4-morpholinopropanesulphonic acid

Endpoint summary

Description of key information

As an analogue substance and two structurally closely related substances did not induce skin irritation and only minor eye irritation that does not require classification, the target substance is considered to be not skin and not eye irritating.

Skin irritation: In a key study according to OECD TG 404, no skin irritation effects have been observed for the source substance CAS 71119 -22 -7 (reference 7.3.1 -1).

Eye irritation: In a key study according to OECD TG 405 with the source substance CAS 71119-22-7, the substance induced minor conjunctival effects and chemosis, which were fully reversible within 72 h. Therefore, the source substance is considered as not eye irritating (reference 7.3.2-1).

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:

1997-08-14 to 1997-08-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

Commission Directive 92/69/EEC

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 17 July 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.49-2.61 kg
- Housing: individually, suspended metal cages
- Diet: ad libitum, STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 74
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

day before treatment

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Amount applied: 0.5 mL
- used to moisture test material on test site, not mixed before application

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm on back of animal
- Type of wrap: The cotton gauze patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing: gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h after removal of patch

SCORING SYSTEM:
Effects were scored according to the scale from Draize J H, (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Very slight erythema was noted at two treated skin sites at the 1 hour observation. No other evidence of skin irritation was noted during the study.

Other effects:

No other effects were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item showed no skin irritation potential in an in vivo study under semi-occlusive conditions in rabbits.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single 4 hour, semi-occluded application of the test material to the intact skin of three rabbits was done. Very slight erythema was noted at two treated skin sites at the 1 hour observation. No other evidence of skin irritation was observed during the study. The test material produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize Classification scheme. No corrosive effects were noted.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-08-19 to 1997-08-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

Commission Directive 92/69/EEC

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24 February 1987

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.85-3.07 kg
- Housing: individually housed in suspended metal cages
- Diet: ad libitum, STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 74-78
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL (approx. 81 mg)

Duration of treatment / exposure:

application without removal by washing

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
Test item was not removed.

SCORING SYSTEM:
Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49

TOOL USED TO ASSESS SCORE: ophthalmoscope

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

2.2

Max. score:

110

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Other effects:

Moderate conjunctival irritation was noted in all treated eyes at 1 hour. Minimal conjunctival irritation was observed in all treated eyes after 24 and 48h. No other evidence of eye irritation was noted.
No further effects were detected.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item showed no eye irritation potential in an in vivo study in rabbits.

Executive summary:

A study was performed to assess the irritancy potential of the test material following a single application to eye of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and Method B5 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A test material amount of 0.1 mL was introduced to each eye and no washing procedure was performed. Moderate conjunctival irritation was noted in all treated eyes at the 1 hour observation. Minimal conjunctival irritation was noted in all treated eyes at the 24 and 48 hour observations. No other evidence of eye irritation was noted. All observed effects were reversible within 72 h after application. The mean scores for 24/48/72 h for conjunctivae, chemosis, cornea opacity and iris were 0.7 (fully reversible within 72 h), 0.3 (fully reversible within 48 h), 0 and 0, respectively. No further effects were detected. The test material is therefore considered to be non-irritant to rabbit eyes.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No study is available for the target substance. However, in vivo and in vitro studies on skin and eye irritation are available for three structural similar substances and have been used in a read-across approach to address both endpoints.

Skin irritation

A key study was performed to assess the irritancy potential of the test material CAS 71119-22-7 to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single 4 hour, semi-occluded application of the test material to the intact skin of three rabbits was done. Very slight erythema was noted at two treated skin sites at the 1 hour observation. No other evidence of skin irritation was observed during the study. The test material produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize Classification scheme. No corrosive effects were noted.

A supporting study according OECD TG 439 has been performed with the structurally similar substance CAS 1266615-59-1 to predict the irritation potential of the test item by measurement of its cytotoxic effect, as reflected in the MTT assay. Triplicates of the human skin model EPISKIN (Reconstructed Human Epidermis) were treated with test item and incubated for 15 minutes at room temperature. Exposure of the reconstructed human epidermis skin units with test item was terminated by rinsing with PBS 1x solution. Epidermis units were then incubated at 37 °C for 42 hours in an incubator with 5 % CO2. The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37°C in 5 % CO2 protected from light. The precipitated formazan was then extracted using acidified isopropanol and quantified spectrophotometrically. SDS (5 % aq.) and 1×PBS treated epidermis (three units / positive and negative control) were used as positive and negative controls respectively. For each treated tissue viability was expressed as a percentage relative to negative control. In this in vitro skin irritation test using the EPISKIN model, the test item did not show significantly reduced cell viability in comparison to the negative control (mean value: 103 %). All obtained test item viability results were far above 50 % when compared to the viability values obtained from the negative control. Therefore the test item was considered to be non-irritant to skin. Positive and negative controls showed the expected cell viability values within acceptable limits. The experiment was considered to be valid.

