Propane-2-thiol

Endpoint summary

Description of key information

No studies are available on the registered substance, therefore, the acute toxicity was evaluated on the basis of the data available on propane-1 -thiol and propane-2 -thiol. For the registered substance, the calculated acute toxicity estimates are approximately 3066 mg/kg bw, higher than 20 mg/l and higher than 2000 mg/kg bw by the oral, inhalation and dermal routes, respectively.

 

Oral route

Studies on propane-2-thiol

In a pre-guideline study (Latven, 1977), male WBS/W rats were dosed (gavage) with propane-2-thiol at doses of 2000 and 5000 mg/kg bw and followed for 7 days. Mortality was 0/6 and 5/6 in the 2000 and 5000 mg/kg groups, respectively. Signs included hypotonia, ataxia, loss of righting reflex and body weight loss. Recovery was complete in 4 days. The LD50was between 2000 and 5000 mg/kg bw and approximately 3730 mg/kg bw when calculated with the standard probit method .

 

Studies on propane-1-thiol

In an acute oral toxicity study, groups of Wistar male rats (5/sex) were given a single oral dose of propane-1-thiol undiluted at doses of 1327, 1672, 2107, 2654, or 3344 mg/kg bw and observed for 15 days (Fairchild and Stokinger, 1958). Toxicity signs included sedative action, and maximal sublethal doses resulted in deep comatose sleep for approximately 48 hours. Diarrhea was also pronounced for the highest doses. Gross pathology generally did not show significant gross or microscopic tissue changes. Survivors of near lethal doses showed changes which, although inconsistent, were indicative of liver and kidney damage. Body weights were not measured. The oral LD50was determined to be 1790 mg/kg bw in males.

 

Inhalation route

Studies on propane-2-thiol

In a key study similar to OECD TG 403 (Pence, 1983), Sprague-Dawley rats (5/sex) were exposed (whole-body) for four hours to propane-2-thiol at a measured concentration of 32.24 mg/l [10368 ppm]. Animals were observed for 14 days following the exposure. No mortality was observed. Beginning 30 minutes after initiation of exposures, all animals exhibited hyperactivity and ataxia, labored respiration, prostration, and squinted eyes. All animals appeared normal throughout the rest of the study with the exception of one female exhibiting urine stains through Day 3 post-exposure. The males exhibited reduced mean body weights through Day 4 post-exposure and the females exhibited reduced mean body weights through Day 7 post-exposure. There was no evidence of macroscopic changes attributable to exposure. The 4-hour LC0was > 32.24 mg/L (> 10368 pm).

 

In a supporting study similar to OECD TG 403 (Hardy and Jackson, 1987), Sprague-Dawley rats (5/sex) were exposed (whole body) for four hours to a sham atmosphere or to propane-2-thiol at analytical concentration of 18,440 mg/m3 (5917 ppm). Animals were observed for 14 days following the exposure. There were no deaths. During exposure were observed, signs of irritant effects, including partial closing of eyes, reduced respiratory rate, abnormal respiratory movements, restlessness and adoption of a hunched body posture. An increased respiratory rate persisting for 1 day was observed post-exposure. Weight gain by rats exposed to propane-2-thiol was reduced for up to 2 days (males) or 5 days (females) post exposure. At necropsy, dark areas were observed on lungs of 3 rats exposed to propane-2-thiol and lung weight to bodyweight ratios was within normal limits. The LC0 (4-hour) is therefore in excess of 18.44 mg/l (5917 ppm).

 

In a supporting study similar to OECD TG 403 (Hardy and Jackson, 1987), Sprague-Dawley rats (5/sex) were exposed (whole body) for four hours to a sham atmosphere or to propane-2-thiol at analytical concentration of 5,500 mg/m3 (1765 ppm) Animals were observed for 14 days following the exposure. There were no deaths. During exposure were observed, signs of irritant effects including closing or partial closing of the eyes, adoption of a hunched body posture and disturbances to the respiratory pattern. Weight gain by rats exposed to propane-2-thiol was reduced for up to 2 days post exposure. At necropsy, no treatment-related findings were observed and lung weight to bodyweight ratios was within normal limits. The LC0 (4-hour) is therefore in excess of 5.5 mg/l (1765 ppm).

 

Studies on propane-1-thiol

In an acute inhalation toxicity study, groups of young adult albino Sprague-Dawley rats (5/sex) were exposed whole body to propane-1-thiol for 4 hours to an analytical concentration of 5.663 mg/L (Hardy and Jackson, 1987). Animals then were observed for 14 days. There were no deaths following exposure to propane-1-thiol vapor at a concentration of 5.663 mg/l. During exposure there were signs of irritant effects including partial closing of the eyes, reduced respiration rate, abnormal respiration movements and adoption of a hunched body posture. Rats showed increased respiratory rate immediately following exposure, which subsequently returned to normal. Weight gain by rats exposed to propane-1-thiol was reduced for 1 day for males or up to 4 days for females post exposure. Lung weight to bodyweight ratios was within normal limits for all rats with the possible exception of one rat that was exposed to propane-1-thiol vapor. Macroscopic pathology revealed no treatment-related findings. The inhalation LC0 was determined to be greater than 5.663 mg/l in males and females.

