Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
8th April - 12th August 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. Study conducted on middle weight fraction of shale oils.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

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:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Identification: Shale oil, middle fraction
Description :Liquid
Batch number: 1
Purity min.: 99 %
Density: 980 kg/m^3
Composition: Complex mixture of hydrocarbons and oxygen compounds
Stability of test item: Stable under storage conditions
Expiry date: 04-MAR-2006
Storage conditions: At room temperature (range of 20 ± 5 °C), light protected.
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Males: 8 weeks. Female: 12 weeks
- Weight at study initiation: NDA
- Fasting period before study: NDA
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard provided ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 8th - 12th April 2005

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 5
- Humidity: 30 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark with music played during the daytime period

IN-LIFE DATES: From: 8th April 2005 To: 27th April 2005

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: NDA
- % coverage: 10 %
- Type of wrap if used: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin flushed with luke warm water
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.04 mL/kg bw
- Concentration (if solution): N/A
- Constant volume or concentration used: yes
- For solids, paste formed: N/A

VEHICLE
N/A
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, local signs
Statistics:
No statistical analysis used.

Results and discussion

Preliminary study:
not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
No systemic signs of toxicity were observed during the course of the study.
Due to brown discoloration of the application site in all animals, local symptoms could not be assessed on test day 2.
Slight general erythema was observed in six animals at the reading on test day 3 and persisted up to test day 5, 6, 10 or 15 and was noted additionally from test day 7 to 8 in one of these animals. Moderate general erythema was found in four animals on test day 3 and was still noted in two animals at the reading on test day 4 or 5. One female showed this symptom on test day 6 and 7. In these last four animals, slight general erythema was found from the reading on test day 4, 5, 6 or 8 until test day 6, 8, 10 or 15.
Slight formation of fissures was seen in eight animals at the reading on test day 3 or 4 and persisted up to the observation on test day 5 in one animal or test day 6 in the remaining animals.
Slight formation of crusts was observed in eight animals from the reading on test day 3, 4, or 6 up to the observation on test day 6, 7, 8 or 12 and returned in four of these animals from test day 8, 9, 11 or 13 to test day 12 or the end of the observation period. In three of these animals moderated crust formation was seen at the reading on test day 7 and persisted up to the observation on test day 8 in one animal.
Moderate crust formation was observed in two animals on the reading from test day 3 to test day 5 or on test day 7 only in one animal. Slight crust formation occurred in these animals from test day 6 to 7 or test day 13 to 15, respectively.
Slight scaling was observed in all animals from test day 8, 9, 12 or 13 to the end of the observation period.
(see attached tables)
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Other findings:
NDA

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of Shale oil after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight.
Executive summary:

Five male and five female HanRcc:WIST (SPF) rats were treated with Shale oil at 2000 mg/kg by dermal application in accordance with OECD 402 and to GLP standard. The test item was applied undiluted as delivered from the sponsor at a volume dosage of 2.04 mL/kg. The application period was 24 hours.

No mortality, clinical signs or abnormal body weight changes were observed. Mild to moderate skin irritation effects were observed in all animals.

The median lethal dose of Shale oil after single dermal administration to rats of both sexes, observed over a period of 14 days is:

LD50 (rat): greater than 2000 mg/kg body weight.

Based on the rationale for read-across, it is considered acceptable to use this study to address the same endpoint for light fraction of shale oil.