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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 rat 175 mg/kg bw/day (o- and p-cresol)
Effect on developmental toxicity: via oral route
Dose descriptor:
175 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.

Justification for classification or non-classification