title: Skin irritation, basal epithelial cell proliferation, and carcinogenicity evaluations of a representative specialty acrylate and methacrylate.
abstract: Specialty acrylates and methacrylates (SAM) comprise a large family of industrial monomers. In the late 1980s, the United States EPA and the industry SAM Panel collaborated to evaluate the potential effects, particularly carcinogenesis, of this family of chemicals. As part of this arrangement, the SAM Panel, with EPA input and approval, conducted four studies with a representative acrylate, triethyleneglycol diacrylate (TREGDA), and methacrylate, triethyleneglycol dimethacrylate (TREGDMA). All studies used unoccluded skin application to male mice as follows: Study 1, evaluation of skin irritation compared to cell proliferation in the basal epithelium (BE) following 7 or 14 days of treatment; Study 2, 14-day dose range-finding study; Study 3, 90-day subchronic toxicity study; and Study 4, chronic bioassays employing the EPAs draft guidelines for dermal chronic bioassays. BE cell proliferation was determined in subchronic and carcinogenicity studies (Studies 1, 3, and 4). Organ weight changes (Studies 3 and 4) and increased mortality (Study 4) were observed for the highest dose of TREGDMA. However, there was no related histopathology. Both chemicals induced cell proliferation (7 days through 78 weeks) that correlated with acute and chronic inflammation of the skin. No skin tumors were observed in this study. TREGDA resulted in skin lesions at doses approximately 20-fold lower than TREGDMA. Most of the skin lesions showed similar patterns of microscopic cutaneous alteration suggestive of nonspecific irritation for both chemicals. However, the high concentration TREGDA group in the 78-week study also had evidence of epidermal cell necrosis. In contrast to earlier studies with acrylates, dose selection was based on careful examination of skin irritation and cell proliferation to avoid excessive skin damage. Under these conditions, TREGDA and TREGDMA were not carcinogenic.
authors.affiliation: Toxicology/Regulatory Services, Charlottesville, VA 22911, USA. jvanmiller@toxregserv.com
authors.forename: J P
authors.initials: JP
authors.lastname: Van Miller
authors.forename: R H
authors.initials: RH
authors.lastname: Garman
authors.forename: S J
authors.initials: SJ
authors.lastname: Hermansky
authors.forename: J C
authors.initials: JC
authors.lastname: Mirsalis
authors.forename: C B
authors.initials: CB
authors.lastname: Frederick
mesh_terms: D000179:Acrylates / Q000633:toxicity*; D000279:Administration, Cutaneous; D000818:Animals; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000187:drug effects; D000078404:Epidermal Cells; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011092:Polyethylene Glycols / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D023422:Skin Irritancy Tests / Q000379:methods
chemical_list: D000179:Acrylates; D011109:Polymethacrylic Acids; D018809:Proliferating Cell Nuclear Antigen; C020946:triethylene glycol dimethacrylate; C032705:triethylene glycol diacrylate; D011092:Polyethylene Glycols