Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-398-6
CAS number: 106-44-5
In vitro studies:
p-Cresol yielded a negative result in several Ames tests performed
according to OECD TG 471 in the presence and in the absence of a
metabolic activation system and tested up to cytotoxicity (Pool and Lin
1982, Haworth 1993). p-Cresol was not mutagenic in the mouse lymphoma
forward mutation assay according to OECD TG 476 with and without
metabolic activation (CMA 1988). In 2 SCE (sister chromatid exchange)
assays p-cresol was negative under the conditions of these assays.
p-Cresol induced chromosome aberrations in a test according to OECD TG
473 with Chinese Hamster Ovary cells in the presence and in the absence
of a metabolic activation system and tested up to cytotoxicity (CMA
In vivo studies:
Several in-vivo genetic toxicity assays are available:
When p-cresol was tested according to OECD TG 478 /Rodent Dominant
Lethal Assay the substance did not induce dominant lethal mutations in
male germ cells of mice (CMA 1989).
In an additional assay p-cresol was evaluated for mutagenic activity
using the Drosophila melanogaster Sex-Linked recessive Lethal Test. The
test was negative; the treatment did not increase the frequency of
sex-linked recessive lethal mutations, indicating that the test
substance was not mutagenic in Drosophila under the conditions of this
assay (CMA 1989).
Furthermore, there is a Micronucleus Test in vivo using m/p-cresol
mixture evaluating erythrocytes for micronuclei after a treatment period
of 13 weeks. This study can be considered because - as already discussed
in the section Repeated Dose Toxicity - m/p-cresol mixture in repeated
dose toxicity studies caused histopathological changes which are
consistent with the observed effects of cresols in general.
In the respective study, male and female B6C3F1 mice were fed with diet
containing 0, 625, 1250, 2500, 5000, and 10000 ppm m/p-cresol mixture
for 13 weeks . At termination of the 13 week study peripheral blood
samples were obtained by cardiac puncture to prepare smears. Slides were
stained with Hoechst 33258/pyronin Y. At least 10000 normochromatic
erythrocytes from each animal were scored for micronuclei. In addition,
the percentage of polychromatic erythrocytes (PCEs) among the total
erythrocyte population was scored as measure of bone marrow toxicity. No
indication of clastogenicity is reported in this study because no
increases in the frequencies of micronucleated erythrocytes were seen in
male or female mice in either study (US Department of Health and Human
Services 1991, 2007; Witt 2000).
Additional, p-cresol was evaluated in an in vivo SCE assay. p-Cresol did
not induce significant increases in SCE frequencies in any of the cell
types examined: bone marrow cells, alveolar macrophages, liver cells.
p-Cresol was negative under the condition of this assay (Cheng, 1984).
Overall, considering the available data on clastogenicity there is
reliable and sufficient information to conclude that clastogenic
activity of p-cresol is unlikely in vivo.
Additional comment: On 2011-11-24 ECHA has sent to the registrant a
draft decision for p-cresol, CAS 106-44-5 (EC No 203-398-6),
communication number: CCH-C-0000002106-84-02/F.
ECHA stated: lf there is a positive result in any of the in vitro
genotoxicity studies conducted to fulfil the Information requirements
specified in Annex VII or VIII, a second in vivo test may be necessary
depending on the quality and relevance of all available data. The
absence of an appropriate second in vivo study has not been justified.
ECHA proposed pursuant to Article 12 (1) e and Annex X, 8.4 of REACH,
you should provide a justification to show whether or not a second in
vivo test is necessary.
In the updated IUCLID dataset, four in-vivo genetic toxicity tests are
included. All tests were negative. From our opinion further in vivo
tests are not necessary and not justified.
Furthermore ECHA stated: We have noted that you have not provided in
your dossier information that is available in the public domain on the
frequency of micronuclei in peripheral blood erythrocytes of mice
exposed to m- and p-cresols (NTP report on the toxicity studies of
cresol, NTP, 1992).
The requested information was added in the IUCLID dataset: Male and
female B6C3F1 mice were fed with diet containing 0, 625, 1250, 2500,
5000, and 10000 ppm m/p-cresol mixture for 13 weeks . At termination of
the 13 week study peripheral blood samples were obtained by cardiac
puncture to score micronuclei. No increases in the frequencies of
micronucleated erythrocytes were seen in male or female mice in either
study (US Department of Health and Human Services 1992, 2007; Witt 2000).
Overall conclusion: In four in-vivo genetic toxicity tests p-cresol was
negative. No increases of micronuclated erythrocytes were seen in male
of female mice in an MNT.
Therefore further in-vivo genetic toxicity tests are not justified.
No classification and labelling is necessary.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again