Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 21, 2008 - November 04, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material: B508
- Physical state: powder

Test animals

Species:
rat
Strain:
other: Sprague Dawley strain (Crl:CD(SD))
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Japan Inc. (3-17-6 Shinyokohama, Kouhoku, Yokohama, Kanagawa, Japan)
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: 252 to 258 g (male), 203 to 220 g (female)
- Housing: One animal per cage (wire-mesh stainless steel cage)
- Diet: Free access to pelleted diet MF (Lot No. 080820, 080522, Oriental Yeast Co., Ltd.)
- Water: Free access to tap water (filtered through a 5 µm cartidge filter and sterilized with an ultraviolet water sterilizer).
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.9 – 24.4
- Humidity (%): 45.3 - 61.7
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
The hair of the back was removed with electric clipper and shaver on the previous day of administration. A piece of lint cloth (4x5 cm) moistened with the dosing material was directly on the administration site. The lint cloth was fixed by non-permeable adhesive tape and adhesive elastic bandage to improve adhesiveness.

Frequency: Single dosage, on Day 0.

Washing: After the contact period the patch was carefully removed and the treated skin wiped with cotton wool moistened with water for injection to remove any residual test substance.
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:
Dose volume: 10 mL/kg body weight

DOSAGE PREPARATION: To prepare a 20 w/v% formulation of the test substance, 7000 g of the test substance was weighed in a mortar and mixed with propylene glycol using a pestle and 35 mL was finally made in a brown volumetric tube.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Body weight of each animal was measured on the start day of application and on Days 1, 2, 3, 4, 7 and 14
Clinical signs: Observation was conducted continuously for one hour after the start of application and thereafter at 2, 3 and 6 hours on the start day of application and once a day from the following day.
- Necropsy of survivors performed: yes
Statistics:
None.

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:
Although neither male nor female animals showed any abnormality in their appearance and behavior, there was bluish staining on the application sites and bluish feces 1 day (patch removal day) and 2 days (the next day after patch removal) after the start of application, respectively.
Body weight:
Reduction in body weight was observed in both sexes on the first day (patch removal day) when compared with the body weight just before treatment. But a satisfactory increase of the body weight was observed after the patch removal and the body weight gains during the observation period were 75 to 93 g in males and 40 to 63 g in females.
Gross pathology:
No abnormalities were observed in appearance, the organs and tissues in the cranial, thoracic and abdominal cavities, and lymph nodes in both sexes.
Other findings:
None.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD 402 guideline and GLP Principles, an LD50 >2000 mg/kg bw was determined.
Executive summary:

B508 was administered to rats by a single dermal application at 2000 mg/kg bw for 24 hours according to OECD 402 guideline and GLP Principles.

No mortality occurred. No adverse clinical signs were observed. No effect on body weight gain after patch removal was noted. No macroscopic abnormalities were observed. The dermal LD50 of B508 in rats was established to exceed 2000 mg/kg bw.