1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-C12-14 acyl derivs., hydroxides, inner salts

Endpoint summary

Description of key information

Studies of skin and eye irritation in vivo are available for the substance.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 May 1995 to 27 July 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

Betadet SHR
Lot number: 7049
pH 7.48
Appearance: viscous yellowish liquid
Storage: Room temperature protected from light

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Source: Accredited supplier
Weight on receipt: 2.0-2.1 kg
Age on receipt: 9-10 weeks
Acclimatisation period: 7 days
Weight on dosing: 2.3-2.4 kg
Housing: Individually in stainless steel cages with grille floor
Temperature: 18-22 degrees C
Humidity: 50-85%
Photoperiod: 12 hour light/dark cycle
Food: Standard rabbit diet UAR 112, ad libitum
Water: Compañia de Aguas de Sabadell, S. A., ad libitum

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL of test substance

Duration of treatment / exposure:

Four hours and then removed by washing

Observation period:

30-60 minutes and 24, 48 and 72 hours after the end of the exposure period.

Number of animals:

Three

Details on study design:

The animals were shaved approximately 24 hours before test substance administration using a razor leaving the back and sides from the scapula to the pelvis exposed. One square test zone of 6 cm2 was delimited on the shaved intact skin of one side of the animals. The test substance was applied in a single dose of 0.5 mL. The substance was placed on a 2.5 x 2.5 cm squares of surgical gauze and applied to the corresponding test area. The resulting patches were held close to the body using strips of adhesive tape. The animals were observed for a few moments and returned back to their cages. After 4 hours, the bandage and patches were removed and the remainder of the product eliminated with water.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slight erythema (grade 1) was observed in all animals approximately 60 minutes following removal of the patch; this persisted to 48 hours in one rabbit. No oedema was observed in any rabbit.

Irritation scores

	60 minutes	24 hours	48 hours	72 hours	Mean (24-72 hours)
Erythema	1,1,1	0,0,1	0,0,1	0,0,0	0.22
Oedema	0,0,0	0,0,0	0,0,0	0,0,0	0.00

Interpretation of results:

GHS criteria not met

Conclusions:

Betadet SHR was found to cause minimal transient skin irritation in this study and does not require classification as a skin irritant under CLP.

Executive summary:

A skin irritation study was conducted with Betadet SHR according to OECD Test Guideline 404. The test material was applied to the skin of 3 rabbits (0.5 mL) for 4 hours. The animals were observed for 7 days. The treatment sites were assessed after 1, 24, 48 and 72 hours. Very slight erythema (grade 1) was observed in all animals approximately 60 minutes following removal of the patch; this persisted to 48 hours in one rabbit.  No oedema was observed in any rabbit. Betadet SHR was found to cause minimal transient skin irritation in this study and does not require classification as a skin irritant under CLP.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 May 1995 to 28 July 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

Betadet SHR
Lot number: 7049
pH 7.48
Appearance: viscous yellowish liquid
Storage: Room temperature protected from light

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three New Zealand White male rabbits were used.
Weight on receipt: 2.0-2.2 kg
Age on receipt: approximately 9-10 weeks
Source: B and K Universal G.J., S.L.
Housing: Individually in stainless steel cages with a grill floor
Acclimatisation period: seven days
Weight at administration of test substance: 2.2-2.4 kg
Temperature: 18-22 degrees C
Humidity: 50-85%
Photoperiod: 12 hour dark/light cycle
Diet: Standard rabbit diet UAR 112, supplied by PANLAB, S. L., ad libitum
Water: Supplied by Compañia de Aguas de Sabadell, ad libitum

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

21 days after treatment

Duration of post- treatment incubation (in vitro):

.

Number of animals or in vitro replicates:

Three

Details on study design:

Following administration of the test substance, the eyelids were held closed for approximately 10 seconds. The behaviour of the animals was observed following instillation of the test substance. The animals were then returned to their cages.

The degree of eye irritation as evaluated for each rabbit at 1, 24, 48 and 72 hours after treatment. Additional observations were made on Days 7, 14 and 21 after treatment to check the reversibility of the reactions.

Observations were made after applying 2% aqueous sodium fluorescein to test the area and washing with physiological saline, with the exception of the 1 hour observations. Corneal alterations were made with the aid of a transilluminator with a cobalt blue filter.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.78

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.89

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks:

Reversible in two rabbits; findings persisted (grade 1) to 21 days in one rabbit

Eye irritation scores

	60 minutes	24 hours	48 hours	72 hours	Mean (24-72 hours)	7 days	14 days	21 days
Cornea	0,0,0	1,1,1	1,1,1	1,1,1	1.00	1,0,0	1,0,0	0,0,0
Iris	1,1,1	1,1,1	1,1,1	1,1,1	1.00	1,1,0	0,0,0	0,0,0
Erythema	3,2,2	3,3,3	3,3,3	2,3,2	2.78	1,2,1	0,1,1	0,0,0
Chemosis	2,3,2	2,3,2	1,2,2	1,2,2	1.89	1,1,1	1,0,1	0,0,1

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Instillation of the submission substance into the eyes of three rabbits caused marked eye irritation (corneal opacity, iridial infllammation, conjunctival erythema and chemosis). Irritation was reversible in two rabbits but persisted (grade 1 conjunctival chemosis only) in one rabbit at 21 days.

Executive summary:

The submission substance Betadet SHR was instilled (0.1 mL) into one eye of three New Zealand White rabbits in accordance with OECD TG 405. Ocular irritation was scored for up to 21 days after instillation, using the Draize scale. Signs of irritation included corneal opacity (Grade 1 in all animals, fully reversible by 21 days); iridial inflammation (Grade 1 in all animals, fully reversible by 14 days); conjunctival erythema (Grade 3 in all animals, fully reversible by Day 21); and conjunctival chemosis (Grade 2-3). Grade 1 conjunctival chemosis persisted in one rabbit at 21 days. The mean scores for corneal opacity (mean score ≥1), iridial inflammation (mean score ≥1) and conjunctival erythema (mean score ≥2) result in classification of the substance as a Category 2 eye irritant according to the CLP Regulation; however the lack of complete reversibility of conjunctival chemosis in one rabbit at 21 days triggers classification in Category 1.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A skin irritation study was conducted with the substance Betadet SHR according to OECD Test Guideline 404. The test material was applied to the skin of 3 rabbits (0.5 mL) for 4 hours. The animals were observed for 7 days. The treatment sites were assessed after 1, 24, 48 and 72 hours. Very slight erythema (grade 1) was observed in all animals approximately 60 minutes following removal of the patch; this persisted to 48 hours in one rabbit.  No oedema was observed in any rabbit. Betadet SHR was found to cause minimal transient skin irritation in this study and does not require classification as a skin irritant under CLP.

Eye irritation

The substance Betadet SHR was instilled (0.1 mL) into one eye of three New Zealand White rabbits in accordance with OECD TG 405. Ocular irritation was scored for up to 21 days after instillation, using the Draize scale. Signs of irritation included corneal opacity (Grade 1 in all animals, fully reversible by 21 days); iridial inflammation (Grade 1 in all animals, fully reversible by 14 days); conjunctival erythema (Grade 3 in all animals, fully reversible by Day 21); and conjunctival chemosis (Grade 2-3). Grade 1 conjunctival chemosis persisted in one rabbit at 21 days. The mean scores for corneal opacity (mean score ≥1), iridial inflammation (mean score ≥1) and conjunctival erythema (mean score ≥2) result in classification of the substance as a Category 2 eye irritant according to the CLP Regulation; however the lack of complete reversibility of conjunctival chemosis in one rabbit at 21 days triggers classification in Category 1.

Justification for classification or non-classification

Based on the results of the skin irritation study, classification is not required. Based on the results of the eye irritation study, classification for eye irritation in Category 1 is required.