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gamma-Hexachlorocyclohexane (gamma-HCH) (CASRN 58-89-9)

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gamma-Hexachlorocyclohexane (gamma-HCH); CASRN 58-89-9

Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data, as outlined in the IRIS assessment development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached during the assessment development process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website.


File First On-Line 01/31/1987

Category (section)
Last Revised
Oral RfD Assessment (I.A.) on-line 03/01/1988
Inhalation RfC Assessment (I.B.) no data 07/01/1992
Carcinogenicity Assessment (II.) no data 10/01/1993

_I.  Chronic Health Hazard Assessments for Noncarcinogenic Effects

_I.A. Reference Dose for Chronic Oral Exposure (RfD)

Substance Name — gamma-Hexachlorocyclohexane (gamma-HCH)
CASRN — 58-89-9
Primary Synonym — Lindane
Last Revised — 03/01/1988

The oral Reference Dose (RfD) is based on the assumption that thresholds exist for certain toxic effects such as cellular necrosis. It is expressed in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Please refer to the Background Document for an elaboration of these concepts. RfDs can also be derived for the noncarcinogenic health effects of substances that are also carcinogens. Therefore, it is essential to refer to other sources of information concerning the carcinogenicity of this substance. If the U.S. EPA has evaluated this substance for potential human carcinogenicity, a summary of that evaluation will be contained in Section II of this file.

__I.A.1. Oral RfD Summary

Critical Effect
Experimental Doses*

Liver and kidney

Rat, Subchronic Oral

Zoecon Corp., 1983

NOAEL: 4 ppm diet
[0.33 mg/kg/day

LOAEL: 20 ppm diet
[1.55 mg/kg/day


*Conversion Factor -- Converted dose calculated from actual food consumption data

__I.A.2. Principal and Supporting Studies (Oral RfD)

Zoecon Corporation. 1983. MRID No. 00128356. Available from EPA. Write to FOI, EPA, Washington D.C. 20460.

Twenty male and 20 female Wistar KFM-Han (outbred) SPF rats/treatment group were administered 0, 0.2, 0.8, 4, 20, or 100 ppm lindane (99.85%) in the diet. After 12 weeks, 15 animals/sex/group were sacrificed. The remaining rats were fed the control diet for an additional 6 weeks before sacrifice. No treatment-related effects were noted on mortality, hematology, clinical chemistry, or urinalysis. Rats receiving 20 and 100 ppm lindane were observed to have greater-than-control incidence of the following: liver hypertrophy, kidney tubular degeneration, hyaline droplets, tubular distension, interstitial nephritis, and basophilic tubules. Since these effects were mild or rare in animals receiving 4 ppm, this represents a NOAEL. The reviewers of the study calculated the dose to be 0.29 mg/kg/day for males and 0.33 mg/kg/day for females, based on measured food intake.

In a 2-year feeding study (Fitzhugh, 1950), 10 Wistar rats/sex/group were exposed to 5, 10, 50, 100, 400, 800, or 1600 ppm lindane. Slight liver and kidney damage and increased liver weights were noted at the 100 ppm level. If a food intake equal to 5% body weight is assumed, a NOAEL of 2.5 mg/kg bw/day (50 ppm) can be determined from this assay. In a 2-year bioassay (Rivett et al., 1978), four beagle dogs/sex/group were administered 0, 25, 50, or 100 ppm lindane in the diet. Treatment-related effects noted in the animals of the 100 ppm group were increased serum alkaline phosphatase and enlarged dark friable livers. A NOAEL was determined to be 50 ppm (1.6 mg/kg bw/day).

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF — A factor of 10 each was employed for use of a subchronic vs. a lifetime assay, to account for interspecies variation and to protect sensitive human subpopulations.

MF — None

__I.A.4. Additional Studies/Comments (Oral RfD)

Data on reproductive effects of lindane are inconclusive. Most reports indicate that hexachlorocyclohexane isomers are nonteratogenic.

