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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 10, 1990 to August 07, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: E.E.C.: Directive 84/449
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium 2-mercaptopropionate
EC Number:
236-526-4
EC Name:
Ammonium 2-mercaptopropionate
Cas Number:
13419-67-5
Molecular formula:
C3H9NO2S
IUPAC Name:
ammonium 2-sulfanylpropanoate
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species, strain: Ico rat OFA.SD. (IOPS Caw),
Supplier: Iffa-Credo (69592 L'Arbresle Cedex - France),
Age: young adults between 5 and 7 weeks old.
Weight at the start of treatment (main study): from 117 g to 160 g (the individual weighs for each sex varied by no more than 20 % of the mean weight of the animals).

Environmental conditions:
Cages housed by sex and in groups of 5 (or 2 for the preliminary study), in type FI polycarbonate cages (interior dimensions 305 x 180 x 184 mm) for the preliminary study and in type MI (interior dimensions 365 x 225 x 180 mm) for the main study.
Air changes: at least 10 per hour
Temperature: 22 ± 3 °C
Humidity: 30 to 70 %
Lighting: artificial, 12 hours out of 24.
Hygiene: bedding changed once a week; cages changed for each study.
Diet: complete pelleted rat-mouse maintenance diet ad libitum (U.A.R., formula A.04 CR - U.A.R.).
Water: softened and filtered (0.6 µm) mains drinking water ad libitum. Bacteriological and chemical analyses checked twice a year.
Acclimatisation period: 8 days before the start of treatment.
Clinical examinations: at reception then before the start of treatment to ensure that only healthy animals are included in the study.
Identification of animals: perforation of ear pinna before the start of treatment.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Single oral administration by gestric gavage - round –ended curved stainless-steel oesophageal probe, 3 mm diameter, Perfektum.
Doses:
Preliminary test: 499, 998 and 2007 mg/kg
Main test: 1125, 1415, 1601 and 1786 mg/kg
No. of animals per sex per dose:
Preliminary study: 6 males, 6 non-pregnant females;
Main study:
control group - 5 males, 5 non-pregnant females;
groups 2 to 5 (treated) - 20 males, 20 non-pregnant females.
Control animals:
yes
Details on study design:
Preliminary test:
3 groups each composed of 2 males and 2 females were treated, at dose levels of 499, 998 and 2007 mg/kg respectively at a volume of 0.43, 0.86 and 1.73 ml/kg of test substance as supplied. The test substance was administered after about 18 h of a water regime and received food 4 h after intubation.

Main test:
Five groups of 5 females and 5 males were dosed with at the levels of 1125, 1415, 1601 and 1786 mg/kg, corresponding to 0.97, 1.22, 1.38 and 1.54 ml/kg respectively. The control group was treated with the distilled water under the same conditions. The test article was administered once only after about 17 h of a water regime and received food 4 h after intubation.

Following examinations were performed:
- Clinical examinations: 15 minutes after intubation, then at 1, 2 and 4 hours and then daily for 14 days.
The daily observations performed, amongst others, included changes in the skin and fur, the eyes, mucous membranes, respiratory system, circulatory system, autonomic and central nervous systems, as well as somato-motor activity and behaviour. Shivering, convulsions, salivation, diarrhoea, lethargy, sleeping and coma were noted with particular attention.
- Observation of body weight: Day -1, Days 1 (before administration of the test article), 8 and 15, as well as at the time of death from Day 2 onwards.
- Necropsy examination of all animals. The abdominal and thoracic cavities were opened and particular attention was paid to the following organs: liver, heart, kidneys and lungs.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 518 mg/kg bw
Based on:
test mat.
95% CL:
> 1 435 - < 1 606
Mortality:
20 % in 1415 mg/kg dose level; 80 % in 1601 mg/kg dose level; 90 % in 1786 dose level.
Clinical signs:
other: At all tested doses: all animals showed subdued behaviour 15 min, 1, 2 and 4 h after administration of the test substance. At 1125 mg/kg: all surviving animals were normal on the day following treatment. At 1415 mg/kg: one rat showed tremors at 1 h. All
Gross pathology:
Animals which died during the study showed congested area in the lungs. No macroscopic determinable abnormality was noted in animals killed on study termination.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Under the study conditions, the LD50 of the test substance in the rat (male and female) was determined to be 1518 mg/kg bw (1435-1606) by the Bliss method and 1522 mg/kg bw (1421-1630) by the Litchfield & Wilcoxon’s method.
Executive summary:

A study was conducted to determine the potential toxic effect of the test substance when administered as a single oral dose to Wistar rats according to OECD Guideline 401 and EC Directive 84/449. Five groups of 5 females and 5 males were dosed with the test substance at the levels of 1125, 1415, 1601 and 1786 mg/kg. The control group was treated with the distilled water under the same conditions. Mortality and abnormal clinical signs were noted 15 minutes after intubation, then at 1, 2 and 4 h, and then daily for the 14 d study period. All the animals were weighed the day before treatment (Day -1), immediately before administration of the test substance (Day 1), on Days 8 and 15, as well as at time of death from Day 2 onwards. A necropsy was performed for all the animals dead during the study and for all surviving rats after the 14 d study period and the final observation (Day 15). Under the study conditions, the LD50 of the test substance in the rat (male and female) was determined to be 1518 mg/kg bw (1435-1606) by the Bliss method and 1522 mg/kg bw (1421-1630) by the Litchfield & Wilcoxon’s method (Lheritier, 1990).