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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: Testing Methods for New Chemical Substances according to the Revised Japanese Chemical Substance Law (March 31, 1987).
GLP compliance:
yes (incl. QA statement)
Remarks:
RCC, Holding Company Ltd. 4452 Itinqen Switzerland
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): FAT 45'168/A
- Synonym: Reactive Black 2506-MS
- Ident-Nr.: 078312.3
- Purity: ca. 80%
- Lot/batch No.: 316904.36
- Expiration date of the lot/batch: June 1998
- Stability of test article: Stable under storage conditions
- Stability of Test Article in Vehicle: Stable in water for two hours
- Storage condition of test material: In the original container at room temperature away from direct sunlight
Specific details on test material used for the study:
None

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, 4414 Füllinsdorf/Switzerland
- Age at study initiation: males: 9 weeks, females: 11 weeks
- Weight at study initiation: males: 253.6 - 286.2 g; females: 196.6 - 212.8 g
- Housing: during acclimatization in groups of five in Makrolon type-4 cages (size: 33 x 55 x 20 cm) with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz). During treatment and observation individually in Makrolon type-3 cages (size: 22 x 37.5 x 15 cm) with standard softwood bedding.
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch no.73/94 rat maintenance diet ("Kliba", Klingentaimuehie AG, CH-4303 Kaiseraugst) available ad libitum.
- Water (e.g. ad libitum): community tap water from Füllinsdorf, available ad libitum.
- Acclimation period: one week under laboratory conditions, after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 36-64
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12, music during light period

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
bi-distilled water
Details on dermal exposure:
TREATMENT
Approximately 24 hours before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface. Only those animals without injury or irritation on the skin were used in the test.
On test day 1, the test article was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage. Application volume/ kg body weight: 4.0 mL/kg. Twenty-four hours after the application the dressing was removed and the skin was washed with lukewarm tap water and dried with disposable paper towels.

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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:
Mortality / Viability*: Four times during test day 1 and daily during days 2-15.
Body Weights: On test days 1 (pre-administration), 8 and 15.
Clinical Signs: Each animal was examined for changes in behaviour and appearance (with special emphasis on the application area, except for the time when the semi-occlusive dressing was in place) four times during day 1, and once daily during days 2-15. All abnormalities were recorded, (general behaviour, respiration, eyes, motor susceptibility, nose, motility, body posture, skin)

* The computerised system does not show that the mortality/viability checks were recorded at the same time as the clinical signs.

- Necropsy of survivors performed:
Necropsies were performed by experienced prosectors. At the end of the observation period all animals were anesthetized by intraperitoneal injection of NARCOREN (Rhone Merieux GmbH, D-88417 Laupheim) at a dose of at least 2.0 mL/kg body weight (equivalent to at least 320 mg/kg sodium pentobarbitone/kg body weight) and sacrificed by exsanguination. The animals were examined macroscopically.
Statistics:
The LOGIT-Model could not be used as no deaths occurred.

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:
There were no deaths as a result of treatment with the test article.
Clinical signs:
No clinical signs of systemic toxicity were observed during the observation period.
Discoloration of the skin at the application site was evident in all animals after the removal of the dressing on test day two and persisted until study termination.
Body weight:
Slight loss of body weight (2.2 and 2.0 g) was noted in female animals no. 7 and 9 respectively during the first observation week. The other animals gained weight over the observation period.
Gross pathology:
No organ abnormalities were observed at necropsy.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The toxicity of the read across substance was estimated to be greater than 2000 mg/kg bw.
Executive summary:

In a GLP compliant dermal toxicity study, performed according to OECD guideline 402, Wistar rats (5/sex) were administered the read across substance (2000 mg/kg bw). The test substance was dissolved in water and applied on the skin with a syringe and covered with a semi-occlusive dressing for 24 hours. The treated skin was washed after 24 hours and a 14-day observation period followed. No mortality, clinical signs of systemic toxicity, or organ abnormalities were observed during this period. The pigment in the test article caused a discolouration of the skin at the application site which persisted throughout the observation period. There were no test article-related effects on the body weight of the animals during the observation period. The minimal to slight loss of body weight in two female animals during the first observation week was considered to be a consequence of the semi-occlusive dressing. Commonly female animals prove to be more sensitive in relation to effects on body weight caused by semi-occlusive dressing than males. The mean lethal dose of test substance after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated, because no deaths occurred at the maximal dose of 2000 mg/kg bw.