Registration Dossier

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Repeated dose dermal irritation study, histopathology of skin only, study purpose was to investigate skin reactions of dilutions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986

Materials and methods

Principles of method if other than guideline:
Method: other: application on the shaved backs of mice , male ICR-mice, 8 animals/dose group
100 ul per mouse/day for a total of 9 treatment days
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity approx. 100 %

Test animals

Species:
mouse
Strain:
other:
Sex:
male

Administration / exposure

Duration of treatment / exposure:
3 weeks
Frequency of treatment:
3 time/week
Doses / concentrations
Remarks:
Doses / Concentrations:
4 % aq. sol. of MAA and 4.8 - 19.2 % aqueous solution of methacrylic acid in acetone
Basis:

No. of animals per sex per dose:
8 animals/dose group
Control animals:
other: yes (solvent)
Details on study design:
100 ul per mouse/day for a total of 9 treatment days

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
see results
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Details on results:
With MAA as an aqueous solution of 4.8 % (= approx. 150 mg/kg) no skin irritation was observed after single or repeated dermal exposure up to 21 d (treatment interval 2-3 days, 9 exposures). When methacrylic acid was diluted in acetone and applied similarly, concentration-related irritation was observed. At 4.8 % in acetone, there was minimal irritation within the first 72 hours which progressed to slight after 21 d. Moderate to severe irritation was observed with 9.6 % (= approx. 300 mg/kg) and  19.3 % (= approx. 600 mg/kg) solutions with hyperplasia, hyperkeratosis, fibrosis, ulceration and necrosis. No clinical signs indicative of systemic toxicity were observed at any dose in any of the mice.

Effect levels

Dose descriptor:
NOAEL
Effect level:
600 mg/kg bw/day
Sex:
male
Basis for effect level:
other: (= 19.3 % / 2.24 M) Local irritation, but no clinical signs of systemic effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Dilutions if MAA in acetone and water show mild irritation at 4.8 % in a study in mice, in which dilutions of MAA were applied for 21 d in succession, while the effects are more pronounced at 9.6 % in acetone and progress to severe irritation at 19.2 % in acetone.
Executive summary:

Dilutions if MAA in acetone and water show mild irritation at 4.8 % in a study in mice, in which dilutions of MAA were applied for 21 d in succession, while the effects are more pronounced at 9.6 % in acetone and progress to severe irritation at 19.2 % in acetone.