1,4-Benzenedicarboxylic acid, dimethyl ester, manuf. of, by-products from

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 September 2009 - 09 October 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to EC and/or OECD guidelines and in compliance with GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,4-Benzenedicarboxylic acid, dimethyl ester, manuf. of, by-products from

EC Number:

273-521-6

EC Name:

1,4-Benzenedicarboxylic acid, dimethyl ester, manuf. of, by-products from

Cas Number:

68988-22-7

Molecular formula:

Molecular formula, molecular weight range, SMILES notation, InChi and structural formula are not available, because DMT byproducts (CAS # 68988-22-7) is a UVCB subsance.

IUPAC Name:

1,4-Benzenedicarboxylic acid, dimethyl ester, manuf. of, by-products from

Details on test material:

- Name of test material (as cited in study report): Terate® 091 Residue
- Substance type: Dark brown solid with soft lumps
- Physical state: Solid
- Analytical purity: 100%
- Composition of test material, percentage of components: by-product from the manufacture of 1,4-Benzenedicarboxylic acid, dimethyl ester
- Lot/batch No.: NB8322-091
- Expiration date of the lot/batch: 14 July 2010
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 9-11 weeks or 18-20 weeks
- Weight at study initiation: 1599, 1636 and 3017 grams

- Housing: Animals were individually housed in labeled cages with perforated floors and shelters
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1 ¿ 20.0ºC
- Humidity (%): 36 - 78%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 28 September 2009 To: 09 October 2009

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye of each rabbit remained untreated and served as the reference control

Amount / concentration applied:

100 mg (range 100.0 - 100.5 mg) of the unchanged test substance (maximum amount required)

Duration of treatment / exposure:

Test substance was instilled in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The eyes were not washed.

Observation period (in vivo):

Up to 72 hours after instillation

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM:
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster): 0
Scattered or diffuse areas of opacity, details of iris clearly visible: 1
Easily discernible translucent area, details of iris slightly obscured: 2
Nacreous area, no details of iris visible, size of pupil barely discernible: 3
Opaque cornea, iris not discernible through the opacity: 4

Area of cornea involved:
No ulceration or opacity: 0
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

IRIS
Normal: 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive): 1
No reaction to light, hemorrhage, gross destruction (any or all of these): 2

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal: 0
Some blood vessels definitely hyperaemic (injected): 1
Diffuse, crimson color, individual vessels not easily discernible: 2
Diffuse beefy red: 3

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

Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals): 0
Any amount different from normal and/or lacrimation: 1
Discharge with moistening of the lids and hairs just adjacent to lids: 2
Discharge with moistening of the lids and hairs (considerable area around the eye): 3


TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no irritation observed

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no irritation observed

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness, chemosis and discharge

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: Irritation of the conjunctivae, which consisted of redness, chemosis and discharge was observed at 1 hour after instillation. The irritation completely resolved within 24 hours in all animals.

Irritant / corrosive response data:

Instillation of approximately 100 mg of Terate® 091 Residue (maximum amount required) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation completely resolved within 24 hours in all animals.
No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Other effects:

None

Any other information on results incl. tables

Remnants of the test substance were present on the outside of the eyelids after instillation and throughout the observation period.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on these results Terate® 091 Residue does not have to be classified and has no obligatory labeling requirement for eye irritation according to the:
- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures,
- EC criteria for classification and labeling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and amendments of this Directive published in the Official Journal of the European Union),
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007).

Executive summary:

Eye irritancy of the test substance was determined in a guideline study (OECD TG 405) in rabbits. The test substance was found to be not irritating to eyes.