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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-06-14 - 1993-07-26
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:
target record
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1993-06-14 - 1993-07-26
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 406 (Skin Sensitisation)
Version / remarks:
OECD guideline for the testing of chemicals (OECD 406, May 12, 1981)1981) with particular reference to the following publications by B. Magnusson and A. M. Kligman: "The identification of contact allergens by animal assay. The guinea pig maximization test" (J. Invest. Dermatol., 52, 268-276, 1969) and "Allergic Contact Dermatitis in the Guinea Pig" (Thomas Publishers, Springfield, Illinois, 1970).
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was performed prior to the implementation of REACH and the acceptance of the guidelines for alternative methods, e.g. the LLNA.
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
- stable for at least 1 year
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Harlan Winkelmann, Versuchstierzucht, Gartenstr. 27, 33178 Borchen
- Females (if applicable) nulliparous and non-pregnant: not specified
- Weight at study initiation: male: 320 - 428 g, female: 304 - 443 g
- Housing: Collective housing up to a maximum of 5 animals per cage (Makrolon® type IV), Bedding: "LIGNOCEL 3/4 Fasern" from pure soft wood; dried, freed from dust and sterilized, by Rettenmaier & Söhne GmbH + Co., 73494 Ellwangen-Holzmühle
- Diet (e.g. ad libitum): Ssniff-G (Alleindiät für Meerschweinchen), pellets, 1.0 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 ad libitum from Makrolon® drinking bottles, Becker & Co., 44579 Castrop-Rauxel
- Acclimation period: Prior to test initiation, all animals were acclimatized to laboratory conditions for 34 days (range finding) and 12 and 16 days (main test).
- Indication of any skin lesions: none stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3°C
- Humidity (%):30-70%
Measurement: with thermohygrometer twice daily
- Photoperiod (hrs dark / hrs light): artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.
Date of receipt: May 19, 1993 (range finding); June 2 and 16, 1993 (main test
Route:
intradermal
Vehicle:
water
Remarks:
aqua ad iniect.
Concentration / amount:
Test group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad iniect.
2. 0.1 ml test article diluted in aqua ad iniect. (final concentration: 5 %)
3. 0.1 ml test article diluted in FCA/aqua ad iniect. (final concentration: 5 %)
Control group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad iniect.
2. 0.1 ml aqua ad iniect.
3. 0.1 ml aqua ad iniect. 50 % (w/w) diluted in FCA
Day(s)/duration:
first day
Adequacy of induction:
other: in the range-finding study, no skin reactions were observed after the injection of the test article at the concentration of 5%.
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
aqua ad iniect
Concentration / amount:
Because the test article was non-irritating at the highest permissible concentration in the pilot study, the area was reclipped and pretreated with 10 % sodium lauryl sulfate (SLS) in vaseline 24 h before application of the test article at a concentration of 50 % in vaseline. The test article was spread in a thick layer [to saturation] over a 4 x 5 cm patch (filter paper). The latter was firmly secured over the previous injection sites by an occlusive dressing for 48 h. Control animals received a patch loaded with the vehicle alone.
Day(s)/duration:
7 days after the intradermal injections for 48 hours.
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
Both control and test animals were subjected to a challenge exposure. The challenge test was performed on a 5 x 5 cm clipped area on each flank. The maximal non-irritating concentration of the test article (50 % in vaseline) was applied to the left flank and the vehicle to the right in a volume of 0.5 g using the patch technique described above. In each case the duration of exposure was 24 h under an occlusive dressing.
Day(s)/duration:
14 days after epidermal induction
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 test and 20 control animals
Details on study design:
RANGE FINDING TESTS:
Pilot study (range finding)
Intradermal Injection:
The test article was diluted with aqua ad iniect. and Freund's complete adjuvant (FCA; Sigma, 80241 Deisenhofen) to give a final concentration of 5 %. Two animals were employed, skin reactions being recorded 48 h after treatment.
Dermal Application:
The test article was incorporated in vaseline to provide a final concentration of 50 % (w/w). A closed patch exposure was effected by means of an occlusive bandage using Hill-Top Chambers (Hill Top, Cincinnati, USA) and non-irritating tape Elastoplast® (Beiersdorf AG, Hamburg), which enveloped the whole of the animal's trunk. Two animals were employed and skin reactions were recorded 48 h post applicationem.