A further supporting study according to OECD TG 439 has been performed to predict the irritation potential of the test item CAS 71119-23-8 by measurement of its cytotoxic effect, as reflected in the MTT assay. Triplicates of the human skin model EPISKIN (Reconstructed Human Epidermis) were treated with test item and incubated for 15 minutes at room temperature. Exposure of the reconstructed human epidermis skin units with test item was terminated by rinsing with PBS 1x solution. Epidermis units were then incubated at 37 °C for 42 hours in an incubator with 5 % CO2. The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37 °C in 5 % CO2 protected from light. The precipitated formazan was then extracted using acidified isopropanol and quantified spectrophotometrically. SDS (5 % aq.) and 1×PBS treated epidermis (three units / positive and negative control) were used as positive and negative controls respectively. For each treated tissue viability was expressed as a percentage relative to negative control. In this in vitro skin irritation test using the EPISKIN model, the test item did not show significantly reduced cell viability in comparison to the negative control (mean value: 116 %). All obtained test item viability results were far above 50 % when compared to the viability values obtained from the negative control. Therefore the test item was considered to be non-irritant to skin.

Eye irritation

A key study was performed to assess the irritancy potential of the test material CAS 71119-22-7 following a single application to eye of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and Method B5 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A test material amount of 0.1 mL was introduced to each eye and no washing procedure was performed. Moderate conjunctival irritation was noted in all treated eyes at the 1 hour observation. Minimal conjunctival irritation was noted in all treated eyes at the 24 and 48 hour observations. No other evidence of eye irritation was noted. All observed effects were reversible within 72 h after application. The mean scores for 24/48/72 h for conjunctivae, chemosis, cornea opacity and iris were 0.7 (fully reversible within 72 h), 0.3 (fully reversible within 48 h), 0 and 0, respectively. No further effects were detected. The test material is therefore considered to be non-irritant to rabbit eyes.

A supporting study according OECD TG 438 was performed to evaluate the potential ocular corrosivity and irritancy of the test item CAS 1266615-59-1 by its ability to induce toxicity in enucleated chicken eyes. This test identifies chemicals either inducing "serious eye damage", or not requiring classification for eye irritation or serious eye damage according to the GHS. The test item was applied in a single dose (30 mg/eye) onto the cornea of isolated chicken eyes and rinsed after 10 seconds with saline. Tested corneas were evaluated pre-treatment and at approximately 30, 75, 120, 180, and 240 minutes after the post-treatment rinse. The endpoints evaluated were corneal opacity, swelling, fluorescein retention, and morphological effects. The test item and Imidazole (positive control) were ground before use in the study. Test item and positive control were applied in an amount of 30 mg/eye by powdering the entire surface of the cornea attempting to cover the cornea surface uniformly with the test substance or positive control. Three test item treated eyes and three positive control eyes were used in this study. One negative control eye was treated with 30 μL saline solution. After an exposure period of 10 seconds from the end of the application the cornea surface was rinsed thoroughly with approximately 20 mL saline solution at ambient temperature and this procedure was repeated for each eye. In this ICET, the test item did not cause ocular corrosion or severe irritation in the enucleated chicken eyes. The overall ICE class was 3xI. Positive and negative controls showed the expected results. The experiment was considered to be valid.

A further supporting study was conducted according OECD TG 438. The purpose of this Isolated Chicken Eye Test (ICET) was to evaluate the potential ocular corrosivity and irritancy of the test item CAS 71119-23-8 by its ability to induce toxicity in enucleated chicken eyes. The test item was applied in a single dose (30 mg/eye) onto the cornea of isolated chicken eyes and rinsed after 10 seconds with saline. Tested corneas were evaluated pre-treatment and at approximately 30, 75, 120, 180, and 240 minutes after the post-treatment rinse. The endpoints evaluated were corneal opacity, swelling, fluorescein retention, and morphological effects. All of the endpoints, with the exception of fluorescein retention (which was determined only at pre-treatment and 30 minutes after test substance exposure) were determined at each of the above time points. The Imidazole (positive control) was ground before use in the study. The test item and positive control were applied in an amount of 30 mg/eye by powdering the entire surface of the cornea attempting to cover the cornea surface uniformly with the test substance or positive control. Three test item treated eyes and three positive control eyes were used in this study. One negative control eye was treated with 30 μL saline solution. After an exposure period of 10 seconds from the end of the application the cornea surface was rinsed thoroughly with approximately 20 mL saline solution at ambient temperature and this procedure was repeated for each eye. In this ICET, the test item did not cause ocular corrosion or severe irritation in the enucleated chicken eyes. With the overall ICE score of 2xI and 1xII, the substance is classified as "No Category". Positive and negative controls showed the expected results. The experiment was considered to be valid.

Conclusion

Based on the results obtained with the structurally similar source substances the target substance is not considered to be irritant to skin and eyes.

Justification for classification or non-classification

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

The available data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No 1272/2008, as amended for the fifteenth time in Regulation (EU) 2020/1182.