 

Male Wistar rats (6/group) were exposed (whole body) to propane-1-thiol for four hours at analytical concentrations of 3050, 4500, 8340, or 11260 ppm (9.5, 14.0, 26.0, 35.1 mg/L) (Fairchild and Stockinger, 1958). Although this study was conducted prior to adoption of GLP and guidelines for acute inhalation studies, there was sufficient detail to consider it comparable to OECD TG 403. All animals survived exposure at 3050 and 4500 ppm. At 8340 ppm, four of the five animals died; three died by 4-hours, and one by 24 hours. All 5 animals died within 4 hours following exposure to 11260 ppm. Increased respiration, restlessness, uncoordinated movement, staggering gait, muscular weakness, cyanosis and sedation were seen at higher concentrations, including those causing mortality. Irritation of the mucous membrane evidenced by rubbing of the eyes and nose, eye closure, watering of the eyes, cortical opacities and retracting of the head were the major clinical signs. The 4-hour LC50 was 7300 ppm (22.8 mg/L).

 

In the same study, male Swiss mice were exposed (whole body) to propane-1-thiol for four hours at concentrations of 3050, 4500, 8340, 11260 ppm (9.51, 14.03, 26.01, 35.11 mg/L). All animals survived exposure at 3050 ppm. At 4500 ppm, 14 of the 20 animals died by 15 days. All animals died within 4 hours following exposure to 8340 and 11250 ppm. Increased respiration, restlessness, uncoordinated movement, staggering gait, muscular weakness, cyanosis and sedation were seen at higher concentrations, including those causing mortality. Irritation of the mucous membrane evidenced by rubbing of the eyes and nose, eye closure, watering of the eyes, cortical opacities and retracting of the head were the major clinical signs. The 4-hour LC50 was 4010 ppm (12.5 mg/L) (Fairchild and Stockinger, 1958).

 

Dermal Route

Studies on propane-2-thiol

In a pre-guideline study, each of six rats (male WBS/W) was treated dermally with 2000 mg/kg bw (2.46 ml/kg bw) of propane-2-thiol (Latven, 1977). Doses were applied under an impervious sleeve, which was pre-fitted upon the fur-clipped trunk of each rat. The sleeves were removed 24 hours later and the animals were then observed for seven days. Initial vocalization and weight losses lasting up to 4 days were observed. The LD0 was > 2000 mg/kg bw.

 

Studies propane-1-thiol:

In an acute dermal toxicity study, groups of New Zealand Albino rabbits (5/sex) were dermally exposed to propane-1-thiol for 24 hours to 10% of body surface area at doses of 2000 mg/kg bw (Shapiro, 1985). Animals then were observed for 14 days. The rabbit that died on day 5 displayed the following clinical signs: lethargy, apparent loss of appetite, loss of gross reflexes, apparent drop In body temperature (i.e. cold to the touch) and loss of weight (1.0 kg). The surviving rabbits appeared active and behaved normally. Several rabbits, sporadically, did not eat on isolated days. The test application site on each of the rabbits was erythematous and in some instances the skin was thickened. Gross necropsy of the deceased and surviving animals revealed evidence of pulmonary hemorrhage and discoloration of the liver and spleen. The dermal LD50 was determined to be greater than 2,000 mg/kg in males and females.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

Undiluted propane-2-thiol was administered by stomach tube to 2 groups of 6 rats. Surviving animals were observed for 7 days

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: WBS/W

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 g

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 and 5000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes

Statistics:

Not appropriate

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 - < 5 000 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

3 730 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Calculated with the standard probit method

Mortality:

0/6 at 2000 mg/kg.
6/6 at 5000 mg/kg (time for death (h): 3, >4, >4, >4, 20, 96)

Clinical signs:

other: Muscular hypothonia, motor ataxia, loss of righting reflex, recovery of righting reflex.

Gross pathology:

Findings were not significant

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was between 2000 and 5000 mg/kg bw.

Executive summary:

In a pre-guideline study, male WBS/W rats were dosed with iso-propyl mercaptan at doses of 2000 and 5000 mg/kg bw and followed for 7 days. Mortality was 0 and 5 of the 6 animals per group, respectively.  Signs included hypotonia, ataxia, loss of righting reflex and body weight loss. Recovery was complete in 4 days. The LD₅₀ was between 2000 and 5000 mg/kg bw and approximately 3730 mg/kg bw when calculated with the standard probit method .

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1958

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: local commercial breeder
- Weight at study initiation: 180 to 220 grams
- Diet (e.g. ad libitum): Rockland Rat Diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: one week

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4 ml/kg (3344 mg/kg bw )

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: doses were at geometric progression ( factor 1.26 to 2.0)

Doses:

1327, 1672, 2107, 2654, and 3344 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Observed on days 1, 2, 3, 5, 10, and 15 no weighing was conducted
- Necropsy of survivors performed: yes
- Other examinations performed: pathology

Statistics:

LD50 calculated by the method of Weil (Weil, C.S.: Tables for Convenient Calculation of Median-Effective Dose (LD50 or ED50) and Instruction in Their Use. Biometrics, 8: 249-304 (1954).)

