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Administrative data

Description of key information

The first acute oral toxicity study, conducted according to a protocol similar to OECD 420 Test Guideline and prior to CLP, reported a LD50 value of 1790 mg/kg bw for propane-1-thiol (Fairchild, 1958).

The second acute oral toxicity study, conducted according to a protocol similar to the now deleted OECD 401 Test Guideline and in compliance with GLP, reported a LD50 value of 1848 mg/kg bw for propane-1-thiol (UBTL, 1981).

The key acute inhalation toxicity study, conducted according to a protocol similar to OECD 436 Test Guideline without information on GLP compliance, reported a LC50 value of greater than 5.663 mg/L for propane-1-thiol (Hardy, 1987).

The first acute dermal toxicity study, conducted according to a protocol similar to OECD 402 and in compliance with GLP, reported a LD50 value greater than 2000 mg/kg bw for propane-1-thiol (Shapiro, 1985).

The second acute dermal toxicity study, conducted according to a protocol similar to OECD 402 and in compliance with GLP, reported a LD50 value greater than 1680 mg/kg bw for propane-1-thiol (Moon, 1981).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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:
guideline study with acceptable restrictions
Remarks:
well conducted and documented and generally follows OECD Guideline 420
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
yes
Remarks:
maximum three doses exceeded guideline recommended dose; animal fasting was not reported; animals were not weighed; pathology and clinical observations were generalized across dose levels of all chemicals tested
GLP compliance:
not specified
Test type:
fixed dose procedure
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:
VEHICLE : No vehicle used

MAXIMUM DOSE VOLUME APPLIED: 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).)
Preliminary study:
No data reported
Key result
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:
Toxicity signs included sedative action, and maximal sublethal doses resulted in deep comatose sleep for approximately 48 hours. Diarrhoea was also pronounced for the highest doses.
Body weight:
No data reported
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 (4th)

1/5

1/5

2107

2/5

3/5

3/5

4/5 (9th)

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 propanethiol 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 propanethiol 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. Diarrhoea 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. This study is classified as Toxicity Category IV by EU classification.

 

This study was classified as supporting because of limited detailed clinical and necropsy findings. This study received a Klimisch score of 2 and is classified as reliable with restrictions because it was well conducted and documented and generally follows OECD Guideline 420. This study may influence the DNEL.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Method: other: Similar to OECD 401 and OPPTS 870.1100
GLP compliance:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: none
Details on oral exposure:
fasting prior to dose administration
Doses:
2.0(1.68), 2.4(2.02), 2.9(2.44), 3.5(2.94) ml/kg bw (g/kg bw)
No. of animals per sex per dose:
5
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed daily, weighed prior to study initiation and days 7 and 14
- Necropsy of survivors performed: yes
Statistics:
LD50 calculated with Probit analysis.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 848 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2.2 mL/kg bw
95% CL:
> 1.04 - < 2.62
Mortality:
All five (5) low dose females died by day 2 post-dosing. All low dose males survived. Four (4) of five females died  in the 2.02 g/kg bw dose group on day 1.  All 2.02 g/kg bw dose males survived. All five (5) 2.44 g/kg bw females died, three (3) on day 1 and two (2) on day 2 post-dosing. Three (3) of five 2.44 g/kg bw males died, one (1) on day 1 and two (2) on day 2 post-dosing.
Clinical signs:
All low dose female animals exhibited docility, staggering and ruffed fur. The low dose males displayed signs similar to the females, along with eye closure but  returned to normal by day 6 post-dosing.  Signs of the 2.02 g/kg bw females were similar to those seen in low dose males and females, along with blood stains around the nose. The surviving female returned to normal by day 7 post-dosing. Males showed similar signs. Surviving 2.44 g/kg bw males returned to normal by day 3 post-dosing. For the females, signs prior to death included ruffed fur, docility, lacrimation, staggering, and blood stains about the nose. The surviving high-dose male returned to normal by day 6 post-dosing.
Gross pathology:
Post-mortem examination of animals dying on test was conducted within 16 hours of death. Survivors were necropsied immediately after study termination (day 14 post-dosing). In all four dose groups animals showed abnormalities in some of the following tissues (details of these findings were not included): lungs, liver, stomach, intestines, kidneys, brain, spleen, adrenals. Thymic abnormalities were noted at 2.44 and 2.94 mg/kg bw.

