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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was classified as reliable without restriction because it is a guideline GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Source: Pennwalt Corporation
Batch: no data
Purity at least 98%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., USA
- Age at study initiation: 7-9 weeks for males, 9-10 weeks for females
- Weight at study initiation: 202-306 g for males, 192-215 for females
- Housing: doubly-housed the singly in suspended stainless steel wire mesh cage
- Diet (e.g. ad libitum): Purina Rodent Laboratory chow #5001
- Water (e.g. ad libitum): tap water
- Acclimation period: 7-15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67-76
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
- Chamber Operation:
The Plexiglas® exposure chamber had a total volume of 100 liters. The chamber was operated dynamically at an initial airflow rate of 25 liters per minute (lpm). This flow rate was calculated to provide one complete air change at least every 4.0 minutes and a 99% equilibrium time of 18.4 minutes. For Groups I, II, IV-VI, the 100 liter Plexiglas® eposure chamber was contained inside a 1 m3 glass and stainless steel exposure chamber, under slightly negative pressure.

- Exposure Procedure:
Appropriate amounts (milliliters, mls) of the test substance were placed in each of two 500 ml fritted-bottom bubblers for Groups I and II, or each of three 500 ml fritted-bottom bubblers for Groups IV-VI. House-supply air was delivered through a Union Carbide regulator and 3/8" Tygon® tubing to each bubbler via a Nupro metering valve, a Dwyer flowmeter and a Union Carbide pressure gauge. The resultant vapor-laden airstream was directed to a five-neck flask which served as a mixing vessel and a trap. (The trap contained glass wool to facilitate trapping of any aerosol present.) Additional diluted air was delivered to the five-neck flask via a Union Carbide pressure gauge, a Nupro metering valve and a Dwyer flowmeter. This generation system was contained inside a wood and Plexiglas® glove box under slightly negative pressure. The resultant vapor-laden air stream was directd from the five-neck flask into the lm' chamber which contained the 100 liter Plexiglas® exposure chamber, via 1/2" Teflon® tubing.
Control animals (Group III) were exposed to house-supply air only during the four-hour in-chamber period while in a 100 liter Plexiglas® exposure chamber.

- Method of particle size determination:
Measurements for the presence of any particulate in the chamber were made twice during the exposure for Groups I and II and once during exposure for Groups III-VI. In-chamber particle count for all groups was less than five times the background (room air) using the widest channel, therefore the aerosol concentration was considered to be negligible. Measurements were performed using a Royco Model 227 Portable Particle Monitor.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Samples were taken and using a Miran lA Ambient Air Analyzer and strip chart recorder. The exposure level was determined by comparison of the resultant absorbance to a calibrated response using the same instrumental settings.
Duration of exposure:
4 h
Concentrations:
0, 14400, 19900, 22900, 32400, or 36000 ppm (nominal)
0, 14900, 22400, 27800, 30100, 36100 ppm (analytical)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
In-Life Observations:
Day 1 (Day of Exposure): All animals were observed individually, immediately prior to exposure, as a group at approximately fifteen minute intervals during the first hour of exposure, each half hour for hours 1 through 2, and hourly for the remainder of the exposure period. Ail survivors were observed individually upon removal from the chamber (half hour after exposure was completed) and four hours post-exposure. Detailed physical observations were recorded at each interval.
Days 2 through 15 (Post-exposure): Detailed observations were recorded for survivors twice daily; viability was assessed twice daily.

Body Weight:
Day 1 (immediately prior to exposure) and on Days 2, 3, 5, 8, 11 and 15 (just prior to sacrifice).

Postmortem:
A complete gross postmortem examination was performed on all animals dying spontaneously during the course of the study as well as those animals surviving to the end of the 14-day post-exposure observation period. The gross postmortem examinations included examination of the nasal passages, trachea, external surface, all orifices, the cranial cavity, carcass, the brain and spinal cord, the thoracic, abdominal and pelvic cavities and their viscera and the cervical tissues and organs.



Statistics:
A calculation of median lethal concentration and 95% confidence limits was performed according to the method of Litchfield and Wilcoxon.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
26 643 ppm
95% CL:
22 733 - 31 227
Exp. duration:
4 h
Remarks on result:
other: = 98,300 mg/m3
Mortality:
All deaths occurred during exposure or prior to removal from the chamber (see table below)
Clinical signs:
Exposure Period:
During exposure, the most commonly noted signs of toxicity were lacrimation, labored breathing, reduced activity and prostration. Several notations of ataxia were made for the 14,900 and 22,400 ppm exposures and observations of tremors were noted for the 22,400 and 27,800 ppm exposures. All animals that died as a result of exposure did so during exposure or prior to removal from the chamber.

