Risk Assessment of Toxaphene and its Breakdown Products: Time for a Change?

Abstract

Technical toxaphene (TT) was last used in commerce in about 1982. Any environmental exposure to toxaphene in this century is to environmentally degraded forms of toxaphene, termed weathered toxaphene. Several hundred chlorinated bornane congeners have been identified in technical toxaphene. The degradation of technical toxaphene to weathered toxaphene can result in various congener mixtures, but the primary mode of degradation is dechlorination. The U.S. Environmental Protection Agency (EPA) presently estimates the risk of exposure to toxaphene by relying upon rat and mouse toxicology studies performed on technical toxaphene. No adjustment is made for the dechlorination of toxaphene in the environment. The European Union (EU), however, has modeled toxaphene risks from eating fish with chlorinated bornane residues through a series of studies on toxaphene degraded by either ultraviolet light, or biodegradation in fish. The EU risk assessment relies upon rat liver studies in vivo and mouse in vitro studies on the inhibition of gap junction intercellular communication (GJIC).This article reviews the current state of knowledge of technical and weathered toxaphene toxicology. We discuss the various current methods and opportunities to advance the risk assessment of weathered toxaphene beyond the existing U.S. EPA assessment of technical toxaphene.

Identification of the critical timing of sex determination in Daphnia magna (Crustacea, Branchiopoda) for use in toxicological studies

“…As a result, it is still commonly found in wildlife and human tissue samples (Lamb et al, 2008;Champoux et al, 2010). Toxaphene has harmful effects such as reproductive impairment, and continues to be a major contaminant in marine and freshwater biota (de Geus et al, 1999;Xia et al, 2009;Lamb et al, 2008;Martyniuk et al, 2009;Champoux et al, 2010;Kucklick et al, 2010). Kashian (2004) showed that toxaphene affects sexual differentiation by stimulating the production of males in concentrations as low as 50 lg l -1 .…”

“…Although toxaphene has been banned from use, it is persistent in the environment due to its lipophilic and volatile characteristics, which result in the bioaccumulation and biomagnification of toxaphene in ecosystems (de Geus et al, 1999). As a result, it is still commonly found in wildlife and human tissue samples (Lamb et al, 2008;Champoux et al, 2010). Toxaphene has harmful effects such as reproductive impairment, and continues to be a major contaminant in marine and freshwater biota (de Geus et al, 1999;Xia et al, 2009;Lamb et al, 2008;Martyniuk et al, 2009;Champoux et al, 2010;Kucklick et al, 2010).…”

Mechanistic Investigation of Toxaphene Induced Mouse Liver Tumors

“…Toxaphene has shown limited evidence of genotoxicity in in vitro assays that diminishes in the presence of metabolic activation and has not shown mutagenicity in in vivo assays (Lamb et al, 2008). Mechanistic data suggest that the dose-response curve for toxaphene induced tumors in mice was nonlinear and possibly exhibits a threshold (Goodman et al, 2000).…”

Toxaphene-induced mouse liver tumorigenesis is mediated by the constitutive androstane receptor

“…Because of the dearth of mechanistic toxicity data on toxaphene, the mode of action for the liver tumor induction by toxaphene in mouse was unable to be defined. A panel evaluation of the available scientific evidence led to the conclusion that toxaphene is a mouse liver tumor promoter functioning through a non‐DNA reactive/non‐genotoxic mode of action in producing liver tumors in mice in a manner similar to that of phenobarbital (Goodman et al , ; Lamb et al , ).…”

“…Chronic dietary treatment of B6C3F1 mice with toxaphene increased the incidence of mouse liver tumors in both male and female mice, with male mice showing a greater tumor response (Litton‐Bionetics, ; NCI, ). Examination of toxaphene for genotoxicity has shown mixed results with only limited evidence of genotoxicity, and no evidence for mutagenicity in in vivo assays (Epstein et al , ; Hooper et al , ; Lamb et al , ; Mortelmans et al , ). The overall weight of evidence has led to the proposal that the toxaphene‐induced mouse liver tumors are a non‐linear, non‐genotoxic, threshold‐dependent process (Goodman et al , ).…”