O,O,O-tris(2(or 4)-C9-10-isoalkylphenyl) phosphorothioate

Endpoint summary

Description of key information

The substance caused transient irritation of the rabbit skin. Very slight to well-defined erythema were observed. Erythema were fully reversible in all animals within 7 days following termination of exposure. Very slight edema which were reversible within 72 hours after the exposure were observed. The test substance also caused mild conjunctival and iridial reactions. The effects on the conjunctivae were fully reversible in all animals within 7 days following instillation.

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:

January 17, 1989 - January 24, 1989

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:

1981

Deviations:

yes

Remarks:

(occlusive treatment)

GLP compliance:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12-14 wks
- Weight at study initiation: 2230 - 2530 g
- Housing: individually in metal cages
- Diet: standard rabbit pellet (Nafag No. 814), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 d
- OTHER: All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer. The quality of the drinking water was according to the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: the other flank of the same animal (treated with water)

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL of undiluted test article

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 12-16 cm² (flanks)
- % coverage: at least 10
- Type of wrap if used: aluminium foil held in place with adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg)

REMOVAL OF TEST SUBSTANCE
- Washing: no data
- Time after start of exposure: 4 h

SCORING SYSTEM: according to the OECD draize system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Other effects:

At the reading 72 hours the application site of 2 animals appeared somewhat dry and slight scaling was observed. A slight loss of weight was observed in 1 animal on day 3 (considered not to be treatment-related).

Bodyweights (g):

animal #1: (day 1) 2430; (day 3) 2430; (day 7) 2640

animal #2: (day 1) 2530; (day 3) 2530; (day 7) 2680

animal #3: (day 1) 2230; (day 3) 2200; (day 7) 2280

Interpretation of results:

GHS criteria not met

Executive summary:

In an acute dermal irritation/corrosion study following OECD guideline 404 and in compliance with GLP, three rabbits were exposed to 0.5 mL of the test substance for four hours. The test substance was applied onto the shaved flanks of the animals using an occlusive dressing. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. Erythema and edema reactions were caused by the treatment, reversible within 7 days the latest. Because the mean values of the recordings 24 to 72 hours after application are below the threshold of significance, the test article can be classified as non-irritant.

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:

January 24, 1989 - January 27, 1989

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

GLP compliance:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12-14 wks
- Weight at study initiation: 2560-2700 g
- Housing: individually in metal cages
- Diet: standard rabbit pellet (Nafag No. 814), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 d
- OTHER: All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer. The quality of the drinking water was according to the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the other eye of the animal served as control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

The test item was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article. The eyes were not washed after instillation.

Observation period (in vivo):

3 d

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: according to the OECD draize system
TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: no effect

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect

Bodyweights (g):

animal #1: (day 1) 2660; (day 3) 2610

animal #2: (day 1) 2560; (day 3) 2550

animal #3: (day 1) 2700; (day 3) 2730

Interpretation of results:

GHS criteria not met

Conclusions:

Under the exerimental conditions employed the test item induced mild irritation of the conjunctiva when instilled into the conjunctival sac of albino rabbits. Because the mean values of the readings 24 to 72 hours after instillation are below the threshold of significance, the test item is regarded as non-irritant.

Executive summary:

In an acute eye irritation/corrosion study according to OECD guideline 405 and in compliance with GLP, single samples of 0.1 mL of the undiluted test article was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article. The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation according to the OECD scoring system. A slit-lamp was used to facilitate the evaluation. Instillation of the test substance resulted in mild redness of the conjunctivae, reversible within 2 days the latest. Based on these results and according to the GHS (EU) criteria for classification the test substance does not need to be classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation / Corrosion

In the key study performed according to the protocols of OECD 404 (Irritation / Corrosion Study (dermal)), groups of 3 approx. 12 - 14 weeks old albino rabbits were dermally exposed to 0.5 ml of the undiluted test article (96.2% pure) applied for 4 hours to the flank (12 -16 cm²; at least 10% of the body surface) under occlusive conditions. Animals were observed for 7 days. Irritation was scored by the method of OECD draize system. Skin reactions were observed within 3 days, but were fully reversible within 7 days. Erythema (means 24 -72h): 1.66, 1.66 and 0.33 (animal 1, 2 and 3, respectively); Edema (means 24 -72h): 0.66, 0.66 and 0.0 (animal 1, 2 and 3, respectively).

The supporting study performed according to the protocols of OECD 404 (Irritation / Corrosion Study (dermal)), groups of 3 approx. 12 - 14 weeks old albino rabbits were dermally exposed to 0.5 ml of the undiluted test article (96.2% pure) applied for 4 hours to the flank (12 -16 cm²; at least 10% of the body surface) under occlusive conditions. Animals were observed for 7 days. Irritation was scored by the method of OECD draize system. Skin reactions were observed within 3 days, but were fully reversible within 7 days. Erythema: 1.0, 0.33 and 1.33 (animal 1, 2 and 3, respectively); Edema: 0.33, 1.0 and 0.66 (animal 1, 2 and 3, respectively).

 

Eye Irritation

In the key eye irritation study (OECD 405), 0.1 ml of the undiluted test article (96.2% pure) was instilled into the conjunctival sac of one eye of young adult New Zeeland White rabbits (3 female) for 24 hours. Eyes were not washed after instillation. Animals then were observed for 3 days. Irritation was scored by the method of OECD draize system. Conjunctivae (redness): 0.33, 0.33 and 0.0 (animal 1, 2 and 3, respectively); Chemosis, Cornea and Iris scores were 0.0 at all time points in all animals.

In the supporting eye irritation study (OECD 405), 0.1 ml of the undiluted test article (96.2% pure) was instilled into the conjunctival sac of one eye of young adult New Zeeland White rabbits (3 female) for 24 hours. Eyes were not washed after instillation. Animals then were observed for 3 days. Irritation was scored by the method of OECD draize system. Conjunctivae (redness): 1.66, 1.33 and 1.33 (animal 1, 2 and 3, respectively); Chemosis: 0.66, 0.33 and 1.0 (animal 1, 2 and 3, respectively); Cornea were 0.0 at all time points in all animals; Iris score: 0.0, 0.0 and 0.33 (animal 1, 2 and 3, respectively).

Based on the results above, the test item is considered to be not irritating to both skin and eyes.

Justification for classification or non-classification

Classification, Labelling, 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 not considered to be classified for skin or eye irritation under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218.