Propanoic acid, 3-[[bis(2-methylpropoxy)phosphinothioyl]thio]-2-methyl-

Endpoint summary

Description of key information

No indication of skin irritation was observed in rabbits in a GLP-compliant study following OECD testing guidelines 404 (1992). Highly irritating properties to rabbit eyes were observed in a GLP-compliant study following OECD testing guideline 405 (1987). Slight corneal opacity in one animal and reddening of the conjunctivae in two animals were still observed 21 days after the single application.

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:

26-OCT-1999 - 05-NOV-1999

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:

(1992)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in original container at room temperature protected from sunlight

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: both sexes 16 weeks
- Weight at study initiation: 2906 g (male) 3063 g (female), 2878 g (female)
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418, rabbit maintenance diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin area served as control

Amount / concentration applied:

- Amount of test substance applied: 0.5 ml of undiluted test article per animal
- Concentration: 100 %

Duration of treatment / exposure:

Animals were treated for 4 hours

Observation period:

72 hours
Animals were observed daily for mortality and clinical signs. Bod weights were measured at start of acclimatization, on the day of application and at
termination of observation.

Number of animals:

3 animals, 1 male 2 females

Details on study design:

As a liquid, 0.5 mL (per animal) was measured with a syringe and applied undiluted.
Approximately four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined approximately 24 hours before treatment, and, if necessary, regrown fur was again clipped.
Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, 0.5 ml of CG 37-1586 was put on a surgical gauze patch (ca. 2.5 cm x 2.5 cm).
This gauze patch was applied to approximately 6 cm2 of the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing.
The dressing was wrapped around the abdomen and anchored with tape. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

SCORING SYSTEM:
ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema reading 4

EDEMA FORMATION
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (edges raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

three animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

three animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of skin irritation were seen.

Other effects:

No signs of systemic toxicity, no mortality and no staining of the skin were observed.

Interpretation of results:

GHS criteria not met

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:

04-NOV-1999 - 02-DEC-1999

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:

(1987)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in original container at room temperature protected from sunlight

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 2 animals 16 weeks (one male, one female) 1 animal 14 weeks (female)
- Weight at study initiation: 2821 (male), 2803 (female), 2876 (female)
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418, rabbit maintenance diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL of undiluted test article per animal into left eye
- Concentration: 100 %

Duration of treatment / exposure:

The eye was not rinsed after application

Observation period (in vivo):

Scoring of irritation effects was performed approximately 1 h, 24 h, 48 h, 72 h and 7 d, 14 d, 21 d.

Number of animals or in vitro replicates:

3 animals, 1 male and 2 female

Details on study design:

As a liquid, 0.1 ml (per animal) of CG 37-1586 was applied undiluted. The eyes of the animals were examined one day prior to test article administration. Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, the test article was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test article.

Scoring system
Grading of Ocular Lesions according toEEC 92/69/EEC COMMISSION DIRECTIVE, (1992)

CORNEA
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster),
details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4
IRIS
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction (any or all of these) 2
CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with control eye)
Blood vessels normal 0
Some blood vessels definitely hyperemic (injected) 1
Diffuse, crimson color, individual vessels not easily discernible 2
Diffuse beefy red 3
Chemosis: lids and/or nictitating membranes
No swelling 0
Any swelling above normal (including nictitating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half-closed 3
Swelling with lids more than half-closed 4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.11

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: Animal 2 showed iritis graded 1 after 1h, which disappeared within 24 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.56

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Irritant / corrosive response data:

Two of three animals still showed redness of conjunctiva (grade 1) after 21 days; in addition, one of these animals showed corneal opacity (graded 1).

Other effects:

No corrosion was observed at any of the measuring intervals.
Yellow residues around the eye and/or on the lids were observed at 1 h in all animals and in one animal still 24 h after treatment.
No clinical signs of systemic toxicity were observed and no mortality occurred.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

The primary skin irritation potential was investigated by topical application of 0.5 ml to 6 cm2intact skin of the left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. The test article caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Eye irritation

The primary eye irritation potential was investigated by instillation of 0.1 mL into one eye of each of three young adult New Zealand White rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7, 14 and 21 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. A slight opacity persisted through 7 or 21 days in two animals. The cornea of the third animal showed a moderate opacity at the 24-hour examination which diminished to a slight opacity at the 48-hour reading through 72 hours to disappear by day 7. Hyperemic conjunctival blood vessels were noted in all animals at 24 hours to persist through 72 hours (one animal) or up to the end of the study (day 21, two animals). Slight swelling (one animal) to swelling with partial eversion of lids (two animals) were observed at the 24-hour examination and persisted through 72 hours. Yellow remnants around the eye and/or on lids by the test article were observed from 1 hour (all animals) to 24 hours (one animal). No corrosion was observed at any of the measuring intervals.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified as Irreversible effects on the eye (Category 1) under Regulation (EC) No. 1272/2008. Classification for skin irritation is not warranted under Regulation (EC) No. 1272/2008.