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

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

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

Test guideline 2

Qualifier:

equivalent or similar to guideline

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

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
- 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

Test animals / tissue source

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

Test system

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

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Applicant's summary and conclusion

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).