Clinical Observations: All five (5) low dose females died by day 2 post-dosing. These animals exhibited docility, staggering and ruffed fur. All low dose males survived. The males displayed signs similar to the females, along with eye closure but returned to normal by day 6 post-dosing. Four (4) of five females died in the 2.02 g/kg bw dose group on day 1. Signs were similar to those seen in low dose males and females, along with blood stains around the nose. The surviving female returned to normal by day 7 post-dosing. All 2.02 g/kg bw dose males survived and displayed signs similar to the females.    

 

All five (5) 2.44 g/kg bw females died, three (3) on day 1 and two (2) on day 2 post-dosing. Three (3) of five 2.44 g/kg bw males died, one (1) on day 1 and two (2) on day 2

post-dosing. Signs prior to death were similar to those reported for the females.  

 

Surviving 2.44 g/kg bw males returned to normal by day 3 post-dosing.  Nine (9) high-dose males and females died (5/5 females; 4/5 males). Four (4) of five females died on day 1, while one (1) male died. The remaining female died on day 2, while two (2) males died on day 2 and one (1) on day 3 post-dosing. Signs prior to death included ruffed fur, docility, lacrimation, staggering, and blood stains about the nose. The surviving high-dose male returned to normal by day 6 post-dosing.  

 

Gross Pathology:  

Post-mortem examination of animals dying on test was conducted within 16 hours of death.  Survivors were necropsied immediately after study termination (day 14 post-dosing). In all four dose groups animals showed abnormalities in some of the following tissues (details of these findings were not included): lungs, liver, stomach, intestines, kidneys, brain, spleen, adrenals. Thymic abnormalities were noted at 2.44 and 2.94 mg/kg bw.

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Using probit analysis, the oral LD50 is 2.2 mL/kg with 95% confidence limits of 1.04 to 2.62 mL/kg. The LD50 was corrected using density of 0.84 to 1848 mg/kg.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 790 mg/kg bw

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:
1987-09-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No information on GLP compliance
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Deviations:
yes
Remarks:
only one concentration was tested
GLP compliance:
not specified
Test type:
acute toxic class method
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 study initiation: 6 to 8 weeks
- Housing: polypropylene cages that had detachable wire mesh tops and floors and were suspended on a movable rack
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
No data reported
Duration of exposure:
>= 4
Concentrations:
5.663 mg/L
No. of animals per sex per dose:
5 per sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.663 mg/L air
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:
Food and water consumption was reduced among exposed males and females for 1 day. 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.
Other findings:
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 observed at gross necropsy (no further details presented in report).
Interpretation of results:
GHS criteria not met
Conclusions:
This study reported no toxic effects in rabbits exposed via inhalation to propane-1-thiol.
Executive summary:

In an acute inhalation toxicity study, groups of young adult albino Sprague-Dawley rats (5/sex) were exposed by inhalation route to propane-1-thiol for 4 hours to whole body at a 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. The inhalation LC50 was determined to be greater than 5.663 mg/l in males and females.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because, although only summary results were presented, there was good data on test conditions and substance but no mention of GLP compliance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 663 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1981-01-05 to 1981-02-13
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
This study is classified as reliable with restrictions because it was GLP compliant and follows OECD guideline 402 except that less animals then required by current guidelines were used.
Qualifier:
according to guideline
Guideline:
other: UBTL test protocol No. 05-50
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
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: The University of Utah Vivarium
- Housing: stainless steel cages with screen floors and a stainless steel pan containing a sheet of absobent material
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3
- Humidity (%): between 30 and 60 with a median of 45
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: heavy plastic bag that has been wraped with fabric and secured with tape

