Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not applicable
Qualifier:
according to guideline
Guideline:
other: Methods in 40 CFR, Part 163, Section 163.81-2, Federal register, August 22, 1978
Deviations:
not specified
GLP compliance:
no
Remarks:
Conducted prior to GLP
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
5,5'-dithiodi-1,3,4-thiodiazole-2(3H)-thione
IUPAC Name:
5,5'-dithiodi-1,3,4-thiodiazole-2(3H)-thione
Constituent 2
Chemical structure
Reference substance name:
5,5'-dithiodi-1,3,4-thiadiazole-2(3H)-thione
EC Number:
276-763-0
EC Name:
5,5'-dithiodi-1,3,4-thiadiazole-2(3H)-thione
Cas Number:
72676-55-2
Molecular formula:
C4-H2-N4-S6
IUPAC Name:
5-[(5-sulfanylidene-4,5-dihydro-1,3,4-thiadiazol-2-yl)disulfanyl]-2,3-dihydro-1,3,4-thiadiazole-2-thione
Test material form:
solid: particulate/powder

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Ten animals in total were used in the study (5 males and 5 females).

Weight: 200 - 300g Animals were housed and maintained according to the Animal Welfare Act (Pub. L-94-279) 9 C.F.R. Part 3.

Animal Husbandry Conditions:
Temperature - 70ºF ± 2ºF
Relative Humidity - 45% ± 5%
Light - 12 hour light/dark cycle
Diet Wayne 15% Rabbit Ration and tap water were provided ad libitum.
Caging - Stainless steel with elevated wire mesh flooring 1 Rabbit per cage.
Weight: 2.0 - 3.0 kg
Age: 9-10 weeks old
Acclimatisation: at least 5 days

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A group of ten rabbits (5 male & 5 female) had their backs clipped free of hair 24 hours prior to testing. All animals had their backs abraded within 2 hours prior to dosing.
The sample material dosed as supplied.
The substance was applied to approximately 10% of the body surface on each animal. The treated areas were covered with large gauze patches and an impervious material wrapped snugly around the trunk of each animal.
Duration of exposure:
The duration of exposure was 24 hours. After 24 hours, the wrapping was removed, excess material was removed by wiping but not washing, and the approximate amount remaining was noted. The animals were observed for a 14 day period for signs of toxicity (systematic and topical) and for mortalities.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male and 5 female rabbits.
Control animals:
no
Details on study design:
Animals were observed frequently on the day of dosage, and twice per day thereafter (morning and afternoon). Individual weights were recorded on the day of dosage, weekly thereafter, and prior to sacrifice. Gross autopsies were performed on all animals that either dies during the 14 day observation period or on surviving animals that were sacrificed with carbon dioxide at the conclusion of the 14 day observation period.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: One animal died.
Mortality:
1 female animal found dead on day 12 of the study.
Clinical signs:
Males: All animals appeared normal throughout the duration of the 14 day observation period.

Females: One female lost weight during the first 7 days, exhibited diarrhea on day 8 and was found dead on day 12. The other four animals appeared normal throughout the 14 day observation period.
Body weight:
Average day 7 weights were as follows:
Males: 2.79 kg
Females: 2.88 kg.
Gross pathology:
No gross abnormalities were noted in any of the ten animals necropsied.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 of 5,5'-dithiodi-1,3,4-thiadiazole-2(3H)-thione in male and female New Zealand White rabbits is greater than 2000 mg/kg body weight