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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2,3-epoxypropyl) cyclohex-4-ene-1,2-dicarboxylate
EC Number:
244-435-6
EC Name:
Bis(2,3-epoxypropyl) cyclohex-4-ene-1,2-dicarboxylate
Cas Number:
21544-03-6
Molecular formula:
C14H18O6
IUPAC Name:
1,2-bis[(oxiran-2-yl)methyl] cyclohex-4-ene-1,2-dicarboxylate
Test material form:
liquid

Test animals

Species:
rat
Strain:
other: Tif: RAIf (SPF) strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals
Healthy random bred rats of the Tif: RAIf (SPF) strain raised on our premises were used for these experiments.
They were kept at a room temperature of 22 + 1 °C, at a relative humidity of 55 + 5 % and on a 10 hours light cycle day. They received ad libitum rat food - NAFAG, Gossau SG - and water. Prior to treatment the animals were adapted to our laboratories for a
minimum of 4 days and the initial body weight ranged from 160 to 180 grams.

Administration / exposure

Route of administration:
other: Oral intubation
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
The test item was diluted with carboxymethyl-cellulose 2 %.

Treatment and observations
During the treatment and observation period the animals were housed in groups of 5 in Macroion cages (type 3).
Animals fasted overnight were treated by oral intubation. Physical condition and rate of deaths were monitored throughout the whole observation period.
Doses:
1000 / 2150 / 3590 / 4640 mg/Kg
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not observed
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, physical conditions

The surviving animals were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.
Statistics:
Not applicable

Results and discussion

Preliminary study:
N/A
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 938 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 453 - <= 3 518
Remarks on result:
other: LD 50 including 95 % confidence limits were calculated by the probit analysis method (Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404-408).
Mortality:
Please see "Any other information on resultzs incl. tables" field
Clinical signs:
Signs and symptoms
Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. Sedation became more
accentuated as the dose was increased.
Body weight:
Not observed
Gross pathology:
No substance related gross organ changes were seen.
Other findings:
The surviving animals recovered within 7 to 11 days. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.

Any other information on results incl. tables

Rate of deaths:

                                    Died within
 Dose mg/kg  Concentration % of Formulation     N° of animals    1 hour  24 hours     48 hours    7 days     14 days    
     male female   male female  male  female  male  female  male  female  male  female 
 1000  10  5  5  0  0  0  0  0  0  0  0  0  0
 2150  20  5  5  0  0  0  2  0  2  0  0  0  2
 3590  40  5  5  0  0  4  2  4  2  4  2  4  2
 4640  50  5  5  0  0  5  5  5  5  5  5  5  5

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute oral LD50 of TK 12198 in rats of both sexes observed over a period of 14 days is 2938 (2453-3518) mg/kg* .
*LD 50 including 95 % confidence limits were calculated by the probit analysis method (Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404-408).
Executive summary:

In this study, female and male rats ( 5 male and 5 female per dose) were traited with thetest item diluted in carboxymethyl-cellulose.

Rats were traited at 1000/2150/3590 and 4640 mg/kg by oral intubation. The observation period was 14 days.

The surviving animals recovered within 7 to 11 days. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.

Signs and symptoms

Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. Sedation became more accentuated as the dose was increased.

The surviving animals recovered within 7 to 11 days. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.

Dead and killedAnimals: No substance related gross organ changes were seen.

Rate of death:

                                    Died within
 Dose mg/kg  Concentration % of Formulation     N° of animals    1 hour  24 hours     48 hours    7 days     14 days    
     male female   male female  male  female  male  female  male  female  male  female 
 1000  10  5  5  0  0  0  0  0  0  0  0  0  0
 2150  20  5  5  0  0  0  2  0  2  0  0  0  2
 3590  40  5  5  0  0  4  2  4  2  4  2  4  2
 4640  50  5  5  0  0  5  5  5  5  5  5  5  5

The acute oral LD50 of the test item in rats of both sexes observed over a period of 14 days is 2938 (2453-3518) mg/kg* .