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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
450 mg/kg bw/day
Additional information

Reproductive toxicity of cresols was examined in three independent two-generation toxicity studies according to "TSCA Health Effects Test Guideline for specific organ/tissue toxicity - Reproduction/Fertility effects" (EPA, 1983, Union Carbide for CMA 1988 and 1989). Sprague-Dawley rats were given daily 0, 30, 175, or 450 mg/kg bw/day o-, m- or p-cresol in corn oil continuously by gavage for two generations. General toxicity including increased mortality at 450 mg/kg bw/d and in clinical signs of toxicity including hypoactivity, ataxia, twitches, tremors, prostration, gasping, rapid respiration and perioral wetness were observed at >= 175 mg/kg bw/d (NOAEL general toxicity: 30 mg/kg bw/day). No reproductive parameters were affected by treatment in either of the two generations (NOAEL fertility: 450 mg/kg bw/day). The NOAEL for the offspring is 175 mg/kg bw/day based on reduced body weights (F1, F2), pup body weight gain (F2), lactational index (F2) and pup mortality (F2) at the highest dose.

Additionally, testing for reproductive toxicity of o-cresol in mice using the NTP continuous breeding protocol (0, 0.05 - 0.5 %, approximately 66 - 660 mg/kg bw/d in the diet) resulted in a NOAEL for reproduction as well as for general toxicity of 0.2 % (ca. 263 mg/kg bw/d US Department of Health and Human Services 1992).

Short description of key information:
Two generation study: NOAEL fertility rat: 450 mg/kg bw/day (o-, m- and p-cresol)

Effects on developmental toxicity

Description of key information
Developmental toxicity: NOAEL rabbit 50 mg/kg bw/day (o-cresol)
Effect on developmental toxicity: via oral route
Dose descriptor:
50 mg/kg bw/day
Additional information

To determine developmental toxicity according to "TSCA Health Effect Guidelines for Specific Organ/Tissue Toxicity - Developmental Toxicity" (EPA 1984, 1987, CMA 1988) o-, m- or p-cresol were administered by gavage to timed-pregnant Sprague-Dawley rats during organogenesis (gestation day 6-15; 0.0, 30.0, 175.0, 450.0 mg/kg bw/d) in three independent studies. Gavage resulted in significant maternal toxicity at 450 mg/kg bw/day including treatment related clinical signs (hypoactivity, ataxia, tremor, twitches, prone positioning, audible respiration, perioral wetness), mortality of 4 dams (dependent on the tested cresol), statistically significant reduction in body weights and body weight gain leading to a NOAEL for maternal toxicity of 175 mg/kg bw/day for all components of the mixed cresols. Slight fetotoxicity was observed only at 450 mg/kg bw/day for o-cresol as one visceral variation (dilateted lateral ventricles of the brain with no tissue compression) and for p-cresol as reduced ossification in three skeletal districts in addition with reduced fetal body weight. m-Cresol did not induce fetotoxicity or malformations at any dose level tested. Thus the NOAEL for developmental toxicity for cresols was determined to be 175 mg/kg bw/day.

Administration of m-, o- or p-cresols by gavage to New Zealand white rabbits during organogenesis resulted in evidence of maternal toxicity at 50 and 100 mg/kg bw/day for all three isomers. No embryotoxicity or tertagenicity was observed at any dosage employed for any of the three isomers. Slight fetotoxicity (increased incidence of one external variation and one skeletal variation) was observed at 100 mg/kg bw/day for o-cresol only in the absence of any other indications of toxicity for the fetus. The NOEL for maternal toxicity was 5 mg/kg bw/day for all three isomers. The NOEL for developmental toxicity was 50 mg/kg bw/day for o-cresol and at least 100 mg/kg bw/day for m- and p-cresol.

Justification for classification or non-classification

Additional information