m-Cresol - ipcs inchem

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m- / p-CRESOL
removed from the study and 550 mg/kg bw was assigned as the new high dose to be evaluated. p-
Cresol did not induce dominant lethal mutations in the germ cells of male mice (Hazleton 1989a)
Single intraperitoneal injection of 0.75 mg/kg bw dissolved in sunflower oil was given to 2 or 3
intact or hepatectomized male mice. Negative and positive controls received sunflower oil (intact
and hepatectomized mice) and cyclophosphamid (intact mice), respectively. p-Cresol did not induce
significant increases in SCE frequencies in any of the cell types examined (Cheng and Kligerman
1984).
m/p-Cresol
Groups of 10 mice/dose were given 0, 625, 1250, 2500, 1000 and 10,000 ppm of a m/p-cresol
mixture (60:40). The mean test substance intake was 0, 96, 194, 402, 776, 1513 mg/kg bw/day for
males and 0, 116, 239, 472, 923, 1693 mg/kg bw/day for females, respectively. To determine the
frequency of micronuclei in peripheral blood erythrocytes smears were prepared from blood
samples obtained by cardiac puncture of dosed and control mice at the termination of the 13 week
study. No significant elevation in the frequency of micronucleated erythrocytes was observed in
either male or female mice (NTP 1991).
Conclusion:
In vivo, m-cresol showed no clastogenic activity in mouse bone marrow cells, even at clearly toxic
dose levels (up to 960 mg/kg bw by gavage). p-Cresol did not induce dominant lethal mutations in
germ cells of mice after single oral doses that elicited marked toxicity (up to 550 mg/kg bw by
gavage). The sister chromatid exchange rate was not increased in mice after intraperitoneal injection
of 0.75 mg p-cresol/kg). m/p-Cresol mixture (60:40) did not elevate the frequency of
micronucleated erythrocytes in peripheral blood of mice fed for 13 weeks with up to 10,000 ppm.
Overall evaluation
In vitro, m- and p- cresol did not induce gene mutations in bacterial and mammalian cell systems
and m/p-Cresol mixture did not induce gene mutations in bacteria. m-Cresol was negative for
clastogenic activity in vitro, and in vivo. p-Cresol, was clastogenic in vitro, but has not been
adequately tested in somatic cells in vivo. p-Cresol was, however, negative for dominant lethal
mutations in germ cells in male mice at clearly toxic exposure levels. A 60:40 m-/p-Cresol mixture
did not increase the frequency of micronucleated erythrocytes in the peripheral blood erythrocytes
of mice. In vitro, it is possible that m- and p-cresol and m/p-cresol mixtures have the potential to
interact with DNA either directly or indirectly via metabolites.
Table 10:
Results of Mutagenicity Tests
m-Cresol p-Cresol m/p-Cresol
Genotoxicity
Clastogenicity
In vitro negative negative negative
In vivo
negative
In vitro negative positive
In vivo negative negative negative
o-Cresol can induce chromosomal aberrations and increase SCE in vitro but not in vivo (UNEP
1998).
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