Two-year toxicology and carcinogenesis studies of chlorinated trisodium phosphate, an inclusion complex of trisodium phosphate and sodium hypochlorite used in various cleaning compounds, were conducted by administering 0, 500, or 1,000 mg/kg (dose volume: 10 ml/kg) of the chemical in water by gavage, 5 days per week for 103 weeks, to groups of 50 male and 50 female B6C3F1 mice. Groups of mice receiving 250 mg/kg were included in these studies but were removed after 6 months because of a lack of toxicity in the 500 and 1,000 mg/kg groups. Two-year studies were begun in male and female F344/N rats at doses of 0, 500, 1,000, or 2,000 mg/kg of chlorinated trisodium phosphate in water by gavage (10 ml/kg). The 2,000 mg/kg groups were killed at 15 weeks because of poor survival, and the other groups were killed at 35 weeks because of toxicity in the 1,000 mg/kg group. The doses selected for the 2-year studies were based on the general lack of adverse effects seen in the 14-day and 13-week studies in which rats received 0-1,000 mg/kg and mice received 0-2,000 mg/kg by gavage in water.
No compound-related histopathologic effects were observed in the 14-day or the 13-week studies in mice. In the 2-year studies, survival and mean body weights of dosed and vehicle control male mice groups were comparable (survival-- vehicle control, 39/50; low dose, 35/50; high dose, 32/50). Survival of the dosed female mice was lower than that of the vehicle controls (30/50; 16/50; 21/50), although at week 80 survival of female mice was 42/50, 39/50, and 36/50. The mean body weights of the high dose female mice were lower than those of the vehicle control mice, primarily after week 32; final body weights were 11% lower in the high dose group compared with that in the vehicle controls. The lower survival and mean body weights of the dosed female mice may have been due to a greater incidence of uterine/ovarian infections in these mice rather than to a direct toxic effect of chlorinated trisodium phosphate. Nine of 20 vehicle control, 20/34 low dose, and 21/29 high dose female mice that died before the end of the studies had such infections. This reduced survival decreased the sensitivity of the study of female mice for detecting the presence or absence of carcinogenic effects.
At no site was the incidence of neoplasms considered to be related to the administration of chlorinated trisodium phosphate. Minimal necrosis and fatty changes were observed in the livers of male mice. Kidneys in male mice were characterized by small, multifocal areas of mineralization, primarily in the cortex but not at the corticomedullary junction or in the tubes of the medulla. Neither effect was considered compound related. Five different types of ovarian neoplasms were found in six dosed female mice; because these lesions were from tissues of different embryonic origin, they were considered unrelated to administration of chlorinated trisodium phosphate.
Chlorinated trisodium phosphate was weakly mutagenic in strain TA1535 of Salmonella typhimurium in the presence of Aroclor 1254-induced male Sprague-Dawley rat or male Syrian hamster liver S9. This compound was not mutagenic in strains TA97, TA98, or TA100.
An audit of the experimental data was conducted for these 2-year studies of chlorinated trisodium phosphate. No data discrepancies were found that influenced the final interpretation of these experiments.
Under the conditions of these 2-year gavage studies, there was of carcinogenicity no evidence for either male or female B6C3F1 mice given chlorinated trisodium phosphate by gavage in water for 103 weeks at doses of 500 or 1,000 mg. Survival of dosed female mice was 78% and 72% after 80 weeks and 32% and 42% at the termination of the study. The studies in male and female F344/N rats were considered to be of carcinogenicity inadequate studies because the experiments were terminated at 35 weeks due to poor survival.