Registration Dossier

Diss Factsheets

Administrative data

Description of key information

In a subchronic guideline study similar to OECD 408 (Bayer (1982) T7010745), 20 Wistar rats/sex/dose were exposed to 0, 30, 300, 3000 ppm 4-(1,1,3,3-tetramethylbutyl)phenol (OCT) for 90 days. The dose equals 0, 2, 23, 228 mg/kg bw/day in males based on the average bw (week 1-13). 
In a subacute GLP guideline study according to OECD 407 (Huntington Research centre (1994) SAZ 464/9424419), OCT was administered to 5 SD rats/sex/dose at 0, 15, 150, and 300 mg/kg bw/day by gavage. A similar GLP study was conducted according to a Japanese "Guidelines for 28-Day Repeated Dose Toxicity Test of Chemicals", using 6 SD rats/sex/dose at 0, 15, 70, and 300 mg/kg bw/day (Matsuura 1992). The study is in Japanese. Only abstract and tables are translated into English.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
22.5 mg/kg bw/day
Study duration:

Additional information

Feeding 300 ppm 4 -(1,1,3,3 -tetramethylbutyl)phenol (OCT) (93.1%) to 20 Wistar rats/sex/dose for 90 day causes no adverse effects (Bayer 1982). Based on the mean body weight, 300 ppm equals 22.5 mg/kg bw/day in male rats and 24.9 mg/kg bw/day in female rats, respectively. No treatment related mortality or clinical signs of toxicity were reported at the highest dose of 3000 ppm. No significant reduction in food consumption was reported. Water uptake was increased in the highest dose group, but only in females. Haematological parameters in all treated male rats were unaffected. A decrease in haemoglobin and haematocrit was reported among females at the high dose level at the end of the testing period. The values were in the normal range for females of this age. Thus this effect is considered to be incidental. No histopathological indications of dose-related effects on haematopoiesis were observed. The thyroxin (T4) content was increased in females in the highest dose group after one month, but decreased to control levels after 3 month. This effect can be traced back to considerably increased thyroxin concentrations in two female test animals and might be dose-related. Histopathologically the thyroids of randomly selected animals of this dose group were normal. Pathological-anatomical and histopathological investigations as well as clinical and chemical effects and organ weight indicated no adverse effects on liver and kidney up to dosages of 3000 ppm. Body weight gain was slightly reduced in male rats in the 300 ppm dose group (significant only in week 3 and 10). Some significant reduced organ weights were attributed to the delay in body weight gain and were not considered to be toxicological effects. At 3000 ppm body weight gain was clearly delayed in both sexes. This delayed body weight gain and associated changes in organ weights are base for an NOAEL of 300 ppm (~ 22.5 mg/kg bw/day).   In a 28 day study 0, 15, 150, 250 mg/kg bw/day OCT (98,7%.) was administered by gavage to 5 SD rats/sex/dose (Huntington Research Centre Ltd., 1994). No treatment related effects were noted for clinical signs, bodyweight gains, haematology and macroscopic pathology. Adjusted liver and kidney weights were statistically significantly higher than control for female rats treated at 250 mg/kg/day. Basophilic epithelium occasionally with mitotic figures in proximal convoluted tubules was reported in male and female rats receiving 250 mg/kg/day and male rats receiving 150 mg/kg/day. Interstitial inflammation was reported in kidneys of male rats receiving 250 mg/kg/day. A LOAEL of 150 mg/kg bw/day was determined based on epithelial changes in the kidney of male rats. The NOAEL was 15 mg/kg bw/day. The subacute NOAEL of 15 mg/kg bw/day was supported by an additional 28 day study (Matsuura, 1992). The study is available in Japanese only (Klimisch 4). The abstract and tables are translated into English. The study followed the Guidelines for 28-Day Repeat Dose Toxicity Test of Chemicals. OCT (98.24%) was administered daily by gavage to groups of six SD rats/sex/dose for 28 day at dosage levels of 15, 70 and 300 mg/kg/day. The test substance caused salivation in both sexes, a decrease in the body weight gain in males and an increase in water intake in both sexes of the high dose group. Blood chemical analyses revealed an increase in Na in both sexes, and additional aberrations in females of the medium and high-dose group. The high dose group demonstrated increased urine volumes and urinalysis showed decreases in specific gravity, Na, Cl and K. Increases in organ weights of the kidney and liver were found in the high dose group. Pathological examination revealed greyish kidney patches and regeneration of renal tubules. However, changes attributable to OCT disappeared or tended to recover after discontinuation of administration.

Justification for classification or non-classification

No severe systemic toxicity was reported in rats following subchronic and subacute repeated oral exposure to 4 -tert-octylphenol.