4-tert-butylphenol

Endpoint summary

Description of key information

ptBP is of low  acute toxicity following oral exposure. Reported LD50 values for ptBP were greater than 2000 mg/kg body weight  in rats. Clinical signs of systemic toxicity were only observed at doses causing mortality. 
The LD50 of ptBP by the dermal route of exposure has been reported to be greater than 16 000 mg/kg body weight or equal to 2318 mg/kg body weight in rabbits.  Dermal application of ptBP to rabbits was observed to result in severe skin irritation at doses of 2000 mg/kg body weight and greater, as well as systemic toxicity at doses of 8000 mg/kg body weight and greater. 
The LC50 of ptBP by the inhalational route of exposure is greater than 5600 mg/m3 in rats.  Acute inhalational exposure to a substantially saturated vapour of ptBP did not result in systemic toxicity in rats. Systemic toxicity, however, was observed following exposure of rats to the dust aerosol at a ptBP concentration of 5600 mg/m3.
In general, the signs of respiratory distress observed are not considered to justify classification, namely due to the high dose used.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 990 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 318 mg/kg bw

Additional information

Acute Oral Toxicity

Acute oral toxicity studies on ptBP in rats, two of which were performed according to OECD test guidelines, have demonstrated that the compound is of low acute toxicity following oral exposure. The studies conducted (described below) all report on LD50 values of greater than 2000 mg/kg body weight for ptBP in rats. Clinical signs of systemic toxicity were only observed at doses causing mortality.

An acute oral toxicity study on ptBP has been performed in Sprague-Dawley rats (Tuffnell et al., 1991). The study was performed in accordance with OECD Guidelines for the Testing of Chemicals No. 401 and in compliance with GLP, and therefore, was selected as the key study. In this study, 5 male and 5 female rats were orally administered 2000 mg/kg body weight of ptBP in arachis oil (vehicle) by gavage and observed over a 14-day period. No deaths occurred and no signs of systemic toxicity ensued. Additionally, all animals displayed satisfactory body weight gain and no abnormalities were noted at necropsy. Based on the results of this study, the oral LD50 of ptBP was determined to be > 2000 mg/kg body weight/day in rats. In the preliminary dose range finding study for this study, doses of 200, 2000, and 5000 mg/kg body weight were administered to groups of 1 male and 1 female rats. A dose of 5000 mg/kg body weight of ptBP to the one male rat resulted in clinical signs of toxicity, including hunched posture, lethargy, ptosis, red-brown stains around the snout, and ataxia, with death ensuing two days following dosing. Mortality and clinical signs of toxicity were not observed in the one female rat administered 5000 mg/kg body weight of ptBP or in males and females administered 200 or 2000 mg/kg body weight ptBP.

Additional supportive studies confirm the mortality and clinical signs of toxicity observed in the study by Tuffnell et al. (1991) following oral exposure to high doses of ptBP in rats. In one supportive acute oral toxicity study performed according to OECD Guidelines for the Testing of Chemicals No. 401 (Mürmann, 1985), 5 male and 5 female Wistar rats were orally administered 3160 mg/kg body weight ptBP (low-dose) in paraffin oil (vehicle). Additional groups of 10 male and 10 female rats were dosed with 3980 or 5010 mg/kg body weight ptBP (mid- and high-dose groups, respectively). Animals were observed over a 14-day period for mortality and clinical signs of toxicity, and body weights also were measured. Within 48 hours of ptBP administration, 4 males and 8 females in the mid-dose group and 7 males and 5 females in the high-dose group died. In addition, 1 male and 2 females in the low-dose group died within 11 days of ptBP administration. Based on the mortality data, the oral LD50 of ptBP was calculated to be 4000 mg/kg body weight in rats. Clinical signs of toxicity were observed in all animals administered ptBP and included ruffled fur, hunched posture, staggering, severe sedation and ataxia, prostration, trembling, respiratory distressed, half-closed eyes, bloody nose, hypothermia, and jumpy posture shortly after administration. At 24 hours, diarrhoea and diuresis were observed, and at 48 hours, a sporadic, noisy defence reaction with touch was observed. These signs had resolved by day 6 post-administration, and no other clinical signs were observed thereafter. Body weight gains, however, were transiently reduced in surviving animals. Post-mortem examination of the animals that died revealed hyperaemia of the gastric and small intestinal mucosa and of the peritoneum and diaphragm, swelling and discoloration of the liver and pancreas, and liver congestion. In the animals that had survived until study end, adhesion of abdominal organs with the peritoneum and diaphragm was observed at necropsy. In addition, two animals displayed extremely enlarged kidneys and one animal displayed congestion of the spleen and sporadic hyperaemia and swelling of the gastric and small intestinal mucosa.

In another acute oral toxicity study performed in rats, groups of 5 male and 5 female Sprague-Dawley albino rats were orally administered by gavage 2500, 3500, or 5000 mg/kg body weight ptBP in corn oil (vehicle) (Klonne et al., 1988). A fourth group of animals included 5 males dosed with 10 000 mg/kg body weight of ptBP. No test guidelines were followed. Animals were observed for mortality and clinical signs of toxicity and body weights measured over a 14-day period. No mortalities were observed in the group administered 2.5 mg/kg body weight ptBP. At a dose of 3.5 g/kg body weight, however, 2 females, but no males died. In addition, all females and 2 males in the 5000 mg/kg body weight dose group and all males in the 10 000 mg/kg body weight dose group died. Based on the mortality data, the oral LD50 of ptBP was calculated to be 3620 and 5360 mg/kg body weight in female and male rats, respectively. The principal clinical signs of toxicity included mottled lungs and livers in females. No significant gross lesions were observed in male rats that either died during the study or survived until study end.

