Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts

Endpoint summary

Description of key information

Skin irritation, rabbits, OECD 404, not irritating to the skin
Skin irritation, rabbits, not irritating to the skin
Eye irritation, rabbits, OECD 405, not irritating to eyes
Eye irritation, rabbits, OECD 405, not irritating to eyes

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin 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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied, based on the chemical structure of the potential analogues, their toxicokinetic behaviour and other available (eco-)toxicological data.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
C20-24 calcium sulfonate and Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are members of a category of chemicals described as alkaryl sulfonates, which was established as part of the U.S. Environmental Protection Agency High Production Volume (HPV) Challenge Program. The substances of this category have a common functional group - the salt of aryl sulfonic acid. Furthermore, they all have a divalent alkaline earth metal, one or more linear and/or branched alkyl groups of variable chain length and branching characteristics or extended heterocyclic carbon system from the sulfonated benzene ring. Finally, they have common precursors and/or the likelihood of common breakdown products via physical and biological processes, resulting in structurally similar chemicals, and similar physicochemical properties, environmental fate, ecotoxicity and mammalian toxicity.
Concerning skin irritation/ corrosion the physico-chemical properties have to be evaluated. CAS 70024-69-0 is believed to be metabolised by the same mechanisms by mammalian organisms. Therefore they are expected to follow the same pattern. For the detailed procedure of the read-across principle and justifications, please refer to the analogue approach justification depicted below and the separate Read-Across Statement (Chemservice S.A., 2017).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical: Benzenesulfonic acid, mono C16-24-alkyl derivs., calcium salts (CAS 70024-69-0, EC 274-263-7)
Target chemical: Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts (C20-24 calcium sulfonate, CAS No none, EC No none)

3. ANALOGUE APPROACH JUSTIFICATION
C20-24 calcium sulfonate and Benzenesulfonic acid, mono C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are UVCB substances that are produced using similar manufacturing process and raw materials and are manufactured in mineral oil. They are members of a category of chemicals described as alkaryl sulfonates, which was established as part of the U.S. Environmental Protection Agency High Production Volume (HPV) Challenge Program. These substances are similar in that they have a common functional group, the salt of aryl sulfonic acid. TOXMATCH and OECD Toolbox QSAR structure similarity assessments using Tanimoto distance fingerprint, Hellinger distance atom environment, Euclidian distance and Dice calculations indicate that these substances are very similar. Likewise, they have similar physicochemical properties, similar environmental fate characteristics, and similar ecotoxicity and mammalian toxicity profiles. For example, these substances can dissociate only in the presence of strong acids such as in the stomach but are not expected to dissociate under environmental conditions. For further details on this, please refer to the separate Read-Across Statement (Chemservice S.A., 2017). The similar toxicity profiles indicate that they have a similar MOA. C20-24 calcium sulfonate and Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are classified as Skin Sens Cat. 1B.
The similar findings (refer to data matrix outlined below and the separate Read-Across Statement) for both substances support the conclusion that similar molecules are expected to be formed from both substances, and in consequence, similar effects can be reasonably expected. Hence, the analogue may perfectly serve as read-across substance for the C20-24 calcium sulfonate and vice versa. So, based on the WOE of these data, the available data on CAS 70024-69-0 can be used to cover the systemic endpoints currently lacking for C20-24 calcium sulfonate and read across is scientifically justified, making further testing obsolete.

4. DATA MATRIX
There is mainly data available on the toxicological properties of the analogues CAS 61789-86-4 / its overbased version CAS 68783-96-0 and for CAS 70024-69-0 / its overbased version CAS 70024-71-4. Data on Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts covers merely the physico chemical properties. Hence, the identification and discussion of common properties of the analogues and the C20-24 calcium sulfonate will be mainly based on this physicochemical data.
The available data for the following physico-chemical properties, which are relevant for absorption into living organisms, are very similar. The substances are rather huge molecules and have a similar molecular weight range, which triggers already similarities in their absorption behaviour. Furthermore, the physico-chemical properties like their partition coefficient, water solubility and vapour pressure are similar. Regarding the application of these substances, the substances are usually solved in an inert mineral oil to enable handling. The C20-24 calcium sulfonate and all analogous substances are hydrolytically stable in the natural environment and at least CAS 70024-69-0 and CAS 61789-86-4 are not readily biodegradable, and the available data suggests this to apply also for C20-24 calcium sulfonate. Taking into account the vast amount of data available for partition coefficient data on various calcium sulfonates it can be concluded that they do not have a significant potential for bioaccumulation in aquatic and terrestrial organisms. However, they are expected to be adsorbed to a significant extent to the sediment and soil and to be thereby not bioavailable, which was confirmed by the results of short-term toxicity tests to fish, daphnia and algae for CAS 70024-71-4; CAS 115733-09-0 and CAS 61789-64-4, in which the lowest LL50 was already > 100 mg/L WAF.
For the following toxicological endpoints there is data available derived from CAS 70024-69-0/ CAS 70024-71-4, Analogue of CAS 70024-69-0, CAS 115733-09-0, CAS 61789-86-4/ CAS 68783-96-0 and CAS 75975-85-8: Acute toxicity, Skin irritation / corrosion, Eye irritation /corrosion, Skin sensitization, Repeated dose toxicity, Genetic toxicity in vitro and in vivo and Toxicity to reproduction (fertility / developmental toxicity). Furthermore a rather extensive data package is available concerning the human sensitization potential of numerous analogous substances. For the acute oral toxicity, the values for all read across substances are very high, all LD50 values being above 2000 mg/kg (reaching in older tests up to greater than 20,000 mg/kg) and the values for the substances can be considered as similar within normal biological variations. The substances are also not toxic via the inhalation or the dermal route of exposure. Regarding Skin/Eye Irritation, the available data on CAS 70024-69-0 and CAS 61789-86-4 shows both substances to be not irritating to the skin or the eyes. The skin sensitization data in animals and humans (for CAS 75975-85-8; CAS 61789-86-4 and EC 939-141-6) evaluated in a weight-of-evidence approach indicates that low TBN calcium sulfonates (TBN < 300) are skin sensitizers with a specific concentration limit (SCL) of 10% and that high TBN calcium sulfonates (TBN ≥ 300) are not skin sensitizers. Last but not least, the available genetic toxicity data for Analogue of CAS 70024-69-0, CAS 61789-86-4 and its overbased version CAS 68783-96-0 prove all of these substances to be not mutagenic. The NOAELs derived for the endpoints Repeated dose toxicity (Analogue of CAS 70024-69-0 and CAS 61789-86-4) and Toxicity to reproduction (fertility / developmental toxicity for CAS 115733-09-0)) have been also found to be in a similar range.
For further details please refer to the separate Read-Across Statement (Chemservice S.A., 2017) and/or the robust study summaries of the respective studies in this IUCLID file.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Remarks:

Animal 1

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 6 days

Irritation parameter:

erythema score

Remarks:

Animal 2

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 6 days

Irritation parameter:

erythema score

Remarks:

Animal 3

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Remarks:

Animal 4

Basis:

mean

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Remarks:

