Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 June 2011 - 20 June 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
No further details
Specific details on test material used for the study:
- Name of test material (as cited in study report): XTJ-568
- Substance type: Clear colorless liquid
- Physical state: Liquid
- Lot/batch No.: 0G704
- Storage conditions: Room temperature, 21-27°C
- Purity: A Certificate of Analysis was not provided with this study. However, the same batch was used for the acute oral toxicity study (OECD 425), where a certificate of analysis was available and indicated a purity (primary amine) of 97%.
- Other: No stability data on bulk test material were available.

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: 12 to 14 weeks; records of dates of birth for animals used in this study are retained in the Calvert archives
- Weight at study initiation: males: 345-382 grams; females: 223-268 grams
- Fasting period before study: No
- 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): ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: for a minimum for 5 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 25°C
- Humidity (%): 29 to 74%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: 5 June 2011 To: 20 June 2011

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area of the trunk of the test animals
- % coverage: >= 10%
- 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
- Post-exposure, the site was unwrapped and wiped appropriately (with gauze and water) to remove residual test article.

TEST MATERIAL
- Dosage levels were calculated on a mg/kg basis for each individual animal based on body weight. For the liquid test article, the dose was adjusted for test article relative density (0.94 g/mL).
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: frequency: clinical observations were recorded immediately after unwrap and daily thereafter through Day 15. At the time of clinical observations, the dose site was also evaluated for dermal irritation.
Body weight: frequency: Animals were weighed prior to dosing on Day 1 and on Days 8 and 15 or upon death.
- Necropsy of survivors performed: yes: A gross necropsy was performed by Calvert peronnel at study termination or when animals were found dead. The necropsy included examination of:
the exernal body surface
all orifices
the thoracic, abdominal and pelvic cavities and their contents
At the completion of necropsy, carcasses were disposed of according to Calvert SOP
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 observed in two female animals at 2000 mg/kg (day 3 and 5).
Clinical signs:
Abnormal gait and stance, hunched posture, decreased activity, decreased body tone, piloerection, black fur around eyes, yellow wet fur of the lower ventral area were observed throughout the study. All animals exhibited necrosis at the application site during the study.
Body weight:
A general decline in body weight was seen in the majority of animals on Day 8; however, by Day 15 body weights were comparable to Day 1.
Gross pathology:
No visible lesions were observed in the surviving animals at terminal necropsy. Dark red intestines were observed in the animal found dead on Day 5 of the study. No lesions were observed in the animal found dead on Day 3 of the study.
Other findings:
No data

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the results of the acute dermal toxicity study in rats with the substance, the estimated LD50 was considered to be greater than 2000 mg/kg. Therefore, according to the criteria of the CLP Regulation, the substance should not be classified for acute dermal toxicity.