Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: early study report, scientifically acceptable, equivalent or similar to OECD 402

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
5 doses were applied once only to the backs of rabbits for 24 hours and were observed the following 14 days.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

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

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: H.A.R.E. Rabbits for Research, Hewitt, New Jersey
- Weight at study initiation: 2300 to 2805 g
- Housing: individually in hanging wire-mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 12 days

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: 20 - 30% of body surface
- Type of wrap if used: gauze banding

REMOVAL OF TEST SUBSTANCE
- Washing: tepid tap water
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
1250; 2500; 5000; 10000 and 20000 mg/kg bw
No. of animals per sex per dose:
2 animals per sex per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 24 hours and daily for 14 days
- Frequency of weighing: prior to test material administration and on day 7 and 14
- Necropsy of died animals performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 500 mg/kg bw
Based on:
test mat.
95% CL:
> 1 301 - < 4 806
Mortality:
1250 mg/kg bw: 1/4
2500 mg/kg bw: 1/4
5000 mg/kg bw: 4/4
10000 mg/kg bw: 4/4
20000 mg/kg bw : 4/4
Clinical signs:
Animals exposed up to 2500 mg/kg bw showed dermal irritations like moderate to marked erythema, edema, desquamation and necrosis, which were not reversible until day 14.
Body weight:
Female rabbits lost weight 7 days following the exposures but gain body weight up to day 14.
Gross pathology:
The animals died during the test exposed to doses higher than 5000 mg/ kg bw showed dermal irritation and ulceration and hyperemia of mucose of the stomach and discoloration of the liver. Males were more sensitive to the test item than females.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with TBPPI in rabbits a LD50 value of 2500 mg/kg bw was determined.
Executive summary:

Twenty male and twenty female New Zealand White rabbits were used for an acute dermal toxicity study with TBPPI. The rabbits were divided into five groups of 2 male and 2 female rabbits each. The hair was removed from the back of each rabbit (20 -30% of the body surface) with an electric clipper. The test material was applied once only to the backs of the rabbits at the following dosage levels: 1250; 2500; 5000; 10000 and 20000 mg/ kg bw. Following dosing, the application sites were wrapped with gauze bandaging and overwrapped with Saran Wrap. 24 hours following application, the bandages were removed and the test sites were washed with tepid tap water. The rabbits were observed at 24 hours and daily thereafter for a total of 14 days for pharmacotoxic signs, mortality and dermal irritation. Body weights were recorded immediately prior to the test material administration and at 7 and 14 days of the observation period. All rabbits which died on study were subjected to gross necropsy examination.

All animals exposed to 5000 mg/kg bw and higher died during the testing period. One female and one male rabbit died in the lowest and the 2500 mg/kg bw dose level respectivly. In all surviving animals moderate to marked dermal irritation and necrosis occured and were not reversible until 14 days. Necropsy of died animals showed ulceration and hyperemia of the mucosa of the stomach and discoloration of the liver. No adverse effects on body weights of surviving animals could be observed.

The acute dermal LD50 values were 2500 mg/kg bw in males and females and the 95th confidence limits were 1250 - 5000 mg/kg bw in males and 625 - 10000 mg/kg bw in females.