Animal 5

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 5 days

Irritation parameter:

erythema score

Remarks:

Animal 6

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 6 days

Irritation parameter:

edema score

Remarks:

Animal 1

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 4 days

Irritation parameter:

edema score

Remarks:

Animal 2

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Remarks:

Animal 3

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Remarks:

Animal 4

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Remarks:

Animal 5

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Remarks:

Animal 6

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

Mean score calculated by average of results at 24h, 48h and 72h for each animal.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test Score at time point/ Reversibility Erythema Max Score 2 Oedema Max Score 1 24 hours 1/1/1/2/1/1 1/0/1/0/1/0 48 hours 1/1/1/2/1/1 1/0/0/0/0/0 72 hours 1/1/1/1/1/1 1/0/0/0/0/0 Average, 24, 48 and 72 hours 1.2/1.2/1 0.5/0.2/0.2 Reversibility Fully Fully Average time for reversibility 7 days 48 hours   Very slight to slight erythema and desquamation were noted for all animals. Very slight oedema was noted for three animals. All dermal irritation completely subsided by day 8. The Primary Irritation Index (PII) was calculated to be 1.4, using the 24-, 48- and 72 -hour observations. The test article, CAS 70024-69-0, received a descriptive rating classification of slightly irritating. Dermal Observations (Table 2) Erythema: Animal Sex Site 1 H 24 H 48 H 72 H 4 D 5 D 6 D 7 D 8 D 29982 M A 1s 1s 1 1 1 1 0d - - 29983 M A 0s 1s 1 1 1 1 0d - - 29984 M A 0s 1s 1 1d 1d 1d 1d 1d 0 29993 F A 1 2 2 1d 1d 1d 1d 0d - 29994 F A 1 1 1 1d 1d 0d - - - 29995 F A 1 1 1 1 1 1d 0d - - Total - - 4 7 7 6 6 5 2 1 0   Dermal Observations (Table 2) Oedema: Animal Sex Site 1 h 24 h 48 h 72 h 4 d 5 d 6 d 7 d 8 d 29982 M A 0 1 1 1 0 0 0 - - 29983 M A 0 0 0 0 0 0 0 - - 29984 M A 0 1 0 0 0 0 0 0 0 29993 F A 0 0 0 0 0 0 0 0 - 29994 F A 1 1 0 0 0 0 - - - 29995 F A 0 0 0 0 0 0 0 - - Total - - 1 3 1 1 0 0 0 0 0     PII calculated using test periods: 24h, 48h, 72 h Primary Irritaton Index (PII) = [(7+7+6)/18] + [(3+1+1)/18] (PII) = [20/18] + [5/18] (PII) = 1.1 + 0.3 PII  = 1.4 = SLIGHTLY IRRITATING PII calculated using test periods: 24h, 72 h Primary Irritaton Index (PII) = [(7+6)/12] + [(3+1)/12] (PII) = [13/12] + [4/12] (PII) = 1.1 + 0.3 PII  = 1.4 = SLIGHTLY IRRITATING  H = HOURS       D = DAYS  F = FEMALE M = MALE  d = DESQUAMATION   s = DOSE SITE STAINED YELLOW  - = DERMAL IRRITATION PREVIOUSLY SUBSIDED; ANIMAL TERMINED FROM STUDY   Body Weights (Table 3): There were no remarkable body weight changes during the study. Animal Sex Weight (g) Initial Weight (g) Termination 29982 M 2480 2693 (Day 6) 29983 M 2218 2320 (Day 6) 29984 M 2329 2504 (Day 8) 29993 F 2071 2294 (Day 7) 29994 F 2213 2507 (Day 5) 29995 F 2311 2596 (Day 6)

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

Mean scores for each animal at 24h, 48h and 72 h for erythema and oedema, respectively, were 0. Therefore, the calcium sulfonate Read-Across substance (CAS 70024-69-0) is not irritating to skin under the conditions of this test. These results can be used to fulfill the information requirements for the chemical substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts, due to the high structural similarity of these substances. For the detailed procedure of the read-across principle and justifications, please refer to the separate Read-Across Statement (Chemservice S.A., 2017).

Executive summary:

The primary dermal irritation potential of the calcium sulfonate (CAS 70024 -69 -0) was evaluated in this study with New Zealand White rabbits. There was one group of six young adult albino rabbits that received a single, four-hour, semioccluded exposure. Each 0.5 mL dose of the test article was applied to the clipped, unabraded skin. At completion of exposure, the bandages were removed and the sites washed. Application sites were evaluated in accordance with the method of Draize at approximately 30-60 minutes and 24, 48 and 72 hours after patch removal and daily through day 8, if irritation persisted. Very slight to slight erythema and desquamation were noted for all animals. Very slight oedema was noted for three animals. All dermal irritation completely subsided by day 8. The Primary Irritation Index (PII) was calculated to be 1.4, using the 24-, 48- and 72 -hour observations. The calcium sulfonate read across substance (CAS 70024 -69 -0) received a descriptive rating classification of slightly irritating. This is, however, not considered to be irritating taking into account the classification criteria for skin irritation by the european global harmonised system (a dermal irritant is a substance which causes a primary irritation index of >2.3 < 4).

These results can be used to fulfill the information requirements for the chemical substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts, due to the high structural similarity of these substances. For the detailed procedure of the read-across principle and justifications, please refer to the separate Read-Across Statement (Chemservice S.A., 2017).

Reference 2

Endpoint:

skin 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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied, based on the chemical structure of the potential analogues, their toxicokinetic behaviour and other available (eco-)toxicological data.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
C20-24 calcium sulfonate and Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are members of a category of chemicals described as alkaryl sulfonates, which was established as part of the U.S. Environmental Protection Agency High Production Volume (HPV) Challenge Program. The substances of this category have a common functional group - the salt of aryl sulfonic acid. Furthermore, they all have a divalent alkaline earth metal, one or more linear and/or branched alkyl groups of variable chain length and branching characteristics or extended heterocyclic carbon system from the sulfonated benzene ring. Finally, they have common precursors and/or the likelihood of common breakdown products via physical and biological processes, resulting in structurally similar chemicals, and similar physicochemical properties, environmental fate, ecotoxicity and mammalian toxicity.
Concerning skin irritation/ corrosion the physico-chemical properties have to be evaluated. CAS 70024-69-0 is believed to be metabolised by the same mechanisms by mammalian organisms. Therefore they are expected to follow the same pattern. For the detailed procedure of the read-across principle and justifications, please refer to the analogue approach justification depicted below and the separate Read-Across Statement (Chemservice S.A., 2017).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical: Benzenesulfonic acid, mono C16-24-alkyl derivs., calcium salts (CAS 70024-69-0, EC 274-263-7)
Target chemical: Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts (C20-24 calcium sulfonate, CAS No none, EC No none)

