Phosphorodithioic acid, O,O-di-dodecyl-esters, zinc salts, neutral and basic

Endpoint summary

Description of key information

Skin irritation (rabbit): not irritant

RA from CAS 4259-15-8

Eye irritation (rabbit): serious eye damage

RA from CAS 4259-15-8

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

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)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10-15 weeks
- Housing: Housed individually in wire-bottom cages
- Diet: rationed
- Water: ad libitum
- Acclimation period: 15-36 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8-22.2
- Humidity (%): 31-74
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Number of animals:

12

Details on study design:

TEST SITE
- Type of wrap if used: gauze wrapped in plastic sheet

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with gauze pads moistened with mineral oil followed by a dry gauze pad
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Interpretation of results:

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

Conclusions:

CLP: not classified

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:

weight of evidence

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: LSR Industries Inc.
- Housing: singly in wire mesh suspension cages
- Diet: ad libitum
- Water: ad libitum.
- Acclimation period: at least 1 day

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: 01 June 1992 – 18 June 1992

Vehicle:

other: mineral oil

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Test material was instilled into one eye of the test animal while the other eye remained untreated to serve as a control. The test material was not washed from the eyes.

Observation period (in vivo):

The eyes were examined and graded for ocular reaction at 24, 48, and 72 hours following instillation of test material into the eyes

Number of animals or in vitro replicates:

12 rabbits (three males and three females per group)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing
- Time after start of exposure: not applicable

SCORING SYSTEM: Interpretation of the results was made in accordance with the Draize technique for scoring ocular lesions.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

not reversible

Remarks:

by day 3 in 2/6 animals

Remarks on result:

other: concentration as supplied

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.6

Max. score:

2

Reversibility:

not reversible

Remarks:

by day 3 in 4/6 animals

Remarks on result:

other: concentration as supplied

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.6

Max. score:

3

Reversibility:

not reversible

Remarks:

in 4/6 animals

Remarks on result:

other: concentration as supplied

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

4

Reversibility:

not reversible

Remarks:

by day 3 in 6/6 animals

Remarks on result:

other: concentration as supplied

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: 50% in mineral oil

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: 50% in mineral oil

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.4

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: 50% in mineral oil

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.4

Max. score:

4

Reversibility:

not reversible

Remarks:

by day 3 in 1/6 animals

Remarks on result:

other: 50% in mineral oil

Interpretation of results:

other: Eye Dam. 1, H318 according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: Eye Dam. 1, H318

Executive summary:

In a primary eye irritation study, 0.1 mL of undiluted test substance or 50% in mineral oil was placed into one eye of each of the New Zealand White rabbits. The test substance produced serious eye damage up to 72 hours when tested as supplied and was not an ocular irritant when tested as a 50% formulation in mineral oil.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according 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
- Weight at study initiation: 2.38 to 2.64 kg
- Housing: Housed individually in wire mesh suspension cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8-26.1
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Number of animals or in vitro replicates:

9 (6 rinsed, 3 unrinsed)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): for 3 animals rinsed for one minute 200 mL of lukewarm tap water
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.17

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Non-rinsed

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.6

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Non-rinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.17

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: Non-rinsed

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Non-rinsed

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: Rinsed

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Rinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.55

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: Rinsed

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.44

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: Rinsed

Irritant / corrosive response data:

According to the study conducted, the test substance causes persistent eye irritation through 21 days. Rinsing the test material out of the eyes 30 seconds after the exposure resulted in eye irritation that was reversible within 21 days.

