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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
Study period:
27 April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
; 24 hour exposure, occlusive dressing, abraded and non-abraded skin

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: U.S. Federal Hazardous Substances Act Consumer Product Safety Commission16 CFR § 1500.41 - Method of testing primary irritant substances
Version / remarks:
Formerly U.S. Federal Hazardous Substances Act Food and Drug Commission 21 CFR § 191.11
Principles of method if other than guideline:
- Principle of test: The method of testing the dermal corrosivity and primary irritation of substances referred to in § 1500.3(c)(3) and (4), respectively, is a patch-test technique on the abraded and intact skin of the albino rabbit, clipped free of hair. An equal number of exposures are made on areas of skin that have been previously abraded. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.
- Short description of test conditions: Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of the albino rabbit, clipped free of hair. A minimum of six subjects are used in abraded and intact skin tests. Introduce under a square patch, such as surgical gauze measuring 1 inch by 1 inch and two single layers thick, 0.5 milliliter (in the case of liquids) or 0.5 gram (in the case of solids and semisolids) of the test substance. Dissolve solids in an appropriate solvent and apply the solution as for liquids. The animals are immobilized with patches secured in place by adhesive tape. The entire trunk of the animal is then wrapped with an impervious material, such as rubberized cloth, for the 24-hour period of exposure. This material aids in maintaining the test patches in position and retards the evaporation of volatile substances.

- Parameters analysed / observed: After 24 hours of exposure, the patches are removed and the resulting reactions are evaluated on the basis of the following designated values:

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formations (injuries in depth) 4

Edema formation:
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and extending beyond the area of exposure) 4

The “value” recorded for each reading is the average value of the six or more animals subject to the test. Readings are again made at the end of a total of 72 hours (48 hours after the first reading). Evaluate the reactions of the abraded skin at 24 hours and 72 hours, as described in this paragraph. Add the values for erythema and eschar formation at 24 hours and at 72 hours for intact skin to the values on abraded skin at 24 hours and at 72 hours (four values). Similarly, add the values for edema formation at 24 hours and at 72 hours for intact and abraded skin (four values). The total of the eight values is divided by four to give the primary irritation score
GLP compliance:
no
Remarks:
Study predates GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Mobil Chemical Company (Edison, NJ) Lot# 1086
- Expiration date of the lot/batch: not specified
- Purity test date: not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, humidity
- Stability under test conditions: stable for duration of test
- Solubility and stability of the test substance in the solvent/vehicle: not applicable

Test animals

Species:
rabbit
Strain:
not specified
Remarks:
Albino
Details on test animals and environmental conditions:
Details on test animals and environmental conditions not provided.

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Remarks:
Abraded and Non-Abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
Both abbraded and intact skin of the albino rabbit, clipped free of hair were used in this study. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding. The test material is held against the skin for 24 hours by a dermal patch covered with an occlusive dressing.
Observation period:
24 and 72 hours post application
Number of animals:
Six
Details on study design:
TEST SITE
- Area of exposure: 1 inch x 1 inch
- Type of wrap if used: impervious material such as rubberized cloth

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: 24 hours

OBSERVATION TIME POINTS (indicate if minutes, hours or days): 24 and 72 hours

SCORING SYSTEM:
- Method of calculation: After 24 hours of exposure, the patches are removed and the resulting reactions are evaluated on the basis of the following designated values:

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formations (injuries in depth) 4

Edema formation:
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and extending beyond the area of exposure) 4

The “value” recorded for each reading is the average value of the six or more animals subject to the test. Readings are again made at the end of a total of 72 hours (48 hours after the first reading). Evaluate the reactions of the abraded skin at 24 hours and 72 hours, as described in this paragraph. Add the values for erythema and eschar formation at 24 hours and at 72 hours for intact skin to the values on abraded skin at 24 hours and at 72 hours (four values). Similarly, add the values for edema formation at 24 hours and at 72 hours for intact and abraded skin (four values). The total of the eight values is divided by four to give the primary irritation score. A primary irritation index score of 5.0 or more was considered to indicate a primary dermal irritant.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Time point:
other: 24h / 72h
Score:
0.95
Remarks on result:
other: includes both abraded and non-abraded scores
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
ca. 1
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks:
Effect persisted at 72 hours in 4 of 6 rabbits
Remarks on result:
other: 24 hour exposure, non-abraded
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
ca. 0.7
Max. score:
1
Reversibility:
not specified
Remarks:
Study terminated at 72 hours
Remarks on result:
other: 24 hour exposure non-abraded
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
ca. 0.2
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: 1 animal had slight edema
Remarks:
24 hour exposure, non-abraded
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
ca. 0
Max. score:
0
Remarks on result:
no indication of irritation
Remarks:
24 hour exposure, non-abraded
Other effects:
Abraded skin Irritation scores (irritation parameter; basis; timepoint; value; max score; reversibility; remarks):
Erythema; mean; 24 hours; ca. 1.0; max score = 1.0; Effect persisted in 4 out of 6 rabbits at 72 hours; 24 hour exposure, abraded
Erythema; mean; 72 hours; ca. 0.7; max scoe = 1.0; not specified, study terminated at 72 hours; 24 hour exposure, abraded
Edema; mean; 24 hours; ca. 0.2; max score = 1.0; Fully reversible within 72 hours; 24 hour exposure, abraded
Edema; mean; 72 hours; ca. 0.0; max score = 0.0; 24 hour exposure, abraded

Applicant's summary and conclusion

Interpretation of results:
other: Not Irritating
Conclusions:
Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone did not produce evidence of primary skin irritation or corrosion in an in-vivo assay. While the exposure conditions do not align with current GHS criteria, the occlusive dressing and prolonged exposure time represent a worse case sceanrio. The low mean erythema and edema scores following such a prolonged exposure do not warrant classification of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as a dermal irritant.
Executive summary:

The mean erythema and edema scores for Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone on unabraded skin were 1.0 and 0.2 respectively. These findings do not warrant classification of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as a dermal irritant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).