3. ANALOGUE APPROACH JUSTIFICATION
C20-24 calcium sulfonate and Benzenesulfonic acid, mono C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are UVCB substances that are produced using similar manufacturing process and raw materials and are manufactured in mineral oil. They are members of a category of chemicals described as alkaryl sulfonates, which was established as part of the U.S. Environmental Protection Agency High Production Volume (HPV) Challenge Program. These substances are similar in that they have a common functional group, the salt of aryl sulfonic acid. TOXMATCH and OECD Toolbox QSAR structure similarity assessments using Tanimoto distance fingerprint, Hellinger distance atom environment, Euclidian distance and Dice calculations indicate that these substances are very similar. Likewise, they have similar physicochemical properties, similar environmental fate characteristics, and similar ecotoxicity and mammalian toxicity profiles. For example, these substances can dissociate only in the presence of strong acids such as in the stomach but are not expected to dissociate under environmental conditions. For further details on this, please refer to the separate Read-Across Statement (Chemservice S.A., 2017). The similar toxicity profiles indicate that they have a similar MOA. C20-24 calcium sulfonate and Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are classified as Skin Sens Cat. 1B.
The similar findings (refer to data matrix outlined below and the separate Read-Across Statement) for both substances support the conclusion that similar molecules are expected to be formed from both substances, and in consequence, similar effects can be reasonably expected. Hence, the analogue may perfectly serve as read-across substance for the C20-24 calcium sulfonate and vice versa. So, based on the WOE of these data, the available data on CAS 70024-69-0 can be used to cover the systemic endpoints currently lacking for C20-24 calcium sulfonate and read across is scientifically justified, making further testing obsolete.

4. DATA MATRIX
There is mainly data available on the toxicological properties of the analogues CAS 61789-86-4 / its overbased version CAS 68783-96-0 and for CAS 70024-69-0 / its overbased version CAS 70024-71-4. Data on Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts covers merely the physico chemical properties. Hence, the identification and discussion of common properties of the analogues and the C20-24 calcium sulfonate will be mainly based on this physicochemical data.
The available data for the following physico-chemical properties, which are relevant for absorption into living organisms, are very similar. The substances are rather huge molecules and have a similar molecular weight range, which triggers already similarities in their absorption behaviour. Furthermore, the physico-chemical properties like their partition coefficient, water solubility and vapour pressure are similar. Regarding the application of these substances, the substances are usually solved in an inert mineral oil to enable handling. The C20-24 calcium sulfonate and all analogous substances are hydrolytically stable in the natural environment and at least CAS 70024-69-0 and CAS 61789-86-4 are not readily biodegradable, and the available data suggests this to apply also for C20-24 calcium sulfonate. Taking into account the vast amount of data available for partition coefficient data on various calcium sulfonates it can be concluded that they do not have a significant potential for bioaccumulation in aquatic and terrestrial organisms. However, they are expected to be adsorbed to a significant extent to the sediment and soil and to be thereby not bioavailable, which was confirmed by the results of short-term toxicity tests to fish, daphnia and algae for CAS 70024-71-4; CAS 115733-09-0 and CAS 61789-64-4, in which the lowest LL50 was already > 100 mg/L WAF.
For the following toxicological endpoints there is data available derived from CAS 70024-69-0/ CAS 70024-71-4, Analogue of CAS 70024-69-0, CAS 115733-09-0, CAS 61789-86-4/ CAS 68783-96-0 and CAS 75975-85-8: Acute toxicity, Skin irritation / corrosion, Eye irritation /corrosion, Skin sensitization, Repeated dose toxicity, Genetic toxicity in vitro and in vivo and Toxicity to reproduction (fertility / developmental toxicity). Furthermore a rather extensive data package is available concerning the human sensitization potential of numerous analogous substances. For the acute oral toxicity, the values for all read across substances are very high, all LD50 values being above 2000 mg/kg (reaching in older tests up to greater than 20,000 mg/kg) and the values for the substances can be considered as similar within normal biological variations. The substances are also not toxic via the inhalation or the dermal route of exposure. Regarding Skin/Eye Irritation, the available data on CAS 70024-69-0 and CAS 61789-86-4 shows both substances to be not irritating to the skin or the eyes. The skin sensitization data in animals and humans (for CAS 75975-85-8; CAS 61789-86-4 and EC 939-141-6) evaluated in a weight-of-evidence approach indicates that low TBN calcium sulfonates (TBN < 300) are skin sensitizers with a specific concentration limit (SCL) of 10% and that high TBN calcium sulfonates (TBN ≥ 300) are not skin sensitizers. Last but not least, the available genetic toxicity data for Analogue of CAS 70024-69-0, CAS 61789-86-4 and its overbased version CAS 68783-96-0 prove all of these substances to be not mutagenic. The NOAELs derived for the endpoints Repeated dose toxicity (Analogue of CAS 70024-69-0 and CAS 61789-86-4) and Toxicity to reproduction (fertility / developmental toxicity for CAS 115733-09-0)) have been also found to be in a similar range.
For further details please refer to the separate Read-Across Statement (Chemservice S.A., 2017) and/or the robust study summaries of the respective studies in this IUCLID file.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

animal #4

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

animal #5

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

animal #6

Time point:

48 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Mean score calculated by average of results at 24h, and 72h for each animal.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test Score at time point/ Reversibility Erythema (max Score 0) Oedema Max Score 0) 24 h 0/0/0/0/0/0 0/0/0/0/0/0 72 h 0/0/0/0/0/0 0/0/0/0/0/0 Average 24, 72 h 0/0 0/0 Reversibility No indication of irritation No indication of irritation

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

Mean scores for each animal at 24h, and 72 h for erythema and oedema, respectively, were 0. Therefore, the calcium sulfonate Read-Across substance (CAS 70024-69-0) is not irritating to skin under the conditions of this test. These results can be used to fulfill the information requirements for the chemical substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts, due to the high structural similarity of these substances. For the detailed procedure of the read-across principle and justifications, please refer to the separate Read-Across Statement (Chemservice S.A., 2017).

Executive summary:

In a primary dermal irritation study, 6 young adult albino rabbits were dermally exposed to 0.5 mL of the calcium sulfonate read across substance (CAS 70024-69-0) for 24 hours. Animals then were observed for 72 hours. The mean erythema scores as well as the mean oedema scores were permanently 0 for all treated animals. Thus, in this study, the calcium sulfonate read across substance (CAS 70024-69-0) is not a dermal irritant.

These results can be used to fulfill the information requirements for the chemical substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts, due to the high structural similarity of these substances. For the detailed procedure of the read-across principle and justifications, please refer to the separate Read-Across Statement (Chemservice S.A., 2017).

