Trimethylolpropane triacrylate is a multifunctional monomer with a wide range of industrial applications. It is used in the production of ultraviolet-curable inks, electron beam irradiation-curable coatings, and
polymers and resins; as a component of photopolymer and flexographic printing plates and photoresists; and as an ingredient in acrylic
glues and anaerobic sealants. The chemical is also used in paper and wood impregnates, wire and cable extrusion,
polymer-impregnated concrete, and
polymer concrete structural composites.
Trimethylolpropane triacrylate was nominated by the National Cancer Institute for testing due to its high production volume and use, its potential for consumer exposure, and a lack of adequate testing of the chemical. Male and female F344/N rats and B6C3F(1) mice were administered technical grade
trimethylolpropane triacrylate (it is reactive and therefore not available as pure
trimethylolpropane triacrylate) in
acetone dermally for 2 weeks or 3 months. Male and female Tg.AC hemizygous mice were administered technical grade
trimethylolpropane triacrylate in
acetone for 6 months. Genetic toxicology studies were conducted in B6C3F(1) and Tg.AC hemizygous mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female F344/N rats were administered 0, 12.5, 25, 50, 100, or 200 mg
trimethylolpropane triacrylate/kg
body weight in
acetone 5 days per week for 16 days. All rats survived to the end of the study, and mean
body weights of dosed groups were similar to those of the vehicle controls. Dosed rats had irritation at the site of application; this clinical finding was most commonly seen in rats administered 50 mg/kg or greater. Male and female rats had epidermal
hyperplasia, hyperkeratosis, sebaceous gland
hyperplasia,
inflammation of the epidermis and dermis, ulceration, epidermal degeneration, and
parakeratosis at the site of application. 2-WEEK STUDY IN B6C3F(1) MICE: Groups of five male and five female B6C3F(1) mice were administered 0, 12.5, 25, 50, 100, or 200 mg
trimethylolpropane triacrylate/kg
body weight in
acetone 5 days per week for 16 days. All mice survived to the end of the study. The final mean
body weight gain of 200 mg/kg males was less than that of the vehicle controls; 100 and 200 mg/kg females had significantly increased final mean
body weights. Irritation at the site of application occurred in all dosed males, all 100 and 200 mg/kg females, and one 50 mg/kg female. Thymus weights of males administered 50 mg/kg or greater were significantly decreased. Dosed male and female mice had epidermal
hyperplasia, hyperkeratosis, chronic active
inflammation of the dermis, sebaceous gland
hyperplasia,
ulcer, epidermal degeneration,
parakeratosis, and/or suppurative
inflammation of the epidermis at the site of application.
Atrophy of the thymus occurred in 100 and 200 mg/kg male mice. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were administered 0, 0.75, 1.5, 3, 6, or 12 mg
trimethylolpropane triacrylate/kg
body weight in
acetone 5 days per week for 14 weeks. All rats survived to the end of the study, and mean
body weights of dosed groups were similar to those of the vehicle controls. Irritation at the site of application was noted in five males and all females administered 12 mg/kg. Hematology results indicated that
trimethylolpropane triacrylate at the doses selected induced a neutrophil count increase at 12 mg/kg that would be consistent with an inflammatory response related to the
dermatitis observed histopathologically. Thymus weights of 12 mg/kg males and 0.75 and 12 mg/kg females were decreased. Incidences of epidermal
hyperplasia, degeneration, and
necrosis (females only); chronic active
inflammation of the dermis, hyperkeratosis, and sebaceous gland
hyperplasia were generally increased at the site of application in 1.5 mg/kg or greater males and in 3 mg/kg or greater females. 3-MONTH STUDY IN B6C3F(1) MICE: Groups of 10 male and 10 female B6C3F(1) mice were administered 0, 0.75, 1.5, 3, 6, or 12 mg
trimethylolpropane triacrylate/kg
body weight in
acetone 5 days per week for 14 weeks. All animals survived to the end of the study; mean
body weights of dosed groups were similar to those of the vehicle controls. Irritation at the site of application occurred in male and female mice administered 12 mg/kg. Hematology results indicated that
trimethylolpropane triacrylate induced a neutrophil count increase at 12 mg/kg that would be consistent with an inflammatory response related to the
dermatitis observed histopathologically. Increased incidences of several nonneoplastic lesions occurred at the site of application in 3 mg/kg and greater males and females, including
hyperplasia of the epidermis, hyperkeratosis, epidermal degeneration (except 3 mg/kg females) and
necrosis, chronic active
inflammation of the dermis, and sebaceous gland
hyperplasia. Epidermal suppurative
inflammation and
necrosis and dermal
fibrosis occurred in 12 mg/kg males and females. 6-MONTH STUDY IN Tg.AC HEMIZYGOUS MICE: Groups of 15 male and 15 female Tg.AC hemizygous mice were administered 0, 0.75, 1.5, 3, 6, or 12 mg
trimethylolpropane triacrylate/kg
body weight in
acetone 5 days per week for 28 weeks. Additional groups of 15 male and 15 female mice maintained as positive controls received dermal applications of 1.25 microg 12-O-tetradecanoylphorbol-13-acetate per 100 mL
acetone 3 days per week for 28 weeks; the dosing volume was held constant at 100 microL. Survival and mean
body weights of dosed groups were similar to those of the vehicle controls throughout the study. Treatment-related clinical findings included
papillomas at the site of application in 3 mg/kg and greater males and 6 and 12 mg/kg females. The heart weights of males and females administered 12 mg/kg and the kidney and lung weights of 12 mg/kg females were significantly increased. The lung weights of 6 and 12 mg/kg males and females were decreased.
Squamous cell neoplasms at the site of application were associated with dermal application of
trimethylolpropane triacrylate. At 6 months, the incidences of
squamous cell papilloma were significantly increased in 6 and 12 mg/kg males and females. One female in each of the 1.5, 6, and 12 mg/kg groups also had
squamous cell carcinoma. The incidence of
squamous cell papilloma of the forestomach in 12 mg/kg females was significantly greater than that in the vehicle control group. Nonneoplastic skin lesions at the site of application in dosed mice included epidermal
hyperplasia, hyperkeratosis, and chronic active
inflammation. A hematopoietic disorder (myelodysplasia) also occurred in some 12 mg/kg males and females.
GENETIC TOXICOLOGY: