Registration Dossier

Administrative data

Description of key information

1. 1982, skin irritation in vivo rabbits, not irritating
2. 1982, eye irritation in vivo rabbits, not irritating
3. Prediction using Toxtree (Chemservice S.A. 2011)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982-11-25 - 1982-12-02
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
only 4 days of acclimatisation
Qualifier:
according to guideline
Guideline:
other: ETAD (ecological and toxicological association of the dye stuffs manufacturing industries) Methods 001-003 (1979)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, 4414 Fuellingsdorf, Switzerland
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 2.3 - 3.0 kg
- Housing: cages individually in stainless steel cages with automatic drinking water supply and cleaning system (Dipl. Ing. W. Ehret GmbH/Versuchstiertechnik, 7830 Mendingen, Germany).
- Diet (e.g. ad libitum): pelleted standard KLIBA 23/341/1 rabbit maintenance dies (Klingentalmuehle AG, 4303 Kaiseraugust, Switzerland)
defined for acceptable contaminant level, ad libitum.
- Water (e.g. ad libitum): tap water ad libitum (water quality according to the requirements of the "schweiz. Lebensmittelbuch".
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10 %
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IDENTIFICATION: individually by numbered ear tags (Eisenhut Vet. AG, 4123 Allschwil, Switzerland) and cage number.
Type of coverage:
occlusive
Preparation of test site:
other: back and flanks of each rabbit were closely clipped with electric clippers
Vehicle:
other: polyethylene glycol (PEG400) + Saline (70 : 30 parts)
Controls:
other: the not-treated skin served as control site
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 gram
- Concentration (if solution): 50% solution of the test substance in polyethylene glycol (PEG400) + Saline (70 : 30 parts)

VEHICLE
- Concentration (if solution): polyethylene glycol (PEG400) + Saline (70 : 30 parts)
Duration of treatment / exposure:
The bandages and gauze patches remained in place for 4 hours. The animals were not restrained during this period.
Observation period:
72 hours
Number of animals:
3 (2 males, 1 female)
Details on study design:
TEST SITE
- Area of exposure: Twenty four hours before treatment the back and flanks of each rabbit were closely clipped with electric clippers, exposing an area of skin of approximately 10 X 10 cm.

SCORING SYSTEM:
1. Erythema and Eschar formation
no erythema = 0
very light erythema (barely detectable) = 1
well-defined erythema = 2
moderate to severe erythema = 3
severe erythema (beet redness) to slight eschar formation (injuries in depth) = 4
total possible erythema score: 4
2. Oedema
no oedema = 0
very light oedema (barely perceptible) = 1
light oedema (edges of area well defined by definitive raising) = 2
moderate oedema (raised approximately 1 mm) = 3
severe oedema (raised more than 3 mm and extending beyond area of exposure) = 4
total possible oedema score: 4

The skin reaction of the treated site was observed 1 hour/ 48 / 72 hours following removal of bandages and gauze patch.
In addition the corrosion effect to the skin of the rabbits was recorded and the number of affected animals was registered.
Mortality and clinical symptoms were monitored once daily.

SACRIFICE AND NECROPSY
Termination and post-mortem examination: the study was terminated 72 hours after substance application. All rabbits were killed by an intravenous injection of T61 (Hoechst) in the ear vein. Due to the results obtained, no macroscopical organ examination was indicated.
Irritation parameter:
other: Index of colouration
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
1-(3-Sulfopropyl)-Pyridinium-Betain (PPS) showed no irritation, when applied to intact rabbit skin.
No destructions or irreversible alterations of the treated skin were observed. Thus it was concluded that no corrosion effect had occurred on the skin. In the area of application no discolouration f the skin was observed which could be related to compound effects. No acute toxicological signs were observed in the animals during the test period.
Other effects:
No other effects were reported.

