N,N'-di-sec-butyl-p-phenylenediamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study. No internationally accepted protocol followed, but study well documented and acceptable protocol.

Justification for type of information:

Key study, GLP, Klimisch score 2

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Two yound adult New Zealand White rabbits were randomly assigned to this study from a pool of animals which had been determined to have no previous corneal damage by the use of sterile fluorescein sodium. A volume of 0.1 mL test material, as received, was instilled into the conjunctival sac of the right eye of each test animal by gently pulling the lower eyelid away from the eyeball to form a cup. The lids were then held together for approximately one second, after which the animals were returned to their cages.
Observations for signs of ocular irritation and other clinical effects were conducted on the first, second, third, seventh, tenth, fourteenth and seventeenth day after dosing. The untreated eye of each animal served as the negative control. As considered necessary for evaluation of potential corneal involvement, sterile fluorescein sodium was applied to the eyes. After approx. 10 seconds, the excess fluorescein was flushed from the eyes with physiological saline, and an ultraviolet lamp was used to determine whether staining persisted. The method of Draize was used for scoring of eye irritation.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-di-sec-butyl-p-phenylenediamine

EC Number:

202-992-2

EC Name:

N,N'-di-sec-butyl-p-phenylenediamine

Cas Number:

101-96-2

Molecular formula:

C14H24N2

IUPAC Name:

N,N'-di-sec-butyl-p-phenylenediamine

Details on test material:

- Physical state: dark red/brown liquid
- Analytical purity: 96.09%
- Lot/batch No.: S
- Stability under test conditions: the test material was stated to react with strong oxidizing agents. According to the study report, it was exposed to no such materials, with the exceptions of those potenially present in the testing environment.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Isaac's Farm, Litchfield, Illinois
- Age at study initiation: young adults
- Weight at study initiation: 2.73 and 2.92 kg
- Housing: individually, stainless steel cages
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: quarantine, at least 5 days

ENVIRONMENTAL CONDITIONS: no data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Left eye served as negative control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

single treatment, no rinsing reported

Observation period (in vivo):

17 days

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: average of 24, 48 and 72 hours

Score:

28

Max. score:

110

Results 2

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

other: average of 24, 48 and 72 hours

Score:

16.3

Max. score:

110

Other effects:

All corneal and iridal involvement in both animals' eyes has subsided by the 7th day after exposure, and all conjunctival irritation had abated by day 14. Hardened skin around the eye occurred in both animals and was observed from the first through tenth day after exposure. The male also had blistered conjunctival tissue on the first two days after dosing. By day 14, scabs and/or scars were evident near each rabbit's eye, and scarring of perioccular skin was also observed in both animals on day 17, when the study was terminated. Since these changes in the skin near the eyes appeared to be the result of topical contact with the test material, it is likely that some material was expelled from the eyes after instillation.

Any other information on results incl. tables

Applicant's summary and conclusion

Executive summary:

0.1 mL of test substance was administered to the right eye of each of one male and one female albino rabbits. Observations for signs of ocular irritation and other clinical effects were conducted on days 1, 2, 3, 7, 10, 14 and 17 after exposure. The method of Draize was used for the scoring of eye irritation.

Eye irritation effects were observed at the cornea, iris and conjunctivae on the first 3 days after exposure. All corneal, iridal and conjunctival irritation had subsided by the fourteenth day after exposure. However, scarring of the exterior of the upper eyelid and/or skin near the eye had occurred in both animals by the 17th day after dosing, at which time the study was terminated.