Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 10 -24, 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 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
(1984)
Deviations:
no
GLP compliance:
yes
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): KY-MA
- Physical state: Light yellow solid

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.
- Housing: Individually housed in labelled polycarbonate cages
- Diet: Free access to standard pelleted laboratory 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

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The formulation was applied in an area of approx. 25 cm² (5x5 cm) for males and 18 cm² (3.5x5 cm) for females by application on a gauze patch fixed successively to aluminium foil and flexible bandage, with drops of petrolatum.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using a tissue moistened with tap-water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg


No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Dose volume: 10 mLkg body weight

DOSAGE PREPARATION: The formulation was 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 using an electric blender, an electric shaker and magnetic stirrer.

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 application (Day 1) and once daily thereafter. The time of onset, degree and duration were recorded.
- Necropsy of survivors performed: All animals were sacrificed by oxygen/carbon dioxide asphyxiation. All animals assigned to the study were subjected to necropsy and descriptions of all macroscopic abnormalities recorded.
- Other examinations performed: none.
Statistics:
None.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Lethargy was noted in two males on the day of dosing. Scales and/or focal erythema was noted on the dorsal skin of one male and all females tretaed with KY-MA, between days 4 and 15.
Body weight:
Low body weight gain was noted in the majority of animals over week 1 of the observation period. The body weight gain shown by the animals over the second week of 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 revealed red-brown scab formation on the treated skin area of 4/5 females.
Dilation of the renal pelvis, as noted in one male, was considered to be of no toxicological significance as this is commonly noted among rats of this age and strain.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD 402 (1987) and EC B.3 (1984) test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

KY-MA was administered by dermal application, to five rats of each sex, at 2000 mg/kg body weight. No animals died during the study. Lethargy was noted in two males on the day of dosing. Scales and/or focal erythema was noted on the dorsal skin of one male and all females treated with KY-MA, between days 4 and 15. Low body weight gain was noted in the majority of animals over week 1 of the observation period. The body weight gain shown by the animals over the second week of 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 revealed red-brown scab formation on the treated skin area of 4/5 females.

Dilation of the renal pelvis, as noted in one male, was considered to be of no toxicological significance as this is commonly noted among rats of this age and strain.

Based on these results, KY-MA does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.