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Mutagenic/carcinogenic potential of DEHP and MEHP
Abstract:
The mutagenic/carcinogenic activities of DEHP and MEHP were studied in bacteria and mammalian cells. MEHP but not DEHP exerted a dose-dependent DNA damaging effect to B. subtilis in Rec-assay. DEHP and MEHP showed mutagenic activities to S. typhimurium TA-100, with and without S-9 mix, respectively. MEHP produced not only the mutation in E. coli WP2B/r but also sister chromatid exchanges (SCE) in Chinese hamster V79 cells. It also induced 8AG/6TG-resistant gene mutations and chromosomal aberrations in the V79 cells. Transplacental administration of DEHP or MEHP to the Syrian golden hamster embryos was carried out by administering DEHP or MEHP to gravid animals on day 11 of gestation, followed by the cultivation of embryonic cells for 15-20 days. Both DEHP and MEHP induced 8AG/6TG-resistant mutation, chromosomal aberrations and morphological transformation in the embryonic cells of the Syrian golden hamster.
Insights
Mono(2-ethylhexyl) phthalate (MEHP) demonstrated significant DNA damage and mutagenic effects in bacterial and mammalian cells. Di(2-ethylhexyl) phthalate (DEHP) also showed mutagenicity, with both compounds inducing mutations and chromosomal damage in hamster embryos.
Area of Science:
- Toxicology
- Genetics
- Cell Biology
Background:
- Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer with potential health concerns.
- Understanding the mutagenic and carcinogenic activities of DEHP and its primary metabolite, mono(2-ethylhexyl) phthalate (MEHP), is crucial for risk assessment.
Purpose of the Study:
- To investigate the mutagenic and carcinogenic potential of DEHP and MEHP.
- To evaluate the DNA damaging effects of these compounds in various in vitro and in vivo models.
Main Methods:
- Bacterial mutagenicity assays (Rec-assay, Ames test with Salmonella typhimurium TA-100).
- Mammalian cell assays including gene mutation (8-azaguanine/6-thioguanine resistance), sister chromatid exchanges (SCE), chromosomal aberrations, and morphological transformation in Chinese hamster V79 cells.
- Transplacental exposure study in Syrian golden hamsters, followed by embryonic cell analysis.
Main Results:
- MEHP induced dose-dependent DNA damage in B. subtilis.
- Both DEHP and MEHP exhibited mutagenicity in S. typhimurium TA-100.
- MEHP caused gene mutations, SCE, and chromosomal aberrations in V79 cells.
- Transplacental exposure to DEHP and MEHP resulted in mutations, chromosomal aberrations, and morphological transformation in embryonic cells.
Conclusions:
- MEHP is a potent mutagen and genotoxic agent.
- DEHP also possesses mutagenic properties.
- Both compounds pose risks for developmental toxicity and carcinogenicity, warranting further investigation and regulatory consideration.