N-(1,1-dimethylethyl)bis(2-benzothiazolesulfen)amide

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: GLP study according to USEPA and EU protocols. Minor deviations from animal housing and care AAALAC standards were reported, but were considered to have had no effect on the oucome of this study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

Test guideline 2

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:

N-(1,1-dimethylethyl)bis(2-benzothiazolesulfen)amide

EC Number:

407-430-1

EC Name:

N-(1,1-dimethylethyl)bis(2-benzothiazolesulfen)amide

Cas Number:

3741-80-8

Molecular formula:

C18H17N3S4

IUPAC Name:

bis(1,3-benzothiazol-2-ylsulfanyl)(tert-butyl)amine

Details on test material:

- Name of test material (as cited in study report): CP-22595
- Physical state: off white powder
- Analytical purity: 89.0 - 93.3%
- Purity test date: 21 December 1989 and 06 April 1990.
- Lot/batch No.: 4064285
- Stability under test conditions: confirmed by HPLC experiment
- Storage condition of test material: room temperature

The test material was ground in a mortar prior to instillation.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Mohican Valley Trabbitry, Loudonville, Ohio
- Age at study initiation: young adult
- Weight at study initiation: 2.6-3.2 kg
- Housing: individually housed in suspended stainless steel cages in an environment-controlled room
- Diet (e.g. ad libitum): Prolab Rabbit Ration, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days
- Animal identification: plastic ear tags + cage cards

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 61-70°F (= ca. 16-21°C)
- Humidity (%): 40-60%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Remarks:

test substance was ground prior to instillation

Controls:

other: contralateral eye of each test rabbit.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.027g (0.1 ml equivalent)
- Concentration (if solution): not applicable

Duration of treatment / exposure:

No-rinse procedure. Immediately after dosing, the eyelids were held together for approcimately one second.

Observation period (in vivo):

Both eyes (test and control) of each animal were examined for signs of irritation at 1, 24, 48 and 72 hours after dosing.

Number of animals or in vitro replicates:

6: 1 male, 5 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: n/a

SCORING SYSTEM:
A detailed scoring system is described in the study protocol. Separate scores for cornea, iris and conjunctivae are assigned.

TOOL USED TO ASSESS SCORE: macroscopical examination + fluorescein dye

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: conjunctival redness

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

other: conjunctival edema

Results 5

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Remarks on result:

other: not specified

Other effects:

Exposure to the test substance produced iritis in 5/6 rabbits at the 1 hour scoring interval which resolved by 24 hours postdose. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 animals at 1 hour postdose. The conjunctival irritation diminished over the test period and resolved by the 48 hour scoring interval. Corneal epithelial sloughing was observed in one test eye but was not considered significant due to the lack of accompanying corneal opacity.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the EEC Evaluation Criteria, the calculated mean ocular irritation scores (for 24, 48 and 72 hours) and irritation classifications for corneal opacity, iris lesion, conjunctival redness and conjunctival edema were 0.00 (non-irritant), 0.00 (non-irritant), 0.33 (non-irritant) and 0.00 (non-irritant), respectively.