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Evidence for Carcinogenicity:
Cancer Classification: Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess Human Carcinogenic Potential
[USEPA Office of Pesticide Programs, Health Effects Division, Science Information Management Branch: "Chemicals Evaluated for Carcinogenic Potential" (April 2006)] **QC REVIEWED**
A3; Confirmed animal carcinogen with unknown relevance to humans.
[American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH 2010, p. 37] **QC REVIEWED**
Lindane: reasonably anticipated to be a human carcinogen. /Lindane and Other Hexachlorocyclohexane Isomers/
[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Lindane (58-89-9) and Other Hexachlorocyclohexane Isomers (January 2005). Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s102lind.pdf **QC REVIEWED**
Non-Human Toxicity Excerpts :
/ALTERNATIVE IN VITRO TESTS/ gamma-Hexachlorocyclohexane-induced hepatotoxicity is associated with oxidative stress. ... The hypothesis that gamma-hexachlorocyclohexane triggers the redox activation of nuclear factor-kappaB (NF-kappaB), leading to proinflammatory cytokine expression /was tested/. Liver NF-kappaB activation (electrophoretic mobility shift assay), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1alpha (IL-1alpha) mRNA expression (reverse transcription-polymerase chain reaction), and their serum levels (enzyme-linked immunosorbent assay) were measured at different times after gamma-hexachlorocyclohexane treatment (50 mg/kg). The relationship between these and hepatic O(2) uptake, glutathione and protein carbonyl levels, and sinusoidal lactate dehydrogenase (LDH) efflux in liver perfusion studies was determined. gamma-Hexachlorocyclohexane increased liver NF-kappaB DNA binding at 14-22 hr after treatment, concomitantly with significant glutathione depletion and an increase in the rate of O(2) consumption, the content of protein carbonyls, and the sinusoidal LDH efflux. In these conditions, the expression of TNF-alpha and IL-1alpha is enhanced, with maximal increases in their respective mRNA content and serum levels of the cytokines being elicited at 18 hr after gamma-hexachlorocyclohexane treatment. All these changes are suppressed by the administration of alpha-tocopherol (100 mg/kg) or the Kupffer cell inactivator gadolinium chloride (10 mg/kg) prior to gamma-hexachlorocyclohexane. gamma-Hexachlorocyclohexane-induced TNF-alpha levels in serum are suppressed by pretreatment with an antisense oligonucleotide (ASO TJU-2755; daily doses of 10 mg/kg for 2 days) targeting the primary transcript for the cytokine, whereas those of IL-1alpha are not modified. It is concluded that gamma-hexachlorocyclohexane-induced liver oxidative stress triggers the DNA binding activity of NF-kappaB, with the consequent increase in the expression of NF-kappaB-dependent genes for TNF-alpha and for IL-1alpha, factors that may mediate the hepatotoxicity of the insecticide.