Sodium 3-(2-propyn-1-yloxy)-1-propanesulfonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-06-15 - 1993-06-21 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

under GLP, sufficiently documented

Justification for type of information:

see target record

Cross-reference

Reason / purpose for cross-reference:

read-across source

Remarks:

link to target

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1993-06-15 - 1993-06-21 (experimental phase)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Klimisch 1 source record, but performed on read-across substance

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The rational for the analogue approach is the high structural similarity between the source and the target substance. Propargyl 3-sulfopropyl ether, potassium salt, and Propargyl 3-sulfopropyl ether, sodium salt, are structurally identical except the inorganic counterion, potassium resp. sodium. This difference is considered very minor as both cations are ubiquitously present in the body fluids, and the organic moieties are identical containing three functional groups in the molecules which are considered more relevant for their toxicological behaviour, i.e. the alkine, ether and sulfo group.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)

Source Chemical: Propargyl 3-sulfopropyl ether, potassium salt, EC 618-959-4, CAS 93637-00-4, SMILES Code C#CCOCCCS(=O)(=O)[O-].[K+], molecular formula C6H9O4KS, Mol. Weight 216.2994 g/mol

Target Chemical: Propargyl 3-sulfopropyl ether, sodium salt, EC 608-454-7, CAS 30290-53-0, SMILES Code C#CCOCCCS(=O)(=O)[O-].[Na+], molecular formula C6H9O4NaS, Mol. Weight 200.19 g/mol

Both substances do not contain impurities to an extent which is expected to alter the outcome of the experimental results or read-across approach.

3. ANALOGUE APPROACH JUSTIFICATION
According to REACH Annex XI, chapter 1.5, “Substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or "category" of substances.”… “The similarities may be based on:
1) a common functional group;
2) the common precursors and/or the likelihood of common breakdown products via physical and biological processes, which result in structurally similar chemicals…”.
Hence, Propargyl 3-sulfopropyl ether, sodium salt was analyzed regarding these criteria in the order as stated above:
1) Propargyl 3-sulfopropyl ether, sodium salt, is an organic salt with a sodium cation as inorganic counterion. The inorganic cation sodium (Na+) is widely distributed throughout the body and a normal constituent in the electrolyte system of vertebrates. Hence, it suggests itself to predominantly focus on the organic anion and regard it unchanged as a first step. So, the complete organic cation shall serve as a ‘functional group’ in this case. Further analogues can therefore be easily found by exchanging the inorganic counterion into a similar one of a similar size and low or no intrinsic toxic properties. Obvious here are e.g. potassium, hydrogen or ammonium.
2) Due to the ionic structure of all above mentioned salts, they all dissociate readily into the respective ions when getting into contact with water, which can be scientifically concluded. Propargyl 3-sulfopropyl ether, sodium salt, is distributed as a 50% aqueous solution and hence very soluble in water; the registered substance containing water is fully miscible in water. A similar behaviour can be assumed for POPS-K. In consequence, both substances can be reasonably expected to be present completely dissociated in the body fluids predominantly consisting of water. So, the organic moiety is identical in both substances and can be regarded as common breakdown product according to the Regulation. The substances structurally only differ in their inorganic cation, which can be considered as a very minor difference as both cations are ubiquitously present in the body fluids.
The data matrix displays exemplarily the chlorides of the inorganic counterions in question, sodium and potassium. Both salts show mild to moderate irritating effects, data available on POPS-K indicate very minor irritating effects not sufficient for classification. In general, the observed effects can be considered as rather consistent given the magnitude of effects, ionic structure of the cations, the content of the cations in the actual source and target chemical and the available data quality.
In both RTECS and GESTIS Substance Database of the German IFA providing various information on hazardous substances at the workplace, no information is given that NaCl or KCl are sensitizing which is comprehensible out of the following reasons: both sodium and potassium are ubiquitously present in the body and no information is given on autoimmune diseases associated with these ions. Further, these cations are not capable to act as (pre-)haptene or allergen. Immune responses are associated with proteins, and those ion are neither a protein nor capable of binding on them or modify them in a manner that the immune system is capable of recognizing them. Hence, a immune response could maximally be caused by the organic anion, which is identical in both source and target substance.
With regard to acute toxicity, also here possible differences may only arise from the cation. As displayed in the data matrix, potassium is in general of higher toxicity compared to sodium. Hence, a read-across is unlikely to underestimate the actual hazard of the registered substance, and more likely to overestimate it. Hence, read-across does not pose a potential risk and can be justified.