Sex:

male

Dose descriptor:

LD50

Effect level:

1 790 mg/kg bw

Based on:

test mat.

95% CL:

1 632 - 1 963

Mortality:

Mortality occurred in all animals by 20 hours of administration for the 3344 mg/kg dose, 50 hours for the 2654 mg/kg dose, and day 10 for the 2107 mg/kg dose. One of the five animals died in the 1672 mg/kg dose level; and no mortality occurred at the 1327 kg/mg dose level.

Clinical signs:

other: Toxicity signs included sedative action, and maximal sublethal doses resulted in deep comatose sleep for approximately 48 hours. Diarrhea was also pronounced for the highest doses.

Gross pathology:

Gross pathology generally did not show significant gross or microscopic tissue changes. All animals that survived near lethal doses and were sacrificed within 20 days post-treatment, frequently showed pathologic changes which, although inconsistent, were indicative of liver and kidney damage. Microscopic examination revealed occasional marked changes in the kidneys of rats which included: degeneration with swelling and some necrosis of the tubular epithelium, thickening of Bowman’s capsule, and hyaline deposition in glomerular tufts. More often only minor lesions with varying degrees of cloudy swelling of the tubules and hyaline casts in the lumina were present. In general, liver changes were characterized by lymphocytic infiltration, occasional necrotic foci with small hemorrhages, and varying degrees of fatty degeneration. Only rarely did tissue studies show significant pathologic conditions as the result of relatively small doses of the chemical.

Other findings:

No data reported

Toxicity Data for Rats Following Single Oral Dose of Propanethiol

Dose (mg/kg)	Cumulative Mortality following Administration for the Day
	1	2	3	5	10	15
1327	0/5	0/5	0/5	0/5	0/5	0/5
1672	0/5	0/5	0/5	1/5 (4^th)	1/5	1/5
2107	2/5	3/5	3/5	4/5 (9^th)	5/5
2654	3/5	5/5 (4/5 dead 42 hrs; 5/5 dead 50 hours)
3344	5/5 (1/5 dead 4hrs; 5/5 dead 10-20 hrs)
LD50(mg/kg)	2362	2055				1790
Confidence Limits	2014-2770	1836-2300				1632-1963

 

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In an acute oral toxicity study, groups of Wistar male rats (5/sex) were given a single oral dose of propane-1-thiol undiluted at doses of 1327, 1672, 2107, 2654, or 3344 mg/kg bw and observed for 15 days. The oral LD50 was determined to be 1790 mg/kg bw in males. This study is classified as Toxicity Category IV by EU classification.

Executive summary:

In an acute oral toxicity study, groups of Wistar male rats (5/sex) were given a single oral dose of propane-1-thiol undiluted at doses of 1327, 1672, 2107, 2654, or 3344 mg/kg bw and observed for 15 days. Toxicity signs included sedative action, and maximal sublethal doses resulted in deep comatose sleep for approximately 48 hours. Diarrhea was also pronounced for the highest doses. Gross pathology generally did not show significant gross or microscopic tissue changes. Survivors of near lethal doses showed changes which, although inconsistent, were indicative of liver and kidney damage. Body weights were not measured. The oral LD₅₀ was determined to be 1790 mg/kg bw in males. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 066 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

no information on the test compound

GLP compliance:

no

Test type:

standard acute 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: Charles River laboratories, Inc.
- Age at study initiation: no data
- Weight at study initiation: 200-350 g
- Housing: individually
- Diet (ad libitum): Purina lab chow #5001
- Water (ad libitum): tap water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 70 +/- 4
- Humidity (%): 40-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass and stainless steel chambers
- Exposure chamber volume: 38 liters
- Method of holding animals in test chamber: individually in stainless-steel wire-mesh cage
- Source and rate of air: 10 l/min
- System of generating vapors: water-jacketed counter-flow column maintained at ca. 80°F
- Treatment of exhaust air: no data
- Temperature, humidity in air chamber: 75 +/- 3°F, 50-70%

TEST ATMOSPHERE
- Brief description of analytical method used: Total hydrocarbon analysis
- Samples taken from breathing zone: no data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Total hydrocarbon analysis

Duration of exposure:

4 h

Concentrations:

22.55 mg/l (nominal)
10368.75 +/- 1202.66 ppm (32.24 mg/l, analytical)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: during exposure and twice daily
- Body weight: prior exposure and on days 2,3, 4, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

Not appropriate

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 32.24 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: > 10368 ppm, no mortality

Mortality:

No mortality was observed

Clinical signs:

other: Beginning 30 minutes after initiation of exposures, all animals exhibited hyperactivty and ataxia (for the first 3 hours of exposure), labored respiration, prostration (last 30 minutes of exposure), and squinted eyes. One male and two females had bloody c

Body weight:

The males exhibited reduced mean body weights through Day 4 post-exposure and the females exhibited reduced mean body weights through Day 7 post-exposure when compared to the respective pre-exposure mean body weights.

