Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
UK Department of Health, 21 November 2005
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NExBTL Biodiesel
- Description: Clear colourless liquid
- Date received: 04 July 2006

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK)
- Age at study initiation: 8-12 wk
- Weight at study initiation: males 240-255 g; females 210-238 g
- Housing: individually housed during treatment, group-housed (5/cage) thereafter
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12 (lights on 0600-1800 hr)


IN-LIFE DATES: From: 13 September 2006 To: 27 September 2006

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Skin on the back and flank was clipped free of hair on the day before treatment. Calculated amount of test material (based on measured specific gravity of 0.782) applied the following day to an area of clipped skin equivalent to approx. 10% of body surface area. Treatment site covered with surgical gauze and semi-occlusive self-adhesive bandage. Wrappings removed 24 hr later and test site wiped with cotton wool moistened with distilled water.
Duration of exposure:
24 hr
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male, 5 female
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 0.5, 1, 2 and 4 hr post-treatment then daily until day 14
- Frequency of weighing: days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: test site examined daily for local reactions on study days 1-14, any responses recorded using Draize criteria

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no clinical signs or mortality
Mortality:
None
Clinical signs:
None
Body weight:
Animals showed expected body weight gains
Gross pathology:
None
Other findings:
No local responses at the treatment site were present in males, however hyperkeratinisation and crust formation was noted in all females from day3. This generally resolved after days 8-12 but persisted in one animal until day 14. Small superficial scatter scabs were present in three females during the second part of the study (i.e. on days 7-14). Based on experience with other test substances the report concluded the reactions probably reflected drying/defatting of skin at the test site.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dermal LD50 >2000 mg/kg bw
Executive summary:

Acute dermal toxicity was determined in GLP-compliant guideline study (method B3 of directive 2004/73/EC) using groups of 5 male and 5 female SD rats . The test material was applied undiluted to an area of clipped dorsal skin (approx. 10% of body surface) at a dose of 2000 mg/kg bw, the site covered (semi-occlusive dressing) for 24 hr and the animals housed individually. The wrappings were then removed, the test skin wiped clean with cotton wool moistened with distilled water and the animals returned to group housing. Skin at the test site was examined daily for evidence of primary irritation and any reactions present recorded using Draize criteria. There were no deaths or significant clinical findings either during or following treatment and all animals gained weight normally during the 14 day observation period. No dermal reactions at the test site noted in males, however all females showed evidence of hyperkeratinisation or crust formation from the third day after removal of the dressings which generally resolved after days 8-12 but persisted in one animal until day 14. Small superficial scatter scabs were present in three females during the second part of the study (i.e. on days 7-14). No gross abnormalities were detected at necropsy. The results demonstrate that the acute dermal LD50 of NExBTL renewable diesel in the rat is greater 2000 mg/kg bw. Dermal responses recorded in the females were considered to reflect drying/defatting of the test site.