Comparison of effects of estradiol (E2) with those of octylmethoxycinnamate (OMC) and 4-methylbenzylidene camphor (4MBC)--2 filters of UV light - on several uterine, vaginal and bone parameters.
OMC and 4MBC are 2 absorbers of ultraviolet light which are used in unknown quantities in sunscreens, cosmetics and plastic products to protect against UV light-induced damage of the skin or of fragrances or plastic material. From there, they were shown to reach surface water and/or by direct contamination or ingestion the human. Under various conditions in mice and rats, both substances were shown to be estrogenic. Therefore, we compared in vitro and in vivo the effects of chronic application of these compounds at 2 doses with those of E2, all administered via food. No signs of toxicity were observed under application of 0.6 mg E2, 57.5 or 275 mg of OMC, 57.5 or 250 mg of 4MBC; these amounts were ingested with 21 g of control food, 17.8 g E2 food, 20.6 g or 22.3 g OMC food and 23.7 or 22.8 g 4MBC food. In the uterus, vagina and bone, E2 exerted the expected stimulatory effects which were minimally shared by OMC and 4MBC in the uterus and vagina as assessed by histology and determination of a variety of estrogen-regulated genes such as insulin-like growth factor-1, progesterone receptor and estrogen receptor beta. In the bone, OMC had no effect, while 4MBC shared the antiosteoporotic effects of E2 as measured by quantitative computer tomography in the metaphysis of the tibia. The mechanism of action of 4MBC, however, appears to be different as E2 reduced serum osteocalcin and the C-terminal breakdown products of collagen-1alpha1 which were both increased by 4MBC. Taken together, these data indicate a very weak estrogenic effect of OMC and 4MBC in the uterus and in the vagina but not in the bone where 4MBC exerted antiosteoporotic effects by a different mechanism than E2.
Seidlová-Wuttke
D
D
Department of Clinical and Experimental Endocrinology, University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
Jarry
H
H
Christoffel
J
J
Rimoldi
G
G
Wuttke
W
W
D000818:Animals; D015519:Bone Density; D002164:Camphor / Q000031:analogs & derivatives* / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D009929:Organ Size / Q000187:drug effects; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013473:Sunscreening Agents / Q000494:pharmacology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D014621:Vagina / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism
D002934:Cinnamates; D004967:Estrogens; D013473:Sunscreening Agents; D004958:Estradiol; C118580:octylmethoxycinnamate; D002164:Camphor; C038939:enzacamene