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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): KMC
- Physical state: colorless and transparent oily liquid
- Analytical purity: ≥ 99.5%
- Isomers composition: no data
- Lot/batch No.: TR-
- Stability under test conditions: more than 1 year at room temperature
- Storage condition of test material: no data

Test animals

Species:
rat
Strain:
other: Crjh : CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: no data
- Weight at study initiation: males 115 - 166 g, females 102 - 127 g
- Fasting period before study: yes
- Housing: 5 per cage in polycarbonate cages
- Diet (e.g. ad libitum): pelletized rat diet (rat.MF, Oriental Yeast Co.), ad libitum
- Water (e.g. ad libitum): tap water through polycarbonate bottles, ad libitum
- Acclimation period: more than a week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 50 - 60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.18 - 0.7 mL TS/mL olive oil according to dose
- Amount of vehicle (if gavage): 1 mL/100 g bw
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g bw
Doses:
males: 1.73, 2.21, 2.78, 3.46, 4.32, 5.38, and 6.72 g/kg bw (1.8, 2.3, 2.9, 3.6, 4.5, 5.6, 7.0 mL/kg)
females: 2.78, 3.46, 4.32, 5.38, 6.72 (2.9, 3.6, 4.5, 5.6, 7.0 mL/kg)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several times at day of administration, once or more times daily thereafter until 14 days
(time of sacrifice). Body weights were measured shortly before, 7 and 14 days after administration.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 values were determined using the method of Litchfield and Wilcoxon.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
4 130 mg/kg bw
95% CL:
3 550 - 4 800
Remarks on result:
other: LD50 is reported as 4.3 mL/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
4 320 mg/kg bw
95% CL:
3 650 - 5 090
Remarks on result:
other: LD50 is reported as 4.5 mL/kg bw
Mortality:
1.58 g/kg group:  0/10
2.20 g/kg group: 1/10 (day 2)
2.78 g/kg group:   1/20 (day 3)
3.46 g/kg group:   6/20 (days 2-4)
4.32 g/kg group:  11/20 (days 1-5)
5.38 g/kg group:  14/20 (days 1-5)
6.72 g/kg group:  20/20 (days 1-6)
Clinical signs:
Reduced activity, reduced muscle tonus, toe walking, diarrhea, incontinence, haemic nasal discharge, emaciation
Body weight:
Compared to the day of treatment (start of the experiment), the body weights measured were increased at day 7 and further increased at day 14.
Gross pathology:
Dead animals
Dose-related discolored liver, discolored and atrophic spleen and kidneys, reddish purple appearance of the adrenal glands, hypertrophy of the adrenal glands, scattered reddish spots in and reddish appearance of the lungs, hemorrhage in the thymus gland
Surviving animals
Occasionally in male, but not in female animals, scattered reddish spots in the lung, atrophy of spleen and hypertrophy of mesentery lymph nodes.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a valid acute oral toxicity study according to OECD test guideline 401, LD50 values of 4130 and 4320 mg/kg bw were determined for male and female rats respectively.