LBX98

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

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

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:

rat

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

migrated dataset

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

other: migrated dataset

Vehicle:

other: migrated dataset

Remarks on MMAD:

MMAD / GSD: migrated dataset

Details on inhalation exposure:

migrated dataset

Details on analytical verification of doses or concentrations:

migrated dataset

Duration of treatment / exposure:

4 months

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:0.01 mg/lBasis:

No. of animals per sex per dose:

migrated dataset

Control animals:

other: no data specified

Details on study design:

Post-exposure period: 2 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

Dose descriptor:

LOAEL

Effect level:

0.01 other: mg/l

Sex:

female

Basis for effect level:

body weight and weight gain

clinical signs

dermal irritation

organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

RS-Freetext:
Clinical signs of toxicity included loss of appetite, marked emaciation and decreased locomotor activity. Irritative effects, which persisted throughout recovery, were seen on
the nose, eye and skin.  Decreased body weight gain and lung weight, increased liver weight, oliguria and dystrophic changes in the lung and liver occurred. 

Throughout recovery the body weights remained depressed and urinary excretion remained low.

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.