Reaction mass of sodium hydrogen N,N-dibutyl-10-(sulphonatooxy)octadecanamidate and sodium sulphooctadecanoate

Endpoint summary

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:

key study

Study period:

1985-12-11 to 1985-12-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, U.K
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.30 - 2.59 kg
- Housing: individually housed in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS

- Temperature (°C): 18 – 21 °C
- Humidity: (%): 45 - 70
- Photoperiod: 12 hours light and 12 hours darkness

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

The test material was found to be irritant to rabbit skin

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test material was found to be irritant to rabbit skin

Executive summary:

The study was performed according to OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" and was carried out in order to assess the irritancy potential of the test item following a single 4-hour, semi-occluded application to the intact rabbit skin. The test system was chosen because the rabbit has been shown to be a suitable model for this type of study and is recommended by the test method. For this purpose, a suitable test site was selected on the back of each of 3 rabbits. A quantity of 0.5 mL of the test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position over the test material with two lengths of adhesive strapping (SLEEK) in the form of a cross. To prevent the animals from interfering with the patches the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRI P) and the animals were returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water. Approximately one hour following removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale of Draize J.H. (1959). Well-defined erythema with moderate edema was noted at 3/3 treated skin sites one hour after removal of the patches. 0ne test site showed slight dermal haemorrhage over the test site. The irritation increased at the 24 -hour observation. One treated skin site showed light brown eschar at this time; the remaining treated skin sites showed moderate to severe erythema. The edema at all treated skin sites remained moderate. The dermal irritation gradually regressed and only one treated skin site showed very slight erythema on day 7: all skin sites showed desquamation. The test item was found to be irritant to rabbit skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

intact and scarified skin examined; additional exposures to dilution series.

GLP compliance:

no

Remarks:

predates GLP

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.5 – 2.0 kg
- Housing: single
- Diet: ad libitum
- Water: ad libitum

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: 100 %

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 6.25 m²
- Type of wrap: occlusive
REMOVAL OF TEST SUBSTANCE
- Washing: no
- Time after start of exposure: 24 hours
SCORING SYSTEM: Code of Federal Regulations, Title 21, Chapter 1, § 191.11, S. 243 - 244, 1972

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

72 h

Score:

ca. 8

Reversibility:

other: no data

Remarks on result:

other: The PDII was determined. No rating of erythema was done and no information on individual animals is available.

Irritant / corrosive response data:

The undiluted material cause moderate erythema and moderate edema in 24 hours. The findings worsened within 72 hours to severe erythema and severe edema (primary irritation index = 8). Even a diluted solution (0.1 %) still caused very slight erythema and edema 24 hours after application in 4 of 6 animals.

Other effects:

no data

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test item was highly irritating to skin of rabbits after occlusive exposure for 24 hours.

Executive summary:

Six rabbits were treated dermally with undiluted test item for 24 hours under occlusive conditions. The material caused moderate erythema and moderate edema in 24 hours. The findings worsened within 72 hours to severe erythema and severe edema (Index = 8). Even a diluted solution (0.1 %) still caused very slight erythema and edema 24 hours after application in 4 of 6 animals.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1977-08-22 to 1977-08-26

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

intact as well as scarified skin tested

GLP compliance:

no

Remarks:

Pre-dates GLP

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

- Strain: Hoe: HIMK (SPFWiga)
- Weight at study initiation: 1.5 - 2 kg
- Diet: ad libitum
- Water: ad libitum

Type of coverage:

occlusive

Preparation of test site:

other: one site each: shaved and shaved & abraded

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL per site

Duration of treatment / exposure:

24 h

Observation period:

72 h after start of exposure

Number of animals:

3

Irritation parameter:

other: description

Basis:

other: 2 of 3 animals showed severe erythema and edema. 1 animal died

Remarks on result:

other: results are given quantitatively

Irritant / corrosive response data:

severely irritant

Other effects:

one animal died during the study on the day after treatment

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test material was severely irritating to intact and abraded skin of rabbits

Executive summary:

Three rabbits were treated with the test material on intact and abraded skin for 24 hours using the undiluted test material. Two of them exhibited severe erythema and edema. The third animal died on day 2 of the study. Findings were not clearly reversible within 72 hours after the start of exposure.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: no GLP; short report, few details on test substance as well as on results

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Observation ended at 72 hours after start of exposure

Principles of method if other than guideline:

Eyes were washed using physiologic salt solution after 24 hours.
Eyes were treated with 0.01 % fluorescine sodium in water before observations at 48 and 72 hours.

