1,3,4-Thiadiazolidine-2,5-dithione, reaction products with tert-dodecanethiol and hydrogen peroxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline study. No GLP compliance is claimed, however, the final report includes an audit as well as quality assurance inspections. This result is read-across from ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol’. Read-across is justified as the two substances ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’ and ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol’ are virtually the same: the only difference between those two UVCB substances is that one of the used raw materials (alkanethiol) has a diversity in the C-range, i.e. on the one hand a tert. C12-alkanethiol is used in the manufacturing process, on the other hand a tert. C9. Hence, based on the (structural) similarity of both substances it is safe to say that the physicochemical, toxicological and ecotoxicological properties are likely to be similar.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

no

Remarks:

The final report includes an audit and quality assurance inspections.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol

EC Number:

293-927-7

EC Name:

1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol

Cas Number:

91648-65-6

Molecular formula:

not applicable (UVCB substance)

IUPAC Name:

1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol

Test material form:

not specified

Details on test material:

- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Portage, MI
- Weight at study initiation: approximately 135 g
- Fasting period before study: yes, animals were fasted for 18 h prior to dose administration
- Housing: individually in suspended, stainless steel cages (25 x 17.8 x 17.8 cm)
- Diet (e.g. ad libitum): Purina Rodent Chow 5001 (Ralston Purina Co.) ad libitum except 18 h fasting period prior to dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 40
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 333.3 and 666.7 mg/mL
- Amount of vehicle (if gavage): 15 mL/kg
- Lot/batch no.: Lot no. 790670 (Fischer)

MAXIMUM DOSE VOLUME APPLIED: 10000 mg/kg

Doses:

5000 mg/kg and 10000 mg/kg

No. of animals per sex per dose:

2 male and 2 female at 5000 mg/kg
5 male and 5 female at 10000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation are performed once daily for 14 days and more frequently on the day of dosing
- Necropsy of survivors performed: gross necropsy performed on all animals
- Other examinations performed: body weights performed prior to dosing

Statistics:

No statistical methods reported.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during this study.

Clinical signs:

other: Decreased motor activity was seen in 9 out of 10 animals in the high dose group within 24 hours following the high dose administration. During this same period, diarrhoea was observed in 2 of 5 high dose female rats and 1 of 5 low dose male rats. All rat

Gross pathology:

One male in the high dose group was found to have dark red edges on the spleen.

Other findings:

No other findings were reported.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The test report describes a valid guideline study, with auditation and quality assurance inspections of the final report.The acute oral median lethal dose (LD50) for the test material was determined to be greater than 10000 mg/kg in male and female rats. Thus, the test substance can be considered as not acutely toxic via the oral route. The test item ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol’ is virtually the same as the registered substance ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’. The only difference between those two UVCB substances is that one of the used raw materials (alkanethiol) has a diversity in the C-range, i.e. on the one hand a tert. C12-alkanethiol is used in the manufacturing process, on the other hand a tert. C9. Hence, based on the (structural) similarity of both substances it can safely be concluded that the results can be safely transferred to the registered substance and so, ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’ does not need to be classified, too.

Executive summary:

An acute oral study was conducted using a similar procedure to that described in the current OECD Guideline 401 (Reckers, 1981). The test material (CAS No. 91648-65-5) was administered at dose levels of 5000 mg/kg, to two male and two female rats, and 10000 mg/kg to five male and five female rats by oral gavage. The rats were observed for 14 days after test material administration. General signs of intoxication exhibited by the rats following dosing included decreased motor activity and diarrhoea. There were no mortalities in either dose group. No gross pathologic alterations were noted among the animals at study termination. The acute oral median lethal dose (LD50) for the test material was determined to be greater than 10000 mg/kg in male and female rats. The read-across from the test item to ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’ is scientifically justified and so the registered substance does not need to be classified as acute toxic according to Regulation 1272/2008/EC, too.