Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1996-06-04 to 1996-09-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Version / remarks:
Toxic Substances Control Act Test Guidelines, 40 CFR Part 798, Subpart B, Section 798.1100, July 1, 1992.
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
OECD Guidelines for the Testing of Chemicals, Section 4, Health Effects, Subsection 402, February 24, 1987.
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
The EEC Guidelines Part B: Methods for the Determination of Toxicity, No. L 383 A/121, B.3, December 29, 1992.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
Lot No.: 0998603612
Purity: 59.6 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD®BR VAF/Plus®
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adults
- Weight at study initiation: males: 264 - 351 g; females: 221 - 243 g
- Housing: individually in suspended stainless steel cages
- Diet: PMI Certified Rodent Chow #5002 (Purina Mills, Inc.) was provided ad libitum to the animals throughout the study.
- Water: Municipal tap water treated by reverse osmosis was available ad libitum throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 20.5 °C (59 - 69 °F)
- Humidity (%): 52 - 80
- Air changes (per hr): 10- 15
- 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: the dorsal trunk area of the animals, the fur was shaved and the area was clipped
- % coverage: ≥ 10% of the animal's body surface area (BSA)
- Type of wrap: an appropriately sized 4 ply porous gauze dressing, a plastic wrap and an elastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test article was removed using gauze moistened with distilled water followed by dry gauze.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 4 mL/kg
- Concentration: 2000 mg/kg
Duration of exposure:
24 h exposure, 14 days observation after exposure
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were obtained for the limit test animals prior to dosing on day 0 and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed:
= clinical signs: Limit test animals were observed for clinical abnormalities a minimum of two times on study day 0 (postdose) and daily thereafter (days 1-14). A general health/mortality check was performed twice daily.
= dermal observations: Limit test animals were examined for erythema and edema following patch removal on study day 1 and daily thereafter (days 2-14) according to the Macroscopic Dermal Grading System based on Draize. The dermal test sites were reclipped as necessary to allow clear visualization of the skin.
Statistics:
Data from the limit test were analyzed and an LD50 value estimated as follows:
< 50% Mortality: LD50 was estimated as greater than the administered dose.
= 50% Mortality: LD50 was estimated as equal to the administered dose.
> 50% Mortality: LD50 was estimated as less than the administered dose.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the limit test.
Clinical signs:
The most notable clinical abnormalities observed during the study included dark material around facial area, and urine stain. Dermal irritation was noted at the site of test article application.
Body weight:
Body weight gain was noted for all animals during the test period.
Gross pathology:
No significant gross internal findings were observed at necropsy on study day 14.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this test, the acute dermal LD50 of the test item was estimated to be greater than 2000 mg/kg in the rat.
Executive summary:

The single-dose dermal toxicity of the test item was evaluated on Sprague-Dawley rats. A limit test was performed in which one group of five male and five female rats received a single dermal administration of the test item at a dose of 2000 mg/kg body weight. Following dosing, the rats were observed daily and weighed weekly. A gross necropsy examination was performed on all limit test animals at the time of death or scheduled euthanasia (day 14).

No mortality occurred during the limit test. The most notable clinical abnormalities observed during the study included dark material around facial area, and urine stain. Dermal irritation was noted at the site of test article application. Body weight gain was noted for all animals during the test period. No significant gross internal findings were observed at necropsy on study day 14.

Under the conditions of this test, the acute dermal LD50 of the test item was estimated to be greater than 2000 mg/kg in the rat.