Specific Accumulation and Elimination Kinetics of Tris(4-Chlorophenyl)methane, Tris(4-Chlorophenyl) Methanol, and Other Persistent Organochlorines in Humans from Japan. (Articles)

By Minh, Tu Binh; Watanabe, Mafumi et al. | Environmental Health Perspectives, September 2001 | Go to article overview

Specific Accumulation and Elimination Kinetics of Tris(4-Chlorophenyl)methane, Tris(4-Chlorophenyl) Methanol, and Other Persistent Organochlorines in Humans from Japan. (Articles)


Minh, Tu Binh, Watanabe, Mafumi, Tanabe, Shinsuke, Yamada, Taketo, Hata, Jun-ichi, Watanabe, Shaw, Environmental Health Perspectives


We examined human adipose tissue, liver, and bile from humans in Japan to understand the contamination status, specific accumulation, and elimination of two newly identified environmental contaminants, tris(4-chlorophenyl)methane (TCPMe), tris(4-chlorophenyl)methanol (TCPMOH), and other persistent organochlorines such as polychlorinated biphenyls (PCBs), DDT and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), and chlordane compounds (CHLs). TCPMe and TCPMOH concentrations in Japanese human adipose tissue were slightly higher than those reported previously, indicating widespread exposure to these compounds in humans. Elevated residues of PCBs and DDTs are found in adipose tissue and liver. Concentrations in bile strongly correlated with concentrations in adipose fat and liver, which may suggest an equilibration in adipose fat/bile and liver/bile and possible biliary excretion of persistent organochlorines in humans. Composition of the organochlorines accumulated further indicates a metabolic capacity in humans higher than that of marine mammals. We observed age-dependent accumulation for TCPMe, TCPMOH, and other organochlorines, but there were no significant gender differences, p,p'-DDE and TCPMe were estimated to have low biliary excretion rate. Elimination potential of persistent organochlorines may be related to their octanol-water partition coefficient. The relationship between excretion rate and octanol-water partition coefficient may be used to predict the biliary excretion potential of some other lipophilic organochlorines such as dioxins and dibenzofurans in humans. The presence of organochlorines in bile suggests that the hepatic excretory system plays a major role in the elimination of xenobiotics in humans. To our knowledge, this is the first study of accumulation and elimination of TCPMe and TCPMOH in humans. Key words: age-dependent accumulation, biliary excretion, humans, persistent organochlorines, tissue distribution, tris(4-chlorophenyl) methane, tris(4-chlorophenyl) methanol. Environ Health Perspect 109:927-935 (2001). [Online 24 August 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p927-935minh/abstract.html

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During the last few decades, numerous studies have been conducted on global contamination by and toxic effects of persistent organochlorines (OCs) such as DDTs, polychlorinated biphenyls (PCBs), and hexachlorocyclohexane isomers (HCHs). These are highly bioaccumulative and have serious effects on environmental quality as well as human health and wildlife. Recently there has been a growing concern that these synthetic chemicals can act as estrogen or androgen mimics and hence disrupt normal endocrine function, possibly leading to various reproductive abnormalities in wildlife and humans (1). Among these chemicals, DDT and its metabolites, particularly o,p'-DDT and p,p'-DDE, are potent estrogen- and androgenreceptor antagonists, respectively (2). In addition, other compounds with structures similar to DDT, such as dicofol, also have been reported as environmental endocrine disruptors (3). Tris(4-chlorophenyl)methane (TCPMe) and tris(4-chlorophenyl)methanol (TCPMOH) are among the most recently detected environmental contaminants. These compounds have structures similar to DDT and dicofol, respectively, and are thought to be derived mainly from technical DDT (4-7). In recent in vitro studies, TCPMe and TCPMOH have been shown to possess high binding affinity for both androgen and estrogen receptors (8,9). Although the endocrine-disrupting effects of these compounds have not been adequately validated in vivo, these findings suggest that TCPMe and TCPMOH may act as estrogen mimics at relatively low concentrations. However, understanding of environmental exposure to these new environmental endocrine disrupters, particularly in humans, is still limited.

Over the last few years, we have extensively investigated the global distribution, transport, behavior, and bioaccumulation of TCPMe and TCPMOH in higher trophic animals, including marine mammals and humans.

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Specific Accumulation and Elimination Kinetics of Tris(4-Chlorophenyl)methane, Tris(4-Chlorophenyl) Methanol, and Other Persistent Organochlorines in Humans from Japan. (Articles)
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