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Description of key information

They key studies for dermal irritation are based on the read across substance Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with 1-aminopropane-2-ol. To determine the potential skin effects of Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine, the substance was tested in two in vitro studies with the use of reconstructed human epidermis models (EPISKINTM). The principle of the assays is based on the measurement of cytotoxicity in the human epidermal cultures following topical exposure to the test material, with the MTT reduction assay. Both test gave negative results, suggesting that the substance has no skin corrosive or irritating properties.

A key study for eye irritation (Liggett and Parcell 1986A) examined the potential of the read across substance (Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts) to cause irritation to eyes. Groups of three rabbits had 0.1 ml of test substance placed in each of their eyes. In one group, the eyes were not rinsed. In the second group, the eyes were rinsed after 4 seconds of exposure. In the third group, the eyes were rinsed after 30 seconds of exposure. Observations were made one hour and 1, 2, 3, 4, 7, 14, and 21 days after exposure. Severe irritation was noted in the animals whose eyes were not rinsed. This irritation was not resolved in one of these animals at the end of 21 days. Irritation was also seen in the animals rinsed after 30 seconds, although the irritation was not as severe, and the effects were fully reversible within 14 days. Mild irritation was seen in the animals rinsed after 4 seconds. These effects were fully reversible within 7 days. Since OECD guideline 405 for eye irritation studies calls for an exposure of at least 24 hrs, the results for unrinsed eyes were used for classification. According to these results, the test substance is a Category 1 eye irritant because it caused damage that was not reversible within 21 days (H318: Causes serious eye damage).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: not applicable
Details on test animals or test system and environmental conditions:
Three-dimensional reconstructed human epidermis- EPISKIN model kit purchased from SkinEthic Laboratories (Nice, France).
Type of coverage:
other: not applicable
Controls:
other: not applicable
Amount / concentration applied:
not applicable
Duration of treatment / exposure:
3, 60 and 240 min
Details on study design:
Pre-test: Test MTT reduction by the test material: 50 ul test material + 2.2 ml 0.3 mg/ml MTT solution incubated for 3 h. The blue colour indicates reduced MTT.
MAIN TEST
DAY 1-Application of test item
Exposure: 3, 60 and 240 min
Amount applied: 50 ul
Negative control: 50 ul of 0.9% w/v sodium chloride
Positive control: 50 ul glacial acetic acid
Washing: PBS with Ca++ and Mg++
MTT solution was applied: 2.2 ml of 0.3 mg/ml per well, incubation followed for 3 h ± 5 min
Biopsy of the epidermis was performed. The tissue was then transfered in micro tubes with 850 ul acidified isopropanol.

DAY 2-Absorbance/Optical Density
at 540 nm with Anthos 2001 microplate reader
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
240 minutes
Value:
66.5
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
60 minutes
Value:
83.8
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3 minnutes
Value:
87.9

Table 1: Mean OD540 Values and Viabilities for the Negative Control Item, Positive Control Item and Test Item

Item

Exposure Period

Mean OD540 of

duplicate tissues

Relative mean

viability (%)

Negative Control Item

240 min

0.173

100

Positive Control Item

240 min

0.033

19.1

Test Item

240 min

0.115

66.5

60 min

0.145

83.8

3 min

0.152

87.9

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this in vitro test MARLON AMI 80, and hence benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1), are not corosive to the skin.
Executive summary:

The skin corrosion potential of MARLON AMI 80 (78% benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1) in  1,2-propylene glycol) was examined in this in vitro test with the EPISKINTMreconstructed human epidermis model. Exposure to the substance lasted 3, 60, and 240 minutes.The principle of the assay was based on the measurement of cytotoxicity in the human epidermal cultures following topical exposure to the test item, with the MTT reduction assay.

