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Administrative data

Description of key information

An in vivo skin irritation test was performed with an aqueous formulation with 20-37% Registered substance on intact and abraded skin. In this study, no irritation or corrosion was observed. It is of note that the test substance was tested in formulation, thus the data can only be used as supplementary information. Additionally, the absence of skin effects in an acute dermal study and in a human patch study were considered in a weight of evidence approach to fill this endpoint.
In a bovine corneal opacity and permeability (BCOP) test, performed according to OECD guideline and GLP principles, disodium isodecyl sulfosuccinate induced a mean IVIS of 38.1. An IVIS > 3 and ≤ 55 does not allow conclusion on classification for eye irritancy according to UN GHS. Furthermore, an in vivo eye irritancy test is available, in which an aqueous formulation with 20-37% disodium isodecyl sulfosuccinate was tested. The formulation was found not to be irritating to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1971
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Limited report with only basic information on test substance purity.
Qualifier:
according to
Guideline:
other: Federal Hazardous Substances Act (FHSA) procedures
Principles of method if other than guideline:
Six instead of three animals were tested.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Controls:
not specified
Amount / concentration applied:
0.5mL
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
SCORING SYSTEM: Draize et al, J. Pharmacol. exptl. therap., 82:377, 1944
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
24 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: effect on intact skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no erythema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no erythema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no erythema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24/72 h mean
Score:
0
Max. score:
4
Reversibility:
other: no erythema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24/72 h mean
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24/72 h mean
Score:
0
Max. score:
4
Reversibility:
other: no erythema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: effect on intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no edema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no edema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no edema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no edema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no edema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no edema observed at 24 and 72 h
Remarks on result:
other: effect on intact skin
Remarks:
No observation reported at 48 h
Irritant / corrosive response data:
The structure of the tissue at the site of contact was not destroyed or changed irreversibly.
Other effects:
No edema was noted on abraded skin. the erythema score (mean of 6 animals ) was 1 after 24 hours (3 rabbits with score 2) and 0.17 after 72 hours (1 animal with score 1).
Conclusions:
In an in vivo skin irritation test performed with 0.5mL of an aqueous formulation with appr. 50% disodium isodecyl sulfosuccinate on intact and abraded skin, no irritation or corrosion was observed.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
03 Oct 2005 - 11 Oct 2005
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Test substance was applied as received (aqueous formulation with appr. 20% test substance). The study can be used as supportive evidence: no corrosive or irritating effects were seen. As the test substance was tested in formulation, the test is not considered sufficient to cover this endpoint.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Clipped skin of three rabbits was exposed to 0.5 mL formulated test substance semi-occlusively for 4 hours. Skin effects were observed at 1, 24 and 72 hours postdose.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA, USA
- Age at study initiation: appr. 2 months
- Weight at study initiation:3.2-3.4 kg
- Housing: individual, in suspended cages
- Diet: PMI rabbit chow, daily portions
- Water: ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature-controlled rooms
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03 Oct 2005 To: 11 Oct 2005
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped (intact and abraded skin)
Vehicle:
other: aqueous formulation
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5*2.5 cm (left side)
- Type of wrap if used: surgical gauze, secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 hours

SCORING according to Draize et al (1944)
Irritation parameter:
erythema score
Remarks:
(and eschar formation)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Remarks:
(and eschar formation)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Remarks:
(and eschar formation)
Basis:
animal #1
Remarks:
intact skin / abraded skin
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: The dermal effects on the abraded skin were identical to the effects on intact skin.
Irritation parameter:
erythema score
Remarks:
(and eschar formation)
Basis:
animal #2
Remarks:
intact skin / abraded skin
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: The dermal effects on the abraded skin were identical to the effects on intact skin.
Irritation parameter:
erythema score
Remarks:
(and eschar formation)
Basis:
animal #3
Remarks:
intact skin / abraded skin
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: The dermal effects on the abraded skin were identical to the effects on intact skin.
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
intact skin / abraded skin
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: The dermal effects on the abraded skin were identical to the effects on intact skin.
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
intact skin / abraded skin
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: The dermal effects on the abraded skin were identical to the effects on intact skin.
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
intact skin / abraded skin
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: The dermal effects on the abraded skin were identical to the effects on intact skin.
Irritant / corrosive response data:
There was no erythema or edema noted at 3 minutes, 1 hour and 4 hours after dosing. Slight erythema was noted at 24 hours after patch removal in 2/3 rabbits and absent in the third rabbit. Erythema was absent at 48 and 72 hours. Edema was absent at any time.
Other effects:
No clinical signs were noted.

