Publications : 2019

McIntyre B, Zorilla L, Borghoff, S, Foster P. Assessment of avobenzone, ensulizole, homosalate, and padimate-O in endocrine disruptor screening panel studies. Poster at Society of Toxicology Annual Meeting, Baltimore, MD, March 2019.

Abstract

Avobenzone (ABZ), Ensulizole (ESZ), homosalate (HMS) and padimate-O (PMO) are UV absorbing agents commonly used in sunscreens. The potential estrogen and androgen effects of these compounds were evaluated in vitro; estrogen receptor (ER) and androgen receptor (AR) binding and transcriptional activation and in vivo; rat uterotrophic and Hershberger bioassays, respectively. ABZ, ESZ, HMS, and PMO did not increase ERα-mediated luciferase activity in the HeLa-9903 system at any of the viable concentrations tested up to the limit of solubility. All four agents were classified as “non-interacting” in the ER binding assay. Administration of ABZ, ESZ, HMS, and PMO for 3 days did not affect respective uterine weights when assessed up to a limit dose of 1g/kg in the uterotrophic assay. In the MDA-kb2 transcriptional AR activation cell assay, ABZ, ESZ and PMO did not exhibit AR agonist or antagonist activity. HMS did not demonstrate AR agonism, however there was an apparent exposure-dependent antagonism of AR-mediated transactivation at ~10-4M. UV filters were assessed for binding to ARs isolated from rat prostate at exposure levels 10-10 to 10-3 (ESZ) or 10-5 M. All four were classified as a “non-binders”. Inhibition of aromatase was assessed by measuring human CYP19 and P450 reductase activation. ABZ, ESZ, HMS and PMO, were all classified as non-inhibitors, with mean aromatase activities of 115, 102, 89, and 98%, respectively, at the highest soluble test concentration. In the rat Hershberger bioassay, each UV filter was assessed for androgen agonist and antagonist activity (in the presence of 0.4mg/kg testosterone propionate (TP)). After 10 days of dosing, oral administration of ABZ, ENZ, HMS, or PMO up to the limit dose of 1 g/kg did not induce any organ weight changes suggestive of androgen agonist activity. PMO at 1 g/kg in combination with TP was associated with lower levator ani bulbocavernous muscle complex (LABC), glans penis and ventral prostate weights. Administration 1 g/kg of HMS and TP was associated with lower LABC weight compared to controls. These changes occurred in the presence of ~10% lower relative body weights. ABZ and ENZ did not display respective antagonist activity. These findings collectively demonstrate that ABZ, ESZ, HMS, and PMO have minimal, if any, in vitro AR, ER or aromatase activity, and are negative in the uterotrophic bioassay. HMS and PMO displayed some antagonist activity in the Hershberger bioassay which occurred in the presence of lower relative body weights at the limit dose.