1-Octanamine, N,N-dimethyl-, N-oxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

between 28th November 2007 and 25th December 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Schedule 1 (Good Laboratory Practice Regulations 1999 (SI 1999/3106 as amended by 2004/0994))

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethyl-N-octylhydroxylamine

EC Number:

607-854-9

Cas Number:

2605-78-9

Molecular formula:

CH3(CH2)7N(CH3)2O

IUPAC Name:

N,N-dimethyl-N-octylhydroxylamine

impurity 1

Reference substance name:

Dimethyl(octyl)amine

EC Number:

230-939-3

EC Name:

Dimethyl(octyl)amine

Cas Number:

7378-99-6

Molecular formula:

C10H23N

IUPAC Name:

N,N-dimethyloctan-1-amine

impurity 2

Reference substance name:

Methanol

EC Number:

200-659-6

EC Name:

Methanol

Cas Number:

67-56-1

Molecular formula:

CH4O

IUPAC Name:

Methanol

impurity 3

Test material form:

liquid: viscous

Specific details on test material used for the study:

- Analytical purity: 82.3%
- Purity test date: Not available
- Lot/batch No.: GN-8
- Expiration date of the lot/batch: Not available
- Appearance: Amber coloured, extremely viscous liquid
- Storage: In the dark at room temperature
- Additional information on test material used for the study: It was attempted to purify the substance to a purity of >80% by using an alternative synthetic route, as opposed to the usual commercial route of synthesis which results in a purity of the substance of approximately 40% in water. This alternative synthetic route generated the substance at 82.3% purity, however it also generated an impurity (methanol at 4.0%) which is not present in the commercial substance. Based on the classification and labelling of methanol, it is considered that this additional impurity would not have an influence on any of the endpoints discussed in this dossier other than the acute oral toxicity study. Therefore all studies (including the one covering this endpoint) contained in this dossier (other than the acute oral toxicity study) were conducted on the 82.3% pure substance containing the 4.0% methanol impurity. The acute oral toxicity study has been conducted on the commercially generated substance at a purity of approximately 40% in water.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Uk Limited, Bicester, Oxan UK
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.0-3.5 kg
- Housing: Individually housed in suspended cages.
- Diet: Ad libitum, Certified rabbit diet (both water and food were considered not to contain any contaminent of a level which would affect the results of the test.)
- Water: Ad libitum, free access to mains water
- Acclimation period: 5 days
- pH: pH determined at 6.9-7.0

ENVIRONMENTAL CONDITIONS
- Temperature : 17-23°C
- Humidity : 30-70%
- Air changes: 15 changes per hour
- Photoperiod: 12 hours continous light and 12 hours continual dark.

Animals were provided with environmental enrichment items which did not contain any contaminents to a level that would affect the results of the test.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5ml of test material was applied to the three test sites.

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours.

Observation period:

3 days (extended to 7 and 14 days to assess reversibility)

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Flank and Dorsal
- % coverage: 30%
- Type of wrap if used: semiocclusive elasticated corset wrap


REMOVAL OF TEST SUBSTANCE
- Washing : Test material removed from test area via gentle swabbing of the test areas with cotton wool soaked in distilled water.
- Time after start of exposure: 3 minutes, 1 hour and 4 hours.


SCORING SYSTEM:

Evaluation of Skin Reactions:

Erythema and Eschar Formation

No erythema = 0
Very slight erythema (barely perceptible) = 1
Well defined erythema = 2
Moderate to severe erythema =3
Severe erythema (beef redness to eschar formation preventing grading of erythema = 4

Oedema Formation

No oedema = 0
Very slight oedema (barely perceptible) = 1
Slight oedema (edged of area well-defined by definite raising) = 2
Moderate oedema (raised approximately 1 millimetre) = 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) = 4

Any other skin reactions, if present, were also recorded.

Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

1

Reversibility:

fully reversible

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

1

Reversibility:

fully reversible

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Max. score:

1

Reversibility:

fully reversible

Results 7

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hour

Score:

2.7

Reversibility:

not fully reversible within: 14 days

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

The primary irritation index of the test material was determined to be 2.7 and was therefore classified as a MODERATE IRRITANT. However it was discovered not to be corrosive.

Other effects:

Loss of elasticity was noted at the treated skin site at the 72 hour observation and slight desquamation was noted at the 7 day observation.

Any other information on results incl. tables

Skin Reaction Observation Time Individual Scores – Rabbit Number and Sex 66826 Male 3 Minute Exposure 1 Hour Exposure Erythema/Eschar Formation 1 Hour 24 Hours 48 Hours 72 Hours 7 Days 0 0 0 0 0 0 2 2 2 Le 0 D Oedema Foundation 1 Hour 24 Hours 48 Hours 72 Hours 7 Days 0 0 0 0 0 0 1 1 1 0 D = Slight desquamation Le = Loss of skin elasticity Skin Reaction Observation Time Individual Scores – Rabbit Number and Sex Total 66826 Male 66898 Male 66899 Male Erythema/Eschar Formation 1 Hour 24 Hours 48 Hours 72 Hours 7 days 14 Days 0 2 2 2 Lef 0 D - 0 2 2 2Le 0Cf 0 0 1 2 2 Le 0 Cf 0D (0) 5 (6) 6 (0) (0) Oedema Formation 1 Hour 24 Hours 48 Hours 72 Hours 7 days 14 Days 0 1 1 1 0 - 0 1 1 1 0 0 0 0 1 1 0 0 (0) 2 (3) 3 (0) (0) Sum of 24 and 72-hour readings (S) : 16 Primary Irritation Index (S/6) : 16/6 = 2.7 Classification : Moderate Irritant ( ) = Total values not used for calculation of primary irritation index - = Observation not required Cf = Crust formation D = Slight desquamation Le = Loss of skin elasticity Lf = Loss of skin flexibility On day 14 one treatment site had recovered.

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: Draize classification scheme

Conclusions:

The test material was determined to be a Moderate Irritant to Rabbit skin. With a Primary irritation index of 2.7

Executive summary:

Introduction:       The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

-       OECD Guidelines for the testing of Chemicals No 404 " Acute Dermal Irritation/Corrosion" (adopted 24 April 2002)

-       Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC

Results:      3 -minute and 1 -hour semi occluded applications of the test material to the intact of one rabbit produced no corrosive effects.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well defined erythema and very slight oedema. Crust formation, slight desquamation and loss of skin flexibility and/or elasticity were also noted. One treated skin site apperaed normal at the 14 -day observation. No corrosive effects were noted.

Conclusion:      The test material produced a primary irritation index of 2.7 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.