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Registration Dossier
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EC number: 905-287-4 | CAS number: 1638758-52-7
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- No data are available for the target substance. 90-day repeated dose oral toxicity studies are available for individual (o-, m- and p-) cresol isomers and all report NOAEL and LOAEL values of 50 and 150 mg/kg bw/d, respectively. Critical findings in the study with o-cresol included central nervous system depression and reductions in body weight and body weight gain. Critical findings in the study with m-cresol included reductions in body weight and body weight gain. Critical findings in the study with p-cresol include increased mortality, clinical signs (including lethargy, excessive salivation, tremor, occasional convulsions and coma), hepatotoxicity and nephrotoxicity. The data therefore demonstrate a higher degree of toxicity for p-cresol, which has a metabolic basis (see discussion above). OECD 422 screening studies available for xylenol (mixed isomers) and ethylphenol (mixed isomers) both report NOAEL values of 100 mg/kg bw/d. The xylenol study reports clinical signs (stained fur) and increased relative weights of the kidneys, liver and ovaries at the NOAEL of 245 mg/kg bw/d. The ethylphenol study reports clinical signs (stained fur, salivation) and increased relative weights of the kidneys, liver and ovaries at the NOAEL of 245 mg/kg bw/d. Read-across is therefore proposed to the study with xylenol as the closest structural analogue among the Category members.
Data source
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Reaction mass of 2,4-xylenol and 2,5-xylenol
- EC Number:
- 905-287-4
- Cas Number:
- 1638758-52-7
- Molecular formula:
- (CH3)2C6H3OH
- IUPAC Name:
- Reaction mass of 2,4-xylenol and 2,5-xylenol
- Test material form:
- solid: bulk
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD (SD)IGS BR VAF/Plus
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- The test substance was prepared as a solution in the vehicle and administered orally by gavage.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- GC/FID analysis of dosing preparation concentration, stability and homogeneity.
- Duration of treatment / exposure:
- 28 days for males and 54 days for females.
- Frequency of treatment:
- Daily administration beginning 14 days prior to cohabitation and continuing until the day before sacrifice.
Doses / concentrations
- Remarks:
- Doses / Concentrations:0, 30, 100 and 245 mg/kg/dayBasis:actual ingested
- No. of animals per sex per dose:
- 10 rats per sex per group
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes- Time schedule: At least 2/dayDETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: 2/dayBODY WEIGHT: Yes- Time schedule for examinations: WeeklyObservations were performed for viability, clinical signs of toxicity, food consumption, body weight gain, functional observational battery and motor activity, hematology, clinical chemistry, developmental toxicity and reproductive performance, gross and microscopic post-mortem examination.
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes
- Statistics:
- Body weight, weight gains and reproductive end points analysed by ANOVA and Dunnett's. Reproductive data analysed by Fisher's exact test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Relative weights of kidney, liver and ovaries were increased in the high dose group.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Due to clinical observations (urine-stained fur, increased kidney, liver and ovarian relative weight).
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
All rats survived the treatment. In males, urine stained fur was observed at the 245 mg/kg/day level. Body weight gain and food consumption were unaffected by treatment. Mating frequency was reduced at the 245 mg/kg/day level. Neurotoxicity was not observed during the study and there were no treatment related effects observed at gross necropsy or histopathologically. Urine staining of the fur was observed in females at the 245 mg/kg/day level. F1 animals showed no treatment related clinical or necropsy signs. Haematology and clinical pathology parameters were unaffected.
Reproductive indices are discussed under section 7.8.1.
Applicant's summary and conclusion
- Conclusions:
- The test substance mixed xylenol isomers was administered to rats by oral gavage at 0, 30, 100 and 245 mg/kg/day. The general toxicological No Observable Adverse Effect Level was shown to be 100 mg/kg/day. The reproductive NOAEL is discussed under section 7.8.1.
- Executive summary:
The above results are suitable to be used for read across for Reaction mass of 2,4-xylenol and 2,5-xylenol, due to the category being based on structural similarity and comparable physicochemical properties, leading to similar (eco)toxicological properties.
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