Table 1: Skin irritation scores

Skin irritation scores
Time period Animal / Sex Erythema Oedema
Intact Abraded Intact Abraded
After 1 hour 101H 1 - 0 -
102M 1 - 0 -
103F 1 - 0 -
After 24 hours 101M 0 - 0 -
102M 0 - 0 -
103F 0 - 0 -
After 48 hours 1.01M 0 - 0 -
  1.02M 0 - 0 -
  1.03F 0 - 0 -
After 72 hours 101M 0 - 0 -
  102M 0 - 0 -
  103F 0 - 0 -

Table 2: Primary skin irritation index

PRIMARY SKIN IRRITATION INDEX
SELECTED OBSERVATIONS INTACT SKIN ABRADED SKIN
After1 hour 1.0 -
After24hours 0.0 -
After48hours 0.0 -
After 72hours 0.0 -
Mean irritation index 0.2 -
primary skin irritation index  0.2 -

Score according to :

0 to 0.5 (none)

0.6 to 3.0 (slight)

3.1 to 5.0 (moderate)

5. to 8.0 (marked)

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The study was performed according to the OECD Guideline 404 with only negligible deviations and even though no information was available whether it was performed according to the good laboratory practice principles, it is considered to be of high quality (reliability Klimisch 2). The criteria of validity of the test system are fulfilled. The test material did not induce any irritation or corrosion on the intact skin of rabbits. The test material was considered to be not irritating under the conditions of the test.
Executive summary:

The skin irritation potential of the test substance was investigated in New Zealand White rabbits according to OECD TG404 (Claus and Ullmann, 1982). The test substance (1 gram of a 50% dilution of the test substance in polyethylene glycol/water) was applied occlusively to the intact skin for 4 hours; thereafter the skin reactions were monitored for 72 hours. Under the conditions of this experiment the test material was found to cause no irritation. In the area of application no discoloration of the skin was observed in the rabbits which could be related to compound effects. No corrosion effect had occurred on the skin at each measuring interval. The calculated primary irritation index was found to be 0.2 (Mean irritation index for intact skin).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982-11-25 - 1982-12-02
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report, which meets basic scientific principles
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: ETAD (Ecological and toxicological association of the dye stuffs manufacturing industry, Methods 001-003 (1979)
Qualifier:
according to guideline
Guideline:
other: VCI (Verband der chemischen Industrie, BRD) Sicherheitsdatenblatt
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, 4414 Fuellinsdorf, Switzerland
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 2.3 - 3.0 kg
- Housing: caged individually in stainless steel cages, with automatic drinking water supply and cleaning system (Dipl. Ing. W. Ehret GmbH, Versuchstier Technik, 7830 Emmendingen, Germany).
- Diet (e.g. ad libitum): pelleted standard KLIBA 23/341/1, rabbit maintenance diet (Klingentalmuehle AG, 4303 Kaiseraugust /- Switzerland). Defined for acceptable contaminant level, ad libitum
- Water (e.g. ad libitum): tap water ad libitum (water quality according to the requirements of the "SCHWEIZ. LEBENSMITTELBUCH")
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10 %
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Other:
- Identification: individually by numbered ear tags (Eisenhut Vet AG, 4123 Allschwil, Switzerland) and cage numbers.
Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye served as untreated control
Amount / concentration applied:
0.1g
Duration of treatment / exposure:
single application into the conjunctival sac of the left rabbit eye, without rinsing out
Observation period (in vivo):
1/ 24/ 48/ 72 hours after treatment
Number of animals or in vitro replicates:
3 in total (2 males, 1 female) - the same animals were used for the skin and eye irritation experiment.
Details on study design:
SCORING SYSTEM:

Cornea

A) opacity and the degree of opacity (most dense area scored).
No opacity = 0
Scattered or diffuse area (details of iris clearly visible) = 1
Easily discernible translucent areas, details of iris slightly obscured =2
Opalescent areas, no details of iris visible, size of pupil barely discernible = 3
Opal opacity, iris invisible = 4

B) area of cornea involved
No area involved = 0
One quarter (or less, but not 0) = 1
more than one quarter, less than half = 2
greater than half, but less than three quarters = 3
greater than three quarters up to the whole area = 4
A x B x 5 Total maximum = 80

Iris

A. Values
Normal = 0
Fold above normal, congestion, swelling, circumcornea injection (any or all of these or combination of any thereof) Iris still reacting to light (sluggish reaction is positive) = 1
No reaction to light, haemorrhage, gross destruction (any or all of these) = 2
A x 5 = Total Highest number = 10

Conjunctiva

A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris)
Vessels normal = 0
Vessels definitively injected more than normal = 1
More diffuse, deeper crimson red, individual vessels not easily discernible = 2
Diffuse beefy red = 3

