Registration Dossier

Administrative data

Description of key information

In-Vivo Skin Irritation - Not Irritating for rabbit (equivalent or similar to U.S. Federal Hazardous Substances Act Consumer Product Safety Commission16 CFR § 1500.41 - Method of testing primary irritant substances)

Acute Dermal Toxicity - Not Irritating for rabbit (OECD TG 402)

In-Vivo Eye Irritation - Not irritating for rabbit (equivalent or similar to U.S. Federal Hazardous Substances Act Consumer Product Safety Commission 16 CFR § 1500.42- Test for eye irritants/ OECD TG 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Reason / purpose:
data waiving: supporting information
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
02 March 1978 - 12 April 1978
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
; Dermal reactions noted as part of Acute Dermal LD50 study
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: The method of testing the dermal toxicity of the test substance is a patch-test technique on the abraded and intact skin of the New Zealand White rabbit, clipped free of hair. The animals were observed daily for 14 days for clinical signs of toxicity and mortality, and once on Day 1 for skin reactions.
- Short description of test conditions: Twelve New Zealand White Rabbits were clipped free of abdominal hair. Epidermal abrasions were made longitudinally every 2 to 3 cm over the exposed area on even numbered rabbits. The abrasions were sufficiently deep to penetrate the stratum corneum but not deep enought to produce bleeding. The area was covered with gauze and the trunk was wrapped with impervious material for 24 hours. At 24 hours, the rabbits were cleansed and dermal reactions were evaluated by the Draize technique.
- Parameters analysed / observed: Erythema and edema were evaluated at 24 hours post application.
GLP compliance:
no
Remarks:
Study predates GLP
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# CRU 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: not specified
- Stability under test conditions: not specified
- Solubility and stability of the test substance in the solvent/vehicle: not applicable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Details on test animals and environmental conditions not provided
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.0 g/kg and 10.0 g/kg
Duration of treatment / exposure:
Epidermal abrasions were made longitudinally every 2 to 3 cm over the exposed area on even numbered rabbits. The abrasions were sufficiently deep to penetrate the stratum corneum but not deep enought to produce bleeding. The area was covered with gauze and the trunk was wrapped with impervious material for 24 hours.
Observation period:
The animals were observed daily for 14 days for clinical signs of toxicity and mortality, and once on Day 1 for skin reactions.
Number of animals:
5.0 g/kg- 4 rabbits; 10.0 g/kg - 8 rabbits
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
ca. 1.75
Max. score:
2
Reversibility:
other: Observations of skin reactions terminated at 24 hours
Remarks on result:
other: 5.0 g/kg
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
other: Observations of skin reactions terminated at 24 hours
Remarks on result:
other: 5.0 g/kg
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
ca. 1.75
Max. score:
3
Reversibility:
other: Observations of skin reactions terminated at 24 hours
Remarks on result:
other: 10.0 g/kg
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
ca. 0.875
Max. score:
3
Reversibility:
other: Observations of skin reactions terminated at 24 hours
Remarks on result:
other: 10.0 g/kg
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. These findings do not meet OECD testing criteria necessary for classification. However, this study should only be used as supporting information due to the limited range of observations and documentation.
Executive summary:

The primary dermal irritation potential for Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone was evaluated by application of 5.0 and 10.0 g/kg test material to the intact and abraded skin of 12 albino rabbits in an acute dermal toxicity study. Mild erythema and edema was observed at 24 hours at bose dose levels. However, due to the limited documentation and deviations from OECD skin irritation testing guidelines such as longer exposure duration (24 hours), occlusive dressing, and abraded skin, this study should only be used as supporting information.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Reason / purpose:
data waiving: supporting information
Endpoint:
eye 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
Qualifier:
equivalent or similar to
Guideline:
other: U.S. Federal Hazardous Substances Act Consumer Product Safety Commission 16 CFR § 1500.42- Test for eye irritants.
Version / remarks:
Formerly U.S. Federal Hazardous Substances Act Food and Drug Commission 21 CFR § 191.12
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
- Principle of test: In the method of testing the ocular irritation of a substance referred to in § 1500.3(c)(4), six albino rabbits are used for each test substance.

