Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
1975
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: unknown
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Test animals

Species:
rabbit
Strain:
other: albino
Sex:
male

Administration / exposure

Type of coverage:
open
Vehicle:
water
Details on exposure:
The dose was gently massaged, using a glass test tube as the applicator, into the clipped skin on the belly. As the daily dose of 3-(trimethoxysilyl)propyl methacrylate was so large that it couldn't be applied in one inunction, one-fourth of the dose was applied for one minute of each 15 minute-interval during a one-hour period. One hour after the last application, the skin was gently blotted with cleansing tissue to remove any unabsorbed liquid. The animals were weighed before each dose to recalculate dosage application and at study termination.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
7 applications over 17 days
Frequency of treatment:
approximately 2 hours/day on days applied
Doses / concentrations
Dose / conc.:
2 other: ml/kg
No. of animals per sex per dose:
4 males/test material; 4 males/distilled water
Control animals:
yes
Details on study design:
A group of four male albino rabbits received 7 inunctions, two the first week, three the second week and two the third week at 2.0 ml/kg of 3-(trimethoxysilyl)propyl methacrylate. Based on an LD50 of 20 ml/kg, a maximum dose of 2.0 ml/kg was chosen. A control group was inuncted with 2.0 ml/kg of distilled water.



Examinations

Observations and examinations performed and frequency:
All abnormal responses and signs of toxicity, as well as dermal irritation responses were recorded.
Sacrifice and pathology:
The study was terminated after 17 days and animals subjected to gross necropsy.
Other examinations:
Liver and kidney weights were obtained.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Details on results:
No deaths occurred during the study. There were no differences in body, kidney or liver weights between the treated and control animals. The only abnormal skin response noted on the treated animals was desquamation, which occurred following the third inunction and lasted through study termination. There were no abnormal dermal responses noted in the control group.

Effect levels

Dose descriptor:
NOAEL
Effect level:
2 other: ml/kg bw
Sex:
male

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a short-term repeated dose dermal toxicity study, not conducted to any guideline but pre-GLP, the observed effect on the treated animals was desquamation which occurred following the third inunction and lasted through to the study termination. The study is not considered to be reliable.