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: GLP-guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1987
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit, München, Germany
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
other: WISTAR Crl: WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 8 - 9 weeks (males), 12 - 13 weeks (females)
- Weight at study initiation: 256 - 278 g (males), 211 - 224 g (females)
- Housing: The animals were housed in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding.
- Diet: Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water: tap water, sulphur acidified to a pH value of approximately 2.8, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 16 Aug 2012
To: 30 Aug 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped, healthy skin of the dorsal area of the trunk
- % coverage: approximately 10%
- Type of wrap if used: gauze and non-irritant tape, fixed with a semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After an exposure period of 24 h, the residual test substance was removed using the vehicle.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made several times on the day of dosing (especially during the first 30 min until 4 h after application) and once daily thereafter until the end of the study period. The animals were weighed on Day 1 prior to application and on Days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: primary skin irritation (Draize scoring system)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived until the end of the study period.
Clinical signs:
No signs of sytemic toxicity were observed.
Body weight:
A slight weight loss was recorded for 1/5 males and 3/5 females during the first week, but all animals showed weight gain during the second week (Table 1).
Gross pathology:
The necropsy revealed no test substance-related findings.
Other findings:
Skin irritation:
No erythema and oedema formation was noticed during the observation period. In 1/5 males, eschar formation was observed on Day 8, that resolved within 24 h (Table 2). In 4/5 females, scratches, eschar formation or wounds were noticed which were fully reversible within the observation period in 3/5 females (Table 3).

Any other information on results incl. tables

Table 1: Absolute Body Weights and Body Weight Gain

Animals

Body weight (g)

Increase (%)

Sex

Number

Day 1

Day 8

Day 15

Day 1 - 15

male

21

274

305

339

24

22

264

285

310

17

23

256

255

273

7

24

278

291

319

15

25

270

281

313

16

female

26

213

213

219

3

27

224

221

221

-1

28

211

215

216

2

29

212

206

211

0

30

213

211

215

1

Table 2: Skin irritation – individual data – males

Days after Application

Animal No. 21

Animal No. 22

Animal No. 23

Animal No. 24

Animal No. 25

E/O

Comments

E/O

Comments

E/O

Comments

E/O

Comments

E/O

Comments

2

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

3

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

4

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

5

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

6

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

7

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

8

0/0

nsf

0/0

nsf

0/0

es

0/0

nsf

0/0

nsf

9

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

10

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

11

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

12

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

13

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

14

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

15

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

Comments:

E = erythema, O = oedema; 1, 2, 3, 4 = scoring system laid down in OECD Guideline 404 (Draize scoring system)

es = eschar, s = scratches, es* = eschar on large patches; w = small wounds; w (2) = wound (2 mm diameter) nsf = no specific finding

Table 3: Skin irritation – individual data – females

Days after Application

Animal No. 26

Animal No. 27

Animal No. 28

Animal No. 29

Animal No. 30

E/O

Comments

E/O

Comments

E/O

Comments

E/O

Comments

E/O

Comments

2

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

3

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

4

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

0/0

nsf

5

0/0

nsf

0/0

nsf

0/0

nsf

0/0

es*

0/0

es

6

0/0

nsf

0/0

nsf

0/0

nsf

0/0

es*

0/0

es

7

0/0

s

0/0

s

0/0

nsf

0/0

es*

0/0

nsf

8

0/0

w (2)

0/0

es

0/0

nsf

0/0

es*

0/0

nsf

9

0/0

w (2)

0/0

es

0/0

nsf

0/0

es*

0/0

nsf

10

0/0

w (2)

0/0

es

0/0

nsf

0/0

w

0/0

nsf

11

0/0

w (2)

0/0

es

0/0

nsf

0/0

w

0/0

nsf

12

0/0

w (2)

0/0

es

0/0

nsf

0/0

w

0/0

nsf

13

0/0

w

0/0

nsf

0/0

nsf

0/0

w

0/0

nsf

14

0/0

w

0/0

nsf

0/0

nsf

0/0

w

0/0

nsf

15

0/0

nsf

0/0

nsf

0/0

nsf

0/0

w

0/0

nsf

Comments:

E = erythema, O = oedema; 1, 2, 3, 4 = scoring system laid down in OECD Guideline 404 (Draize scoring system)

es = eschar, s = scratches, es* = eschar on large patches; w = small wounds; w (2) = wound (2 mm diameter) nsf = no specific finding

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