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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
01 June 2012 - 30 August 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

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)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Details on strain: Wistar / Crl:WI (Han) SPF
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks (males) and 13 weeks (females), respectively
- Weight at study initiation: mean (males): 273.0 ± 6.63g; mean (females): 225.8 ± 3.19g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cage, type III
- Diet (ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water (ad libitum): Tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C
- Humidity: 30 – 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
deionized water
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped epidermis (dorsal and dorsolateral parts of the trunk)
- % coverage: about 40 cm² (corresponds to at least 10% of the body surface)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.71 mL/kg bw
- Concentration (if solution): 35 g/100 mL
- Constant volume or concentration used: yes
- For solids, paste formed: no
- Form of application: solution in deionized water
- Test item preparation and homogenization: For better handling the test item was ground with mortar and pestle. The test item preparation was produced shortly before application by stirring with a magnetic stirrer.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical signs: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.

Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
The evaluation of skin reactions was performed according to Draize, J.H. (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.

Body weight: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.

Pathology: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.

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.
Clinical signs:
No systemic clinical signs were observed during clinical examination.
Body weight:
Males:
The mean body weight of the male animals increased within the normal range throughout the study period.

Females:
The mean body weight of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of observation period.
Other findings:
Local effects:
No local effects were observed.

Any other information on results incl. tables

Body weight changes:

Individual body weight changes

Dose [mg/kg bw]

2000

Sex

male

Animal No.

1

2

3

4

5

mean

sd.

Body weight at study day [g]

 

 

 

 

 

 

 

0

274

267

282

266

276

273.0

6.63

7

278

284

301

281

285

285.8

8.93

14

307

304

330

299

308

309.6

11.93

 

Individual body weight changes

Dose [mg/kg bw]

2000

Sex

female

Animal No.

1

2

3

4

5

mean

sd.

Body weight at study day [g]

 

 

 

 

 

 

 

0

224

222

230

225

228

225.8

3.19

7

231

220

234

226

230

228.2

5.40

14

237

238

240

239

238

238.4

1.14

sd. = standard deviation

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