Reaction products of 2,5-dimercapto-1,3,4-thiadiazole, sodium salt, with 1-octanethiol and hydrogen peroxide

Endpoint summary

Description of key information

Acute toxicity: Oral

Under the conditions of the study, the oral LD50 for both male and female Sprague-Dawley rats has been determined to be greater than 5000 mg/kg bw.

Acute toxicity: Inhalation

Under the conditions of the study, the sex combined LC50 was 3.08 mg/L with lower and upper 95% confidence intervals of 2.78 mg/L and 3.50 mg/L, respectively.

Acute toxicity: Dermal

Under the conditions of the study, the dermal LD50 of the test material has been determined for both sexes as greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 1983 to September 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: - Young adult male and female Sprague-Dawley rats were obtained from an external source.
- Fasting period before study: Food was withheld the night prior to dosing.
- Housing: - All housing and care· conformed to the standards established in the "Guide for the Care and Use of Laboratory Animals" DHEW Publication No. (NIH) 78-23 . Animals were individually housed in wire mesh bottom cages in environment controlled rooms.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

On the first day of the study, animals received a single oral dose of 5000 mg/kg body weight of the test article.

Doses:

A single oral dose of 5000 mg/kg body weight of the test article.

No. of animals per sex per dose:

5/sex.

Control animals:

no

Details on study design:

Procedure
A range finding study was conducted to determine dose levels for the main study. Based on the results of the range finder, a limit test was conducted using ten animals.
Observations and Body Weights
Animals were observed frequently on the day of dosing and twice daily thereafter. Body weights were recorded initially, on day 8 and 15 or at death.

Necropsy
All animals that died during the study and those sacrificed at termination were subjected to a gross necropsy and abnormalities were noted.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the 15 day post- dose observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the oral LD50 for both male and female Sprague-Dawley rats has been determined to be greater than 5000 mg/kg bw.

Executive summary:

A study has been performed to determine the acute oral toxicity of the test material. The study has been conducted under GLP conditions and to OECD guidelines. The study has been given a Klimisch Score of 1.

The test material was dosed to five male and five female Sprague-Dawley rats at a level of 5000 mg/kg body weight. All animals survived the 15 day post- dose observation period. Based on the data obtained from this study, the acute oral LD₅₀is considered to be greater than 5000 mg/kg body weight. The test article is not considered to be toxic when administered by gavage to Sprague-Dawley rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 August 1983 to 26 September 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Sponsor ID: OD-826

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Animals and Animal Husbandry: All housing and care conformed to the standards established in "Guide for the Care and Use of Laboratory Animals" DHEW publication No. (NIH) 78-23.
- Species/Strain: Sprague-Dawley Rats
- Source: External
- Age at Initiation: Young adult
- Number/Sex: 5/sex/dosage level
- Housing: Individually housed in wire mesh bottom cages
- Food: ad libitum, (except during the exposure period); supplied fresh each week
- Water: Tap water, ad libitum, except during the exposure period
- Environment: All animals housed in environment controlled rooms with temperature and
relative humidity regulated as per "Guide for the Care and Use of Laboratory Animals". Filtered air supplied provided 12 - 15 air changes per hour. A 12 hour light-dark cycle was maintained.
- Quarantine: Minimum of 5 days

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Aerosol Generation and Exposure
Each group was exposed (wholebody) for 262 minutes in a 309 L stainless steel and glass. Twenty- two minutes were added to the 240 minute exposure period in order to allow the test atmosphere to reach its equilibrium concentration.
The test article was atomized by means of one or two ball jet nebulizers. The aerosol was mixed and diluted with ambient air as it entered the chamber. Total airflow through the chamber was maintained at a rate of 65 L/minute using a transvector jet mounted to the chamber exhaust.
Airflow through the system was monitored using a pre-standardized pressure gauge attached to the transvector jet. The test atmosphere was vented via an air treatment system consisting of a glass fiber prefilter, Micretain® HEPA filter and an activated charcoal bank.
The animals remained in the chamber for at least 25 minutes following exposure. The system was operated at the designated flow rate using ambient air only during this period.

Duration of exposure:

4 h

Concentrations:

0, 0.30, 1.68, 2.48, 3.17, or 3.28 mg/L

No. of animals per sex per dose:

5 per sex per dose

Details on study design:

Morbidity, mortality, and clinical signs were recorded twice daily for 14 days. Body weights were recorded on days 1, 4, 8, and 15.
Actual chamber aerosol concentration was determined twice each hour by gravimetric analyses.
Particle size analyses were performed twice per hour for all groups using a multijet cascade impactor.
Greater than 97% of the particles were less than or equal to 10 µm in size. Gross necropsies were performed.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

3.08 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: lower and upper 95% confidence intervals of 2.78 mg/L and 3.50 mg/L, respectively

Other findings:

