The Chemical UV‐Filter 3‐Benzylidene Camphor Causes an Oestrogenic Effect in an <i>in vivo</i> Fish Assay

Holbech, Henrik; Nørum, Ulrik; Korsgaard, Bodil; Bjerregaard, Poul

doi:10.1111/j.1742-7843.2007.auindex_1.x-i1

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…Schreurs et al (2002) observed no estrogenicity in transgenic zebrafish exposed for 96 h at 10 lM of OMC (2.90 mg/l), OD-PABA (2.77 mg/l), HMS (2.62 mg/l), BP3 (2.28 mg/l), and 1 lM of 4MBC (0.25 mg/l), which is consistent with our data with these UV filters analyzed at similar concentrations but for a longer period of time. Injection of high concentrations of 3BC (27, 68, 137 mg/kg and higher) induced VTG in rainbow trout (Holbech et al, 2002). In medaka, estrogenic activity of 4MBC and OMC was observed only at about 200 times higher concentrations (Inui et al, 2003), but it was not found at 20 times higher concentrations than in our study.…”

Section: Comparison Of In Vivo Activitiescontrasting

confidence: 70%

“…Estrogenic activity has also been observed experimentally in vivo in rats (Durrer et al, 2005;Schlumpf et al, 2001;Seidlová-Wuttke et al, 2004). In fish, high concentrations of 3-benzylidene camphor, 4-methyl-benzylidene camphor, and octyl-methoxycinnamate (Holbech et al, 2002;Inui et al, 2003) were found to be estrogenic after short-term exposure. Contrary to these studies, no estrogenicity was observed at 10 lM octyl-methoxycinnamate, benzophenone-3, homosalate, octyl dimethyl-p-aminobenzoic acid, butyl methoxydibenzoylmethane, and 1 lM 4-methyl-benzylidene camphor after short-term exposure of transgenic zebrafish (Schreurs et al, 2002).…”

Section: Introductionmentioning

confidence: 85%

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Comparison of In Vitro and In Vivo Estrogenic Activity of UV Filters in Fish

Kunz¹,

Galicia²,

Fent³

2006

Toxicological Sciences

242

112

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In this work, we evaluate whether in vitro systems are good predictors for in vivo estrogenic activity in fish. We focus on UV filters being used in sunscreens and in UV stabilization of materials. First, we determined the estrogenic activity of 23 UV filters and one UV filter metabolite employing a recombinant yeast carrying the estrogen receptor of rainbow trout (rtERalpha) and made comparisons with yeast carrying the human hERalpha for receptor specificity. Benzophenone-1 (BP1), benzophenone-2 (BP2), 4,4-dihydroxybenzophenone, 4-hydroxybenzophenone, 2,4,4-trihydroxy-benzophenone, and phenylsalicylate showed full dose-response curves with maximal responses of 81-115%, whereas 3-benzylidene camphor (3BC), octylsalicylate, benzylsalicylate, benzophenone-3, and benzophenone-4 displayed lower maximal responses of 15-74%. Whereas the activity of 17beta-estradiol was lower in the rtERalpha than the hERalpha assay, the activities of UV filters were similar or relatively higher in rtERalpha, indicating different relative binding activities of both ER. Subsequently, we analyzed whether the in vitro estrogenicity of eight UV filters is also displayed in vivo in fathead minnows by the induction potential of vitellogenin after 14 days of aqueous exposure. Of the three active compounds in vivo, 3BC induced vitellogenin at lower concentrations (435 microg/l) than BP1 (4919 microg/l) and BP2 (8783 microg/l). The study shows, for the first time, estrogenic activities of UV filters in fish both in vitro and in vivo. Thus we propose that receptor-based assays should be used for in vitro screening prior to in vivo testing, leading to environmental risk assessments based on combined, complementary, and appropriate species-related assays for hormonal activity.

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Section: Comparison Of In Vivo Activitiescontrasting

confidence: 70%

Section: Introductionmentioning

confidence: 85%

Comparison of In Vitro and In Vivo Estrogenic Activity of UV Filters in Fish

Kunz¹,

Galicia²,

Fent³

2006

Toxicological Sciences

242

112

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“…So far UV filters have been evaluated for estrogenic activity in fish by investigating VTG induction only. This was observed in juvenile fathead minnows for 3BC, BP1, and BP2 , and also found after injection of 3BC (68 mg/kg) in rainbow trout (Holbech et al, 2002), and after aqueous exposure to 100 mg/l 4MBC and 10 mg/l OMC in male medaka (Inui et al, 2003). The benefit of measuring VTG induction as a biomarker for estrogenicity is obvious.…”