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:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied, based on the chemical structure of the potential analogues, their toxicokinetic behaviour and other available (eco-)toxicological data.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
C20-24 calcium sulfonate and Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are members of a category of chemicals described as alkaryl sulfonates, which was established as part of the U.S. Environmental Protection Agency High Production Volume (HPV) Challenge Program. The substances of this category have a common functional group - the salt of aryl sulfonic acid. Furthermore, they all have a divalent alkaline earth metal, one or more linear and/or branched alkyl groups of variable chain length and branching characteristics or extended heterocyclic carbon system from the sulfonated benzene ring. Finally, they have common precursors and/or the likelihood of common breakdown products via physical and biological processes, resulting in structurally similar chemicals, and similar physicochemical properties, environmental fate, ecotoxicity and mammalian toxicity.
Concerning eye irritation/ corrosion the physico-chemical properties have to be evaluated. CAS 70024-69-0 is believed to be metabolised by the same mechanisms by mammalian organisms. Therefore they are expected to follow the same pattern. For the detailed procedure of the read-across principle and justifications, please refer to the analogue approach justification depicted below and the separate Read-Across Statement (Chemservice S.A., 2017).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical: Benzenesulfonic acid, mono C16-24-alkyl derivs., calcium salts (CAS 70024-69-0, EC 274-263-7)
Target chemical: Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts (C20-24 calcium sulfonate, CAS No none, EC No none)

3. ANALOGUE APPROACH JUSTIFICATION
C20-24 calcium sulfonate and Benzenesulfonic acid, mono C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are UVCB substances that are produced using similar manufacturing process and raw materials and are manufactured in mineral oil. They are members of a category of chemicals described as alkaryl sulfonates, which was established as part of the U.S. Environmental Protection Agency High Production Volume (HPV) Challenge Program. These substances are similar in that they have a common functional group, the salt of aryl sulfonic acid. TOXMATCH and OECD Toolbox QSAR structure similarity assessments using Tanimoto distance fingerprint, Hellinger distance atom environment, Euclidian distance and Dice calculations indicate that these substances are very similar. Likewise, they have similar physicochemical properties, similar environmental fate characteristics, and similar ecotoxicity and mammalian toxicity profiles. For example, these substances can dissociate only in the presence of strong acids such as in the stomach but are not expected to dissociate under environmental conditions. For further details on this, please refer to the separate Read-Across Statement (Chemservice S.A., 2017). The similar toxicity profiles indicate that they have a similar MOA. C20-24 calcium sulfonate and Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are classified as Skin Sens Cat. 1B.
The similar findings (refer to data matrix outlined below and the separate Read-Across Statement) for both substances support the conclusion that similar molecules are expected to be formed from both substances, and in consequence, similar effects can be reasonably expected. Hence, the analogue may perfectly serve as read-across substance for the C20-24 calcium sulfonate and vice versa. So, based on the WOE of these data, the available data on CAS 70024-69-0 can be used to cover the systemic endpoints currently lacking for C20-24 calcium sulfonate and read across is scientifically justified, making further testing obsolete.

4. DATA MATRIX
There is mainly data available on the toxicological properties of the analogues CAS 61789-86-4 / its overbased version CAS 68783-96-0 and for CAS 70024-69-0 / its overbased version CAS 70024-71-4. Data on Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts covers merely the physico chemical properties. Hence, the identification and discussion of common properties of the analogues and the C20-24 calcium sulfonate will be mainly based on this physicochemical data.
The available data for the following physico-chemical properties, which are relevant for absorption into living organisms, are very similar. The substances are rather huge molecules and have a similar molecular weight range, which triggers already similarities in their absorption behaviour. Furthermore, the physico-chemical properties like their partition coefficient, water solubility and vapour pressure are similar. Regarding the application of these substances, the substances are usually solved in an inert mineral oil to enable handling. The C20-24 calcium sulfonate and all analogous substances are hydrolytically stable in the natural environment and at least CAS 70024-69-0 and CAS 61789-86-4 are not readily biodegradable, and the available data suggests this to apply also for C20-24 calcium sulfonate. Taking into account the vast amount of data available for partition coefficient data on various calcium sulfonates it can be concluded that they do not have a significant potential for bioaccumulation in aquatic and terrestrial organisms. However, they are expected to be adsorbed to a significant extent to the sediment and soil and to be thereby not bioavailable, which was confirmed by the results of short-term toxicity tests to fish, daphnia and algae for CAS 70024-71-4; CAS 115733-09-0 and CAS 61789-64-4, in which the lowest LL50 was already > 100 mg/L WAF.
For the following toxicological endpoints there is data available derived from CAS 70024-69-0/ CAS 70024-71-4, Analogue of CAS 70024-69-0, CAS 115733-09-0, CAS 61789-86-4/ CAS 68783-96-0 and CAS 75975-85-8: Acute toxicity, Skin irritation / corrosion, Eye irritation /corrosion, Skin sensitization, Repeated dose toxicity, Genetic toxicity in vitro and in vivo and Toxicity to reproduction (fertility / developmental toxicity). Furthermore a rather extensive data package is available concerning the human sensitization potential of numerous analogous substances. For the acute oral toxicity, the values for all read across substances are very high, all LD50 values being above 2000 mg/kg (reaching in older tests up to greater than 20,000 mg/kg) and the values for the substances can be considered as similar within normal biological variations. The substances are also not toxic via the inhalation or the dermal route of exposure. Regarding Skin/Eye Irritation, the available data on CAS 70024-69-0 and CAS 61789-86-4 shows both substances to be not irritating to the skin or the eyes. The skin sensitization data in animals and humans (for CAS 75975-85-8; CAS 61789-86-4 and EC 939-141-6) evaluated in a weight-of-evidence approach indicates that low TBN calcium sulfonates (TBN < 300) are skin sensitizers with a specific concentration limit (SCL) of 10% and that high TBN calcium sulfonates (TBN ≥ 300) are not skin sensitizers. Last but not least, the available genetic toxicity data for Analogue of CAS 70024-69-0, CAS 61789-86-4 and its overbased version CAS 68783-96-0 prove all of these substances to be not mutagenic. The NOAELs derived for the endpoints Repeated dose toxicity (Analogue of CAS 70024-69-0 and CAS 61789-86-4) and Toxicity to reproduction (fertility / developmental toxicity for CAS 115733-09-0)) have been also found to be in a similar range.
For further details please refer to the separate Read-Across Statement (Chemservice S.A., 2017) and/or the robust study summaries of the respective studies in this IUCLID file.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Remarks:

Animal 1

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

Animal 2

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

Animal 3

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

Animal 4

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

Animal 5

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

Animal 6

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

Animal 1

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

Animal 2

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

Animal 3

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

Animal 4

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

Animal 6

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

Animal 1

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Remarks:

Animals 2 and 3 and 6

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

Animals 4 and 6

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Remarks:

Animal 1

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Remarks:

Animal 2

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Remarks:

Animal 3

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Remarks:

Animals 4 and 5

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Remarks:

Animal 6

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 4 days

Other effects:

One animal had clear discharge from the eye, one hour post dosing. There were no deaths or changes in bodyweight throughout the study.

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis was 0 for all animals. Mean scores for conjuntival redness and oedema were less than 2 in all animals. Therefore, the calcium sulfonate read across substance (CAS 70024-69-0) is not irritating to rabbit eyes. These results can be used to fulfill the information requirements for the chemical substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts, due to the high structural similarity of these substances. For the detailed procedure of the read-across principle and justifications, please refer to the separate Read-Across Statement (Chemservice S.A., 2017).