MAIN STUDY
The main study was performed on 20 test and 20 control animals. On the basis of the results of the range finding the concentrations of 5 % of the test article was considered to be suitable for intradermal injection and the concentration of 50 % for dermal application.
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1st day & seven days later for 48h
Induction Procedure
First stage - an area of 4 x 6 cm over the shoulders was clipped short with electric clippers and cleaned with 70 % (v/v) ethanol. Three pairs of intradermal injections were then made symmetrically in two rows on either side of the spine;
Test group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad iniect.
2. 0.1 ml test article diluted in aqua ad iniect. (final concentration: 5 %)
3. 0.1 ml test article diluted in FCA/aqua ad iniect. (final concentration: 5 %)
Control group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad iniect.
2. 0.1 ml aqua ad iniect.
3. 0.1 ml aqua ad iniect. 50 % (w/w) diluted in FCA
Second stage - 7 days after the intradermal injections, dermal application was initiated. Because the test article was non-irritating at the highest permissible concentration in the pilot study, the area was reclipped and pretreated with 10 % sodium lauryl sulfate (SLS) in vaseline 24 h before application of the test article at a concentration of 50 % in vaseline. The test article was spread in a thick layer [to saturation] over a 4 x 5 cm patch (filter paper). The latter was firmly secured over the previous injection sites by an occlusive dressing for 48 h. Control animals received a patch loaded with the vehicle alone.

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 14 days
Both control and test animals were subjected to a challenge exposure 14 days after the second stage of induction. The challenge test was performed on a 5 x 5 cm clipped area on each flank. The maximal non-irritating concentration of the test article (50 % in vaseline) was applied to the left flank and the vehicle to the right in a volume of 0.5 g using the patch technique described above. In each case the duration of exposure was 24 h under an occlusive dressing.
- Evaluation (hr after challenge): 24 and 48 h after patch removal, the treated skin areas were evaluated on a numerical scale according to Draize.

OTHER: EVALUATIONS OF SKIN REACTIONS (according to Draize)
Erythema and Eschar Formation Value
no erythema 0
very slight erythema (barely perceptible) 1
well-defined erythema 2
moderate to severe erythema 3
severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
Oedema Formation Value
no oedema 0
very slight oedema (barely perceptible) 1
slight oedema (edges of area well defined by definite raising) 2
moderate oedema (raised approximately 1 mm) 3
severe oedema (raised more than 1 mm and extending beyond area of exposure) 4

Classification: According to the OECD guideline for testing of chemicals (OECD 406, May 12, 1981), if no animal showed an allergic response the test article may be classified as a "non-sensitizer".
Challenge controls:
control animals
Positive control substance(s):
yes
Remarks:
The reaction to the positive control substances 2,4-dinitrochlorobenzene (extreme sensitizer) and benzocaine (mild sensitizer) is tested periodically.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no adverse reactions stated
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no adverse reactions stated
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no adverse reactions stated
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no adverse reactions stated
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
no additional information given
Interpretation of results:
GHS criteria not met
Conclusions:
The study was conducted according to OECD 406 under GLP and is sufficiently documented. Hence, the available study is sufficiently reliable to assess the skin sensitizing potential of propargyl-3-sulfopropyl ether, potassium salt, and the given scoring data allows classification acc. GHS. In the available study (GPMT), none of the animals showed any reaction after challenge. According to Regulation 1272/2008, when an adjuvant type guinea pig test method for skin sensitisation is used, a response of at least 30 % of the animals is considered as positive. Hence, no classification as skin sensitizer is required.
Executive summary:

The potential skin sensitizing properties of "POPS" were assessed in the guinea pig maximization test using 20 test and 20 control animals in a OECD 406 study under GLP. Following induction exposure to the test article or the vehicle, the animals were subjected two weeks later to a challenge exposure with the test article. The treated skin areas were evaluated 24 and 48 h after the end of the exposure period.

Classification: According to the OECD guideline for testing of chemicals (OECD 406, May 12, 1981), since no animal showed an allergic response, the test article "POPS" applied as a 50 % preparation, may be classified as a "non-sensitizer".

