Metabolism of Drugs. XLVII. Metabolic Fate of p-Hydroxybenzoic Acid and its Derivatives in Rabbit. (4)

Tsukamoto, Hisao; Terada, Seisuke

doi:10.1248/cpb.12.765

Cited by 48 publications

(18 citation statements)

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“…Parabens are quickly absorbed from the gastrointestinal tract and from blood, hydrolysed to p-hydroxybenzoic acid, conjugated and the conjugate excreted in the urine (Jones et al, 1956;Heim et al, 1957;Tsukamoto & Terada, 1960, 1962, 1964Derache & Gourdon, 1963;Phillips et al, 1978;Kiwada et al, 1979). Parabens also can be absorbed rapidly through intact skin (Whitworth & Jun, 1973;Fischmeister et al, 1975;Komatsu & Suzuki, 1979) and this can be influenced by the presence of penetration enhancers found in cosmetic preparations (Kitagawa et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Concentrations of parabens in human breast tumours

Darbre

Aljarrah

Miller

et al. 2004

J of Applied Toxicology

716

371

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Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng x g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng x g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues.

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Section: Introductionmentioning

confidence: 99%

Concentrations of parabens in human breast tumours

Darbre

Aljarrah

Miller

et al. 2004

J of Applied Toxicology

716

371

View full text Add to dashboard Cite

show abstract

“…Animal studies have shown that parabens are quickly absorbed from the gastrointestinal tract and from the blood, hydrolysed to p-hydroxybenzoic acid, conjugated and the conjugate excreted in urine (Jones et al, 1956;Heim et al, 1957;Tsukamoto and Terada, 1960, 1962, 1964Derache and Gourdon, 1963;Phillips et al, 1978;Kiwada et al, 1979). Parabens also can be absorbed rapidly through skin (Whitworth and Jun, 1973;Fischmeister et al, 1975;Komatsu and Suzuki, 1979;Bando et al, 1997;Kitigawa et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Oestrogenic activity ofp-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines

2005

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This paper addresses the question of whether p-hydroxybenzoic acid, the common metabolite of parabens, possesses oestrogenic activity in human breast cancer cell lines. The alkyl esters of p-hydroxybenzoic acid (parabens) are used widely as preservatives in consumer products to which the human population is exposed and have been shown previously to possess oestrogenic activity and to be present in human breast tumour tissue, which is an oestrogen-responsive tissue. Recent work has shown p-hydroxybenzoic acid to give an oestrogenic response in the rodent uterotrophic assay. We report here that p-hydroxybenzoic acid possesses oestrogenic activity in a panel of assays in human breast cancer cell lines. p-Hydroxybenzoic acid was able to displace [(3)H]oestradiol from cytosolic oestrogen receptor of MCF7 human breast cancer cells by 54% at 5 x 10(6)-fold molar excess and by 99% at 10(7)-fold molar excess. It was able to increase the expression of a stably integrated oestrogen responsive reporter gene (ERE-CAT) at a concentration of 5 x 10(-4) M in MCF7 cells after 24 h and 7 days, which could be inhibited by the anti-oestrogen ICI 182 780 (Faslodex, fulvestrant). Proliferation of two human breast cancer cell lines (MCF7, ZR-75-1) could be increased by 10(-5) M p-hydroxybenzoic acid. Following on from previous studies showing a decrease in oestrogenic activity of parabens with shortening of the linear alkyl chain length, this study has compared the oestrogenic activity of p-hydroxybenzoic acid where the alkyl grouping is no longer present with methylparaben, which has the shortest alkyl group. Intrinsic oestrogenic activity of p-hydroxybenzoic acid was similar to that of methylparaben in terms of relative binding to the oestrogen receptor but its oestrogenic activity on gene expression and cell proliferation was lower than that of methylparaben. It can be concluded that removal of the ester group from parabens does not abrogate its oestrogenic activity and that p-hydroxybenzoic acid can give oestrogenic responses in human breast cancer cells.

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“…However, several carboxylesterase isozymes catalyzing hydrolysis of parabens have been identified in rat and human hepatic and small-intestinal microsomes (Ozaki et al, 2013). The main metabolic pathway in mammals is hydrolysis to 4-hydroxybenzoic acid and alcohols, which are excreted after conjugation with glucuronide, sulfate or glycine (Tsukamoto and Terada, 1964). In the presence of alcohols, transesterified parabens were formed by tissue microsomes (Fujino et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450-inhibitory activity of parabens and phthalates used in consumer products

et al. 2016

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-The in vitro cytochrome P450 (CYP)-inhibitory effects of 11 parabens and 7 phthalates used in consumer products, as well as their hydrolytic metabolites, were investigated, using rat liver microsomes as an enzyme source. The effects on individual CYP isozymes were evaluated by assaying inhibition of activities towards specific substrates, i.e., ethoxyresorufin O-dealkylase (EROD), methoxyresorufin O-dealkylase (MROD), pentoxyresorufin O-dealkylase (PROD), 7-benzyloxy-4-trifluoromethylcoumarin dealkylase (BFCD), 7-methoxy-4-trifluoromethylcoumarin dealkylase (MFCD) and 7-ethoxy-4 -trifluoromethylcoumarin dealkylase (EFCD) activities. These activities were dose-dependently inhibited, most potently by medium-side-chain parabens (C6-9) and phthalates (C4-6), and less potently by shorterand longer-side-chain esters. The hydrolytic product of parabens, 4-hydroxybenzoic acid, was not inhibitory, while those of phthalates, phthalic acid monoesters, showed lower inhibitory activity than the parent phthalates. Parabens showed relatively potent inhibition of MFCD activity, considered to be mainly due to CYP2C, and phthalates showed relatively potent inhibition of PROD activity, considered to be mainly due to CYP2B.

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Metabolism of Drugs. XLVII. Metabolic Fate of p-Hydroxybenzoic Acid and its Derivatives in Rabbit. (4)

Cited by 48 publications

References 0 publications

Concentrations of parabens in human breast tumours

Concentrations of parabens in human breast tumours

Oestrogenic activity ofp-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines

Cytochrome P450-inhibitory activity of parabens and phthalates used in consumer products

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