Benzene, mono-C10-13-alkyl derivs., distn. residues, sulfonated, barium salts

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitization

Overview

In the lubricant additive industry, a common name such as calcium sulfonate or barium sulfonate is used for natural and synthetic long-chain alkylbenzenesulfonic acids, calcium or barium salts. Barium and calcium sulfonates are used as detergents in a broad variety of lubricant applications. Calcium or barium sulfonates with a large excess of calcium or barium carbonate are referred to as high overbased or high total base number (TBN) calcium or barium sulfonates, whereas calcium or barium sulfonates with small amounts of added calcium or barium carbonate are called low overbased or low TBN calcium or barium sulfonates. 

Barium sulfonate:

1.In a key study, the dermal sensitisation of this low TBN substance (Benzene, mono-C10-13-alkyl derivs., distn. residues, sulfonated, barium salts, CAS 93820-55-4) was evaluated in a Buehler test in guinea pigs (Smedley, J.W., 2062, according to OECD 406, Table S1). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 250% concentration of the test substance.Following challenge with 25%of the test substancein mineral oil, dermal scores of 1 or 2 were noted in 17/20 test animals and 1/10 challenge control animals at the 24-hour scoring interval. At the 48-hour scoring interval, dermal scores of 1 or 2 were noted in 19/20 test animals and 1/10 challenge control animals. Dermal reactions in the remaining test and challenge control animals were scores of 0 or ±. Group mean dermal scores were higher in the test animals (1.2 to 1.3) as compared to challenge control animals (0.2 to 0.2).The animal test results meet the specifications set in the Guidance on the Application of the CLP Criteria (≥15 % responding at > 20 % topical induction dose, Version 4.1, June 2015), and the data are sufficient for subclassification of the calcium sulfonate test substance (CAS 93820-55-4) into subcategory 1B.

 

Table S1. Dermal Sensitisation Study (Modified Buehler Design) in Guinea Pigs with a 100% Low TBN Benzene, mono-C10-13-alkyl derivs., distn.residues, sulfonated, barium salts Induction: Challenge Results (Smedley, 2016)

Group	Concentration	Mean Draize Score		# Positive	Conclusion
		24 hours	48 hours
Test	25%	1.2	1.3	19/10
Control	25%	0.2	0.2	0/10	Sensitizer (subcategory 1B)
Control = Topical application of test article to naive animals to account for primary irritation reactions

 

2.In a key study, the dermal sensitisation of this low TBN substance (Benzene, mono-C10-13-alkyl derivs., distn. residues, sulfonated, barium salts, CAS 93820-55-4) was evaluated in a Buehler test in guinea pigs (A.H.B.M. van Huygevoort, 2012, according to OECD 406, Table S2). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 100% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 100%, were 7/20, and the mean 24/48 hour Draize scores were 0.35/0.15, respectively. The mean 24/48 hour Draize scores for the naïve controls at 1000 were 0/0, respectively. The animal test results meet the specifications set in the Guidance on the Application of the CLP Criteria (≥15 % responding at > 20 % topical induction dose, Version 4.1, June 2015), and the data are sufficient for subclassification of the calcium sulfonate test substance (CAS 93820-55-4) into subcategory 1B.

Table S2. Dermal Sensitisation Study (Modified Buehler Design) in Guinea Pigs with a 100% Low TBN Calcium Sulfonate (Benzene, mono-C10-13-alkyl derivs., distn.residues, sulfonated, barium salts) Induction: Challenge Results (van Huygevoort, 2012)

Group	Concentration	Mean Draize Score		# Positive	Conclusion
		24 hours	48 hours
Test	100%	0.35	0.15	07/10
Control	100%	0	0	0/10	Sensitizer (subcategory 1B)
Control = Topical application of test article to naive animals to account for primary irritation reactions

Calcium sulfonate:

