Comparative toxicology of chlorinated compounds on mammalian species

Allen, James; Hargraves, Walter A.; Hsia, M.T.Stephen; Lin, Francis S.D.

doi:10.1016/0163-7258(79)90041-x

Cited by 32 publications

(11 citation statements)

References 217 publications

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“…PCBs have been used extensively for various industrial purposes, including constituents of insecticides and as an insulating material [4]. Although PCBs have been banned from use in industrialized countries since the 1970s [4], they are one of the most persistent and widespread of the xenobiotics in the ecosystem because of their chemical stability and their ability to bioaccumulate [1, 3, 58,59]. PCBs have been shown to act through the Ah receptor to bring about their biological effects [34]; however, new evidence indicates that they also act through the oestrogen receptor [60].…”

Section: Review Articlementioning

confidence: 99%

“…Taken together, these data are consistent with the hypothesis that Linuron brings about its effects in the male by acting as an antiandrogen. The hexachlorocyclohexanes (HCHs) are mixtures of stereoisomers differing in the relative positions of chlorine around the boat and chair forms of the hexane ring [59]. The k-isomer (HCHk) is sold as the commercial insecticide, Lindane.…”

Section: Review Articlementioning

confidence: 99%

“…We [27] have shown that the l isomer of HCH (HCHl) binds to the androgen receptor, to androgen-binding protein (ABP) and to sex hormone-binding globulin (SHBG) [27]. Cyclodiene insecticides, such as dieldrin, have been shown to have detrimental effects on reproduction and fertility in several species [59]. Compounds of this class have been shown to decrease oestrogen-sensitive reporter activity in a yeast system [72], providing evidence for a possible antioestrogenic activity.…”

Section: Review Articlementioning

confidence: 99%

“…Chlorophenols are herbicides and antimicrobial agents used in the preservation of wood [59]. Pentachlorophenol has been used as an agricultural fungicide.…”

Section: Review Articlementioning

confidence: 99%

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The effects of environmental hormones on reproduction

Danzo¹

1998

Cellular and Molecular Life Sciences (CMLS)

114

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Considerable attention has been given in the past few years to the possibility that man-made chemicals (xenobiotics) in the environment may pose a hazard to human reproductive health. The endocrine-disrupting effects of many xenobiotics can be interpreted as interference with the normal regulation of reproductive processes by steroid hormones. Evidence reviewed here indicates that xenobiotics bind to androgen and oestrogen receptors in target tissues, and to androgen-binding protein and to sex hormone-binding globulin. Although environmental chemicals have weak hormonal activity, their ability to interact with more than one steroid-sensitive pathway provides a mechanism by which their hazardous nature can be augmented. A given toxicant may be present in low concentration in the environment and, therefore, harmless. However, we are not exposed to one toxicant at a time, but, rather, to all of the xenobiotics present in the environment. Therefore, numerous potential agonists/antagonists working together through several steroid-dependent signalling pathways could prove to be hazardous to human reproductive health.

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Section: Review Articlementioning

confidence: 99%

Section: Review Articlementioning

confidence: 99%

Section: Review Articlementioning

confidence: 99%

“…Chlorophenols are herbicides and antimicrobial agents used in the preservation of wood [59]. Pentachlorophenol has been used as an agricultural fungicide.…”

Section: Review Articlementioning

confidence: 99%

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The effects of environmental hormones on reproduction

Danzo¹

1998

Cellular and Molecular Life Sciences (CMLS)

114

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“…For dieldrin, the oral LD 50 in mammals was estimated to be 38 to 87 mg/kg b.wt. in rats (Allen et al, 1979). In comparison, the topical LD 50 in American cockroaches was 1.3 to 1.5 mg/kg (Giannotti et al, 1959;O'Brien, 1967).…”

mentioning

confidence: 96%

Differential Actions of Fipronil and Dieldrin Insecticides on GABA-Gated Chloride Channels in Cockroach Neurons

Zhao

Salgado

Yeh³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

120

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Fipronil and dieldrin are known to inhibit GABA receptors in both mammals and insects. However, the mechanism of selective toxicity of these insecticides between mammals and insects remains to be seen. One possible mechanism is that insect GABA receptors are more sensitive than mammalian GABA A receptors to fipronil and dieldrin. We examined differential actions of fipronil and dieldrin on GABA-gated chloride channels in insects and compared them with the data on mammalian GABA A receptors. Neurons were acutely dissociated from the American cockroach thoracic ganglia, and currents evoked by GABA were recorded by the whole-cell patch-clamp technique. GABA-evoked currents were carried by chloride ions, blocked by picrotoxinin, but not by bicuculline. Fipronil inhibited GABA currents with an IC 50 value of 28 nM, whereas dieldrin exhibited a dual action potentiation with an EC 50 value of 4 nM followed by inhibition with an IC 50 value of 16 nM. Fipronil and dieldrin acted on the resting receptor at comparable rates, whereas fipronil blocked the activated receptor 10 times faster than dieldrin. Fipronil inhibition was partially reversible, whereas dieldrin inhibition was irreversible. Fipronil was 59 times more potent on cockroach GABA receptors than on rat GABA A receptors. However, the potentiating and inhibitory potencies of dieldrin in cockroach GABA receptors were comparable with those in rat GABA A receptors. It was concluded that the higher toxicity of fipronil in insects than in mammals is due partially to the higher sensitivity of GABA receptors. The mechanism of dieldrin's selective toxicity must lie in factors other than the sensitivity of GABA receptors.The selective toxicity between mammals and insects is one of the most important factors for the development of new insecticides. In fact, most insecticides on the market are more toxic to insects than to mammals. However, the mechanisms underlying high insecticidal activity and low mammalian toxicity of insecticides are not fully understood. Although the selective toxicity of certain insecticides (e.g., organophosphates) is due primarily to the differences in metabolism (O'

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