Species and gender differences in the carcinogenic activity of trimethylolpropane triacrylate in rats and mice

Abstract

Trimethylolpropane triacrylate (TMPTA) is a multifunctional monomer with industrial applications. To determine the carcinogenic potential, male and female F344/N rats and B6C3F1/N mice were administered TMPTA (0, 0.3, 1.0, or 3.0mg/kg) in acetone dermally for 2 years. There were no differences in the body weights and survival in the treated animals compared to controls. Nonneoplastic skin lesions at the site of application included epidermal hyperplasia and hyperkeratosis in both rats and mice. There were no incidences of tumors at the site of application in rats and mice. Rare malignant liver neoplasms were observed in female mice that included hepatoblastoma in the 0.3 and 3.0mg/kg groups, and hepatocholangiocarcinoma in the 1.0 and 3.0mg/kg groups. The incidences of uterine stromal polyp and stromal polyp or stromal sarcoma (combined) in female mice occurred with positive trends and the incidences were significantly increased in the 3.0mg/kg group. A marginal increase in the incidences of malignant mesothelioma in male rats may have been related to TMPTA treatment. In conclusion, our studies show that TMPTA is a dermal irritant in both rats and mice of either sex. Increased incidences of tumor formation were observed in female mice and male rats.

Keywords: Carcinogenicity; Liver; Skin; Trimethylolpropane triacrylate; Uterine.

Fig. 1

Malignant mesothelioma in the mesentery of a male F344/N rat administered 3.0 mg/kg TMPTA in the 2-year dermal study. The malignant mesothelioma is papillary and consists of one or more layers of neoplastic mesothelial cells. H&E.

Fig. 2

Hepatoblastoma in the liver of a male B6C3F1/N mouse administered 3.0 mg/kg TMPTA in the 2-year dermal study. An expansile mass within the hepatic parenchyma is composed of small, deeply basophilic neoplastic cells and contains blood-filled cystic spaces. H&E.

Fig. 3

Hepatocholangiocarcinoma in the liver of a male B6C3F1/N mouse administered 1.0 mg/kg TMPTA in the 2-year dermal study. The neoplasm contains both neoplastic hepatocytes and neoplastic bile duct epithelial cells with necrotic and cystic areas. H&E.

Fig. 4

Stromal polyp in the uterus of a female B6C3F1/N mouse administered 3.0 mg/kg TMPTA in the 2-year dermal study. The polyp is a pedunculated mass that protrudes into the lumen and contains marked cellular pleomorphism. H&E.