅₀tests in mice and rats, have shown lindane to have high acute toxicity from oral exposure. (4)

Chronic Effects (Noncancer):

* Chronic exposure to lindane by inhalation in humans has been associated with effects on the liver, blood, and nervous, cardiovascular, and immune systems. (1,3)

* Effects noted in animal studies from oral exposure to lindane include effects on the blood (decrease in numbers of red and white blood cells), musculoskeletal, immune, and nervous systems, and the liver and kidney. (1)

* The RfD for lindane is 0.0003 mg/kg/d based on liver and kidney toxicity in rats. (5)

* EPA has medium confidence in the principal study on which the RfD was based because it used an adequate number of animals and measured multiple endpoints; confidence in the database is medium because there are other reported chronic and subchronic studies; and, consequently, medium confidence in the RfD.

* The RfC for lindane is under review by EPA. (4)

Reproductive/Developmental Effects:

* Limited information is available regarding the reproductive or developmental effects of lindane in humans. The one available study reported increased levels (not statistically significant) of follicle stimulating hormone and decreased levels of testosterone in men occupationally exposed to lindane. It is not known whether these hormonal changes could result in diminished reproductive capability. (1)

* Animal studies have reported reproductive effects, such as decreased sperm count, increased testicular weight, and disruption of spermatogenesis from oral exposure to lindane. (1,3)

* Lindane has not been reported to cause developmental effects, such as birth defects, in animals via oral exposure. (1,3)

Cancer Risk:

* No studies are available concerning carcinogenic effects in humans or animals following inhalation exposure to lindane. (1)

* Lindane has been demonstrated to be a liver carcinogen in rats and mice via oral exposure. (1)

* EPA considers lindane to be a possible human carcinogen (cancer-causing agent) and has ranked it in EPA's Group B2/C. (6)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has ranked lindane in the nonthreshold category. The 1/ED₁₀ value is 7.4 per (mg/kg)/d and this would place it in the low to medium category under Superfund's ranking for carcinogenic hazard. (2,6)

Physical Properties

* The chemical formula for lindane is C₆H₆Cl_6, and it has a molecular weight of 290.83 g/mol. (1)

* Lindane is a white solid that is volatile in air and insoluble in water. (1)

* Lindane vapor is colorless and has a slight musty odor; the odor threshold is 12 ppm. (1)

* The vapor pressure for lindane is 9.4 H 10^-6 mm Hg at 20 EC, and it has a log octanol/water partition coefficient (Log K_ow) of 3.3. (1)

Uses

* Lindane is used as an insecticide on fruit and vegetable crops, for seed treatment, in forestry, and for animal treatment. (1)

* Lindane is no longer produced in the United States (however, it is still formulated in this country), and aerial application of the chemical is prohibited. (1)

* Lindane is also used topically for the treatment of head and body lice and scabies; it is available in 1 percent preparations as a lotion, cream, or shampoo. (1)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
1000.0
_ _ _ _ 100.0	* Oral LD₅₀ (rats) (125 mg/kg) * Oral LD₅₀ (mice) (100 mg/kg)		4 4
_ _ _ _ 10.0
_ _ _ _ 1.0
_ _ _ _ 0.1		* OSHA PEL (skin), ACGIH TLV (skin), NIOSH REL (skin) (0.5 mg/m³)	1

ACGIH TLVCAmerican Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effects.

LD₅₀ (Lethal Dose₅₀)CA calculated dose of a chemical in water to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population.

NIOSH RELCNational Institute of Occupational Safety and Health's recommended exposure limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure and/or ceiling.

OSHA PELCOccupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.

^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for a -, b -, g -, and d -Hexachlorocyclohexane. Draft. U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1992.

2. U.S. Environmental Protection Agency. Deposition of Air Pollutants to the Great Waters. First Report to Congress. EPA-453/R-93-055. Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.

3. U.S. Department of Health and Human Services. Hazardous Substances Databank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online databse). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

5. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Lindane. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

6. U.S. Environmental Protection Agency. Technical Background Document to Support Rulemaking Pursuant to the Clean Air ActCSection 112(g). Ranking of Pollutants with Respect to Hazard to Human Health. EPAB450/3-92-010. Emissions Standards Division, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.