B) Chemosis
No swelling = 0
Any swelling above normal (includes nictitating membrane) = 1
Obvious swelling with partial eversion of the lids = 2
Swelling with lids about half closed = 3
Swelling with lids about half closed to completely closed = 4

C) Discharge
No discharge = 0
Any amount different from normal (does not include small amounts observed in the inner canthus of normal animals) = 1
Discharge with moistening of lids and hairs just adjacent to lids = 2
Discharge with moistening of the lids and hairs, and considerable area around the eye = 3
(A + B + C) x 2 Total maximum = 20

In addition the coloration of the sclera/cornea was recorded in connection with the colour of the test material.
The total score for the eye is the sum of all points for cornea, iris and conjunctiva.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
1.4
Max. score:
110
Reversibility:
other: not applicable
Remarks on result:
other: no irritation or corrosivity
Irritation parameter:
other: mean reaction score
Basis:
mean
Time point:
other: 1 hour
Score:
5.3
Reversibility:
fully reversible
Irritation parameter:
other: mean reaction score
Basis:
mean
Time point:
other: 24 hours
Score:
0.6
Reversibility:
fully reversible
Irritation parameter:
other: mean reaction score
Basis:
mean
Time point:
other: 48 hours and 72 hours
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
other: animal 1, 2 and 3
Time point:
other: 1 hour, 24 hours, 48 hours and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
other: animal 1, 2 and 3
Time point:
other: 1 hour, 24 hours, 48 hours and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
other: conjunctiva redness
Basis:
other: animal 1, 2 and 3
Time point:
other: 1 hour,
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
other: conjunctiva redness
Basis:
animal #1
Time point:
other: 24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
other: conjunctiva redness
Basis:
other: animal 2 and 3
Time point:
other: 24 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
other: conjunctiva chemosis
Basis:
animal #1
Time point:
other: 1 hour
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
other: conjunctiva chemosis
Basis:
other: animal 2 and 3
Time point:
other: 1 hour
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
other: conjunctiva chemosis
Basis:
other: animal 1, 2 and 3
Time point:
other: 24 hours, 48 hours and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
other: conjunctiva discharge
Basis:
other: animal 1 and 3
Time point:
other: 1 hour
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
other: conjunctiva discharge
Basis:
animal #2
Time point:
other: 1 hour
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
other: conjunctiva discharge
Basis:
other: animal 1, 2 and 3
Time point:
other: 24 hours, 48 hours and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
1 -(3 -sulfopropyl)-pyridinium-betain (PPS) showed no irritation when applied to the rabbit eye mucosa.
No discoloration of the cornea and conjunctivae was observed in the rabbits during the entire test period which could be related to effects of the test material.
No corrosion effect was observed at each of the measuring intervals.
No acute toxicological signs were observed in the test animals during the test period.
Other effects:
no other effects reported

Table 1: Coloration index

Coloration index (mean of 3 animals)
males / females - not rinsed

Hours / days after application

1 hour 24 hours 48 hours 72 hours
Cornea 0 0 0 0
Conjunctivae 0 0 0 0
0 = none    
1 = slight  
2 = moderate
3 = severe

Table 2: eye irritation scores

Animal & sex Cornea  Iris Conjunctivae
Opacity Area inv.  Redness Chemosis Discharge
After 1 hour
101 M not rinsed 0 0 0 1 1

1

102 M not rinsed 0 0 0 1 0 2
103 F not rinsed 0 0 0 1 0 1
After 24 hours
101 M not rinsed 0 0 0 1 0 0
102 M not rinsed 0 0 0 0 0

0

103 F not rinsed 0 0 0 0 0 0
After 48 hours
101 M not rinsed 0 0 0 0 0 0
102 M not rinsed 0 0 0 0 0 0
103 F not rinsed 0 0 0 0 0 0
After 72 hours
101 M not rinsed 0 0 0 0 0 0
102 M not rinsed 0 0 0 0 0 0
103 F not rinsed 0 0 0 0 0 0

Table 3: mean reaction scores

Time period unrinsed eye
After 1 hour 5,3
After 24 hours 0,6
After 48 hours 0
after 72 hours 0

