4-(α,α-dimethylbenzyl)phenol

Endpoint summary

Description of key information

In a repeated dose oral study performed per OECD Test Guideline 422 the NOAEL in the rat was 50 mg/kg.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

50 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

A guideline compliant study conducted under GLP conditions is available. The quality of the database is therefore considered to be good.

System:

urinary

Organ:

kidney

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The repeated dose oral toxicity was investigated per OECD Test Guideline 422 under GLP conditions (RTI International; Center for Life Sciences and Toxicology, 2005). The study exceeded the guideline by following the F1 offspring to adulthood and includes an assessment of neurologic function.

P-cumylphenol, administered by gavage once daily at 0, 5, 50 and 300 mg/kg/day to parental Sprague-Dawley rats (10/sex/group) by gavage in corn oil through pre-breed, mating, gestation and lactation and direct dosing to F1 offspring from weaning to scheduled sacrifice resulted in systemic toxicity (manifested as renal tubular necrosis) at 300 mg/kg/day in the parental males. The LOAEL was determined to be 300 mg/kg/day for parental males. A slight decrease in uterine implantations at 300 mg/kg/day in the parental females was noted; however, based on the lack of other associated effects on reproductive parameters and the screening nature of this study a LOEL for females was established at 300 mg/kg/day. No toxicity in the F1 offspring from birth through 7 weeks of post-weaning dosing were observed. 

The NOAEL for the Parental rats was determined to be 50 mg/kg/day and the NOAEL for the F1 generation was determined to be 300 mg/kg/day.

Supporting information is provided in the form of a publication (Nakazawa et al., 2009). The sequential changes in the development of renal tubular cysts in newborn rats treated with p-cumylphenol (PCP) were investigated. Fifteen animals per sex were treated orally with 300 mg/kg/day of PCP for up to 18 days from postnatal day (PND) 4 and were sacrificed on PNDs 8, 12, 19 and 22 and after a 7 day recovery period.

Under the conditions of this study, PCP induced multiple renal cysts that developed in the collecting ducts of the outer medulla in neonatal rats, and it is suggested that epithelial cell proliferation may play some role in the induction of cystic lesions.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance requires classification with respect to repeated dose toxicity as STOT RE Category 2 (H373: May cause damage to organs).