The dermal effects on the abraded skin were identical to the effects on intact skin.

Interpretation of results:
other: data insufficient for classification purposes
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
In an in vivo skin irritation test performed with an aqueous formulation with 20-37% disodium isodecyl sulfosuccinate on intact and abraded skin, no irritation or corrosion was observed.
Executive summary:

An in vivo skin irritation test was performed with an aqueous formulation with 20-37% disodium isodecyl sulfosuccinate. Clipped skin of 3 male rabbits was exposed semi-occlusively to 0.5 ml for 4 hours (both intact and abraded skin was tested). There was no erythema or edema noted at 3 minutes, 1 hour and 4 hours after dosing. Slight erythema was noted at 24 hours after patch removal in 2/3 rabbits and absent in the third rabbit. Erythema was absent at 48 and 72 hours. Edema was absent at any time.

Based on these results, it is concluded that an aqueous formulation with 20-37% disodium isodecyl sulfosuccinate is not irritant to the skin. It is of note that since the test substance was tested in formuation, the data cannot be used for classification purposes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 Oct 2014 - 21 Oct 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Version / remarks:
Adopted July 26, 2013
Deviations:
no
Qualifier:
according to
Guideline:
EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
Version / remarks:
EAmended by EC No. 1152/2010 No. L142, 09 December 2010
Deviations:
no
Qualifier:
according to
Guideline:
other: The Ocular Toxicity Working Group (OTWG) of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Interagency Centre for the Evaluation of Alternative Toxicological Methods (NICEATM), March 2006
Deviations:
no
Qualifier:
according to
Guideline:
other: In Vitro Techniques in Toxicology Database (INVITTOX) protocol 127. Bovine Opacity and Permeability (BCOP) Assay, 2006
Deviations:
no
Qualifier:
according to
Guideline:
other: Gautheron P., Dukic M., Alix D. and Sina J.F., Bovine corneal opacity and permeability test: An in vitro assay of ocular irritancy. Fundam Appl Toxicol 18:442-449, 1992
Deviations:
no
GLP compliance:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount applied: approx. 750 µl of 10% (w/v) dilution in physiological saline per cornea
- The stock solution was treated with ultrasonic waves until the test substance had completely dissolved

NEGATIVE CONTROL
- Amount applied: 750 µl of physiological saline per cornea

POSITIVE CONTROL
Amount applied: 750 µl per cornea
Concentration: 10% (w/v) benzalkonium chloride in physiological saline


Duration of treatment / exposure:
10 minutes
Details on study design:
TEST SITE
- Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing: yes (with MEM with phenol red (Eagle’s Minimum Essential Medium, Invitrogen Corporation) and thereafter with cMEM)
- Time after start of exposure: 10 minutes

SCORING SYSTEM:
- After exposure the cornea is thoroughly rinsed to remove the test substance followed by incubation for 120 ± 10 minutes in cMEM. Then, corneas were incubated in sodium-fluorescein solution for 90 ± 5 minutes (both incubations at 32 ± 1°C).

- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:

In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).


TOOL USED TO ASSESS SCORE:
- opacitymeter and microplate reader

DATA EVALUATION:
A test substance that induces an IVIS ≤ 3 is not classified for eye irritancy (UN GHS: no category);
A test substance that induces an IVIS > 55 is defined as a corrosive or severe irritan (UN GHS: category 1);
For a test substance that induces an IVIS >3 and ≥ 55, no prediction on irritant potency can be made (UN GHS: no prediction can be made)
Irritation parameter:
in vitro irritation score
Run / experiment:
10 minutes
Value:
>= 15.8 - <= 51.4
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: mean score 38.1
Other effects / acceptance of results:
The opacity value was 10 in all three corneas treated with disodium isodecyl sulfosuccinate and permeability values ranged from 0.406 to 2.785. The corneas were turbid with spots after the 10 minutes of treatment with disodium isodecyl sulfosuccinate. No pH effect of the test substance was observed on the rinsing medium. Hence, the in vitro irritancy scores ranged from 15.8 to 51.4 after 10 minutes of treatment with Disodium isodecyl sulfosuccinate.