Skin sensitization studies are available for structurally similar natural and synthetic calcium sulfonates. For Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) classification and labelling, EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008 applies. Animal studies show that calcium sulfonates with a TBN greater than 300 are not skin sensitizers, the results in animals at a TBN of 300 exhibit a mixed response, however, human repeat insult patch tests clearly show that high TBN overbased calcium sulfonates (TBN≥300) are not sensitizers (data not shown). Barium sulronate has low TBN and animal test results showed sensitizing potential. However, low TBN calcium sulfonates do not cause sensitization in a substantial number of persons at concentrations of 10% or lower within the definition of sensitisation under EU Regulation (EC) No 1272/2008, more specifically, there are no any TSCA 8(c) allegations of skin sensitization for calcium sulfonates, thus 10% is proposed as the SCL for Calcium sulfonate. The human data is summarized in the following table:

Repeated Insult Patch Test Result Summary

EC# TBN Conc Patch Name Area Volume Amount Subject Male Female age Result 939-141-6 10 100% Webril Cotton Fabric 2cm x 2cm Assumed 0.2ml  50,000µg/cm2 53 11 42 20-65 some evidence of sensitization but number not given. 44 subjects completed test 939-141-6 10 20% Webril Cotton Fabric 2cm x 2cm Assumed 0.2ml 8500µg/cm2 55 11 44 18-66 14 /45 619-278-7 at 10% 10 10% Parke-Davis Readi-Bandage  2cm x 2cm 0.2ml 4250µg/cm2 159 37 122 18-65 4/154 616-278-7 85 10% Webril Cotton Fabric 2cmx2cm Assumed 0.2ml 4250µg/cm2 53 8 45 24-63 positive in 3/48 616-278-7 10 10%   3/4"x3/4" (3.629 cm2) 0.2ml 4685µg/cm2 223     16-70 12/199 at 10% 0% at 1% 939-141-6 10 10% or 1%   3/4"x3/4" (3.629 cm2) 0.2ml 10%= 4685µg/cm2; 1%= 425µg/cm2 227     18-75 15/210 @10%,  0/210 at 1% 939-141-6 10 10% Parke-Davis Readi-Bandage   0.2ml 4250µg/cm2 157 28 129 18-65 4/140 263-093-9 30 10/% Parke-Davis Readi-Bandage  assume 2cm x 2cm 0.2ml 4250µg/cm2 166 26 140 19-68 8/142 263-093-9 30 10% or 1%   3/4"x3/4" (3.629 cm2) 0.2ml 4685µg/cm2 220     19-72 12/205 at 10% 0% at 1% 263-093-9 82 10%   2cm x 2cm Assumed 0.2ml 4250µg/cm2 60 11 49 18-66 0/56 263-093-9 100 10%   2cm x 2cm 0.2g 5000µg/cm2 53 3 50 19-63 0/51 939-141-6 10 1% Parke-Davis Readi-Bandage  assume 2cm x 2cm 0.2ml 425µg/cm2 53 11 42 18-64 0/48

 

Low TBN Calcium Sulfonate Skin Sensitisation:

 (1) Animal Studies

3.In another key study, the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 10) was evaluated in a Buehler test in guinea pigs (Bonnette, 1993b, according to OECD 406, Table S3). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 50% concentration of the test substance. After approximately one week the animals were re-challenged with a 25% concentration of the test substance. Following the first rechallenge, the animals then were re-challenged with a 10% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 50%, 25%, and 10% were 9/10, 10/10, and 9/10, respectively, and the mean 24/48 hour Draize scores were 1.9/2.1, 1.6/2.0, and 1.5/1.5, respectively. The mean 24/48 hour Draize scores for the naïve controls at 50%, 25%, and 10% were 0.2/0.2, 0.7/0.6, and 0.5/0.5, respectively. The animal test results meet the specifications set in the Guidance on the Application of the CLP Criteria (≥15 % responding at > 20 % topical induction dose, Version 4.1, June 2015), and the data are sufficient for subclassification of the calcium sulfonate test substance (EC 939-141-6) into subcategory 1B.