Section: Effects Of 3-benzylidene Camphor On Fish Reproductionmentioning

confidence: 52%

“…However, its lipophilic nature makes 3BC prone for bioaccumulation in aquatic organisms. 3BC was shown to have estrogenic activity in vitro (Holbech et al, 2002; and in vivo leading to significant VTG induction in fish (Holbech et al, 2002;. So far, it was unknown whether 3BC affects reproduction in fish in addition.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the fact that estrogenic activity has been observed in fish in vitro (Kunz and Fent, in press) and in vivo makes UV filters of potential environmental concern for aquatic organisms. 3-Benzylidene camphor (3BC), benzophenone-1, and benzophenone-2 led to vitellogenin (VTG) induction in juvenile fathead minnows , and this was also found for 3BC in rainbow trout (Holbech et al, 2002), 4-methyl benzylidene camphor (4MBC), and octylmethoxycinnamate (OMC) in male medaka (Inui et al, 2003). Among the UV filters, 3BC showed highest estrogenic potency in vivo in fish but also in rats (Schlumpf et al, 2004).…”

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confidence: 91%

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The Ultraviolet Filter 3-Benzylidene Camphor Adversely Affects Reproduction in Fathead Minnow (Pimephales promelas)

Kunz

Gries²,

Fent³

2006

Toxicological Sciences

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The ultraviolet (UV) filter 3-benzylidene camphor (3BC) is used in personal care products and in a number of materials for UV protection. 3BC has been shown in vitro and in vivo in fish to be estrogenic, but possible effects on fertility and reproduction are unknown. In this study we evaluate whether 3BC affects reproduction of fish Pimephales promelas. After a preexposure period of 21 days, reproductively mature fathead minnows were exposed to increasing concentrations of 3BC for 21 days in a static-renewal procedure. Actual 3BC concentrations decreased to 23% of initial levels and median concentrations were 0.5, 3, 33, 74, and 285 microg/l. 3BC affected reproduction in a dose-dependent manner with weak effects on fecundity at 3 microg/l, a significant decrease at 74 microg/l, and a cessation of reproduction at 285 microg/l. 3BC was accumulated in fish with an average bioconcentration factor of 313 +/- 151. Dose-dependent demasculinization in secondary sex characteristics of male fish and dose-dependent induction of plasma vitellogenin occurred, which was significant at 74 microg/l and higher. 3BC had a profound and dose-dependent effect on the histology of gonads of male and female fish at 3 microg/l and higher. At 74 and 285 microg/l, oocyte and spermatocyte development was inhibited in male and female gonads. Testes of exposed males had much fewer spermatogenic cysts, and ovaries of exposed females had much fewer mature but more atretic, follicles. This study shows significant effects of the UV filter 3BC on fertility, gonadal development, and reproduction of fish after short-term exposure that may have negative consequences on the population level.

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Environmental Endocrine Toxicology

Bjerregaard

2009

General, Applied and Systems Toxicology

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Disorders in sexual development have increased in frequency in certain geographical regions during the latter half of the 20th century. In humans, this is expressed as elevated prevalence of testicular cancer, cryptorchidism and hypospadias and decreased sperm counts, collectively termed the ‘Testicular Dysgenesis Syndrome’ (TDS). A fairly large number of chemicals in widespread use (i.e. alkylphenols, phthalates, bisphenol, PCBs, pesticides) have been shown to interfere with the synthesis and/or the function of sex hormones, and exposure to some of these chemicals (individually or in mixtures) compromises normal sexual development in animals in tests in the laboratory. The occurrence of TDS in humans seems to be associated with general life style factors, but although associations between TDS and exposure to certain chemicals (e.g. PCBs, phthalates, pesticides) have been demonstrated, firm causal relationships have not yet been established. In nature, effects caused by exposure to discharged hormones or chemicals with endocrine disrupting properties have been firmly documented among snails, fish, amphibians, reptiles, birds and mammals: The anti‐fouling biocide tributyltin masculinizes female snails, synthetic p‐pill estrogens and natural estrogens feminize male fish downstream discharges from sewage treatment plants, effluents from pulp and paper mills masculinize female fish and various chlorinated hydrocarbons have feminized higher vertebrates such as alligators and birds.

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The Chemical UV‐Filter 3‐Benzylidene Camphor Causes an Oestrogenic Effect in an in vivo Fish Assay

Cited by 6 publications

References 19 publications

Comparison of In Vitro and In Vivo Estrogenic Activity of UV Filters in Fish

Comparison of In Vitro and In Vivo Estrogenic Activity of UV Filters in Fish

The Ultraviolet Filter 3-Benzylidene Camphor Adversely Affects Reproduction in Fathead Minnow (Pimephales promelas)

Environmental Endocrine Toxicology

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