Gross pathology:

All animals appeared normal at the terminal sacrifice with the exception of one male observed with an enlarged left cervical lymph node.

Interpretation of results:

GHS criteria not met

Executive summary:

In a key study similar to OECD TG 403, Sprague-Dawley rats (5/sex) were exposed (whole-body) for four hours to propane-2-thiol at a measured concentration of 32.24 mg/l [10368 ppm]. Animals were observed for 14 days following the exposure. No mortality was observed. Beginning 30 minutes after initiation of exposures, all animals exhibited hyperactivty and ataxia, labored respiration, prostration, and squinted eyes. All animals appeared normal throughout the rest of the study with the exception of one female exhibiting urine stains through Day 3 postexposure. The males exhibited reduced mean body weights through Day 4 postexposure and the females exhibited reduced mean body weights through Day 7 postexposure. There was no evidence of macroscopic changes attributable to exposure. The 4-hour LC₀ was > 32.24 mg/L (> 10368 pm).

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

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: Charles River UK Ltd., Margate, Kent, England
- Age at study initiation: no data
- Weight at study initiation: ca. 200 g
- Housing: 5 males or 5 females to a polypropylene cage
- Diet (ad libitum): Labsure LAD 1
- Water (ad libitum): tap water
- Acclimation period: least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 53 +/- 7.7
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The whole-body exposure chambers used for the exposures were of square section and were fitted with pyramidal tops. The chambers were made of perspex and had an internal volume of approximately 130 l. Each chamber was divided by wire mesh partitions to provide 10 separate animal compartments. The test atmosphere entered through a port at the base centre of the chamber and passed out through small holes in the lower edge of the square section. Each chamber was positioned inside a large cabinet equipped with an extract fan exhausting to atmosphere through a collection filter.
A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 25 litres per minute. An in-line flow meter was used to monitor air flow throughout the exposure. The water bath was set to 36°C.
A syringe filled with the test substance was fitted to the syringe pump and connected to the generator with PTFE tubing. The flow rate was set at the rate selected during the preliminary work (0.62 ml/min). This was expected to give an atmosphere concentration of approximately 6000 ppm.

TEST ATMOSPHERE
- Brief description of analytical method used:
Five air samples were taken from the chamber during each completed exposure to determine the concentration of the test substance by gas chromatography.
The samples were drawn at a rate of 2 l/minute, through a gas absorption trap containing approximately 20 ml of methanol. The trap was maintained at -70°C (cardice/acetone) during sampling.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
A sample of air was withdrawn from the exposure chamber at 1 hour 30 mins and 3 hours 30 mins using a Royco model 218 optical particle counter. The particle count indicated a maximum of 66 particles <0.5 µm diameter in a 1 minute count. There were therefore no droplets of the test substance present.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

18.44 mg/l (5917 ppm)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical signs: the rats were observed continuously during exposure for signs of reaction to the test substance and at least twice daily during the observation period.
- Bodyweights: all rats were weighed daily from the day following delivery to the Huntingdon Research Centre until the end of the observation period.
- Food and water consumption: the food and water consumption for each cage of rats was determined daily by weight loss from the food hoppers and water bottles.
- Terminal studies: at the end of the 14-day observation period the rats were anaesthetised by intraperitoneal injection of pentobarbitone sodium and killed by exsanguination. The rats killed at termination were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear of surrounding tissue and weighed in order to calculate the lung weight to bodyweight ratio. The lungs were infused with and preserved in buffered 10% formalin together with samples of the liver and kidneys for possible microscopic examination.

Statistics:

Not appropriate

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 18.44 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: > 5917 ppm, no mortality

Mortality:

There were no deaths following exposure to ISOPROPYL MERCAPTAN.

Clinical signs:

other: - During exposure: The signs seen in rats exposed to ISOPROPYL MERCAPTAN were considered to be due to the irritant nature of the vapour. The signs evident in the majority of rats included partial closing of the eyes, reduced respiration rate, abnormal res

Body weight:

The rats exposed to ISOPROPYL MERCAPTAN lost weight or had a reduced rate of bodyweight gain for up to 2 days (male rats) or 5 days (female rats) following exposure.
Subsequently the rate of bodyweight gain was similar to that of the control rats.

Gross pathology:

- Lung weight to bodyweight ratio:
The lung weights for all rats were within normal limits.
- Macroscopic pathology:
The dark areas seen on the lungs of 3 rats exposed to ISOPROPYL MERCAPTAN were considered unlikely to be related to treatment although the possibility of a treatment-related effect cannot be excluded.

Other findings:

- Food and water consumption:
Food consumption was reduced for 1 day in both sexes and water consumption was reduced for 1 day in male rats following exposure to ISOPROPYL MERCAPTAN.

Interpretation of results:

study cannot be used for classification

Conclusions:

The LC0 (4-hour) for ISOPROPYL MERCAPTAN vapour is in excess of 18.44 mg/1 of air (5917 ppm).

