3-(N-p-methoxy cinnamidopropyl-N,N-dimethyl ammonium)-2-hydroxypropane-1-sulphonate

Endpoint summary

Description of key information

Skin Irritation/Corrosion

Two studies to assess skin irritation have been carried out. The key study was carried out to determine the primary skin irritation potential of "Galaxy Sunbetaine" in rabbits following the Gaitonde Committee protocol.

Theremaining study was carried out to determine the Cumulative Dermal Irritation of "Galaxy-Sunbetaine-MM-30" in rabits, following the IS 1324: 1992 Protocol.

Both studies were assigned a reliability rating of 2.

An additional two studies were included as supporting information only as these were assigned a reliability ratig of 4. These studies were as follows:

A study was performed as described in Galaxy Surfactants Protocol 01 and was designed to assess the skin irritancy of seven sunscreen products and a marketed comparator product after repeated application to the skin of healthy volunteer subjects. The study design was that of a repeat insult patch test consisting of 3 applications over a 7 day period. This technique maximises the cutaneous stimulus from a topical preparation.

A study on Galaxy-SUnbeat-MM-30 for Photoirritation and photo allergy tests in albino guinea pigs.

The substance was considered to be non-irritant in all studies.

Eye Irritation

The objective of the study was reported here was to determine the mucous membrane irritation potential of "Galaxy Sunbetaine" in rabbits following the Gaitonde Committee Protocol.

The test material "Galaxy Sunbetaine" caused no irritation to the eye in rabbits.

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:

supporting study

Study period:

27 August to 17 September 2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: IS 13424: 1992 Specifications

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

Applied daily for 5 days a week for three weeks.

Observation period:

24 hours after each exposure and then daily for a total of 16 readings.

Number of animals:

Six rabits, 3 male, 3 female

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 - 16 days

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin reactions noted in any animal at any timepoint.

Interpretation of results:

GHS criteria not met

Conclusions:

The cumulative irritation index of the test material, in albino rabbits by the dermal route was found to be 0.00. The test material is termed as non-irritant.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 August 2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.

Qualifier:

according to guideline

Guideline:

other: Gaitonde Committee Annexure III

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species: Albino rabbits
Source: National Toxicology Centre
Weight range: 1.8 to 2.0 kg
Age: 6 to 9 weeks
Sex: male and female
Number: 3 per sex
Housing: The animals were housed singly.
Diet: Pelleted feed
Water: Community tap water ad libitum
Room temperature: 19 - 22°C
Relative humidity: 35% - 75%
Light cycle: 12 hours light, 12 hours dark.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

Test substance used directly in 0.5 ml quantity.

Duration of treatment / exposure:

Once the test material was applied the animals were housed singly with a plastic collar around their neck to avoid ingestion of test material. After 24 hours any unabsorbed test material was removed.

Observation period:

Each site of application was carefully examined, observed and the reaction evaluated according to Draize's method at 24, 48 and 72 hours post application.

Number of animals:

Six rabbits, three per sex were used for this study.

Details on study design:

The hair of the back on both sides of the vertebral column was removed with the help of electric clippers, one day before the treatment. The test material in the amount of 0.50 ml was applied to the intact and abraded skin sites of each test animal. Care was taken to note that the abrasions penetrate the Stratum correum but not the dermis. A gauze patch was secured over each treated area by means of an adhesive tape.

The animals were house singly with a plastic collar around their neck for 24 hours to avoid the ingestion of the test material. The patch and the unabsorbed test material were removed after 24 hours.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: test substance was non-irritant

Irritation parameter:

erythema score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No eryhema or odema observed in an animal at any timepoint.
Primary skin irritation score: 0.00

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance caused no irritation to thh skin in rabbits.

Executive summary:

The test material was applied in the amount of 0.5 ml to the shaven back skin, both intact and abraded skin sites, of six rabbits (three per sex). Each site of application was carefully observed and the reaction evaluated according to Draize's method at 24, 48 and 72 hours post application.

The test material caused no irritation to the skin in rabbits till the end of the observation period.

The primary skin irritation index was 0.00.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

31 March 2003 to 07 April 2003

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study is well conducted but its design not sufficient to cover the endpoint

Qualifier:

according to guideline

Guideline:

other: Galaxy Surfactants Protocol 01

Qualifier:

according to guideline

Guideline:

other: ICH Harmonised Tripartite Guidelines for Good Clinical Practice.

Qualifier:

according to guideline

Guideline:

other: The Guidelines for Medical Experiments in no-patient human volunteers,

GLP compliance:

no

Species:

human

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

Day 1: Material applied under occlusion.
Day 3: Patch removed for a period of 10 minutes then re-applied.
Day 5: Patch removed for a period of 10 minutes then re-applied.
Day 8: Patch removed for a period of 10 minutes and sites assessed. Patch not re-applied.

Observation period:

Day 3, day 5 and day 8.

