Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1994
Report Date:
1994
Reference Type:
publication
Title:
Review of the toxicology of multifunctional acrylates
Author:
Andrews LS, Clary JJ
Year:
1986
Bibliographic source:
J Toxicol Environ Health 19:149-164

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
abraded skin, occlusive conditions
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Physical state: liquid
- Analytical purity: no data
- Storage condition of test material: room temperature away from heat and light

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratory Animals, Denver, Pennsylvania, USA
- Age at study initiation: young adults
- Weight at study initiation: males: 2.3-2.5 kg, females: 2.3-3.0 kg
- Fasting period before study: no data, not required
- Housing: individually housed in suspended stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 17 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22 °C (65-71 °F)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of the body surface, abraded skin
- Type of wrap if used: a layer of 8-ply gauze was wrapped around the animal to cover the application site. The animal was then wrapped in an
impervious plastic sleeve, designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and
Elizabethan collars were placed on all animals.


REMOVAL OF TEST SUBSTANCE
Following approximately 24 hours of exosure, the wrappings were removed and the test site wiped free of excess test material. After 30 minutes,
dermal observations were made.


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.9 ml/kg bw
- Concentration (if solution): 2000 mg/kg bw
- Constant volume or concentration used: no, volume appplied according to body weight

Duration of exposure:
24 hours of occlusive exposure on abraded skin
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: viability check: twice a day; observations of pharmacologic and toxicologic signs: 1, 2 and 4 hours after
dosing and daily thereafter for 14 days; body weights at the time of clipping, day of dosing, day 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
no data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
all animals survived (5 male, 5 female)
Clinical signs:
No abnormalities were noted during the four hours after dosing. Three males exhibited fecal staining at 24 hours and one female exhibited this sign
at 24 hours and on Day 2. One female exhibited decreased food consumption at 24 hours. One female exhibited clear nasal discharge on a single
occasion and clear ocrilar discharge on several occasions. Another female was noted to have an apparent broken leg or lower back on Day 9 and
exhibited soft stool, fecal staining and/or urinary staining, decreased food consumption, decreased activity and/or prostration from Day 9 through
termination.
At the 24-hour dermal observation, the males exhibited well-defined to severe erythema accompanied by very slight or moderate edema. The females exhibited very slight or well-defined erythema accompanied by severe edema.
Body weight:
Four males and three females exhibited slight weight gains during the fourteen-day post-dose observation period. One male and one female
exhibited no net change in weight at Day 14. One female exhibited a slight weight loss at day 7 and an overall weight loss of 0 .7 kg by day 14. This
animal was noted to have a possible broken leg or lower back injury during the second week of study.
Gross pathology:
no findings in 4/10 animals, 6/10 animals with findings which included: 5/10 animals with slightly irregular, slightly diminished or purplish spleen, 2/10 animals mottled pale liver (20%-40%), 2/10 animals with pale kidneys, 1/10 animals with slight fecal staining, 1/10 animals with empty stomach,
1/10 animals with broken leg

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study a single dermal dosing with 2000 mg/kg test substance did not cause mortality of rabbits after treatment of the abraded skin. Therefore, the LD50 of the test item is greater then the tested limit dose.
Executive summary:

Acute dermal toxicity was investigated with 10 albino rabbits (five/sex) treated with a single dose of 2000 mg/kg similar to OECD protocol of guideline 402 (GLP not specified, reliability 2). Single occlusive dosing at a dose volume of 1.9 ml/kg was performed on abraded skin for 24 hours. Under this study conditions no mortality was observed during the observation period of 14 days. Four males and three females exhibited slight weight gains, whereas one male and one female rabbit exhibited no net change in theig bodyweight. One female animal exhibited a weight loss, however, this animal was noted to have a possible broken leg or lower lack injury during the second week of the study. Well defined to severe erythema accompanied by very slight or moderate edema were observed in males after 24 hours. Females exhibited very slight or well-defined erythema accompanied by severe edema. No abnormalities of clinical signs were noted during the four hours after dosing. Three males exhibited fecal staining at 24 hours and one female exhibited this sign at 24 hours and on Day 2. One female exhibited decreased food consumption at 24 hours. One female exhibited clear nasal discharge on a single occasion and clear ocrilar discharge on several occasions. Another female was noted to have an apparent broken leg or lower back on Day 9 and exhibited soft stool, fecal staining and/or urinary staining, decreased food consumption, decreased activity and/or prostration from Day 9 through termination. Six of the tested ten animals had gross pathology findings which included: 5/10 animals with slightly irregular, slightly diminished or purplish spleen,  2/10 animals mottled pale liver (20%-40%), 2/10 animals with pale kidneys, 1/10 animals with slight fecal staining, 1/10 animals with empty stomach, 1/10 animals with broken leg.

Due to the abscence of mortality under the tested conditions of this study no LD50 value was derived.