Genotoxicity studies of di(2-ethylhexyl)phthalate and its metabolites in CHO cells

Phillips, Barry; James, Terena; Gangoli, S.D.

doi:10.1016/0165-1218(82)90139-2

Cited by 66 publications

(22 citation statements)

References 11 publications

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“…The clastogenic effect of MEHP on CHO cells, reported previously (5), was confirmed in the present study and demonstrated also in an unrelated cell line of rat liver origin (RL4). In RL4 cells an increase in endoreduplication was also observed.…”

Section: Discussionsupporting

confidence: 75%

“…However, such a reaction seems unlikely on chemical grounds and has not been demonstrated in vivo or in vitro (14). In addition, negative results have been reported for MEHP in a variety of mutagenicity test systems, including the sister chromatid exchange tests and HGPRT cell mutation assay in CHO cells in our laboratory (5). The possibility that a clastogenic metabolite of MEHP is formed within CHO and RL4 cells cannot be ruled out.…”

Section: Discussionmentioning

confidence: 79%

“…Chromosome analysis was carried out as described previously (5). Both CHO and RL4 cells were exposed for 2 hr to medium containing MEHP and treated with colcemid (0.1 ,ug/mL) from 22 Figure 1 shows the relationship between Trypan Blue uptake at the end of the 2-hr treatment with MEHP and the ability to MEHP-treated cells to grow into colonies.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Studies on the genetic effects of phthalic acid esters on cells in culture.

Phillips¹,

Anderson²,

Gangolli³

1986

Environ Health Perspect

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Mono(2-ethylhexyl) phthalate (MEHP) induced chromosome aberrations in cells of two culture lines, one derived from Chinese hamster ovary cells (CHO) and the other from rat liver cells (RL4). In CHO cells, the clastogenicity of MEHP was unaffected by the presence of an exogenous metabolic activation system (S-9 mix). 2-Ethylhexanol, o-phthalic acid, and phthalic anhydride were without effect.Cytochemical methods and assays for carnitine acetyltransferase and KCN-insensitive palmitoyl CoA oxidation were employed to determine whether chromosome damage was associated with peroxisome proliferation. No evidence of an increase in peroxisome numbers or of induction of marker enzymes was found in CHO cells treated with MEHP for up to 72 hr. Clofibric acid and BR931 were also ineffective.Observations on changes in CHO cell structure and permeability, and on the haemolytic effects of phthalate monoesters, suggest that the cytotoxicity of MEHP may be due primarily to its action on cell membranes. Since chromosome damage was observed only at cytotoxic concentrations, it is suggested that damage to lysosomal membranes and the release of endonucleases may be responsible for the observed clastogenicity of MEHP in vitro.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 79%

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Studies on the genetic effects of phthalic acid esters on cells in culture.

Phillips¹,

Anderson²,

Gangolli³

1986

Environ Health Perspect

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“…Taken together, the in vivo and in vitro studies suggest that EHD is unlikely to pose a significant genotoxic hazard. The overall absence of genotoxic potential with EHD accords with the lack of genotoxic activity in multiple studies with 2-ethylhexanol, which differs from EHD only by the absence of a hydroxyl group on the third carbon atom (Phillips et al, 1982;Kirby et al, 1983;Putman et al, 1983;Zeiger et al, 1985).…”

Section: Genetic Toxicologysupporting

confidence: 67%

Toxicology Update

Ballantyne¹

2005

J. Appl. Toxicol.

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“…The other negative data in this study support this conclusion. Furthermore, although toxic effects other than mutagenicity are known to induce sperm abnormalities (41,42), such appears not to be the case with DEHP The genotoxicity that is observed with phthalates by others (3,(5)(6)(7)12,13,15) occurs at very high concentrations. Accordingly, the influences of limited solubility, impurities, or an indirect genotoxic effect resulting from primary toxicity should be considered seriously as a causative factor in these cases.…”

Section: Discussionmentioning

confidence: 99%

Genetic toxicology of phthalate esters: mutagenic and other genotoxic effects.

Douglas¹,

Hugenholtz²,

Blakey³

1986

Environ Health Perspect

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was examined in both adult mice and rats, while peripheral blood micronuclei were scored in mice up to 4 weeks after treatment. In mice, DEHP at 1/6 LD50 significantly depressed body weight gain for up to 12 weeks after treatment, and reduced epididymal sperm number by 4 weeks. Numbers of morphologically abnormal sperm did not differ from controls in the 12 weeks following treatment. In addition, DEHP did not increase the numbers of peripheral blood micronuclei.Studies in the rat indicated that exposure to doses of 1/6 and /12 of the LD50 per day of DEHP resulted in a reduced gain in body weight compared to controls. Testis weight, sperm number, and numbers of morphologically abnormal sperm were unaffected by DEHP following treatment. In separate experiments, DEHP did not induce sister chromatid exchange (SCE) or DNA damage in Chinese hamster ovary (CHO) cells. Although DEHP is known to cause testicular atrophy in rats and to a lesser extent in mice, it did not cause an increase in abnormal sperm in either species. Together with the CHO and micronucleus data, these findings suggest that DEHP has a low probability of causing genetic damage capable of being transmitted through the male germ line.

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Genotoxicity studies of di(2-ethylhexyl)phthalate and its metabolites in CHO cells

Cited by 66 publications

References 11 publications

Studies on the genetic effects of phthalic acid esters on cells in culture.

Studies on the genetic effects of phthalic acid esters on cells in culture.

Toxicology Update

Genetic toxicology of phthalate esters: mutagenic and other genotoxic effects.

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