Number of animals:

25 subjects.
18 female and seven male

Irritation parameter:

overall irritation score

Remarks:

Sunscreen C

Basis:

mean

Time point:

other: Day 3, day 5 and day 8

Score:

0

Irritation parameter:

overall irritation score

Remarks:

Sunscreen D

Basis:

mean

Time point:

other: Day 3, day 5 and day 8

Score:

0

Sunscreen C:

There were no grade 1 or grade 2 of higher reactions recorded with Sunscreen C at any time during the course of the study.

Sunscreen D:

There were no grade 1 or grade 2 of higher reactions recorded with Sunscreen D at any time during the course of the study.

Interpretation of results:

not irritating

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

09 October 2001 to 03 November 2001

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study is well conducted but its design not sufficient to cover the endpoint

Qualifier:

according to guideline

Guideline:

other: IS 13424, 1992.

Species:

guinea pig

Strain:

Hartley

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

water

Remarks:

50%

Controls:

yes

Duration of treatment / exposure:

To each guinea pig in the control and test group, 0.1 ml of 50% solution of the test substance was applied on one side of the spine. Solution was applied as spcified above. Similarly, 0.1 ml of 5% solution of the positive control was applied on the other side.
Thirty minutes after application each animal in the test group was irradiated with non-erythrogenic radiation from a UV lamp (100 watts) from a distance of about 25 cm for 30 minutes.The animals in the control group did not receive any irradiation.

Observation period:

The treated sites were examined at 4, 24, 48 and 72 hours after irradiation for dermal reactions viz., erythema, oedema, spots and scaling. The dermal reactions are graded using the following scale.

0: Normal
2: Faint trace of erythema
4: Slight erythema
6: Definite erythema
8: well developed erythema

Number of animals:

12 male
6 used in the control group
6 used in the test group

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 4, 24, 48 and 72 hours

Score:

0

Interpretation of results:

not irritating

Conclusions:

Treatment of guinea pigs with the substance followed by UV irradiation did not produce any evidence of skin irritation. Following the scoring and evaluation of results, the test substance was considered to be a non-photo irritant.

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:

30th July 2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.

Qualifier:

according to guideline

Guideline:

other: Gaitonde Committee Guidelines

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test Animal:

Species: Albino rabbits
Strain: New Zealand White
Source: National Toxicology Centre
Weight range: 1.7 to 2.1 kg
Age: 6 to 9 weeks
Sex: male and female
Number: 3 per sex
Housing: The animals were housed singly
Diet: Pelleted feed supplied by Nav Maharasthra Chakan Oil Mills Ltd., Pune
Water: Community tap water ad libitum
Room temperature: 19 to 22 degrees Celsius
Relative humidity: 35 to 75%
Lighty cycle: 12 hours day 12 hours dark

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

The test material in the amount of 0.10 ml was placed directly into animals eye. The other eye was untreated as a control.

Duration of treatment / exposure:

Once the test material was applied the eyelid was held down for two seconds to prevent loss of test substance.

Observation period (in vivo):

Each eye was carefully examined, observed at 24, 48 and 72 hours and the observations extended to determine the reversibility or irreversibility.

Number of animals or in vitro replicates:

Six rabbits, three per sex were used for this study.

Details on study design:

Six rabbits, three per sex, were used for this study. The test material in the amount of 0.10 ml was placed in the conjuctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for approximately two seconds in order to prevent the loss of the test material. The other eye remained untreated and served as a control. The animals were housed singly.

Clinical Observations:
Each eye was carefully examined, observed at 24, 48 and 72 hours and the observations extended to deterimine the reversibility or irreversibility. Any redness, chemosis and discharge was recorded.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks:

Not applicable as overall irritation score = 0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Irritaion score = 0

Other effects:

None observed

A summary of the individiual irritant response following application of "Galaxy Sunbetaine"

Rabbit No.	Sex	Cornea	Iris	Conjuctivae
				Redness	Chemosis	Discharge
1	M	0	0	0	0	0
2	M	0	0	0	0	0
3	M	0	0	0	0	0
4	F	0	0	0	0	0
5	F	0	0	0	0	0
6	F	0	0	0	0	0

 

Hours                         24                   48              72

SCORE                      0                    0                 0

Grand Total: 0.00

Where 0 = no reaction

Irritation Score: 0.00

Interpretation of results:

GHS criteria not met

Conclusions:

The test material "Galaxy Sunbetaine" caused no irritation to the eye in rabbits.

The test material is termed as non-irritant.

Executive summary:

The objective of the study was reported here was to determine the mucous membrane irritation potential of "Galaxy Sunbetaine" in rabbits following the Gaitonde Committee Protocol.

The test material in the amount of 0.10 ml was instilled in the conjuctival sac of one eye of each animal. Each eye was carefully observed and the reaction evaluated at 24, 48 and 72 hours post instillation.

The test material caused no irritation to the eye in rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of irritation studies carried out on both the skin and eye, the test material is not considered to be classified as an irritant for either skin or eyes.