Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 June 2012 to 04 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2008
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute dermal toxicity (2-1-2), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.
Version / remarks:
2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): Rikabinol HB
- Substance type: Monomer
- Physical state: White solid
- Analytical purity: 95.6%
- Impurities (identity and concentrations):
- Lot/batch No.: 7095
- Expiration date of the lot/batch: 31 December 2012
- Storage condition of test material: Room temperature in the dark
- Other: Date received 12 December 2011

Test animals

Species:
rat
Strain:
other: CD (Crl:CD ‘SD’)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: approximately eight to twelve weeks
- Weight at study initiation: 333 to 375 g for males and 246 to 281 g for females
- Fasting period before study: no data
- Housing: The cages were solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding.
- Diet: The animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet). This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
- Water: Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: The animals were allowed to acclimatise to the conditions described below for 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 23°C.
- Humidity: 40 to 70%.
- Air changes (per hr): The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light): Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 mm x 50 mm
- % coverage: approximately 10%
- Type of wrap if used: porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing: the treated area of skin was washed with warm water (30 - 40°C), to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight
- Concentration (if solution): 500 mg/mL
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg bodyweight
Duration of exposure:
24 hours
Doses:
Dose - 2000 mg/kg bw
Concentration - 500 mg/mL
Dose volume - 4 mL/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight, macroscopic pathology and dermal reactions

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Cages of rats were checked at least twice daily for any mortalities. There were no deaths and no systemic response to treatment in any animal.
Clinical signs:
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation.
All animals were observed for 14 days after dosing.
There were no systemic response to treatment in any animal.
Body weight:
The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
A low bodyweight gain was noted for one female (D10) on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.
Other findings:
Dermal reactions: no dermal reactions were observed in any animal during the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal dermal dose (LD50) to rats of Rikabinol HB was demonstrated to be greater than 2000 mg/kg bodyweight.