Hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2-undecanone

Skin irritation / corrosion

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

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

Test material information

Constituent 1

Reference substance name:

Hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2-undecanone

EC Number:

270-151-7

EC Name:

Hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2-undecanone

Cas Number:

68411-85-8

Molecular formula:

C19H32N4O2

IUPAC Name:

2-{[(6-oxocyclohexa-2,4-dien-1-ylidene)methyl]amino}guanidine; undecan-2-one

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 or test system 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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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).