1,3,4-Thiadiazolidine-2,5-dithione, reaction products with tert-dodecanethiol and hydrogen peroxide

Endpoint summary

Description of key information

Skin irritation:
- in vivo, rabbit (New Zealand White) male, semiocclusive, OECD 404, on ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’: not irritating
- in vivo, rabbit (New Zealand White) m/f, semiocclusive, OECD 404, on ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol’: not irritating
- in vivo, rabbit (New Zealand White) female, semiocclusive, OECD 404, on ‘5-(dodecyldithio)-1,3,4-thiadiazole-2(3H)-thione’: Category 3 (mild irritant), does not require classification
Eye irritation:
- in vivo, rabbit (New Zealand White) male, OECD 405, on ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’: not irritating
- in vivo, rabbit (New Zealand White), OECD 405, on ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol’: not irritating
- in vivo, rabbit (New Zealand White) female, OECD 405, on ‘5-(dodecyldithio)-1,3,4-thiadiazole-2(3H)-thione’: not 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

Study period:

1988-03-15 - 1988-03-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented OECD guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source/Breeder: Interfauna UK Ltd.
- Age: adult animals
- Sex: male
- Weight: 3.1 – 3.4 kg
- Animal Health was examined routinely, only healthy, symptom-free animals were used.
- Identification: by cage number and ear tattoo
- Housing: individually in wire cage type III – high, with a drawer for the faeces below filled with an absorbant, dust-free wood granulate type S 8/15 /Ssniff, Soest
- Diet: Standard diet “ssniff K 4” (Versuchstierdiäten GmbH, Soest/Westfalen), approx. 100-120 g/d and animal
- Water: Tap water, drinking water quality, ad libitum
-Acclimation period: at least 14 d

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 2 °C
- Humidity (%): ca. 50 %
- Air changes: ca. 10/h
- Photoperiod (hrs dark / hrs light): 12 / 12
- Luminance intensity: ca. 27 Watt/m²

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated contralateral skin area served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500µL

Duration of treatment / exposure:

4 h

Observation period:

7 d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: flank, approx. 6cm²
- % coverage: semiocclusive
- Type of wrap if used: band-aid and elastic adhesive

REMOVAL OF TEST SUBSTANCE
- Washing: with water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize (as set out in OECD 404)

Irritation parameter:

erythema score

Basis:

animal: O49

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal: N30

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal: O14

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal: O49

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal: N30

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal: O14

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

No evidence of skin irritation and corrosion was noted during the study.

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU-GHS

Conclusions:

The study was conducted according OECD Guideline 404 and is well-documented. Hence, the study can be considered as valid and the results as reliable. Consequently, the test item is considered as not irritating and not corrosive.

Executive summary:

In a dermal irritation study according to OECD Guideline 404 (Bayer AG, Märtins, 1988), 3 male adult albino-rabbits (strain: New Zealand White) were dermally exposed to 0.5 mL of the test item (1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol) for 4 hours to ca. 6cm² clipped skin. Afterwards, the exposed skin areas were washed with water and animals were observed for 7 days.

No erythema, eschar or oedema were observed at any time point.

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

Study period:

1988-03-15 - 1988-03-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented OECD Guideline study without deviations on ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’.

Qualifier:

according 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/Breeder: Interfauna UK Ltd.
- Age: adult animals
- Sex: male
- Weight: 3.1 – 3.4 kg
- Animal Health was examined routinely, only healthy, symptom-free animals were used.
- Identification: by cage number and ear tattoo
- Housing: individually in wire cage type III – high, with a drawer for the faeces below filled with an absorbant, dust-free wood granulate type S 8/15 /Ssniff, Soest
- Diet: Standard diet “ssniff K 4” (Versuchstierdiäten GmbH, Soest/Westfalen), approx. 100-120 g/d and animal
- Water: Tap water, drinking water quality, ad libitum
-Acclimation period: at least 14 d

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 2°C
- Humidity (%): ca. 50%
- Air changes: ca 10/h
- Photoperiod (hrs dark / hrs light): 12 / 12
- Luminance intensity: ca. 27 Watt/m2

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100µL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 d

Number of animals or in vitro replicates:

3

Details on study design:

APPLICATION OF TEST SUBSTANCE
100µL of the test item were applied in the conjunctival sac of one eye. The second eye remains untreated as control.

