Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted in accordance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
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): TKA 40135 (CGI 819)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd, Bicester, Oxon, England
- Age at study initiation: approximately seven to ten weeks
- Weight at study initiation: approximately 212 to 290 g
- Fasting period before study: access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Housing: individually in metal cages
- Diet (e.g. ad libitum): standard laboratory rodent diet (SDS LAD 1), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: 24 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12hrs/12 hrs

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day prior to treatment hair was removed from the dorso-lumbar region of each rat exposing an area equivalent to approximately 10% of the total body surface. The test substance was applied by spreading it evenly over the prepared skin. The treated area (approximately 5 cm x 5 cm) was then covered with gauze which was held in place with a non-irritative dressing encircled firmly around the trunk. Aluminium foil was incorporated in the dermal dressings in an attempt to reduce photoinduced disintegration of the chemical on the skin.
At the end of the 24 hours exposure period, the dressings were carefully removed and the treated area of skin was washed with lukewarm water and blotted dry with absorbent paper.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five animals per sex and group
Control animals:
no
Details on study design:
MORTALITY AND CLINICAL SIGNS OF TOXICITY
The animals were checked at least twice daily for any mortalities. They were observed for clinical signs soon after dosing and for 3 hours following application of the test material. On subsequent days animals were observed twice a day until ending of the observation period. The animals were observed for 14 days after dosing.

SKIN REACTION
Local dermal irritation at the treatment site was assessed daily using the following numerical system:

Erythema and eschar formation:
No erythema 0
Slight erythema 1
Well-defined erythema 2
Moderate erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Edema formation:
No edema 0
Slight edema 1
Well-defined edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm) and extending beyond the area of exposure) 4

BODYWEIGHT
The bodyweight of each rat was recorded on days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.

PATHOLOGY
The animals were sacrificed for the purpose of necropsy on day 15 by cervical dislocation. They were subjected to gross pathological examination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities were observed at the tested dose level of 2000 mg/kg bw.
Mortality:
All animals survived the single dermal treatment with 2000 mg/kg bw of the test material.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
A slightly low bodyweight gain was recorded for one male and one female on day 8, with a similar trend noted for three males and one female on day 15. All other rats achieved satisfactory bodyweight gains throughout the study. For details, see tables below.
Gross pathology:
Necropsy was inconspicuous in all animals sacrificed on day 15.
Other findings:
Referring to dermal reaction, neither irritation nor other dermal changes were noticed.

Any other information on results incl. tables

Bodyweight changes:

Sex

Dose

Animal Number

Body weight (g) at

Day 1

Day 8

 Day 15

Males

2000 mg/kg bw

1

280

331

383

2

262

295

335

3

265

307

348

4

264

314

361

5

290

337

377

mean

272

317

361

Females

2000 mg/kg bw

6

223

242

262

7

217

240

250

8

221

250

266

9

223

243

258

10

212

216

242

mean

219

238

256

 

Body weight gains during the observation period:

Sex

Dose

Animal Number

Body weight gain (g) for

Week 1

Week 2

Males

2000 mg/kg bw

1

51

52

2

33

40

3

42

41

4

50

47

5

47

40

Females

2000 mg/kg bw

6

19

20

7

23

10

8

29

16

9

20

15

10

4

26

 

Applicant's summary and conclusion