Comparative toxicity of di-(2-ethylhexyl)phthalate (dehp) in rats and marmosets

Rhodes, Christopher; Elcombe, Clifford R.; Batten, Peter L.; Bratt, H.; Jackson, Shaun; Pratt, Iona; Orton, Terry C.

doi:10.1016/0378-4274(83)90405-8

Cited by 2 publications

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“…This relationship has a great impact on the systemic burdens of potentially effective monoesters and thus could be one reason why phthalates with straight chain lengths of the alcohol moieties of C3-C7 (total C of the alcohol ≤ 8) were reproductive toxicants in contrast to those with longer straight chains (Furr et al, 2014;Gray et al, 2000;Poon et al, 1997). Since the kinetics of phthalates can be species-specific (shown for DEHP: Kessler et al, 2004Kessler et al, , 2012Kurata et al, 2012;Rhodes et al, 1986), the present data set in rats will be compared with the outcome of current investigations in humans in order to support the risk assessment of DPHP.…”

Section: Discussionmentioning

confidence: 99%

“…Foster et al, 1981;Oishi and Hiraga, 1980;Sjöberg et al, 1986). Regarding the species-specific burdens of the primary monoesters in venous blood, large species differences were identified in studies with DEHP (Kessler et al, 2004(Kessler et al, , 2012Kurata et al, 2012;Rhodes et al, 1986). As a basis for a risk estimation of DPHP, it is therefore reasonable to compare the burdens of the metabolically formed monoesters in blood of rats and humans.…”

Section: Introductionmentioning

confidence: 99%

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Di-(2-propylheptyl) phthalate (DPHP) and its metabolites in blood of rats upon single oral administration of DPHP

et al. 2016

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Di-(2-propylheptyl) phthalate (DPHP) does not act as a reproductive toxicant or endocrine disruptor in contrast to other phthalates. Considering adverse effects of phthalates to be linked to their metabolism, it was the aim of the present study to investigate in the rat the blood burden of DPHP and its metabolites as a basis for understanding the toxicological behavior of DPHP. Rats were administered single oral doses of DPHP of 0.7 and 100mg/kg body weight. Concentration-time courses of DPHP and metabolites were monitored in blood. The areas under the concentration-time curves in blood (AUCs), normalized for the dose of DPHP, showed the following order: DPHP

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Di-(2-propylheptyl) phthalate (DPHP) and its metabolites in blood of rats upon single oral administration of DPHP

et al. 2016

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Hepatocarcinogenic Potential of Di(2-Ethylhexyl)phthalate in Rodents and its Implications on Human Risk

Huber

Grasl‐Kraupp

Schulte‐Hermann

1996

Critical Reviews in Toxicology

283

140

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The plasticizer di(2-ethylhexyl) phthalate (DEHP), to which humans are extensively exposed, was found to be hepatocarcinogenic in rats and mice. DEHP is potentially set free from objects made of synthetic materials (e.g., those used in medicine). Chronically, the greatest amounts are transferred to persons undergoing hemodialysis (up to 3.1 mg/kg b.w. per day) who would thus be considered the individuals most endangered by tumorigenesis. Although toxicokinetics seem to play a certain unclear role in the course of DEHP-related toxicity, toxicodynamic factors appear more decisive. DEHP is a representative of "peroxisome proliferators" (PP), a distinct group of substances that, in rodents, do not only induce peroxisomes but also specific enzymes in other organelles, organ growth, and DNA synthesis. The cluster of the characteristic effects of PP is generally, although perhaps not quite appropriately summarized as "peroxisome proliferation," and is strongest in the liver. The lowest observed effect level (LOEL) and the no observed effect level (NOEL) of peroxisome proliferation in the rat, as determined by the induction of specific enzymes (peroxisomal beta-oxidation, carnitine-acetyl-transferase, cytochrome P-452), DNA synthesis, and hepatomegaly, may be assumed as 50 and 25 mg/kg b.w. per day, respectively. DEHP and other carcinogenic PP are neither genotoxic nor tumor initiators, but they appear to be tumor promoters, also implicating a threshold level for the carcinogenic effect. Although a causal relationship between a particular effect of peroxisome proliferation and hepatocarcinogenesis is as yet unknown, peroxisome proliferation as a whole phenomenon appears to be associated with the potential of tumor induction, as shown by comparison of the relative strength of individual PP and by comparison of species and organ specificities. Likewise, LOEL and NOEL of rodent carcinogenesis, that is, 300 and 50 to 100 mg/kg b.w. per day, respectively, are above but not too far from the corresponding values for the investigated parameters of peroxisome proliferation. Thus, with respect to dose alone, worst-case exposure in hemodialysis patients is at least 16-fold below the LOEL of any characterized PP-specific effect of DEHP and approximately 100-fold below that of DEHP-related tumorigenesis. Also, primates are less responsive to PP than rats with respect to the investigated biochemical and morphological parameters. If this lower primate responsiveness is extrapolated to estimate carcinogenicity in humans, we might thus arrive at an even larger safety margin than when based on exposure alone. Doses of PP hypolipidemics that had clearly induced several indicators of peroxisome proliferation in rats did not cause any clear-cut enhancements in the peroxisomes of patients, even though most of these hypolipidemics were considerably stronger PP than DEHP. Thus, an actual threat to humans by DEHP seems rather unlikely. Accordingly, hepatocarcinogenesis was neither enhanced in workers exposed to DEHP nor in patients treated with ...

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Comparative toxicity of di-(2-ethylhexyl)phthalate (dehp) in rats and marmosets

Cited by 2 publications

References 0 publications

Di-(2-propylheptyl) phthalate (DPHP) and its metabolites in blood of rats upon single oral administration of DPHP

Di-(2-propylheptyl) phthalate (DPHP) and its metabolites in blood of rats upon single oral administration of DPHP

Hepatocarcinogenic Potential of Di(2-Ethylhexyl)phthalate in Rodents and its Implications on Human Risk

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