Dimethyl isophthalate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl isophthalate

EC Number:

215-951-9

EC Name:

Dimethyl isophthalate

Cas Number:

1459-93-4

Molecular formula:

C10H10O4

IUPAC Name:

1,3-dimethyl benzene-1,3-dicarboxylate

Test material form:

solid: flakes

Details on test material:

Morflex 1129 flake, batch No. 99275, Material No. 101149
Purity: 99.85%. Impurities: dimethyl terephthalate, 0.5% maximum.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 3.0 to 3.5 kg
- Housing: individually in suspended cages
- Diet (e.g. ad libitum): PMI rabbit chow (diet # 5321)
- Water (e.g. ad libitum): at libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature controlled

IN-LIFE DATES: From: 26 November 2012 To: 28 November 2012

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

61.1 mg

Duration of treatment / exposure:

throughout 72 hour test period

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

The material was placed by a syringe-type applicator into the conjunctival sac of one eye; the other eye served as a control. The lids were gently held together for approximately one second to insure adequate distribution of the test article.
A Mini-mag flashlight with a high intensity bulb was use to observe irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours post-dosing. Sodium fluorescein dye was used at the 24-hour observation interval, and the eye was examined with the use of a fluorescent source. Ocular reactions were scored according to the Draize technique.

Value*
Cornea
A. Opacity-degree of density
No Opacity 0
Scattered or diffuse area, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescent areas, no details of iris visible, size of pupil barely discernible 3
Opaque, iris invisible 4
B. Area of cornea involved
One quarter (or less) but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4
AxBx5 Total 80
Iris
A Values
Normal 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all 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
A x 5 Total 10
Conjunctivae
A Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson red, individual vessels not easily discernible 2
Diffuse beefy red 3
B. Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half-closed 3
Swelling with lids about half-closed to completely closed 4
C. Discharge
No discharge 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal 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 (A + B + C) x 2 Total 20

The maximum total score is the sum of all scores obtained for the cornea, iris and conjunctivae. Total maximum score possible: Total: 110


Serious corneal lesions as pannus and phylctenar reactions are not recorded. Any substance eliciting such damaging reactions is deemed to be too severely irritating for use about the eyes. A substance which has elicited corneal and iris lesions which have not cleared by the seventh day is considered a severe eye irritant.
Draize J.H., Woodard G., Calvery H.O. (1944). "Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes". J. Pharmacol. And Exp. Therapeutics 82: 377–390.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48 hours

Score:

0

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 hour

Score:

6.66

Max. score:

110

Reversibility:

fully reversible

Results 3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 hours

Score:

2.66

Max. score:

110

Reversibility:

fully reversible

Irritant / corrosive response data:

Conjunctival irritation was observed in 3 rabbits at the 1 hour time point, and in 2 rabbits at the 24 hour time point. All irritation had resolved by 48 hours.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dimethyl isophthalate (DMIP) was tested for eye irritation in New Zealand white rabbits using an OECD 405 protocol. Irritation was observed in the conjunctival but not in cornea or iris. DMIP is concluded to be an eye irritant.