REMOVAL OF TEST SUBSTANCE
- Washing: physiological NaCl-solution
- Time after start of exposure: 24h

SCORING SYSTEM: Draize (as set in OECD Guideline 405)

TOOL USED TO ASSESS SCORE: optical aids / fluorescein

Irritation parameter:

other: cornea opacity

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

other: cornea area

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

other: conjunctivae redness

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0.2

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

other: conjunctivae swelling

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

other: conjunctivae lacrimation

Basis:

mean

Time point:

other: 1 h, 24h, 48h, 72h, 7d

Score:

0.2

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h, 7d

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

Under the conditions of this test, the test item was considered to be non-irritating to the eye.

Table 1. Raw data

Animal No.	Observed Endpoint	Draize-Scoring					Mean
		1h	24h	48h	72h	7d
O39 ♂ (3.5kg)	Cornea opacity	0	0	0	0	0	0.0
	Cornea area	0	0	0	0	0
	Iris	0	0	0	0	0	0.0
	Conjunctivae redness	0	0	0	0	0	0.0
	Conjunctivae swelling	0	0	0	0	0	0.0
	Conjunctivae lacrimation	0	0	0	0	0
	Fluorescein	---	n	---	---	---
O44 ♂ (3.1kg)	Cornea opacity	0	0	0	0	0	0.0
	Cornea area	0	0	0	0	0
	Iris	0	0	0	0	0	0.0
	Conjunctivae redness	0	0	0	0	0	0.0
	Conjunctivae swelling	0	0	0	0	0	0.0
	Conjunctivae lacrimation	0	0	0	0	0
	Fluorescein	---	n	---	---	---
N63 ♂ (3.1kg)	Cornea opacity	0	0	0	0	0	0.0
	Cornea area	0	0	0	0	0
	Iris	0	0	0	0	0	0.0
	Conjunctivae redness	1	0	0	0	0	0.2
	Conjunctivae swelling	0	0	0	0	0	0.0
	Conjunctivae lacrimation	1	0	0	0	0	0.2
	Fluorescein	---	n	---	---	---

--- = not examined; n = negative

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU-GHS

Conclusions:

The study was conducted according to OECD Guideline 405 and is well-documented. Hence, the study can be considered as valid and the results as reliable (Klimisch 2). Consequently, the test item is considered as not irritating to the eye.

Executive summary:

In an eye irritation study according to OECD Guideline 405 (Bayer AG, Märtins, 1988), 100 µL of the test item (1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol) was instilled into the conjunctival sac of one eye of each 3 male adult albino rabbits (strain: New Zealand White) for 24 hours. The untreated eye served as control. After the exposure period, the treated eye was washed with physiological saline. The animals were then observed for 7 days. Irritation was scored according to the method of Draize. Except a slight, fully reversible conjunctivae redness and lacrimation 1 h after exposure in one animal, no other effects were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The dermal irritation key study was conducted according to OECD Guideline 404 (Märtins, 1988), the dermal irritation potential of the target substance '1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol' was tested. In this study, 3 male adult albino-rabbits (strain: New Zealand White) were dermally exposed to 0.5 mL of the test item for 4 hours to ca. 6cm² clipped skin. Afterwards, the exposed skin areas were washed with water and theanimals were observed for 7 days.

No erythema, eschar or oedema were observed at any time point.

