p-cresol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Short description of key information:
p-Cresol was tested in-vitro in several Ames tests, a mouse lymphoma test, several chromosome aberration, sister chromatid exchange and UDS tests.
Additional p-cresol or m/p-cresol was tested in vivo in an MNT test, a Rodent Dominant Lethal Test, a Drosophila melanogaster Sex-Linked recessive Lethal Test and an in vivo SCE test. All in vivo tests were negative.

Endpoint Conclusion: No adverse effect observed (negative)

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Principles of method if other than guideline:

The objective of this in vitro assay was to evaluate the ability of p-cresol to induce chromosomal aberrations in chnese hamster ovary (CHO) cells with and without metabolic activation.

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Target gene:

no data

Species / strain / cell type:

other: Chinese Hamster ovary (CHO) cells

Details on mammalian cell type (if applicable):

- Type and identity of media: McCoy's medium
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

treatment time: 20 hrs:
-S9-mix, 100, 150, 200, 301 ug/ml performed twice; +S9-mix: 301, 601, 902 ug/ml;
treatment time: 10 hrs:
+S9-mix: 150, 225, 300 ug/ml performed twice.

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: MitomycinC (for nonactivation assay); Cyclophosphamide ( in the metabolic activated assay)

Details on test system and experimental conditions:

doses were chosen following a rangefinding assay.

Evaluation criteria:

positive if an significant increase in chromosoally aberrrant cells were observed.

Statistics:

Fisher's Exact Test with an adjustment for multiple  comparisons.

Species / strain:

other: Chinese Hamster Ovary cells

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

other: Preliminary range-finding assays were performed (3.01-3010 µg/ml) to determine cytotoxicity: -S9-mix: >=301 µg/ml; +S9-mix: >=100µg/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

see section "Remarks on results"

Remarks on result:

other: Chinese hamster ovary cells

Non-activation assay and incubation for 20 hrs:
Increases in chromosomally aberrant cells ranging between 6.5 % and 11 % cell with aberrations (versus 1.0% of solvent control) or between 4% and 14 %.
Cells with aberrations (versus 2.0 % of solvent control), respectively.
Positive control was functional in each trial
Incubation for 20 hours with metabolic activation:
Increases in the chromosomally aberrant cells ranging between 18 % and 40.5 % cells with aberrations(902 μg/ml was toxic, versus 1.5% of solvent control) and between 17 % and 43 % cells with aberrations (902 μg/ml was toxic, versus 3.0% of solvent control, respectively.
Positive control was functional in each trial .
Incubation for 10 hours in the presence of S9-mix: no significant difference to the
solvent controls; positive controls were functional.

Conclusions:

Interpretation of results: positive

Executive summary:

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.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No differentiation between large and small colony mutants;statistical evaluation not mentioned.

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

yes

Remarks:

No differentiation between sarge and small colony mutants

Principles of method if other than guideline:

p-Cresol was assayed for mutagenic activity at the thymidine kinase (TK) locus in cultured mouse lymphoma cells (L5178Y TK +/-).

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

S9 fraction of rat liver homogenate and necessary co -factors.

Test concentrations with justification for top dose:

with activation: 0.256 ug/ml, 0.511 ug/ml, 0.767 ug/ml, 1.02 ug/ml, 1.53 ug/ml, and 3.07 ug/ml.
without activation: 51.1 ug/ml, 102 ug/ml, 153 ug/ml, 204 ug/ml, 307 ug/l, and 409 ug/ml.

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: ethylmethane sulfonate, 3-methylcholantrene,

Details on test system and experimental conditions:

Mouse lymphoma assay, according the respective OECD guideline.

Evaluation criteria:

The experimental mutant frequency will be cosidered acceptable for evalualtion only if th relative colony efficiency is 10 percent or greater and the total number of viable clones exceeds about 60.
A test result is evaluated positive if a dose-related increase in mutant frequency should be observed or if a >= two-fold increase over the concurrent background frequency is observed.

