Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.

Endpoint summary

Description of key information

The potential for dermal irritation was examined in a study on the test substance. The shaved backs of three male and three female rabbits were exposed for 4 hours to 0.5 ml of the LAB Sulfonic Acid and observed for up to 14 days. Significant reddening was observed throughout at least day 9. Swelling was perceptible throughout and appeared to become more noticeable with time. Bloody wounds and scar formation were observed through at least observation day 9. The test substance is considered highly irritating to the skin of rabbits. The primary dermal irritation index was 5.25 (mean of 1, 24, 48 and 72 hours). In another study, the test article was applied at a dose of 0.5 mL to three skin sites on a clipped area of each of six albino rabbits. The three sites were designated for application of test article as follows; Site A - three minute occluded contact, Site B - one hour occluded contact, and Site C - four hour occluded contact. Three minute occluded contact produced minimal irritation, and necrosis was not observed in any of the six test subjects. The test article is not corrosive following a three minute contact period. One hour occluded contact produced severe irritation, and necrosis was observed in five of the six test subjects. The test article is corrosive following a one hour contact period. Based on this information, the test substance is considered a Category 1B irritant/corrosive according to CLP guidelines based on persistent irritation (H314: Causes severe skin burns and eye damage).

The potential for irritation to eyes was examined in a study on the test substance. The eyes of six rabbits were treated with LAB Sulfonic Acid and observed for six days. Treatment was to the right eye with lower lid removed. The left eye was untreated and served as the control. The eyes were not washed out during the test. Observations were made at 1, 24, 48, and 72 hours and at 6 days after application. Results indicate that the substance was moderately irritating but because of the intensity of the necrosis formation the study was stopped at day 6. According to these results, the test substance is a category 1 eye irritant according to CLP because it caused damage that was not reversible within the 6 days of the study (H318: Causes serious eye damage).

LAB Sulfonic Acid is corrosive to the skin and eyes at a 100% undiluted, unrinsed dose and is classified under the CLP as category 1B for skin, and category 1 for eye.

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:

experimental study

Adequacy of study:

supporting study

Study period:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Laboratory study in experienced testing laboratory.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Male and female white New Zealand rabbits weight between 4 and 5.6 kg each. Animals were marked with a 5 digit number and held in steel cages. They were acclimated for 14 days prior to testing. Standard rabbit diet and water was provided ad libitum. Room temperature was held at 20 degrees C +/- 1 degree C, humidity at 60 +/- 5%, with a 12/12 hour light/dark cycle.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

Observations were made after 1, 24, 48, 72 hours and 6, 9, and 14 days.

Number of animals:

6 (3 male, 3 female)

Details on study design:

The shaved treated area (about 6 m2) was covered with gauze and covered by polyethylene film for the first 4 hours, at which time the test area was rinsed with warm water. Observations were made after 1, 24, 48, 72 hours and 6, 9, and 14 days.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: Mean of 1, 24, 48 and 72 hours.

Score:

5.25

Max. score:

6

Reversibility:

not reversible

Remarks on result:

other: highly irritating

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24, 48, 72 hr readings

Score:

5.33

Max. score:

8

Reversibility:

not fully reversible within: 14 days

Other effects:

Significant reddening effects were observed at all times and were persistent. Bloody wounds and scar formation were observed through at least observation day 9.