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg (1,680 mg/kg)
Duration of exposure:
24 hours
Doses:
one
No. of animals per sex per dose:
three
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 680 mg/kg bw
Mortality:
Animal death was not observed
Clinical signs:
All 6 rabbits exhibited erythema and induration. One male and two females also exhibited eschar formation.
Body weight:
The combined mean weight gain from day of dosing to day 7 was approximately 96 grams, while the combined mean weight gain from day 7 to day 14 was approximately 82 grams.
Gross pathology:
All rabbit tissue appeared to be normal with the exception of one, whose upper right lung lobe appeared blistery and rough.

Mean Weights (grams)

 

Males

Females

Combined

Day of Dosing

2638.7

2177.0

2407.9

Day 7

2663.0

2344.7

2503.9

Day 14

2723.0

2449.0

2586.0

Interpretation of results:
GHS criteria not met
Conclusions:
This study reported no toxic effects in rabbits exposed dermally to propane-1-thiol.
Executive summary:

In an acute dermal toxicity study, 6 young adult New Zealand albino rabbits (3/sex) were dermally exposed to propane-1-thiol for 24 hours at doses of 1680 mg/kg bw (2 mL/kg). Animals then were observed for 14 days for signs of toxicity. Animals were necropsied and organs examined for gross pathology at study termination.

 

No treatment-related symptoms of mortality or toxicity were observed, with the exception of local effects such as erythema and induration. One male and two females also exhibited eschar formation. One female also exhibited docility for 1 day and nasal drainage for 1 day. Gross necropsy was performed and all rabbit tissue appeared to be normal with the exception of on animal whose upper right lung lobe appeared blistery and rough. The combined mean weight gain from day of dosing to day 7 was approximately 96 grams, while the combined mean weight gain from day 7 to day 14 was approximately 82 grams.  Because animal death was not observed, the Dermal LD50 for propane-1 -thiol is greater than 1680 mg/kg (2 ml/kg) in rabbits.

 

This study received a Klimisch score of 1 and is classified as reliable with restrictions because it was GLP compliant and follows OECD guideline 402 except that less animals then required by current guidelines were used. This study may influence the DNEL.

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:
comparable to guideline study with acceptable restrictions
Remarks:
This study is classified as reliable with restrictions because it was conducted according to GLP regulations, and sufficient number of rabbits used. Close to OECD guidelines.
Qualifier:
according to guideline
Guideline:
other: PSL Protocol No. 013
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
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
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:
2 g/kg bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
not specified
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
Key result
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:
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.
Body weight:
At the end of the observation period one male gained 0.3 kg; two males remained at their initial weight and the remaining survivors lost 0.1 - 0.2 kg.
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)

1stWeek (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:
GHS criteria not met
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 2 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.

 

This study received a Klimisch score of 1 and is classified as reliable with restrictions because it was conducted according to GLP regulations, was well documented and a sufficient number of rabbits used. This study may influence the DNEL.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
1 680 mg/kg bw

Additional information

The first acute oral toxicity study, conducted according to a protocol similar to OECD 420 Test Guideline and prior to CLP, reported a LD50 value of 1790 mg/kg bw (Fairchild, 1958). 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. Diarrhoea 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. 

The second acute oral toxicity study, conducted according to a protocol similar to the now deleted OECD 401 Test Guideline and in compliance with GLP, reported a LD50 value of 1848 mg/kg bw (UBTL, 1981). Using probit analysis, the oral LD50 is 2.2 mL/kg with 95% confidence  limits of 1.04 to 2.62 mL/kg.  The LD50 was corrected using density of  0.84 to 1848 mg/kg.

