Evacuate non-essential personnel

TOXICOLOGICAL INFORMATION

(CONTINUED) Skin Contact - CHRONIC Prolonged or repeated skin contact may cause irritation with redness, swelling, and dermatitis. Toxicological - Eye . This product is a mild irritant to rabbit eyes. Toxicological - Ingestion Slightly toxic; the acute oral LDSO for this material is 3160 mg/kg in male rats. Ingestion - CHRONIC Chronic ingestion effects of this product are not known; however, symptoms of cholinesterase inhibition may occur (see "Note to Phy- Sicians, Section 5). CARCINOGENICITY/MUTAGENICITY This product was examined for mutagenic activity in a series of in vitro microbial assays employing Salmonella and Escherichia indicator organisms. Mutagenic activity was not demonstrated in any of the assays conducted. The product was also examined in the Sex-Linked Recessive Lethal Test in Drosophila melanogaster. No mutagenic activity was induced in this assay. Tributyl phosphate did not produce genotoxic effects in standard tests using mammalian cells and is not considered to be mutagenic or clastogenic. Data from a lifetime study in rats has shown an increased incidence of urinary bladder tumors at a very high dose level. These tumors appeared to have developed in response to long-term irritation of the bladder wall by bladder stones that formed in response to the lifetime administration of large amounts of the test article. In addition, a recent risk assessment has shown no risk to human health from occupational exposure to tributyl phosphate. Tributyl phosphate was administered in the diet of mice for 18 months at concentrations of 100, 150 and 3500 ppm. The onl treatment related change other than an increase in liver weight at 1000 and 3500 ppm was an increase in the incidence of benign liver tumors in the high dose males. REPRODUCTIVE EFFECTS This material was not teratogenic or embryotoxic when administered orally to pregnant rats at levels up to 750 mg/kg/day. A decrease in fetal body weight was observed at the maternally toxic dose of 750 mg/kg/day. It was not maternally toxic, embryotoxic, fetotoxic or teratogenic when orally administered to pregnant rabbits at levels up to 150 mg/kg/day. Equivocal embryotoxicity was observed only at the maternally toxic dose of 400 mg/kg/day. In a two generation reproductive toxicity study, rats were dosed with tributyl phosphate at concentrations of 200, 700 or 3000 ppm (approximately 15, 53 or 225 mg/kg/day). There was no evidence of reproductive organ histopathology and no effect of pre-natal or postnatal mortality at any dose. The NOEL was greater than 3000 ppm. 4 SECTION 11. TOXIGOLOGICAL INFORMATION (CONTINUED) NEUROTOXICITY There was no evidence that this material affected nervous system function and structure of rats following both acute (single dose) and subchronic (repeated dosing over a 90 day period) exposure. This material is not considered neurotoxic based on these tests.