Decreased activity was noted during the first 3 days in rats of 2.48, 3.17, and 3.28 mg/L groups as activity levels of surviving animals returned to normal by Study Day 4. Laboured breathing was observed among all surviving animals at 2.48 mg/L and in one male at 3.17 mg/L. Respiratory rates returned to normal during the first week. Decreased body weight gain was noted during the first week in males of treated groups but was comparable at Study Day 15. Transient weight loss occurred during the first week in the surviving female exposed to 3.28 mg/L. No treatment related lesions or abnormalities were noted at necropsy of surviving animals. However, pulmonary erythema (reddened lungs) was present in animals found dead in the 3.17 and 3.28 mg/L dose groups. Moderate oedema (fluid present in the lungs) was noted among animals found dead in the 3.28 mg/L dose group. The mortality occurred during the first 2 days, 1/5 male, 4/10 (3 males and 1 female), and 8/10 (4/sex) animals were found dead in the 2.48, 3.17, and 3.28 mg/L dose groups, respectively.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of the study, the sex combined LC50 was 3.08 mg/L with lower and upper 95% confidence intervals of 2.78 mg/L and 3.50 mg/L.

Executive summary:

A study has been performed to determine the acute inhalation toxicity of the test material. The study has been conducted under GLP conditions and to OECD guidelines. The study has been given a Klimisch Score of 1. Test substance batch number is included in the study report, but test substance characterization is not included in the study report. Sprague-Dawley rats, 5 per sex per dose were used in this study. The animals were with dosed liquid droplet aerosol containing 0, 0.30, l.68, 2.48, 3.17, or 3.28 mg/L test substance for 4 hours via the inhalation route utilizing whole body exposure. Morbidity, mortality, and clinical signs were recorded twice daily for 14 days. Body weights were recorded on days 1, 4, 8, and 15. Actual chamber aerosol concentration was determined twice each hour by gravimetric analyses. Particle size analyses were performed twice per hour for all groups using a multijet cascade impactor. Greater than 97% of the particles were less than or equal to 10 µm in size. Gross necropsies were performed. Decreased activity was noted during the first 3 days in rats of 2.48, 3.17, and 3.28 mg/L groups as activity levels of surviving animals returned to normal by Study Day 4. Laboured breathing was observed among all surviving animals at 2.48 mg/L and in one male at 3.17 mg/L. Respiratory rates returned to normal during the first week. Decreased body weight gain was noted during the first week in males of treated groups but was comparable at Study Day 15. Transient weight loss occurred during the first week in the surviving female exposed to 3.28 mg/L. No treatment related lesions or abnormalities were noted at necropsy of surviving animals. However, pulmonary erythema (reddened lungs) was present in animals found dead in the 3.17 and 3.28 mg/L dose groups. Moderate oedema (fluid present in the lungs) was noted among animals found dead in the 3.28 mg/L dose group. The mortality occurred during the first 2 days, 1/5 male, 4/10 (3 males and 1 female), and 8/10 (4/sex) animals were found dead in the 2.48, 3.17, and 3.28 mg/L dose groups, respectively. The sex combined LC₅₀was 3.08 mg/L with lower and upper 95% confidence intervals of 2.78 mg/L and 3.50 mg/L.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

3.08 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 September 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: External
- Age at study initiation: Young adult
- Fasting period before study:
- Housing: The rabbits were individually housed in wire mesh bottom cages in an environment controlled room
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: A minimum of 5 days

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Immediately after application, the trunk of each animal was wrapped with an occlusive binder that consisted of a layer of plastic wrap and a stockinette sleeve all secured in place with masking tape.

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 per sex per dose

Details on study design:

At the end of 24 hours, the occlusive binders were removed and the exposure sites were gently wiped with clean gauze to remove as much non-·absorbed test article as possible. The animals were observed for mortality and toxic signs frequently on the day of dosing and twice daily thereafter for 14 days. The animals were weighed prior to initiation of the study and on days 8, 15 or at death.

All animals dying during the 14 day post-dose observation period and those sacrificed at the termination of the study were subjected to a gross necropsy and abnormalities were noted.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the 15 day post- dose observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the dermal LD50 of the test material has been determined for both sexes as greater than 2000 mg/kg bw.

Executive summary:

A study has been performed to determine the acute dermal toxicity of the test material. The study has been conducted under GLP conditions and to OECD guidelines. The study has been given a Klimisch Score of 1. The test material was evaluated for in male and female New Zealand White rabbits. The test material was applied to each of ten rabbits at a level of 2000 mg/kg body weight, followed byocclusive coverage for a 24 hour treatment period. Dressings were removed approximately 24 hours after application and excess test substance was removed. Morbidity, mortality, and clinical signs were recorded twice daily for 14 days. Body weights were recorded prior to initiation of the study and on days 8 and 15. Gross necropsies were performed. All animals survived the 15 day post- dose observation period.Under the conditions of the study, the dermal LD₅₀of the test material has been determined for both sexes as greater than 2000 mg/kg bw. Thetest material is not considered to be toxic when applied dermally to New Zeal and White rabbits

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

The substance is classified as acutely harmful by inhalation exposure.