Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-07-02 till 1996-08-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study under GLP without restrictions

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))
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CA 2342 A (Intermediate of CGA 293343)
- Substance type: Intermediate
- Physical state: solid
- Analytical purity: 98%
- Purity test date: reanalysis December 1997
- Lot/batch No.: P.601014
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
other: white albino (Tif: RAI f (SPF), bred ahd raised on the premises)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Stein / Switzerland
- Age at study initiation: no data
- Weight at study initiation: 173 to 205 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight
- Housing: The animals were housed in Macrolon cages type 4, with standardized soft wood bedding
- Diet (e.g. ad libitum): Rat diet - NAFAG 890 provided ad libitum
- Water (e.g. ad libitum): provided ad libitum
- Acclimation period: at least for 5 days before administration


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2 °C
- Humidity (%): relative humidity of 55 +/- 10%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours day light cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: test substance concentration in vehicle 200 mg/ml
- Amount of vehicle (if gavage): 10 ml per kg body weight
- Justification for choice of vehicle: no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 2.05 ml
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily for 14 days
- Frequency of weighing: before administration and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: There were no in-life observations indicating treatment related systemic effects
Statistics:
no statistical analysis was used

Results and discussion

Preliminary study:
The dose level was selected according to OECD 401 (limit test; single application of 2000 mg/kg body weight).
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived to the scheduled sacrifice.
Clinical signs:
There were no in-life observations indicating treatment-related systemic effects
Body weight:
A loss of body weight was recorded in one female rat (no. 102) during the second week after treatment
Gross pathology:
At necropsy, no deviations from normal morphology were found in all animals

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The substance is not classified as acute oral toxic by EU-GHS (CLP), since LD50 > 2000 mg/ kg body weight, which is the cut-off in the EU's GHS classification system. UN-GHS has a Category 5 for acute oral toxicity for the dose range 2000 mg/kg bw < LD50 < 5000 mg/kg bw, a concentration range which has not been tested. However acute toxicity Category 5 is applied by some authorities only. Furthermore, acc. to GHS 3.1.2.5 testing animals in the Category 5 range is discouraged unless "there is a strong likelyhood that results of such testing would have a direct relevance to the protection of human health", which is not the case.
Executive summary:

An acute oral toxicity test on the rat was performed acc. to OECD Guideline 401. Upon single dose, oral administration of 2000 mg/kg to male and female rats (Limit test) and a 14 day post-treatment observation period, the LD50 of CA 2342 A (Intermediate of CGA 293343) was determined to be greater than 2000 mg/kg body weight in both sexes.

All animals survived to the scheduled sacrifice. There were no in-life observations indicating treatment related systemic effects. A loss of body weight was recorded in one female rat during the second week after treatment. At necropsy, no deviations from normal morphology were found in all animals.

The substance is not classified as acute oral toxic by EU-GHS (CLP), since LD50 > 2000 mg/ kg body weight, which is the cut-off in the EU's GHS classification system. UN-GHS has a Category 5 for acute oral toxicity for the dose range 2000 mg/kg bw < LD50 < 5000 mg/kg bw, a concentration range which has not been tested. However acute toxicity Category 5 is applied by some authorities only. Furthermore, acc. to GHS 3.1.2.5 testing animals in the Category 5 range is discouraged unless "there is a strong likelyhood that results of such testing would have a direct relevance to the protection of human health", which is not the case.