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

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-(octyldisulfanyl)octane; 2-(octyldisulfanyl)-5-[(octylsulfanyl)disulfanyl]-1,3,4-thiadiazole; 2-(octyldisulfanyl)-5-{[5-(octyldisulfanyl)-1,3,4-thiadiazol-2-yl]sulfanyl}-1,3,4-thiadiazole; bis(octyldisulfanyl)-1,3,4-thiadiazole

EC Number:

948-020-7

Molecular formula:

N/A

IUPAC Name:

1-(octyldisulfanyl)octane; 2-(octyldisulfanyl)-5-[(octylsulfanyl)disulfanyl]-1,3,4-thiadiazole; 2-(octyldisulfanyl)-5-{[5-(octyldisulfanyl)-1,3,4-thiadiazol-2-yl]sulfanyl}-1,3,4-thiadiazole; bis(octyldisulfanyl)-1,3,4-thiadiazole

Test material form:

liquid

Details on test material:

EC Number: 948-020-7

Specific details on test material used for the study:

Sponsor ID: OD-826

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.