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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1981-02-81 to 1981-04-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: UBTL protocol no. 04-50
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
UBTL Laboratory Notebook/Data File #035

Test material

Constituent 1
Chemical structure
Reference substance name:
Propane-1-thiol
EC Number:
203-455-5
EC Name:
Propane-1-thiol
Cas Number:
107-03-9
Molecular formula:
C3H8S
IUPAC Name:
propane-1-thiol
Details on test material:
- Name of test material (as cited in study report): propane-1-thiol

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Simonson Labs
- Weight at study initiation: 150 to 300 grams
- Fasting period before study: 1 day
- Housing: caged individually in stainless steel cages with screen floors and pans or in polycarbonate boxes using wood shavings
- 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 (%): 30 to 60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
An oral screen was completed on 5 animals per sex at 4,200 mg / kg. Nine of these animals had died by day 2 of the study, making further testing necessary at lower dose levels. A range finding study was completed at varying doses ranging from 840 mg / kg to 4,200 mg/kg; 4 dose levels were selected from these data for the LD50 study: 1,680 mg/ kg, 2,016 mg / kg, 2,436 mg / kg, 2,940 mg / kg
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 2 times per day for the first 3 days, then 1 time per day for 14 days total.
- Necropsy of survivors performed: yes
- Other examinations performed: body weight

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 864 mg/kg bw
Mortality:
During the acute oral screen, nine out of the 10 animals dosed at 5 ml/kg (4,200 mg / kg) had died by the end of day two. Mortality occured at all dosage levels during the acute toxicity study, but varied based on the dose. Ten animals were exposed at each dose, 5 died at 1,680 mg/kg, 4 died at 2,016 mg/kg, 8 died at 2,436 mg/kg, and 9 died at 2,940 mg/kg.
Clinical signs:
In group 1 (1,680 mg/kg), all 5 females died by day 2. Prior to death, these animals exhibited the pharmacological symptoms of staggering, docile to no activity, and ruffed fur. Some of the males in group I demonstrated such symptoms as ruffed fur, docile, and eye closure, but returned to normal by day 6 of the observation period. In group 2 (2,016 mg/kg), 4 females died on day 1. Prior to death, some of these animals exhibited such symptoms as ruffed fur, no activity, staggering, and a respiratory condition (i.e. blood stains around nose). Some of the remaining animals in group 2 demonstrated a variety of symptoms such as ruffled fur, docility and eye closure, but returned to normal by day 7 of the observation period. All 5 females died in group 3 (2,436 mg/kg), 3 on day 1 and 2 on day 2. Prior to death, some of these animals exhibited such symptoms as ruffed fur, staggering, and no activity. Three males died in group 3, 1 on day 1 and 2 on day 2. Prior to death, some of these animals exhibited symptoms of ruffed fur, squinting eyes, docile to no activity, and one animal developed paralysis. The remaining two males demonstrated ruffed fur, but returned to normal by day 3 of the observation period. All 5 females died in group 4 (3.5 ml/kg), 4 on day 1 and 1 on day 2. Prior to death animals exhibited ruffed fur, lacrimation, docile to no activity, staggering, paralysis and a respiratory condition (i.e., blood stains around nose). Four males died in group 4 (2,940 mg/kg), 1 on day I, 2 on day 2, and 1 on day 3. Prior to death, these males developed symptoms similar to the females, except for 1 animal which developed squinting eyes. The surviving male developed ruffed fur and was docile but returned to normal by day 6 of the observation period.
Body weight:
On day of dosing, all groups showed comparable mean fasted body weights. On day 7, all 4 groups showed a weight gain, with the weight gain being greatest in group 2. From day 7 to day 14, all 4 groups gained weight, with group 2 gaining less weight than the other 3 groups.
Gross pathology:
In all 4 groups, the animals showed abnormalities in some of the following tissue: lungs, liver, stomach, intestines, kidneys, spleen, adrenals, and 1 animal in each group exhibited a mushy brain. Thymus abnormalities were also observed in groups 3 and 4. The skin of 1 animal in group 2 exhibited a green tint, and the skin of 1 animal in group 3 had diffused blood vessels.

Any other information on results incl. tables

Table 1. Acute Oral Trxicity LD 50 Study - DemonstratingNumberof AnimalsResponding

UBTL # 05450-4

Sample # Phillipsn-propyl mercaptan

Group #

1

2

3

4

Dose Level

1,680 mg / kg

2,016 mg / kg

2,436 mg / kg

2,940 mg / kg

Sex (no. of animals)

Male

(5)

female

(5)

Male

(5)

female

(5)

Male

(5)

female

(5)

Male

(5)

female

(5)

SYMPTOMS:

 

Cardiovascular cond.

0

0

0

0

0

0

0

0

Respiratory cond.

0

0

0

1

0

0

2

1

Excretory cond.

0

0

0

0

0

0

0

0

Behavioral cond.

1

5

1

4

2

5

5

3

Staggering

0

1

0

1

0

1

0

1

Lack of coordination

0

0

0

0

0

0

0

0

Paralysis

0

0

0

0

1

0

0

1

Pupillary reaction

0

0

0

0

0

0

0

0

Eyes

1

0

0

1

1

0

1

1

Other

4

5

3

4

3

2

3

1

OUTCOME:

 

Normalthroughout test

1

0

2

0

0

0

0

0

Normalat end of test

4

0

3

1

2

0

1

0

Symptoms present at day 14

0

0

0

0

0

0

0

0

death

0

5

0

4

3

5

4

5

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
This study reported mortality and toxicity in rats exposed to a single oral dose of propane-1-thiol.
Executive summary:

In an acute oral toxicity study, groups of fasted, adult Sprague-Dawley albino rats (5/sex) were given a single oral dose of propane-1-thiol by oral gavage at doses of 1,680, 2,016, 2,436, or 2,940 mg/kg bw and observed for 14 days. 

 

An acute oral screen was conducted on 5 animals per sex at 4,200 mg/kg. Nine of these animals had died by day 2 of the study, and therefore further testing was necessary. Clinical signs were observed at all dose levels in the subsequent acute oral toxicity study. Clinical signs observed in rats included staggering, docile to no activity, eye closure, and ruffled fur. On day of dosing for the acute oral toxicity study, all groups showed comparable mean fasted body weights. On day 7, all 4 groups showed a weight gain, with the weight gain being greatest in group 2. From day 7 to day 14, all 4 groups gained weight, with group 2 gaining less weight than the other 3 groups. Mortality occurred at all dosage levels during the acute toxicity study, but varied based on the dose. Ten animals were exposed at each dose, 5 died at 1,680 mg/kg, 4 died at 2,016 mg/kg, 8 died at 2,436 mg/kg, and 9 died at 2,940 mg/kg. The oral LD50 was determined to be 1,864 mg / kg bw in males and females.

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because it was conducted in accordance to GLP and was reviewed by Quality Assurance. There were no deviations from protocol. This study may influence the DNEL.