Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 December 2010 - 27 December 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
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:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: no data
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (15-30°C)
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was dosed neat as received from the sponsor.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: 7-8 weeks
Protocol deviation:
The protocol stated the age range for the animals was 8-24 weeks. The actual age of the male animals on study was 7 weeks. This deviation of one week was not of a magnitude to have had an impact on the outcome or integrity of the study since the animals were still considered young adults and were within the weight range of the protocol.
- Weight at study initiation: 190-226 grams
- Housing: Animals were group housed by sex upon receipt and individually housed upon assignment to study in compliance with the National Research Council "Guide for the Care and Use of Laboratory Animals." Calvert is a USDA registered and fully AAALAC accredited facility. The room in which the animals were kept was documented in the study records. No other species were kept in the same room.
- Diet (e.g. ad libitum): All animals had access to Harlan Teklad Rodent Diet (certified) ad libitum, as per Calvert SOP
- Water (e.g. ad libitum): tap water was available ad libitum
- Acclimation period: Study animals were acclimated to their housing for a minimum of five days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 22°C
- Humidity (%): 18 to 52%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Protocol deviations:
The temperature and relative humidity recorded in the animal room were not within the protocol limits of 22 ± 3°C and 30 to 70% on several occations during the course of the study. The ranges were 16 to 22°C and 18 to 52%, respectively. These deviations had no impact on the study outcome since the animals were observed daily and were considered to be normal.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- Type of wrap if used: The test article was applied on an intact skin site for each animal, covered with a gauze patch/dental dam, wrapped with an elastic bandage and secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure the site was unwrapped and wiped with water or mineral oil and gauze to prevent ingestion.
- Time after start of exposure: twenty-four (±0.5) hours.

TEST MATERIAL
One group of animals received the test article at 2000 mg/kg, 1.98 mL/kg. Since no mortality occurred in the Limit Test, a full Definitve Test was not necessary.
Duration of exposure:
The test article was applied once and remains in contact with the skin site for twenty-four (±0.5) hours.
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:
Mortality/morbidity: once daily;
Clinical observations: Clinical observations were recorded immediately after unwrap from the 24 hour exposure (Day 2) and daily thereafter through Day 15. At the time of clinical observations, the dose site was also evaluated for dermal irritation.
Body weight: Animals were weighed prior to dosing on Day 1 and on Days 8 and 15.
- Necropsy of survivors performed: yes,
All animals were euthanized by CO2 asphyxiation.
The necropsy included examination of the external body surface, all orifices, the thoracic, abdominal and pelvic cavities and their contents
Statistics:
Body weights were summarized using descriptive statistics (mean and standard deviation).

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:
Mortality was not observed in any of the animals at 2000 mg/kg.
Clinical signs:
Abnormal gait and stance was observed immediately after unwrap from the 24 hour exposure (Day 2) of the study. No other abnormal clinical signs were observed during the study. No erythema or edema was observed at the application sites during the study.
Body weight:
No biologically significant effect was seen on body weight in the animals on Days 8 and 15. All of the animals gained weight during the course of the study.
Gross pathology:
No visible lesions were observed in any of the animals at terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based upon the results of the Acute Dermal Toxicity Study in Rats with the test substance, the estimated LD50 was considered to be greater than 2000 mg/kg body weight. Therefore, according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS), the test substance was considered to be Category 5 test article. An EEC Risk Phrase is not required and it is Not WHMIS Controlled.