A dose-response study on the estrogenic activity of benzophenone-2 on various endpoints in the serum, pituitary and uterus of female rats.
The tetrahydroxylated biphenyl-ketone 2,2',4,4'-tetrahydroxybenzophenone (BP2), one of twelve benzophenone-derived UV-filters, is used in cosmetic products and in packaging materials to protect these products from light induced damage. Recently published studies showed that BP2 exerts estrogenic activity; thus, it is an endocrine active chemical. We present data from a pharmacodynamic dose-response experiment with five dosages of BP2 applied per gavage to adult ovariectomized (ovx) rats for 5 days. Estradiol-valerate (E2) served as a control compound. The uterotrophic assay, proposed by the OECD, was modified to have a broader view on endocrine activity outside the urogenital tract to prevent that undesirable actions in other organs regulated by estrogens are missed. The gene expression levels of marker genes of estrogenic action were measured by semi-quantitative RT-PCR. Metabolic parameters were assessed by determination of the serum concentrations of leptin, cholesterol, high- and low-density lipoproteins, and triglycerides in the serum. Administration of BP2 at dosages of 10-1,000 mg/kg bodyweight led to changes of these parameters comparable to the changes in the E2 group with 0.6 mg/kg bodyweight. For the observed estrogenic activities of BP2, the "no observed adverse effect levels" were determined. Additionally, the data were further analyzed using the benchmark approach. If BP2 is transcutaneously absorbed in the human, the obtained threshold values would suggest refraining from the further use of BP2 as UV-filter in cosmetic products although additional toxicological studies should be conducted to clarify possible adverse effects.
Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Str. 40, 37099 Goettingen, Germany.
Christiane
C
Schlecht
Holger
H
Klammer
Wolfgang
W
Wuttke
Hubertus
H
Jarry
D000818:Animals; D001577:Benzophenones / Q000633:toxicity*; D003176:Complement C3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D037101:Luteinizing Hormone, beta Subunit / Q000378:metabolism; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D018570:Risk Assessment; D013473:Sunscreening Agents / Q000633:toxicity; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D001577:Benzophenones; D003176:Complement C3; D047629:Estrogen Receptor beta; D004967:Estrogens; D015292:Glycoprotein Hormones, alpha Subunit; D020738:Leptin; D008055:Lipids; D037101:Luteinizing Hormone, beta Subunit; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013473:Sunscreening Agents; C118565:TERP-1; D007334:Insulin-Like Growth Factor I; C035476:2,2',4,4'-tetrahydroxybenzophenone