Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is used for read-across and therefore has been assigned a reliability of 2 (reliable with restrictions). Otherwise the study has a reliability of 1 (reliable without restriction). This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment. Compliant to GLP and testing guideline; adequate coherence between data, comments and conclusions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
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): AZDN
- Physical state: solid (white powder)
- Analytical purity: 99.2%
- Lot/batch No.: 6089
- Expiration date of the lot/batch: March 2010
- Storage conditions of test material: below 15°C and protected from light

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: 8 weeks old
- Weight at study initiation: 371 ± 9 g for the males and 235 ± 7 g for the females
- Fasting period before study: none
- Housing: polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm)
- Diet (e.g. ad libitum): SSNIFF R/M-H pelleted maintenance diet
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: From 03 March 2010 to 17 March 2010

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm x 7 cm for the males and 5 cm x 6 cm for the females
- % coverage: 10% of the total body surface of the animals
- Type of wrap if used: gauze pad held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test item was removed using a dry cotton pad
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: yes (substance moistened with 2 mL of purified water)

Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
other: historical control animals
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed frequently during the hours following administration of the test item, and then at least once a day until day 15. Animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None.
Clinical signs:
None.
Body weight:
When compared to historical control data, a lower body weight gain was noted in all the males (16 to 35 g vs. 47 g ± 7 g in historical data base) and 1/5 females (7 g vs. 25 g ± 11 g in historical data base) between day 1 and day 8; returning to normal thereafter.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Under the experimental conditions of this study, the dermal LD50 of the test item AZDN (batch No. 6089, purity: 99.2%) was higher than 2000 mg/kg in rats.
Executive summary:

The acute dermal toxicity of the test item, AZDN, was evaluated in rats according to OECD (No. 402, 24th February 1987) and Commission Regulation (EC) (No. 440/2008, Part B.3, 30 May 2008) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

Methods

The test item was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females). The application was performed with the test item in its original form at the dose-level of 2000 mg/kg. The test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test item.

All animals were subjected to necropsy.

 

Results

No mortality, no clinical signs and no cutaneous reactions were observed during the study. When compared to historical control data, a lower body weight gain was noted in all the males (16 to 35 g vs.47 ± 7 g in historical data base) and 1/5 females (7 g vs. 25 g ± 11 g in historical data base) between day 1 and day 8; returning to normal thereafter. No apparent abnormalities were observed at necropsy in any animal.

 

Conclusion

Under the experimental conditions of this study, the dermal LD50 of the test item AZDN (batch No. 6089, purity: 99.2%) was higher than 2000 mg/kg in rats.