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EC number: 215-089-3
CAS number: 1300-71-6
7.7 Carcinogenicity:SS - m/p cresol (male rat). NTP, 2007. KL.3SS - m/p cresol (female mice). NTP, 2007. KL.3
following discussion below has been taken from the NTP technical report
on Cresols. It however is important to note that due to the design of
these studies NOAEL for either neoplastic or non-neoplastic findings
could be determined. These dietary study designs resulted in effectively
nutritional effects due to the high doses of test material given.
2007, US Health and Human Services published a Toxicity and
Carcinogenicity Study in which only male rats or only female mice were
fed m/p-cresol mixture over a period of two years without interim kill.
Neither absolute/relative organ weights nor blood biochemistry data were
reported. The report contains only histopathological data.
NTP generated carcinogenicity data has been discussed below in light of
the NTP technical Report on cresols (2008).
study Male F344/N rats received in feed 0, 1500, 5000 and 15000 ppm
daily for 105 weeks. Under the condition of these 2 -year studies, there
was equivocal evidence of carcinogenic activity on m/p-cresol based on
the 4/50 male rats with renal tubular adenomas. The incidence of these
neoplasms was not significant but exceeded the historical control data
of the laboratory (1/297[feed studies]). In NTP studies the kidney is
the second most commonly affected site for chemically induced neoplasms
in the male rat and these are most adenomas (NTP, 2006). In this study
it could be speculated that the increased incidence of adenoma in the
15000 ppm group arose by mechanisms of action similar to that proposed
for hydroquinone. Hydroquinone markedly increases the number of renal
tubular cell adenomas when administered to F344/N male (but not female)
rats at nephrotoxic doses. There is speculation that this is attributed
to a minor metabolite 2,3,5 -tris(glutathione-S-yl)hydroquinone a potent
toxic and redox-active species. The formation of benzoquinones from m
and p-cresol and quinone methide from p-cresol is inferred from
identification of specific glutathione conjugates formed in rat and
human liver microsomal incubations. In rats, cresols are detoxicated
primarily by conjugation to glucuronic acid of sulphate. It is likely
that minor amounts of cresol-derived glutathione conjugates are also
formedin vivo. However the potential for formation of quinone
like reactive metabolites from cresols should be much lower than from
hydroquinone itself. Therefore the potential non-neoplastic response in
the kidney should be much weaker in cresol-exposed rats than in rats
exposed to similar doses of hydroquinone. No increased incidences of
other neoplasms were observed in any other tissues of cresol exposed
rats. However due to the presence of renal tubule adenomas in the high
exposure concentration group the evidence of carcinogenicity in rats in
the NTP study was considered equivocal.
study Female B6C3F1 mice received in feed 0, 1000, 3000, 10000 ppm for
106-107 weeks. Under the conditions of these 2-year studies there was
some evidence of carcinogenic activity of m/p-cresol mixture based on
the increased incidence of forestomach squamous cell papillomas.
However, there is no human counterpart for the rodent forestomach.
Therefore, the forestomach squamous cell paplillomas are of minor
significance for the human situation. In addition, due to the corrosive
property of the test substance, chronic irritation is expected to be the
mode of action.
increased incidences of respiratory epithelial hyperplasia of the nose
were significantly increased in the 3000 and 10000 ppm groups. However
cresols have been shown to be respiratory irritants in humans and
animals following inhalation exposure. The non-neoplastic lesions were
most likely due to inhalation exposure of the p-isomer volatising from
the feed during consumption and not from direct systemic exposure
following oral absorption. Such lesions are considered to be an adaptive
response and are among those commonly observed in NTP inhalation studies
of chemicals that are known irritants (NTP, 2000).
the conditions of these 2 year studies, there was equivocal evidence of
carcinogenic activity of m/p cresol in male F344/N rats based on the
marginally increased incidence of renal tubule adenoma. There was some
evidence of carcinogenic activity of m/p cresol in female B6C3F1 mice
based on the increased incidence of forestomach squamous cell papilloma.
to m/p cresol resulted in increased incidences of non-neoplastic lesions
in the kidney (hyperplasia), nose (inflammatory, hyperplasia and
metaplasia) and liver (eosinophilic focus) of rats. Increased incidences
of non-neoplastic lesions were observed in the respiratory tract
(hyperplasia in the nose and lung), thyroid gland (follicular
degeneration) and liver (eosinophilic focus) of mice.
Toxicology Program (NTP, 2000). NTP Technical report on the toxicology
and carcinogenesis studies of napthalene (CAS no. 91 -20 -3) in F344/N
rats (inhalation studies). Technical report series No. 500. NIH
publication No. 01 -4434. National Institutes of Health, Public Health
Services, US Department of Health and Human Services, Research Triangle
Toxicology Program (NTP, 2006). NTP Technical report on the toxicology
and carcinogenesis studies of benzophenone (CAS no. 119 -61 -9) in
F344/N rats and B6C3F1 mice (feed studies). Technical report series No.
533. NIH publication No. 06 -4469. National Institutes of Health, Public
Health Services, US Department of Health and Human Services, Research
Triangle Park, NC.
Toxicology Program (NTP, 2008). NTP Technical report on the toxicology
and carcinogenesis studies of cresols (CAS No. 1319 -77 -3) on male
Fe44/N rats and female B6C3F1 mice (feed studies). Technical report
series No. 550. NIH publication No. 08 -5891. National Institutes of
Health, Public Health Services, US Department of Health and Human
Services, Research Triangle Park, NC.
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