Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(allyloxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-isocyanatobenzoate
EC Number:
695-953-8
Cas Number:
204918-22-9
Molecular formula:
C15H14ClNO5
IUPAC Name:
1-(allyloxy)-2-methyl-1-oxopropan-2-yl 2-chloro-5-isocyanatobenzoate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd. Biotechnology & Animal Breeding Division. CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: 8 - 10 weeks.
- Weight at study initiation: Males: 222.1 - 236.4 g Females: 172.5 - 187.2 g.
- Housing: Groups of three.
- Diet: ad libitum (fasting for 1 hour prior to dosing and for 3 hours after dosing).
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 -24°C
- Humidity (%): 36 - 57 %
- Air changes (per hr): 10- 15 changes/hour
- Photoperiod: 12 hours light / 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
300
Details on oral exposure:
VEHICLE
- Concentration in vehicle (mg of test item/kg body weight): 200 mg/kg females, 200 mg/kg males, 2000 mg/kg females
- Amount of vehicle (if gavage): 10 ml
- Lot/batch no. (if required): 4053741/1 30600

DOSAGE PREPARATION: The prepartion was made shortly before dosing.

- Rationale: Oral administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item
Doses:
200 mg test item/kg body weight females, 200 mg test item/kg body weight males, 2000 mg test item/kg body weight females.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
OBSERVATIONS
Mortality/Viability: One, two, three and five hours after the test item administration for the surviving animals. Twice daily during
days 2 – 15 for the surviving animals.
Body weights: On test days 1 (pre-administration), 8 and 15 for surviving animals.
Clinical signs: Each animal was examined for changes in appearance and behaviour four times during day 1, and once daily for
surviving animals during dyas 2 – 15. All abnormalities were recorded.

TERMINAL SACRIFICE
At the end of the observation period (test day 15) all surviving animals were sacrificed.
Animals which had died spontaneously during the observation were necropsied as soon as they were found dead.
Statistics:
The toxicity was estimated without the use of a statistical model.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All male and female animals treated at 200 mg/kg survived until scheduled necropsy. All female animals treated at 2000 mg/kg were found dead, on test day 2 (2 animals), 1 on test day 3 (1 animal).
Clinical signs:
No clinical signs were observed during the observation period in all 200 mg/kg treated animals. Hunched posture and somnolence were observed on test day 1 in all females treated at 2000 mg/kg and persisted in one female animal on test day 2.
Body weight:
The body weight of the animals was within the range commonly recorded for animals of this strain and age.
Gross pathology:
Grey weight distended stomach with gas was observed at the necropsy of all female animals treated at 2000 mg/kg. No macroscopic findings were observed at the necropsy of the 200 mg/kg animals.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these observations and according to the Annex 3b of the OECD 423, the median lethal dose for the acute oral toxicity of CA 2814 B (Intermediate of CGA 276854) in rats of both sexes observed for a period of 14 days is estimated to be:

LD50 (male rat): >200 mg/kg body weight.

LD50 (female rat): >200 mg/kg body weight, <2000 mg/kg body weight

Executive summary:

Groups of HanIbm: WIST (SPF) rats were treated with CA 2814 B (Intermediate of CGA 276854) at 200 mg/kg (3 males/females) or 2000 mg/kg (3 females) by oral gavage. The test item was diluted in vehicle (polyethylene glycol, PEG 300) at a concentration of 0.02 or 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2 – 15. Mortality/viability was recorded together with clinical signs at the same time intervals on test day 1 and then twice daily on test days 2 – 15. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. 

 

All male and female animals treated at 200 mg/kg survived until scheduled necropsy. All female animals treated at 2000 mg/kg were found dead, on test day 2 (2 animals), 1 on test day 3 (1 animal). 

 

No clinical signs were observed during the observation period in all 200 mg/kg treated animals. Hunched posture and somnolence were observed on test day 1 in all females treated at 2000 mg/kg and persisted in one female animal on test day 2. 

 

The body weight of the animals was within the range commonly recorded for animals of this strain and age. 

 

Grey weight distended stomach with gas was observed at the necropsy of all female animals treated at 2000 mg/kg. No macroscopic findings were observed at the necropsy of the 200 mg/kg animals. 

Based on these observations and according to the Annex 3b of the OECD 423, the median lethal dose for the acute oral toxicity of CA 2814 B (Intermediate of CGA 276854) in rats of both sexes observed for a period of 14 days is estimated to be:

 

LD50(male rat): >200 mg/kg body weight.

 

LD50 (female rat): >200 mg/kg body weight, <2000 mg/kg body weight