Table S3. Dermal Sensitisation Study (Modified Buehler Design) in Guinea Pigs with a 100% Low TBN Calcium Sulfonate (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, Calcium Salts; EC 939 -141 -6; TBN = 10) Induction: Challenge Results (Bonnette, 1993b)

 

Group		Concentration		Mean Draize Score			# Positive		Conclusion
				24 hours		48 hours
Test		50%		1.9		2.1		09/10		Sensitizer (subcategory 1B)
Control		50%		0.2		0.2		1/10
Test		25%		1.6		2.0		10/10		Sensitizer (subcategory 1B)
Control		25%		0.7		0.6		3/10
Test		10%		1.5		1.5		09/10		Sensitizer (subcategory 1B)
Control		10%		0.5		0.5		1/10
Control = Topical application of test article to naive animals to account for primary irritation reactions

4.In another key study, the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939 -141 -6; TBN = 10) was evaluated in a Buehler test in guinea pigs (Shults, 1993, according to OECD 406; Table S4). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 25% concentration of the test substance. After approximately one week the animals were rechallenged with a 10% concentration of the test substance. Following the first rechallenge, the animals then were rechallenged with a 10% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 25%, 10% rechallenge, and 10% second rechallenge were 10/10, 9/10, and 7/10, respectively, and the mean 24/48 hour Draize scores were 1.4/1.15, 0.8/0.95, and 0.8/0.85, respectively. The mean 24/48 hour Draize scores for the naïve controls at 25%, 10% rechallenge, and 10% second rechallenge were 0.8/0.06, 0.55/0.6, and 0.3/0.65, respectively. The animal test results meet the specifications set in the Guidance on the Application of the CLP Criteria (≥15 % responding at > 20 % topical induction dose, Version 4.1, June 2015), and the data are sufficient for subclassification of the calcium sulfonate test substance (EC 939-141-6) into subcategory 1B.

Table S4. Dermal Sensitisation Study (Modified Buehler Design) in Guinea Pigs with a 100% Low TBN Calcium Sulfonate (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, Calcium Salts; EC 939 -141 -6; TBN = 10) Induction: Challenge Results (Shults, 1993)

 

Group	Concentration	Mean Draize Score		# Positive	Conclusion
		24 hours	48 hours
Test	25%	1.4	1.15	10/10	Sensitizer (subcategory 1B)
Control	25%	0.8	0.06	6/10
Test	10%	0.8	0.95	09/10	Sensitizer (subcategory 1B)
Control	10%	0.55	0.6	3/10
Test	10%	0.8	0.85	07/10	Sensitizer (subcategory 1B)
Control	10%	0.3	0.65	3/10
Control = Topical application of test article to naive animals to account for primary irritation reactions

5.In a key study, the dermal sensitisation of a low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 10) was evaluated in the local lymph node assay (LLNA) (Lees, 1996, according to OECD 429). Groups of male mice (4/group) were dose with approximately 25 µL of 0.1, 1, 10 or 30% concentrations of the test material in DMF on the dorsal surface of each ear for three consecutive days. The animals were then injected with 3H-methylthymidine, and the auricular lymph nodes where then collected and prepared for scintillation counting. A three-fold or greater increase in isotope incorporation was observed at all test concentrations (subcategory 1A). The positive response in this study is supportive of the sensitisation response for low TBN calcium sulfonates noted in other sensitisation studies. . However, this substance is surface active, literature data have shown limitations in LLNA for predicting skin sensitization potential of surfactants and their intermediates.

(2) Human Data  

1.In another key study, the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN =10) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1993a; Table S5). A panel of 53 subjects was identified for this test. In the induction phase the undiluted (100% concentration) test substance was administered directly to the skin and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 44 subjects that completed the induction phase was topically challenged with the undiluted (100% concentration) test substance. Positive responses (scores≥1) were observed in 9/44 and 6/44 at the 24 and 72 hour readings, respectively. Rechallenge of the six subjects suspected of exhibiting allergic reactions confirmed allergic contact dermatitis in four (4/44 or 9%). In the present study an induction dose per unit area of 50,000 µg/cm² is assumed as the pure substance (100%) was used for exposure of a skin area of 4 cm² (“A sufficient quantity of the calcium sulfonate test article was applied directly to the skin with a cotton-tip applicator. In addition, a thin layer was also placed onto a 2 cm x 2 cm square of Webril cotton fabric affixed to Scanpor (Allerderm) semi-occlusive surgical tape which was applied to the back of each subject, between the scapulae and waist, adjacent to the spinal mid-line.”), which leads to classification of the calcium sulfonate test substance (EC 939-141-6) as a sensitizer (subcategory 1B).