Results of Skin Irritation Study in Rabbits

Observation	Endpoint	Male 11499	Male 11887	Male 11901	Female 11580	Female 11658	Female 11802
1 hr	Erythema	4 X	4 X	4 X	4 X	4 X	4 X
1 hr	Edema	1	1	1	1	1	1
24 hrs	Erythema	4 X	4 X	4 X	4 X	4 X	4 X
24 hrs	Edema	1	1	1	1	1	1
48 hrs	Erythema	4 X	4 X	4 X	4 X *	4 X	4 X *
48 hrs	Edema	1	1	1	1	1	1
72 hrs	Erythema	4 *	4 *	4 X *	4 X *	4 *	4 *
72 hrs	Edema	2	2	2	2	2	2
6 days	Erythema	4 +	4 *	4 *	4 * -	4 +	4 + -
6 days	Edema	2	2	2	2	2	2
9 days	Erythema	W	W	W	+	W	+
9 days	Edema	C N	C N	N		N	W
14 days	Erythema	N	N	N	N	N	N
14 days	Edema	N	N	N	N	N	N

X ¿ Necrosis in application area bordered by swelling

* - Application area hardened

+ - Wavy crust

- - Application area paper-like

W ¿ Bloody wounds

C - Crust formation

N ¿ Scar formation

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

Result: Highly irritating

Executive summary:

The shaved backs of three male and three female rabbits were exposed for 4 hours to 0.5 ml of the test substance and observed for up to 14 days. Significant reddening was observed throughout at least day 9. Swelling was perceptible throughout and appeared to become more noticeable with time. Bloody wounds and scar formation were observed through at least observation day 9. The test substance is considered highly irritating to the skin of rabbits. The test substance is considered corrosive to skin according to OECD GHS guidelines.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Qualifier:

equivalent or similar to guideline

Guideline:

other: Department of Transportation, Method of Testing Corrosion to Skin. Federal Register, Vol. 41, No. 118, Sept. 27, 1976, p.42572.

Qualifier:

equivalent or similar to guideline

Guideline:

other: 49 Code of Federal Regulations, part 173, Appendix A, Dec. 31, 1991, pp. 594, 595, and 471. Part 171, Dec. 19, 1994.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kuiper Rabbitry, Gary, Indiana
- Age at study initiation: 8 to 10 weeks
- Housing: The rabbits were individually housed in stainless steel cages in a temperature, humidity, and light controlled room. The rabbits were maintained according to the recommendations contained in the National Academy Press 1996: "Guide for the Care and Use of Laboratory Animals".
- Diet: Purina Rabbit Chow, ad libitum
- Acclimation period: At least three days

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL test article

Duration of treatment / exposure:

For 3 minutes (site A), 1 hour (site B) and 4 hours (site C)

Observation period:

Up to 14 days

Number of animals:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Performed by wiping .
- Time after start of exposure: At the conclusion of the contact periods.

OBSERVATION TIME POINTS
Observations for irritation, ulceration and necrosis were performed and findings recorded at the end of each contact period, again at 60 minutes for the 3 minute contact and also at 24, 48, and 72 hours following test article application for the 1 and 4 hour contacts. Additional readings were continued up to 14 days to confirm Packing Group.

SCORING SYSTEM:
- Method of calculation: Corrosion is considered to have resulted if the substances in contact with the rabbit skin, produced full thickness destruction or irreversible alteration of the tissue. Tissue destruction is considered to have occurred if. at any of the readings there is ulceration and/or necrosis. Tissue destruction would not include merely sloughing of the epidermis, erythema, oedema or fissuring. Scoring was performed according to the scoring schemes presented in Tables 1 to 3 in the "Any other information on materials and methods incl. tables" field.

Irritation parameter:

erythema score

Remarks:

Site A - 3 minutes of exposure

Basis:

mean

Remarks:

Animal #1 to #6

Time point:

other: 1 hour

Score:

0.5

Max. score:

4

Remarks on result:

other:

Remarks:

No necropsy observed

Irritation parameter:

erythema score

Remarks:

Site B - 1 hour of exposure

Basis:

mean

Remarks:

Animal #1 to #6

Time point:

72 h

Score:

4

Max. score:

4

Remarks on result:

other:

Remarks:

Necropsy observed in 5 out of 6 animals.

