Thiophanate-methyl

Endpoint summary

Description of key information

The substance was tested for skin irritation in rabbits in a study similar to OECD TG 404. No skin irritation was observed in any of the six rabbits. The substance can be regarded as non-irritant to the skin.

TPM was tested for eye irritation in rabbits in a study similar to OECD TG 405. Instillation into the rabbit eye did not elicit a positive response in any of the six treated animals. Therefore, TPM was considered non-irritant to the rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 July 1986 - 21 November 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sizuoka Laboratory Animal Center (Sizuoka)
- Age at study initiation: about 3 months
- Weight at study initiation: 3.02 ± 0.20 kg (at dosing)
- Housing: individually housed in a steel mesh cages (33 x 45 x 35 cm)
- Diet: Standardized pellets of dry diet, RC-4 (Oriental Yeast Co., Ltd., Tokyo), ad libitum
- Water: tap water, ad libitum
- Acclimation period: quarantined for a week prior to use

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19 - 25 (mean temperature: 21.1)
- Humidity (%): 40 - 80 (mean humidity at 9 am: 59.6)
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

Skin changes such as erythema and edema were scored at 0, 0.5, 1, 24, 48 and 72 hours after the removal of the test item.

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 3 cm²

REMOVAL OF TEST SUBSTANCE
- At the end of the exposure period, the patch was removed and the skin was wiped (but not washed) to remove any test substance still remaining.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- 0, 0.5, 1, 24, 48 and 72 hours after the removal of the test item

SCORING SYSTEM:
- Method of calculation: Draize scoring

Irritation parameter:

erythema score

Basis:

animal: #1 -#6

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal: #1 - #6

Time point:

24/48/72 h

Score:

0

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was determined not to be irritating to the skin.

Executive summary:

In this assessment of the primary dermal irritation, 0.5 g of the test item moistened with water was spread over lint patches which were kept in contact the skin of 6 rabbits. Four hours after the application the patch was removed and the skin was wiped to remove any test substance still remaining. The dermal irritation scores were recorded after removal of the patches. No skin reaction was observed in any rabbits treated with the test item. The test item was determined not to be irritating to the skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

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

Study period:

21 July 1986 - 13 November 1986

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)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Sizuoka Laboratory Animal Center (Sizuoka)
- Age at study initiation: about 3 months
- Weight at study initiation: 2.91 ± 0.19 kg (at dosing)
- Housing: individually housed in a steel mesh cages (33 x 48 x 35 cm)
- Diet: Standardized pellets of dry diet, RC-4 (Oriental Yeast Co., Ltd., Tokyo), ad libitum
- Water: tap water, ad libitum
- Acclimation period: quarantined for a week prior to use

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19 - 25 (mean temperature: 20.7)
- Humidity (%): 40 - 80 (mean humidity at 9 am: 68.3)
- Photoperiod (hrs dark / hrs light): 12 / 12

Controls:

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g

Duration of treatment / exposure:

6 animals: eyes were not washed out
3 animals: eyes washed with water 2 minutes after treatment

Observation period (in vivo):

Readings of ocular lesions were made at 1 hour, 24 hours, 48 hours and 72 hours after the treatment.

Number of animals or in vitro replicates:

3 animals (eyes washed with water) and 6 animals (eyes not washed out)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: 6 animals: no washing; 3 animals: washing with water
- Time after start of exposure: 2 minutes

SCORING SYSTEM: in accordance with scoring system according to OECD 405

Irritation parameter:

cornea opacity score

Basis:

animal: #1-#6 (unwashed)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: #1 - #3 (washed)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #1 - #6 (unwashed)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: #1 - #3 (washed)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal: #1 - #6 (unwashed)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal: #1 - #3 (washed)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal: #1 - #6 (unwashed)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal: #1 - #3 (washed)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was determined not to be irritating to the eye.

Executive summary:

In this assessment of the primary irritation to the eye, 0.1 g of the test item was applied to each left eye of 9 rabbits. The treated eyes of 3 rabbits were washed by water and those of 6 rabbits were not washed. The readings of ocular lesions were made at 1 hour, 24 hours, 48 hours and 72 hours after the application of the test item in comparison with the untreated right eyes. Very mild changes were observed in treated eyes of all animals whose eyes have been washed out and in 4 animals whose eyes have not been washed out. No irritation to the eyes was observed after 24, 48 or 72 hours. Therefore, the test item was determined not to be irritating to the eye.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In this assessment of the primary dermal irritation, 0.5 g of the test item moistened with water was spread over lint patches which were kept in contact the skin of 6 rabbits. Four hours after the application the patch was removed and the skin was wiped to remove any test substance still remaining. The dermal irritation scores were recorded after removal of the patches. No skin reaction was observed in any rabbits treated with the test item. The test item was determined not to be irritating to the skin.

Eye irritation

In this assessment of the primary irritation to the eye, 0.1 g of the test item was applied to each left eye of 9 rabbits. The treated eyes of 3 rabbits were washed by water and those of 6 rabbits were not washed. The readings of ocular lesions were made at 1 hour, 24 hours, 48 hours and 72 hours after the application of the test item in comparison with the untreated right eyes. Very mild changes were observed in treated eyes of all animals whose eyes have been washed out and in 4 animals whose eyes have not been washed out. No irritation to the eyes was observed after 24, 48 or 72 hours. Therefore, the test item was determined not to be irritating to the eye.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for skin irritation/corrosion and eye irritation/corrosion are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is neither considered to be classified for skin irritation/corrosion nor for eye irritation/corrosion under Regulation (EC) No 1272/2008, as amended for the seventeenth time in Regulation (EU) 2021/849.