 

The relative mean viability of the test item treated tissues was 66.5, 83.8 and 87.9%, after the exposure periods of 240 60, and 3 minutes, respectively. Therefore, MARLON AMI 80 is not corrosive to the skin. Based on this result, benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1) shall not be considered as skin corrosive.

The study is considered acceptable based on the quality criteria. The test was performed according to the OECD Guidelines for the Testing of Chemicals No. 431 “In VitroSkin Corrosion” (adopted April 2004).

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: not applicable
Details on test animals or test system and environmental conditions:
Three-dimensional reconstructed human epidermis- EPISKIN model kit purchased from SkinEthic Laboratories (Lyon, France).
Type of coverage:
other: not applicable
Controls:
other: not applicable
Amount / concentration applied:
not applicable
Duration of treatment / exposure:
15 min
Details on study design:
Test MTT reduction by the test material: 10 ul test material + 2 ml 0.3 mg/ml MTT solution incubated for 3 h. The blue colour indicates reduced MTT.

MAIN TEST
DAY 1-Application of test item
Exposure: 15 min
Amount applied: 10 ul
Negative control: 10 ul DPBS
Positive control: 10 ul 5% w/v SDS
Washing: DPBS with Ca++ and Mg++
Post-exposure incubation: 42 h

DAY 3-MTT Loading/Formazan Extraction
Plate shaker: 15 min
MTT solution: 2 ml of 0.3 mg/ml per well
Incubation: 3 h
Biopsy of the epidermis was performed. The tissue was then transfered in micro tubes with 500 ul acidified isopropanol and refrigerated till day 6.

DAY 6-Absorbance/Optical Density
at 540 nm with Anthos 2001 microplate reader


Irritation / corrosion parameter:
% tissue viability
Value:
60

Table 1: Mean OD540Values and Percentage Viabilities for the Negative Control Item, Positive Control Item and Test Item

Item

OD540 of

tissues

Mean OD540

of triplicate

tissues

± SD of

OD540

Relative

individual

tissue

viability (%)

Relative

mean

viability (%)

± SD of

Relative

mean

viability (%)

Negative

Control Item

0.811

0.821

0.012

98.8

100

1.5

0.835

101.7

0.817

99.5

Positive

Control Item

0.084

0.105

0.027

10.2

12.8

3.4

0.136

16.6

0.095

11.6

Test Item

0.530

0.497

0.062

64.6

60.6

7.5

0.535

65.2

0.426

51.9

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this in vitro test MARLON AMI 80, and hence, benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1) are not skin irritants.
Executive summary:

The skin irritation potential of MARLON AMI 80 (78% benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1) in  1,2-propylene glycol) was examined in this in vitro test withthe EPISKINTMreconstructed human epidermis model. Exposure to the substance lasted 15 minutes and it was followed by a post-exposure incubation period of 42 hours. The principle of the assay was based on the measurement of cytotoxicity in the human epidermal cultures following topical exposure to the test item, with the MTT reduction assay.

 

The relative mean viability of the test item treated tissues was 60.6% after the15-Minute exposure period and hence, MARLON AMI 80 is not a skin irritant. Based on this result, benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1) shall not be considered a skin irritant.

 

The study is considered acceptable based on the quality criteria. The test was performed according to the OECD Guidelines for the Testing of Chemicals No. 439 “In Vitro Skin Irritation” (adopted 22 July 2010).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

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:
March 24, 1986-May 12, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield Rabbits and Buckmasters
- Age at study initiation: 9-13 weeks
- Weight at study initiation: 2.1-3.1 kg
- Housing: individually housed in metal cages, identified by aluminum ear tags
- Diet (e.g. ad libitum): SDS Standard Rabbit Diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation: yes


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 degree C
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark


IN-LIFE DATES: From: March 24, 1986 To: May 12, 1986
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1 mL aliquot of P-500 N-Na
Duration of treatment / exposure:
For three rabbits the eyelids were then gently held together for one second before releasing.
For three other rabbits the eyes were irrigated with water for 5 minutes following a 4-second exposure.
For the remaining three rabbits the eyes were irrigated for 5 minutes following a 30-second exposure.
Observation period (in vivo):
Eyes were examined after 1 hour and 1, 2, 3, 4, 7, 14 and 21 days after exposure.
Number of animals or in vitro replicates:
9
Details on study design:

SCORING SYSTEM: Draize scale
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
1.75
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: not rinsed
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: rinse after 4 seconds
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
1.06
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: rinsed after 30 seconds
Irritant / corrosive response data:
The following results were noted:
1) Three animals without any rinsing:  averaged irritation scores (24, 48, 72 hours) for each animal: cornea 2.3, 1.7, 2; iris: 1.3, 0, 0; conjunctivae redness: 3, 1.7, 2; conjunctivae chemosis: 3, 2, 2.  In the first animal the effects were persistent at day 21.
2) Three animals with rinsing for five minutes following a 30 second exposure: averaged scores: cornea 0.7, 1, 1.3; iris: 0, 0.7, 0.3; conjunctivae redness: 1.7, 2, 1.3; conjunctivae chemosis: 2, 1.3, 2.  The eyes were normal 7 or 14 days after instillation.
3) Three animals with rinsing for five minutes following a 4 second exposure: averaged scores: cornea 0.7, 2.3, 0.7; iris: 0, 0, 0; conjunctivae redness: 1.7, 1.7, 1; conjunctivae chemosis: 1.3, 2, 1.  The eyes were normal 7 days after instillation.

Findings lead to a definition of irritating for LAS at 47% applied without rinsing, irritating (even if with lower effects, mainly as cornea opacity and conjunctivae redness) with rinsing after 30 second of exposure, and not irritating with rinsing after 4 second of exposure.

