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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Remarks:
42 days
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Cross-reference
Reason / purpose:
read-across source
Reference
Endpoint:
short-term repeated dose toxicity: dermal
Remarks:
42 days
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: special study and only one dose used, no dose-response relationship can be derived and thus no NOAEL or LOAEL can be deduced.
Principles of method if other than guideline:
Hair pigmentation was studied following plucking or clipping the caudal half of the back and repeated application of laundry ink or its pure component chemicals incl. p-cresol in a concentration of 0.5% in acetone. p-Cresol was applied to the skin of 30 males. Hair colour was observed weekly for the subsequent 6 months. Microscopic examinations of post-treatment hairs and skin biopsies of areas of non-pigmented and normally pigmented hair were made. Control groups of animals received acetone.
GLP compliance:
not specified
Species:
mouse
Strain:
C57BL
Sex:
female
Details on test animals and environmental conditions:
no data
Type of coverage:
not specified
Vehicle:
acetone
Details on exposure:
no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
6 weeks
Frequency of treatment:
3x/week
Dose / conc.:
0.5 other: % in acetone
No. of animals per sex per dose:
30 male animals
Control animals:
not specified
Details on study design:
Post-exposure period: 6 months
Positive control:
no data
Observations and examinations performed and frequency:
Hair colour was observed weekly for the subsequent 6 months. Microscopic examinations of post-treatment hairs and skin biopsies of areas of non-pigmented and normally pigmented hair were made
Sacrifice and pathology:
no data
Other examinations:
no data
Statistics:
no data
Details on results:
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.
Key result
Dose descriptor:
NOAEL
Effect level:
< 0.5 other: %
Based on:
test mat.
Sex:
female
Basis for effect level:
other: 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
Key result
Dose descriptor:
LOAEL
Effect level:
<= 0.5 other: %
Based on:
test mat.
Sex:
female
Basis for effect level:
other: 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
Critical effects observed:
not specified
Conclusions:
p-Cresol was applied to the skin of 30 males. Hair colour was observed weekly for the subsequent 6 months. Microscopic examinations of post-treatment hairs and skin biopsies of areas of non-pigmented and normally pigmented hair were made. Control groups of animals received acetone. 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.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Remarks:
mouse
Effect level:
< 0.5 other: %
Based on:
test mat.
Sex:
female
Basis for effect level:
other: 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
Remarks on result:
other: Source, CAS 106-44-5, p-cresol, Shelly, 1974
Key result
Dose descriptor:
LOAEL
Effect level:
<= 0.5 other: %
Based on:
test mat.
Sex:
female
Basis for effect level:
other: 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
Remarks on result:
other: Source, CAS 106-44-5, p-cresol, Shelly, 1974

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The available data is not reliable for hazard assessment of Tar acids, Xylenol fraction (CAS 84989-06-0). Further testing is, however, not required, as there are reliable oral repeated dose toxicity data available for the hazard assessment of Tar acids, Xylenol fraction (CAS 84989-06-0) and therefore, the requirements defined in Regulation (EC) No 1907/2006, Annex IX, 8.6 are fulfilled.
Executive summary:

p-Cresol was applied to the skin of 30 males. Hair colour was observed weekly for the subsequent 6 months. Microscopic examinations of post-treatment hairs and skin biopsies of areas of non-pigmented and normally pigmented hair were made. Control groups of animals received acetone. 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.

The available data is not reliable for hazard assessment of Tar acids, Xylenol fraction (CAS 84989-06-0). Further testing is, however, not required, as there are reliable oral repeated dose toxicity data available for the hazard assessment of Tar acids, Xylenol fraction (CAS 84989-06-0) and therefore, the requirements defined in Regulation (EC) No 1907/2006, Annex IX, 8.6 are fulfilled.