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 406 (Skin Sensitisation)
Version / remarks:
OECD guideline for the testing of chemicals (OECD 406, May 12, 1981)1981) with particular reference to the following publications by B. Magnusson and A. M. Kligman: "The identification of contact allergens by animal assay. The guinea pig maximization test" (J. Invest. Dermatol., 52, 268-276, 1969) and "Allergic Contact Dermatitis in the Guinea Pig" (Thomas Publishers, Springfield, Illinois, 1970).
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was performed prior to the implementation of REACH and the acceptance of the guidelines for alternative methods, e.g. the LLNA.

Test material

Constituent 1
Chemical structure
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
- stable for at least 1 year

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Harlan Winkelmann, Versuchstierzucht, Gartenstr. 27, 33178 Borchen
- Females (if applicable) nulliparous and non-pregnant: not specified
- Weight at study initiation: male: 320 - 428 g, female: 304 - 443 g
- Housing: Collective housing up to a maximum of 5 animals per cage (Makrolon® type IV), Bedding: "LIGNOCEL 3/4 Fasern" from pure soft wood; dried, freed from dust and sterilized, by Rettenmaier & Söhne GmbH + Co., 73494 Ellwangen-Holzmühle
- Diet (e.g. ad libitum): Ssniff-G (Alleindiät für Meerschweinchen), pellets, 1.0 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 ad libitum from Makrolon® drinking bottles, Becker & Co., 44579 Castrop-Rauxel
- Acclimation period: Prior to test initiation, all animals were acclimatized to laboratory conditions for 34 days (range finding) and 12 and 16 days (main test).
- Indication of any skin lesions: none stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3°C
- Humidity (%):30-70%
Measurement: with thermohygrometer twice daily
- Photoperiod (hrs dark / hrs light): artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.
Date of receipt: May 19, 1993 (range finding); June 2 and 16, 1993 (main test

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
water
Remarks:
aqua ad iniect.
Concentration / amount:
Test group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad iniect.
2. 0.1 ml test article diluted in aqua ad iniect. (final concentration: 5 %)
3. 0.1 ml test article diluted in FCA/aqua ad iniect. (final concentration: 5 %)
Control group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad iniect.
2. 0.1 ml aqua ad iniect.
3. 0.1 ml aqua ad iniect. 50 % (w/w) diluted in FCA
Day(s)/duration:
first day
Adequacy of induction:
other: in the range-finding study, no skin reactions were observed after the injection of the test article at the concentration of 5%.
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
aqua ad iniect
Concentration / amount:
Because the test article was non-irritating at the highest permissible concentration in the pilot study, the area was reclipped and pretreated with 10 % sodium lauryl sulfate (SLS) in vaseline 24 h before application of the test article at a concentration of 50 % in vaseline. The test article was spread in a thick layer [to saturation] over a 4 x 5 cm patch (filter paper). The latter was firmly secured over the previous injection sites by an occlusive dressing for 48 h. Control animals received a patch loaded with the vehicle alone.
Day(s)/duration:
7 days after the intradermal injections for 48 hours.
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
Both control and test animals were subjected to a challenge exposure. The challenge test was performed on a 5 x 5 cm clipped area on each flank. The maximal non-irritating concentration of the test article (50 % in vaseline) was applied to the left flank and the vehicle to the right in a volume of 0.5 g using the patch technique described above. In each case the duration of exposure was 24 h under an occlusive dressing.
Day(s)/duration:
14 days after epidermal induction
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 test and 20 control animals
Details on study design:
RANGE FINDING TESTS:
Pilot study (range finding)
Intradermal Injection:
The test article was diluted with aqua ad iniect. and Freund's complete adjuvant (FCA; Sigma, 80241 Deisenhofen) to give a final concentration of 5 %. Two animals were employed, skin reactions being recorded 48 h after treatment.
Dermal Application:
The test article was incorporated in vaseline to provide a final concentration of 50 % (w/w). A closed patch exposure was effected by means of an occlusive bandage using Hill-Top Chambers (Hill Top, Cincinnati, USA) and non-irritating tape Elastoplast® (Beiersdorf AG, Hamburg), which enveloped the whole of the animal's trunk. Two animals were employed and skin reactions were recorded 48 h post applicationem.