- Short description of test conditions: Both eyes of each animal in the test group shall be examined before testing, and only those animals without eye defects or irritation shall be used. The test material is placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance is dropped. The lids are then gently held together for one second and the animal is released. The other eye, remaining untreated, serves as a control. For testing liquids, 0.1 milliliter is used. For solids or pastes, 100 milligrams of the test substance is used, except that for substances in flake, granule, powder, or other particulate form the amount that has a volume of 0.1 milliliter (after compacting as much as possible without crushing or altering the individual particles, such as by tapping the measuring container) shall be used whenever this volume weighs less than 100 milligrams. In such a case, the weight of the 0.1 milliliter test dose should be recorded. The eyes are not washed following instillation of test material except if noted.
- Parameters analysed / observed: The eyes are examined and the grade of ocular reaction is recorded at 24, 48, and 72 hours.
GLP compliance:
no
Remarks:
Study predates GLP
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
- Stability under test conditions: stable through duration of test
- Solubility and stability of the test substance in the solvent/vehicle: not applicable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable
Species:
rabbit
Strain:
New Zealand White
Remarks:
mixed sex
Details on test animals or tissues and environmental conditions:
Details on test animals and environmental conditions not provided

TEST ANIMALS
- Source: not specified
- Age at study initiation: not specified
- Weight at study initiation: 1.8 -2.0 kg
- Housing: not specified
- Diet (e.g. ad libitum): not specified
- Water (e.g. ad libitum): not specified
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
The test material is placed in one eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance is dropped. The lids are then gently held together for one second and the animal is released.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing
- Time after start of exposure:

SCORING SYSTEM: Scale of Weighted Scores for Grading the Severity of Ocular Lesion (Draize et al 1944)
Cornea
A. Opacity: Degree of density (area most dense taken for reading).
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacrous area, no details or iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4
B. Area of cornea involved
One quarter (or less), but not zero 1
Greater than one quarter, but less than one-half 2
Greater than one-half but less than three quarters 3
Greater than three quarters up to whole area 4
Score equals A x B x 5 Total maximum = 80

Iris
A. Values
Normal 0
Markedly deepened rugae, congestion, swelling moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) *1
No reaction to light, hemorrhage, gross destruction (any or all of these) *2
Score equals A x 5 Total possible maximum =10

Conjunctivae
A. Redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris).
Blood vessels normal 0
Some blood vessels definitely hyperemic (injected) 1
Diffuse, crimson color, individual vessels not easily discernible *2
Diffuse beefy red *3
B. Chemosis (refers to lids and/or nictitating membranes)
No swelling 0
Any swelling above normal (includes nictitating membranes) 1
Obvious swelling with partial eversion of lids *2
Swelling with lids about half closed *3
Swelling with lids more than half-closed *4
C. Discharge
Any amount different from normal (does not include small amount observed in inner canthus of normal rabbits) 1
Discharge with moistening of the lids and hairs just adjacent to the lids 2
Discharge with moistening of the lids and considerable area around the eye 3
Score equals (A + B + C) x 2 Total maximum = 20

TOOL USED TO ASSESS SCORE: not specified
Irritation parameter:
cornea opacity score
Remarks:
non-weighted Draize
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Remarks:
non-weighted Draize
Basis:
mean
Time point:
24/48/72 h
Score:
0.17
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
non-weighted Draize
Basis:
mean
Time point:
24/48/72 h
Score:
0.22
Reversibility:
fully reversible within: 72 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Remarks:
non-weighted Draize
Basis:
mean
Time point:
24/48/72 h
Score:
0.16
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone did not produce evidence of eye irritation or corrosion in an in-vivo assay. These findings do not warrant classification of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as a Category 1 Serious Eye Damage or Category 2 Eye Irritant under the Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).
Executive summary:

The primary eye irritation potential of Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone was evaluated by application of test material to the eye of six albino rabbits. Mean non-weighted Draize scores for 24/48/72 hours were 0, 0.17, 0.22 and 0.16 for Cornela opacity, Iris, Conjuctival Redness, and Chemosis respectively. These findings do not warrant classification of  Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone as an eye irritant under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone did not produce evidence of skin irritation or corrosion in an in-vivo assay. These findings do not warrant classification of the substance as a Category 1 Skin Corrosive or Category 2 Skin Irritant under the Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Hydrazine Carboximidamide, 2-((2-hydroxyphenyl)methylene)-, reaction products with 2 undecanone did not produce evidence of serious eye damage or irritation in an in-vivo assay and does not warrant classification as Eye Damage Category 1 or Eye Irritant Category 2 under the Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).