In an acute oral toxicity screening study performed in rats, groups of 10 male and 10 female Gassner rats were orally administered by gavage 200, 1600, 3200, 3600, 4000, 5000 or 6400 mg/kg body weight ptBP as an aqueous suspension in Tylose (vehicle) (BASF, 1971). The study was performed according to an internal standard guideline. Animals were observed for mortality and clinical signs of toxicity over a 14-day period. The following mortalities were observed at 14 days: 200 mg/kg: 1/20; 1600 mg/kg: 0/20; 3200 mg/kg: 3/20; 3600 mg/kg: 12/20; 4000 mg/kg: 12/20; 5000 mg/kg: 16/20 and 6400 mg/kg: 20/20. Based on the mortality data, the oral LD50 of ptBP was calculated to be greater than or equal to 3500 mg/kg body weight in rats. The principal clinical signs of toxicity included staggering, apathy, abdominal position, atony, dyspnea and spastic gait.

In the EU Risk Assessment on ptPB, an oral LD50 value of 3.25 mL/kg body weight (2990 mg/kg body weight) in rats also was identified. This LD50 value for ptBP was determined by Smyth et al. (1969) using 5 male Carworth-Wistar rats and following oral gavage administration of ptBP. No further information was available.

Acute dermal toxicity

Acute dermal toxicity studies that follow current test guidelines have not been performed, and therefore, are not available. Based on the results of the study described below, the LD50 of ptBP by the dermal route of exposure has been reported to be greater than 16 000 mg/kg body weight in rabbits in one study, but equal to 2318 mg/kg body weight in another. The study was not reported to be performed according to any test guideline.  Dermal application of ptBP to rabbits was observed to result in severe skin irritation at doses of 2000 mg/kg body weight and greater, as well as systemic toxicity at doses of 8000 mg/kg body weight and greater.

In an acute dermal toxicity study conducted in New Zealand White rabbits, groups of 5 male and 5 female animals were dermally administered 2000 (low-dose), 8000 (mid-dose), or 16 000 (high-dose) mg/kg body weight of ptBP (Klonne et al., 1988). The study was not reported to be performed according to any test guideline; however, the study was deemed reliable, and therefore, was considered as the key study. PtBP was moistened with distilled water and applied to the clipped skin of trunks under occlusive conditions for an exposure period of 24 hours. Rabbits were observed for 14 days for signs of local inflammation and systemic toxicity, and body weights also were measured. Signs of sever skin irritation (erythema, edema, necrosis, ulceration, desquamation, fissuring, and scabs) were apparent at the site of application in both sexes of all groups. In the low-dose group, erythema, necrosis, and fissuring were present through day 7; however, desquamation and scabs remained present at Day 14. In contrast, signs of skin irritation generally persisted for the entire 14-day observational period in animals of the mid-and high-dose groups. No deaths occurred, and the only signs of systemic toxicity were temporary prostration in 1 female in the high-dose group, and reduced body weight gains in the mid- and high-dose groups from days 0 to 7. Furthermore, gross pathology revealed no remarkable lesions.

In addition to the above data, the EU Risk Assessment on ptBP has cited that the dermal LD50 value for ptBP has been reported to be 2.52 mL/kg body weight (2318 mg/kg body weight) in rabbits as determined by Smyth et al. (1969). The study was apparently conducted using 4 male albino rabbits, with the test substance applied to the clipped trunk of animals and retained for 24 hours beneath an impervious plastic film. The animals were reported to be observed over a 14-day period and a modified Draize method was followed for scoring of skin reactions. No further information was available.

Acute Inhalation Toxicity

Acute inhalational toxicity studies that follow current test guidelines have not been performed, and therefore, are not available. Based on the results of the studies described below, the LC50 of ptBP by the inhalational route of exposure is greater than 5600 mg/m3 in rats. Exposure to the substantially saturated vapour did not result in signs of systemic toxicity. Systemic toxicity, however, was observed following exposure of rats to the dust aerosol at a ptBP concentration of 5600 mg/ m3.

One acute inhalation toxicity study has been conducted among the series of acute toxicity tests conducted by Klonne et al. (1988). The study was not reported to be performed according to any test guideline; however, the study was deemed reliable, and therefore, was considered as the key study. In this study, 5 male and 5 female Sprague-Dawley rats were exposed to a substantially saturated vapour of ptBP, consisting of 100 g of ptBP in a 120 L chamber, under static conditions for 6 hours. Alternatively, 5 male and 5 female rats were exposed to a dust aerosol of ptBP at a concentration of 5.6 mg/L, or 5600 mg/m3, in a 120 L chamber for 4 hours. Animals were observed for mortality and clinical signs of toxicity and body weights measured over a 14-day period. Following exposure to the dust aerosol, 1 male and 1 female rat died within 1 to 2 days, a mortality rate of 20%. Clinical signs observed in this group of animals on the day of exposure and up to 7 days post-exposure included signs of mucosal irritation (perinasal, perioral, and periocular encrustation) and signs of respiratory distress (audible respiration, gasping, and a decreased respiration rate). In addition, a loss of mean body weight was observed for both sexes on day 7, but body weight gains were exhibited by day 14. Upon necropsy, dark red or purple discoloration of the lungs and/or kidneys was observed in the two rats that died, but no macroscopic lesions were observed in rats that survived until study end. No deaths, clinical signs, effects on body weight, or gross abnormalities were reported to be observed in animals exposed to the vapour.

In an inhalation hazard screening study, 11 male and female rabbits were exposed to ptBP vapors (BASF, 1971). At 20°C and an 8-h exposure there were no abnormalities. At 120°C and a 5-h exposure, the rabbits attempted to escape and mucosal irritations occurred.

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) NO. 1272/2008.