The individual in vitro irritancy scores for the negative controls ranged from -0.4 to 0.7. The individual positive control in vitro irritancy scores ranged from 156 to 168 for benzalkonium chloride (mean IVIS = 161.6). The corneas treated with the positive control substance were turbid after the 10 minutes of treatment.

Interpretation of results:
other: the outcome does not allow conclusion on classification
Remarks:
Criteria used for interpretation of results: other: UN GHS
Conclusions:
In a bovine corneal opacity and permeability (BCOP) test, performed according to OECD guideline and GLP principles, disodium isodecyl sulfosuccinate induced a mean IVIS of 38.1. Based on an IVIS > 3 and ≤ 55, no prediction on eye irritancy of the test substance can be made.

Executive summary:

A bovine corneal opacity and permeability (BCOP) test was performed with disodium isodecyl sulfosuccinate according to OECD guideline and GLP principles. Reliable positive and negative controls were included. The corneas treated with disodium isodecyl sulfosuccinate were turbid with spots after the 10 minutes of treatment. Mean in vitro irritancy score was 38.1 after 10 minutes of treatment. The opacity value was 10 in all three corneas treated with disodium isodecyl sulfosuccinate and permeability values ranged from 0.406 to 2.785. based on an IVIS > 3 and ≤ 55, no conclusion on classification for eye irritancy can be drawn according to GHS UN.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Effects on skin: irritating with limit concentration of 50% for non-irritation

The conclusion on the skin irritant properties of the test substance is drawn in a weight-of-evidence approach based on all available data based upon Registered substance. Two in vivo skin irritation tests are available performed with either formulation of 20-37% (Cerven, 2005) or 50% (Carpenter, 1971). Based on these results, it is concluded that aqueous formulations up to 50% of Registered substance are not irritant to the skin.

In a Guinea pig maximisation test, 0.5 mL of the Registered substance was applied semi-occlusively to 6cm2skin at concentrations of 5%, 10%, 20% and 40% for 24 hours (2 animals/ concentration). The exposure to 20% solution correlates to application of 0.1g to 6cm2. At this dose, no oedema was seen, but signs of superficial necrosis were seen. The test substance was held in contact to the skin for 24 hours, which is regarded as worst case. Application of 0.05g did not result in an effect on the skin (Latour, 2015).

Additionally, the absence of skin effects in an acute dermal study in rabbits (See also Section 7.2.3) and in a modified Draize-Shelanski repeat insult patch test (See Section 7.4), the substance did not result in skin effects (Kliggman, 1976).

Taken all data together, it is concluded that Registered subsstance is not expected to be corrosive to the skin, but from a conservative viewpoint the group classification as irritating Category 2 (H315) is concluded, wiht limit concentration of 50% for non-irritation.

 

Effects on eye: irritating with limit concentration of 50% for non-irritation

In a key bovine corneal opacity and permeability (BCOP) test, Registered substance induced a mean IVIS of 38.1. An IVIS > 3 and ≤ 55 does not allow conclusion on classification for eye irritancy, however the substance does not lead to eye damage (WIL Research Europe, 2014).

Two supporting in vivo skin irritation tests were performed, one with an aqueous formulation with 50% and the other with a 20-37% of Registered substance on intact and abraded skin (Carpenter, 1971; Cerven, 2005). These formulations were not irritating. In these studies, no irritation or corrosion was observed. Additionally, the absence of skin effects in an acute dermal study in rabbits (See also Section 7.2.3) and in a human patch study (see Section 7.4.1) were considered in a weight of evidence approach to fill this endpoint.

The Registered substance was concluded not to be corrosive to the eye, but from a conservative viewpoint the Registered substance is considered to be irritating for eye, with limit concentration of 50% for non-irritation.

Justification for classification or non-classification

Based on the available data, Registered substance is concluded to be non-corrosive and not irritating to the skin, however a conservative (group) classficition for irritation Category 2 (H315) is proposed according to CLP Regulation (EC) No. 1272/2008, with limit concentration of 50%.

Based on the available data, Registered substance is concluded not to induce eye damage, however from a conservative viewpoint, the substance is classified as irritating for eye Category 2 (H319) according to CLP Regulation (EC) No. 1272/2008, with limit concentration of 50%.