Executive summary:

Sprague-Dawley rats (5/sex) were exposed (whole body) for four hours to a sham atmosphere or to iso-propyl mercaptan at analytical concentration of 18,440 mg/m³ (5917 ppm). The design of the study was comparable to OECD guideline 403. Animals were observed for 14 days following the exposure. There were no deaths. During exposure were observed, signs of irritant effects, including partial closing of eyes, reduced respiratory rate, abnormal respiratory movements, restlessnes and adoption of a hunched body posture. An increased respiratory rate persisting for 1 day was observed postexposure. Weight gain by rats exposed to isopropyl mercaptan was reduced for up to 2 days (males) or 5 days (females) post exposure. At necropsy, dark areas were observed on lungs of 3 rats exposed to isopropyl mercaptan and lung weight to bodyweight ratios was within normal limits. The LC₀ (4-hour) is therefore inexcess of 18.44 mg/l (5917 ppm).

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

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: Charles River UK Ltd., Margate, Kent, England
- Age at study initiation: 6-8 week old
- Weight at study initiation: ca. 200 g
- Housing: 5 males or 5 females to a polypropylene cage
- Diet (ad libitum): Labsure LAD 1
- Water (ad libitum): tap water
- Acclimation period: least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 60 +/- 4.1
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The whole-body exposure chambers used for the exposures were of square section and were fitted with pyramidal tops. The chambers were made of perspex and had an internal volume of approximately 130 l. Each chamber was divided by wire mesh partitions to provide 10 separate animal compartments. The test atmosphere entered through a port at the base centre of the chamber and passed out through small holes in the lower edge of the square section. Each chamber was positioned inside a large cabinet equipped with an extract fan exhausting to atmosphere through a collection filter.
A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 25 litres per minute. An in-line flow meter was used to monitor air flow throughout the exposure.
A syringe filled with the test substance was fitted to the syringe pump and connected to the generator with PTFE tubing. The flow rate was set at 0.15 ml/min.

TEST ATMOSPHERE
- Brief description of analytical method used:
Five air samples were taken from the chamber during each completed exposure to determine the concentration of the test substance by gas chromatography.
The samples were drawn at a rate of 0.5 l/minute, through a gas absorption trap containing approximately 20 ml of methanol. The trap was maintained at -70°C (cardice/acetone) during sampling.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
A sample of air was withdrawn from the exposure chamber at 2 hour 30 mins using a Royco model 218 optical particle counter. The particle count indicated a maximum of 23 particles in the range 0.5-1 µm and no particles larger than 1µm in a 1 minute count. There were therefore no droplets of the test substance present.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.5 mg/l (1765 ppm)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical signs: the rats were observed continuously during exposure for signs of reaction to the test substance and at least twice daily during the observation period.
- Bodyweights: all rats were weighed daily from the day following delivery to the Huntingdon Research Centre until the end of the observation period.
- Terminal studies: at the end of the 14-day observation period the rats were anaesthetised by intraperitoneal injection of pentobarbitone sodium and killed by exsanguination. The rats killed at termination were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear of surrounding tissue and weighed in order to calculate the lung weight to bodyweight ratio. The lungs were infused with and preserved in buffered 10% formalin together with samples of the liver and kidneys for possible microscopic examination.

Statistics:

Not appropriate

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 5.5 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: > 1765 ppm, no mortality

Mortality:

There were no deaths following exposure to ISOPROPYL MERCAPTAN.

Clinical signs:

other: - During exposure: The signs seen in rats exposed to ISOPROPYL MERCAPTAN were considered to be due to the irritant nature of the vapour. The signs evident in the majority of rats included closing or partial closing of the eyes, adoption of a hunched body

Body weight:

The rats exposed to ISOPROPYL MERCAPTAN lost weight or had a reduced rate of bodyweight gain for up to 2 days following exposure. Subsequently the rate of bodyweight gain was similar to that of the control rats.

Gross pathology:

- Lung weight to bodyweight ratio:
The lung weights for all rats were within normal limits.
- Macroscopic pathology:
There were no findings that were considered to be related to treatment.

Conclusions:

The LC0 (4-hour) for ISOPROPYL MERCAPTAN vapour is in excess of 5.5 mg/l of air.

Executive summary:

Sprague-Dawley rats (5/sex) were exposed (whole body) for four hours to a sham atmosphere or to iso-propyl mercaptan at analytical concentration of 5,500 mg/m³. The design of the study was comparable to OECD guideline 403. Animals were observed for 14 days following the exposure. There were no deaths. During exposure were observed, signs of irritant effects including closing or partial closing of the eyes, adoption of a hunched body posture and disturbances to the respiratory pattern. Weight gain by rats exposed to isopropyl mercaptan was reduced for up to 2 days post exposure. At necropsy, no treatment-related findings were observed and lung weight to bodyweight ratios was within normal limits.The LC₀ (4-hour) is therefore inexcess of 5.5 mg/l.

Reference 4

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

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.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

acute toxic class method

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 25 to 28 grams
- Diet: Rockland Rat Diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 1 week

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

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.

