Influence of Polysorbate 20 and Sodium Cholate on Uptake of p-Hydroxybenzoates by the Frog, Rana pipiens

Whitworth, Clyde W.; Jun, H. W.

doi:10.1002/jps.2600621139

Cited by 15 publications

(11 citation statements)

References 5 publications

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“…If no alternatives to parabens can be found for effective use as preservatives in the many thousands of food, drug and cosmetic products to which they are added (Elder, 1984), then it might at least be worth considering using methylparaben in preference to the larger parabens. Despite its lower antimicrobial activity (Murrell and Vincent, 1950), the advantages of reduced absorption through the skin (Whitworth and Jun, 1973) and lower oestrogenic activity would make the preferential use of methylparaben a sensible precaution option.…”

Section: Discussionmentioning

confidence: 99%

Oestrogenic activity of benzylparaben

Darbre

Byford

Shaw

et al. 2003

J of Applied Toxicology

146

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Previous work has demonstrated that the alkyl esters of p-hydroxybenzoic acid (parabens) possess oestrogenic activity, which increases with length of alkyl chain from methylparaben to n-butylparaben and with branching in the alkyl chain from n-butylparaben to isobutylparaben. This study reports on the oestrogenic activity of benzylparaben in a variety of assays in vitro and in vivo. Benzylparaben was able to displace [(3)H]oestradiol from cytosolic oestrogen receptor (ER) of MCF7 human breast cancer cells by 22% at 1000-fold molar excess, by 40% at 10,000-fold molar excess, by 57% at 100 000-fold molar excess and by 100% at 1,000,000-fold molar excess. It was able to increase expression of a stably transfected oestrogen responsive reporter gene (ERE-CAT) in MCF7 cells after 24 h at 10(-5)M/10(-4)M and after 7 days at 10(-6)M/10(-5)M/10(-4)M. Proliferation of MCF7 cells could be increased by 10(-6)M/10(-5)M benzylparaben and this could be inhibited by 10(-7)M pure anti-oestrogen ICI 182,780, indicating that growth effects were ER mediated. Further evidence for ER-mediation was provided from the ability of benzylparaben to increase the growth of a second oestrogen-dependent human breast cancer cell line ZR-75-1, but not the oestrogen-insensitive MDA-MB-231 cell line. When tested in the presence of 10(-10)M 17beta-oestradiol, benzylparaben gave no antagonist response on the growth of either MCF7 or ZR-75-1 cells. Finally, benzylparaben could increase uterine weight in the immature mouse following topical application of three daily doses of 33 mg to dorsal skin. These results demonstrate that the oestrogenicity of methylparaben can be increased by the addition of an aryl group as well as by lengthening or branching the alkyl grouping.

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Section: Discussionmentioning

confidence: 99%

Oestrogenic activity of benzylparaben

Darbre

Byford

Shaw

et al. 2003

J of Applied Toxicology

146

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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). However, the presence of carboxylesterases in skin and subcutaneous fatty tissues results in varying hydrolysis to phydroxybenzoic acid (Lobemeier et al, 1996) and this can also influence absorption (Bando et al, 1997).…”

Section: Introductionmentioning

confidence: 95%

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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“…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). Human skin has been shown to possess isoforms of carboxylesterase (Lobemeier et al, 1996) and it has been suggested that this enzyme activity would result in hydrolysis of dermally applied paraben esters to p-hydroxybenzoic acid in the skin (Flower, 2004;Jeffrey and Williams, 2004).…”

Section: Introductionmentioning

confidence: 97%

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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Influence of Polysorbate 20 and Sodium Cholate on Uptake of p-Hydroxybenzoates by the Frog, Rana pipiens

Cited by 15 publications

References 5 publications

Oestrogenic activity of benzylparaben

Oestrogenic activity of benzylparaben

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

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