In vitro and in vivo evaluation of the developmental toxicity of various polychlorinated biphenyls, chlorophenols and related compounds /
Data pertaining to the developmental toxicity of PCBs are
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1996.
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| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=739364211&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Data pertaining to the developmental toxicity of PCBs are very limited in the literature. Studies were performed to determine the teratogenicity of 3,3',4,4',5 pentachlorobiphenyl utilizing the chick embryotoxicity screening test (CHEST), and to evaluate the effects of 2,2',4,4',5,5'-hexachlorobiphenyl and indole-3-carbinol (13C) on 3,3',4,4',5-pentachlorobiphenyl-induced teratogenesis in the CHEST bioassay and C57BU6 mice. 3,3',4,4',5- Pentachlorobiphenyl alone produced dose-dependent increases in mortality, toxicity and malformations in chicken embryos. 2,2',4,4',5,5'-Hexachlorobiphenyl antagonized the embryotoxic and teratogenic effects of 3,3',4,4',5pentachlorobiphenyl (2.0 mg/kg) in chicken embryos. A concentration-dependent increase in the incidence of cleft palate was observed in mice treated with 3,3',4,4',5-pentachlorobiphenyl. Cotreatment of the dams with 3,3',4,4',5-pentachlorobiphenyl plus 2,2',4,4',5,5'-hexachlorobiphenyl significantly reduced the number of cleft palate in all treatment groups except in the highest treatment group. 2,2',4,4',5,5'- Hexachlorobiphenyl did not antagonize the 3,3',4,4',5-penta chlorobiphenyl-induced hydronephrosis. While 13C alone did not induce any toxic effects, cotreatment of 2.0 mg/kg 3,3',4,4',5-pentachlorobiphenyl plus 2.0 mg 13C/kg (in the CHEST assay) and 1044 mg 3,3',4,4',5-pentachlorobiphenyl/kg plus 200 mg 13C/kg (in mice) revealed neither agonist nor antagonist effects on 3,3',4,4',5- pentachlorobiphenyl- induced teratogenic effects. The CHEST bioassay confirmed the results in mice and may be useful to delineate interactions between complex mixtures of environmental toxins. Human embryonic palatal mesenchymal (HEPM) cell growth inhibition bioassay was used to evaluate the developmental toxicity of chlorophenols (CPs). This assay demonstrated a linear relationship between the IC50 values of the CPs and degree of chlorine substitution. A clear structure-activity relationship was observed between toxicity of CPs and the degree of chlorine substitution. The rank order of CP toxicity (i.e., C5p > C4p > C3p > C2P > Cp > phenol) was in excellent agreement with previous in vitro and in vivo studies. However, contrary to published reports, the HEPM assay predicted that all CPs were teratogenic (false positives). These findings suggest that the HEPM cell growth inhibition bioassay may be useful to discriminate between subtle differences in structure-activity of diverse chemicals. Also, this assay in combination with other bioassays, might facilitate the rapid detection and prioritization of various developmental toxicants. Importantly, conclusions about the teratogenicity of a test chemical (via HEPM testing) should be approached with caution and confirmed with other teratogensensitive systems. |
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| Item Description: | Vita. "Major Subject: Toxicology". |
| Physical Description: | xii, 170 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references: pages 119-168. |