2.In another key study, the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 10) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994c, Table S5). A panel of 55 subjects was identified for this test. In the induction phase a 20% concentration of the test substance in mineral oil was administered directly to the skin and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 45 subjects that completed the induction phase was topically challenged with a 20% concentration of the test substance in mineral oil. Positive responses (scores ≥ 1) were observed in 16/45 and 16/45 at the 24 and 72 hour readings (or 48 or 96 hour make up readings), respectively. Approximately 31 % (14/45) of the test population exhibited skin reactivity patterns that were suggestive or indicative of low to moderate grade, induced allergic contact dermatitis. In the present study an induction dose per unit area of 8500 µg/cm² is assumed as a dilution of the pure substance (20%) was used for exposure of a skin area of 4 cm² (“A sufficient quantity of the calcium sulfonate test article to cover the test site was applied directly to the skin with a cotton-tipped applicator. In addition, a thin layer was placed onto a 2 cm x 2 cm square of Webril cotton fabric affixed to Scanpor (Allerderm) semi-occlusive surgical tape which was applied to the back of each subject, between the scapulae and waist, adjacent to the spinal mid-line.”), which leads to classification of the calcium sulfonate test substance (EC 939-141-6) as a sensitizer (subcategory 1B).

Table S5. Human Repeat Insult Patch Tests (HRIPT) with a Low TBN Calcium Sulfonate (Benzenesulfonic Acid, 4-(Mono-C15-36 Branched Alkyl Derivs., C24 Rich) and Benzenesulfonic Acid, 4-Octadecyl, Calcium Salts; EC 939-141-6; TBN = 10): Challenge Results (Shanahan & Erianne, 1993a; Shanahan & Erianne, 1994c)

 

Test Phase	Concentration	# Positive Responses		Conclusion	Reference
		24 hours	72 hours
Induction	100%
Challenge	100%	09/44	06/44
Rechallenge	100%	Observed up to 96h 04/44		Sensitizer (subcategory 1B)	Shanahan & Erianne, 1993a
Induction	20%
Challenge	20%	16/45*	16/45*	Sensitizer (subcategory 1B)	Shanahan & Erianne, 1994c

* 48 or 96 hour make-up readings were required for some subjects.

  

Low TBN Specific Concentration Limit (SCL): 

The weight-of-evidence of all the animal and human studies demonstrates that low TBN calcium sulfonates are skin sensitizers. However, well-conducted, reliable, controlled HRIPT studies show that these substances do not cause sensitisation in a substantial number of subjects at concentrations of 10% and lower.

3.In another key study, the dermal sensitisation of a low TBN analogue of this substance (Benzene, polypropene derivs., sulfonated, calcium salts; CAS 75975-85-8; EC 616-278-7; TBN = 10) was evaluated in a human repeat insult patch test (Alworth, Schwartz & Erianne, 1995a; Table S6). Five panels consisting of a total of 159 subjects were identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 154 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 4/154 (2.6%) of the subjects exhibited sensitisation responses. Based on the testing protocol: 0.2 mL of 10% solution was used for exposure of a skin area of 4 cm² for induction and challenge (“A sufficient amount of the calcium sulfonate test article (approximately 0.2 mL) was placed onto a Parke-Davis ReadiBandage occlusive patch, which was applied to the back of each subject between the scapulae and waist, adjacent to the spinal mid-line.”), an induction dose per unit area of 4250 µg/cm² was derived which leads to classification of the calcium sulfonate test substance (CAS 75975-85-8) as a sensitizer (subcategory 1B).

