Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 15 to 29, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Adopted 24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on August 19, 2008/ signed on March 04, 2009)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Remarks:
paste / solid block
Details on test material:
- Physical state: solid, pale yellow to yellow block, or pasty
- Stability under test conditions: no data
- Storage condition of test material: in the dark, preferably at about 4-10°C and under nitrogen.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: At least 200 g
- Housing: Animals were housed individually during the 24 h exposure period and in groups of five by sex for the remainder of the study in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: Food (2014 Teklad Global Rodent diet supplied by, Harlan Teklad, Bicester, Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: July 15, 2009 To: July 29, 2009

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back and flank area
- % coverage: Approximately 10 % of the total body surface area.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24 h contact period, the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: Yes; 1.78 mL/kg bw
- For solids, paste formed: Yes; the test material was melted in a warming bath set at 60 °C and allowed to cool prior to dosing.
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: Animals were observed for mortality or clinical signs of toxicity at 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes; at the end of the study animals were killed by cervical dislocation and subjected to gross necropsy.

Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed.
Mortality:
- No mortality was observed.
Clinical signs:
- No signs of dermal irritation and systemic toxicity were observed.
Body weight:
- Animals showed expected gains in bodyweight over the study period, except for two females which showed no gain in bodyweight and one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
- No abnormalities were noted at necropsy.
Other findings:
None

Any other information on results incl. tables

Table 7.2.3/1: Individual bodyweights and bodyweight changes

Dose level

(mg/kg bw)

Animal number

and sex

Body weight (g)

at Day

Body weight gain (g)

during week

0

7

14

1

2

2000

1-0 Male

312

314

332

2

18

1-1 Male

312

322

342

10

20

1-2 Male

319

325

342

6

17

1-3 Male

316

336

343

20

7

1-4 Male

312

316

333

4

17

2-0 Female

200

196

212

-4

16

2-1 Female

201

205

217

4

12

2-2 Female

202

202

212

0

10

2-3 Female

201

207

218

6

11

2-4 Female

208

208

219

0

11

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the dermal LD50 for the registered substance is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a group of Wistar (HsdRccHan®™:WIST®™) rats (5/sex) was given a single dermal application of the undiluted test material at 2000 mg/kg bw to intact skin of the back and flank area at the dose volume of 1.78 mL/kg bw. Test sites were covered with a semi-occlusive dressing for 24 h. Animals were observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Skin irritation was assessed and scored according to the Draize scale at 24 h after removal of the dressings and then daily for 14 days.

 

No mortality, dermal irritation or systemic toxicity were observed. Animals showed expected gains in bodyweight over the 14 day study period, except for two females which showed no gain in bodyweight and one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

 

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.