MAIN STUDY
The main study was performed on 20 test and 20 control animals. On the basis of the results of the range finding the concentrations of 5 % of the test article was considered to be suitable for intradermal injection and the concentration of 50 % for dermal application.
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1st day & seven days later for 48h
Induction Procedure
First stage - an area of 4 x 6 cm over the shoulders was clipped short with electric clippers and cleaned with 70 % (v/v) ethanol. Three pairs of intradermal injections were then made symmetrically in two rows on either side of the spine;
Test group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad iniect.
2. 0.1 ml test article diluted in aqua ad iniect. (final concentration: 5 %)
3. 0.1 ml test article diluted in FCA/aqua ad iniect. (final concentration: 5 %)
Control group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad iniect.
2. 0.1 ml aqua ad iniect.
3. 0.1 ml aqua ad iniect. 50 % (w/w) diluted in FCA
Second stage - 7 days after the intradermal injections, dermal application was initiated. Because the test article was non-irritating at the highest permissible concentration in the pilot study, the area was reclipped and pretreated with 10 % sodium lauryl sulfate (SLS) in vaseline 24 h before application of the test article at a concentration of 50 % in vaseline. The test article was spread in a thick layer [to saturation] over a 4 x 5 cm patch (filter paper). The latter was firmly secured over the previous injection sites by an occlusive dressing for 48 h. Control animals received a patch loaded with the vehicle alone.

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 14 days
Both control and test animals were subjected to a challenge exposure 14 days after the second stage of induction. The challenge test was performed on a 5 x 5 cm clipped area on each flank. The maximal non-irritating concentration of the test article (50 % in vaseline) was applied to the left flank and the vehicle to the right in a volume of 0.5 g using the patch technique described above. In each case the duration of exposure was 24 h under an occlusive dressing.
- Evaluation (hr after challenge): 24 and 48 h after patch removal, the treated skin areas were evaluated on a numerical scale according to Draize.

OTHER: EVALUATIONS OF SKIN REACTIONS (according to Draize)
Erythema and Eschar Formation Value
no erythema 0
very slight erythema (barely perceptible) 1
well-defined erythema 2
moderate to severe erythema 3
severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
Oedema Formation Value
no oedema 0
very slight oedema (barely perceptible) 1
slight oedema (edges of area well defined by definite raising) 2
moderate oedema (raised approximately 1 mm) 3
severe oedema (raised more than 1 mm and extending beyond area of exposure) 4

Classification: According to the OECD guideline for testing of chemicals (OECD 406, May 12, 1981), if no animal showed an allergic response the test article may be classified as a "non-sensitizer".
Challenge controls:
control animals
Positive control substance(s):
yes
Remarks:
The reaction to the positive control substances 2,4-dinitrochlorobenzene (extreme sensitizer) and benzocaine (mild sensitizer) is tested periodically.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no adverse reactions stated
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no adverse reactions stated
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% test item
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
no adverse reactions stated
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% test item
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no adverse reactions stated
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
no additional information given

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The study was conducted according to OECD 406 under GLP and is sufficiently documented. Hence, the available study is sufficiently reliable to assess the skin sensitizing potential of propargyl-3-sulfopropyl ether, potassium salt, and the given scoring data allows classification acc. GHS. In the available study (GPMT), none of the animals showed any reaction after challenge. According to Regulation 1272/2008, when an adjuvant type guinea pig test method for skin sensitisation is used, a response of at least 30 % of the animals is considered as positive. Hence, no classification as skin sensitizer is required.
Executive summary:

The potential skin sensitizing properties of "POPS" were assessed in the guinea pig maximization test using 20 test and 20 control animals in a OECD 406 study under GLP. Following induction exposure to the test article or the vehicle, the animals were subjected two weeks later to a challenge exposure with the test article. The treated skin areas were evaluated 24 and 48 h after the end of the exposure period.

Classification: According to the OECD guideline for testing of chemicals (OECD 406, May 12, 1981), since no animal showed an allergic response, the test article "POPS" applied as a 50 % preparation, may be classified as a "non-sensitizer".