Results of Eye Irritation Study: No Rinsing

Hours

Days

Animal

1

24

48

72

4

7

14

21

1

Cornea

2

1

2

4

3B

3B

3BC

3BC

Iris

0

1

1

2

1

1

1

0

Conjunctiva - Erythema

1

3

3

3

3

3

2

1

Conjunctiva - Chemosis

2

3

3

3

3

2

2

1

2

Cornea

1

1

2

2

2

1

0

Iris

0

0

0

0

0

0

0

Conjunctiva - Erythema

1

1

2

2

1

0

0

Conjunctiva - Chemosis

1

2

2

2

1

0

0

3

Cornea

1

2

2

2

2

1

0

Iris

0

0

0

0

1

0

0

Conjunctiva - Erythema

1

2

2

2

2

1

0

Conjunctiva - Chemosis

1

2

2

2

2

0

0

Results of Eye Irritation Study: Rinsing after 4 Seconds

Hours

Days

Animal

1

24

48

72

4

7

1

Cornea

0

0

1

1

1

0

Iris

0

0

0

0

1

0

Conjunctiva - Erythema

1

2

2

1

2

0

Conjunctiva - Chemosis

2

2

1

1

1

0

2

Cornea

0

2

3

2

0

0

Iris

0

0

0

0

0

0

Conjunctiva - Erythema

1

2

2

1

2

0

Conjunctiva - Chemosis

2

2

2

1

1

0

3

Cornea

0

1

0

1

1

0

Iris

0

0

0

0

0

0

Conjunctiva - Erythema

1

1

1

1

2

0

Conjunctiva - Chemosis

2

1

1

1

1

0

Results of Eye Irritation Study: Rinsing after 30 Seconds

Hours

Days

Animal

1

24

48

72

4

7

14

1

Cornea

0

1

0

D

D

1

0

Iris

0

0

0

0

0

0

0

Conjunctiva - Erythema

1

2

2

1

1

1

0

Conjunctiva - Chemosis

2

1

1

0

0

0

0

2

Cornea

0

1

1

1

2

0

Iris

0

0

1

1

0

0

Conjunctiva - Erythema

1

2

2

2

2

0

Conjunctiva - Chemosis

2

1

2

1

1

0

3

Cornea

0

1

2

1

2A

2AB

0

Iris

0

0

0

1

1

1

0

Conjunctiva - Erythema

1

1

1

2

2

2

0

Conjunctiva - Chemosis

2

2

2

2

1

1

0

A - Loss of Corneal Epithelium

B - Vascularization

C - Pannus

D - Dulling of the Cornea

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
When not rinsed, damage to the eyes due to the test substance was not reversed within 21 days. According to EU GHS guidelines the test substance is a category 1 eye irritant.
Executive summary:

This study examined the potential of the test substance to cause irritation to eyes. Groups of three rabbits had 0.1 ml of test substance placed in each of their eyes. In one group, the eyes were not rinsed. In the second group, the eyes were rinsed after 4 seconds of exposure. In the third group, the eyes were rinsed after 30 seconds of exposure. Observations were made one hour and 1, 2, 3, 4, 7, 14, and 21 days after exposure. Severe irritation was noted in the animals whose eyes were not rinsed. This irritation was not resolved in one of these animals at the end of 21 days. Irritation was also seen in the animals rinsed after 30 seconds, although the irritation was not as severe, and the effects were fully reversible within 14 days. Mild irritation was seen in the animals rinsed after 4 seconds. These effects were fully reversible within 7 days. Since OECD guideline 405 for eye irritation studies calls for an exposure of at least 24 hrs, the results for unrinsed eyes were used for classification. According to these results, the test substance is a category 1 eye irritant because it caused damage that was not reversible within 21 days.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Additional information

Skin Irritation

Two in vitro tests were performed in order to assess the skin corrosive/irritating potential of LAS MIPA. Both studies gave a negative result, and hence the substance is not irritating to the skin.

In a supporting key study for dermal irritation (Liggett and Parcell 1986) examined the potential for the read across substance (Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts) to cause dermal irritation. Three rabbits were exposed to 0.5 ml of the test substance dermally for 4 hrs on clipped skin under a gauze pad held in place by an adhesive dressing. Examination of the treated skin was made approximately 30 minutes after removal of the patch and daily through 14 days. Grading and scoring of the dermal reactions was performed using the standard numerical scoring system. Irritation was noted in all animals at the first observation (maximum score of 2). Symptoms worsened, and desquamation, necrosis, and hyperkeratinization was noted by day 4. Symptoms resolved in one animal by day 12, but in the other two animals, symptoms were seen through the end of the observation period. The primary dermal irritation index was 2.17. The test substance is considered a Category 2 irritant according to CLP Regulation based on persistent irritation (H315: Causes skin irritation).

In an additional supporting study, MIPA was considered corrosive to skin. This data point is not considered relevant for the classification of the registered substance and it supported by in vitro data on Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with 1-aminopropane-2-ol.

Eye Irritation

In eyes, administration of Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts resulted in severe irritation in the animals whose eyes were not rinsed and the effect was not resolved by day 21. Milder irritation was observed in animals that had the test substance rinsed from their eye after 4 or 30 seconds, and effects seen in these rinsed animals were reversible within 7 or 14 days. Based on the irreversible irritation observed in the unrinsed animals, Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts is considered a Category 1 eye irritant.

In a supporting study, MIPA was also considered corrosive to eyes.

In a final supporting study, Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with 1-aminopropane-2-ol was tested an in vitro eye irritation test performed with the use of the SkinEthic Human Corneal Epithelium model. In that study the substance was considered an irritant. However, since the test is not so far officially accepted for regulatory purposes, it is proposed that the test material is classified as damaging to the eye similar to Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts.

Justification for classification or non-classification

No classification for skin irritation is based on 2 in vitro dermal studies on Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with 1-aminopropane-2-ol, while a Category 1 Eye Irritant classification is based on results from an in vivo study on Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts.