In vitro and in vivo estrogenicity of UV screens.
Ultraviolet (UV) screens are increasingly used as a result of growing concern about UV radiation and skin cancer; they are also added to cosmetics and other products for light stability. Recent data on bioaccumulation in wildlife and humans point to a need for in-depth analyses of systemic toxicology, in particular with respect to reproduction and ontogeny. We examined six frequently used UVA and UVB screens for estrogenicity in vitro and in vivo. In MCF-7 breast cancer cells, five out of six chemicals, that is, benzophenone-3 (Bp-3), homosalate (HMS), 4-methyl-benzylidene camphor (4-MBC), octyl-methoxycinnamate (OMC), and octyl-dimethyl-PABA (OD-PABA), increased cell proliferation with median effective concentrations (EC(50)) values between 1.56 and 3.73 microM, whereas butyl-methoxydibenzoylmethane (B-MDM) was inactive. Further evidence for estrogenic activity was the induction of pS2 protein in MCF-7 cells and the blockade of the proliferative effect of 4-MBC by the estrogen antagonist ICI 182,780. In the uterotrophic assay using immature Long-Evans rats that received the chemicals for 4 days in powdered feed, uterine weight was dose-dependently increased by 4-MBC (ED(50 )309mg/kg/day), OMC (ED(50) 935 mg/kg/day), and weakly by Bp-3 (active at 1,525 mg/kg/day). Three compounds were inactive by the oral route in the doses tested. Dermal application of 4-MBC to immature hairless (hr/hr) rats also increased uterine weight at concentrations of 5 and 7.5% in olive oil. Our findings indicate that UV screens should be tested for endocrine activity, in view of possible long-term effects in humans and wildlife.
Schlumpf
M
M
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. schlumpm@pharma.unizh.ch
Cotton
B
B
Conscience
M
M
Haller
V
V
Steinmann
B
B
Lichtensteiger
W
W
D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D002164:Camphor / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D045166:Estradiol Congeners / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051381:Rats; D020318:Rats, Long-Evans; D011960:Receptors, Estrogen / Q000187:drug effects*; D013473:Sunscreening Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014466:Ultraviolet Rays; D014599:Uterus / Q000187:drug effects*
D001577:Benzophenones; D002934:Cinnamates; D045166:Estradiol Congeners; D011960:Receptors, Estrogen; D013473:Sunscreening Agents; C118580:octylmethoxycinnamate; D002164:Camphor; C005290:oxybenzone