GLP compliance:

no

Remarks:

pre-dates GLP

Species:

rabbit

Strain:

Himalayan

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL per eye

Duration of treatment / exposure:

Observations were recorded at 1, 7, 24, 48 and 72 hours after instillation

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Irritation parameter:

cornea opacity score

Remarks:

slight turbidity

Basis:

animal: 2 out of 3 animals

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: no scores, but a narrative description given in the report

Irritation parameter:

conjunctivae score

Remarks:

obvious swelling

Basis:

animal: all animals

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: no scores, but a narrative description given in the report

Irritation parameter:

iris score

Basis:

animal: all animals

Time point:

24/48/72 h

Remarks on result:

other: No effects reported, no data on individual animals available

Irritation parameter:

chemosis score

Basis:

animal: all animals

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

other: no scores, but a narrative description given in the report

Irritant / corrosive response data:

Two of three animals showed slight corneal opacity and all animals diffuse reddening of conjunctivae and moderate chemosis. Additionally severely increased secretions were recorded.
The material was evaluated as moderately irritant.

Other effects:

no data

Interpretation of results:

other: moderately irritating

Conclusions:

The test material was moderately irritating to rabbit eyes instillation of 0.1 mL.

Executive summary:

Three rabbits were treated by instillation of 0.1 mL of the undiluted test material into the conjunctival sac of one eye each. Observations were recorded at 1, 7, 24, 48, and 72 hours after instillation. Eyes were washed using physiologic salt solution after 24 hours.

Eyes were treated with 0.01% fluorescine sodium in water before further observations. The test material elicited slight corneal opacity in 2 of 3 rabbits and diffuse erythema, moderate chemosis and severe discharge in all animals.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2012-05-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 750 µL per cornea

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

Duration of treatment / exposure:

- Exposure: 10 minutes
- Post incubation period: 120 minutes

Details on study design:

TEST SITE
- Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 10 minutes

SCORING SYSTEM:
- After exposure the cornea was thoroughly rinsed to remove the test substance and incubated for 2 hours with fresh medium followed by opacity measurement and the permeability of the corneas was determined after a 90 minutes incubation period with sodium fluorescein.
- 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 ≥ 55.1 is defined as a corrosive or severe irritant

Irritation parameter:

in vitro irritation score

Run / experiment:

mean, 10 minutes

Value:

-0.4

Vehicle controls validity:

not specified

Negative controls validity:

valid

Positive controls validity:

valid

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is not irritant or corrosive in the Bovine Corneal Opacity and Permeability test.

Executive summary:

The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 126 and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. The test item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.4 after 10 minutes of treatment.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1974

Reliability:

4 (not assignable)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

other: Gelb-Silber-Kaninchen

Details on test animals or tissues and environmental conditions:

no data

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: 100 - 10 - 5 -1 %

Duration of treatment / exposure:

no washing

Observation period (in vivo):

1, 3, 7, 24, 48, 72, and 144 hours

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE: none
TOOL USED TO ASSESS SCORE: fluorescein (0.1 mL of 1/10000 solution) used at 24 h.

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not reversible

Remarks on result:

other: No numbers, but a narrative description is given in the report. See below.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No data on individual animals available

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No data on individual animals available

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No data on individual animals available

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: No data on individual animals available

Irritant / corrosive response data:

At 100 % irreversible effects (5 days) on cornea (moderate turbidity) and conjunctivae (severe swelling and redness) were observed with increasing intensity over time. Application of Fluorescine did not show corneal damage at any concentration.
At 10 % the findings were less intense and animals completely recovered within 144 hours.
At 5 % and 1 % the findings were still slighter and complete recovery was achieved within 48 hours.

Interpretation of results:

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

Conclusions:

The test item is considered severely irritant to eyes with irreversible effects at high concentrations.

Executive summary:

Six rabbits were treated by instillation of 0.1 mL of the undiluted test material into the conjunctival sac of one eye each. Observations were recorded at 1, 3, 7, 24, 48, 72 and 144 hours after instillation. Eyes were not washed. Eyes were treated with 0.01 % fluorescine sodium in water before observations and at 24 hours.