Table 4: primary eye irritation index

Selected observations

unrinsed eyes

After 1 hour

5.3

After 24 hours

0.6

After 48 hours

0.0

After 72 hours

0.0

primary irritation index

1.4

Assessment of irritation
0 to 10 = none
11 to 25 = slight
26 to 56 = moderate
57 to 110 = marked
Score according to ETAD, toxicological Methods 001-003 and VDI (Verband der chemischen Industrie), Sicherheitsdatenblatt
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The study was performed according to the OECD TG405 without deviations and even though no information was available whether it was performed according to the good laboratory practice principles, it is considered to be of high quality (reliability Klimisch 2). The criteria of validity of the test system are fulfilled. The test material did not induce any irritation or corrosion on rabbit eyes. The test material was considered to be not irritating under the conditions of the test.
Executive summary:

The test substance 1 -(3 -sulfopropyl)-pyridinium-betain (PPS) was investigated for its potential to cause irritation in the rabbit eye according to OECD TG405. 0.1 g of pure substance were instilled into the conjunctival sac, the untreated eye served as control. Under the conditions of this experiment 1 -(3 -sulfopropyl)-pyridinium-betain (PPS) was found to cause no irritation when applied to the rabbit eye mucosa. No corrosion effect was observed at each of the measuring intervals. No discoloration of the cornea and conjunctivae which could be related to effects of the test material was observed. Additionally no corrosive or acute toxicological signs were observed in the animals during the test period. The primary irritation index was found to be for the unrinsed eye: 1.4.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation:

The skin irritation potential of the test substance was investigated in New Zealand White rabbits (Claus and Ullmann, 1982) according to OECD TG404 with only negligible deviations and even though no information was available whether it was performed according to the good laboratory practice principles, it is considered to be of high quality (reliability Klimisch 2). The test substance (1 gram of a 50% dilution of the test substance in polyethylene glycol/water) was applied occlusively to the intact skin for 4 hours; thereafter the skin reactions were monitored for 72 hours. The criteria of validity of the test system are fulfilled. Under the conditions of this experiment the test material was found to cause no irritation or corrosion when applied to intact rabbit skin. In the area of application no discoloration of the skin was observed in the rabbits which could be related to compound effects. No corrosion effect had occurred on the skin at each measuring interval. The calculated primary irritation index was found to be 0.2 (Mean irritation index for intact skin). The test material was considered to be not irritating under the conditions of the test.

Eye irritation:

The test substance 1 -(3 -sulfopropyl)-pyridinium-betain (PPS) was investigated for its potential to cause irritation in the rabbit eye (Ullmann and Suter, 1982). The study was performed according to the OECD TG405 without deviations and even though no information was available whether it was performed according to the good laboratory practice principles, it is considered to be of high quality (reliability Klimisch 2). 0.1 g of pure substance was instilled into the conjunctival sac, the untreated eye served as control. The criteria of validity of the test system are fulfilled. Under the conditions of this experiment 1 -(3 -sulfopropyl)-pyridinium-betain (PPS) was found to cause no irritation when applied to the rabbit eye mucosa. No corrosion effect was observed at each of the measuring intervals. No discoloration of the cornea and conjunctivae which could be related to effects of the test material was observed. Additionally no corrosive or acute toxicological signs were observed in the animals during the test period. The primary irritation index was found to be for the unrinsed eye: 1.4. The test material was considered to be not irritating under the conditions of the test.

Prediction using Toxtree

For the estimation of eye irritation/corrosion potential of 3-(1-Pyridinio)-1-propanesulfonate was entered into the Toxtree modelling tool. 3-(1-Pyridinio)-1-propanesulfonate is assessed as not eye and skin corrosive. “No skin corrosion R34 or R35” is predicted (taking into account the estimated melting point of 278°C) for eye irritation and corrsion. No skin corrosion or irritation potential is identified (taking into account the estimated melting point of 278°C).

Justification for classification or non-classification

Skin irritation:

According to the European regulation (EC) No. 1272/2008, the test material does not meet the criteria for classification and will not require labelling as irritating to the skin.

Eye irritation:

The mean grades of ocular reactions at 24, 48 and 72 h p.a. were lower than the value classified as irritating to the eyes by the European regulation (EC) No. 1272/2008, therefore the substance should not be classified.