Interpretation of results:

other: Eye Dam. 1, H318 according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: Eye Dam. 1, H318

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

(non-GLP, no individual scores given, 14 days of observation instead of 21 days)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.25 - 2.75 kg
- Housing: Housed individually in wire bottom cages
- Diet: 4 ounces daily
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM:
Modification of Draize:

Cornea:
1 = Slight opacity
2 = moderate opacity
3 = dense opacity
4 = complete opacity

Iris:
1 = mild iritis
2 = severe iritis

Conjuctivae (redness and discharge):
1 = slight
2 = moderate
3 = severe

Conjuctivae (chemosis):
1 = slight
2= moderate
3 = severe
4 = extreme

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

31

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

1.1

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0.8

Max. score:

2

Reversibility:

fully reversible within: 10 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Interpretation of results:

other: Eye Dam. 1, H318 according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: Eye Dam. 1, H318

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(non-GLP, individual scores were not given)

Qualifier:

equivalent or similar to guideline

Guideline:

other: 16CFR 1500.42- Federal Hazardous Substances Act Regulations

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: stainless steel with elevated wire mesh flooring, 1 rabbit/cage
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.6-23.8
- Humidity (%): 40-50
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 21 March 1983 – 11 April 1983

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Test material was instilled into one eye of the test animal while the other eye remained untreated to serve as a control. The test material was not washed from the eyes.

Observation period (in vivo):

The eyes were examined and graded for ocular reaction at 1, 2, 3, 4, 7, 14 and 21 days following instillation of test material into the eyes.

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing.

SCORING SYSTEM: Interpretation of the results was made in accordance with the Draize technique for scoring ocular lesions.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: day 21

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.6

Max. score:

2

Reversibility:

fully reversible within: day 14

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.6

Max. score:

3

Reversibility:

not reversible

Remarks:

in 1/6 animals

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

not reversible

Remarks:

in 4/6 animals

Interpretation of results:

other: Eye Dam. 1, H318 according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: Eye Dam. 1, H318

Executive summary:

In a primary eye irritation study, 0.1 mL of undiluted test substance was placed into one eye of each of the New Zealand White rabbits. The test substance produced ocular irritation that did not resolve by 21 day.

The test substance is classified as Category 1 in accordance with the classification system of GHS.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for read-across

There are no reliable data available on irritation / corrosion forPhosphorodithioic acid, O,O-di-dodecyl-esters, zinc salts, neutral and basic(CAS 4563-56-8). Read-across from an appropriate substance Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.1 and 8.2. Common functional groups, structural similarities and comparable toxicological properties of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin irritation / corrosion

The skin irritancy potential of Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) was investigated in NZW rabbits similar to OECD Guideline 404 and GLP (Key, 1986). In this study, 0.5 mL of the undiluted test substance was applied to the dorsal back of NWZ rabbits for 4 h under semi-occlusive conditions. After 4 h, the test substance was removed using a gauze pad moistened with mineral oil followed by a dry gauze pad. The mean erythema score of all animals (24/48/72 h) was 1.0 and the mean edema score (24/48/72 h) was 0.22. The individual scores were not given. Based on the results of this study, the test substance is not considered to have an irritancy potential towards the skin.

In a further study 6 NZW rabbits were treated with 0.5 mL Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) under semi-occlusive conditions (Supporting, 1987, RL1) similar to OECD 404 and GLP for 4 h. The intent of the experiment was to compare two methods of test material removal. Each animal had two test sites. The test material was removed with a dry gauze pad from one site and from a gauze pad moistened with mineral followed by a dry gauze pad on the other site. Based on the results of the conducted study, the test substance showed an irritancy potential when the test material was removed with a dry gauze wipe (edema score of 2; erythema score of 3.5), but no irritancy potential when removed with mineral oil wipe (edema score of 0.4; erythema score of 1.4).

Repeated application of 10% Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) in mineral oil to the skin of rabbits results in accumulating and increasing irritation (Supporting, 1987, RL2). However, this procedure is not according to the current OECD guideline 404, therefore the study was not used for classification.

Eye irritation

Four equal reliable eye irritation studies were available with Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8).

