Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 January - 11 February 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP - guideline study. The test substance was applied under occlusive conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
The test substance was applied under occlusive conditions.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
The test substance was applied under occlusive conditions.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: white solid
- Lot/batch No.: 85-36
- Expiration date of the lot/batch: 18 December 1998
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
other: Wistar Crl:(WI)BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: 283-315 g (males), 186-211 g (females)
- Fasting period before study: Food was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands)
- Diet: Free access to standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhout, Belgium)
- Water: Free access to tap water
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): app. 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: app. 5 x 7 cm on the back of the animal (clipped 1 day before exposure)
- % coverage: approximately 10% of body surface
- Type of wrap if used: a gauze patch (5x5 cm for males and 3.5x5 cm for females) was fixed successively to aluminium foil and Coban elastic bandage (with drops of petrolatum). A piece of Micropore tape was used in addition to fix the dressings in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after dressings were removed, residual test substance was removed using a tissue moistened with tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg body weight of solution
- Concentration: 200 g/L (formulation)
- Constant concentration used: volume was adapted according to body weight
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/kg body weight
- Concentration (if solution): pure (undiluted)
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations of mortality made twice daily, observations of signs of toxicity were made several times on day 1 and daily thereafter, weighing weekly on day 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes, internal macroscopic abnormalities were examined
- Other examinations performed: clinical signs.The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1)

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:
There were no systemic signs of toxicity.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study (see attached document with test results).
Gross pathology:
No abnormalities were found during macroscopic post mortem examination of the animals.
Other findings:
Erythema (grade 1 or 2 on a scale of 4), scales and/or scabs were noted in the treated skin area of all animals from the second day after removal of the bandage. The erythemahad cleared completely in all animals by day 9 and the scales/scabs by day 11 (see attached document).

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Executive summary:

An assessment of the acute dermal toxicity with TS-2863 in the rat was performed according to EU method B.3 and OECD guideline 402.

TS-2863 was applied to the shaved skin of 5 rats of each sex under occlusive conditions at a concentration of 2000 mg/kg bw for 24 hours. The animals were observed twice daily for mortality, daily for signs of toxicity and the body weight was determined weekly. Macroscopic examination was performed after the terminal sacrifice (day 15). No mortality occurred.

Erythema, scales and/or scabs were seen in the treated skin area of all animals after removal of the dressing. The animals had recovered from the local skin effects within 11 days. The body weight gain during the observation period was within the range expected for rats used in this type of study. No gross macroscopic abnormalities were found during necropsy.

The dermal LD50 value of TS-2863 in rats was established as > 2000 mg/kg bw.

According to the criteria for classification and labelling requirements, CLP Regulation (EC) No. 1272/2008 and DSD (Directive 67/548/EEC), TS-2863 does not have to be classified.