Hydrolysis of phthalate esters by the gastro-intestinal contents of the rat

Rowland, Ian; Cottrell, Richard C.; Phillips, John C.

doi:10.1016/s0015-6264(77)80257-5

Cited by 90 publications

(35 citation statements)

References 14 publications

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“…As discussed elsewhere (38), we believe this to be due to damage to the membranes of the peroxisomes. Second, the overall levels of cytochrome P-450 rose above control levels at 3 (40) and humans (41) to hepatotoxins often varies with age and, indeed, age changes (and lowers) the ability of the rat liver to hydrolyze DEHP to MEHP (42), although the relevance of the last observation to rats administered DEHP in the diet must be open to doubt as in this case most hydrolysis occurs in the gut (43,44).…”

Section: Stage 4 the Lysosomal Enzyme -D-galactosidasementioning

confidence: 99%

Effects of phthalic acid esters on the liver and thyroid.

Hinton¹,

Mitchell²,

Mann³

et al. 1986

Environ Health Perspect

126

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The effects, over periods from 3 days to 9 months of administration, of diets containing di-2-ethylhexyl phthalate are very similar to those observed in rats administered diets containing hypolipidemic drugs such as clofibrate. Changes occur in a characteristic order commencing with alterations in the distribution of lipid within the liver, quickly followed by proliferation of hepatic peroxisomes and induction of the specialized P450 isoenzyme(s) catalyzing w oxidation of fatty acids. There follows a phase of mild liver damage indicated by induction of glucose-6-phosphatase activity and a loss of glycogen, eventually leading to the formation of enlarged lysosomes through autophagy and the accumulation of lipofuscin. Associated changes are found in the kidney and thyroid. The renal changes are limited to the proximal convoluted tubules and are generally similar to changes found in the liver. The effects on the thyroid are more marked. Although the levels of thyroxine in plasma fall to about half normal values, serum triiodothyronine remains close to normal values while the appearance of the thyroid varies, very marked hyperactivity being noted 7 days after commencement of treatment, this is less marked at 14 days, but even after 9 months treatment there is clear cut evidence for hyperactivity with colloid changes which indicate this has persisted for some time. Straight chain analogs of di-2-ethylhexyl phthalate, di-n-hexyl phthalate and di-n-oxtyl phthalate differ entirely in their short-term effects on the liver and kidney but have similar effects on the thyroid.The short-term in vivo hepatic effects of the three phthalate esters can be reproduced in hepatocytes in tissue culture. All three phthalate esters, as well as clofibrate, have early marked effects on the metabolism of fatty acids in isolated hepatocytes. The nature of these changes is such as to increase storage of lipid in the liver. A hypothesis is presented to explain the progress from these initial metabolic effects to the final formation of liver tumors.

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Section: Stage 4 the Lysosomal Enzyme -D-galactosidasementioning

confidence: 99%

Effects of phthalic acid esters on the liver and thyroid.

Hinton¹,

Mitchell²,

Mann³

et al. 1986

Environ Health Perspect

126

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“…7,8) DEHP is rapidly absorbed from the rodent gut, mostly in the form of the monoester because of the rapid hydrolysis of the DEHP by gut lipases. 15,16) The present studies showed that MBP and MEHP were formed by the monohydrolysis of DBP and DEHP in human saliva.…”

Section: Hydrolysis Of Dbp and Dehp By Saliva To Formmentioning

confidence: 99%

“…6) Orally-ingested PAE is hydrolyzed to its monoester by endogenous esterases of many tissues, such as the small intestine. 7,8) Monoesters are thought to be more hepatocarcinogenic than their parent compound. 9) The rate of DINP release from PVC toys chewed by children has been measured using two general migration tests.…”

Section: Introductionmentioning

confidence: 99%

Monoester Formation by Hydrolysis of Dialkyl Phthalate Migrating from Polyvinyl Chloride Products in Human Saliva.

Niino

Ishibashi

Itho

et al. 2001

JOURNAL OF HEALTH SCIENCE

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“…DEHP is known to be hydrolyzed to MEHP and 2-ethylhexanol (6-8). The hydrolysis is catalyzed by pancreatic lipase (9), acid and alkaline esterases in intestinal mucosa (10,11), plasma (12), and liver (6). Tissue distribution of MEHP after the oral administration of DEHP (or MEHP) has been reported by several investigators in pregnant or nonpregnant rats (7,13,14).…”

Section: Introductionmentioning

confidence: 99%

Fetotoxic Effects of Mono-2-Ethylhexyl Phthalate (MEHP) in Mice

Tomita¹,

Nakamura²,

Yagi³

et al. 1986

Environmental Health Perspectives

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Mono(2-ethylhexyl) phthalate (MEHP), one of the main metabolites of di(2-ethylhexyl) phthalate (DEHP), exerted embryo/fetotoxic effects similar to those of DEHP at lower doses. Oral administration of MEHP (1 mL/kg) to the mice of 8 days gestation resulted in less than 32% of live fetuses, all of which were deformed.When DEHP (10 mL/kg) was given to the pregnant mice of 8 days gestation, approximately 0.03% and 0.003% of the administered dose was found in fetuses as DEHP and MEHP, respectively, after 12 hr.The presence of the MEHP in fetuses is probably due to the transplacental crossing of the MEHP formed in the maternal body, since the fetuses of mice up to day 9 of pregnancy showed no hydrolytic activity of DEHP to MEHP. Crossing of MEHP through the placenta was proven by an experiment in which MEHP was administered in pregnant mice.A single injection of MEHP (25 or 50 mg/kg), but not DEHP (500 mg/kg) into pregnant mice, induced a significantly high incidence of somatic mutations in the coat hair of offspring of mice (KYG, 9 x PW, d; C57BL/6Crj, 9 x PW, 6). All these data suggest that MEHP could be responsible for the embryotoxic/ fetotoxic effects observed with DEHP.

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Hydrolysis of phthalate esters by the gastro-intestinal contents of the rat

Cited by 90 publications

References 14 publications

Effects of phthalic acid esters on the liver and thyroid.

Effects of phthalic acid esters on the liver and thyroid.

Monoester Formation by Hydrolysis of Dialkyl Phthalate Migrating from Polyvinyl Chloride Products in Human Saliva.

Fetotoxic Effects of Mono-2-Ethylhexyl Phthalate (MEHP) in Mice

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