Zinc dodecyl hydrogen disulphate

Endpoint summary

Description of key information

skin irritation (OECD 404): irritating
eye irritation (OECD 405): highly irritating/corrosive
SCLs according to GHS:
>=10% - <20% Eye Irrit. Cat.2
<10% No Classification

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Refer to the Analogue Approach Justification document provided in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

GLP compliance:

no

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24+72 h

Score:

2.2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: source CAS 151-21-3, BASF, 1976

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24+72 h

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: source CAS 151-21-3, BASF, 1976

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

3.9

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: source CAS 90583-12-3, BASF, 1987

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

3.5

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: source CAS 90583-12-3, BASF, 1987

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

C12-14AS Zn is considered to be irritating to skin and has to be classified as skin irritant Cat. 2 (H315) according to CLP.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Refer to the Analogue Approach Justification document provided in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: source CAS 151-21-3, 25%, BASF, 1987

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: source CAS 151-21-3, 25%, BASF, 1987

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.6

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: source CAS 151-21-3, 25%, BASF, 1987

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: source CAS 151-21-3, 25%, BASF, 1987

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: source CAS 90583-12-3, 30%, BASF, 1988

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: source CAS 90583-12-3, 30%, BASF, 1988

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: source CAS 90583-12-3, 30%, BASF, 1988

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: source CAS 90583-12-3, 30%, BASF, 1988

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: source CAS 68585-47-7, 30%, Hansa, 1984

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: source CAS 68585-47-7, 30%, Hansa, 1984

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: source CAS 68585-47-7, 30%, Hansa, 1984

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2.9

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: source CAS 68585-47-7, 30%, Hansa, 1984

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: Days 1-3

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: source CAS 91783-22-1, 22%, P&G, 1978

Irritation parameter:

iris score

Basis:

mean

Time point:

other: Day 1-3

Score:

0.8

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: source CAS 91783-22-1, 22%, P&G, 1978

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: Day 1-3

Score:

2.1

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: source CAS 91783-22-1, 22%, P&G, 1978

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: Day 1-3

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: source CAS 91783-22-1, 22%, P&G, 1978

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: source CAS 68585-47-7, 10%, Stepan, 1980a

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: source CAS 68585-47-7, 10%, Stepan, 1980a

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: source CAS 68585-47-7, 10%, Stepan, 1980a

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: source CAS 68585-47-7, 10%, Stepan, 1980a

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: source CAS 68585-47-7, 10%, Stepan, 1980b

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: source CAS 68585-47-7, 10%, Stepan, 1980b

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: source CAS 68585-47-7, 10%, Stepan, 1980b

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: source CAS 68585-47-7, 10%, Stepan, 1980b

Interpretation of results:

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

Conclusions:

C12 -14AS Zn (CAS n.a.) contains 1.5% of ZnSO4 which is classified as Eye Dam. Cat.1. Assuming 100% of C12 -14 AS Zn (CAS n.a.) would lead to a classification of Eye Irrit. 2 due to 1.5% ZnSO4. 20% C12 -14 AS Zn (CAS n.a.) which would contain 0.3% ZnSO4 would not lead to a classification as an Eye irritant.Therefore, contribution of ZnSO4 to the eye irritating potential is considered to be negligible when assessing eye irritating potential of C12 -14 AS Zn (CAS n.a.).
Thus, based on the results found with different Alkylsulfates C12-14AS Zn is considered to be damaging to eyes and has to be classified as Eye Damage Cat. 1 (H318) according to CLP. It could be shown with experimental data on eye irritation that at 10 to 20% active substance only the classification Eye Irritating Category 2 according to Regulation (EC) No 1272/2008 remains. Below 10% active substance no classification at all is necessary. Hence, the Generic Concentration Limits (GCLs) can be substituted by the mentioned specific ones (SCLs).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is no study regarding skin and eye irritation/corrosion available for C12-14 AS Zn (CAS n.a.). Therefore this endpoint is covered by read across to structurally related alkyl sulfates (AS), i.e. C12-16 AS NH4 (CAS 90583-12-3) and C12 AS Na (CAS 151-21-3) for skin irritation and C12 AS Na (CAS 151-21-3), C12-16 AS NH4 (CAS 90583-12-3), C10-16 AS Na (CAS 68585-47-7) and C12-13 AS K (CAS 91783-22-1) for eye irritation/corrosion.

The possibility of a read-across to other alkyl sulfates in accordance with Regulation (EC) No 1907/2006 Annex XI 1.5 “Grouping of substances and read-across approach” was assessed. In Annex XI 1.5 it is given that a read-across approach is possible for substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. The AS reported within the AS analogues show structural similarity. The most important common structural feature of the members of the analogue approach is the presence of a predominantly linear aliphatic hydrocarbon chain with a polar sulfate group, neutralized with a counter ion. This structural feature confers the surfactant properties of the alkyl sulfates. The surfactant property of the members of the AS analogues in turn represent the predominant attribute in mediating effects on mammalian health. Therefore, the AS of the AS analogues have similar physicochemical, environmental and toxicological properties, validating the read-across approach. The approach of grouping different AS for the evaluation of their effects on human health and the environment was also made by the OECD in the SIDS initial assessment profile [1] and by a voluntary industry program carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS.