According to the RTECS database, for both NaCl and KCl, there are positive effects noted in various assays related to mutagenicity. According to the GESTIS database however, „There are no indications that NaCl has any mutagenic effects. NaCl solutions of very low concentrations have been used as solvents for test substances in a variety of mutagenicity tests (because of their inactivity). Positive reactions found in isolated cases on cultivated mammalian cells or in microorganisms were probably caused by osmotic effects and are not attributable to mutagenicity. There are no indications that NaCl has any carcinogenic effects.“ (http://gestis-en.itrust.de/nxt/gateway.dll/gestis_en/000000.xml?f=templates$fn=default.htm$vid=gestiseng:sdbeng$3.0). For KCl, that information is not given, but expectable, as also potassium is contained in cell culturing media, and the same osmotic effects in higher concentrations are expectable. Summarizing, there is no indication given that the exchange of the cation (Na+ or K+) would result in a different outcome of gene mutation testing in bacteria, hence, read-across is justified.
An obvious difference is that the potassium salt may be isolated as solid, whereas the sodium salt undergoes slight changes during isolation, can hence not be isolated as such and so the water must be considered as stabilizer in its identification. However, when being dissolved resp. diluted in the body fluids predominantly consisting of water, this difference can be neglected.

4. DATA MATRIX
There is not sufficient data on both complete, non-dissociated substances available to allow a direct comparison. Further, QSAR estimation revealed identical phys.-chem. properties, as e.g. for EpiSuite (US EPA) estimations, the inorganic ion is not regarded. However, as stated above, both organic salts immediately dissociate into the respective ions. Hence, the toxicity of the more relevant organic anion, Propargyl 3-sulfopropyl ether, does not need to be regarded for depicting possible differences or similarities, as it is identical in both molecules, and it is sufficient to compare the different cations only. Exemplarily, sodium and potassium chloride are compared, data is derived from RTECS (http://ccinfoweb.ccohs.ca/rtecs/search.html)

For the table, please refer to the attached justification

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

OECD guideline for the testing of chemicals no. 405 (February 24, 1987)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: sponsor

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient, protected from light

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harald Schriever, Kaninchenfarm, 27432 Bremervörde, Neuendamm 88
- Housing: individual housing (50 x 45 x 40 cm, L x B x H) in a battery of cages, each equipped with a paper roll disposal system
- Diet (e.g. ad libitum): Ssniff K - Haltung (Alleindiät fur Zuchtkaninchen), pellets, 1.0-1.5 cm long, 0.5 cm diameter, by Ssniff Spezialdiäten GmbH, 59494 Soest/Westfalen, ad libitum
- Water (e.g. ad libitum): drinking water as for human consumption via drinking nipples ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3°C
- Humidity (%):30-70%
Measurement: twice daily
- Photoperiod (hrs dark / hrs light): artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
- Concentration (if solution): undiluted

Duration of treatment / exposure:

Ocular reactions were assessed 1, 24, 48 and 72 h after treatment, no wash-out is stated.

Observation period (in vivo):

Ocular reactions were assessed 1, 24, 48 and 72 h after treatment.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none stated

SCORING SYSTEM: grading as stipulated by the OECD 405 guideline

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

not fully reversible within: 72h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

not fully reversible within: 72h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

Clinical observations: All animals showed slight conjunctival redness up to 24 - 48 h p.a. Slight chemosis of the conjunctivae and hyperemia of the iris were also evident at 1 h p.a.
Reversibility: The observed findings were reversible within 24 - 72 h p.a.

Other effects:

No other toxic effects were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The study was conducted according to OECD 405 under GLP and is sufficiently documented. Hence, the available study is sufficiently reliable to assess the eye irritating potential of propargyl-3-sulfopropyl ether, potassium salt, and the given scoring data allows classification acc. GHS. According to Regulation (EC) 1272/2008 table 3.3.2, a substance must be classified as Irritating to eyes (Category 2), if, when applied to the eye of an animal, a substance produces:
— at least in 2 of 3 tested animals, a positive response of:
— corneal opacity ≥ 1 and/or
— iritis ≥ 1, and/or
— conjunctival redness ≥ 2 and/or
— conjunctival oedema (chemosis) ≥ 2
— calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days
The mean grades of ocular reactions at 24, 48 and 72 h p.a. were lower than the value classified as irritant, and completely reversible, hence, the test item does not need to be classified according to Regulation (EC) 1272/2008.

Executive summary:

The potential toxicity of propargyl-3-sulfopropyl ether, potassium salt, was assessed in an acute eye irritation/corrosion test on 3 albino rabbits according to OECD 405 under GLP. In each animal, 0.1 g of the test article was introduced into the conjunctival sac of one eye, the untreated eye serving as a control. Both eyes were examined at 1, 24, 48 and 72 h post applicationem.