Irritation parameter:

erythema score

Remarks:

Site C - 4 hours of exposure

Basis:

mean

Remarks:

Animal #1 to #6

Time point:

72 h

Score:

4

Max. score:

4

Remarks on result:

other:

Remarks:

Necropsy observed in all animals.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Other time points were assessed for classification purposes for corrosive chemicals.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Other time points were assessed for classification purposes for corrosive chemicals.

Irritant / corrosive response data:

Three minute occluded contact produced minimal irritation, and necrosis was not observed in any of the six test subjects. The test material is not corrosive following a three minute contact period. One hour occluded contact produced severe irritation, and necrosis was observed in five of the six test subjects. The test material is corrosive following a one hour contact period.

Table 1. Site A, Erythema scores- Contact time: 3 minutes

ANIMAL NUMBER	3 Minutes	1 Hour
1	0	1
2	0	1
3	0	0
4	0	0
5	0	1
6	0	0

Table 2. Site B, Erythema scores- Contact time: 1 hour

ANIMAL NUMBER	1 Hour	Day 1	Day 2	Day 3
1	2	3	4	N
2	2	3	4	N
3	2	4	4	N
4	2	4	4	N
5	1	3	4	N
6	2	3	4	4

Table 3. Site C, Erythema scores - Contact time: 4 hours

ANIMAL NUMBER	4 Hours	Day 1	Day 2	Day 3
1	4	4	4	N
2	4	4	N	N
3	4	4	N	N
4	4	4	N	N
5	N	N	N	N
6	4	N	N	N

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

In accordance with D.O.T. Guidelines, Federal Register, Volume 55, No. 246, the test substance is a corrosive agent and would be classified as packing group II.

Executive summary:

The test article was tested for corrosivity in accordance with Department of Transportation Guidelines. The test article was applied at a dose of 0.5 mL to three skin sites on a clipped area of each of six albino rabbits. The three sites were designated for application of test article as follows; Site A - three minute occluded contact, Site B - one hour occluded contact, and Site C - four hour occluded contact.

Three minute occluded contact produced minimal irritation, and necrosis was not observed in any of the six test subjects. The test article is not corrosive following a three minute contact period. One hour occluded contact produced severe irritation, and necrosis was observed in five of the six test subjects. The test article is corrosive following a one hour contact period.

In accordance with D.O.T. Guidelines, Federal Register, Volume 55, No. 246, the sample is a corrosive agent and would be classified as packing group II.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Laboratory study in experienced laboratory.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Male and female white New Zealand rabbits weight between 3.7 and 6.0 kg each. Animals were marked with a 5 digit number and held in steel cages. They were acclimated for 14 days prior to testing. Standard rabbit diet and water was provided ad libitum. Room temperature was held at 20 degrees C +/- 1 degree C, humidity at 60 +/- 5%, with a 12/12 hour light/dark cycle.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

Single treatment that was not washed out.

Observation period (in vivo):

1, 24, 48, and 72 hours and at 6 days after application.

Number of animals or in vitro replicates:

6 (3 male, 3 female)

Details on study design:

Treatment was to the right eye with lower lid removed. The left eye was untreated and served as the control. The eyes were not washed out during the test. Observations were made at 1, 24, 48, and 72 hours and at 6 days after application.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48, and 72 hrs and 6 days

Score:

46.9

Reversibility:

not fully reversible within: 6 days

Remarks on result:

other: moderately irritating

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 6 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 6 days

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 6 days

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 6 days

Irritation parameter:

iris score

Basis:

animal: #1 to #6

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 6 days

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: #1 to #6

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 6 days

Irritation parameter:

chemosis score

Basis:

animal: #1 and #5

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 6 days

Irritation parameter:

chemosis score

Basis:

animal: #2, #3, #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 6 days

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 6 days

Irritant / corrosive response data:

Results indicated a moderate irritancy, but because of the intensity of the necrosis formation, the study was stopped at day 6.

