4'-tert-butyl-2',6'-dimethyl-3',5'-dinitroacetophenone

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12-09-1996 to 21-02-1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4'-tert-butyl-2',6'-dimethyl-3',5'-dinitroacetophenone

EC Number:

201-328-9

EC Name:

4'-tert-butyl-2',6'-dimethyl-3',5'-dinitroacetophenone

Cas Number:

81-14-1

Molecular formula:

C14H18N2O5

IUPAC Name:

1-(4-tert-butyl-2,6-dimethyl-3,5-dinitrophenyl)ethanone

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: RIFM; 9615500072

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: ground in a mortar with a pestle, and passed through a No. 40 mesh sieve

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Myrtle’s rabbitry, TN, USA
- Age at study initiation: adult
- Weight at study initiation:2.8 kg
- Housing: Individually in stainless stain cages
- Diet: PMI certified rabbit chow #5322 (Purina Mills Inc) ad libitum
- Water: Municipal tap water treated by reverse osmosis ad libitum
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18.2-20.5°C
- Humidity: 26-31%
- Air changes (per hr): 10-15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):70 mg

Duration of treatment / exposure:

Rinsed group: 30 seconds
Non-rinsed group:72 hours

Observation period (in vivo):

Rinsed and non-rinsed groups: 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

Rinsed group: 3 females
Non-rinsed group: 2 males and 1 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes (rinsed group)
- Time after start of exposure: Approximately 30 seconds after instillation of the test article, with physiological saline.

SCORING SYSTEM & TOOL USED TO ASSESS SCORE: The eyes were macroscopically examined with the aid of an auxillary light source for signs of irritation at 1, 24, 48 and 72 hours after dosing according to the Ocular Grading System presented in Protocol Appendix A which is based on Draize. Following macroscopic observations at the 24 hour scoring interval, the fluorescein examination procedure was repeated on all test and control eyes and any residual test article was gently rinsed from the eye at this time (if possible) using physiological saline. If any fluorescein findings were noted at 24 hours, a fluorescein exam was conducted on the affected eyes at each subsequent interval until a negative response was obtained.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

No rinse group

Basis:

animal: 1, 2, 3

Time point:

24/48/72 h

Score:

0

Results 2

Irritation parameter:

iris score

Remarks:

No rinse group

Basis:

animal: 1, 2, 3

Time point:

24/48/72 h

Score:

0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

No rinse group

Basis:

animal #1

Time point:

24 h

Score:

4

Reversibility:

fully reversible

Results 4

Irritation parameter:

conjunctivae score

Remarks:

No rinse group

Basis:

animal #1

Time point:

other: 48/72 h

Score:

0

Results 5

Irritation parameter:

conjunctivae score

Remarks:

No rinse group

Basis:

animal #2

Time point:

24 h

Score:

2

Reversibility:

fully reversible

Results 6

Irritation parameter:

conjunctivae score

Remarks:

No rinse group

Basis:

animal #2

Time point:

other: 48/72 h

Score:

0

Results 7

Irritation parameter:

conjunctivae score

Remarks:

No rinse group

Basis:

animal #3

Time point:

24 h

Score:

2

Reversibility:

fully reversible

Results 8

Irritation parameter:

conjunctivae score

Remarks:

No rinse group

Basis:

animal #3

Time point:

other: 48/72 h

Score:

0

Results 9

Irritation parameter:

cornea opacity score

Remarks:

Rinse group

Basis:

animal: 1, 2, 3

Time point:

24/48/72 h

Score:

0

Results 10

Irritation parameter:

iris score

Remarks:

Rinse group

Basis:

animal: 1, 2, 3

Time point:

24/48/72 h

Score:

0

Results 11

Irritation parameter:

conjunctivae score

Remarks:

Rinse group

Basis:

animal: 1, 2

Time point:

24/48/72 h

Score:

0

Results 12

Irritation parameter:

conjunctivae score

Remarks:

Rinse group

Basis:

animal #3

Time point:

24/48 h

Score:

2

Reversibility:

fully reversible

Results 13

Irritation parameter:

conjunctivae score

Remarks:

Rinse group

Basis:

animal #3

Time point:

72 h

Score:

0

Results 14

Irritation parameter:

chemosis score

Basis:

animal: 1, 2, 3

Time point:

24/48/72 h

Score:

0

Remarks on result:

other:

Remarks:

Included in conjunctival score

Irritant / corrosive response data:

Iris scores = Iritis X 5
Cornea scores = Opacity x Area x 5
Conjunctival scores = (Redness + Swelling + Discharge) X 2

No rinse group: Exposure to the test article produced conjunctivitis (redness, swelling and/or discharge) in the 3/3 test eyes at the 1 hour scoring interval (Table 1). The conjunctival irritation resolved completely in all animals by the 48 hours scoring interval. No corneal opacity or iritis was observed in the test eyes at any time-point. No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

Rinsed group: Exposure to the test article produced conjunctivitis (redness and swelling) in 3/3 test eyes at the 1 hour scoring interval (Table 2). The conjunctival irritation resolved completely in all animals by the 72 hour scoring interval. No corneal opacity or iritis was observed in the test eyes at any time-point. No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an in vivo eye irritation study in rabbits, musk ketone is not irritating.

Executive summary:

In a primary eye irritation study (29495), 70 mg of musk ketone (undiluted) was instilled into the conjunctival sac of the right eye of adult New Zealand rabbits (3 females; rinsed group and 2 males and 1 female; non-rinsed group). Approximately 30 seconds after instillation of the test article, eyes of the rinsed group were washed with physiological saline. The remaining rabbits were not rinsed. Animals then were observed for 3 days.  Irritation was scored on a method based on Draize.

In the group of animals with no rinsing, exposure to the test article produced conjunctivitis (redness, swelling and/or discharge) in the 3/3 test eyes at the 1 hour scoring interval . The conjunctival irritation resolved completely in all animals by the 48 hours scoring interval. No corneal opacity or iritis was observed in the test eyes at any time-point. No corneal opacity, iritis or conjunctivitis was observed in the control eyes. In the group of animals with rinsing, exposure to the test article produced conjunctivitis (redness and swelling) in 3/3 test eyes at the 1 hour scoring interval. The conjunctival irritation resolved completely in all animals by the 72 hour scoring interval. No corneal opacity or iritis was observed in the test eyes at any time-point. No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

In this study, musk ketone is not an eye irritant.