In the study performed according to OECD 405 and GLP 0.1 mL of the undiluted test substance and 0.1 mL of the 50% test substance in mineral oil was instilled into the eye of each of 6 rabbits without washing, respectively (WoE, 1992). The respective untreated eye served as control. The eyes were examined and graded for ocular reaction at 24, 48, and 72 h days following instillation of test material into the eyes. The 50% dilution of the test material resulted in a mean cornea opacity score and a mean iris score of 0 (24/48/72 h). The mean score (24/48/72 h) for conjunctivae and for chemosis was 0.4. Conjunctivae was fully reversible within 72 h, chemosis was not reversible by day 3 in 1/6 animals. The undiluted test material resulted in a mean cornea opacity score (24/48/72 h) of 0.5 which was not reversible by day 3 in 2/6 rabbits and in a mean iris score (24/48/72 h) of 0.6 which was not reversible by day 3 in 4/6 animals. The mean scores (24/48/72 h) for conjunctivae and chemosis were 1.6 and 1.8, respectively. Both effects were not reversible in 4/6 rabbits and in 6/6 rabbits, respectively. The individual scores were not given.

Based on the results of the conducted study, the undiluted test material caused serious eye damage while the 50% formulation in mineral oil showed no irritant potential towards the eyes.

 

In the second study performed according to OECD 405 and GLP 0.1 mL of the undiluted test substance was instilled into the eye of 9 NZW rabbits (WoE, 1996). For 3 animals, the eyes were rinsed after a treatment period of 30 s for one minute with 200 mL of lukewarm tap water. The eyes of 6 rabbits were not washed. The respective untreated eye served as control. The undiluted test material without washing resulted in a mean cornea opacity score (24/48/72 h) of 1.17 which was not reversible and in a mean iris score (24/48/72 h) of 0.6 which was fully reversible within 14 days. The mean scores (24/48/72 h) for conjunctivae and chemosis were 2.17 and 2.67, respectively. Both effects were not reversible. The experimental approach with washing revealed a mean cornea score (24/48/72 h) of 0.33, a mean iris score (24/48/72 h) of 0.0, a mean conjunctivae score (24/48/72 h) of 1.55 and a mean chemosis score (24/48/72 h) of 1.44. These effects were fully reversible. The individual scores were not given.

Based on the results of the conducted study, the undiluted test material causes serious eye damage. Rinsing the test material out of the eyes 30 seconds after the exposure resulted in eye irritation that was reversible within 21 days.

 

In the third study, 0.1 mL of the undiluted test material without washing was investigated similar to OECD 405 in NZW rabbits (WoE, 1975). After instillation of the test material the animals were observed for 14 days. The mean cornea opacity score (24 - 72 h) was 1.1 which was not reversible within 14 days. The mean iris score (24 - 72 h) was 0.8 and was reversible within 10 days. The mean conjunctivae score (24 - 72 h) of 1.55 and the mean chemosis score (24 - 72 h) were 3.0 and 1.7, respectively. Both effects were not reversible within 14 days. Based on the results of the conducted study, the test substance was considered to cause serious eye damage.

 

In a study conducted similar to 16CFR 1500.42- Federal Hazardous Substances Act Regulations, 0.1 mL of undiluted Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) was instilled into one eye each of NZW rabbits while the other eye remained untreated to serve as a control (WoE, 1983). The test material was not washed from the eyes. The eyes were examined and graded for ocular reaction at 1, 2, 3, 4, 7, 14 and 21 days following instillation of test material into the eyes. A mean cornea opacity score (24/48/72 h) of 0.3 was determined, which was not reversible by day 21 and a mean iris score (24/48/72 h) of 0.6 was determined, which was not reversible by day 14. The mean scores (24/48/72 h) for conjunctivae and chemosis were 1.6 and 3.5 and not reversible in 1/6 and 4/6 animals, respectively.

In conclusion, based on the results with the source substance, the target substance is not considered to have an irritancy potential towards the skin, but is considered to cause serious eye damage.

Justification for classification or non-classification

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

Applying the RA-approach, the available data on eye irritation meet the classification criteria, Eye Dam. 1, H318 according to Regulation (EC) 1272/2008.