4,4'-isopropylidenedi-2,6-xylol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-isopropylidenedi-2,6-xylol

EC Number:

227-033-5

EC Name:

4,4'-isopropylidenedi-2,6-xylol

Cas Number:

5613-46-7

Molecular formula:

C19H24O2

IUPAC Name:

4,4'-isopropylidenedi-2,6-xylol

Test material form:

solid: particulate/powder

Details on test material:

- Purity: 99.74%
- Synonym: 4,4’-(1-methylethylidene)-bis(2,6-dimethylphenol)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three male New Zealand White rabbits, 9 weeks of age, weighing 2.3 to 2.6 kg (at start of dosing) were obtained from Millbrook Breeding Labs, Amherst, MA. The animals were housed in compliance with USDA guidelines and were acclimated for 6 days prior to dosing. They were provided water ad libitum and certified feed as per the laboratory’s SOPs. Room temperature was 16-23°C and the relative humidity ranged between 45-78%. Room lights were on a 12-hour light/dark cycle.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

dosed as received; 0.1 mL (~0.075 - g)

Duration of treatment / exposure:

Test substance was instilled once into the right eye of each rabbit without rinsing.

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours after dose administration

Number of animals or in vitro replicates:

3

Details on study design:

Dose preparation: The test substance was administered as received from the Sponsor (undiluted). The powder was ground slightly and packed into a 1 cc syringe to a volume of 0.1 mL and the weights were recorded (0.062 g, 0.076 g and 0.087 g, for animals 1, 2 and 3, respectively).

Within the 24 hours prior to dosing, the eyes of the animals selected for the test were examined to insure that the eyes were free of abnormality, damage and disease. Animals were selected for use on study based on the results of the eye exam, body weight, sex and clinical evaluation.

A preanesthetic (2 drops of Tetracaine) was applied to the corneal surface to both eyes of each rabbit approximately 5 minutes prior to dosing. The test substance was then instilled into the right eye (conjunctival sac). The upper and lower lids were held together for approximately one second to minimize loss of the test substance. The left eye remained untreated and served as the control.

One animal was dosed initially and evaluated at one hour post-dose before the remaining 2 animals were dosed.

The eyes of the 3 test animals remained unrinsed throughout the study. 24 hours after instillation of the test substance, a wash out of the right eye was deemed unnecessary.

The eyes were examined at 1, 24, 48 and 72 hours after treatment and scored according to the Grades for Ocular Lesions provided below. Animals were observed daily for mortality and clinical signs of toxicity. Animals were weighed at study start (Day 0). All animals were euthanized following the final ocular grading at 72 hours.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 1 hour

Score:

7.3

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

other: Mean Total Score

Basis:

mean

Time point:

other: 24 hours

Score:

1.3

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

other: Mean Total Score

Basis:

mean

Time point:

other: 48 hours

Score:

0

Irritant / corrosive response data:

No corneal or iris involvement was observed in the treated (right) eyes of any animal at any time point. Only slight conjunctival redness, slight to obvious chemosis with slight to moderate discharge were observed in the three animals at 1 hour. By 24 hours, only slight conjunctival redness and discharge were noted in one animal. All animals showed no signs of ocular irritation, redness or discharge at 48 and 72-hours.

Other effects:

No systemic signs of toxicity were observed during the course of the study. No irritation was observed in the untreated control (left) eyes at any scoring interval.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Conclusions:

Under the conditions of this study, TMBPA was found to be slightly irritating to the eye of rabbits according to the Kay and Calandra criteria (MMTS = 7.3 at 1 hour observation). In accordance with the GHS Classification, TMBPA was considered non-irritating since the criteria for a positive response were not met for any of the three animals.