2,2-bis(methylthio)propane

Endpoint summary

Description of key information

2,2-Bis(methylthio)propane was slightly irritant when applied topically and irritant when administered by ocular route to rabbits.

 

Skin irritation

The potential of 2,2-Bis(methylthio)propane to induce skin irritation was evaluated in rabbits according to OECD guideline 404 (Rokh, 2007b). The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. 2,2-Bis(methylthio)propane was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since 2,2-Bis(methylthio)propane was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals. A single dose of 0.5 mL of the undiluted 2,2-Bis(methylthio)propane was applied to the closely-clipped skin of one flank. 2,2-Bis(methylthio)propane was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily for 15 days. The mean values of the scores for erythema and edema were calculated for each animal.

After a 3-minute exposure (one animal), no cutaneous reactions were observed. After a 1-hour exposure (one animal), a very slight erythema was noted from day 1 until day 4. After a 4-hour exposure (three animals), a very slight to moderate erythema was noted in all animals from day 1 until day 3, 5 or 15 (end of the observation period). A dryness of the skin was recorded in 2/3 animals from day 4 until day 10 or 15. Mean scores over 24, 48 and 72 hours for each animal were 1.0, 2.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema. 2,2-Bis(methylthio)propane was slightly irritant when applied topically to rabbits.

 

Eye irritation

The potential of 2,2-Bis(methylthio)propane to induce ocular irritation was evaluated in rabbits according to OECD guideline 404 (Rokh, 2007c). The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. 2,2-Bis(methylthio)propane was first administered to a single male New Zealand White rabbit. Since 2,2-Bis(methylthio)propane 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 2,2-Bis(methylthio)propane 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. 2,2-Bis(methylthio)propane was irritating when administered by ocular route to rabbits.

 

Respiratory tract irritation

The acute inhalation toxicity of 2,2-Bis(methylthio)propane was evaluated in a study performed following the OECD guideline 403 (Schuler, 2008; see section Acute Toxicity)). A group of five male and five female Wistar was exposed by nose-only, flow-past inhalation to the test item at an analytically determined mean concentration of 20.2 mg/L air. No sign of respiratory tract irritation was observed in the exposed animals.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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: 2.9 ± 0.2 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 23 January 2007 to 08 February 2007

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

1 hour, 24, 48 and 72 hours, then daily up to 15 days

Number of animals:

3

Details on study design:

TEST SITE
The test item was first evaluated on a single animal (No. 782). The durations of exposure were 3 minutes, 1 hour and 4 hours.
Since the test item was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals (Nos. 799 and 800). Doses of 0.5 mL of the undiluted test item were placed on a dry gauze pad, which was then applied to an area of approximately 6 cm2 of the anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) or the posterior right flank (application for 4 hours) of the animals.
The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.
The untreated skin served as control.
No residual test item was observed on removal of the dressing.

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

SCORING SYSTEM:
Kay and Calandra scale

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 15 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

edema score

Basis:

animal: #1, 2 & 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

After a 3-minute exposure (one animal)
No cutaneous reactions were observed.

After a 1-hour exposure (one animal)
A very slight erythema (grade 1) was noted from day 1 until day 4.

After a 4-hour exposure (three animals)
A very slight to moderate erythema (grade 1 to 3) was noted in all animals from day 1 until day 3, 5 or 15 (end of the observation period).
A dryness of the skin was recorded in 2/3 animals from day 4 until day 10 or 15.

Interpretation of results:

GHS criteria not met

Conclusions:

BISMETHYLTHIOPROPANE was slightly irritant when applied topically to rabbits.

Executive summary:

The potential of BISMETHYLTHIOPROPANE (BMTP) to induce skin 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 applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since BMTP was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals. A single dose of 0.5 mL of the undiluted BMTP was applied to the closely-clipped skin of one flank. BMTP was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily for 15 days. The mean values of the scores for erythema and edema were calculated for each animal.

After a 3-minute exposure (one animal), no cutaneous reactions were observed. After a 1-hour exposure (one animal), a very slight erythema was noted from day 1 until day 4. After a 4-hour exposure (three animals), a very slight to moderate erythema was noted in all animals from day 1 until day 3, 5 or 15 (end of the observation period). A dryness of the skin was recorded in 2/3 animals from day 4 until day 10 or 15. Mean scores over 24, 48 and 72 hours for each animal were 1.0, 2.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema. BISMETHYLTHIOPROPANE was slightly irritant when applied topically to rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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

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

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

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

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

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

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

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

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

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.

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.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

According to the available skin, eye and respiratory tract irritation data, 2,2-Bis(methylthio)propane should be classified as irritant to the eyes following REGULATION (EC) No 1272/2008 (Category 2, H319). No classification is warranted for skin and respiratory tract irrtation.