Pyrasulfotole

Endpoint summary

Description of key information

Skin irritation (OECD 404), rabbit: not irritating

Eye irritation (EPA OPPTS 870.2400), rabbit: 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:

14 Apr - 17 May 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 24 Apr 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 28 Jul 2015

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was pulverized.

Species:

rabbit

Strain:

New Zealand White

Remarks:

Crl:KBL(NZW)BR

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kisslegg, Germany
- Age at study initiation: approximately 6 months
- Weight at study initiation: 3020 - 3175 g
- Housing: individually in metal cages with excrement tray
- Diet: "Ssniff K-2" 4mm (manufacturer: Ssniff Spezialdiaeten GmbH, Soest, Germany), approximately 100 g/animal/day; once per day in the moming
- Water: tap water, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 20
- Photoperiod (hrs dark / hrs light): approximately 12/12

IN-LIFE DATES: From: 14 Apr 2004 To: 17 Apr 2004

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Remarks:

(approximately 24 h before application)

Vehicle:

water

Controls:

other: the untreated contralateral skin area served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 500 - 502 mg

Duration of treatment / exposure:

1st animal: 3 min, 1 h, 4 h
2nd and 3rd animal: 4 h

Observation period:

72 h

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: The test material was applied to the dorsolateral area of the trunk (treated skin was approximately 2.5 x 2.5 cm in size).
- Type of wrap if used: The test material was moistened with sterile water and was covered with a gauze patch which was held in place with "Surgifix No. 5" (Schumacher, Medical Produkte, Krefeld, Germany)

REMOVAL OF TEST SUBSTANCE
- Washing: The exposed skin was carefully washed with water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1st animal: immediately after patch removal (3 min and 1 h treatment); 1, 24, 48 and 72 h after patch removal (4 h treatment)
2nd and 3rd animal: 1, 24, 48 and 72 h after patch removal

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals (4 h treatment)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals (4 h treatment)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation or corrosion were noted after treatment for 3 min or 1 h. No signs of irritation or corrosion were noted immediately after treatment for 4 h.

Other effects:

- Other adverse systemic effects: There were no relevant systemic intolerance reactions.

Interpretation of results:

other: CLP/GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

The study was performed in accordance to OECD TG 404 under GLP conditions and is considered reliable. The test substance was non-irritant.

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:

13 Dec - 16 Dec 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 09 Oct 2017 (corrected 14 Jun 2021)

Deviations:

yes

Remarks:

no pre-treatment with systemic analgesic and topical anesthesia

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

adopted 1998

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was instilled as received.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Robinson Services, Inc. Clemmons, NC, USA
- Age at study initiation: Young adult
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors.
- Diet: Pelleted Purina Rabbit Chow #5326
- Water: Filtered tap water was supplied, ad-libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 Dec 2005 To: 16 Dec 2005

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 40 mg (corresponding to 0.1 mL)

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Duration of post- treatment incubation (in vitro):

not applicable

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no washing was done
SCORING SYSTEM: scoring was done according to Draize

TOOL USED TO ASSESS SCORE: Ocular irritation was evaluated using a high-intensity white light (Mag Lite). A fluorescein dye evaluation was performed 24 h after instillation and as needed at subsequent scoring intervals to evaluate the extent of corneal damage or to verify reversal of effects.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1 and animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: no indication of corneal opacity

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1 and animal # 3

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within:

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: no indication of iritis

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

all aniamls

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: no indication of chemosis

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2 and animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritant / corrosive response data:

One hour after test substance instillation, all three treated eyes exhibited iritis and conjunctivitis. By 24 h, corneal opacity (score 1) developed in one animal. The overall incidence and severity of irritation decreased thereafter. All animals were free of ocular irritation by 72 h.
Ocular discharge (score 2) was noted 1 h after treatment and to a lesser degree (score 1) 24 h after treatment in all animals. In animal #3 this discharge persisited until 48. The finding was fully reversible in all animals within 72 h.

Other effects:

All animals appeared active and healthy during the study. Apart from the eye irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior.

Table 1: Individual irritation scores

Animal number	Effects	1 h	24 h	48 h	72 h	Mean scores*
1	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Discharge	0 1 3 1 2	0 1 2 0 1	0 0 1 0 0	0 0 0 0 0	0.00 0.33 1.00 0.00 0.33
2	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Discharge	0 1 2 1 2	0 0 2 1 1	0 0 1 0 1	0 0 0 0 0	0.00 0.00 1.00 0.33 0.67
3	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Discharge	0 1 3 2 2	1 1 2 1 1	1 0 1 1 1	0 0 0 0 0	0.67 0.33 1.00 0.67 0.67

* calculated from 24 to 72 h scores

Interpretation of results:

other: CLP/GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008"

Conclusions:

The study was performed in accordance to EPA OPPTS 870.2400 (Acute Eye Irritation) under GLP conditions and is considered reliable. Based on the study results, the test substance is considered to be mildly irritating to eyes. However, the slight signs of irritation observed in this study were not sufficient to warrant classification for eye irritation.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

20 Apr - 18 May 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24 Apr 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 9 Oct 2017 (corrected 14 Jun 2021)

Deviations:

yes

Remarks:

no pre-treatment with systemic analgesic and topical anesthesia

GLP compliance:

yes

Specific details on test material used for the study:

FORM AS APPLIED IN THE TEST (if different from that of starting material): The test material was pulverized.

