N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-09-16 - 1996-12-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The protocol was designed and the study was conducted in general compliance with the OECD 404 and DOT, 49 CFR 173.137 and Principles of Good Laboratory Practice.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Dermal observations made in accordance with the method of Draize. Since severe irritation (erythema) and corrosion were observed after the 60-minutes exposure period no further testing was conducted and the study was terminated.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

EC Number:

221-220-5

EC Name:

N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Cas Number:

3033-62-3

Molecular formula:

C8H20N2O

IUPAC Name:

{2-[2-(dimethylamino)ethoxy]ethyl}dimethylamine

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): A-99
- Physical state: Clear, colorless liquid
- Analytical purity: 99,8% (gas chromatographic analysis)
- Purity test date: 1996-10-03
- Stability under test conditions: Under the conditions employed during the testing of this material, the Sponsor has indicated that the material is stable, provided the sample is not contaminated, is properly sealed, and stored under normal conditions as dictated by good manufacturing practice
- Storage condition of test material: Original container at room temperature
- Lot/batch No.: T208 091296

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc.
- Age at study initiation: Young adult
- Weight at study initiation: 5079g
- Housing: Individual suspended wire-mesh cages. The animal was maintained by the animal husbandry staff of WIL Research Laboratories, Inc., in accordance with Standard Operating Procedures
- Diet (e.g. ad libitum): PMI Feeds, Inc.© Certified Rabbit LabDiet© 5322 ad libitum
- Water (e.g. ad libitum): municipal water provided ad libitum
- Acclimation period: for a minimum of five days prior to initiation of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): animal room 68.1°F
- Humidity (%): animal room 53,6%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): animal room 12 hours leight/12 hours dark

IN-LIFE DATES: From: To: September 17, 1996

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/site

Duration of treatment / exposure:

One screen animal received two separate semi-occluded applications of the test material for 3- and 60- minute exposure periods

Observation period:

The 3- and 60-minute dose sites were observed immediately after bandage removal. In addition, the 3-minute application was evaluated 60 minutes after patch removal
Mortality: the rabbit was observed on the day of dosing

Number of animals:

one female

Details on study design:

TEST SITE
- Area of exposure: approximately 1" x 1"
- % coverage: no data
- Type of wrap if used: a two-ply gauze patch secured with Dermiform®

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with disposable paper towels moistened with tepid tap water
- Time after start of exposure: at the end of each exposure

SCORING SYSTEM:
The 3- and the 60-minutes doses sites were observed for the presence or absence of corrosion. Dermal irritation was also evaluated and graded in accordance with the method of Draize:

Evaluation of Dermal Reactions (OECD Guideline 404, Adopted July 17, 1992)

Value
Erythema and Eschar Formation

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


4 Total possible erythema score

Edema Formation

0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well defined by definite raising)
3 Moderate edema (raised approximately 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

4 Total possible erythema score
8 Total possible Primary Irritation Score



Descriptive Ratings
Mean Primary Dermal Irritation Index

Range of Values Descriptive Rating

0 Nonirritating
0.1 - 2.0 Slightly Irritating
2.1 - 5.0 Moderately Irritating
5.1 - 8.0 Severely Irritating

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 3-minute exposure; dose site evaluated immediately following unwrap

Remarks on result:

other: Corrosion: not evident

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 3-minute exposure; dose site evaluated immediately following unwrap

Score:

3

Max. score:

4

Reversibility:

other: Not after 60 minutes

Remarks on result:

other: moderate to severe erythema

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 3-minute exposure; dose site evaluated immediately following unwrap

Score:

0

Max. score:

4

Remarks on result:

other: no edema

Results 4

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 3-minute exposure; dose site evaluated approximately 60 minutes following unwrap

Remarks on result:

other: corrosion: not evident

Results 5

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 3-minute exposure; dose site evaluated approximately 60 minutes following unwrap

Score:

4

Max. score:

4

Reversibility:

no data

Remarks on result:

other: severe erythema (beet redness) to eschar formation preventing grading of erythema; fissuring

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 3-minute exposure; dose site evaluated approximately 60 minutes following unwrap

Score:

1

Max. score:

4

Reversibility:

no data

Remarks on result:

other: very slight edema (barely perceptible)

Results 7

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 60-minutes exposure; dose site evaluated immediately following unwrap

Reversibility:

no data

Remarks on result:

other: corrosion: present

Results 8

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 60-minutes exposure; dose site evaluated immediately following unwrap

Score:

4

Max. score:

4

Reversibility:

no data

Remarks on result:

other: severe erythema (beet redness) to eschar formation preventing grading of erythema; blanching

Results 9

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 60-minutes exposure; dose site evaluated immediately following unwrap

Score:

0

Max. score:

4

Remarks on result:

other: no edema

Results 10

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: other timepoints used due to nature of substance

Results 11

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: other timepoints used due to nature of substance

Other effects:

The animal did not die during the study. There was no remarkable body weight change on the day of dosing

Applicant's summary and conclusion

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The 3 minute dose site had moderate erythema immediately following unwrap. Severe erythema, very slight edema and fissuring were noted one hour later on the 3-minute exposure site. Corrosion, severe erythema and blanching were noted following the 60-minute exposure. There were no other dermal findings. Due to the severe irritation and corrosion noted on the single animal screen, no further testing on additional animals was conducted and the study was immediately terminated.

Executive summary:

The primary dermal irritation potential of A-99 was evaluated in general compliance with OECD 404 and GLP. A single screen animal (New Zealand White rabbit) was dosed to evaluate the irritative/corrosive potential of the test material for three and 60 minutes. The study consisted of two sequential single 0.5-milliliter doses of the test material that were applied to the clipped, intact skin of one rabbit under semi-occlusive dressings.

Moderate erythema was observed on the 3-minute site immediately following unwrap. Approximately one hour following bandage removal, the 3-minute site had severe erythema, very slight edema and fissuring. There was no evidence of corrosion following the 3-minute exposure.

The 60-minute site had corrosion, severe erythema and blanching. Since severe irritation (erythema) and corrosion were observed after the 60-minutes exposure period no further testing was conducted and the study was terminated. Based on the results, a four-hour exposure was not evaluated.