Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
sub-chronic toxicity: dermal
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

Principles of method if other than guideline:
Method: other: see freetext RM
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
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

Test animals

Species:
mouse
Strain:
C57BL
Sex:
male
Details on test animals or test system and environmental conditions:
migrated dataset

Administration / exposure

Details on exposure:
Route of Administration: dermal
Details on analytical verification of doses or concentrations:
migrated dataset
Duration of treatment / exposure:
6 weeks
Frequency of treatment:
3x/week
Doses / concentrations
Remarks:
Doses / Concentrations:0.5 % in acetoneBasis:
No. of animals per sex per dose:
migrated dataset
Control animals:
other: no data specified
Details on study design:
Post-exposure period: 6 months
Positive control:
migrated dataset

Examinations

Observations and examinations performed and frequency:
migrated dataset
Sacrifice and pathology:
migrated dataset
Other examinations:
migrated dataset
Statistics:
migrated dataset

Results and discussion

Results of examinations

Details on results:
migrated dataset

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
ca. 0.5 < mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
clinical signs
mortality
Dose descriptor:
LOAEL
Effect level:
ca. 0.5 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
clinical signs
mortality

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

RS-Freetext:
Topical application caused depigmentation of the hair and pigmented epidermis, especially of the tail.  Large amounts of p-cresol were lethal and had a local caustic, 

erosive effect.

Applicant's summary and conclusion

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.