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EC number: 203-398-6
CAS number: 106-44-5
Mortality: 8/28 males and 5/25 females at 450 mg/kg bw; 1/25 females at 30 mg/kg bw Clinical signs of toxicity occurred in F0 and F1 males and females at 450 mg/kg bw/day and included hypoactivity, ataxia, twitches, tremors, prostration, urine stains, audible respiration, perinasal encrustation (not in F0 males), and perioral wetness occurred at >= 175 mg/kg bw. body weight: F0 adult males, sign reduced (p<0.01) week1 to week 13 in the 450 mg/kg bw group; F0 adult females: sign. reduced week 1 (p<0.05) in the 450 mg/kg bw-group, gestational weight gain not significantly different from control group, lactational body weight sign. reduced (p<0.05) at d4 at 450 mg/kg bw group
F1 or F2: No reproductive parameters were affected in either of the two generations (mating index of male and females, fertility index of males and females, gestational index.
Still births in the F1 and F2 generations: in F1 pups increased at 175 mg/kg/day (7/13 of one dam), but not at 450 mg/kg bw/day (low, mid, high dose versus control: 4/290 born pups, 13/312 born pups with 7/13 on one dam, 6/193 born pups) in F2 pups increased at 30 and 450 mg/kg bw, but not at 175 mg/kg/bw (low, mid, high dose versus control: 7/307 born pups, 4/265 born pups,9/163 born pups versus 0/318 born pups).
There was some variability in the number of stillborn in control groups in F1 and F2 generation (2 versus 0). There was no clear dose-dependent effect in both generations (control/low/mid/high dose: F1 pups: 2/4/13/6; F2 pups: 0/7/4/9).
F1,F2: Pup survival indices in both generations were not affected by treatment (4-day survival index, 7-day survival index, 14-day survival index 21-day survival index and lactation index), except live birth indices in F2 (but not F1) which were reduced at 30 and 450 mg/kg bw, but not at 175 mg/kg/day. Without any other effects especially in the 30 mg/kg bw-group it is unclear whether the effects on live birth indices were substance related gross lesions of parental males and females which died prior to scheduled sacrifice included diffuse, focal or multifocal color changes in the lung and stained skin for males and lung congestion and congestion in the nasal turbinates and erythrocytes on the skin surface for females. There were no treatment related histologic lesions observed in the examination of organs from parental F0 and F1 adults which survived to scheduled sacrifice.
Reproductive toxicity was examined in a two-generation toxicity study
according to TSCA Health Effects Test Guideline for specific
organ/tissue toxicity - Reproduction/Fertility effects. Sprague-Dawley
rats were given daily 0, 30, 175, or 450 mg/kg bw/day p-cresol in corn
oil by gavage. No effects on fertility were detected despite overt
general toxicity including increased mortality and reduced body weight
gain at 450 mg/kg bw and at >= 175 mg/kg bw/day hypoactivity ataxia,
twitches, tremors, prostration, urine stains, audible respiration and
perioral wetness. Thus, the NOAEL(fertility) was 450 mg/kg bw/day and
the NOAEL(general toxicity) was 30 mg/kg bw/day. The NOAEL(offspring) is
175 mg/kg bw/day due to toxic effects in the F2 litters of the high dose
group animals and no clear evidence of toxic effects in F1 pups.
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