Comparative distribution, excretion and metabolism of di-(2-ethylhexyl) phthalate in rats, dogs and miniature pigs

Ikeda, George J.; Sapienza, P.P.; Couvillion, J.L.; Färber, Theodore M.

doi:10.1016/s0015-6264(80)80012-5

Cited by 30 publications

(10 citation statements)

References 9 publications

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“…Low detections of phthalates in the liver may be related to the activity of metabolic enzymes which are high in the liver. Following oral exposure to radiolabeled phthalates, the highest proportions of residues were found in the gastro-intestinal tract, bile, and liver of various mammals (e.g., [22], [23]). After 4 days, a majority of the radioactivity was found in the urine and feces, suggesting that the previous tissues were primarily responsible for metabolic breakdown.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Relative Importance of Oral and Dermal Contaminant Exposure in Reptiles: Insights from Studies Using the Western Fence Lizard (Sceloporus occidentalis)

et al. 2014

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Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals.

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Section: Discussionmentioning

confidence: 99%

Unraveling the Relative Importance of Oral and Dermal Contaminant Exposure in Reptiles: Insights from Studies Using the Western Fence Lizard (Sceloporus occidentalis)

et al. 2014

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“…Studies of bile in several species (Ikeda et al 1980) indicate that DEHP metabolites undergo entero-hepatic circulation. There is an indication of entero-hepatic circulation of MEHP in our study since the plasma concentration-time profile was biphasic during the absorption phase.…”

Section: Discussionmentioning

confidence: 99%

“…Most studies on the kinetics of DEHP and/or its metabolite mono(2-ethylhexyl) phthalate (MEHP) have been performed in rodents, but also to a limited degree in other species such as dogs, miniature pigs and primates (Ikeda et al 1980;Oishi and Hiraga 1982;Rhodes et al 1986;Schmid and Schlatter 1985). These studies have demonstrated differences between species, as well as between different routes of administration, for parameters such as systemic bioavailability of DEHP and MEHP (Ikeda et al 1980, Oishi andHiraga 1982;Rhodes et al1986;Sjo¨berg et al 1985).…”

Section: Introductionmentioning

confidence: 99%

Kinetics of orally administered di(2-ethylhexyl) phthalate and its metabolite, mono(2-ethylhexyl) phthalate, in male pigs

et al. 2004

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Di(2-ethylhexyl) phthalate (DEHP) is used as a plastic softener in the polymer industry and is widespread in medical devices. DEHP has been incriminated as an endocrine-disrupting chemical, and the effects of DEHP in various species have included disturbances in the reproductive system. The effects of the chemical have varied, depending upon exposure routes and species. This study was performed in order to characterise the kinetics of DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) in the young male pig, an omnivore model-species for research in reproductive toxicology. Eight pigs were given 1000 mg DEHP/kg bodyweight by oral gavage. The concentrations of DEHP and MEHP were then measured in the plasma and tissues of the pigs at different time points after administration. There was no consistent rise above contamination levels of concentrations of DEHP in the plasma of the pigs. However, the metabolite MEHP reached the systemic blood circulation. The half-life of MEHP in the systemic blood circulation was calculated to be 6.3 h. Absorption from the intestine was biphasic in six of the eight pigs and the mono-exponential elimination-phase started 16 h after the after the administration of DEHP. To conclude, MEHP consistently reaches the systemic circulation in the pig when DEHP is administered orally. The kinetic pattern of the parent substance on the other hand is more difficult to characterise.

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Section: Introductionmentioning

confidence: 99%

“…Choosing species other than rodents as model animals may improve our knowledge in this matter. The kinetics of DEHP in different species has been studied and, for example, it has been shown that DEHP is eliminated mainly through urine excretion in the rat, whereas in the pig, faecal excretion dominates (Ikeda et al, 1980). The pig also seems to absorb less DEHP and MEHP after oral administration of DEHP compared with the rat (Ljungvall et al, 2004), which makes it more similar to primates (Rhodes et al, 1986;Kessler et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Does exposure to di(2‐ethylhexyl) phthalate in pre‐pubertal boars affect semen quality post‐puberty?

et al. 2006

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Di(2-ethylhexyl) phthalate (DEHP), a plastic softener used in polyvinyl chloride (PVC) products, has been ascribed to have toxic effects on animal reproduction. The present study aimed at determining potential late effects of pre-pubertal oral exposure to DEHP on semen quality in young pigs. Ten pairs of cross-bred male siblings were used. One brother in each pair became, at random, the test animal while the other acted as control. Test males were exposed to 300 mg/kg body weight (bw) of DEHP administered orally three times a week from 3 to 7 weeks of age. The control group was given placebo (water). Semen analyses started when the boars reached 6 months of age, with semen collected twice weekly, until animals were 9 months of age. Semen was evaluated for ejaculate volume, sperm concentration, total sperm count, sperm motility, sperm morphology (including presence of cells other than spermatozoa) and sperm plasma membrane integrity. Total sperm motility tended to be lower while local motility was higher in the DEHP-exposed group compared with controls (p = 0.07) when assessed by computer-assisted sperm analysis. The DEHP-exposed group had a significantly (p < 0.05) lower percentage of spermatozoa with tailless, defective heads (at 7-8 months of age) and double-folded tails (at 6-7, 7-8 and 6-9 months of age), compared with controls (albeit always under 5%). In summary, there were no obvious adverse effects of early oral exposure to 300 mg/kg bw of DEHP on sperm output and sperm quality in post-pubertal young boars.

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Comparative distribution, excretion and metabolism of di-(2-ethylhexyl) phthalate in rats, dogs and miniature pigs

Cited by 30 publications

References 9 publications

Unraveling the Relative Importance of Oral and Dermal Contaminant Exposure in Reptiles: Insights from Studies Using the Western Fence Lizard (Sceloporus occidentalis)

Unraveling the Relative Importance of Oral and Dermal Contaminant Exposure in Reptiles: Insights from Studies Using the Western Fence Lizard (Sceloporus occidentalis)

Kinetics of orally administered di(2-ethylhexyl) phthalate and its metabolite, mono(2-ethylhexyl) phthalate, in male pigs

Does exposure to di(2‐ethylhexyl) phthalate in pre‐pubertal boars affect semen quality post‐puberty?

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