Registration Dossier

Administrative data

Description of key information

oral: 90d rat: NOAEL 50 mg/kg bw/day (o-, m- and p-cresol) 
dermal: cresols are corrosive
inhalation: no valid data available

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

The NOAEL of cresols was 50 mg/kg bw/day achieved in 3 independent 90 day subchronic studies with all three cresol isomers respectively. The LOAEL that was derived from these studies was 150 mg/kg bw/day.

 

According to Sontag JM, Page NP, Saffotti U (NCI, DHEW Publication No (NIH)78-ß01 Guidelines for Carcinogen Bioassay in small rodents) male and female rats were applied with 0, 50, 175, 600 mg o-cresol/kg bw/day by gavage for 13 weeks. The NOAEL was determined to be 50 mg/kg bw/day based on adverse effects from the dose level of 175 mg/kg bw/day (LOAEL) onwards including central nervous system depression and statistically significant reduction in body weight and body weight gain (RTI 1988).

In a study according to OECD TG 408, male and female Sprague Dawley rats received 0, 50, 150, 450 mg m-cresol/kg bw/day diluted in corn oil for a period of 13 weeks by gavage. Dose-dependant body weight decrease resulted in a NOAEL (male rat) of 50 mg/kg bw/day. The NOAEL (female rat) was 150 mg/kg bw/day based on reduced body weight gain in the highest dose group (RTI 1988). The LOAELs were therfore 150 mg/kg bw/day for male and 450 mg/kg bw/day for female rats.

In a subchronic toxicity study according to OECD TG 408 p-cresol was administered daily to male and female Sprague-Dawley rats by gavage at dose levels of 0, 50, 175 , 600 mg/kg bw/day diluted in corn oil (RTI1988). Based on increased mortality, clinical signs including lethargy, exessive salivation, tremor and occasional convulsions and comas, hepatotoxicity and nephrotoxicity from 175 mg/kg bw/d onwards. The NOAEL was determined to be 50 mg/kg bw/day and the LOAEL 175 mg/kg bw/day.

 

There are no valid data available to characterize the repeated dosing using the dermal application route. In addition, cresols are known to be corrosive. Adequate inhalation studies are also not not available.

 

Justification for classification or non-classification

Cresols have not to be classified according to DSD and CLP because the guidance values were lower than the lowest effective dose level (LOAEL: 175mg/kg bw/day).