Pyridinium, 2,6-dihydroxy-4-methyl-1-[3-(methylamino)propyl]-, sulfate (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2,6-dihydroxy-4-methyl-1-[3-(methylazaniumyl)propyl]pyridin-1-ium sulfate

EC Number:

931-673-7

Cas Number:

1333469-72-9

Molecular formula:

C10 H18 N2 O6 S1

IUPAC Name:

2,6-dihydroxy-4-methyl-1-[3-(methylazaniumyl)propyl]pyridin-1-ium sulfate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.59-2.66 kg
- Housing: individual suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21ºC
- Humidity (%): 56-67%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 ml of the test material was introduced under a 2.5*2.5 cm gauze patch and placed in position on the shorn skin. Patch secured in position with a strip of surgical adhesive tape.

Duration of treatment / exposure:

4 hours

Observation period:

1h, 24, 48 and 72 h later after removal of the patches.

Number of animals:

3

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

male

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 7d

Results 2

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 7d

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7d

Results 4

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

male

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

female

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 7d

Results 6

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 7d

Irritant / corrosive response data:

The individual scores for erythema/eschar and oedema are given in table 1. Mean values required for EEC labelling regulations are given in table 2.

Very slight erythema was noted at all treated skin sites one hour after patch removal with very slight to well defined erythema at the 24-hour observation. Very slight erythema was noted at one treated skin site at the 48 and 72-hour observation.
Very slight to slight oedema was noted at all treated skin sites one hour after patch removal. Slight oedema persisted at one treated skin site at the 24 and 48-hour observations with sligth oedema at the 72-hour observation.
All treated skin sites appeared normal seven days after treatement.

Any other information on results incl. tables

HYMAP: Acute Dermal Irritation test in the rabbit

Table 1: Individual skin reactions

 

Skin reaction	Observation time	Individual scores - Rabbit Number and Sex (bodyweight Kg)			Total
		195 Male (2.66)	199 Female (2.59)	203 Male (2.60)
Erythema/Eschar formation	1 hour	1	1	1	(3)
	24 hours	2	1	1	4
	48 hours	1	0	0	(1)
	72 hours	1	0	0	1
	7 days	0	0	0	(0)
Oedema formation	1 hour	2	1	1	(4)
	24 hours	2	0	0	2
	48 hours	2	0	0	(2)
	72 hours	1	0	0	1
	7 days	0	0	0	(0)
Sum of 24 and 72-hour reading (S)		8
Primary Irritation Index (S/6)		8/6=1.3
Classification		Mild irritant

 

( ) = Total values not used for calculation of primary irritation index

 

 

HYMAP: Acute Dermal Irritation test in the rabbit

Table 2: Individual daily and individual mean scores for dermal irritation following 4-hour exposure required for EEC labelling regulations

 

Skin reaction	Reading (Hours)	Individual scores - Rabbit Number and Sex (bodyweight Kg)
		195 Male (2.66)	199 Female (2.59)	203 Male (2.60)
Erythema/Eschar formation	24	2	1	1
	48	1	0	0
	72	1	0	0
Total		4	1	1
Mean score		1.3	0.3	0.3
Oedema formation	24	2	0	0
	48	2	0	0
	72	1	0	0
Total		5	0	0
Mean score		1.7	0.0	0.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The results of the available studies were evaluated according to the criteria of CLP Regulation 1272/2008. None of the 3 animals used get a mean score ≥ 2.3 and triggered classification according to CLP Regulation.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for testing of chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC (Which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under annex VI of council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 91/325/EEC).

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to sligth oedema. All treated skin sites appeared normal seven days after the treatment.

The test material produced a primary irritation index of 1.3 and was classified as mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test material did not produce positive criteria in any rabbit according to the EEC labelling regulations and was classified as non-irritant to rabbit skin. No symbol and risk phrase are therefore required.