2,2-bis(methylthio)propane

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 guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

478-900-1

EC Name:

-

Cas Number:

6156-18-9

Molecular formula:

C5 H12 S2

IUPAC Name:

2,2-bis(methylthio)propane

Details on test material:

- Name of test material (as cited in study report): BISMETHYLTHIOPROPANE
- Synonym: BMTP
- Chemical name: 2,2-bis-methylthiopropane
- Batch number: 2KS149
- Description: colorless liquid
- Storage conditions: at room temperature and protected from light
- Purity: 97.76%
- Date of analysis: 8 November 2006
- Expiry date: November 2007.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 3.1 ± 0.1 kg
- Housing: individually in Pajon cages (50 cm x 57 cm x 75 cm)
- Diet: free access to 110C pelleted diet (SAFE, Villemoisson, Epinay sur-Orge, France)
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 30 January 2007 to 10 February 2007

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

Not rinced

Observation period (in vivo):

1 hour, 24, 48 and 72 hours then daily up to 10 days

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Kay and Calandra scale

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 9 days

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal: #1 & 2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 8

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 9

Irritation parameter:

iris score

Basis:

animal: #1, 2 & 3

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Slight or moderate chemosis (grade 1 or 2) was observed in all animals from day 1 until day 7 (two animals) or day 9 (one animal).
Slight or moderate redness of the conjunctiva (grade 1 or 2) was observed in all animals from day 1 until day 7 (two animals) or day 8 (one animal).
A clear discharge was noted in 2/3 animals on day 2; it persisted until day 4 in one of them.
An iritis (grade 1) was noted in 2/3 animals on day 1 then in all animals on day 2.
A slight corneal opacity (grade 1) was recorded in all animals on day 2; it persisted on day 3 in one of them.

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.7, 2.0 and 2.0 for chemosis, 1.7, 1.3 and 2.0 for redness of the conjunctiva, 0.3, 0.3 and 0.3 for iris lesions and 0.3, 0.3 and 0.7 for corneal opacity.

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

BISMETHYLTHIOPROPANE was irritant when administered by ocular route to rabbits.

Executive summary:

The potential of BISMETHYLTHIOPROPANE (BMTP) to induce ocular irritation was evaluated in rabbits according to OECD guideline 404. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. BMTP was first administered to a single male New Zealand White rabbit. Since BMTP was not severely irritant on this first animal, it was then evaluated simultaneously in two other animals. A single dose of 0.1 mL of the BMTP was instilled into the left conjunctival sac. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions (day 10 at the latest). The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were

calculated for each animal. Slight or moderate chemosis (grade 1 or 2) was observed in all animals from day 1 until day 7 (two animals) or day 9 (one animal). Slight or moderate redness of the conjunctiva (grade 1 or 2) was observed in all animals from day 1 until day 7 (two animals) or day 8 (one animal). A clear discharge was noted in 2/3 animals on day 2; it persisted until day 4 in one of them. An iritis (grade 1) was noted in 2/3 animals on day 1 then in all animals on day 2. A slight corneal opacity (grade 1) was recorded in all animals on day 2; it persisted on day 3 in one of them.  Mean scores calculated for each animal over 24, 48 and 72 hours were 1.7, 2.0 and 2.0 for chemosis, 1.7, 1.3 and 2.0 for redness of the conjunctiva, 0.3, 0.3 and 0.3 for iris lesions and 0.3, 0.3 and 0.7 for corneal opacity. BISMETHYLTHIOPROPANE was irritant when administered by ocular route to rabbits.