Species:

rabbit

Strain:

New Zealand White

Remarks:

Crl:KBL(NZW)BR

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kisslegg, Germany
- Age at study initiation: approximately 3 months
- Weight at study initiation: 2314 - 2815 g
- Housing: individually in metal cages with excrement trays
- Diet: "Ssniff K-Z" 4mm (manufacturer: Ssniff Spezialdiaeten GmbH, Soest, Germany), approximately 100 g/animal/day; once per day in the morning
- Water: tap water, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 Apr 2004 To: 27 Apr 2004

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 101 - 102 mg

Duration of treatment / exposure:

single application with washing 1 h after instillation

Observation period (in vivo):

7 days
Reading time points 1, 24, 48, 72 h and 7 days after treatment

Duration of post- treatment incubation (in vitro):

not applicable

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The eyes were washed 1 h following instillation.

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: Fluorescein staining was conducted at 24 h after compound instillation.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: no indication of corneal opacity

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: no indication of iritis

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Lacrimation (score 1) was noted 1 h after treatment in all animals and 24 h after treatment in animal #1. This finding was fully reversible in all animals within 48 h.

Other effects:

There were no systemic intolerance reactions.

Table 1: Individual mean irritation scores

Animal number	Effects	1 h	24 h	48 h	72 h	7 d	Mean scores*	Reversible
1	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Lacrimation	0 0 2 2 1	0 0 2 1 1	0 0 2 0 0	0 0 1 0 0	0 0 0 0 0	0.00 0.00 1.67 0.33 0.00	na na 7 d 48 h 48 h
2	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Lacrimation	0 0 2 2 1	0 0 1 1 0	0 0 0 0 0	0 0 0 0 0	- - - - -	0.00 0.00 0.33 0.33 0.00	na na 48 h 48 h 24 h
3	Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae Lacrimation	0 0 2 2 1	0 0 2 1 0	0 0 1 0 0	0 0 0 0 0	- - - - -	0.00 0.00 1.00 0.33 0.00	na na 72 h 48 h 24 h

* calculated from 24 to 72 h scores,    na = not applicable,    - not examined

Interpretation of results:

other: CLP/GHS criteria not met; no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

The study was performed in accordance to OECD TG 405 under GLP conditions and is considered reliable. Based on the study results, the test substance is considered to be mildly irritating to eyes. However, the slight signs of irritation observed in this study were not sufficient to warrant classification for eye irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Reliable in vivo studies regarding eye and skin irritation/corrosion are available.

Skin:

In a primary dermal irritation study (performed according to OECD 404, in compliance with GLP, M-003613-01-3), 3 female New Zealand Albino rabbits were dermally exposed to 0.5 g test substance moistened with water for 4 h under semiocclusive conditions. Animals then were observed for 3 days. Irritation was scored by the method of Draize as described in the OECD 404. The mean scores for the 24, 48 and 72 h reading for erythema and edema for each animal was 0, respectively. No skin reactions were observed at the 1-hour reading point. In this study, the test substance was not a dermal irritant.

 Eye:

An eye irritation test was performed with three female New Zealand Albino rabbits according to OPPTS 870.2400 in compliance with GLP (M-267442-01-1). Eyes were not washed after application of 0.1 mL (corresponding to 0.04 g) test substance and the animals were observed for 3 days. Irritation was scored by the method of Draize. One hour after test substance instillation, all three treated eyes exhibited iritis (score 1 for all animals) and conjunctivitis (score 3 for 2 animals, score 2 for one animal). By 24 h, cornea opacity (score 1) developed in one animal but was fully reversible at 72 h. No cornea opacity developed in the other two animals. Mean scores (24, 48, 72 h) for cornea opacity are 0, 0 and 0.67, respectively. Also iritis (score 1) was noted at 24 h in 2/3 animals being fully reversible within 48 h and resulting in mean iritis scores (24, 48, 72 h) of 0.33, 0.00 and 0.33, respectively. Moderate conjunctival irritation (grade 1-2) were observed in 3/3 animals but were fully reversible within 72 h in all animals. Mean scores (24, 48, 72 h) regarding conjunctival irritation were 1.00 for all animals. Chemosis (grade 1) was also noted in 2/3 animals but was fully reversible within 48 h. Mean scores (24, 48, 72 h) for chemosis were 0, 0.33 and 0.67, respectively. All animals were free of ocular irritation by 72 h.

Based on the study results, the test substance is considered to be mildly irritating to eyes. However, the slight signs of irritation observed in this study were not sufficient to warrant classification for eye irritation.

A second eye irritation test was performed with three female New Zealand Albino rabbits and performed according to OECD 405 in compliance with GLP (M-003615-01-1). Eyes were washed 1 h after application of 0.1 g test substance and the animals were observed for 7 days. Irritation was scored by the method of Draize. The mean scores for the 24-, 48- and 72-h reading for iritis and cornea opacity were 0 for each animal. Moderate conjunctival irritation (mean scores for the 24-, 48- and 72 h-reading: 1.67, 0.33 and 1.0, respectively) were observed in 3/3 animals but were fully reversible within 72 h in 2/3 animals and 7 days in 1/3 animals. Chemosis (mean scores for the 24-, 48- and 72 h-reading: 0.33 for each animal) was also noted in 3/3 animals but was fully reversible within 48 h.

Based on the study results, the test substance is considered to be mildly irritating to eyes. However, the slight signs of irritation observed in this study were not sufficient to warrant classification for eye irritation.

Justification for classification or non-classification

The available data on skin and eye irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.