Registration Dossier
Registration Dossier
Diss Factsheets
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: 202-423-8 | CAS number: 95-48-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
o-cresol reveals no gene mutation activity and the clastogenic activity
in vitro was not confirmed by respective in vivo studies.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: guideline test but no data on GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538
- Additional strain / cell type characteristics:
- other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- A 9000 x g supernatant from Sprague-Dawley rat liver pretreated with Aroclor 1254.
- Test concentrations with justification for top dose:
- 0, 5, 50, 500, 5000 µg/plate dissolved in DMSO
- 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-Aminoacridine, 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 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:
- Positive controls were functional.
- Executive summary:
o-cresol yielded a negative result in the Ames test performed according to OEDCD TG 471 in the presence and in the absence of an additional metabolic activation system.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- 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)
- 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 5a culture 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:
- A 9000 x g supernatant prepared from adult male rat liver induced by Aroclor 1254.
- Test concentrations with justification for top dose:
- without: 150, 200, 250, 300 µg/ml
with: 250, 375, 500, 750, 1000 µg/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: Mitomycin C , Cyclophosphamide
- Details on test system and experimental conditions:
- According to OECD guideline 473.
- Evaluation criteria:
- Concentration related increase.
- Statistics:
- Fisher's exact test with an adjustment for multiple comparisons.
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- other: determined in the range-finding study:| with metabolic activation: >= 1000 µg/ml; without metabolic activation: >= 300 µg/ml
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Executive summary:
o-cresol showed clastogenic activity when tested for chromosome aberrations in Chinese Hamster Ovary (CHO) cells in vitro according to OECD TG 473 in the presence and in the absense of a metabolic activation system.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: no information on colonie size and no information of purity of TS
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- no data
- Species / strain / cell type:
- other: mouse lymphoma cells L5178Y TK+/-
- Details on mammalian cell type (if applicable):
- no further data
- Metabolic activation:
- with and without
- Metabolic activation system:
- A 9000 x g supernatant prepared from Fisher 344 adult male rat liver induced by Aroclor 1254.
- Test concentrations with justification for top dose:
- without: 15.6, 31.3, 62.5, 125.0, 250.0 µg/ml
with: 3.91, 7.816, 15.600, 31.300, 62.5 nl/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: Dimethylnitrosamine, Ethylmethane sulfonate
- Details on test system and experimental conditions:
- Mouse lymphoma assay
- Evaluation criteria:
- The minimum criterium for a positive response in this assay was a mutant frequency exceeding 30.6 x 10 [exp-6].
- Statistics:
- no data
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: without: at and above 500 µg/ml; with: at and above 15.6 nl/ml
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Executive summary:
o-cresol yielded a negative result when tested with the Mouse Lymphoma assay in-vitro according to OECD TG 476 in the presence and in the absence of a metabolic activation system. The positive controls were functional.
Referenceopen allclose all
o-cresol yielded a negative result in the Ames test performed according to OECD TG 471 in the presence and in the absence of an additional metabolic activation system (Pool 1982).
o-cresol showed clastogenic activity when tested for chromosome aberrations in Chinese Hamster Ovary (CHO) cells in vitro according to OECD TG 473 in the presence and in the absense of a metabolic activation system.
No information on colony size. The positive controls were functional.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Description of key information
o-cresol reveals no gene mutation activity and the clastogenic activity
in vitro was not confirmed by respective in vivo studies.
Endpoint Conclusion:No adverse effect observed (negative).
Link to relevant study records
- Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
- 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 ANIMAL
- Age at study initiation: 8 weeks
- Assigned to test groups randomly: yes
- Housing: males : individually females: in groups
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: 4 days
-body weights at initialtion and at termination of the assay
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- no further data
- Duration of treatment / exposure:
- once
- Frequency of treatment:
- once
- Post exposure period:
- 6 weeks
- Remarks:
- Doses / Concentrations:
0, 75, 250, 750 mg/kg bw in corn oil
Basis:
actual ingested - No. of animals per sex per dose:
- 25 males per dose.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Triethylenemelamine
- Justification for choice of positive control(s):
- Route of administration: single i.p. injection
- Doses / concentrations: 0.3 mg/kg as a volume of 10 ml/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.
- Details of tissue and slide preparation:
- no data
- Evaluation criteria:
- Statistically significant dose-related increase in the number of dominant leathals is considered as mutagenic in this system.
- Statistics:
- Chi-square test, ANOVA, Dunnett's one-tailed t test.
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Remarks:
- concentrations were chosen based on dose-range toxicity study
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- see section : "Remarks on results"
- Conclusions:
- The test article was considered negative for inducing dominant lethal mutations in germ cells of male mice under conditions of this assay.
