Registration Dossier

Administrative data

Description of key information

Available information indicates that all AAI subsatnces are corrosive to skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 Mar 2007 - 27 Mar 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Grimaud frères selection S.A.S., La Corbière, Roussay, France
- Age at study initiation: 2 to 4 months
- Weight at study initiation: mean body weight ± standard deviation of 2.9 ± 0.2 kg.
- Housing: individually in Pajon cages (50 cm x 57 cm x 75 cm). Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 13 Mar 2007 To: 27 Mar 2007
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
First animal: 3 minutes, 1 hr, 4 hr
Second animal: 4 hr
Observation period:
Following guidelines: The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. Further observations depending effects up to 14 days.
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: test substance on gauze pad, held in skin contact by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no: After removal of the dressing, any residual test item was wiped off by means of a moistened cotton pad.

SCORING SYSTEM: Standard for eryjthema and oedema:
Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

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

Any other lesions were noted.
Irritation parameter:
erythema score
Remarks:
4-hr exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Dry skin and slight erytheme at day 15.
Irritation parameter:
edema score
Remarks:
4-hr exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 9 days
Remarks on result:
other: slight reversible oedema
Irritation parameter:
erythema score
Remarks:
4-hr exposure
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
severe burn day 2
Remarks on result:
other: sacrificed for ethical reasons
Irritation parameter:
edema score
Remarks:
4-hr exposure
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
severe burn day 2
Remarks on result:
other:
Remarks:
sacrificed for ethical reasons
Irritation parameter:
other: not possible, animal sacificed
Basis:
animal #2
Time point:
24/48/72 h
Reversibility:
not reversible
Remarks:
severe burn day 2
Remarks on result:
other: sacrificed for ethical reasons
Irritant / corrosive response data:
First animal:
3-min: moderate to severe erythema up to day 8 and very slight erythema still at day 15. Slight oedema was visible from day 2 until day 8, and was completely resolved by day 10.
1-hour: moderate to severe erythema up to day 11 and very slight erythema still at day 15. Slight oedema was visible from day 2 until day 13, and was completely resolved on day 14.
4-hours: moderate to severe erythema up to day 13 and very slight erythema still at day 15. Slight oedema was visible from day 2 until day 13, and was completely resolved on day 14.
With all exposure durations, a brownish area at the application site was noted from day 2 until day 10. Crusts and dryness of the skin were noted between day 5 and day 15 (end of the observation period).
Second animal:
4-hours: a moderate then a severe erythema (grade 3 then 4) was noted on days 1 and 2, respectively. A severe edema (grade 4) was noted on days 1 and 2.
A red-brown area was noted on day 2. Cutaneous reactions observed in the second animal were similar to a severe burn, and animal was sacrificed.

 

Dermal irritation

Scores

Mean irritation score

 

1h

24h

48h

72h

Rabbit #

day1

day2

day3

day4

3-minutes

 

1

erythema

1

3

3

3

3.0

 

Oedema

0

2

2

2

2.0

 

Other

*

ZB

ZB

ZB

 

1-hour

 

 

 

 

 

 

1

erythema

1

3

3

3

3.0

 

Oedema

0

2

2

2

2.0

 

Other

*

ZB

ZB

ZB

 

4-hour

 

 

 

 

 

 

1

erythema

2

3

3

3

3.0

 

Oedema

1

2

2

2

2.0

 

Other

*

ZB

ZB

ZB

 

2

erythema

3

4

-

-

(2)

 

Oedema

4

4

-

-

(2)

 

Other

*

ZBR

 

 

 

 

 

Dermal irritation

Scores

Rabbit #

D5

D6

D7

D8

D9

D10

D11

D12

D13

D14

D15

3-minutes

 

 

 

 

 

 

 

 

 

 

 

 

1

Erythema

3

3

3

3

2

2

2

1

1

1

1

 

Edema

2

2

2

2

1

0

0

0

0

0

0

 

Other

ZB/A

ZB/S/A

ZB/S/A

ZB/S/A

ZB/S/A

ZB/S/A

ZB/S/A

S/A

S/A

S

S

1-hour

 

 

 

 

 

 

 

 

 

 

 

 

1

Erythema

3

3

3

3

3

3

3

2

2

1

1

 

Edema

2

2

2

2

2

2

2

2

2

0

0

 

Other

ZB/A

ZB/S/A

ZB/S/A

ZB/S/A

ZB/S/A

ZB/S/A

S/A

S/A

S/A

S

S

4-hour

 

 

 

 

 

 

 

 

 

 

 

 

1

Erythema

3

3

3

3

3

3

3

3

3

2

2

 

Edema

2

2

2

2

2

2

2

2

2

0

0

 

Other

ZB/A

ZB/S/A

ZB/S/A

ZB/S/A

ZB/S/A

ZB/S/A

S/A

S/A

S/A

S

S

2

Erythema

-

-

-

-

-

-

-

-

-

-

-

 

Edema

-

-

-

-

-

-

-

-

-

-

-

 

Other

-

-

-

-

-

-

-

-

-

-

-

 

h = hour

D = day

* = none

ZB = brownish area at the application site

ZBR = red-brown area

S = dryness of the skin

A = crust

(2) = not calculable

- = cutaneous examination not performed (animal sacrificed for ethical reason)

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Corrosive to skin in rabbits following 4-hour appliaction.
Executive summary:

At the request of CECA SA, Paris-la-Défense, France, the potential of the test item IMIDAZOLINE 4900 (batch No. pilote du 27/07/06) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 24th April 2002) and EC (2004/73/EC, B.4, 29th April 2004) guidelines.