Upon Removal From Exposure Chamber and Over the Four-Hour Post-Exposure Observation Period:
Among survivors, secretory responses and labored breathing were commonly noted up to four hours post-exposure, with occasional findings of reduced activity, prostration and tremors only upon removal from the chamber. Other minor observations occurred sporadically.

Daily Observations During the 14-Day Post-Exposure Observation Period :
Observations of secretory responses and labored breathing were commonly made on the day following exposure after which they decreased in incidence and/or became sporadic in nature. Some evidence of labored breathing was noted up to Day 5 in animais exposed to 22,400 ppm and to Day 10 in animals exposed to 27,800 ppm. A few observations of rates were also made on Days 10 and 11 for these exposure groups. In general, however, findings decreased in severity during the recovery period.

Post-exposure observations reported included: secretory responses and labored breathing, with occasional findings of reduced activity, prostration and tremors only upon removal from the chamber. In surviving animals these signs persisted for several days and then abated before the Day 15 sacrifice.
Body weight:
Weight losses of significant magnitude were noted among survivors on the day following exposure. Recovery of weight occurred over time and by 8 days post-exposure, most animals were in excess of their original body weight. Notable exceptions were two male rats exposed to 27,800 ppm which had still not recovered to their individual weights by termination of the study.
Gross pathology:
A number of animals which died spontaneously had red lungs. This is not considered to be unusual in animals which were not exsanguinated prior to postmortem examination. The toxicological significance of this finding, if any, remains undetermined on the basis of gross examination only. Other postmortem findings, observed grossly, occurred sporadically and were not considered to be related to the test article.
Other findings:
no data

Any other information on results incl. tables

Group

Mean Analytical Concentration (ppm)

Nominal Concentration (ppm)

Amount of Test Material Consumed (grams)

Mortality

#dead/#exposed

Male

Female

I

36,100

36,000

883.56

5/5

5/5

VI

30,100

32,400

765.21

5/5

5/5

V

27,800

22,900

537.21

0/5

3/5

IV

22,400

19,900

467.90

1/5

0/5

II

14,900

14,400

337.32

0/5

0/5

III

Control

-

0/5

0/5

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Conclusions:
In an acute inhalation toxicity study, the LC50s were determined to be 26,643 ppm for combined sexes, 26,799 ppm for males and 25,643 ppm for females.
Executive summary:
In an acute inhalation toxicity study (OECD 403), groups of ten rats (5/sex) were exposed to 2 -methylpropane-2 -thiol (CAS Number 75 -66 -1) at concentrations of 0, 14400, 19900, 22900, 32400, or 36000 ppm for four hours. The animals were observed immediately prior to exposure, at approximately 15 minute intervals during the first hour of exposure, every half hour during 1 and 2 hours and hourly until the completion of the 14-day exposure period. All survivors were observed upon removal from the chamber and hourly for four hours post-exposure. The animals were observed twice daily for mortality and detailed observations were recorded daily through the remainder of the 14 -day post-exposure period. Body weights were recorded on Day 1 (prior to exposure), and on Days 2, 3, 5, 8, 11 and 15 (just prior to sacrifice). A gross necropsy was conducted on all animals dying spontaneously during the course of the study and on all animals that survived to study termination.

 

All animals that died did so either during exposure or prior to removal from the chamber (30 minutes after cessation of compound delivery). Lacrimation, labored breathing, reduced activity and prostration were commonly noted during exposure and up to four hours post-exposure. Several instances of ataxia and tremors were also observed. During the recovery period, secretory and respiratory responses were noted initially but signs decreased in incidence and severity as the recovery period progressed. Body weights were significantly decreased in survivors on the day following exposure but, again, there was general recovery by Day 8 post-exposure. A number of animals, which died spontaneously, had red lungs. This is not considered to be unusual in animals which were not exsanguinated prior to postmortem examination. The toxicologicalsignificance of this finding, if any, remains undetermined on the basis of gross examination only. Other postmortem findings, observed grossly, occurred sporadically and were not considered to be related to the test article.

 

The LC50s were determined to be 26,643 ppm for combined sexes, 26,799 ppm for males and 25,643 ppm for females. The substance is not classified according to EC Regulation No 1272/2008.

 

This study received a Klimisch Score of 1 and is classified as reliable without restriction because it is a guideline GLP study.