Considering to be a supporting study, a dermal irritation test was conducted using a similar procedure to that described in the current OECD Guideline 404 (Reckers, 1982). The read-across substance (CAS No. 50530-43-3) was applied at a dose of 0.5 mL to the backs of 6 female rabbits (strain: New Zealand White). The test article was left in contact with the skin for 24 hours and then the test sites were washed with 0.9% sodium chloride and the rabbits observed during this time and for 14 days after its removal. The test sites were scored at 1, 3, 7 and 14 days after removal. Oedema and erythema were observed in all rabbits 3 days following application and in the majority of rabbits 7 days following test article application. Mean erythema scores of 0.66 (1-day observation), 2 (3-day observation) and 1.33 (7-day observation) were reported. In addition, mean edema scores of 1.33 (3-day and 7-day observation, respectively) were determined. All effects were fully reversible within 14 days. Besides, all test animals appeared normal 14 days after application. No rabbits died during the study.

In another supporting study a similar procedure to that described in the current OECD Guideline 404 was used (Reckers, 1982). The short-chain homologue with CAS No. 91648-65-6 was applied at a dose of 0.5 mL to the backs of 3 male and 3 female rabbits (strain: New Zealand White). The test article was left in contact with the skin for 24 hours and then the test sites were washed with 0.9 % sodium chloride and the rabbits observed during this time and for 14 days after its removal. The test sites were scored at 1, 3, 7 and 14 days after removal. Erythema was observed in all rabbits at 1 and 3 days following application. Mean scores of 2 (after 1 day) and 1.8 (after 3 days) were reported. After 7 days any effects were fully reversed. Oedema did not occur. All rabbits appeared normal 14 days after application. No rabbits died during the study.

Eye irritation

The key eye irritation study was conducted according to OECD Guideline 405 (Märtins, 1988). 0.1 mL of the target substance ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’ was instilled into the conjunctival sac of one eye of each 3 male adult albino rabbits (strain: New Zealand White) for 24 hours. The untreated eye served as control. After the exposure period, the treated eye was washed with physiological saline. The animals were then observed for 7 days. Except a slight, fully reversible conjunctivae redness and lacrimation 1 h after exposure in one animal, no other effects were observed.

A supporting eye irritation study was conducted using a similar procedure to that described in the current OECD Guideline 405 (Reckers, 1981). The read-across substance (CAS No. 50530-43-3) was applied at a volume of 0.1 mL to the right eye of six female rabbits (strain: New Zealand White). The test article was left in the right eye (i.e. no rinsing was performed) and the rabbits were observed during application followed by a 14 -day observation period. The left eye served as control. The treated eye was scored at day 1, 2, 3, 4, 7 and 14 following instillation. Ocular irritation was not observed in any animal during the study.

In another supporting eye irritation study using a similar procedure to that described in the current OECD Guideline 405 (Reckers, 1981) the short-chain substance '1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-nonanethiol' (CAS No. 91648-65-6) was applied at a volume of 0.1 mL to the right eye of six rabbits (strain: New Zealand White). The test article was left in the eye (i.e. no rinsing was performed) and the rabbits were observed during application followed by a 14 -day observation period. The left eye served as control. The treated eye was scored at day 1, 2, 3, 4, 7 and 14 following instillation. Ocular irritation was not observed in any animal during the study.

Justification for selection of skin irritation / corrosion endpoint:
Only one study conducted with the target substance is available (key study).

Justification for selection of eye irritation endpoint:
Only one study conducted with the target substance is available (key study).

Justification for classification or non-classification

Skin irritation

In the key study (Bayer AG, 1988), no erythema, eschar or oedema were observed at any time point. Hence, '1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol' does not need to be classified as skin irritant, which is supported by the the other two available studies on read-across substances.

Eye irritation

According to the classification criteria outlined in the section 3.3.2.2. (Guidance on the Application of CLP criteria, 2012), if a substance cause positive but reversible reactions such as corneal opacity (score ≥ 1), iritis (score ≥ 1), conjunctival redness (score ≥ 2) or conjunctical oedema (chemosis) (score ≥ 2) in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after application, the classification as Eye Irritant (Category 2) is assigned. Eye irritation was not observed in any animal at any time point.

Therefore, the substance ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’ does not meet the requirement under EU CLP (Regulation (EC) No. 1272/2008) for classification as irritating to eyes.