Zinc compounds are recognised as zinc category in the OECD HPV program [3]. The zinc category includes six compounds (zinc metal, zinc oxide, zinc distearate, zinc chloride, zinc sulphate, and trizinc bis(orthophosphate). Available data show that zinc metal, zinc oxide, zinc distearate, and zinc phosphate have a low acute toxicity, are not corrosive and irritating to the skin, eyes, or respiratory tract, and are not sensitizing to the skin. In contrast, zinc chloride is corrosive, irritating to the respiratory tract, and acutely toxic after inhalation and ingestion. Zinc sulphate is also acutely toxic after ingestion, as well as severely irritating to the eyes. These effects seems mainly related to the counter ion and not to the zinc cation. C12 -14AS Zn is classified as harmful if swallowed, skin irritating and corrosive to the eyes. Therefore, contribution of zinc to those endpoints is considered to be negligible when assessing human health effects of C12-14AS Zn.

Skin irritation

Regarding skin irritation one relevant study is available for the read-across substances C12-16 AS NH4 (CAS 90583-12-3) and C12 AS Na (CAS 151-21-3), each.

The key study conducted with C12 AS Na (CAS 151-21-3, analytical purity 100%) was performed similar to OECD Guideline 404 under occlusive conditions (BASF, 1976). Each of six New Zealand White rabbits were exposed for 24 h to 0.5 mL of the unchanged test item and was observed for a period of 72 h for erythema and edema. No scoring was done 48 h after application. The mean erythema and edema score after 24 and 72 h were 2.2 and 1.7. Both were not reversible within 72 h. When using the higher value of the 24 and 72 h reading time point as value for the 48 h value (per animal) the mean erythema and edema score of all animals were 2.4 and 2.2, respectively.

The study conducted with C12-16 AS NH4 (CAS 90583-12-3, analytical purity 30%) was performed according to OECD Guideline 404 under semiocclusive conditions (BASF, 1987). Each of five Kleinrusse white rabbits was exposed for 4 h to 0.5 mL of the unchanged test item and was observed for a period of 21 d for erythema and edema. Skin reactions were scored 24, 48 and 72 h after termination of treatment. The mean erythema and edema score after 24, 48 and 72 h were 3.9 and 3.5. The skin reactions were fully reversible within the 21 day observation period.

Based on the results mentioned above the data on the read-across substances justify a classification of C12-14 AS Zn (CAS n.a.) for skin irritation. According to CLP ≥ 10% C12-14 AS Zn (CAS n.a.) needs to be classified as H315, Skin Irrit. 2. No classification is required below 10% C12-14 AS Zn (CAS n.a.).

 

Eye irritation

No data are available for the neat substance allowing a definitive classification of C12-14 AS Zn (CAS n.a.). Therefore a read-across from C12 AS Na (CAS 151-21-3), C12-16 AS NH4 (CAS 90583-12-3), C12-13 AS K (CAS 91783-22-1) and C10-16 AS Na (CAS 68585-47-7) was performed.

The key study was performed according to OECD guideline 405 with 0.1 mL of C12 AS Na (CAS 151-21-3, analytical purity 25%) (BASF, 1987). The test substance was applied to one eye of each of four rabbits (strain: Kleinrusse Chbb:HM). Eye reactions were scored 1, 6, 24, 48 and 72 h and 7, 10, 14, 17 and 21 days after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 1, 0, 2.6 and 1.1. The corneal and the conjunctival findings did not revers fully until days 21. Thus the test item produced irreversible effects on the eye at a concentration of 25%.

In an OECD guideline 405 study 0.1 g of with C12-16 AS NH4 (CAS 90583-12-3, analytical purity 30%) was applied to the eye of one rabbit (strain: Kleinrusse) (BASF, 1988). The observation period was 21 days. Eye reactions were scored 24, 48 and 72 h after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 1, 0, 2 and 1. The corneal and the conjunctival findings as well the chemosis did not revers fully until days 21. Thus the test item produced irreversible effects on the eye at a concentration of 30%.

In a further OECD guideline 405 study 0.1 mL of C10-16 AS Na (CAS 68585-47-7, analytical purity 30%) was applied to one eye of each of three rabbits (Hansa, 1984). Eye reactions were scored 24, 48 and 72 h and 7 days after application. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 2.3, 1, 2.3 and 2.9. The findings did not fully revers within 7 days. Thus the test item produced irreversible effects on the eye at a concentration of 30%.

Setting of Specific Concentration Limits (SCL) for eye irritation

As corrosion and irritation depends on the concentration of the substance in a solvent, further studies with lower concentrations of the read across substances were also considered to assess whether specific concentration limits can be set.

