Tetramethylthiuram monosulphide

Endpoint summary

Description of key information

Based on the rabbit's studies, TMTM is considered to be not skin or eye irritating.

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

duration of observation after exposure : 8 days (and not 14 days).

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: W.Ostrop/Meerbusch
- Age at study initiation: no data
- Weight at study initiation: 2.9 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18 °C
- Humidity (%): 40%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

24 hours

Observation period:

24-48-72 hours, 8 days

Number of animals:

6 rabbits

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: no details
- Type of wrap if used: Double layers of surgical gases

REMOVAL OF TEST SUBSTANCE: no

SCORING SYSTEM: as Draize score

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 rabbits with intact skin

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 72 hr

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 rabbits with intact skin

Time point:

24/48/72 h

Score:

0.83

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritant / corrosive response data:

A very sight erythema was observed in one rabbit at 24 hours after exposure to the test article.
Slight oedemas were observed in rabbit at 24 and 72 hours, and this effect was not reversible at 8 days.

Other effects:

no

Interpretation of results:

GHS criteria not met

Remarks:

Not skin irritating

Conclusions:

According to this study, tetramethylthiuram monosulfide (TMTM) is slightly irritating for skin in rabbits but not classified based on CLP criteria.

Executive summary:

The potential of the test substance tetramethylthiuram monosulfide to induce skin irritation was evaluated in rabbits.

The test substance was applied for periods of 24 hours to a six New Zealand White rabbits. A single dose of 500 mg of the test substance with water was applied to the closely­clipped skin of one flank.

Slight cutaneous reactions (erythema and edema) were observed during the study: the mean erythema score for the 6 rabbits is 0.1/4 (mean 24/72h) and the mean oedema score is 0.83/4 (mean 24/72h). Erythema was fully reversible in 72 hours but oedema was not fully reversible in 8 days.

Under these experimental conditions, the test substance tetramethylthiuram monosulfide is slightly irritating when applied topically to rabbits but not classified based on CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: W.Ostrop/Meerbusch
- Age at study initiation: no data
- Weight at study initiation: 2.9 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18 °C
- Humidity (%): 40%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

100 µl

Duration of treatment / exposure:

24h

Observation period (in vivo):

24-48-72h, 8 days

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE : no
SCORING SYSTEM: Draize score
TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0.44

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: Individual scores = 1-0-0.33-0.33-0 -1

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Individual scores = 0.33-0-0-0.33-0-0.66

Irritant / corrosive response data:

No effect was observed on cornea and iris. Very slight effects on conjunctivae were observed, and are fully reversible in 8 days.

Other effects:

no

Interpretation of results:

GHS criteria not met

Remarks:

Not eye irritating

Conclusions:

According to these results, TMTM was considered as not irritating for eyes in rabbits.

Executive summary:

Tetramethylthiuram monosulfide was placed in the conjunctival sac of one eye of each of six albino rabbits. The irritant reactions were scored until complete recovery. Some of the instilled powder was retained within the eye for at least 24 hours.

No effect was observed on cornea and iris. Very slight effects on conjunctivae were observed, and are fully reversible in 8 days. According to these results, TMTM was considered as not irritating for eyes in rabbits.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

One-tenth gram of the dry powder was placed in the conjunctival sac of one eye of each of six albino rabbits. The irritant reactions were scored until complete recovery.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no

Vehicle:

unchanged (no vehicle)

Controls:

other: the second eye of each animal

Amount / concentration applied:

one-tenth gram

Duration of treatment / exposure:

4 hours

Observation period (in vivo):

48 hours

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

The irritant reactions were scored until complete recovery.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The only effects was mild conjunctivitis without chemosis which dissipated completely within 24 or 48 hours.
Neither the cornea nor the iris was effected.

Interpretation of results:

GHS criteria not met

Remarks:

Not eye irritating

Conclusions:

According to these results, TMTM was considered as not irritating for eyes in rabbits.

Executive summary:

One-tenth gram of the dry powder was placed in the conjunctival sac of one eye of each of six albino rabbits. The irritant reactions were scored until complete recovery. Some of the instilled powder was retained within the eye for at least 4 hours.

The only effects was mild conjunctivitis without chemosis which dissipated completely within 24 or 48 hours. Neither the cornea nor the iris was effected. According to these results, TMTM was considered as not irritating for eyes in rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation (Schreiber 1980):

The potential of the test substance tetramethylthiuram monosulfide to induce skin irritation was evaluated in rabbits.

The test substance was applied for periods of 24 hours to six New Zealand White rabbits. A single dose of 500 mg of the test substance with water was applied to the closely clipped skin of one flank.

Slight cutaneous reactions (erythema and edema) were observed during the study: the mean erythema score for the 6 rabbits is 0.1/4 (mean 24/72h) and the mean oedema score is 0.83/4 (mean 24/72h). Erythema was fully reversible in 72 hours but oedema was not fully reversible in 8 days. Under these experimental conditions, TMTM is slightly irritating when applied topically to rabbits but not classified according to CLP criteria.

 

Eye irritation:

In the key study (Schreber 1980), TMTM was placed in the conjunctival sac of one eye of each of six albino rabbits. The irritant reactions were scored until complete recovery. Some of the instilled powder was retained within the eye for at least 24 hours.

No effect was observed on cornea and iris. Very slight effects on conjunctivae (chemosis and redness) were observed, and are fully reversible in 8 days. According to these results, TMTM was considered as not irritating for eyes in rabbits.

In the supporting study (Latven 1977), one-tenth gram of the dry powder was placed in the conjunctival sac of one eye of each of six albino rabbits. The irritant reactions were scored until complete recovery. Some of the instilled powder was retained within the eye for at least 4 hours. The only effects was mild conjunctivitis without chemosis which dissipated completely within 24 or 48 hours. Neither the cornea nor the iris was effected. According to these results, TMTM was considered as not irritating for eyes in rabbits.

 

 

 

 

Justification for classification or non-classification

TMTM has a mandatory classification in the Annexe VI of CLP but no classification for irritation is mentionned.

No classification for skin or eye irritation is required for TMTM based on the data available and according to the Regulation EC no.1272/2008.