1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-C18(unsaturated) acyl derivs., hydroxides, inner salts

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19/12/2016 - 24/03/2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The registration substance is a surfactant.

Test material

Test material information

Constituent 1

Reference substance name:

2-[dimethyl({3-[(10E,13E)-nonadeca-10,13-dienamido]propyl})azaniumyl]acetate

Molecular formula:

C25H47N2O3 (if R= C18:2)

IUPAC Name:

2-[dimethyl({3-[(10E,13E)-nonadeca-10,13-dienamido]propyl})azaniumyl]acetate

Test material form:

liquid

Specific details on test material used for the study:

The test material corresponded to the approximately 45% of the registration substance.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Geniron Biolabs Pvt. Ltd., No.93, Solur, Thally Road, Anekal, Bengaluru - 562106, India

- Age at study initiation: 15 to 17 weeks at intra-dermal induction
- Weight at study initiation: Males : 396.74 to 489.13 g, Females : 410.05 to 474.02 g

- Housing: Animals were housed individually in standard polysulfone cages (Size: approximately L 425 x B 266 x H 185 mm)
- Diet (e.g. ad libitum): Guinea pig feed manufactured by Pranav agro Industries Ltd, Pune, Maharashtra
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in ‘Aquaguard’ on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd., Mumbai 400 001, India
- Acclimation period: Start : 28 January 2017 End : 04 February 2017


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 48 to 67%
- Air changes (per hr): 12 to 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

IN-LIFE DATES: From: 28 January 2017 To: 01 March 2017

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

propylene glycol

Remarks:

The test material corresponds ca 45% of the registration substance in water

Concentration / amount:

Site 1: 0.1 mL of 50% Freund's Adjuvant in vehicle
Site 2: 0.1 mL of the test item in vehicle (25% w/v)
Site 3: 0.1 mL of 1:1 mixture of test item in vehicle (50% w/v) and Freund's Adjuvant in vehicle (50%)

Day(s)/duration:

On day 1

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5 mL of test item

Day(s)/duration:

On day 8

Adequacy of induction:

non-irritant substance, but skin pre-treated with 10% SDS

Challenge

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Day(s)/duration:

On day 22

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10 (5 male and 5 female) for control group
20 (10 male and 10 female) for treatment group

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole

Results and discussion

Positive control results:

Skin sensitization rate of 60% at 24h reading and 50% at 48h reading

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no effect

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no effect

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

TABLE 1.             Summaryof Skin Reactions

INDUCTION

 

Group	Observation	Concentration (%w/v)	Application site	INDUCTION PERIOD
				Time (hours)	Injection site	Skin reaction scores and response*
						Erythema	Edema
G1 (Vehicle Control)	Intradermal Induction	‘0’	Shoulder region	24	1 2 3	10**/10 0/10 10**/10	10Ψ/10 0/10 10Ψ/10
				48	1 2 3	10**/10 0/10 10**/10	10Ψ/10 0/10 10Ψ/10
	Topical application	‘0’	Shoulder region	1@	NA	0/10	0/10
				24@	NA	0/10	0/10
G2 (Treatment)	Intradermal Induction	25	Shoulder region	24	1 2 3	20**/20 20**/20 20**/20	20Ψ/20 19Ψ/20 20Ψ/20
				48	1 2 3	20**/20 16**/20 20**/20	20Ψ/20 0Ψ/20 20Ψ/20
	Topical application	0.5 mL of undiluted test item	Shoulder region	1@	NA	0/20	0/20
				24@	NA	0/20	0/20

@ : Observation post removal of test patch;                 NA: Not Applicable

*  : Represents the number of animals showing skin reactions out of the total number

      of animals in each group

** : Skin reaction score of 1-very slight erythema (barely perceptible)

Ψ : Skin reaction score of 1-very slight edema (barely perceptible)

0  : No erythema / No edema – correspondingly

 TABLE 1 contd. Summary of Skin Reactions

 

CHALLENGE

Group	Concentration (%w/v)	Application site	CHALLENGE PERIOD
			Time (hours)	Skin reaction Response	Sensitization rate (%)
G1 (Vehicle Control)	0.5 mL of undiluted test item	Left flank	24	0*/10	0
			48	0*/10	0
G2 (Treatment)	0.5 mL of undiluted test item	Left flank	24	0*/20	0
			48	0*/20	0

 

*

:

Represents the number of animals showing sensitisation response out of the total number of animals challenged in each group

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The skin sensitization property of the registration substance was treated according to the Guideline OECD 406. Based on the result obtained no classification is warranted.

Executive summary:

The skin sensitization property of the registration substance was investigated according to the Guideline OECD 406 in guinea pigs. The test substance corresponded to ca 45% of registration substance in water. For the intradermal and the topical induction the animals were treated at concentration of 25% and 100% of test material respectively, and for the challenge the animals were treated at concentration of 100 % of test material. None of the treated animals responded. The registration substance is not skin sensitizing.