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Administrative data

Description of key information

The Primary Skin Irritation Index after 4h exposure of 3 rabbits to the test substance Formamidopropyldimethylbetain 50 %ig was calculated to be 0. The Primary Eye Irritation Index for the test substance Formamidopropyldimethylbetain 50 %ig was calculated to be "8" from "110" total possible scores at 1 h post application. 48 h after application all three animals were without any sign of ocular irritation.

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:
09. May 2005 - 17. May 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Species: rabbit
Breed: New Zealand White, IVA: NZW
Breeder: Charles River, Extertal, Germany
Date of receipt: 2005-05-03
Sex: 1 male and 2 female
Body weights: 1805.3 g, 1905.8 g, 1949.1 g
Age: - 10 weeks
Identification: dyemarks and cage numbers
Diet: Altromin International, Lage, Germany, 2023 - 1425
Water: Drinking water for the animals consisted of normal tap water from municipal sources: Stadtische Werke Krefeld AG, Abt. 2 TGW, Krefeld, Germany. The composition of the water is regularly determined. The data are retained in the archive. The water was supplied to the animals ad libitum via drinking bottles with rubber stoppers and steel pipes.
Bedding material: Lignocel BK 10/20, Rettenmaier, Jagstzell, Germany
Husbandry: They were housed single in steel cages with a plastic bottom mould and a habitat of 5445 cm2 at the bottom and an overall height of 600 mm. A non-barrier system with air conditioning was used. The air conditioning had the following nominal values: Temperature: 20 ± 3 °C, Humidity: 30 -70 %. Climate control was run automatically. The lightening was in a 12-hour light/dark-cycle. Temperature and humidity were recorded continuously using a thermohygrometer, Lambrecht GmbH, Gottingen, Germany. The data were archived. There have been no deviations from nominal temperature and humidity values during the experiment.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml of the test substance was applied to the left flank
Duration of treatment / exposure:
4 hours
Observation period:
Examination of the treated skin sites was done 1 hour, and approximately 24, 48, 72 hours as well as 7 days after removal of the test Substance.
Number of animals:
3
Details on study design:
Before the experiment was started, the animals had an acclimatization period of at least 5 days. The animals were clearly marked with dye and weighed. Food and drinking water was left for the animals ad libitum. 24 hours before dosing a part of the fur on both sides of the dorso-Iumbal region of each animal was removed by shearing with an electrical shaving machine exposing an area of skin approximately 10 x 15 cm. Care was taken to avoid abrading the skin and only animals with healthy intact skin were used in the experiment. Body weight was recorded immediately before test substance application and on the day of the final observation. As neither corrosive nor strong irritating effects to the skin have been expected the test substance was applied to all three animals for four hours at the same time. 0.5 ml of the test substance was applied to the left flank covered with a gauze pad (3 x 2 cm) which was held in place by strips of Blenderm (3M company, St. Paul, USA). The right flank
served as control region. Semi-occlusive dressings were bandaged with Acrylastic (Beiersdorf AG, Hamburg, Germany) and fixed with Leukoplast (Beiersdorf AG, Hamburg, Germany). Thus access by the animal to the patch and resultant ingestion of the test substance was prevented.
The test substance was removed by washing with tap water after 4 hours exposure time and the application areas were examined.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 - 72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible

Skin Reactions: Only very slight erythema but no oedema was observed in one animal 1 h after removal of the test substance Formamidopropyldimethylbetain 50%ig. The numerical scores to the erythema and oedema formations are presented in the following table:

 

Rabbit 504male

Rabbit 505 RV female

Rabbit 507 female

 

1h

24h

48h

72h

7d

1h

24h

48h

72h

7d

1h

24h

48h

72h

7d

Erythema

0

0

0

0

0

0

0

0

0

0

1

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Mean (24h-72h)

 

0 (E)

0 (Oe)

 

 

0 (E)

0 (Oe)

 

 

0 (E)

0 (Oe)

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
Formamidopropyldimethylbetain 50%ig is not irritating to the skin of rabbits. The mean grades of skin reactions at 24, 48 and 72 h reading correspond to values classified as not irritant by the Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008.
Executive summary:

For labelling and classification purposes the test substance Formamidopropyldimethylbetain 50%ig, a yellowish clear liquid, was tested regarding its skin irritation potential. The potential to cause inflammatory or corrosive changes upon first contact with skin was

assessed by semi-occluded application of the test substance for four hours to the shorn skin of two female and one male rabbit, strain New Zealand White according to the DECO Guideline for the Testing of Chemicals, 404 "Acute Dermal Irritation/Corrosion". As neither corrosive nor strong irritating effects to the skin have been expected Formamidopropyldimethylbetain 50%ig was applied to all three animals for four hours at the same time. Dermal reactions at the treated skin sites were assessed 1 hour after removal of the test substance and approximately 24, 48, and 72 hours as well as 7 days later.

Systemic toxic symptoms after application were not observed at any time during the study. Body weight development of the animals was positive and within normal ranges. Only very slight erythema but no oedema was observed in one animal 1 h after removal of the

test substance. Especially between 24 and 72 hours no erythema and oedema were observed. The mean scores for erythema and oedema formation for the time period 24 h - 72 h were 0. The Primary Skin Irritation Index was calculated to be 0. Under the conditions of this study the test substance Formamidopropyldimethylbetain 50%ig is non irritating and does not have to be classified for skin irritation.

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:
07. Jun. 2005 - 14. Jun. 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species: rabbit
Breed: New Zealand White, IVA: NZW
Breeder: Charles River, Extertal, Germany
Date of receipt: 2005-05-31
Sex: 1 male and 2 female
Number: a total of 3
Body weights: 1793.3 g, 1807.7 g, 1988.1 g
Age: - 10 weeks
Identification: dyemarks and cage numbers
Diet: Altromin International, Lage, Germany, 2023 - 1518
Water: Normal tap water from municipal sources Stadtische Werke Krefeld AG, Krefeld, Germany, was offered. The water is monthly examined for pollutants which might interfere with the study. The data are retained in the archive. The water was supplied to the animals ad libitum via drinking bottles with rubber stoppers and steel pipes.
Husbandry: The rabbits were housed single in steel cages with a plastic bottom mould and a habitat of 5445 square cm2 at the bottom and an overall height of 600 mm. A non-barrier system with air conditioning was used. The air conditioning had the fol/owing nominal values: Temperature: 20 ± 3°C, Humidity: 30 - 70 %. Climate control was run automatically. Temperature and humidity were measured continuously using a thermohygrometer from Lambrecht GmbH, Gottingen, Germany. The data were archived. There have been no deviations from nominal temperature and humidity values during the experiment.
Bedding material: Lignocel BK 10/20, Rettenmaier & Stihne GmbH & Co., Ellwangen-Holzmuhle, Germany.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL of test substance into the right eye of each animal.
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
Examination of the treated eyes was carried out 1 hour and approximately 24, 48, 72 hours and 7 days after application of the test substance.
Number of animals or in vitro replicates:
3
Details on study design:
Before the experiment was started, the animals were clearly marked with dye and weighed. Food and drinking water was left for the animals ad libitum.
Body weight was recorded immediately before test substance application and at the final observation 7 days later. The evaluation of the existing animal and in vitro studies revealed that the test substance is not corrosive or severely irritant. However, due to animal welfare reasons an initial test using one animal was performed. The test substance was applied into the right eye by pulling the lower eyelid away from the
eyeball to form a cup into which 0.1 ml of the test material was sprinkled in. The eyelid was gently held together for one second and then released. The left eye remained untreated and served as a control. As no corrosive or strong irritating effect was observed within one hour after application further two animals were treated in the same way. Examinations of ocular reactions were facilitated without any device. After recording the observations at 24 hours, the eyes of a\l rabbits were further examined with the aid of fluorescein to look for damage of the cornea. One drop of a 0.5 % (w/v) Fluorescein solution in saline solution was poured into both eyes and washed off with saline solution 30 seconds later. Afterwards scoring was executed by use of an UV-light lamp.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: slight ocular reactions 1 h after application of the test substance
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48h
Irritation parameter:
conjunctivae score
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
chemosis score
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible

Ocular Lesions:

Animal No. 504 LV

1h

24h

48h

72h

7d

Mean (24-72h)

1. Cornea opacity

A

0

0

0

0

0

0.00

  Cornea area

B

0

0

0

0

0

0.00

2 Iris

A

0

0

0

0

0

0.00

3 Conjunctivae redness

A

1

1

0

0

0

0.33

  Conjunctivae chemosis

B

1

1

0

0

0

0.33

  Conjunctivae discharge

C

1

0

0

0

0

0.00

 

Animal No. 505 RV

1h

24h

48h

72h

7d

Mean (24-72h)

1. Cornea opacity

A

0

0

0

0

0

0.00

  Cornea area

B

0

0

0

0

0

0.00

2 Iris

A

0

0

0

0

0

0.00

3 Conjunctivae redness

A

1

0

0

0

0

0.00

  Conjunctivae chemosis

B

2

0

0

0

0

0.00

  Conjunctivae discharge

C

1

0

0

0

0

0.00

 

Animal No. 507 LH

1h

24h

48h

72h

7d

Mean (24-72h)

1. Cornea opacity

A

0

0

0

0

0

0.00

  Cornea area

B

0

0

0

0

0

0.00

2 Iris

A

0

0

0

0

0

0.00

3 Conjunctivae redness

A

1

0

0

0

0

0.00

  Conjunctivae chemosis

B

1

0

0

0

0

0.00

  Conjunctivae discharge

C

1

0

0

0

0

0.00

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
The test results indicate a no eye irritation potential of the test substance Formamidopropyldimethylbetain 50 %ig to eyes and mucous membranes. All 3 animals showed slight ocular reactions 1 h after application of the test substance. 48 hours after application all three animals were without any sign of ocular irritation. The mean grades of reactions at 24, 48 and 72 h reading correspond to values classified as not irritant by the Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008.
Executive summary:

For labelling and classification purposes the test substance Formamidopropyldimethylbetain 50 %ig was tested regarding its irritation potential towards eyes and adjacent mucous membranes of experimental animals. The potential to cause damage to the conjunctivae, iris and cornea was assessed by single application of the test substance into the lower conjunctival sac of the eyes of two female and one male rabbit, strain New Zealand White, according to the OECD Guideline for the Testing of Chemicals 405 "Acute Eye Irritation/Corrosion". Due to animal welfare reasons an initial test using one animal was performed. 0.1 ml of the test substance was applied to the eye of one animal. As no corrosive or strong irritating effect was observed within one hour after application further two animals were treated in the same way. Ocular reactions were assessed 1, 24, 48, 72 hours and 7 days after application of the test substance. At 24 hours post application the eyes of all animals were further examined with fluorescein to look for cornea damage. Systemic toxic symptoms after application were not observed at any time during the study. Body weight development was positive and within normal ranges. All 3 animals showed slight ocular reaction (conjunctivae redness 1 score, conjunctivae chemosis 1 or 2 scores and conjunctivae discharge 1 score) 1 h after application of the test substance. In one animal a slight conjunctivae redness and chemosis was still observed 24 h after application. 24 hours later (48 h after application) all three animals were without any sign of ocular irritation. Cornea damage or iris irritation was not observed at any time during the study. The Primary Irritation Index for the test substance Formamidopropyldimethylbetain 50 %ig was calculated to be "8" from "110" total possible scores at 1 h post application. Under the conditions of this study the test substance Formamidopropyldimethylbetain 50 %ig was graded as non-irritating to eyes and mucous membranes according to the Primary Irritation Index.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for testing in the form of an aqueous solution containing about 40% active ingredient:

The physical form of the substance submitted for testing (aqueous solution with 40.1% active ingredient I + II + III + IV) is highest technically feasible active ingredient content concentration. It contains additional substances as water and sodium chloride. The concentration of commercially marketed products, now and in future, do not exceed this concentration. Detailed information is given in a separate document due to confidentiality reasons.

