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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:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline conform GLP study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
other: Rat Ico : OFA.SD. (IOPS Caw)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA-CREDO, L'Arbresle Cedex - France
- Age at study initiation: 5 to 7 weeks
- Weight at study initiation: 130-220 g (males), 120-190 g (females)
- Fasting period before study: overnight (15-20 h before dosing)
- Housing: in groups of up to 5 of the same sex and dose group in polycarbonate cages type FI for preliminary study and type MI for the main study
- Diet (e.g. ad libitum):pelleted complete diet (Diet reference A04 C10, Usine d#Alimentation Rationelle, Villemoisson, Epinay, France), ad libitum
- Water (e.g. ad libitum): softened and filtered drinking water, ad libitum
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 40-70%
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1 % aqueous dispersion of carboxymethylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
2.5%, 5.0% and 10% (w/v) - preliminary study; 5.00%, 6.30% and 7.95% (w/v) - main study
- Amount of vehicle (if gavage): 20 mL/kg
- Lot/batch no. (if required): house preparations 22. Aug 1995 and 12. Sept. 1995



Doses:
- Preliminary study:
500, 1000 and 2000 mg/kg bw
- Main study:
0, 1000, 1260 and 1590 mg/kg bw
No. of animals per sex per dose:
- Preliminary study:
2
- Main study:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration:
14 days
- Frequency of observations and weighing:
Examinations for mortality and abnormal clinical signs were performed 15 min after intubation, then 1, 2 and 4 hours, and then daily for the 14 day study period. All the animals were weighed on the day before treatment, immediately before administration of the test item, on days 8 and 15, as well as at time of death from day 2 onwards
- Necropsy of survivors performed:
yes
Statistics:
LD50 calculation:
- Bliss' method
- Litchfield & Wilcoxon' s method

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 253 mg/kg bw
95% CL:
1 054 - 1 490
Mortality:
Main study:
Male: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 1260 mg/kg bw; Number of animals: 5; Number of deaths: 3
Male: 1590 mg/kg bw; Number of animals: 5; Number of deaths: 4
Female: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 3
Female: 1260 mg/kg bw; Number of animals: 5; Number of deaths: 1
Female: 1590 mg/kg bw; Number of animals: 5; Number of deaths: 4
Clinical signs:
- Mortality
Mortality occurred from 1 hour to 4 hours after treatment in all groups.

- Clinical signs
Abnormal clinical signs in the treated animals appeared 1 hour after administration of the test item. Lethargy, prostratio, subdued behaviour and tremors were observed until 4 hours after treatment.


- Necropsy:
There were no macroscopic findings that could bee associated with treatment in animals which died during the observation period or killed at the end of the study.
Body weight:
- Body weights
The body weight changes in group 2 males (1000 mg/kg bw) and group 3 females (1260 mg/kg bw) were similar to those of the controls throughout the observation period. The mortality rate noted in group 2 females, group 3 males and both sexes of group 4 (1590 mg/k g bw) did not allow analysis of their body weight gain.
Gross pathology:
- Necropsy:
There were no macroscopic findings that could bee associated with treatment in animals which died during the observation period or killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
From the results obtained under the experimental conditions of this OECD 401 study the LD50 was derived at 1253 mg/kg bw.
Executive summary:

The test item was tested for its acute oral toxicity potential. 5male and 5 female rats were treated with doses of 0, 1000, 1260 or 1590 mg/kg bw and observed for 14 days.

The median lethal dose of test item (LD50) was 1253 mg per kg body weight. Based on the result of this study the test substance has to be labelled as harmful (H 302) according to regulatory requirements.