Executive summary:

In the key study, the eye irritation potential of the calcium sulfonate read across substance, (CAS 70024-69-0), was evaluated in accordance with EPA OPPTS 870.2400 (Kern, 1999e). A group of six albino rabbits (3 per sex) was used for the study. Each animal received a single, unwashed exposure of 0.1 mL of the test article instilled into the lower conjunctival sac of the right eye. The eyelid was held closed for approximately one second and released. The left eye was manipulated in a similar manner as the right eye and served as a contralateral control. Observations for eye irritation were made at 1, 24, 48 and 72 hours following dosing and on day 4 in accordance with the method of Draize. One animal had clear discharge from the eye, one hour post dosing. There were no deaths or changes in bodyweight throughout the study. Mean 24, 48, and 72 hour corneal and iris scores were 0 for all animals tested. The conjunctival erythema score were 1.3, 1, 1, 1, 1, and 1, respectively and were all reversible within 7 days. The chemosis scores were 0.3, 1.3, 0.3, 0, 0 and 1, respectively. In this study, the calcium sulfonate read across substance (CAS 70024 -69 -0) is not an eye irritant.

These results can be used to fulfill the information requirements for the chemical substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts, due to the high structural similarity of these substances. For the detailed procedure of the read-across principle and justifications, please refer to the separate Read-Across Statement (Chemservice S.A., 2017).

Reference 2

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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied, based on the chemical structure of the potential analogues, their toxicokinetic behaviour and other available (eco-)toxicological data.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
C20-24 calcium sulfonate and Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are members of a category of chemicals described as alkaryl sulfonates, which was established as part of the U.S. Environmental Protection Agency High Production Volume (HPV) Challenge Program. The substances of this category have a common functional group - the salt of aryl sulfonic acid. Furthermore, they all have a divalent alkaline earth metal, one or more linear and/or branched alkyl groups of variable chain length and branching characteristics or extended heterocyclic carbon system from the sulfonated benzene ring. Finally, they have common precursors and/or the likelihood of common breakdown products via physical and biological processes, resulting in structurally similar chemicals, and similar physicochemical properties, environmental fate, ecotoxicity and mammalian toxicity.
Concerning eye irritation/ corrosion the physico-chemical properties have to be evaluated. CAS 70024-69-0 is believed to be metabolised by the same mechanisms by mammalian organisms. Therefore they are expected to follow the same pattern. For the detailed procedure of the read-across principle and justifications, please refer to the analogue approach justification depicted below and the separate Read-Across Statement (Chemservice S.A., 2017).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical: Benzenesulfonic acid, mono C16-24-alkyl derivs., calcium salts (CAS 70024-69-0, EC 274-263-7)
Target chemical: Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts (C20-24 calcium sulfonate, CAS No none, EC No none)

3. ANALOGUE APPROACH JUSTIFICATION
C20-24 calcium sulfonate and Benzenesulfonic acid, mono C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are UVCB substances that are produced using similar manufacturing process and raw materials and are manufactured in mineral oil. They are members of a category of chemicals described as alkaryl sulfonates, which was established as part of the U.S. Environmental Protection Agency High Production Volume (HPV) Challenge Program. These substances are similar in that they have a common functional group, the salt of aryl sulfonic acid. TOXMATCH and OECD Toolbox QSAR structure similarity assessments using Tanimoto distance fingerprint, Hellinger distance atom environment, Euclidian distance and Dice calculations indicate that these substances are very similar. Likewise, they have similar physicochemical properties, similar environmental fate characteristics, and similar ecotoxicity and mammalian toxicity profiles. For example, these substances can dissociate only in the presence of strong acids such as in the stomach but are not expected to dissociate under environmental conditions. For further details on this, please refer to the separate Read-Across Statement (Chemservice S.A., 2017). The similar toxicity profiles indicate that they have a similar MOA. C20-24 calcium sulfonate and Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts (CAS 70024-69-0) are classified as Skin Sens Cat. 1B.
The similar findings (refer to data matrix outlined below and the separate Read-Across Statement) for both substances support the conclusion that similar molecules are expected to be formed from both substances, and in consequence, similar effects can be reasonably expected. Hence, the analogue may perfectly serve as read-across substance for the C20-24 calcium sulfonate and vice versa. So, based on the WOE of these data, the available data on CAS 70024-69-0 can be used to cover the systemic endpoints currently lacking for C20-24 calcium sulfonate and read across is scientifically justified, making further testing obsolete.

4. DATA MATRIX
There is mainly data available on the toxicological properties of the analogues CAS 61789-86-4 / its overbased version CAS 68783-96-0 and for CAS 70024-69-0 / its overbased version CAS 70024-71-4. Data on Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts covers merely the physico chemical properties. Hence, the identification and discussion of common properties of the analogues and the C20-24 calcium sulfonate will be mainly based on this physicochemical data.
The available data for the following physico-chemical properties, which are relevant for absorption into living organisms, are very similar. The substances are rather huge molecules and have a similar molecular weight range, which triggers already similarities in their absorption behaviour. Furthermore, the physico-chemical properties like their partition coefficient, water solubility and vapour pressure are similar. Regarding the application of these substances, the substances are usually solved in an inert mineral oil to enable handling. The C20-24 calcium sulfonate and all analogous substances are hydrolytically stable in the natural environment and at least CAS 70024-69-0 and CAS 61789-86-4 are not readily biodegradable, and the available data suggests this to apply also for C20-24 calcium sulfonate. Taking into account the vast amount of data available for partition coefficient data on various calcium sulfonates it can be concluded that they do not have a significant potential for bioaccumulation in aquatic and terrestrial organisms. However, they are expected to be adsorbed to a significant extent to the sediment and soil and to be thereby not bioavailable, which was confirmed by the results of short-term toxicity tests to fish, daphnia and algae for CAS 70024-71-4; CAS 115733-09-0 and CAS 61789-64-4, in which the lowest LL50 was already > 100 mg/L WAF.
For the following toxicological endpoints there is data available derived from CAS 70024-69-0/ CAS 70024-71-4, Analogue of CAS 70024-69-0, CAS 115733-09-0, CAS 61789-86-4/ CAS 68783-96-0 and CAS 75975-85-8: Acute toxicity, Skin irritation / corrosion, Eye irritation /corrosion, Skin sensitization, Repeated dose toxicity, Genetic toxicity in vitro and in vivo and Toxicity to reproduction (fertility / developmental toxicity). Furthermore a rather extensive data package is available concerning the human sensitization potential of numerous analogous substances. For the acute oral toxicity, the values for all read across substances are very high, all LD50 values being above 2000 mg/kg (reaching in older tests up to greater than 20,000 mg/kg) and the values for the substances can be considered as similar within normal biological variations. The substances are also not toxic via the inhalation or the dermal route of exposure. Regarding Skin/Eye Irritation, the available data on CAS 70024-69-0 and CAS 61789-86-4 shows both substances to be not irritating to the skin or the eyes. The skin sensitization data in animals and humans (for CAS 75975-85-8; CAS 61789-86-4 and EC 939-141-6) evaluated in a weight-of-evidence approach indicates that low TBN calcium sulfonates (TBN < 300) are skin sensitizers with a specific concentration limit (SCL) of 10% and that high TBN calcium sulfonates (TBN ≥ 300) are not skin sensitizers. Last but not least, the available genetic toxicity data for Analogue of CAS 70024-69-0, CAS 61789-86-4 and its overbased version CAS 68783-96-0 prove all of these substances to be not mutagenic. The NOAELs derived for the endpoints Repeated dose toxicity (Analogue of CAS 70024-69-0 and CAS 61789-86-4) and Toxicity to reproduction (fertility / developmental toxicity for CAS 115733-09-0)) have been also found to be in a similar range.
For further details please refer to the separate Read-Across Statement (Chemservice S.A., 2017) and/or the robust study summaries of the respective studies in this IUCLID file.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

mean

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Chemosis score Animal 4 mean 24, 48, 72 hours, 1, 2 fully reversible within 72 hours
Chemosis score Animal 5 mean 24, 48, 72 hours, 0.3, 1 fully reversible within 48 hours
Chemosis score Animal 6 mean 24, 48, 72 hours, 1, 2 fully reversible within 72 hours