__I.A.5. Confidence in the Oral RfD

Study — Medium
Database — Medium
RfD — Medium

The principal study used an adequate number of animals and measured multiple endpoints. Since there are other reported chronic and subchronic studies, confidence in the database is medium. Medium confidence in the RfD follows.

__I.A.6. EPA Documentation and Review of the Oral RfD

Source Document — U.S. EPA, 1985

The RfD in the Drinking Water Criteria Document has been extensively reviewed by U.S. EPA scientists and selected outside experts.

Other EPA Documentation — None

Agency Work Group Review — 01/22/1986

Verification Date — 01/22/1986

__I.A.7. EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).

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_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — gamma-Hexachlorocyclohexane (gamma-HCH)
CASRN — 58-89-9
Primary Synonym — Lindane

Not available at this time.

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_II.  Carcinogenicity Assessment for Lifetime Exposure

Substance Name — gamma-Hexachlorocyclohexane (gamma-HCH)
CASRN — 58-89-9
Primary Synonym — Lindane

Not available at this time.

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_III.  [reserved]
_IV.  [reserved]
_V.  [reserved]

_VI.  Bibliography

Substance Name — gamma-Hexachlorocyclohexane (gamma-HCH)
CASRN — 58-89-9
Primary Synonym — Lindane
Last Revised — 08/01/1991

_VI.A. Oral RfD References

Fitzhugh, O.G., A.A. Nelson and J.P. Frawley. 1950. The chronic toxicities of technical benzene hexachloride and its alpha, beta and gamma isomers. J. Pharmacol. Exp. Ther. 100: 59-66.

Muller, D., H. Klepel, R.M. Macholz, H.J. Lewerenz and R. Engst. 1981. Electroneurophysiological studies on neurotoxic effects of hexachlorocyclo- hexane isomers and gamma-pentachlorocyclohexene. Bull. Environ. Contam. Toxicol. 27(5): 704-706.

Rivett, K.F., H. Chesterman, D.N. Kellett, A.J. Newman, and A.N. Worden. 1978. Effects of feeding lindane to dogs for periods of up to 2 years. Toxicology. 9: 273-289.

U.S. EPA. 1985. Drinking Water Criteria Document for Lindane. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC.

Zoecon Corporation. 1983. MRID No. 00128356. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

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_VI.B. Inhalation RfC References


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_VI.C. Carcinogenicity Assessment References


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_VII.  Revision History

Substance Name — gamma-Hexachlorocyclohexane (gamma-HCH)
CASRN — 58-89-9
Primary Synonym — Lindane

03/31/1987 IV.A. Additional pesticide AI data added
03/01/1988 I.A.1. Principal study citation corrected
03/01/1988 I.A.1. Dose conversion corrected
03/01/1988 I.A.2. Text revised
03/01/1988 III.A. Health Advisory added
08/01/1990 III.A.10 Primary contact changed
08/01/1990 IV.F.1. EPA contact changed
08/01/1991 VI. Bibliography on-line
01/01/1992 I.A.7. Secondary contact changed
01/01/1992 IV. Regulatory actions updated
07/01/1992 I.B. Inhalation RfC now under review
10/01/1993 II. Inadvertently listed as under review
08/01/1995 I.B. EPA's RfD/RfC and CRAVE workgroups were discontinued in May, 1995. Chemical substance reviews that were not completed by September 1995 were taken out of IRIS review. The IRIS Pilot Program replaced the workgroup functions beginning in September, 1995.
04/01/1997 III., IV., V. Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information.
01/09/2002 I.A., II. This chemical is being reassessed under the IRIS Program.
02/09/2004 I.A., II. This chemical is no longer being reassessed under the IRIS Program. See Federal Register February 9, 2004 (Volume 69, Number 26).

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_VIII.  Synonyms

Substance Name — gamma-Hexachlorocyclohexane (gamma-HCH)
CASRN — 58-89-9
Primary Synonym — Lindane
Last Revised — 01/31/1987

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