Ocular treatment of 6 rabbits with the 0.1 mL of the undiluted test material caused severe irritation at the conjunctiva and moderate turbidity of the cornea. Animals did not recover within the observation time of 5 days and the intensity increased steadily.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Key study

The study was performed according to OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" and was carried out in order to assess the irritancy potential of the test item following a single 4-hour, semi-occluded application to the intact rabbit skin. The test system was chosen because the rabbit has been shown to be a suitable model for this type of study and is recommended by the test method. For this purpose, a suitable test site was selected on the back of each of 3 rabbits. A quantity of 0.5 mL of the test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position over the test material with two lengths of adhesive strapping (SLEEK) in the form of a cross. To prevent the animals from interfering with the patches the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRI P) and the animals were returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water. Approximately one hour following removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale of Draize J.H. (1959). Well-defined erythema with moderate edema was noted at 3/3 treated skin sites one hour after removal of the patches. 0ne test site showed slight dermal haemorrhage over the test site. The irritation increased at the 24 -hour observation. One treated skin site showed light brown eschar at this time; the remaining treated skin sites showed moderate to severe erythema. The edema at all treated skin sites remained moderate. The dermal irritation gradually regressed and only one treated skin site showed very slight erythema on day 7: all skin sites showed desquamation. The test item was found to be irritant to rabbit skin.

 

Supporting studies

In a study similar to OECD 404 six rabbits were treated dermally with undiluted test item for 24 hours under occlusive conditions. The material caused moderate erythema and moderate edema in 24 hours. The findings worsened within 72 hours to severe erythema and severe edema. A primary irritation index of 8 was determined. Even a diluted solution (0.1 %) still caused very slight erythema and edema 24 hours after application in 4 of 6 animals.

 

In a study similar to OECD 404 three rabbits were treated with the test material on intact and abraded skin for 24 hours using the undiluted test material. Two of them exhibited severe erythema and edema. The third animal died on day 2 of the study. Findings were not clearly reversible within 72 hours after the start of exposure.

 

 

Eye irritation

To determine the corrosion or irritation potential of the test item for the eye a weight of evidence approach was done with data from existing in vivo and in vitro studies.

 

An in vitro study according to OECD 437 was conducted with the undiluted test item. As negative control physiological saline and for positive control 10 % (w/v) Benzalkonium Chloride were used. The exposure time was 10 minutes with a post incubation period of 120 minutes. The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 126 and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. The test item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.4 after 10 minutes of treatment.

 

A study similar to OECD 405 was conducted in six rabbits. The test item was applied undiluted or diluted in physiological saline at concentrations of 10, 5 and 1 %. After application of the test item on the eye the effects were recorded after 1, 3, 7, 24, 48, 72 and 144 hours. The eye was not rinsed after application. After 24 hours fluorescein (0.1 mL of 1/10000 solution) was applied to the treated eyes. The pure substance caused effects that were not reversible within 5 days. On cornea moderate turbidity and for conjunctivae severe swelling and redness were observed with increasing intensity over time. With the concentration of 10 % the findings were less intense and animals completely recovered within 144 hours. At 5 % and 1 % the findings were still slighter and complete recovery was achieved within 48 hours. Application of fluorescein did not show corneal damage at any concentration.

 

In study similar to OECD 405 three rabbits were treated by instillation of 0.1 mL of the undiluted test material into the conjunctival sac of one eye each. Observations were recorded at 1, 7, 24, 48, and 72 hours after instillation. Eyes were washed using physiologic salt solution after 24 hours. Eyes were treated with 0.01% fluorescine sodium in water before further observations. The test material elicited slight corneal opacity in 2 of 3 rabbits and diffuse erythema, moderate chemosis and severe discharge in all animals.

 

Conclusion

The in vitro study according to OECD guideline 437 showed no eye irritation potential of the undiluted test item. However, two in vivo studies both conducted without GLP and with limited details in the documentation showed effects of the test item on the eye of rabbits. The observation period in both studies, 144 and 72 hours, was shortened compared to the 21 days described in OECD 405. Therefore, a reversibility of the effects within the 21 day period can’t be excluded. Based on the limits of the in vivo tests and the reliability of the in vitro study the test item is considered to cause eye irritation in this weight of evidence approach

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available studies are considered reliable for this assessment.

 

Skin irritation/corrosion:

Based on the above stated assessment of the irritating properties of the test item, the results from reliable studies show that the substance is not irritating to the skin. Accordingly, the test item does not need to be classified according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council, as amended for the 17th time in Regulation (EU) 2021/849) as implementation of UN-GHS in the EU.

 

Eye irritation/corrosion:

Based on the above stated assessment of the irritating properties of the test item, the results from a reliable study shows that the substance is not corrosive or irritating to the eye. Accordingly, the test item does not need to be classified according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council, as amended for the eighteenth time in Regulation (EU) 2022/692) as implementation of UN GHS in the EU.

 

Classified: Skin Cat 2 (H 315)

Classified: Eye Cat 2 (H 319)

Several skin irritation studies as well as several eye irritation studies in rabbits in vivo consistently indicate that the test item is significantly irritating to skin and mucous membranes. This notion is also confirmed by findings from a 28 day study showing signs of irritation at the portal of entry (stomach)