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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.28 (Sub-Chronic Dermal Toxicity Test: 90-Day Repeated Dermal Dose Study Using Rodent Species)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
C3H
Sex:
male/female
Details on test animals and environmental conditions:
The animals were housed individually in suspended stainless-steel wire cages in a room with controlled lighting. Certified diet (Agway, Ithaca, USA) and water from an automatic watering system were provided ad lib.

Administration / exposure

Type of coverage:
open
Vehicle:
acetone
Details on exposure:
Test substances were applied using an Eppendorf automatic pipette, 50μl per application, to the back of each mouse from which the fur was clipped once weekly. The tip of the pipette was used to spread the test substance from the interscapular area to the lumbar area of each mouse.
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
3 times a week for 13 weeks
Doses / concentrationsopen allclose all
Dose / conc.:
140 mg/kg bw/day (nominal)
Remarks:
male
Dose / conc.:
460 mg/kg bw/day (nominal)
Remarks:
male
Dose / conc.:
2 000 mg/kg bw/day (nominal)
Remarks:
male
Dose / conc.:
160 mg/kg bw/day (nominal)
Remarks:
female
Dose / conc.:
540 mg/kg bw/day (nominal)
Remarks:
female
Dose / conc.:
2 300 mg/kg bw/day (nominal)
Remarks:
female
No. of animals per sex per dose:
15
Control animals:
no

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No clinical signs of toxicity or skin irritation were observed during the study.
Dermal irritation:
no effects observed
Mortality:
mortality observed, non-treatment-related
Description (incidence):
A vehicle control male, a high-dose male and a low-dose femal died during the study.
These deaths were considered unrelated to TEA treatment.
Body weight and weight changes:
no effects observed

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
> 2 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
clinical signs
Key result
Dose descriptor:
NOAEL
Effect level:
> 2 300 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
When TEA was applied to the skin of mice 3 times per week for 95 days, mild epidermal hyperplasia was observed without evidence of systemic toxicity.