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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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
Subchronic inhalational exposure (4 months) of rats to o-cresol causes reduced locomotor activity, inflammation of respiratory tissues and changes in the liver. No NOAEL could be determined for this route. Oral exposure of up to 13 weeks of mice and rats resulted in mortality, tremors, reduced body weights, hematologic effects and increase in organ weights. An overall subchronic NOAEL of 50 mg/kg bw/day can be derived (OECD SIDS for o-Cresol, CAS N°: 95-48-7, UNEP publication).
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: comparable to a guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: Sontag JM, Page NP, Saffotti U, NCI, DHEW Publication No (NIH)78-ß01Guidelines for Carcinogen Bioassay in small rodents
- Principles of method if other than guideline:
- Method: see section" any other information of materials and methods".
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 5-6 weeks
- Fasting period before study: 24 hours
- Housing: individually
- Diet : ad libitum):
- Water : ad libitum):
- Acclimation period: 16 days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72
- Humidity (%): 50
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
test solution was produced on a weekly basis
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- during test week 1, 2, 4, 8 and 13 by
Enseco Inc, Cambridge MA and additionally by American BiogenicsCorporation, Decatur IL - Duration of treatment / exposure:
- 13 w
- Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
50, 175, 600 mg/kg bw/day in corn oil
Basis:
actual ingested - No. of animals per sex per dose:
- 30 animals /sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: no
- Positive control:
- no data
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily for mortality and clinical signs
BODY WEIGHT: Yes
- Time schedule for examinations: day 1 and then weekly
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption
and body weight gain data: Yes , weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: during quarantine period and in test week 13
HAEMATOLOGY: CLINICA CHEMISTRY : Urinalysis Yes
- Time schedule for collection of blood: as baseline clinical pathology, at test week 7 (interim kill) at study termination
- How many animals: 10 rats/sex/dose
- Parameters checked : see section "additional iformation on materials and methods"
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see section " any other information on materials and method"
HISTOPATHOLOGY: Yes (see section"Any other information on materials and method" - Other examinations:
- no data
- Statistics:
- One-Way Analysis of Variance tests, Dunnett's t test.
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- 600 mg/kg bw/day: mortality 19/30 females and 9/30 males,
Body weight:
reduction
body weight of females were unaffected
600 mg/kg bw/d, males: significant during week 2 through 10
175 mg/kg bw/d, males: significant during week 2
Body weight gain
175 and 600 mg/kg bw/d
reduction in body weight gain (males), slight decrease in food intake;
600 mg/kg bw/day, males and females,
175 mg/kg bw/d: 1 female d23 and 1 female d27
Treatment-related depression of the central nervous system: lethargy, dyspnoe, tremor and/or convulsions, recovering within 1 h after dosing
No effects on clinical chemistry, hematology, urinalyses parameters,
No treatment-related ophthalmic lesions,
No effects on organ weights,
No treatment-related gross and histomorphologic lesions; - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: >= 175 mg/kg bw/day animals revealed central nervous system depression and showed statistically significant reduction in body weight and body weight gain
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 175 mg/kg bw/day (nominal)
- System:
- other: central nervous system depression and statistically significant reduction in body weight and body weight gain.
- Organ:
- other: central nervous system
- Treatment related:
- yes
- Dose response relationship:
- yes
- Conclusions:
- The NOAEL is 50 mg/kg bw/day based on adverse effects from 175 mg/kg bw /day onwards.
- Executive summary:
According to Sontag JM, Page NP, Saffotti U, NCI, DHEW Publication No (NIH)78-ß01 Guidelines for Carcinogen Bioassay in small rodents) male and female rats were applied with 0, 50,175, 600 mg/kg bw/day by gavage for 13 weeks. The NOAEL is 50 mg/kg bw/day based on adverse effects from 175 mg/kg bw /day onwards including central nervous system depression and statistically significant reduction in body weight and body weight gain (RTI 1988).
Reference
600 mg/kg bw/day:
Mortality 19/30 females and 9/30 males.
Body weight: reduction body weight of females were unaffected 600 mg/kg
bw/d, males: significant during week 2 through 10, 175 mg/kg bw/d,
males: significant during week 2. Body weight gain 175 and 600 mg/kg
bw/d reduction in body weight gain (males), slight decrease in food
intake.
