The in vitro hydrolysis of some phthalate diesters by hepatic and intestinal preparations from various species

Lake, Brian G.; Phillips, John C.; Linnell, J. C.; Gangolli, S.D.

doi:10.1016/0041-008x(77)90157-0

Cited by 130 publications

(48 citation statements)

References 21 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

View full text Add to dashboard Cite

show abstract

“…However, Lake et al 5) suggested that any toxic effects of PAEs would be governed by the constituent phthalate monoesters and/or alcohols. So in the present work, to examine this idea, we compared the toxicological effects of orally administered DBP, monobutyl phthalate (MBP) and PA in rats.…”

Section: Toxicologicalmentioning

confidence: 99%

Toxicity of dibutyl phthalate and its metabolites in rats.

Murakami

Nishiyama

Higuti

1986

Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene)

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“…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%