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis was 0 for all animals. The scores for conjunctival redness and oedema were less than 2 in 4 animals. Therefore, this clacium sulfonate read across substance (CAs 70024-69-0) is not irritating to rabbit eyes. These results are not used to fulfill the information requirements for the chemical substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts, due to the high structural similarity of these substances. For the detailed procedure of the read-across principle and justifications, please refer to the separate Read-Across Statement (Chemservice S.A., 2017).

Executive summary:

In the other key study, the eye irritation potential of the calcium sulfonate read across substance, (CAS 70024-69-0), was evaluated (Swan, 1972). Adult New Zealand white rabbits (3/sex) were administered 0.1 mL of test substance into one eye. The other eye served as a control. Eyes were scored for corneal, iritis and conjunctival effects 24, 48 and 72 hours following exposure. Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis was 0 for all animals. The scores for conjunctival redness and oedema were less than 2 in 4 animals. Therefore, this calcium sulfonate read across substance (CAs 70024 -69 -0) is not irritating to rabbit eyes and is not an eye irritant.

These results are not used to fulfill the information requirements for the chemical substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts, due to the high structural similarity of these substances. For the detailed procedure of the read-across principle and justifications, please refer to the separate Read-Across Statement (Chemservice S.A., 2017).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The key study was undertaken in 1999 (Kern, 1999a, according to OECD 404) to investigate the skin irritation potential of the calcium sulfonate read across substance (CAS 70024-69-0) in New Zealand White rabbits. 3 males and 3 females were treated semi-occlusively (type of cover: gauze binder) with 0.5 mL of the test material for 4 hours. After removal of the substance the animals were observed for 8 days. The test sites were then evaluated in accordance with the method of Draize at 60 min, 24, 48 and 72 hours and then daily if irritation persisted. The mean erythema score were 1, 1, 1, 1.7, 1 and 1 and were fully reversible by maximally 8 days. Mean oedema scores at 24, 48 and 72 hours were 1, 0, 0.3, 0, 0.3 and 0, and were fully reversible within 48 h or 4 days. Animals did not display any abnormal signs throughout the test period. Bodyweights did not significantly alter. Based on the results of this study this substance is not a skin irritant.

Furthermore, another key study also was conducted to evaluate the skin irritation potential of the calcium sulfonate read across substance (CAS 70024-69-0; Swan, 1972). In this primary dermal irritation study, a dose of 0.5 mL of the undiluted test substance was applied to the abraded an unabraded skin of 6 young adult albino rabbits for 24 hours. Animals then were observed at the end of the 24 hour exposure and at 72 hours. All scores for erythema and oedema in abraded and unabraded skin at both the 24 hour and 48 hour observations were 0 using the method of Draize. Based on the absence of effects after 24 hour exposure, which is longer (more severe) than the current prescribed 4 hour exposure guidance, this substance is not a skin irritant.

In several supporting studies, the read-across substances calcium sulfonates (CAS 70024-69-0 and CAS 61789-86-4) were not irritating to rabbit' skin (Hoff, 2002a, b; Costello, 1986b; Ohees, 1968c; Kern, 1999c).

In a supporting study with the calcium sulfonate read across substance CAS 70024-69-0 (Hoff, 2002a), New Zealand White rabbits (3 animals) were treated semi-occlusively (type of cover: plastic) with 0.5 mL of the test material for 4 hours. After removal of the substance (gently washing with distilled water) the animals were observed for 14 days. The test sites were then evaluated in accordance with the method of Draize at 24, 48 and 72 hours and then daily if irritation persisted. The mean erythema scores were 0.7, 0 and 1.7, and were fully reversible by 72 hours or 14 days for 1.7. Mean oedema scores at 24, 48 and 72 hours were 0, 0 and 1, and were fully reversible within 14 days. Animals did not display any abnormal signs throughout the test period. Bodyweights did not significantly alter. Based on the results of this study this substance is not a skin irritant.

In another supporting study, the dermal irritation potential of the same calcium sulfonate read across substance (CAS 70024-69-0) was tested (Hoff, 2002b). In this study, 3 young adult New Zealand White rabbits were dermally exposed (semi-occlusively) to 0.5 mL of the test item for 4 hours. After removal of the substance (gently mashing with distilled water), animals then were observed for 7 days. The test sites were then evaluated in accordance with the method of Draize at 24, 48 and 72 hours and then daily if irritation persisted. The mean erythema score were 1, 1 and 2, and were fully reversible within 7 days. Mean oedema scores at 24, 48 and 72 hours were 0, 0 and 1.3, and were fully reversible within 7 days. Animals did not display any abnormal signs throughout the test period. Bodyweight was reduced in one animal. Mean scores for each animal at 24, 48 and 72 hours for erythema and oedema were less than 2.3 and fully reversible by maximally 7 days, respectively. Based on the results of this study this substance is not a skin irritant.

In a disregarded skin irritation screening study (Buehler, 1990a) the calcium sulfonate read across substance, CAS 70024-69-0 was investigated in 2 rabbits (1 male and 1 female). A dose of 0.5 mL of the undiluted test material was placed on gauze, which was applied to the shaved skin and then covered with a semi-occlusive wrap. After 4 hours the wrap and gauze were removed and the skin of each animal was evaluated at 24 and 72 hours in accordance with the method of Draize. The mean erythema score were 2.5 in one animal and 2.0 in the other. In the former animal erythema decreased from a score of 3 at 24 hours to a score of 2 at 72 hours indicating the effects are reversible. While the overall mean scores for erythema and oedema (2.5 and 2.25, respectively, with evidence of reversibility) suggest that the substance is not a skin irritant, this study cannot be used to determine classification and labelling because only 2 animals were used and observations were terminated at 72 hours rather than the normal 14 days.

