m-Cresol - ipcs inchem

OECD SIDS
m- / p-CRESOL
p-Cresol
Developmental toxicity was examined in Sprague-Dawley rats and New Zeeland White rabbits
(BRRC 1988a, b).
p-Cresol was given to 25 pregnant rats/ group by gavage on gestation day 6 - 15 at doses of 0, 30,
175 or 450 mg/kg bw/day dissolved in corn oil. At 450 mg/kg bw/day, there was a significant
reduction in maternal body weight gain during the dosing period. Clinical signs of toxicity at 450
mg/kg bw/day included hypoactivity, ataxia, tremors, twitches, prone positioning, audible
respiration, and peroral wetness. p-Cresol caused fetotoxicity at 450 mg/kg/day, as evidenced by
reduced ossification in three skeletal districts. In addition, fetal body weight was reduced at 450
mg/kg/day. There was no treatment-related increase in the incidence of malformations (external,
visceral, skeletal) at any dose level. Gestational parameters which were unaffected by treatment
included number of ovarian corpora lutea, number of total, nonlive or live implants and sex ratio per
litter. Thus, the NOEL for maternal toxicity and developmental toxicity was 175 mg/kg bw/day.
No treatment-related effects on the incidence of any malformations (external, visceral, skeletal) was
found in the progeny of 14 rabbits / group, dosed by gavage on gestation day 6 - 18 with 0, 5, 50,
100 mg/kg bw/day dissolved in corn oil. Clinical signs of toxicity were observed at 50 and 100
mg/kg bw/day (audible respiration and ocular discharge, hypoactivity, gasping and cyanosis). There
were no treatment-related effects on food consumption and no treatment-related lesions in does or
any changes in maternal organ weights. Gestational parameters were unaffected by treatment (no
treatment related abortions, early deliveries or resorptions, and no changes in total, nonlive or live
implants per litter or fetal body weight per litter). Thus, the NOEL for maternal toxicity was 5
mg/kg bw/day and the NOEL for developmental toxicity was 100 mg/kg bw/day.
m/p-Cresol
There is no study available using a m/p-cresol-mixture.
Conclusion:
In developmental toxicity in rats and rabbits, no toxic effects on the developing organism could be
found despite of the toxic effects of m-cresol on the dams as evidenced by hypoactivity, ataxia,
tremor, twitches, prone positioning, audible respiration, perioral wetness, and a reduction in food
consumption in rats, and audible respiration, and ocular discharge in rabbits (NOELs: 175 mg/kg
bw/day (maternal toxicity) and 450 mg/kg bw/day (developmental toxicity) for rats, and 5 mg/kg
bw/day (maternal toxicity) and 100 mg/kg bw/day (developmental toxicity) for rabbits,
respectively).
p-Cresol caused fetotoxicity (delayed ossification, decreased fetal body weight) at maternally toxic
dose levels in rats (NOAEL maternal toxicity, developmental toxicity: 175 mg/kg bw/day). In
rabbits, p-cresol caused no developmental effects even at doses that were maternally toxic (NOEL
maternal toxicity, developmental toxicity: 175 mg/kg bw/day).
Based on the available data it can be assumed that the m-/p-cresol mixtures may have the potential
to induce fetotoxicity in the presence of maternal toxicity.
3.1.10 Other relevant information
Experience with human exposure
The effects of (intentional or accidental) oral intake of cresols (all isomers) are described in several
case reports. The effects comprise irritation of mouth and throat, abdominal pains, vomiting,
haemolytic anemia, increased heart rate, liver and kidney damage, headaches, facial paralysis,
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