600 mg/kg bw/day, males and females, 175 mg/kg bw/d: 1 female d 23 and 1
female d 27.
Treatment-related depression of the central nervous system: lethargy,
dyspnoe, tremor and/or convulsions, recovering within 1 h after dosing.
No effects on clinical chemistry, hematology, urinalyses parameters, no
treatment-related ophthalmic lesions, no effects on organ weights, no
treatment-related gross and histomorphologic lesions.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 50 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Scientifically acceptable and sufficient documented
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
ORAL APPLICATION
According to Sontag JM, Page NP, Saffotti U (NCI, DHEW Publication No (NIH)78-ß01 Guidelines for Carcinogen Bioassay in small rodents) male and female rats were applied with 0, 50, 175, 600 mg/kg bw/day by gavage for 13 weeks. The NOAEL is 50 mg/kg bw/day based on adverse effects from 175 mg/kg bw/day onwards including central nervous system depression and statistically significant reduction in body weight and body weight gain (RTI 1988).
Additionally, in feeding studies according to OECD TG 408 male and female F344 rats were fed 0, 1880, 3750, 7500, 15000, 30000 ppm o-cresol and. male and female B6C3F1 mice were fed 0, 1250, 2500, 5000, 10000, 20000 ppm o-cresol (US Department of Health and Human Services 1991). The NOAEL is 3750 ppm for males and females rats (247 and 256 mg/kg bw/d, respectively) based on increased relative kidney and liver weights from 7500 ppm onwards but no histopathological changes were reported. For male and female mice the NOAEL 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.
DERMAL APPLICATION
There is no valid dermal repeated dose toxicity study available. o-Cresol shall be registered according to REACH Article 10 and a reliable oral sub-chronic study in male and female rats (rodent) is available. Based on toxicokinetic information o-cresol might be absorbed across the gastrointestinal tract and through the intact skin. Therefore, systemic toxicity after dermal exposure can be covered by the available robust oral study (route to route extrapolation) and no additional informacion on systemic tocicity is needed for risk assessment. Due to the corrosive properties of o-cresol it is not appropriate to conduct route to route extrapolation for local effects. The available data for o-cresol in animals are not sufficiently robust to derive a clear threshold value and to calculate a DNEL for local effects after dermal exposure. Based on the available data a qualitative risk assessment approach will be followed as outlined in the REACH "Guidance on informationrequirements and chemical safety assessment R.8: Characterisation of dose [concentration]-exposure for human health (version 2.1), November 2012. Due to the corrosive properties of o-cresol to the skin it will be allocated to the moderate hazard category. No additional animal experiments are necessary in the course of a qualitative risk assessment and, consequently, further animal testing on vertebrates should be omitted for this endpoint taking into account animal welfare reasons.
INHALATION EXPOSURE
There is no adequate inhalation study available.
o-Cresol shall be registered according to REACH Article 10 and the required reliable oral sub-chronic study in male and female rats (rodent) is available. Based on the toxicokinetic information discussed in the respective section, o-cresol is well absorbed across the respiratory tract and the gastrointestinal tract. Therefore, systemic inhalation toxicity can be covered by the available robust oral study (route to route extrapolation) and no additional information on systemic toxicity is needed for risk assessment.
Due to the corrosive properties of o-cresol it is not appropriate to conduct a route-to-route extrapolation for local effects. The available data for o-cresol in animals are not sufficiently robust to derive a clear threshold value and to calculate a DNEL for local effects at the respiratory tract. Based on the available data a qualitative risk assessment approach will be followed as outlined in the REACH “Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health” (Version 2.1), November 2012.
Due to the corrosive properties of o-cresol it will be allocated to the moderate hazard category. Thus, according to ANNEX XI of REACH Regulation further testing does not appear scientifically justified based on the reliable occupational historical human data.
No additional animal experiments are necessary in the course of a qualitative risk assessment and, consequently, further animal testing on vertebrates should be omitted for this endpoint, taking also into account animal welfare reasons
Justification for selection of repeated dose toxicity via oral
route - systemic effects endpoint:
key study used
Repeated dose toxicity: via oral route - systemic effects (target
organ) cardiovascular / hematological: hematopoiesis; neurologic:
behaviour; other: all gross lesions and masses.
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.
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