Statistics:

not mentioned

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: with activation: 7.98 ug/ml. without activation: 511 ug/ml.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

no data

Remarks on result:

other: other: L5178Y TK+/- mouse lymphoma cells

The positive controls were functional

Conclusions:

Interpretation of results: negative

Executive summary:

p-Cresol was negative in the mouse lymphoma forward mutation assay according to OECD TG 476 with and without metabolic activation.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study but no information on GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Principles of method if other than guideline:

In an Ames test p-cresol was tested for mutagenicity at five concentrations up to 500µg/plate with and without S-9 mix using five strains of S. typhimurium.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

other: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Metabolic activation system:

a 9000 xg supernatant from Sprague-Dawley rat liver pretreated with Aroclor 1254

Test concentrations with justification for top dose:

0, 0.5, 5, 50, 500, 5000 ug/plate dissolved in DMSO, highest dose cytotoxic

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: Sodium azide, 2-Nitrofluorene, 9-Amino-acridine, 2-Aminoanthracene

Details on test system and experimental conditions:

Ames test, plate incorporation methodology

Evaluation criteria:

a dose-related significantly increased number of revertants was evaluated as a positive result.

Statistics:

Joncheere test

Species / strain:

other: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

no further data

Remarks on result:

other: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538

p-cresol yielded a negative result in the Ames test performed according to OECD TG 471 in the presence and in the absence of a metabolic activation system.

Positive controls were functional.

Conclusions:

Interpretation of results: negative

Executive summary:

p-cresol yielded a negative result in the Ames test performed according to OECD TG 471 in the presence and in the absence of a metabolic activation system.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

p-cresol or m/p-cresol was tested in vivo in an MNT test, a Rodent Dominant Lethal Test, a Drosophila melanogaster Sex-Linked recessive Lethal Test and an in vivo SCE test. All in vivo tests were negative.

Endpoint Conclusion: No adverse effect observed (negative).

Link to relevant study records

Reference

Reference 1

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: only one dose tested, no information on GLP

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

p-Cresol was evaluated in an in vivo SCE assay.

GLP compliance:

not specified

Type of assay:

sister chromatid exchange assay

Species:

mouse

Strain:

DBA

Sex:

male

Route of administration:

intraperitoneal

Vehicle:

no data

Details on exposure:

no data

Duration of treatment / exposure:

single dose

Frequency of treatment:

single application

Post exposure period:

ca, 21.5 hours

Remarks:

Doses / Concentrations:
0, 75 mg/kg bw in sunflower oil
Basis:
nominal conc.

No. of animals per sex per dose:

3 intact animals and 3 hepatoectomized animals.

Control animals:

yes, concurrent vehicle

Tissues and cell types examined:

bone marrow, alveolar macrophages, regenerating liver cells. 20 metaphases from 3 dishes were analyzed for each cell type from each animal.

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

p-Cresol did not induce significant increases in SCE frequencies in any of the cell types examined: bone marrow cells, alveolar macrophages, liver cells.  
The dose tested was overtly toxic to the mice, causing lethargy, piloerection and lacrimation.
The positive control was functional.

Conclusions:

Interpretation of results: negative

Executive summary:

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.

 

Reference 2

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: effects of m/p-cresol mixture was investigated

Qualifier:

according to guideline

Guideline:

other: MacGregor JT, Wehr CM, Henika PR, Shelby DM (1990): Fundam Appl Toxicol. 14, 513-522

Principles of method if other than guideline:

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.

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 to 6 weeks
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 12-13 days

ENVIRONMENTAL CONDITIONS: standard
-

Route of administration:

oral: feed

Vehicle:

test substance was given with the diet

Details on exposure:

test substance was given with the diet

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

Post exposure period:

none

Remarks:

Doses / Concentrations:
0, 625, 1250, 2500, 5000, 10000 ppm daily for 13 weeks
Basis:

No. of animals per sex per dose:

10 male and 10 female mice/dose

Control animals:

yes, plain diet

Positive control(s):

no data

Tissues and cell types examined:

normochromatic erythrocytes and polychromatic erythrocytes

Details of tissue and slide preparation:

peripheral blood samples were obtained by cardiac punctuire 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.

Evaluation criteria:

In the micronucleus test , an individual trial is considered positiveif the trend test P value is less than or equan to 0.025 or if the P valuu for any single exposed group is less than or equal to 0.025 devided by the number of exposure groups.
A final call of positive for micronucleus induction is preferably based on reproducibly positive trials.

Statistics:

one-tailed Cochran-armitage trend test, followed by a pairwise comparison between each exposed group and the control group

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

not specified

No increases in the frequencies of micronucleated erythrocytes were seen in male or female mice.

Conclusions:

Interpretation of results: negative

Executive summary:

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 1991, 2007; Witt 2000).

Reference 3

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)

Principles of method if other than guideline:

The objective of this dominant lethal assay in mice was to determine the level of fetal death in untreated females following mating to males acutely treated with p-cresol. All stages of male germ cell development were evaluated (six mating periods).