Clinical observations: Slight conjunctival redness and chemosis as well as hyperemia of the iris were apparent which were reversible within 24 - 72 h p.a. Toxic effects other than ocular irritation were not observed.

Assessment: The mean grades of ocular reactions at 24, 48 and 72 h p.a. were lower than the value classified as irritant by the EEC directive 91/325/EEC of March 1, 1991, the Gefahrstoffverordnung (GefStoffV), 1987 (BGB1. I, p. 2721), and Regulation (EC) 1272/2008. When applied to the eye , the test article might therefore be considered to be non-irritant.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

OECD guideline for the testing of chemicals no. 405 (February 24, 1987)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

potassium 3-(prop-2-yn-1-yloxy)propane-1-sulfonate

EC Number:

618-959-4

Cas Number:

93637-00-4

Molecular formula:

C6H9O4KS

IUPAC Name:

potassium 3-(prop-2-yn-1-yloxy)propane-1-sulfonate

Test material form:

solid: particulate/powder

Remarks:

yellowish

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: sponsor

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient, protected from light

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harald Schriever, Kaninchenfarm, 27432 Bremervörde, Neuendamm 88
- Housing: individual housing (50 x 45 x 40 cm, L x B x H) in a battery of cages, each equipped with a paper roll disposal system
- Diet (e.g. ad libitum): Ssniff K - Haltung (Alleindiät fur Zuchtkaninchen), pellets, 1.0-1.5 cm long, 0.5 cm diameter, by Ssniff Spezialdiäten GmbH, 59494 Soest/Westfalen, ad libitum
- Water (e.g. ad libitum): drinking water as for human consumption via drinking nipples ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3°C
- Humidity (%):30-70%
Measurement: twice daily
- Photoperiod (hrs dark / hrs light): artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
- Concentration (if solution): undiluted

Duration of treatment / exposure:

Ocular reactions were assessed 1, 24, 48 and 72 h after treatment, no wash-out is stated.

Observation period (in vivo):

Ocular reactions were assessed 1, 24, 48 and 72 h after treatment.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none stated

SCORING SYSTEM: grading as stipulated by the OECD 405 guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48h

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

not fully reversible within: 72h

Results 9

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

not fully reversible within: 72h

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritant / corrosive response data:

Clinical observations: All animals showed slight conjunctival redness up to 24 - 48 h p.a. Slight chemosis of the conjunctivae and hyperemia of the iris were also evident at 1 h p.a.
Reversibility: The observed findings were reversible within 24 - 72 h p.a.

Other effects:

No other toxic effects were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The study was conducted according to OECD 405 under GLP and is sufficiently documented. Hence, the available study is sufficiently reliable to assess the eye irritating potential of propargyl-3-sulfopropyl ether, potassium salt, and the given scoring data allows classification acc. GHS. According to Regulation (EC) 1272/2008 table 3.3.2, a substance must be classified as Irritating to eyes (Category 2), if, when applied to the eye of an animal, a substance produces:
— at least in 2 of 3 tested animals, a positive response of:
— corneal opacity ≥ 1 and/or
— iritis ≥ 1, and/or
— conjunctival redness ≥ 2 and/or
— conjunctival oedema (chemosis) ≥ 2
— calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days
The mean grades of ocular reactions at 24, 48 and 72 h p.a. were lower than the value classified as irritant, and completely reversible, hence, the test item does not need to be classified according to Regulation (EC) 1272/2008.

Executive summary:

The potential toxicity of propargyl-3-sulfopropyl ether, potassium salt, was assessed in an acute eye irritation/corrosion test on 3 albino rabbits according to OECD 405 under GLP. In each animal, 0.1 g of the test article was introduced into the conjunctival sac of one eye, the untreated eye serving as a control. Both eyes were examined at 1, 24, 48 and 72 h post applicationem.

Clinical observations: Slight conjunctival redness and chemosis as well as hyperemia of the iris were apparent which were reversible within 24 - 72 h p.a. Toxic effects other than ocular irritation were not observed.

Assessment: The mean grades of ocular reactions at 24, 48 and 72 h p.a. were lower than the value classified as irritant by the EEC directive 91/325/EEC of March 1, 1991, the Gefahrstoffverordnung (GefStoffV), 1987 (BGB1. I, p. 2721), and Regulation (EC) 1272/2008. When applied to the eye , the test article might therefore be considered to be non-irritant.