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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Review of the toxicity of multifunctional acrylates
Author:
L. S. Andrews & John J. Clary
Year:
1986
Bibliographic source:
Journal of Toxicology and Environmental Health, 19:2, 149-164, 1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Chronic dermal toxicity study was performed for the test compound Trimethylolpropane triacrylate to evaluate its toxic nature upon repeated exposure by dermal route of exposure
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material: Trimethylolpropane triacrylate
- Molecular formula: C15H20O6
- Molecular weight: 296.317 g/mol
- Substance type: Organic
- Physical state: No data available
- Impurities (identity and concentrations): No data available

Test animals

Species:
other: Mice
Strain:
other: C3H/HeJ
Sex:
male
Details on test animals and environmental conditions:
No data

Administration / exposure

Type of coverage:
not specified
Vehicle:
not specified
Details on exposure:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: No data
- Time intervals for shavings or clipplings: No data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: No data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): 0 or 100 mg/Kg bw
- Constant volume or concentration used: No data
- For solids, paste formed: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): No data
- Lot/batch no. (if required): No data
- Purity: No data

USE OF RESTRAINERS FOR PREVENTING INGESTION: No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
80 weeks
Frequency of treatment:
Twice weekly for 80 wk
Doses / concentrations
Remarks:
Doses / Concentrations:
0 or 100 mg/Kg bw
Basis:

No. of animals per sex per dose:
Total: 150
0 mg/Kg bw: 50 male mice
100 mg/Kg bw: 50 male mice
Negative control: mg/Kg bw: 50 male mice
Positive control: mg/Kg bw: 50 male mice
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: In preliminary pilot study, male C3H/HeJ mice were treated with a 50-mg dose of different dilutions of MFA. A dose and
concentration that produced only minimal skin irritation effects in a 4-wk probe study was determined and selected as the dose for the chronic study.
Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data
Positive control:
Benzo[a]pyrene

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION: No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, skin and body cavities were examined, observation were also made for the presence of tumors.

HISTOPATHOLOGY: Yes, tissues
were taken for histopathological analysis
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Slightly epilated skin was observed
Dermal irritation:
no effects observed
Description (incidence and severity):
There were no remarkable signs of skin irritation, although acanthosis and fibrosis were frequently present
Mortality:
mortality observed, treatment-related
Description (incidence):
Slightly epilated skin was observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No increased incidence of skin or visceral tumors was noted
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
No skin tumors or systemic findings.
Details on results:
No data

Effect levels

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No significant changes were noted

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No observed Adverse Effect Level (NOAEL) for the test compound Trimethylolpropane triacrylate is likely to be 100 mg/Kg bw.
Executive summary:

Chronic dermal toxicity study was performed for the test compound Trimethylolpropane triacrylate to evaluate its toxic nature upon repeated exposure by dermal route of exposure. The study was performed on 50 maleC3H/HeJ mice at dose levels of 0 or 100 mg/Kg bw given twice daily for 80 weeks.

There were no remarkable signs of skin irritation, although acanthosis and fibrosis were frequently present. Also, no increased incidence of skin or visceral tumors was noted.

 

The No observed Adverse Effect Level (NOAEL) for the test compound Trimethylolpropane triacrylate is likely to be 100 mg/Kg bw.