m-Cresol - ipcs inchem

OECD SIDS
m- / p-CRESOL
weights were increased in all dosed groups. There was no effect of treatment on estrous cyclicity or
ovarian, liver or kidney histopathology. NOAEL (F1, general toxicity): 0.25 % (approximately 375
mg/kg bw/day).
In F1, m/p-cresol mixture had no effect of mating index, fertility index, pregnancy index. Number
of live F2 pups per litter, proportion of F2 pups born alive, and sex ratio of F2 pups was not
affected. Only live F2 pup weights and the adjusted live F2 pup weights of the 1.5 % dose group
was significantly reduced. Thus, the NOAEL (F1, fertility) was 1 % (approximately 1500 mg/kg
bw/day).
No effects on sperm motility and concentration, and on oestrus cycle and vaginal cytology were
found following 13 weeks of feeding, groups of 10 mice/sex doses of up to 10,000 ppm (1513
mg/kg bw/day for males and 1693 mg/kg bw/day for females, respectively) (NTP 1991).
Following 13 weeks of feeding groups of 10 rats/sex doses up to 30,000 ppm (ca. 2014 mg/kg
bw/day for males and 2050 mg/kg bw/day for females) the only finding in males was a biologically
insignificant decrease (4 %) in mean sperm motility values which occurred at the high dose level. In
females, a dose-related increase in oestrous cycle length was observed at 7500 ppm (approximately
509 mg/kg bw/day) and 30,000 ppm; slight uterine atrophy was noted at 15,000 ppm (NTP 1991).
Conclusion
Despite general toxicity (hypoactivity, ataxia, twitches, tremors, prostration, urine stains, audible
respiration, perioral wetness), fertility was not affected by treatment with m-cresol or p-cresol
(NOAEL, rat: 450 mg/kg bw/day). The NOAELs for general toxicity were determined as 30 mg/kg
bw/day. Fertility effects including a 20 % reduction in pup survival as well as reductions in the
weights of male reproductive organs were found following treatment of mice with m/p-mixture in a
continuous breeding study at systemically toxic dose levels (reduced food consumption and reduced
body weights, increases in liver and kidney weights) (NOAEL, fertility and general toxicity: 0.25 %
in feed (ca. 375 mg/kg bw/day)).
3.1.9 Developmental toxicity/Teratogenicity
m-Cresol
Developmental toxicity was examined in Sprague-Dawley rats and New Zealand White rabbits
(BRRC 1988a, b).
m-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 periodic maternal body weights and weight gain during the dosing period. Clinical
signs of toxicity at 450 mg/kg bw/day included hypoactivity, ataxia, tremor, twitches, prone
positioning, audible respiration, perioral wetness, and a reduction in food consumption. m-Cresol
did not induce fetotoxicity or malformations at any dose level tested. The NOEL for maternal
toxicity was 175 mg/kg bw/day and the NOEL for developmental toxicity was 450 mg/kg bw/day.
No fetotoxicity and no treatment-related effects on the incidence of any malformation (external,
visceral, skeletal) was found in the progeny of 14 rabbits/group, dosed by gavage on gestation day
6 - 18 with doses of 0, 5, 50, 100 mg/kg bw/day dissolved in corn oil. Clinical signs of toxicity were
observed at 50 mg/kg bw/day (audible respiration and ocular discharge). The NOEL for maternal
toxicity was 5 mg/kg bw/day and the NOEL for developmental toxicity was 100 mg/kg bw/day.
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