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m-Cresol - ipcs inchem

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OECD SIDS<br />

p-CRESOL<br />

5. TOXICITY ID: 106-44-5<br />

DATE: 24.05.2004<br />

adduct with a relative adduct level of 0.28 x 10(exp)-7.<br />

Oxidized p-<strong>Cresol</strong> to a quinone methide and than incubated with calfthymus<br />

DNA resulted in 5 major adducts and a relative adduct level of<br />

20.38 x 10(exp)-7.<br />

The DNA adducts formed by activation of p-cresol with either horseradish<br />

peroxidase or microsomes were the same as that produced by the quinone<br />

methide of p-cresol.<br />

Reliability : (2) valid with restrictions<br />

no validated test method<br />

Flag : Critical study for SIDS endpoint<br />

06.02.2004 (162)<br />

5.6 GENETIC TOXICITY ‘IN VIVO‘<br />

274<br />

Type : Dominant lethal assay<br />

Species : mouse<br />

Sex : male<br />

Strain : ICR<br />

Route of admin. : gavage<br />

Exposure period : Single dose<br />

Doses : 0, 100, 275, 550 (650) mg/kg bw diluted in corn oil<br />

Result : negative<br />

Method : other: EPA OTS 798.5450<br />

Year : 1989<br />

GLP : yes<br />

Test substance : other TS: p-cresol, 99.8% pure<br />

Method : Dose selection based upon the results of a dose range-finding assay<br />

Number of animals:<br />

25 males/group 50 females/group,<br />

vehicle control: corn oil,<br />

positive control: Triethylenemelamine (TEM)<br />

Due to high mortality and toxicity in the 650 mg/kg bw-group during the first<br />

week mice were removed from the study. Two weeks after the initiation of<br />

the assay another group of males dosed with 550 mg/kg bw was assigned<br />

as the new high dose to be evaluated.<br />

Mating scheme:<br />

1 male was mated with 2 virgin females for a period of up to 5 days. Then<br />

females were removed and housed in groups for subsequent necropsy 14<br />

days after the midweek of mating for evidence of pregnancy; the males<br />

were rested for 2 days and then mated with 2 new females. This mating<br />

sequence was followed for 6 consecutive weeks.<br />

Observation of all animals for toxic effects and/or mortality, at termination<br />

record of male body weight, determination of fertility index, total number of<br />

implantations. dead implantations, proportion of females with 2 or more<br />

dead implants, dead implants/total implants<br />

Statistical methods:<br />

Chi-square test, analysis of variance (ANOVA), Dunnett's one-tailed t test<br />

Result : Mortality:<br />

650 mg/kg bw: 10/25 males within the first week;<br />

as signs of toxicity mice exhibited rapid breathing, several became languid<br />

with mild clonic convulsions and squinted eyes and were prostrate and had<br />

scruffy coats<br />

550 mg/kg bw: 6/25 males died during the test<br />

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