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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it was well conducted and documented. The study was conducted prior to adoption of GLP guidelines.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1958

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
This study is pre-guideline but the methods used are considered deemed appropriate as utilized in the report.
GLP compliance:
no
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 1 week


Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: compressed air and compressed nitrogen
Details on inhalation exposure:
The generation of thiol vapors was accomplished by either of two methods: (1) bubbling a stream of nitrogen gas (to prevent possible oxidation to sulfide) through a midget fritted-glass bubbler, which contained the liquid thiol, or (2) by passage of nitrogen into a borosilicate glass nebulizer which contained the thiol.

The bubbler was modified by adding an upright side-arm delivery tube with a 10/30 ground joint distal end into which a separatory funnel was inserted. The funnel served as a reservoir for the thiol being vaporized.

Each of the described methods was used interchangeably, but with some of the lower boiling point thios the bubbler proved more manageable and gave more uniform chamber concentrations than the nebulizer.
Duration of exposure:
>= 4 h
Remarks on duration:
Only studied one sex, males
Concentrations:
6.61, 8.00, 9.08, 11.28, 12.28, 12.37, 12.98, 13.02 mg/L (2600, 3150, 3573, 4438, 4832, 4868, 5100, 5125 ppm)
No. of animals per sex per dose:
5 males per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 days
- Necropsy of survivors performed: yes
Statistics:
LC50 values by inhalation were calculated by the method of Miller and Tainter, using logarithmic-probit graph paper.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
11.23 mg/L air
Exp. duration:
4 h
Remarks on result:
other: (11, 230 mg/m3)
Mortality:
Mortality was first observed at dose levels of 11.28 mg/L (4438 ppm), and were higher at higher dosage levels. The cumulative results are presented in the data table below.
Clinical signs:
Rats showed signs of intoxication from exposure. Maximal sublethal and lethal concentrations of thiol induced charateristic symptoms of toxicity, such as increased respiration and restlessness, incoordinated movements and staggering gait, muscular weakness, partial skeletal muscle paralysis beginning in hind limbs, light cyanosis, tolerance to prone position, and sedation. Exposed animals often remained in a semi-conscious condition of long duration. Irritation to the mucous membranes was observed approximately 15 minutes after exposure in higher dosage groups, which was evidenced by rubbing of the eyes and nose, eye closure, occasional sneezing, watering of the eyes, and retracting of the head.

Any other information on results incl. tables

Toxicity data on four hour inhalation exposure to vapor thiols

Cumulative Mortality During and After Exposure

 

0-4 Hrs

24 Hrs

48 Hrs

15 Days

Analyzed conc. (mg/L)

 

 

 

 

6.61 (2600 ppm)

0/5

0/5

0/5

0/5

8.00 (3150 ppm)

0/5

0/5

0/5

0/5

9.08 (3573 ppm)

0/5

0/5

0/5

0/5

11.28 (4438 ppm)

0/5

0/5

1/5

1/5

12.28 (4832 ppm)

1/6

3/6

3/6

4/6

12.37 (4868 ppm)

1/5

2/5

2/5

2/5

12.98 (5100 ppm)

2/5

5/5

 

 

13.02 (5125 ppm)

2/6

2/6

2/6

2/6

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Toxicity classification based on single 4-hour exposures shows ethanethiol to be slightly toxic (Fairchild & Stokinger, 1958).
Executive summary:

In an acute toxicity inhalation study, five male rats (Wistar derived) per dose were subjected to the inhalation of ethanethiol vapors at concentrations of 6.61, 8.00, 9.08, 11.28, 12.28, 12.37, 12.98, or 13.02 mg/L (2600, 3150, 3573, 4438, 4832, 4868, 5100, 5125 ppm) (Fairchild & Stokinger, 1958). The generation of thiol vapors was accomplished by either of two methods: (1) bubbling a stream of nitrogen gas through a midget fritted-glass bubbler, which contained the liquid thiol, or (2) by passage of nitrogen into a borosilicate glass nebulizer which contained the thiol.

Toxicity data showed that rats were susceptible to the thiol and mortality was observed at all dose levels greater than and equal to 11.28 mg/L (4438 ppm). Rats exhibited signs of intoxication, and maximal sublethal and lethal concentrations of thiols induced characteristic symptoms of toxicity (ie increased respiration and restlessness, incoordinated movement and staggering gait, muscular weakness, partial skeletal muscle paralysis, light to severe cyosis, and tolerance of prone position. The LC50 was determined to be 12.38 (4870 ppm) mg/L at 24 hours, 11.6 mg/L (4565 ppm) at 48 hours, and 11.23 mg/L (4420 ppm) at 15 days after the exposure period.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it was well conducted and documented. The study was conducted prior to adoption of GLP guidelines.