- Executive summary:
The test article was considered negative for inducing dominant lethal mutations in germ cells of male mice under conditions of this assay.
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: no data on the ratio of normochromatic to polychromatic erythrocytes, no positive control
- Reason / purpose for cross-reference:
- reference to same study
- Principles of method if other than guideline:
- Method: Smears were prepared from peripheral blood samples obtained by cardiac punction of dosed and control animals at the termination of the 13 week study. Polychromatic and normochromatic erythrocytes from each animal were scored for 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:
- see the respective record in the chapter 7.5.1
- Route of administration:
- oral: feed
- Vehicle:
- see the respective record in the chapter 7.5.1
- Details on exposure:
- see the respective record in the chapter 7.5.1
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
- Post exposure period:
- no
- Remarks:
- Doses / Concentrations:
0, 5000, 10000, 20000 ppm
Basis:
nominal in diet - No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent no treatment
- Positive control(s):
- no data
- Tissues and cell types examined:
- Erythrocytes from peripheral blood samples.
- Details of tissue and slide preparation:
- Slides were stained with Hoechst 33258/pyrcein Y according to MacGregor et al (1983, no further data).
- Evaluation criteria:
- Positive if a significant elevation in the frequenciy of micronucleated erythrocytes was observed either in males or in females.
- Statistics:
- Yes, but method not mentioned
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- not examined
- Executive summary:
Following repeated oral dosing of mice over a period of 13 weeks with o-cresol, the MNT with peripheral erythrocytes yielded a negative result.
Referenceopen allclose all
--high dose males:
Mortality: 8/25 within 6 days post dosing.
Signs of intoxication: lethary, rough haircoat, languid, tremor,
distended abdomen, squinted eyes; all surviving males recovered from
these effects within 6 days after dosing.
No effects were observed on fertility index, total implants, mean
implants per pregnant female, total live implants, total dead implants,
and body weight gain of males.
The test article was considered negative for inducing dominant lethal
mutations in germ cells of male mice under conditions of this assay.
Compound consumption:
dose---------male------female
[ppm]---------[mg/kg bw/d]
-----------------------------
5000 ---------794 -------935
10000--------2723------1663
20000--------2723------3205
No significant elevation in the frequency of micronucleated erythrocytes
was observed in either male or female mice. NOAEL for systemic toxicity
is 1250 ppm (199 and 237 mg/kg bw/d, respectively) based on increased
relative and absolute liver and kidney weights without histopathological
correlate from 2500 ppm onwards.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
In several Ames tests according to the respective guideline, in the absence and in the presence of a metabolic activation system, tested up to the cytotoxicity o-cresol revealed no genotoxic activity (Pool 1992, Pepper, Hamilton & Scheetz 1981, Haworth 1993). E.Coli or S.typhimurium TA 102 were not included in the tests, but this is not necessary as o-cresol has no oxidising or cross-linking properties nor is it a hydrazine derivative (OECD TG 471). A negative result in the mouse lymphoma assay performed according to the respective guideline with and without a metabolic activation system was found (Pepper, Hamilton& Scheetz 1981).
However, positive results were reported in assays for chromosomal aberrations for o-cresol in Chinese hamster cells (CMA 1988). The available respective in vivo studies do not confirm this result The Dominant Lethal Assay (DLA) in the mouse was negative (CMA 1989). Following repeated dosing of mice with 0, and 1250-20000 ppm for 13 weeks a MNT with peripheral erythrocytes in mice that were dosed with 0, 5000, 10000 and 20000 ppm was carried out. The NOAEL for general toxicity is 1250 ppm based on increased relative kidney and liver weights at higher doses. In the erythrocytes of the chosen mice o-cresol did not induce a significant elevation in the frequency of micronucleated erythrocytes. (US Department of Health and Human Services 1991).
Thus, o-cresol reveals no gene mutation activity and the clastogenic activity in vitro was not confirmed by respective in vivo studies.
In summary, these data indicate that o-cresol can induce chromosomal aberrations and increase SCEs in vitro but does not do so in vivo (OECD SIDS o-Cresol, CAS N°: 95-48-7, UNEP publication).
Overall, cresols do not seem to pose a genotoxic threat to humans under normal environmental exposure conditions (U.S. DEPART- MENT OF HEALTH AND HUMAN SERVICES, Public Health Service, Agency for Toxic Substances and Disease Registry September 2008).
Justification for selection of genetic toxicity endpoint
In vitro assays (Ames tests, SCE assays, CA tests, UDS tests, and a
comet assay) and in-vivo assays (MN tests, dominant lethal tests and a
SCE test) are available.
Justification for classification or non-classification
According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.
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.
