Persistent DDT Metabolite p,p'-DDE is a Potent Androgen Receptor Antagonist

Kelce, William R.; Stone, Christy R.; Laws, Susan C.; Gray, Earl; Kemppainen, Jon; Wilson, Elizabeth M.

doi:10.1097/00006254-199602000-00020

Cited by 209 publications

(331 citation statements)

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“…Toxicity of other less-toxic CP originating from the BKME may be additive to that of PCP, but total concentration of CPs was in the nanogram-per-gram range (11.1 ng/g). Concentrations of DDT (ng/g) were also below those associated with detrimental effects in wildlife (g/ g) [41].…”

Section: Toxic Levelsmentioning

confidence: 85%

Organochlorine Contaminants in Mummichog(fundulus Heteroclitus) Living Downstream From a Bleached-Kraft Pulp Mill in the Miramichi Estuary, New Brunswick, Canada

Couillard¹,

Nellis²

1999

Environ Toxicol Chem

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Abstract-Mummichog, a small-sized sentinel fish species, has been proposed for use in environmental effects monitoring programs conducted by pulp mills that release their effluent in marine waters. In order to evaluate the suitability of mummichog as a sentinel species and to support the interpretation of biological effects data, tissue concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans, (PCDD/Fs), chlorophenolic compounds (CPs), polychlorinated biphenyls (PCBs), and chlorinated pesticides were investigated in mummichog sampled in the Miramichi Estuary, which was receiving a bleached-kraft mill (BKM) effluent, and in a reference estuary, the Bouctouche Estuary. Higher concentrations PCDD/Fs (up to 50 times), CPs (up to 60 times), DDT, and PCBs (up to 10 times) were found in mummichog sampled at the upstream site of the Miramichi Estuary. At this site, 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent concentrations were slightly above the threshold for ethoxy resorufin O-deethylase induction. Multivariate analyses on congener profiles revealed that the contamination by PCDD/Fs and CPs originated both from the BKM and from a former wood-preservation plant and that PCDD/Fs and CPs typical of the BKM were transported 40 km downstream from the mill. Patterns and levels of persistent contaminants differed between sites within the Estuary, indicating that the fish did not mix during their growing period. These findings support the use of mummichog in environmental effects monitoring programs, because this species bioaccumulates chlorinated compounds contained in BKM effluent and is sedentary. The causeeffect relationship between exposure to the BKM effluent and the observed biological responses will have to be demonstrated by laboratory studies because of the presence of multiple sources of contamination.

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Section: Toxic Levelsmentioning

confidence: 85%

Organochlorine Contaminants in Mummichog(fundulus Heteroclitus) Living Downstream From a Bleached-Kraft Pulp Mill in the Miramichi Estuary, New Brunswick, Canada

Couillard¹,

Nellis²

1999

Environ Toxicol Chem

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“…Administration of p,pЈ-DDE to immature male rats delayed puberty, and when administered to adult male rats, p,pЈ-DDE significantly reduced the weights of the seminal vesicle and ventral prostate [32]. These effects are all consistent with the demonstrated ability of p,pЈ-DDE to bind to the mammalian androgen receptor in an antagonistic manner [32]. The establishment of such cause-effect relationships between the mode of action of a chemical and the physiologic response of organisms exposed to the chemical can provide insight into mechanisms responsible for toxicologic responses observed in G.A.…”

Section: Discussionmentioning

confidence: 97%

“…Specific toxicologic responses to a chemical can provide significant insight into the mechanism by which the chemical elicits toxicity. For example, pregnant rats administered the DDT metabolite p,pЈ-DDE bore male offspring that had reduced anogenital distance and retained thoracic nipples [32]. Administration of p,pЈ-DDE to immature male rats delayed puberty, and when administered to adult male rats, p,pЈ-DDE significantly reduced the weights of the seminal vesicle and ventral prostate [32].…”

Section: Discussionmentioning

confidence: 99%

“…For example, pregnant rats administered the DDT metabolite p,pЈ-DDE bore male offspring that had reduced anogenital distance and retained thoracic nipples [32]. Administration of p,pЈ-DDE to immature male rats delayed puberty, and when administered to adult male rats, p,pЈ-DDE significantly reduced the weights of the seminal vesicle and ventral prostate [32]. These effects are all consistent with the demonstrated ability of p,pЈ-DDE to bind to the mammalian androgen receptor in an antagonistic manner [32].…”

