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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst Aktiengesellschaft, Kastengrund, SPF breeding colony
- Females (if applicable) nulliparous and non-pregnant: [yes/no] yes
- Age at study initiation: male 6-8 wk, female 8 wk
- Weight at study initiation: male mean = 182 g+-15
female mean = 173 g +- 6
- Fasting period before study: no data
- Housing: in fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals
- Diet (e.g. ad libitum): ssniff® R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least one day (breeding at identical conditions)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h daily

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sesame oil (Oleum sesami)
Doses:
The following dose levels of Crotonsäureanhydrid were tested:

Dose Concentration Volume applied Number of
mg/kg b.w. in % (w/v) (ml/kg body weight) males females
1250 12.5 10 5
1600 16.0 10 5 -
1800 18.0 10 5 -
2000 20.0 10 5 5
2500 25.0 10 5 -
Control animals:
no
Statistics:
The LD50, the 95 % limits of confidence and the equation of the probitline were established in male animals on the basis of the lethality rates by probit analysis.
(method of FELLER and SIDAK, programs supplied by Pharma Informatic, Hoechst Aktiengesellschaft).

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 061 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 847 - <= 2 512
Mortality:
Under the conditions described above, the following lethality rates were observed:

Lethality
Dose male animals female animals
mg/kg b.w. absolute relative (%) absolute relative (%)

1250 0/5 0
1600 0/5 0
1800 0/5 0
2000 4/5 80 0/5 0
2500 4/5 80
Body weight:
Development of body weight was not impaired.
The following clinical signs were observed after the application of Crotonsäureanhydrid: decreased spontaneous activity, squatting posture, sunken flanks, bristled coat, irregular respiration, panting, respiratory sounds, stilted gait, uncoordinated and ataxic gait, reduced or no placing reaction, reduced pawreflex to pinching, stupor, prone position, narrowed palpebral fissures, pale skin, cyanosis, increased salivation and diarrhea. All clinical signs had reversed in the surviving animals two days after application.
Gross pathology:
Macroscopic examination of the animals found dead revealed the following findings:
- liver light discoloured
- kidneys light discoloured
- diffuse reddening of the stomach mucosa
- stomach full of gas
- diffuse reddening of the intestinal tract
- diffuse reddening of the small intestine
The animals killed at the end of the observation period showed no macroscopically visible changes.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on the results obtained in this study the median lethal dose value (LD50) of Crotonsäureanhydrid was calculated by probit analysis for the male Wistar rat to be 2061 mg/kg body weight.