Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 09 - 23, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles. Limited information available to verify the composition of the used test substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(1984)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): KY-MA
- Physical state: Light yellow solid
- Storage condition of test material: At room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Fasting period before study: overnight prior to dosing until approximately 3-4 hours after administration
- Housing: Group housing of 5 animals per cage in labelled polycarbonate cages
- Diet: Free access to standard pelleted laboratory animal diet (Kliba 343 from Klingentalmuhle AG, Kaiseraugst, Switzerland)
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Occasional fluctuations from the conditions were noted, but were considered not to have affected study integrity.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
Frequency: Twice, on days 1 and 2 (within 24 hours)

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg (twice 2500 mg/kg body weight within 24 hours, 10 mL/kg) body weight.

DOSAGE PREPARATION: The formulations were prepared immediately prior to dosing. The test substance was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added. Adjustment was made for specific gravity (1.036) of vehicle. Homogeneity of the test substance in vehicle was obtained by an electric blender, an electric shaker and a magnetic stirrer.

Doses:
5000 mg/kg (twice 2500 mg/kg body weight within 24 hours)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of the first dosing (Day 1) and once daily thereafter. The time of onset, degree and duration were recorded.
- Necropsy of survivors performed: All animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide asphyxiation. All animals assigned to the study were subjected to necropsy and description of all macroscopic abnormalities recorded.
- Other examinations performed: none
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Three males and two females were noted with clinical changes on day 1 including lethargy and uncoordinated movements.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination of the animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD 401 (1987) and EC B.1 (1984) guidelines, an LD50 >5000 mg/kg bw was determined.
Executive summary:

KY-MA was administered by oral gavage, to five rats of each sex, at 5000 mg/kg body weight (twice 2500 mg/kg body weight within 24 hours). No animals died during the study. Three males and two females were noted with clinical changes on day 1 including lethargy and uncoordinated movements. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Macroscopic post mortem examination of the animals at termination did not reveal any abnormalities. Based on these results, KY-MA does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.