Skin irritation:

For labelling and classification purposes the test substance Formamidopropyldimethylbetain 50%ig , a yellowish clear liquid, was tested regarding its skin irritation potential. The potential to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of the test substance for four hours to the shorn skin of two female and one male rabbit, strain New Zealand White according to the DECO Guideline for the Testing of Chemicals, 404 "Acute Dermal Irritation/Corrosion". As neither corrosive nor strong irritating effects to the skin have been expected Formamidopropyldimethylbetain 50%ig was applied to all three animals for four hours at the same time. Dermal reactions at the treated skin sites were assessed 1 hour after removal of the test substance and approximately 24, 48, and 72 hours as well as 7 days later.

Systemic toxic symptoms after application were not observed at any time during the study. Body weight development of the animals was positive and within normal ranges. Only very slight erythema but no oedema was observed in one animal 1 h after removal of the

test substance. Especially between 24 and 72 hours no erythema and oedema were observed. The mean scores for erythema and oedema formation for the time period 24 h - 72 h were 0. The Primary Skin Irritation Index was calculated to be 0.

Eye irritation:

For labelling and classification purposes the test substance Formamidopropyldimethylbetain 50 %ig was tested regarding its irritation potential towards eyes and adjacent mucous membranes of experimental animals. The potential to cause damage to the conjunctivae, iris and cornea was assessed by single application of the test substance into the lower conjunctival sac of the eyes of two female and one male rabbit, strain New Zealand White, according to the GECD Guideline for the Testing of Chemicals 405 "Acute Eye Irritation/Corrosion". Due to animal welfare reasons an initial test using one animal was performed. 0.1 ml of the test substance was applied to the eye of one animal. As no corrosive or strong irritating effect was observed within one hour after application further two animals were treated in the same way. Ocular reactions were assessed 1, 24, 48, 72 hours and 7 days after application of the test substance. At 24 hours post application the eyes of all animals were further examined with fluorescein to look for cornea damage. Systemic toxic symptoms after application were not observed at any time during the study. Body weight development was positive and within normal ranges. All 3 animals showed slight ocular reaction (conjunctivae redness 1 score, conjunctivae chemosis 1 or 2 scores and conjunctivae discharge 1 score) 1 h after application of the test substance. In one animal a slight conjunctivae redness and chemosis was still observed 24 h after application. 24 hours later (48 h after application) all three animals were without any sign of ocular irritation. Cornea damage or iris irritation was not observed at any time during the study. The Primary Irritation Index for the test substance Formamidopropyldimethylbetain 50 %ig was calculated to be "8" from "110" total possible scores at 1 h post application.


Justification for selection of skin irritation / corrosion endpoint:
Data from a GLP compliant guideline study with reliability 1.

Justification for selection of eye irritation endpoint:
Data from a GLP compliant guideline study with reliability 1.

Justification for classification or non-classification

Justification for testing in the form of an aqueous solution containing about 40% active ingredient:

The physical form of the substance submitted for testing (aqueous solution with 40.1% active ingredient I + II + III + IV) is highest technically feasible active ingredient content concentration. It contains additional substances as water and sodium chloride. The concentration of commercially marketed products, now and in future, do not exceed this concentration. Detailed information is given in a separate document due to confidentiality reasons.

Under the conditions of the study described, the test substance Formamidopropyldimethylbetain 50%ig is non irritating and does not have to be classified for skin irritation according to Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008 and therefore labelling is not necessary.

Under the conditions of this study the test substance Formamidopropyldimethylbetain 50 %ig was graded as non-irritating to eyes and mucous membranes and thus has not to be classified for eye irritation according to Directive 67/548/EEC as well as GHS Regulation EC No 1272/2008 and therefore labelling is not necessary.