For this purpose, two studies with C10-16 AS Na (CAS 68585-47-7) and one study with C12-13 AS K (CAS 91783-22-1) with a concentration range of 10 to 22% were evaluated.

In the study with C12-13 AS K (CAS 91783-22-1, analytical purity 44%) 0.1 mL of the diluted test item (1:1 mixture with water) was applied to one eye of each of three New Zealand White rabbits according to OECD guideline 405 (P&G, 1978) without rinsing. In a second experiment with additional 3 rabbits the procedure was repeated but the treated eye was rinsed with 20 mL of lukewarm tap water 4 sec after application of the test item. The eye reactions were recorded 1, 24, 48, 72 h and 4, 7, 14, 21 and 28 days in both experiments. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores of experiment 1 were 2, 0.8, 2.1 and 1.7. The findings reversed in 2/3 animals within 14 days while 1/3 animals showed signs of irritation after 21 days. However, the signs of irritation show a clear tendency to decrease with time. No reading on day 28 was possible. Findings in the experiment with rinsing of the eye were less pronounced but irritating properties were also observed. As the ocular findings clearly reversed within 21 days the result of the study indicate the concentration of 22% to be the turning point between classification as severe damage to the eye and eye damaging.

The first study with 0.1 mL undiluted C10-16 AS Na (CAS 68585-47-7, analytical purity 10%) was performed similar to OECD guideline 405 (Stepan, 1980a) on three New Zealand White rabbits with an observation period of 7 days. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 1.4, 0.7, 2 and 1.6. Corneal opacity was still observed in 1/3 animals (scored 1) and conjunctival redness was still present in 2/3 animals (both scored 1) upon reading at Day 7. Depending on the classification requirements the test substance is not or only moderate irritating to the eye at a concentration of 10%.

The second study with C10-16 AS Na (CAS 68585-47-7, analytical purity 10%) was performed similar to OECD guideline 405 (Stepan, 1980b). 0.1 mL of the undiluted test item was instilled into one eye of each of three New Zealand White rabbits. Eye reactions were scored at least 24, 48 and 72 h and 14 days after application of the test item. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores were 0.9, 0.7, 1.9 and 1.6. All findings were fully reversible within the observation period. Thus, the test substance showed no eye irritating properties at a concentration of 10%.

C12 -14AS Zn (CAS n.a.) contains 1.5% of ZnSO4 which is classified as Eye Dam. Cat.1. Assuming 100% of C12 -14 AS Zn (CAS n.a.) would lead to a classification of Eye Irrit. 2 due to 1.5% ZnSO4. 20% C12 -14 AS Zn (CAS n.a.) which would contain 0.3% ZnSO4 would not lead to a classification as an Eye irritant.Therefore, contribution of ZnSO4 to the eye irritating potential is considered to be negligible when assessing eye irritating potential of C12 -14 AS Zn (CAS n.a.).

Based on the above mentioned results with different concentrations of structurally related alkyl sulfates and the evaluation of ZnSO4 in C12 -14 AS Zn (CAS n.a.) a cut of value for classification as severe irritating to eyes is set at a concentration of 20% and for classification as irritating at a concentration of 10%. Since the available data of the read-across substance C10-16 AS Na (CAS 68585-47-7) indicates no eye irritation potential at a concentration of 10%, no classification is required below 10% C12-14 AS Zn (CAS n.a.).

 

No data on respiratory irritation are available. AS is mainly used in liquid media and due to its very low vapour pressure [2] inhalation is not viewed as a significant route of exposure. Inhalation of AS may occur by inhalation of aerosols generated by spray cleaners or by inhalation of detergent dusts (e.g. washing powder). In both cases the substance will be used in low concentrations. However in case the substance is available as neat powder the substance will also be classified as STOT Single Exp. Cat 3 according to CLP irritating to the respiratory system at concentrations exceeding 20%

 

[1] SIDS initial assessment profile, (2007); http://www.aciscience.org/docs/Alkyl_Sulfates_Final_SIAP.pdf

[2] (HERA Draft report, 2002); http://www.heraproject.com/files/3-HH-04-%20HERA%20AS%20HH%20web%20wd.pdf

[3]SIDS initial assessment profile, (2005); http://webnet.oecd.org/Hpv/UI/handler.axd?id=fddec5fa-9727-413a-9d67-41c2154cd362

Justification for classification or non-classification

According to the classification criteria of Regulation (EC) No 1272/2008 the test substance needs to be classified with Skin Irritation Category 2, H315 and Eye Dam.1, H318. As the neat substance has to be classified as skin irritating, the substance will also be classified as “may cause respiratory irritation” (STOT SE3, H335) in case the substance is available as neat powder.

It could be shown with experimental data on eye irritation that at 10 to 20% active substance only the classification Eye Irritating Category 2 according to Regulation (EC) No 1272/2008 remains. Below 10% active substance no classification at all is necessary. Hence, the Generic Concentration Limits (GCLs) can be substituted by the mentioned specific ones (SCLs).