During exposure periods the concentrations of thiols within the chamber were determined routinely by absorption of vapors in either isopropyl
alcohol or acetone containing an excess of silver nitrate and titrating the uncombined silver amperometrically.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

3050, 4500, 8340, or 11260 ppm (9.50, 14.02, 25.98, or 35.07 mg/L)

No. of animals per sex per dose:

10 males per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 15 days
- Necropsy of survivors performed: tissue specimens were submitted for pathologic examination after having first been examined grossly and preserved in either buffered formalin or Zenker's fixative.

Statistics:

LC50 values by inhalation were calculated by the method of Miller and Tainter, using logarithmic-probit graph paper.

Sex:

male

Dose descriptor:

LC50

Effect level:

4 010 other: ppm (analytical) (equivalent to 12.49 mg/L)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Mortality was observed after 48 hours at the lowest concentration level, and during the during exposure period for all other concentration groups tested. The cumulative results are presented in the data table below.

Clinical signs:

other: Mice 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 weaknes

Toxicity Data on Four Hour Inhalation Exposures to Propane-1-thiol

Cumulative Mortality During and After Exposure in Mice

Analyzed Concentration (ppm)	0-4 Hours	24 Hours	48 Hours	15 Day
3050 (9.50 mg/L)	0/20	0/20	4/20	4/20
4500 (14.02 mg/L)	8/20	10/20	10/20	14/20
8340 (25.98 mg/L)	20/20
11260 (35.07 mg/L)	10/10 (all dead 2 hrs. 15 min)
LC50(Estimated)			4950 (15.42 mg/L)	4010 (12.49 mg/L)

Interpretation of results:

Category 4 based on GHS criteria

Executive summary:

In an acute toxicity inhalation study, groups of ten male mice (Swiss derived averaging from 25 to 28 grams) were subjected to the whole-body exposure of propane-1-thiol vapors at concentrations of 3050, 4500, 8340, or 11260 ppm (9.50, 14.02, 25.98, or 35.07 mg/L). 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 mice were susceptible to the thiol and mortality was observed at all dose levels greater than after 48 hours at the lowest concentration level, and during the during exposure period for all other concentration groups tested. Mice exhibited signs of intoxication, and maximal sublethal and lethal concentrations of thiols induced characteristic symptoms of toxicity (ie increased respiration and restlessness, uncoordinated movement and staggering gait, muscular weakness, partial skeletal muscle paralysis, light to severe cyanosis, and tolerance of prone position. Corneal opacities or cloudiness in the eyes often occurred in mice just prior to or after death for the mice that died at all exposure levels. The LC₅₀was determined to be 15.42 mg/L (4950 ppm) at 48 hours and 12.49 mg/L (4010 ppm,) at 15 days after the exposure period.

Reference 5

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

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.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Diet: Rockland Rat Diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 1 week

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

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.

During exposure periods the concentrations of thiols within the chamber were determined routinely by absorption of vapors in either isopropyl alcohol or acetone containing an excess of silver nitrate and titrating the uncombined silver amperometrically.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

3050, 4500, 8340, or 11260 ppm (9.50, 14.02, 25.98, or 35.07 mg/L)

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: tissue specimens were submitted for pathologic examination after having first been examined grossly and preserved in either buffered formalin or Zenker's fixative.

Statistics:

LC50 values by inhalation were calculated by the method of Miller and Tainter, using logarithmic-probit graph paper.

Sex:

male

Dose descriptor:

LC50

Effect level:

7 300 other: ppm (analytical) (equivalent to 22.74 mg/L)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Mortality occured during the exposure period for rats exposed to 8340 and 11260 ppm (25.98 and 35.07 mg/L) of test substance. The cumulative results are presented in the data table below.

Clinical signs:

other: 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 weaknes

Toxicity Data on Four Hour Inhalation Exposures to Propane-1-thiol

Cumulative Mortality During and After Exposure in Rats

Analyzed Concentration (ppm)	0-4 Hours	24 Hours	48 Hours	15 Day
3050 (9.50 mg/L)	0/6	0/6	0/6	0/6
4500 (14.02 mg/L)	0/6	0/6	0/6	0/6
8340 (25.98 mg/L)	3/6	4/6	4/6	4/6
11260 (35.07 mg/L)	5/6	6/6
LC50(Estimated)			7300 (22.74 mg/L)

Interpretation of results:

GHS criteria not met

Executive summary:

In an acute inhalation toxicity study, groups of five male rats (Wistar derived) per dose were subjected to the whole-body exposure of propane-1-thiol vapors at concentrations of 3050, 4500, 8340, or 11260 ppm (9.50, 14.02, 25.98, or 35.07 mg/L). 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 during the exposure period for rats exposed to 8340 and 11260 ppm (25.98 and 35.07 mg/L) of test substance. Rats exhibited signs of intoxication, and maximal sublethal and lethal concentrations of thiols induced characteristic symptoms of toxicity such as 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 22.74 mg/L (7300 ppm) at 48 hours and 15 days post-exposure.