Groups of Sprague-Dawley rats were given a single oral dose of propanethiol undiluted at doses of 2.0(1.68), 2.4(2.02), 2.9(2.44), 3.5(2.94) ml/kg bw (g/kg bw) observed for 14 days. All five (5) low dose females died by day 2 post-dosing. All low dose males survived. Four (4) of five females died  in the 2.02 g/kg bw dose group on day 1.  All 2.02 g/kg bw dose males survived.  All five (5) 2.44 g/kg bw females died, three (3) on day 1 and two (2) on day 2 post-dosing.  Three (3) of five 2.44 g/kg bw males died, one (1) on  day 1 and two (2) on day 2 post-dosing.

All low dose female animals exhibited docility, staggering and ruffed fur.  The low dose males displayed signs similar to the females, along with eye closure but  returned to normal by day 6 post-dosing.  Signs of the 2.02 g/kg bw  females were similar to those seen in low dose males and females, along with blood stains around the nose. The surviving female returned to normal by day 7 post-dosing.  Males showed similar signs.  Surviving 2.44 g/kg bw males returned to normal by day 3 post-dosing.  For the females, signs prior to death included ruffed fur, docility, lacrimation, staggering, and blood stains about the nose.  The surviving high-dose male returned to normal by day 6 post-dosing.  Post-mortem examination of animals dying on test was conducted within 16 hours of death.   Survivors were necropsied immediately after study termination (day 14 post-dosing).  In all four dose groups animals showed abnormalities in some of the following tissues (details of these findings were not included):  lungs, liver, stomach, intestines, kidneys, brain, spleen, adrenals.  Thymic abnormalities were noted at 2.44 and 2.94 mg/kg bw.

Another two low reliability acute oral toxicity studies were also available, which supported the findings of the two weight of evidence studies (Moon, 1981 and Pepper, 1981).

The key acute inhalation toxicity study, conducted according to a protocol similar to OECD 436 Test Guideline without information on GLP compliance, reported a LC50 value of greater than 5.663 mg/L (Hardy, 1987).

Groups of young adult albino Sprague-Dawley rats (5/sex) were exposed by inhalation route to propane-1-thiol for 4 hours to whole body at a 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. The inhalation LC50 was determined to be greater than 5.663 mg/l in males and females.

There are five low reliability acute inhalation studies which support the finding of the key study (Fairchild, 1958; Pharmacology Research, 1976; Latven, 1958; Fairchild, 1958; Yates, 1981).

The first acute dermal toxicity study, conducted according to a protocol similar to OECD 402 and in compliance with GLP, reported a LD50 value greater than 2000 mg/kg bw (Shapiro, 1985).

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 2 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 haemorrhage and discoloration of the liver and spleen. The dermal LD50 was determined to be greater than 2,000 mg/kg in males and females.

The second acute dermal toxicity study, conducted according to a protocol similar to OECD 402 and in compliance with GLP, reported a LD50 value greater than 1680 mg/kg bw (Moon, 1981).

In the study, 6 young adult New Zealand albino rabbits (3/sex) were dermally exposed to propane-1-thiol for 24 hours at doses of 1680 mg/kg bw (2 mL/kg). Animals then were observed for 14 days for signs of toxicity. Animals were necropsied and organs examined for gross pathology at study termination. 

No treatment-related symptoms of mortality or toxicity were observed, with the exception of local effects such as erythema and induration. One male and two females also exhibited eschar formation. One female also exhibited docility for 1 day and nasal drainage for 1 day. Gross necropsy was performed and all rabbit tissue appeared to be normal with the exception of on animal whose upper right lung lobe appeared blistery and rough. The combined mean weight gain from day of dosing to day 7 was approximately 96 grams, while the combined mean weight gain from day 7 to day 14 was approximately 82 grams.  Because animal death was not observed, the dermal LD50 for propane-1 -thiol is greater than 1680 mg/kg (2 ml/kg) in rabbits.

There is another acute dermal toxicity study available which supports the findings of the two weight of evidence studies (Latven, 1976).

Justification for classification or non-classification

Based on the available data for propane-1-thiol, classification for acute oral toxicity Category 4 "H302: Harmful if swallowed." is required according to Regulation (EC) No 1272/2008.