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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

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 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147
GLP compliance:
yes (incl. certificate)
Remarks:
Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen/Rhein, Germany

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Borane-tetrahydrofuran complex in tetrahydrofuran 1M
- Physical state: Liquid
- Analytical purity: The test substance was characterized analytically
- Lot/batch No.: 101202350
- Storage condition of test material: Refrigerator, exclusion of oxygen (stored under nitrogen )
- Homogeneity: The test substance was homogeneous by visual inspection.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: 6 - 10 months
- Weight at study initiation: 3.40 kg - 4.01 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm2
- Diet: Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day )
- Water: Tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 h light (6.00 a.m.-6.00 p.m.) 12 h darkness (6.00 p.m.-6.00 a .m.)

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
Right flank (animal Nos. 01-03): 3 minutes
Left flank (animal Nos. 01-03): 1 hour
Right flank (animal Nos. 04-06): 4 hours
Observation period:
14 days
Number of animals:
3 per exposure time
Details on study design:
TEST SITE
- Area of exposure: Dorsolateral part of the trunk: 2.5 cmx2.5 cm
- Clipping of the fur: At least 24 hours before the beginning of the study.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period with Lutrol and Lutrol/ water (1 : 1) .

READINGS
Immediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals maximally up to day 14. Check for dead or moribund animals twice each workday (beginning and end) and once on Saturdays, Sundays and on public holidays. Body weight determination: Just before application of the test substance and after the last reading.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hour
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 3 minutes exposure time
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hour
Score:
2.8
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 3 minutes exposure time
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hour
Score:
2.4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 1 hour exposure time
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hour
Score:
1.9
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: 1 hour exposure time
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hour
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4 hour exposure time
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hour
Score:
0
Max. score:
4
Remarks on result:
other: 4 hour exposure time
Irritant / corrosive response data:
After the exposure period of 3 minutes moderate or marked erythema (grade 2 or 3) was observed in all animals immediately after removal of the patch up to day 7. Marked erythema persisted in one animal up to day 14. In the other two animals moderate erythema decreased to slight (grade 1) on day 14. Moderate to severe edema (grade 2-4) was observed in all animals immediately after removal of the patch up to 72 hours. Severe edema decreased in one animal to marked (grade 3) on day 7 and to moderate (grade 2) on day 14. In two animals moderate edema decreased to slight edema (grade 1) on day 7. Bleeding was noted in a single animal immediately after removal of the patch up to 72 hours. Eczematoid skin change was observed in this animal on day 7. Detachment of superficial altered skin layers in the region of eczematoid skin change with sleek and reddened skin underneath was seen in this animal at study termination on day 14. Additionally scaling and severe scaling were observed in the animals after 7 and/or 14 days. The cutaneous reactions were not reversible in all animals within the study period (14 days after removal of the patch).

After the exposure period of 1 hour, moderate or marked erythema (grade 2 or 3) was observed in all animals immediately after removal of the patch up to 72 hours. In one animal marked erythema increased to severe (grade 4) on day 7 and decreased to marked again on day 14. Slight erythema (grade 1) was noted in two animals on day 7 and in one animal on day 14. Moderate edema (grade 2), observed in all animals immediately after removal of the patch, persisted in two animals up to 24 hours and decreased to slight (grade 1) after 48 and 72 hours. In the third animal moderate edema increased to marked (grade 3) after 1 hour up to day 7 and decreased to moderate (grade 2) on day 14. Bleeding was noted in a single animal immediately after removal of the patch up to 72 hours. Eczematoid skin change was observed in this animal on day 7. Detachment of superficial altered skin layers in the region of eczematoid skin change with sleek and reddened skin underneath was seen in this animal at study termination on day 14. Additionally scaling was observed in the animals after 7 and/or 14 days. The cutaneous reactions were not reversible in two animals within 14 days after removal of the patch.

After the exposure period of 4 hours moderate erythema (grade 2) was observed in all animals immediately after removal of the patch up to 24 hours and in one animal up to 48 hours. Moderate erythema decreased to slight (grade 1) after 48 or 72 hours after removal of the patch. Slight edema (grade 1) was noted up to 1 hour after removal of the patch. Moreover scaling was seen in one animal on day 7. The cutaneous reactions (with the exception of scaling) were reversible in one animal within 72 hours and in two animals within 7 days after removal of the patch.

No clear exposure time dependent increase in severity of skin findings was observed after the three exposure periods of 3 minutes, 1 hour and 4 hours . The maximum irritation score was found after 3 minutes, whereas 4-hour exposure resulted in considerably lower scores . This might be explained by the higher individual sensitivity of the animals used for the 3-minutes / 1-hour test and partly by the evaporation of the test substance over time through the semiocclusive dressing .

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information
Conclusions:
The findings in the animals after 4-hour treatment would not warrant the classification of the test substance as an irritant. However, considering the results obtained in animals after 3 min and 1 h, the test substance is classified as irritating to the skin.