Reference 6

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

April 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd., Margate, Kent
- Age at reception: 6 to 8 weeks
- Housing: 5 males or 5 females to a polypropylene cages that had detachable wire mesh tops and floors and were suspended on a movable rack
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 53+/- 7.7
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

Vapour generator:
The generator was designed to produce and maintain an atmosphere containing the vapour of the test substance. All parts of the generator in contact with the test substance were made of glass. The test substance was supplied to the generator from a syringe driven at a constant rate by a syringe pump. The compressed air supply to the generator was dried, filtered and oil-free.

Exposure chambers:
The whole-body exposure chambers used for the exposures were of square section and were fitted with pyramidal tops. The chambers were made of perspex and had an internal volume of approximately 130L. Each chamber was divided by wire mesh partitions to provide 10 separate animal compartments.
The test atmosphere entered through a port at the base centre of the chamber and passed out through small holes in the lower edge of the square section. Each chamber was positioned inside a large cabinet equipped with an extract fan exhausting to atmosphere through a collection filter.

Procedure:
A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 25 litres per minute. An in-line flow meter was used to monitor air flow throughout the exposure. The water bath was set to 36°C. A syringe filled with the test substance was fitted to the syringe pump and connected to the generator with PTFE tubing. The flow rate was set at the rate selected during the preliminary work (0.18 ml/min). This was expected to give an atmosphere concentration of approximately 5 mg/1. The rats to be exposed were placed into separate compartments of the exposure chamber. The syringe pump was switched on and the exposure timed for 4 hours, following an equilibration period of 11 minutes (1). After 4 hours the supply of test substance was discontinued and the exposure chamber was allowed to clear before the rats were removed for examination. The control group was treated similarly but exposed to air only. Following exposure the rats were kept in a ventilated cabinet overnight and then returned to the holding room for the remainder of the observation period.

Chamber atmosphere analyses:
Five air samples were taken from the chamber during each completed exposure to determine the concentration of the test substance. The samples were drawn at a rate of 2 L/minute, through a gas absorption trap containing approximately 20 ml of methanol. The trap was maintained at -70°C (cardice/acetone} durinq sampling. The volume of the air samples was measured using a wet-type gas meter. Propane-1-thiol was analysed by gas chromatography.

Particle count:
A sample of air was withdrawn from the exposure chamber at 1 hour 30 mins and 3 hours 30 mins using a Royco model 218 optical particle counter. The particle count indicated a maximum of 45 particles <0.5 µm diameter in a 1 minute count. There were therefore no droplets of the test substance present.

Chamber air temperature:
The means and standard deviation (SD) of the means for the temperatures recorded during the exposure of the groups were:
Group Mean (°C) SD
27 {Control) 25 0.7
29 {Test) 22 0.4

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see above

Duration of exposure:

4 h

Concentrations:

5.663 mg/L (analytical)

No. of animals per sex per dose:

5 per sex per dose

Control animals:

yes

Details on study design:

Clinical signs:
The rats were observed continuously during exposure for signs of reaction to the test substance and at least twice daily during the 14-day observation period.

Bodyweights:
All rats were weighed daily from the day following delivery to the Huntingdon Research Centre until the end of the observation period.

Food and water consumption:
The food and water consumption for each cage of rats was determined daily by weight loss from the food hoppers and water bottles.

Terminal studies:
At the end of the 14-day observation period the rats were anaesthetised by intraperitoneal injection of pentobarbitone sodium and killed by exsanguination.
The rats killed at termination were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear of surrounding tissue and weighed in order to calculate the lung weight to bodyweight ratio. The lungs were infused with and preserved in buffered 10% formalin together-with samples of the liver and kidneys for possible microscopic examination.

Statistics:

None

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 5.663 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: No mortality

Mortality:

There were no deaths following exposure to propane-1-thiol vapour at a concentration of 5.663 mg/L

Clinical signs:

other: During exposure Signs of irritant effects including partial closing of the eyes, reduced respiration rate, abnormal respiration movements and adoption of a hunched body posture During the observation period Increased respiratory rate immediately followin

Body weight:

Weight gain by rats exposed to propane-1-thiol was reduced for 1 day (males) or up to 4 days (females) post exposure. No further data were presented.

Gross pathology:

Lung weight to bodyweight ratios were within normal limits for all rats with the possible exception of one that was exposed to propane-1-thiol vapour. No treatment-related findings were obserevd at gross necropsy.

Other findings:

Food consumption was reduced for 1 day for both sexes and water consumption was reduced for 1 day in male rats only following exposure to propane-1-thiol.

