Quaternary ammonium compounds, C12-14-alkyl(hydroxyethyl)dimethyl, chlorides

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 October 1889 - 25 November 1989

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[See concordance under Part B.1. of the CSR]

IUPAC Name:

[See concordance under Part B.1. of the CSR]

Details on test material:

- Name of test material (as cited in study report): HOE S 3855

- Physical state: colourless liquid
- Date of arrival: 14 September 1989
- Storage conditions: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals and Animal Husbandry
Six New Zealand White rabbits were supplied by David Percival Ltd., Moston, Sandbach, Cheshire, U.K. At the start of the study the animals weighed 2.04 to 2.49 kg and were approximately twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study written on the inner surface of the ear and on a cage label using a black indelible marker-pen.
The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K.) was allowed throughout the study.
The animal room was maintained at a temperature of 15 - 22°C and relative humidity of 48 - 65%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

For the purpose of this study the test material was used as supplied. A quantity of 0.5 ml was applied.

Duration of treatment / exposure:

4 hours (initial study)
and
3 minutes (additional study)

Observation period:

1h, 24h, 48h and72 hours, 7days and 14 days

Number of animals:

3 (initial study) and 3 (additional study)

Details on study design:

a) Initial Study 4-hour Exposure
Approximately twenty-four hours prior to the commencement of the test, each of a group of three rabbits was prepared by closely clipping the fur from the dorsal/flank areas using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 ml of the test material was introduced under a 2.5 mm x 2.5 mm gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 mm x 4.0 mm), To prevent the animals from interfering with the patches the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether.
Approximately one hour following removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale i.e. Draize J.H. (1959) Association of Food arid Drug Officials of the United States, Austin, Texas, “The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics”.
b) Additional study 3-minute exposure:
In addition to the initialexperiment a 3-minute semi-ocluded application was performed on another group of three animals to assess the appropriate risk phrase. The procedure used were identical to those used for the initial study with exception of the exposure period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 72h

Score:

2

Max. score:

2

Remarks on result:

other: individual skin reaction following 4-hour exposure

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 72h

Score:

2

Max. score:

2

Remarks on result:

other: individual skin reaction following 4-hour exposure

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 72h

Score:

2

Max. score:

2

Remarks on result:

other: individual skin reaction following 4-hour exposure

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 72h

Score:

0.67

Max. score:

1

Remarks on result:

other: individual skin reaction following 4-hour exposure

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 72h

Score:

1

Max. score:

1

Remarks on result:

other: individual skin reaction following 4-hour exposure

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 72h

Score:

1.67

Max. score:

2

Remarks on result:

other: individual skin reaction following 4-hour exposure

Results 7

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 72h

Score:

0

Max. score:

0

Remarks on result:

other: individual skin reaction following 3-minute exposure

Results 8

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 72h

Score:

0

Max. score:

0

Remarks on result:

other: individual skin reaction following 3-minute exposure

Results 9

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 72h

Score:

0

Max. score:

0

Remarks on result:

other: individual skin reaction following 3-minute exposure

Results 10

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 72h

Score:

0

Max. score:

0

Remarks on result:

other: individual skin reaction following 3-minute exposure

Results 11

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 72h

Score:

0

Max. score:

0

Remarks on result:

other: individual skin reaction following 3-minute exposure

Results 12

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 72h

Score:

0

Max. score:

0

Remarks on result:

other: individual skin reaction following 3-minute exposure

Irritant / corrosive response data:

 
 
 
 
 
 

Time after removal of the patch
30 - 60 min
24 h
48 h
72 h
7 d
Animal no.
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
Erythema and eschar formation
1
2
2
2
2
3
3
3
3
2
3
3
0
0
0
Oedema formation
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
Surface of the skin - dry, brittle
 
 
 
 
 
 
 
 
 
 
 
 
x
x
 
Separation of fine scales
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Any other information on results incl. tables

RESULTS

a) 4-hour Exposure Period

Very slight or well-defined erythema and very slight oedema was noted at all treated skin sites one hour after patch removal. Well-defined erythema and very slight or slight oedema persisted at subsequent 24, 48 and 72-hour observations. The erythema extended beyond the treatment site. Additional adverse dermal reactions noted at one treated skin site were light-brown discolouration of the epidermis and loss of skin elasticity. The dermal reactions noted on days 7 and/or 14 included, hard light-brown coloured scabs, hyperkeratinisation, dried blood, loss of skin elasticity, glossy skin, reduced fur re-growth and very slight oedema. These adverse dermal reactions precluded assessment of the erythema and oedema at two of the treated skin sites. Scar tissue was noted at one treated skin site on day 14; this was considered to be indicative of corrosion.

The test material produced corrosive effects in 1/3 rabbits and was classified as CORROSIVE to rabbit skin. The symbol “C” is therefore required.

An additional group of three rabbits was exposed to the test material for a period of three minutes to assign the appropriate risk phrase.

b) 3-minute Exposure Period

Very slight erythema was confined to two treated skin sites one hour after patch removal. No other adverse skin reactions were noted.

The risk phrase R 34 “CAUSES BURNS” is therefore required.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CONCLUS ION
The test material, HOE S 3855, was found to be corrosive to rabbit skin according to EEC labelling regulations and requires the symbol “C” and risk phrase R 34 „CAUSES BURNS”.

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”.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema, extending beyond the treatment site, very slight or slight oedema. Additional dermal reactions noted 7 or 14 days after treatment included hard, light brown coloured scabs, hyperkeratinisation, dried blood, loss of skin elasticity, glossy skin and reduced fur re-growth. Scar tissue indicative of corrosion was also noted at one treated skin site on day 14 day.

An additional 3-minute semi-occluded application was performed on another group of three animals to assess the appropriate risk phrase.Very slight erythema was confined to two treated skin sites one hour after patch removal. No other adverse skin reactions were noted.

The test material was regarded as corrosive according to EEC labelling regulations. The symbol “C” and risk phrase R 34 “CAUSES BURNS” are therefore required.