4.In another key study, the dermal sensitisation of a low TBN analogue of this substance (Benzene, polypropene derivs., sulfonated, calcium salts; CAS 75975-85-8; EC 616-278-7; TBN = 85), was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994a; Table S6). A panel of 53 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 48 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 3/48 (6.3%) of the subjects exhibited sensitisation responses. Based on the testing protocol: 0.2 mL of 10% solution was used for exposure of a skin area of 4.0 cm² for induction and challenge, an induction dose per unit area of 4250 µg/cm² was derived for induction and challenge. (“A sufficient quantity of the calcium sulfonate test article to cover the test site was applied directly to the skin with a cotton-tipped applicator. In addition, a thin layer was placed onto a 2 cm x 2 cm square of Webril cotton fabric affixed to Scanpor (Allerderm) semi-occlusive surgical tape which was applied to the back of each subject, between the scapulae and waist, adjacent to the spinal mid-line.”), which leads to classification of the calcium sulfonate test substance (CAS 75975-85-8) as a sensitizer (subcategory 1B).

5. In another key study, the dermal sensitisation of a low TBN analogue of this substance (Benzene, polypropene derivs., sulfonated, calcium salts; CAS 75975-85-8; EC 616-278-7; TBN = 10) was evaluated in a human repeat insult patch test (Eisenberg, 1994a; Table S6). A panel of 223 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of ten applications. Following a two week rest period, each of the 199 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 12/199 (6.0%) of the subjects exhibited sensitisation responses following the 10% challenge Based on the testing protocol: 0.2 mL of 10% solution) was used for exposure of a skin area of 3.629 cm² for induction and challenge (“Prior to the initiation of this study, the calcium sulfonate test material was prepared as a 10% solution using white mineral oil as a diluent. Approximately 0.2 mL of the calcium sulfonate test material was applied to the 3/4" x 3/4" gauze portion of an adhesive dressing. This was then applied to the appropriate treatment site to form an occluded patch.”), an induction dose per unit area of 4685 µg/cm² was derived, which leads to classification of the calcium sulfonate test substance (CAS 75975-85-8) as a sensitizer (subcategory 1B). A total of 0/199 (0%) of the subjects exhibited sensitisation responses following the 1% challenge.

6.In another key study, the dermal sensitisation of this substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN =10) was evaluated in a human repeat insult patch test (Eisenberg,1994b; Table S6). A panel of 227 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of ten applications. Following a two week rest period, each of the 210 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 15/200 (7.1%) of the subjects exhibited sensitisation responses following the 10% challenge. Based on the testing protocol: 0.2 mL of 10% solution was used for exposure of a skin area of 3.629 cm² for induction and challenge. (“Prior to the initiation of this study, the calcium sulfonate test material was prepared as a 10% solution using white mineral oil as a diluent. Approximately 0.2 mL of the calcium sulfonate test material was applied to the 3/4" x 3/4" gauze portion of an adhesive dressing. This was then applied to the appropriate treatment site to form an occluded patch.”), an induction dose per unit area of 4685 µg/cm² was derived, which leads to classification of the calcium sulfonate test substance (EC 939-141-6) as a sensitizer (subcategory 1B).

7.In another key study, the dermal sensitisation of this substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN =10) was evaluated in a human repeat insult patch test (Alworth, Schwartz & Erianne, 1995b; Table S6). Four panels consisting of a total of 157 subjects were identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 140 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 4/140 (2.9%) of the subjects exhibited sensitisation responses. Based on the testing protocol: 0.2 mL of 10% solution was used for exposure of a skin area of 4.0 cm² for induction and challenge, an induction dose per unit area of 4250 µg/cm² was derived for induction and challenge (“A sufficient amount of the calcium sulfonate test article (approximately 0.2 mL) was placed onto a Parke-Davis ReadiBandage occlusive patch, which was applied to the back of each subject between the scapulae and waist, adjacent to the spinal mid-line.”), which leads to classification of the calcium sulfonate test substance (EC 939-141-6) as a sensitizer (subcategory 1B).