In another disregarded study of the calcium sulfonate read across substance, CAS 70024-69-0 that was conducted following the disregarded screening study of Buehler (1990a), six animals (3 male and 3 female animals) were used to more fully evaluate the skin irritation potential of the calcium sulfonate read across substance, CAS 70024-69-0 (Buehler, 1991a). A dose of 0.5 mL of four different concentrations (6.25 %, 12.5 %, 25 % and 50%). the test material was placed on gauze, which was applied to the shaved skin and then covered with a semi-occlusive wrap. After 4 hours the wrap and gauze were removed and the skin of each animal was evaluated at 24 and 72 hours in accordance with the method of Draize. The mean erythema score for 6.25 % were 1.5, 2, 2, 2, 2 and 1, and were not fully reversible within 72 hours. Mean oedema scores for 6.25 % at 24 and 72 hours were 0.5, 0.5, 0, 2, 0.5 and 1, and were mainly not fully reversible within 72 hours. The mean erythema score for 12.5 % were 1.5, 2, 2, 2, 2.5 and 2, and were not fully reversible within 72 hours. Mean oedema scores for 6.25 % at 24 and 72 hours were 0.5, 0.5, 0.5, 1, 1.5 and 0.5, and were mainly not fully reversible within 72 hours. The mean erythema score for 25 % were 2, 3, 3, 2.5, 2 and 2, and were not fully reversible within 72 hours. Mean oedema scores for 25 % at 24 and 72 hours were 2, 2.5, 1.5, 2.5, 0.5 and 2, and were mainly not fully reversible within 72 hours. Mean scores for each animal at 24 h, and 72 h for erythema and oedema (concentration ≤ 25%), respectively, were less than 2.3.The mean erythema score for 50 % at 24 and 72 hours were 2, 3, 3, 3, 2.5 and 1.5, and were not fully reversible within 72 hours. Mean oedema scores for 50 % at 24 and 72 hours were 2.5, 3, 2.5, 2.5, 2 and 0.5, and were mainly not fully reversible within 72 hours. However, the skin irritation response in this study, particularly at 50%, is disregarded because it is inconsistent with the skin irritation results from the key and supporting studies on the calcium sulfonate read across substances (CAS 70024-69-0 and CAS 61789-86-4).

In a supporting primary dermal irritation study, 6 albino rabbits were dermally exposed to the test article (as supplied, dose volume 0.5 mL) the calcium sulfonate read across substance (CAS 61789 -86 -4) for 4 hours (Costello, 1986b). The skin was clipped over a wide area on their backs approximately 24 hours prior to application. Animals then were observed for 72 hours. Irritation was scored by the method of Draize. The mean 24, 48, and 72 hour individual animal erythema and oedema scores were 1.33, 1.67, 1.0, 1.67, 1.67, and 1.67 and 0.33, 1.67, 1.33, 2.0, 2.33, and 2.0, respectively. The overall mean 24, 48, and 72 hour erythema and oedema scores were 1.5 and 1.6, respectively. Scores of 1 for erythema and oedema were present in one or more animals at the end of the 14 day observation period. Based on the results of this study this substance is not a skin irritant.

In another supporting primary dermal irritation study, 6 albino rabbits were dermally exposed to the test article (as supplied, dose volume 0.5 mL) the calcium sulfonate read across substance (CAS 61789 -86 -4) for 24 hours (Ohees, 1968c). The test material was applied to two areas, one abraded area and one intact area. The animals were fitted with collars for a 24 hour period at which time the coverings were removed, the test material washed off and the degree of erythema and oedema were recorded. A second reading was taken at 72 hours. The mean 24 and 72 hour individual animal erythema and oedema scores for abraded skin were 0.5, 0.5, 0.5, 0.5, 0.5, and 0.5 and 0.0, 0.5, 0.0, 0.5, 0.5, and 0.0, respectively. The mean 24 and 72 hour individual animal erythema and oedema scores for unabraded skin were 0.5, 0.5, 0.5, 0.5, 0.5, and 0.5 and 1.67 and 0.0, 0.5, 0.0, 0.5, 0.5, and 0.0, respectively. The overall mean 24 and 72 hour erythema and edema scores for abraded and unabraded skin were 0.5 and 0.25, respectively. All erythema and oedema scores in abraded and unabraded skin were 0.0 at the final 72 hour observation period. Based on the results of this study this substance is not a skin irritant.

In another disregarded primary dermal irritation study, 6 albino rabbits were dermally exposed to the sulfonate read across substance (CAS 61789 -86 -4, as supplied, dose 0.5 g) for 24 hours (Gabriel, 1981). The test material was applied to two areas, one abraded area and one intact area. Gauze patches were placed over the treated area and an impervious material was wrapped snugly around the trunks of the animals to hold the patches in place. The skin of each animal was evaluated at 24 and 72 hours in accordance with the method of Draize. The mean erythema scores were 2 (intact skin) and 2 (abraded skin) after 24 hours and 1.83 (intact skin) and 1.67 (abraded skin) after 72 hours. Mean oedema scores at 24 and 72 hours were 1.5 and 0.67 referring to intact skin. In addition, scores of 1.5 and 0.67 were determined for abraded skin. However, this study cannot be used to determine classification and labelling because the exposure period was 24 hours rather than 4 hours and the study was terminated prior to 14 days post exposure. The observed skin irritation scores following 24 hours cannot be used to predict the scores following the shorter (less severe) 4 hour exposure prescribed under current guidance. Therefore, the study is disregarded.

The primary dermal irritation potential of the calcium sulfonate read across substance (CAS 61789-86-4) was evaluated in this study with New Zealand White rabbits (Kern, TG, 1999c). There was one group of six albino rabbits that received a single, four-hour, semioccluded exposure. Each 0.5 mL dose of the test article was applied to the clipped, unabraded skin. At completion of exposure, the bandages were removed and the sites washed. Application sites were evaluated in accordance with the method of Draize at approximately 30-60 minutes and 24, 48 and 72 hours after patch removal and daily through day 13, if irritation persisted. The mean 24, 48, and 72 hour individual animal erythema and oedema scores were 1.0, 1.33, 0.33, 0.0, 0.0, and 0.67 and 0.0, 0.33, 0.0, 0.0, 0.0, and 0.5, respectively. The overall mean 24, 48, and 72 hour erythema and oedema scores were 0.5 and 0.05, respectively. All erythema and oedema was fully reversible by day 13 and 72 hours, respectively. Based on the results of this study this substance is not a skin irritant.

Based on these results, the calcium sulfonates do not meet criteria for classification and labelling as skin irritants in accordance with Regulation (EC) No 1272/2008 (CLP Regulation).

Eye irritation:

In the key study, the eye irritation potential of the calcium sulfonate read across substance, (CAS 70024-69-0), was evaluated in accordance with EPA OPPTS 870.2400 (Kern, 1999b). A group of six albino rabbits (3 per sex) was used for the study. Each animal received a single, unwashed exposure of 0.1 mL of the test article instilled into the lower conjunctival sac of the right eye. The eyelid was held closed for approximately one second and released. The left eye was manipulated in a similar manner as the right eye and served as a contralateral control. Observations for eye irritation were made at 1, 24, 48 and 72 hours following dosing and on day 4 in accordance with the method of Draize. One animal had clear discharge from the eye, one hour post dosing. There were no deaths or changes in bodyweight throughout the study. Mean 24, 48, and 72 hour corneal and iris scores were 0 for all animals tested. The conjunctival erythema score were 1.3, 1, 1, 1, 1, and 1,respectively and were all reversible within 7 days. The chemosis scores were 0.3, 1.3, 0.3, 0, 0 and 1, respectively. In this study, substance is not an eye irritant.