Interpretation of results:

study cannot be used for classification

Executive summary:

In an acute inhalation toxicity study, groups of young adult albino Sprague-Dawley rats (5/sex) were exposed whole body to propane-1-thiol for 4 hours to an analytical concentration of 5.663 mg/L. Animals then were observed for 14 days. There were no deaths following exposure to propane-1-thiol vapour at a concentration of 5.663 mg/l. During exposure there were signs of irritant effects including partial closing of the eyes, reduced respiration rate, abnormal respiration movements and adoption of a hunched body posture. Rats showed increased respiratory rate immediately following exposure, which subsequently returned to normal. Weight gain by rats exposed to propane-1-thiol was reduced for 1 day for males or up to 4 days for females post exposure. Lung weight to bodyweight ratios was within normal limits for all rats with the possible exception of one rat that was exposed to propane-1 -thiol vapeur. Macroscopic pathology revealed no treatrnent-related findings. The inhalation LC₀ was determined to be greater than 5.663 mg/l in males and females.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

20 000 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

Undiluted propane-2-thiol was administered dermally to one group of 6 rats. Surviving animals were observed for 7 days

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: WBS/W

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 210 g

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.46 ml/kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights

Statistics:

Not appropriate

Sex:

male

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

None

Clinical signs:

other: No toxic symptoms were induced. Initial skin contact evoked a mild pain reaction.

Gross pathology:

Not reported

Interpretation of results:

GHS criteria not met

Executive summary:

In a pre-guideline study, each of six rats (male WBS/W) was treated dermally with 2000 mg/kg bw (2.46 ml/kg bw) of iso-propyl mercaptan. Doses were applied under an impervious sleeve which was pre-fitted upon the fur-clipped trunk of each rat. The sleeves were removed 24 hours later and the animals were then observed for seven days. Initial vocalization and weight losses lasting up to 4 days were observed. The LD₀ was > 2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

October 11-25, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

other: EPA 40 CFR 163.81-2

Deviations:

yes

Remarks:

The rabbits were isolated in a specially ventilated room and the room temperature range was reduced to 15.5-22ºC to minimize the noxious odor of the test material. On day 6 the temperature rose to 26ºC due to an HVAC malfunction. The problem was corrected

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, Jamesburg, New jersey
- Weight at study initiation: 2.1 to 2.6 kg
- Housing: housed individually in wire bottomed cages
- Diet (e.g. ad libitum): e.g. ad libitum
- Water (e.g. ad libitum): e.g. ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.6 to 22
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 4-5 cm^2
- % coverage: 10
- Type of wrap if used: non-permeable patch secured with adhesive tape and an elastic sleeve.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped clean with a damp cloth
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g/kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations made twice per day; weights were taken on the day of dosing and on days 7 and 14
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Mortality:

One female rabbit died on day 5 of the observation period.

Clinical signs:

other: The rabbit that died on day 5 displayed the following clinical signs: lethargy, apparent loss of appetite, loss of gross reflexes, apparent drop in body temperature (i.e. cold to the touch) and loss of weight (1.0 kg). The surviving rabbits appeared activ

Gross pathology:

Gross necropsy of the single mortality revealed evidence of pulmonary hemorrhage, nasal discharge, and discoloration of the liver and spleen. Green discoloration around the mouth was also noted.
Gross autopsy of the survivors showed signs of organ discoloration (liver, spleen and thymus) and possible evidence of pulmonary hemorrhage.

Animal #	Sex	Body Weight			Actual Dose	Mortality	Autopsy
		Initial (kg)	1^stWeek (kg)	Final (kg)	g	day
4664	M	2.1	2.7	2.4	5.0	E	PH
4665	M	2.2	2.3	2.1	5.3	E	PH;DGI
4666	M	2.5	2.8	2.5	6.0	E	PH;DGI;DT
4667	M	2.5	2.7	2.3	6.0	E	PH;DGI;DT;DS;DL
4668	M	2.1	2.4	2.1	5.0	E	PH;DT;DL;ND
4669	F	2.2	--	1.2	5.3	5	PH;DL;DS;ND
4670	F	2.3	2.4	2.2	5.5	E	PH;DT;DL;
4671	F	2.4	2.6	2.2	5.8	E	PH;DT;DL
4672	F	2.5	2.6	2.3	6.0	E	PH
4673	F	2.6	2.7	2.4	6.2	E	ND;PH

E - Euthanized

PH - Puimonary hemorrhage

DGI - Distended gaseous Intestine

DT - DIscolored thymus

OS - Discolored spleen

DL - Discolored liver

NO - Nasal discharge

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

In this study, one out of ten rabbits given a single dermal dose of propane-1-thiol died before the end of the 14 day observation period, therefore the LD50 is greater than 2,000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study, groups of New Zealand Albino rabbits (5/sex) were dermally exposed to propane-1-thiol for 24 hours to 10% of body surface area at doses of 2000 mg/kg bw. Animals then were observed for 14 days. The rabbit that died on day 5 displayed the following clinical signs: lethargy, apparent loss of appetite, loss of gross reflexes, apparent drop In body temperature (i.e. cold to the touch) and loss of weight (1.0 kg). The surviving rabbits appeared active and behaved normally. Several rabbits, sporadically, did not eat on isolated days. The test application site on each of the rabbits was erythematous and in some instances the skin was thickened. Gross necropsy of the deceased and surviving animals revealed evidence of pulmonary hemorrhage and discoloration of the liver and spleen. The dermal LD₅₀ was determined to be greater than 2,000 mg/kg in males and females.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Justification for classification or non-classification

No classification is warranted according to CLP criteria.