trans-menthone

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from safety assessment report

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

MAK Value Documentation of test chemical in German language

Author:

The MAK Collection for Occupational Health and Safety

Year:

2012

Bibliographic source:

The MAK Collection for Occupational Health and Safety; 2012

Reference 2

Reference Type:

secondary source

Title:

UNWASHED PRIMARY EYE IRRITATION STUDY

Author:

NTRL REPORT

Year:

1982

Bibliographic source:

NTRL REPORT- 1982

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

An Unwashed Primary Eye Irritation study was conducted in New Zealand White rabbits to assess an eye irritancy of test chemical.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methylcyclohexane

Cas Number:

108-87-2

Molecular formula:

C7H14

IUPAC Name:

Methylcyclohexane

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Methylcyclohexane- Molecular formula: C7H14- Molecular weight: 98.1876 g/mol- Substance type: organic - Physical state: Liquid- Smiles notation: CC1CCCCC1- InChl: 1S/C7H14/c1-7-5-3-2-4-6-7/h7H,2-6H2,1H3

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS- Source: Dutchland laboratory Animals, Inc.- Age at study initiation: Young adult- Weight at study initiation: - Fasting period before study:- Housing: Individual- Diet (e.g. ad libitum): Purina lab Rabbit Chow. ad libitum. Feed will be periodically analyzed for concentrations of specified heavy metals, antibiotics, aflatoxin, pesticides, and nitrosamines.- Water (e.g. ad libitum): Tap water, ad libitum. The water is routinely-analyzed on a retrospective basis for specified microorganisms, pesticides, heavy metals, alkalinity, and halogens.- Acclimation period: Minimum of one week.ENVIRONMENTAL CONDITIONS- Temperature (°C): 70 ± 4°;- Humidity (%):40-60%- Photoperiod (hrs dark / hrs light): 12 hour light-dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

Liquid: Amount: 0.1 ml. concentration applied: 100%Solid or pastes - 100 mg. sample as a normal saline slurry.

Duration of treatment / exposure:

TEST SITE- Area of exposure: the Lower conjunctival sac of the left eye of each test animal:REMOVAL OF TEST SUBSTANCE- Washing (if done): not rinsed - Time after start of exposure:7 days SCORING SYSTEM: According to the Draize system of scoring (Draize, J.H., 1959.Dermal Toxicity, pp. 46-59. In Appraisal of the Safety of Chemicals In Foods, Drugs, and cosmetics. Association of Food and Drug Officials of the U.S•• Austin. Texas.). (refer table given below)

Observation period (in vivo):

7 days

Duration of post- treatment incubation (in vitro):

At one, 24, 48. and 72 hours, and at 4 and 7 days after treatment

Number of animals or in vitro replicates:

6/group (3/sex)

Details on study design:

TEST SITE- Area of exposure: the Lower conjunctival sac of the left eye of each test animal:REMOVAL OF TEST SUBSTANCE- Washing (if done): not rinsed - Time after start of exposure:7 days SCORING SYSTEM: According to the Draize system of scoring (Draize, J.H., 1959.Dermal Toxicity, pp. 46-59. In Appraisal of the Safety of Chemicals In Foods, Drugs, and cosmetics. Association of Food and Drug Officials of the U.S•• Austin. Texas.). (refer table given below)

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

110

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Only conjunctival redness was observed in few treated rabbits.

Any other information on results incl. tables

DRAlZE SCALE FOR SCORING OCULAR LESIONS

Cornea Grade (A)Opacity: degree of density (readings should be taken from most dense area)* No ulceration or opacity = 0 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris slightly obscured = 1 Easily discernible translucent area; details of iris slightly obscured = 2 Opalescent area; no details of iris visible; size of pupil barely discernible = 3 Opaque cornea; iris not discernible through the opacity = 4 (B) Area Of Cornea Involved One quarter (less than ) but not zero=1 Greater than one quarter but less than half=2 Greater than one half quarter but less than three quarter =3 Greater than three quarter upto whole area=4 Score equals: A X B X 5                                                                                                  Maximum Score=80

Iris Normal = 0 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia; or injection; iris reactive to light (a sluggish reaction is considered to be an effect = 1 Hemorrhage, gross destruction, or no reaction to light = 2 Score equals: A X 5                                                                                                           Maximum Score: 10

Conjunctivae (A)Redness (refers to palpebral and bulbar conjunctivae; excluding cornea and iris) Vessels Normal = 0 Vessels definitely injected above normal = 1 Diffuse, crimson colour; individual vessels not easily discernible = 2 Diffuse beefy red = 3 (B )Chemosis Swelling (refers to lids and/or nictating membranes) Normal = 0 Any swelling above normal (includes nictating membrane)= 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 No discharge =0 Any amount different from norm al (does not include small amounts observed in inner canthus of nomal animals) =1 Discharge with moistening of the lids and hairs just adjacent to lids = 2 Discharge with moistening of the lids and hairs. and considerable area around the eye =3 Score equal s (A + B+ C) x 2                                                                                         Maximum Score: 20

The overall Maximum Possible Score is the sum of scores obtained for the cornea. iris and conjunctivae. Total maximum score possible = 110

Applicant's summary and conclusion

Interpretation of results:

other: Not irritating

Conclusions:

The test chemical was considered to be not irritating into the eyes of male and female New Zealand White rabbits using an unwashed procedure.

Executive summary:

An Unwashed Primary Eye Irritation study was conducted in New Zealand White rabbits to assess an eye irritancy of test chemical .

 

The 0.1ml of undiluted chemical was installed into thelower conjunctival sac of the left eye of each test animal.The untreated right eye of each rabbits served as a control. The ocular reactions were scored at one, 24, 48. and 72 hours, and at 4 and 7 days after treatment according to Draize system.

 

The left eye of six albino rabbits will be examined 24 to 72 hours prior to instillation of the test material with fluorescein dye solution. Animals showing corneal damage will not be used on the test.

 

After the reading at 24 hours. The eyes of the rabbits were examined with fluorescein dye solution. Any corneal damage was reconfirmed by examination with fluorescein dye solution at subsequent readings. The treated eye of each animal was re-examined at termination using the fluorescein dye solution to confirm the absence or presence of any corneal damage.

 

The chemical induced only conjunctival redness in few treated rabbits with overall irritation score of 0.0 over a period of 7 days. Thereforethe test chemical was considered to be not irritating in into the eyes of male and female New Zealand White rabbits using an unwashed procedure.