API Publ 4743:2005 pdf download

API Publ 4743:2005 pdf download.Hazard Narrative for Tertiary-Butyl Alcohol (TBA).
2.2 Carcinogenicity Studies
2.2.1 human l)ata
No epidemiological data were Ibund in the literature.
2.2.2 Animal I)ata
The potential for TBA to induce tumors or result in chronic toxicity in laboratory animals has been investigated in a 2-year oral (drinking water) study in rats and mice (Cirvello et al. 1995; NTP 1995). Male and female F344/N rats were administered TBA in drinking water at concentrations resulting in doses of approximately 0, 90, 200, or 420 mg/kg/day in males and 0. 180, 330, or 650 mg/kg/day in females. Male and female B6C3F1 mice were administered TBA in drinking water at concentrations resulting in doses of approximately 0, 540. 1040. or 2070 mg/kg/day in males and 0, 510, 1020, or 2110 mg/kg/day in females. Rats and mice were observed twice daily and body weights and clinical observations were recorded weekly for the first 13 weeks and every 4 weeks thereafler. Water consumption was recorded every 2 weeks.
At 15 months, hematology and urinalysis evaluations were conducted on rats in all exposure groups. At the 15-month interim sacrifice, a complete necropsy and microscopic evaluation was performed and brain, right kidney. and liver weights were recorded. Interim sacrifices were not conducted Ofl mice due to decreased survival in the male high-dose group. Following final sacrifice, a complete necropsy and microscopic examination were performed on all mice and rats.
Survival analysis showed a significant decrease in survival rates in male and female rats in the high-dose groups and in male mice in the high-dose group (NTP 1995). The t’inal mean body weight in male and female rats in the high-dose groups were 24% and 21% less than controls, respectively. Mean body weights in the male rats at 90 and 200 mg/kg/day were similar to controls through week 65 of the study and then decreased through the remainder of the study. Mean body weights in the female rats at 90 and 200 mg/kg/day were similar to control values throughout the study. Mean body weight in the high dosed male mice were significantly lower than the controls from week 9 of the study until the final 10 weeks of the study. Body weights and body weight gains in all other treated male mice were similar to controls. The mean body weights of the female mice in the high-dose group were 10% to 15% less than controls beginning at week 13 of the study and continuing through the end of the study (statistical significance was not reported). The mean body weights in female mice in the mid-dose group were approximately 6% lower than controls, and mean body weights in ihe Low-dose groups were only slightly less than controls throughout the study (statistical significance was not reported)
A dose-related increase in water consumption in male rats was observed during the second year of the study, while a dose-related decrease in water consumption was observed in female rats (NTP 1995). Water consumption was unaffected in male and female treated mice.
Behavioral and general health and appearance was unaffected by treatment in rats and mice of both sexes with the exception of an increased incidence of hyperactivity in the female rats in the high-dose group. Urinary and hematological observations were not considered to be treatment-related. A significant increase in urine specific gravity and a significant decrease in urine volume were noted in the female rats receiving 330 and 650 mg/kg/day, which was consistent with the decreased water consumption noted in the female rats.
At the 15-month interim sacrifice (10 rats per group). mean body weights were significantly decreased in male and female rats in the high-dose group (NTP 1995). In the male rats, relative brain, right kidney, and liver weights were increased in the high-dose group and relative right kidney weights were decreased in the mid-dose group. In the female high-dose group, relative brain and liver weights were significantly increased. Also, in the female rats. absolute and relative right kidney weights were significantly increased in all treated groups at the IS-month interim sacrifice. One renal tubule adenoma was observed in male rats at the 15- month interim sacrifice in the high-dose group. In addition, the incidence and severity of mineralization of the kidney was significantly increased in the high-dose male rats when compared to controls sacrificed at 15-months. Nephropathy was observed in all male and female rats, including controls, at the 15-month interim sacrifice, and the severity was slightly increased in treated male rats and the mid- and high-dose group females. Incidence data for male and fimalc rats at the 15-month interim evaluation are presented in Tables I and 2. Due to decreased survival in mice, a I 5-month interim evaluation was not performed.