Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 203-398-6 | CAS number: 106-44-5
- 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://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
In a subchronic toxicity study according to OECD TG 408 p-cresol was administered daily to male and female Sprague-Dawley rats by gavage at dose levels of 0, 50, 175 , 600 mg/kg bw/day diluted in corn oil (RTI 1988). Based on increased mortality, clinical signs including lethargy, exessive salivation, tremor and occasional convulsions and comas, hepatotoxicity and nephrotoxicity from 175 mg/kg bw/d onwards, the NOAEL is 50 mg/kg bw/d.
Due to the corrosive properties of p-cresol to the skin it will be allocated to the moderate hazard category for local effects.
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: guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- 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 Ladeview,NY
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 152-233 g
- Housing: individually
- Water ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72
- Humidity (%): 50
- Air changes (per hr): 12-17
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- Dosage formulations were prepared fresh weekly throughout the study and stored protected from light at room temperature.
DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Lot/batch no. (if required):
- Purity: - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- the concentration of p-cresol in corn oil was analyzed in week 1, 2, 4, 8 and 13
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- once daily, 7 days/week
- Remarks:
- Doses / Concentrations:
0, 50, 175, 600 mg/kg bw/day dissolved in corn oil
Basis:
actual ingested - No. of animals per sex per dose:
- 30 rats/sex/dose, for baseline examinations additionally 10 rats/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Interim kill at week 7
Post-exposure period: no - Positive control:
- no
- Observations and examinations performed and frequency:
- yes, see section "any other information on materials and method"
- Sacrifice and pathology:
- yes, see section "any other information on materials and method"
- Other examinations:
- yes, see section "amy other information on materials and method"
- Statistics:
- yes, see section "any other information on materials and method"
- 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):
- effects observed, treatment-related
- Food efficiency:
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- see section " Remarks on results"
- 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/d: increased mortality, clinical signs including lethargy, excessive salivation, tremor and occasional convulsions and comas, hepatotoxicity and nephrotoxicity
- Critical effects observed:
- not specified
- Executive summary:
In a subchronic toxicity study according to OECD TG 408 p-cresol was administered daily to male and female Sprague-Dawley rats by gavage at dose levels of 0, 50, 175 , 600 mg/kg bw/day diluted in corn oil. Based on increased mortality, clinical signs including lethargy, exessive salivation, tremor and occasional convulsions and comas, hepatotoxicity and nephrotoxicity from 175 mg/kg bw/d onwards. The NOAEL is 50 mg/kg bw/d (RTI 1988).
Reference
600 mg/kg: 3 females died within the first 3 days of dosing.
Overt signs of toxicity at this dose included lethargy, tremors, convulsions and coma.
BODY WEIGHT was sign. reduced (p</=0.05):
50 mg/kg bw: female, at week 1, 2, 3, 4, 5, and 7 175 mg/kg bw: male, at week 2, 3, and 4 600 mg/kg bw: male, except week 1 in all weeks; female, week 2, 3, 4, 5, 6, 7, 8, 9, and 14
BODY WEIGHT GAIN was sign. reduced (p</=0.05):
50 mg/kg bw: female, week 2, and 3
175 mg/kg bw: male, week 1, 2, and 3; female, week 1 and 2
600 mg/kg bw: male, all weeks; female, week 1, 2, 3, 4, 5, 6, 7, 10, 13
FOOD CONSUMPTION data was sign. reduced (p</=0.05):
50 mg/kg bw: male, week 5, 9; female, week 1 and 2
175 mg/kg bw: male, week 1, and 5
600 mg/kg bw: male, week 1, 2, 3, 4, 5, 6, 7, and 9; female, week1, 2, and 5
CLINICAL PATHOLOGY, only sign. changes (p</=0.05):
Male:
APTT, 600 mg/kg bw, increased; total protein from 175 mg/kg bw increased; Ca, at 175 mg/kg bw increased; phosphate, 600 mg/kg bw, increased
Female:
RBC, HGB, HCT, from 175 mg/kg bw, decreased; CO2, at 175 mg/kg bw, decreased; SGPT, SGOT, Cholesterin, at 600 mg/kg bw increased;
OPHTHALMOLOGY:
Treatment related changes were not seen.