8.In another key study, the dermal sensitisation of a low TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; CAS 61789-86-4; EC 263-093-9; TBN = 30) was evaluated in a human repeat insult patch test (Alworth, Schwartz & Erianne, 1995c; Table S6). Five panels consisting of a total of 166 subjects were identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 142 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 8/142 (5.6%) of the subjects exhibited sensitisation responses. Based on the testing protocol: 10% dilutions sample; sufficient amount of the calcium sulfonate test article (approximately 0.2 mL) was placed onto a Parke-Davis ReadiBandage occlusive patch, which was applied to the back of each subject between the scapulae and waist. adjacent to the spinal mid-line, an induction dose per unit area of 4250 µg/cm² was derived, which leads to classification of the calcium sulfonate test substance (CAS 61789-86-4) as a sensitizer (subcategory 1B).  

9. In another key study, the dermal sensitisation of a low TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; CAS 61789-86-4; EC 263-093-9; TBN = 30) was evaluated in a human repeat insult patch test (Eisenberg, 1994c; Table S6). A panel of 220 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of ten applications. Following a two week rest period, each of the 205 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 12/205 (ca. 5.9%) of the subjects exhibited sensitisation responses following the 10% challenge. Based on the testing protocol: 0.2 mL of 10% solution was used for exposure of a skin area of 3.629 cm² for induction and challenge (“Prior to the initiation of this study, the calcium sulfonate test material was prepared as a 10% solution using white mineral oil as a diluent. Approximately 0.2 mL of the calcium sulfonate test material was applied to the 3/4" x 3/4" gauze portion of an adhesive dressing. This was then applied to the appropriate treatment site to form an occluded patch.”), an induction dose per unit area of 4685µg/cm² was derived, which leads to classification of the calcium sulfonate test substance (CAS 61789-86-4) as a sensitizer (subcategory 1B). A total of 0/205 (ca. 0%) of the subjects exhibited sensitisation responses following the 1% challenge.

10.In another key study, the dermal sensitisation of a low TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; CAS 61789-86-4; , EC 263-093-9; TBN = 82, was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994e; Table S6). A panel of 60 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered to a 2cm x 2cm gauze portion (4250 µg/cm² was derived), and directly applied to the skin and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 56 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 0/56 (0.0%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to not cause a sensitisation response.

11. In another key study, the dermal sensitisation of a low TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; CAS 61789-86-4; EC 263-093-9; TBN = 100) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994f; Table S6). A panel of 53 subjects was identified for this test. In the induction phase 0.2g of 10% concentration of the test substance in mineral oil was administered directly to the skin (2 cm x 2 cm gauze portion, 5000 µg/cm² was derived) and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 51 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 0/51 (0.0%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to not cause a sensitisation response. 

 

Table S6. Calcium Sulfonate Human Repeat Insult Patch Tests (HRIPT) with a 10% Induction Phase Concentration

Substance	Challenge %	Challenge Response	Sensitization Response (%)	Conclusion	Reference
EC 616-278-7 (TBN = 10)	10%	2/154 with mild to moderate erythema with moderate papular reactions; 2/154 with mild to marked erythema and with moderate oedema and moderate papular reactions in the induction phase that were considered sensitised and, therefore were not challenged	4/154 (2.6%)	Sensitizer (subcategory 1B)	Alworth, Schwartz & Erianne, 1995a
EC 616-278-7CAS 75975-85-8;(TBN = 85)	10%	2/48 with mild to moderate erythema 1/48 with moderate oedema and papular that spread beyond contact site during induction were not challenged	3/48 (6.3%)	Sensitizer (subcategory 1B)	Shanahan & Erianne, 1994a
EC 616-278-7 (TBN = 10)	10%	6/199 with mild erythema @ original sites; 5/199 with moderate erythema original site; 1/199 with moderate erythema virgin site	12/199 (6.0%)	Sensitizer (subcategory 1B)	Eisenberg, 1994a
EC 939-141-6 (TBN = 10)	10%	1/210 with mild erythema original and virgin site; 6/210 with BP to mild erythema original site; 5/210 moderate erythema original site; 1/210 with marked erythema original site; 1/210 with mild erythema virgin site; 1/210 with marked erythema original site	15/210 (7.1%)	Sensitizer (subcategory 1B)	Eisenberg, 1994b
EC 939-141-6 (TBN = 10)	10%	3/140 with mild to moderate erythema with mild to moderate oedema and/or mild to severe papular reactions in some; 1/140 with moderate erythema with mild to severe papular reaction including an adverse reaction report of reaction spreading to back/neck @ 96 hrs with erythema deminishing @ 192 hours but papular reaction spreading to the eyes	4/140 (2.9%)	Sensitizer (subcategory 1B)	Alworth, Schwartz & Erianne, 1995b
EC 263-093-9 (TBN = 30)	10%	7/142 with mild to moderate erythema/oedema including mild to moderate papular reactions; 1/142 with moderate erythema @ 24 hours and severe erythema @ 72 hours	8/142 (5.6%)	Sensitizer (subcategory 1B)	Alworth, Schwartz & Erianne, 1995c
EC 263-093-9 (TBN = 30)	10%	3/205 with mild erythema @ original & virgin sites; 1/205 with moderate erythema @ both areas; 7/205 with mild erythema original site; 1/205 with mild erythema virgin site	12/205 (5.8%)	Sensitizer (subcategory 1B)	Eisenberg, 1994c
CAS 61789-86-4; EC 263-093-9 (TBN = 82)	10%	56/56 no reaction	0/56 (0%)	Not a sensitizer	Shanahan & Erianne, 1994e
CAS 61789-86-4; EC 263-093-9 (TBN = 100)	10%	51/51 no reaction	0/51 (0%)	Not a sensitizer	Shanahan & Erianne, 1994f
CAS 61789-86-4; EC 263-093-9 = Sulfonic acids, petroleum, calcium salts CAS 75975-85-8; EC 616-278-7 = Benzene, polypropene derivs., sulfonated, calcium salts EC 939-141-6 =Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts

12.In another key study, the dermal sensitisation of an analogue of this substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts; , EC 939-141-6; TBN = 10) was evaluated in a human repeat insult patch test (DiFiglia, Shanahan & Erianne, 1993b). A panel of 53 subjects was identified for this test. In the induction phase a 1% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 48 subjects that completed the induction phase was topically challenged with 0.2 ml of 1% concentration of the test substance in mineral oil. A total of 0/48 (0%) of the subjects exhibited sensitisation responses following the 1% challenge. Based on these results the test substance was determined not to induce irritation or sensitisation at 1%.

In accordance with EU CLP Regulation (EC) No 1272/2008, classification of low TBN calcium sulfonates is required for sensitisation (subcategory 1B) with a specific concentration limit of 10%. This also applies to low TBN barium sulfonates.

Conclusion

The weight-of-evidence indicates that low TBN calcium and barium sulfonates (TBN < 300) are skin sensitizers with a specific concentration limit (SCL) of 10%. Studies in guinea pigs and human volunteers show that low TBN Benzenesulfonic acid, 4-(mono-C15 -36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts (EC 939-141-6; TBN = 13) are skin sensitizers. Numerous well-conducted, reliable, controlled human (HRIPT) studies with benzene, polypropene derivs., sulfonated, calcium salts (EC 616-278-7; TBN values ranging from 13 to 85), sulfonic acids, petroleum, calcium salts (CAS 61789-86-4; EC 263-093-9; TBN = 30 to 100), and Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and Benzenesulfonic acid, 4-octadecyl, calcium salts (EC 939-141-6; TBN = 13) show that low TBN calcium sulfonates do not cause sensitisation in a substantial number of subjects at concentrations of 10% and lower.

In accordance with EU CLP Regulation (EC) No 1272/2008, classification (subcategory 1B) is required for low TBN calcium and barium sulfonates (TBN < 300) with a specific concentration limit of 10%.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The classification and labelling for Benzene, mono-C10-13-alkyl derivs., distn. residues, sulfonated, barium salts (generic name: C10 -13 barium sulfonate) is based on the results of numerous skin sensitisation animal studies with low and high TBN calcium sulfonates. Results of Human Repeat Insult Test (HRIPT) with low and high TBN calcium sulfonates have also been taken into account (please also refer to the respective section of the CSR).

In accordance with Regulation (EC) No 1272/2008 (CLP Regulation), classification (subcategory 1B) is required for low TBN calcium and barium sulfonates (TBN < 300) with a specific concentration limit of 10%.