LBX98

Repeated dose toxicity: dermal

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.

Materials and methods

Principles of method if other than guideline:

Method: other: see freetext RM

GLP compliance:

not specified

Test material

Test material information

Constituent 1

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

1

Dose descriptor:

NOAEL

Effect level:

ca. 0.5 < mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

clinical signs

mortality

2

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.