ORGAN WEIGHTS (rel. and abs., only sign. changes, p</=0.05):
Male:
Heart, rel., at 600 mg/kg bw increased; liver, 600 mg/kg bw, abs. decrease, rel. increase; spleen, 600 mg/kg bw, absol. decreases; right and left kidney, from 175 mg/kg bw, rel. increased; right and left testis, at 600 mg/kg bw, rel. increased; brain, at 600 mg/kg bw, abs. decreased, rel. increased;
Female:
spleen, at 50 mg/kg bw, rel. increased (no histopathologic correlate); right kidney, at 600 mg/kg bw, rel. increased; right ovary, at 600 mg/kg bw, ovary and brain, abs. decreased
PATHOLOGY:
Gross necropsy examinations did not detect treatment- related changes.
Histological examination:
male:
chronic nephropathy in all rats including controls:
a slight increased incidence in all dosed males when compared to the controls. The increased incidence was significantly greater (p</=0.05) at the low and the high dose but not at the middle dose. The proportion of rats with minimal and mild nephropathy was generally similar for all male rats including controls:
controls: 4/20 = 20%, severity(s): minimal 3/4, mild 1/4;
50 mg-gr.: 11/20 = 55%, s: minimal: 3/11, mild: 2/11
175 mg-gr.: 7/20 = 35%, s: minimal: 7/7, mild:0/7
600 mg-gr.: 12/20 = 60%, s: minimal: 9/12, mild: 3/12
(no dose-response relationship, controls also affected, no increase in percentage of severity in dosed rats when compared to the controls)
male, female:
epithelial metaplasia of the trachea:
sign, at 600 mg/kg bw (p</=0.05), 10/20 males, 9/19 females
The incidence of this lesions was similiar for low dose, mid dose and control.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 50 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- The materials/methods and results are described in detail und are sufficient for evaluation.
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
In a subchronic toxicity study according to OECD TG 408 p-cresol was administered daily to male and female Sprague-Dawley rats by gavage at dose levels of 0, 50, 175 , 600 mg/kg bw/day diluted in corn oil (RTI 1988). Based on increased mortality, clinical signs including lethargy, exessive salivation, tremor and occasional convulsions and comas, hepatotoxicity and nephrotoxicity from 175 mg/kg bw/d onwards, the NOAEL is 50 mg/kg bw/day
In 2007, US Health and Human services published a Toxicity and Carcinogenicity Study in which only male rats or only female mice were fed with a diet containing m/p-Cresol mixture (60:40) over a period of two years. Only gross and microscopic anatomical lesions were reported. Obviously, no organ weights, no clinical chemistry , no hematology and no urinalysis were done to evaluate general toxicity. Based on these limitations these toxicity and carcinogenicity studies were not chosen as key studies. Nevertheless , the reported histopathological changes are consistent with the observed effects of cresols in general.
Male F344/N rats, fed with 0, 1500, 5000 or 15000 ppm in diet , showed increased incidences of non-neoplastic lesions in the kidney (hyperplasia); nose (inflammation, hyperplasia and metaplasia) and liver (eosinophilic focus). A NOAEL could not be derived; the LOAEL (male rat) is 1500 ppm (equivalent to average daily dose of approximately 70 mg/kg bw/day).
From female B6C3F1 mice, fed 0, 1000, 3000 or 10000 ppm in diet , increased incidences in lesions in the respiratory tract (hyperplasia in the nose and lung), thyroid gland (follicular degeneration)and liver (eosinophilic foci were reported with a LOAEL of 1000 ppm (equivalent to average daily doses of approximately 100 mg m/p cresol / kg bw/day).
DERMAL APPLICATION
There is no valid dermal repeated dose study available. p-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 p-cresol might be absorbed across 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 information on systemic toxicity is needed for risk assessment.
Due to the corrosive properties of p-cresol it is not appropriate to conduct a route-to-route extrapolation for local effects. The available data for p-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 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 p-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 also into account animal welfare reasons
INHALATION EXPOSURE
There is no adequate inhalation study available. p-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, p-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 p-cresol it is not appropriate to conduct a route-to-route extrapolation for local effects. The available data for p-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), December 2010.
Due to the corrosive properties of p-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:
The most reliable study was used as key study and for classification.
Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; urogenital: kidneys
Justification for classification or non-classification
According to Regualtion (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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)