GLP compliance:

yes

Type of assay:

rodent dominant lethal assay

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: males: 9.5 weeks
- Weight at study initiation: 26.7 - 36.7 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study:
- Housing: males individually and females in groups
- Diet ad libitum
- Water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
all dosing solutions were prepared immediately prior to dosing

Duration of treatment / exposure:

Single dose

Frequency of treatment:

once

Post exposure period:

6 weeks

Remarks:

Doses / Concentrations:
0, 100, 275, 550 (650) mg/kg bw diluted in corn oil
Basis:
actual ingested

No. of animals per sex per dose:

25 males/group were treated; 50 females /group

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Route of administration: i.p.
- Doses / concentrations: 0.3 mg/kg

Tissues and cell types examined:

All females were examined for the number of live and dead implants within the uterine horn and whether the dead implants had occurred early or late in gestation. Live fetuses were identified as those which appeared to have a functional circulatory capacity.

Evaluation criteria:

statistically significant dose-related increase in the number of dominant lethals is considered as mutagenic in this test system.

Statistics:

Chi-square test, ANOVA, Dunnett's one-tailed t-test

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

see section " remarks on results"

Mortality:
650 mg/kg bw: 10/25 males within the first week; as signs of toxicity mice exhibited rapid breathing, several became languid with mild clonic convulsions and squinted eyes and were prostrate and had scruffy coats; 550 mg/kg bw: 6/25 males died during the test:

 
Body weight:
No significant reduction in body weight were observed in any of the males in any of the dose groups. The statistical evaluation of the parameters indicated that no significant effects of p-cresol were induced at any dose levels.
The treatment had no adverse effects with respect to number of early and late resorptions, and live implants, indicating that the test compound did not induce dominant lethal mutations in male germ cells of mice under the conditions of this assay.
The concurrent positive control substance TEM induced a significant increase in:
the number of dead implantations, in the portion of females with either one or more dead implantations, the frequency of dead implants relative to the total number of implants in each female during mating weeks 1 through 3 TEM induced a significant reduction in total implants relative to the vehicle control group.

Conclusions:

Interpretation of results: negative

Executive summary:

p-Cresol did not induce dominant lethal mutations in male germ cells of mice under  the conditions of this assay when tested according to OECD TG 478 (Rodent Dominant Lethal Assay).

Reference 4

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)

Principles of method if other than guideline:

p-Cresol was evaluated for mutagenic activity using the Drosophila melanogaster Sex-Linked recessive Lethal Test.

GLP compliance:

yes

Type of assay:

Drosophila SLRL assay

Species:

Drosophila melanogaster

Strain:

other: Oregon-R

Sex:

male

Route of administration:

oral: feed

Duration of treatment / exposure:

3 days

Remarks:

Doses / Concentrations:
0, 60, 300 and 600 ug/ml 5 % sucrose
Basis:
nominal in diet

No. of animals per sex per dose:

200 - 300 males for each level of p-cresol
200 males for the vehicle control
100 males for the positive control

Control animals:

yes, concurrent vehicle

Positive control(s):

ethylmethanesulphonate;
- Route of administration: oral as a one-day exposure on the final day of the 3-day dosing schedule
- Doses / concentrations: 0.67 µl/ml 5% sucrose solution

Tissues and cell types examined:

F2 generation: determing the presence or the absence of males with wild type eyes

Details of tissue and slide preparation:

determing the presence or the absence of males with wild type eyes

Evaluation criteria:

F2-generation: absence of males with wild type eyes is evaluated as positive

Statistics:

Fisher exact test,
trend analysis using Cochran-Armitrage test for trend combined with the Fisher-Irvin exact test for heterogenicity

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

other: vehicle control serves as negative control

Positive controls validity:

valid

The test was negative; the treatment did not increase the frequency of sexlinked
recessive lethal mutations, indicating that the test substance was not mutagenic in Drosophila under the conditions of this assay.
The positive control substance ethylmethansulfonate (EMS) was functional.

Conclusions:

Interpretation of results: negative

Executive summary:

p-Cresol was evaluated for mutagenic activity using the Drosophila melanogaster Sex-Linked recessive Lethal Test. Under the conditions of this test p-cresol was evaluated as non-mutagenic in the Drosophila melanogaster Sex-Linked Recessive Lethal Test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

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 1988).

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.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.