The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

 

Methods

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was irritant but not corrosive on this first animal, it was then applied for 4 hours to only one other animal. As the test item showed corrosive properties on this second animal, the study was considered complete and the test item was not evaluated on a third animal.

A single dose of 0.5 mL of the undiluted test item was applied to the closely-clipped skin of one flank. The test item was held in contact with the skin by means of a semi-occlusive dressing.

Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until the end of the observation period.

The mean values of the scores for erythema and edema were calculated.

 

Results

After a 3-minute exposure (one animal)

A very slight to moderate erythema was noted from day 1 until the end of the observation period (day 15).

A very slight or slight edema was observed from day 2 until day 9.

A brownish area at the application site was noted from day 2 until day 11.

Crusts and dryness of the skin were noted between day 5 and day 15 (end of the observation period).

 

After a 1-hour exposure (one animal)

A very slight to moderate erythema was noted from day 1 until the end of the observation period (day 15).

A slight edema was observed from day 2 until day 13.

A brownish area at the application site was noted from day 2 until day 10.

Crusts and dryness of the skin were noted between day 5 and day 15 (end of the observation period).

 

After a 4-hour exposure (two animals)

In the first animal, a slight or moderate erythema was noted from day 1 until the end of the observation period (day 15).

A very slight or slight edema was observed from day 1 until day 13.

A brownish area at the application site was noted from day 2 until day 10.

Crusts and dryness of the skin were noted between day 5 and day 15 (end of the observation period).

 

In the second animal, a moderate then a severe erythema was noted on days 1 and 2, respectively.

A severe edema was noted on days 1 and 2.

A red-brown area was noted on day 2.

Since the cutaneous reactions observed in the second animal were similar to a severe burn of the skin, this animal was sacrificed for ethical reasons. The study was therefore considered completed and the test item was not evaluated on a third animal.

 

Mean scores over 24, 48 and 72 hours for the first animal were 3.0 for erythema and 2.0 for edema.

 

Conclusion

Under our experimental conditions, the test item IMIDAZOLINE 4900 (batch No. pilote du 27/07/06) was corrosive when applied topically to rabbits.

As explained in the category justification, For cross-reading in general use is made with data of same or lower EA-length where available, and that of Tall oil + DETA representing the worst case. This dossier is for the substance "Fatty acids C18 unsat, reaction products with triethylenetetramine" (or TO + TETA). As for the substance itself no toxicological information is available, cross-reading has been applied to TO + DETA.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

As explained in the category justification, For cross-reading in general use is made with data of same or lower EA-length where available, and that of Tall oil + DETA representing the worst case. This dossier is for the substance "Fatty acids C18 unsat, reaction products with triethylenetetramine" (or TO + TETA). As for the substance itself no toxicological information is available, cross-reading has been applied to TO + DETA.

Tall oil + DETA was evaluated in an in vivo dermal irritation/corrosion study in rabbits
The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was irritant but not corrosive on this first animal, it was then applied for 4 hours to only one other animal. As the test item showed corrosive properties on this second animal, the study was considered complete and the test item was not evaluated on a third animal. The study concluded that Tall oil + DETA is corrosive to rabbit skin after 4 hours exposure.

 

Also other in vivo irritation/corrosion studies indicate corrosion to skin following 4 hour application. The table below provides an overview of all available for the group of AAI:

    TO + DETA                           in vivo: Corrosive: Cat.1C

    TO + TEPA                           in vivo: Corrosive: Cat.1C

    C16-18, C18 unsat + TEPA   in vivo: Corrosive: Cat.1C

An indication for possible threshold effects for irritation comes from two available sensitisation studies on Tall oil + DETA.

In a Guinea pig maximization study for dermal sensitization, a preliminary irritation study evaluated irritation from epidermal exposures to the substance for 24 hrs under occlusion. The highest non-irritating concentration for epidermal exposures was established at 0.5% in corn oil. Epidermal concentrations of 1% resulted to signs of superficial necrosis.

In a local lymph node assay (LLNA) the substance evoked at 0.5% dissolved in acetone/olive oil (4/1, v/v) some slightly irritant effects following epidermal application of 25µg on the ears of mice. At 0.25% no irritation was observed.

There are no eye irritation studies available on an AAI substance. Corrosion to the eye is expected based on dermal corrosion.

There are no data from inhalation studies. However, exposure by inhalation is not likely considering the high boiling point (> 300 °C) and very low vapour pressure (0.00017 mPa at 25°C for DETA based AAI). Furthermore, as the substance is classified as corrosive, no acute toxicity testing should normally be conducted.



Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Tall oil + DETA is corrosive to rabbit skin after 4 hours exposure. Consequently, it should be classified Corrosive, Cat. 1C .

Corrosive to eyes is assumed for substances for which dermal corrosion has been established and no additional classification is required.

 

There is no data from inhalation studies. However, in view of the very low vapour pressure of AAI in general, exposure by inhalation is not likely.