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Toxicologic Pathology
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Articles

Topical Application of Representative Multifunctional Acrylates Produced Proliferative and Inflammatory Lesions in F344/N Rats and B6C3F1 Mice, and Squamous Cell Neoplasms in Tg.AC Mice

Adriana M. Doi1, James R. Hailey1, Milton Hejtmancik2, John D. Toft, II2, Molly Vallant1 and Rajendra S. Chhabra1

1 National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
2 Battelle Memorial Institute, Columbus, Ohio 43201, USA

Correspondence: Address correspondence to: Rajendra S. Chhabra, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop EC-35, Research Triangle Park, NC 27709, USA; e-mail:chhabrar{at}niehs.nih.gov

Widespread human exposure to multifunctional acrylates is of concern, due to their inherent reactivity and irritating properties. Trimethylolpropane triacrylate (TMPTA) and pentaerythritol triacrylate (PETA) are industrially important representatives of multifunctional acrylates. The current studies characterized the toxicity of 3-month topical administration of technical grade TMPTA and PETA in F344/N rats and B6C3F1 mice, and evaluated the carcinogenic potential of TMPTA and PETA in hemizygous Tg.AC (v-Ha-ras) transgenic mice. Administration of 0.75, 1.5, 3, 6, and 12 mg/kg TMPTA and PETA for 3 months resulted in hyperplastic, degenerative, and necrotic lesions, accompanied by chronic inflammation of the skin, with severities generally increasing with dose. Lesions were slightly more severe in rats, when compared with mice, and illustrate the irritant potential of TMPTA and PETA. A similar dosage regimen was used for the 6-month study with Tg.AC mice. Topical application of TMPTA and PETA to Tg.AC mice showed dose-dependent increases in squamous cell papillomas at the site of application, with decreases in the latency of their appearance in mice receiving 3 mg/kg or greater. Papillomas, the reporter phenotype in Tg.AC mice, were accompanied by a few squamous cell carcinomas, along with hyperplastic and inflammatory lesions. Although chronic inflammation might have contributed to the development of the skin lesions, the dose-related nature of the induction of the skin papillomas in Tg.AC mice by TMPTA and PETA may reflect a potential for carcinogenicity.

Key Words: Dermal • multifunctional acrylates • transgenic mouse • toxicity • carcinogenicity • squamous cell papillomas • inflammation

Toxicologic Pathology, Vol. 33, No. 6, 631-640 (2005)
DOI: 10.1080/01926230500295615
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