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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
Available data show that there is no significant variation in acute dermal toxicity between members of the category. Therefore, the general hypothesis for the category approach that xylenol isomers exert qualitatively and quantitatively similar toxicity effects applies for the endpoint "acute dermal toxicity".

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
The acute dermal toxicity of 4 individual xylenol isomers was found to be low, with similar rat or rabbit LD50 values in the range from 1000 to 2400 mg/kg bw. See attached read-across justification for further information.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Treatment of closely clipped rabbit skin under occlusive coverage for a 24-hour period
GLP compliance:
no
Test type:
other: range-finding test in 2 animals
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2,5-xylenol
EC Number:
202-461-5
EC Name:
2,5-xylenol
Cas Number:
95-87-4
Molecular formula:
C8H10O
IUPAC Name:
2,5-dimethylphenol
Test material form:
solid: crystalline

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test substance as received, was held under an impervious cuff in continuous 24-hour contact with the closely clipped skin. After the 24-hr exposure, the treated skin was washed with lukewarm water.
Duration of exposure:
24 hours
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
2
Control animals:
not specified
Details on study design:
Clinical observation for a post-dosing period of 14 days, with consecutive gross pathological examination

Results and discussion

Effect levels
Key result
Sex:
male
Dose descriptor:
approximate LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No
Clinical signs:
Skin irritation with severe erythema, severe edema, followed by desiccation, eschar formation and peeling of eschar was noted. After washing the exposed area, the rabbits were observed preening the exposure areas.
Body weight:
Not specified
Gross pathology:
No gross changes were observed in either rabbit.

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS (CLP) criteria not met
Conclusions:
The mixture of xylenol isomers used was considered to be "practically non-toxic" by a single skin application because the rabbit dermal LD50 was estimated to be greater than 5000 mg/kg bw. The skin reactions observed during this study indicate this substance is "severely" irritating to rabbit skin.
Executive summary:

In a non-guideline range finding study, two New Zealand White rabbits were dermally exposed to a limit dose of 5000 mg of a xylenol isomer mixture per kg body weight. The closely clipped skin was treated under occlusive coverage for a 24 -hour period with consecutive washing of the exposed skin area. Local skin irritation with severe erythema, severe edema, followed by desiccation, eschar formation and peeling of eschar was noted but no signs of systemic toxicity. Pathological examination after the 14-day observation period did not reveal gross changes. A dermal LD50 value > 5000 mg/kg was derived from this range-finding study.

This result can be transferred to the target test item 2,5-xylenol based on high structural similarities in the read-across category of xylenol isomers (see 'Read-across statement' in section 13.2).