Section: Discussionmentioning

confidence: 99%

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Molt-Independent Growth Inhibition of Daphnia Magna by a Vertebrate Antiandrogen

LeBlanc¹,

McLachlan²

1999

Environ Toxicol Chem

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Abstract-The objective of this study was to identify specific physiologic parameters in crustaceans that are targeted by chemicals known to be antiandrogenic in vertebrates. We hypothesized that chemicals capable of binding to the vertebrate androgen receptor would also elicit toxicity to crustaceans by binding to specific steroid hormone receptors in an antagonistic manner. This hypothesis was tested by evaluating the effects of the antiandrogen cyproterone acetate on growth, molting, sexual differentiation, and reproduction of Daphnia magna. Exposure of daphnids to concentrations of cyproterone acetate appreciably below those that elicited mortality reduced growth but had no effect on molting. These concentrations of cyproterone acetate had no effect on various developmental and maturation parameters. Cyproterone acetate also reduced the number of offspring produced by parthenogenetically reproducing daphnids, but this effect appeared to be a consequence of the reduced size of the daphnids and their inability to accommodate a brood of more than approximately 10 eggs. These results indicate that the antiandrogen cyproterone acetate specifically targets a process critical to growth of daphnids that is independent of molting. Additional studies are warranted to established whether this is an endocrine-related toxicity to crustaceans that is associated with environmental antiandrogens such as some pesticide metabolites.

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“…Technical DDT has estrogen-like properties (Fry and Toone, 1981;Fry et al, 1987;Bishop et al, 1991;Guillette et al, 1994), which is largely due to the o,p 0 -isomer of DDT, (Metcalf, 1995). However, p,p 0 -dichlorodiphenyldichloroethylene (DDE), the persistent metabolite of DDT, acts both as an androgen receptor antagonist and inhibitor of testosterone (Kelce et al, 1995;Danzo, 1997). Adverse effects on reproductive system associated with in utero DDT or DDE exposure in male animals include, among others, reduced penis size (Guillette and Guillette, 1996), hypospadias (Gray et al, 2001) and cryptorchidism (Facemire et al, 1995;Gray et al, 2001), and abnormal development of ovarian tissue (Fry and Toone, 1981).…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural effects of DDT, DDD, and DDE on neural cells of the chicken embryo model

Bornman¹,

Pretorius²,

Marx³

et al. 2007

Environmental Toxicology

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Human exposure to environmental compounds with estrogenic activity and the potential effects on human health is the subject of ongoing scientific debates. Their potential effects raise concern regarding neurological development after prenatal exposure. Central to this debate is the pesticide 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT). Although it has apparent low acute toxicity in mammals, DDT has a long residual persistence and laboratory research has indicated that it acts on the CNS by interfering with Na(+)/K(+) pump mechanism of the neuronal membranes, causing disruption in Ca(2+) homeostasis. Potentially this may lead to both apoptosis and necrosis. The present study investigates the effects of DDT and two of its metabolites DDD and DDE on the ultramorphology of neural cells, using a previously published chicken embryo model. Results indicate cellular swelling, budding, and increased membrane permeability for all three chemicals, accompanied by karyolysis in the DDE group (typical features of oncosis). These results support the finding of other researchers as well as the concerns of the WHO that DDT and its metabolites may cause neurotoxicity after prenatal exposure.

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Persistent DDT Metabolite p,p'-DDE is a Potent Androgen Receptor Antagonist

Cited by 209 publications

References 0 publications

Organochlorine Contaminants in Mummichog(fundulus Heteroclitus) Living Downstream From a Bleached-Kraft Pulp Mill in the Miramichi Estuary, New Brunswick, Canada

Organochlorine Contaminants in Mummichog(fundulus Heteroclitus) Living Downstream From a Bleached-Kraft Pulp Mill in the Miramichi Estuary, New Brunswick, Canada

Molt-Independent Growth Inhibition of Daphnia Magna by a Vertebrate Antiandrogen

Ultrastructural effects of DDT, DDD, and DDE on neural cells of the chicken embryo model

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