In the other key study, the eye irritation potential of the calcium sulfonate read across substance, (CAS 70024-69-0), was evaluated (Swan, 1972). Adult New Zealand white rabbits (3/sex) were administered 0.1 mL of test substance into one eye. The other eye served as a control. The test material was not washed from the eyes. Eyes were scored for corneal, iritis and conjunctival effects 24, 48 and 72 hours following exposure in accordance with the method of Draize. Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis was 0 for all animals. Mean scores for conjunctival redness were 2, 2, 1.3, 1.3, 1 and 1, respectively. Mean scores for chemosis were 2, 1.7, 0.7, 1, 0.3 and 1, respectively. As the scores for conjunctival redness and oedema were less than 2 in 4 animals, therefore, this substance is not irritating to rabbit eyes.

Moreover, data on calcium sulfonate read-across substance, (CAS 70024-69-0), in rabbits show that this substance is not irritating to the eyes.

In a disregarded eye irritation screening study (Buehler, 1990b) the calcium sulfonate read across substance, CAS 70024-69-0 was investigated in 2 rabbits (1 male and 1 female). Each animal received a single, exposure of 0.1 mL of the test article instilled into one eye. The other eye served as a control. The test material was not washed from the eyes. Animals were observed at 1, 24, 48, 72 hours in accordance with the method of Draize. Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis were 0 for all animals. Mean scores for conjunctival redness was 2 in both animals. Conjunctival oedema scores were 2.0 in one animal and 2.33 for the other. In the latter animal the conjunctival oedema decreased from a score of 3 at 24 hours to a score of 2 at 72 hours indicating the effects being reversible. However, because only 2 animals were used and observations were terminated at 72 hours rather than the normal 21 days, this study cannot be used to determine classification and labelling.

In a follow-up supporting study of the calcium sulfonate read across substance, CAS 70024-69-0, that was conducted following the screening study of Buehler (1990b), six animals (3 male and 3 female animals) were used to more fully evaluate the eye irritation potential of the calcium sulfonate read across substance, CAS 70024-69-0 (Buehler, 1991b). Each animal received a single, exposure of 0.1 mL of the test article instilled into one eye. The other eye served as a control. The test material was not washed from the eyes. Animals were observed at 1, 24, 48, 72 hours in accordance with the method of Draize. Mean scores at 24, 48 and 72 hours for each animal for corneal opacity and iritis was 0 for all animals. Mean scores for conjunctival redness were 1, 0.7, 0.7, 0.3, 0.3 and 1, respectively. Mean scores for chemosis were 1.3, 0.7, 0, 0.7, 0.7 and 1.7, respectively. With the exception of the 1.7 value for chemosis in animal 6, all other signs were fully reversible within 72 hours. The mean scores for all animals for conjunctival redness and oedema were less than 2. Therefore, this substance is not irritating to rabbit eyes.

In another supporting study the calcium sulfonate read across substance (CAS 61789-86-4) was investigated for its eye irritating potential (Ohees, 1968d). Adult albino rabbits of the New Zealand White variety (6) were placed in a collar such that the animals could not rub their eyes. One tenth of a millilitre of test substance was instilled in one eye, the other untreated eye served as a control. The reaction to the test material was read according to the scale of scoring for damage to the cornea, iris and the bulbar and palpebral conjunctivae at 24, 48 and 72 hours after eye instillation. Any residue of the test material and accumulated discharge are flushed from the eye each time they are scored.

Under the conditions specified the product has an eye irritating score of 0 and 0 and 0 at 24, 48 and 72 hours respectively. Therefore the substance is not irritating to the eye.

In a supporting study with the same calcium sulfonate read across substance, CAS 61789-86-4 (Gabriel, 1981c) was investigated for its eye irritating potential in rabbits. Six healthy young adult albino rabbits were used in this study. 0.1 gram of the experimental material was instilled into the right eyes of the test animals, while the other eye remained untreated to serve as a control. The test material was not washed from the eyes. The treated eyes were examined at one, two, three, five and seven days following instillation of the test material into the eyes. Interpretation of the results was made in accordance with the Draize Scale of Scoring Ocular Lesions. The test material is not a primary irritant and requires no cautionary labelling with respect to an eye irritating potential.

Based on these results Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts is not classified as an eye irritating in accordance with Regulation (EC) No 1272/2008 (CLP Regulation).

Justification for selection of skin irritation / corrosion endpoint:
best study available

Justification for selection of eye irritation endpoint:
best study available

Justification for classification or non-classification

The classification and labelling of the target substance Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts (generic name: C20 -24 calcium sulfonate) is based on the results of the in vivo key and supporting studies for the calcium sulfonate read-across substances (CAS 70024 -69 -0 and CAS 61789 -86 -4).

Skin irritation

According to the classification criteria outlined in the section 3.2.2.2. (Guidance on the Application of CLP criteria, 2015), if the mean value of≥2.3 -≤4.0 was reached for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal, the classification as Skin Irritant Category 2 would be assigned. In the skin irritation studies with calcium sulfonate analogues (CAS 70024 -69 -0 and CAS 61789 -86 -4) of the C20-24 calcium sulfonate none of the animals reached the cut-off value of 2.3 for erythema of oedema. The dermal reactions were in all but one supporting study completely reversible within 14 days. In the supporting study Costella, 1986, in some animals an erythema and oedema score of 1 was present at the end of the 14 day observation period. These results, however, are expected to have resolved within an extended observation period of 21 days. Based on this knowledge, the C20-24 calcium sulfonate (Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salts) does not meet criteria of Regulation (EC) No 1272/2008 for classification and labelling as a skin irritant.

Eye irritation

According to the classification criteria outlined in the section 3.3.2.2. (Guidance on the Application of CLP criteria, 2015), if a substance cause positive but reversible reactions such as corneal opacity (score ≥ 1), iritis (score ≥ 1), conjunctival redness (score ≥ 2) or conjunctival oedema (chemosis; score ≥ 2) in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after application, the classification as Eye Irritant (Category 2) is assigned.

The results of eye irritation studies with calcium sulfonate (CAS 70024-69-0; CAS 61789-86-4) and sodium sulfonate (CAS 68608-26-4) analogues summarised in this dossier are used for the purpose of determining the classification and labelling of the C20-24 calcium sulfonate. The results of the eye irritation studies with calcium sulfonates (CAS 70024 -69 -0 and CAS 61789 -86 -4) are negative. In detail, mean 24, 48, and 72 hour corneal and iris scores were 0 for all animals tested. The mean scores for conjunctival redness and oedema were less than 2 in all animals and as such under the cut-off value of 2.0 for this time period. Based on this observation, the C20-24 calcium sulfonate ( Reaction products of benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs. para-, calcium salt) is does not meet criteria of Regulation (EC) No 1272/2008 for classification and labelling as an eye irritant.

Therefore, it is concluded, that the calcium sulfonate target substance (mono-C20 -C24 (even)) does not meet the criteria for classification and labelling for skin or eye irritation in accordance with Regulation (EC) No 1272/2008.