Results of Eye Irritation Study in Rabbits

Observation	Endpoint	Male 11655	Male 11715	Male 11771	Female 11798	Female 11804	Female 11838
1 hr	Cornea ¿ degree	1	1	2	2	2	1
1 hr	Cornea ¿ range	4	4	4	4	4	4
1 hr	Iris	1X	1X	1X	1X	1X	1X
1 hr	Conjunctiva ¿ redness	3N	3N	3N	2N	3N	3N
1 hr	Conjunctiva ¿ edema	1	1	1	1	2	2
1 hr	Conjunctiva - exsudation	3	3	3	3	3	3
24 hrs	Cornea -degree	1	1	2	2	3C	1
24 hrs	Cornea ¿ range	4	4	4	4	2	4
24 hrs	Iris	1*	1*	1*	1*	1*-	1*
24 hrs	Conjunctiva ¿ redness	3N	3N	3N	3N	3N S	3N
24 hrs	Conjunctiva ¿ edema	2	2	2	2	2	3
24 hrs	Conjunctiva - exsudation	2	2	2	2	2	2
48 hrs	Cornea ¿ degree	1	1	2	2	3C	1
48 hrs	Cornea - range	4	4	4	4	2	4
48 hrs	Iris	1*	1*	1*	1*	1*-	1*
48 hrs	Conjunctiva ¿ redness	3N S	3N	3N S	3N S	3N S	3N S
48 hrs	Conjunctiva ¿ edema	2	1	1	1	2	3
48 hrs	Conjunctiva - exsudation	2	2	2	2	2	2
72 hrs	Cornea ¿ degree	1	1	1	2	4C	1
72 hrs	Cornea - range	4	2	4	4	2	4
72 hrs	Iris	1X	1X	1*	1*	1*-	1*
72 hrs	Conjunctiva - redness	3N S	3N S	3N S	3N S	3N S	3N S
72 hrs	Conjunctiva ¿ edema	2	2	2	2	2	2
72 hrs	Conjunctiva - exsudation	2	2	2	2	2	2
6 days	Cornea ¿ degree	2	2	2	2	4C	2
6 days	Cornea -range	3	3	2	3	2	4
6 days	Iris	1X	1X	1*	1*	1*-	1*
6 days	Conjunctiva - redness	3N S L	3N L	3N L H	3N S L	3N S L	3N S L
6 days	Conjunctiva ¿ edema	2	2	2	2	2	2
6 days	Conjunctiva - exsudation	2	1	2	2	2	2

C ¿ Cornea cloudy

X ¿ Parts of the iris turned red

* - Iris turned red

- - Retarded iris reaction

N ¿ Necrosis and corrosion of the conjunctiva

S ¿ Secretion formation

L ¿ Lids became encrusted

H ¿ Holding head inclined

Interpretation of results:

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

Conclusions:

Result: moderately irritating

Executive summary:

The eyes of six rabbits were treated with the test substance and observed for six days. Results indicate that the substance was moderately irritating but because of the intensity of the necrosis formation the study was stopped at day 6.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

LAB Sulfonic Acid was tested and found to be irritating to both the skin and eyes of test animals. In skin, One hour occluded contact produced severe irritation, and necrosis was observed in five of the six test subjects. The test article is corrosive following a one hour contact period. The test substance is considered highly corrosive to the skin of rabbits. In eyes, LAB Sulfonic Acid was moderately irritating but because of the intensity of the necrosis formation the study was stopped at day 6. According to these results, the test substance is classified as CLP category 1B for skin irritation (H314: Causes severe skin burns and eye damage) and CLP category 1 for eye irritation (H318: Causes serious eye damage).

Justification for selection of skin irritation / corrosion endpoint:
Key studies are reliable without restriction, report in vivo experimental results from 2 studies.

Justification for selection of eye irritation endpoint:
Key study is reliable without restriction, reports in vivo experimental results.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Undiluted LAB Sulfonic Acid was tested and found to be corrosive to both the skin and eyes of test animals.