Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 2012- March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and EPA guidelines according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Specific details on test material used for the study:
Identifier: EXP1200078
Appearance: Very dark brown (almost black) viscous liquid
Batch: E00275-350
Sample Expiration Date: end-2013
Purity:100%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, NC
- Age at study initiation: appr. 11 weeks
- Weight at study initiation: 318 to 428 g (males) and 221 to 263 g (females)
The males weighed more than recommended in the OECD guideline, but this deviation did not influence the study outcome.
- Fasting period before study: no
- Housing: individually in stainless steel, wire-mesh cages
- Diet: ad libitum (PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002)
- Water: ad libitum (municipal water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 to 21.6
- Humidity (%): 43.9 to 49.5
- Air changes (per hr): 10 (minimum)
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25OCT2012 To: 08NOV2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: appr. 10% (to unabraded skin)
The test substance was applied to the same area for each animal based on a target area established using the body weight of the first animal/sex. As a result, areas of coverage for 3 male and 4 females were calculated to be 9.7%, 9.1%, 8.9%, 9.1%, 8.9%, 9.5%,
and 9.9%, of the total body surface, respectively. This deviations did not negatively impact the quality or integrity of the data nor the outcome of the study.
- Type of wrap if used: gauze binders secured with nonirritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: exposure sites were wiped with disposable paper towels moistened with tepid tap water and 1% Ivory® soap solution
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2.1 mL/kg (2.0 g/kg)
- Constant volume or concentration used: no
Duration of exposure:
24 hours
Doses:
2000 mg/kg
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: mortality and clinical signs were checked twice daily and 1, 2, and 4 hours post-application. Weighing was done at day 0, 7 and 14.
- Necropsy of survivors performed: yes, major organ systems of the cranial, thoracic, and abdominal cavities were examined.
- Other examinations performed: dermal observations (30-60 minutes after bandage removal and daily thereafter) according to Draize.
Statistics:
None performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical findings observed during the study.
Body weight:
4/5 females had slight body weight loss from day 0-7, gain was noted from day 7-14.
For all other animals no remarkable body weigt changes were noted.
Gross pathology:
There were no macroscopic findings noted at the scheduled necropsy.
Other findings:
One male showed slight erythema on day 7. Two females had erythema scores of 1 and/or 2 starting on day 4 and up to day 7. One female showed desquamination on days 4-7. No edema was observed. Residual test article was observed within dose sites of all animals, up to day 2-4.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal toxicity of EXP1200078 was tested according to OECD/ EPA guidelines acording to GLP principles. The LD50 was determined to be >2000 mg/kg bw.
Executive summary:

An acute dermal toxicity test was conducted with five male and five female rats following OECD and EPA guidelines according to GLP principles. EXP1200078 was applied semi-occlusively at 2000 mg/kg bw for 24 hours. No mortality occurred and no clinical signs were noted. No unexpected changes in body weight gain were reported. Dermal findings noted during the study consisted of very slight (grade 1) to slight (grade 2) erythema and desquamation and were reverted from day 8 onwards.

Based on these results, the test substance has an acute LD50 > 2000 mg/kg bw and is not classified for acute dermal toxicity according to EC regulation No 1272/2008.