Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30.01.2015 to 30.10.2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

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
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: CRL:(WI) rats
- Weight at study initiation: males 226-243 g, females 209-247 g
- Housing: individual caging in Type II cages (polypropylene/polycarbonate)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9-24.8
- Humidity (%): 37-50
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The back of each animal was shaved (approximately 10 % area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose as supplied to the shaved skin and remained in contact with the skin for the 24-hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi-occlusive plastic wrap for 24 hours.
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male
5 female
Control animals:
no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Administration of the test item led to the death of 10/10 animals at the dose level of 2000 mg/kg bw. Seven out of ten animals were found dead, and 3/10 animals were in moribund status at the observation 24 hours post application. Moribund animals were euthanized for animal welfare reason after consultation with the Clinical Veterinary.
Clinical signs:
At 5 hours post application, animals were symptom free. At 24 hours post application, 4 male, 3 female animals were found dead and 1 male, 2 female animals were in a moribund status (verified by the Clinical Veterinary).
During the assessment of the general distress of moribund animals by the Clinical Veterinary, it was found that the moribund eyes of the animals were half closed, natural behaviour become very still or not alert, hydration status of turgor of skin decrease. Moreover decreased respiration rate with abdominal breathing and very weak or lying on cage floor without response were noticed.
Body weight:
Males: 202-217 g
Females: 196-225 g
The animals lost the 6-12% of the starting body weight during 24 hours.
Gross pathology:
A single 24-hour dermal application of N-Butyl-TAD to CRL:(WI) rats at a dose level of 2000 mg/kg bw led to the preterminal euthanasia (three rats) or death (seven rats) on Day 1. Test item-related black diffuse discoloration of the skin (external examination) and red-black diffuse discoloration of the skin (internal examination) were observed at the sites of application. Dark/red discoloration of the collapsed/non-collapsed lungs were typical for found dead animals.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The application of the test item at 2000 mg/kg bw caused extremely severe local dermal signs and led to the death of 10/10 animals (7 dead, 3 euthanized). The acute dermal median lethal dose (LD50) of the test item N-Butyl-TAD was found to be lower than 2000 mg/kg bw in male and female CRL:(WI) rats in a limit test. Due to the corrosive potential of the test item, a full test was not performed for animal welfare reasons.