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Effects on fertility

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

According to TSCA Health Effects Test Guideline for specific organ/tissue toxicity - Reproduction/Fertility effects (EPA, 1983) o-cresol was continuously administered by gavage to Sprague-Dawley rats for two generations and resulted in 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 at >= 175 mg/kg bw/d (NOAEL (genral toxicity) 30 mg/kg bw/d). No reproductive parameters were affected by treatment in either of the two generations (NOAEL (fertility) 450 mg/kg bw/d. The NOAEL (offspring) is 175 mg/kg bw/d based on significantly reduced body weights in F1 males and in significantly reduced lactation index in F2 at 450 mg/kg bw (Union Carbide Corp 1989).

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:
According to TSCA Health Effects Test Guideline for specific organ/tissue toxicity - Reproduction/Fertility effects (EPA, 1983) up to 450 mg/kg bw/dayo-cresol was continuously administered by gavage to Sprague-Dawley rats for two generations and resulted in NOAEL(general toxicity) ) 30 mg/kg bw/d), NOAEL (fertility) 450 mg/kg bw/d and NOAEL (offspring) 175 mg/kg bw/d

Effects on developmental toxicity

Description of key information
In rats and rabbits no developmental effects were observed for o-cresol below the NOAEL used for the systemic toxicity risk assessment (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) o-cresol was 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) and resulted in significant maternal toxicity at 450 mg/kg bw/d including treatment related clinical signs (hypoactivity, ataxia, tremor, twitches, prone positioning, audible respiration, perioral wetness), mortality of 4 dams, statistically significant reduction in body weights and body weight gain leading to a NOAEL (maternal toxicity) 175 mg/kg bw/d). Slight fetotoxicity was observed only at 450 mg/kg bw/d as one visceral variation (dilateted lateral ventricles of the brain with no tissue compression). Thus the NOAEL (developmental toxicity) is 175 mg/kg bw/d (CMA 1988).

Additionally, administration of o-cresol by gavage to time-pregnant New Zealand White rabbits during organogenesis (same guideline, gestaion day 6 through 18, 0.0, 5.0, 50.0 or 100 mg/kg bw/d) caused clinical signs of toxicity in dams including hypoactivity, audible respiration, ocular discharge from 50 mg/kg bw/d onwards (NOAEL general toxicity: 5 mg/kg bw/day) and slight fetotoxicity observed as increased incidence of one external variation and one skeletal variation in the absence of any other indications of toxicity for the conceptus at 100 mg/kg bw/day:: NOAEL (developmental toxicity): 50 mg/kg bw/d  Based on the fact that no abortions, no early deliveries were observed and gestational parameters were not affected: NOAEL (maternal toxicity): 100.0 mg/kg bw/d

                  

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Classification is not required

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