Registration Dossier

Administrative data

Description of key information

Moderately irritating to skin and corrosive to the eyes.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Berolamine AA15. pre-GLP, and not according to standard testing method.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
other: FDA - Fed.Reg. 37(244),27635, 1972
Principles of method if other than guideline:
FDA
Six rabbits, exposed with 0.5 ml of test susbstance and control (10% aqueous SLS) on intact clipped skin, and abraded skin. Under 1 inch square patched, left under occlusion for 24 hours. Scoring immediately after exposure and 48 hours later (72 hour reading). Scoring according FDA scoring system.
GLP compliance:
no
Remarks:
Pre-GLP; signed authentication form present
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Leslie Moore Ltd
- Age at study initiation: not indicated
- Weight at study initiation: Between 2 and 3 kg
- Housing: 1 animal/cage
- Diet (e.g. ad libitum): Spratts Rabbit Diet (Spillers) - ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS: Not indicated
Type of coverage:
occlusive
Preparation of test site:
other: clipped, partially abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): applied unchanged

CONTROL: Aqueous sodium lauryl sulphate (SLS)
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): applied unchanged: 10%
Duration of treatment / exposure:
24 hours
Observation period:
72 hours from start of exposure
Number of animals:
6 animals, 4 sites per animal:
- Test substance and control
- Clipped and abraded
Details on study design:
TEST SITE
- Area of exposure: Under seperate 1" square patches of chromatography paper
- % coverage: not indicated
- Type of wrap if used: overlapping patch of impermeable plastic adheasive tape (Blenderm). The whole area was bound by Sleek occlusive tape wrapped round the entire trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The site was 'gently cleaned'
- Time after start of exposure: After 24 hours

SCORING SYSTEM: FAD scoring system
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 and 72 hour
Score:
2.6
Max. score:
8
Reversibility:
no data
Remarks on result:
other: PII 10% SLS = 3.6

Primary Skin Irritation in Rabbits: Mean scores and primary irritation scores

  Reading time (h) Reaction score
A B
Erythema & Eschar Formation      
Intact skin 24 1,17 1,83
Intact skin 72 0,92 1,00
Abraded skin 24 1,83 2,33
Abraded skin 27 1,33 1,83
Sub total   5,25 6,99
Oedema formation      
Intact skin 24 1,00 1,83
Intact skin 72 0,92 1,17
Abraded skin 24 2,00 2,33
Abraded skin 27 1,33 2,17
Sub total   5,25 7,50
Total   10,50 14,49
Primary Irritation Score   2,6 3,6

A = Berolamine AA15

B = 10% SLS

The reaction score is the average value of results from the 6 test animals. The primary irritation score calculation: Values for erythema and eschar formation at 24 h and 72 h (4 values) are added to the values for oedema at 24 h and 72 h ( 4 values) and the resulting figure is divided by 4.

The primary irritation score of Berolamine AA15 calculated for intact skin and abraded skin seperately:

Intact skin:       2.0

Abraded skin:  3.2

Same for SLS:

Intact skin:       2.9

Abraded skin:  4.3

Scoring:

Value - Erythema and Eschar Formation

0 - No erythema

1 - Very slight erythema (barely perceptible, edges of area not well defined)

2 - Slight erythema (pale red in color and edges definable)

3 - Moderate to severe erythema (definite red in color and area well defined)

4 - Severe erythema (beet or crimson red) to slight eschar formation (injuries in depth)

Edema Formation:

0 - No edema

1 - Very slight edema (barely perceptible, edges of area not well defined)

2 - Slight edema (edges of area well defined by definite raising)

3 - Severe edema (raised more than 1 mrn and extending beyond area of exposure)

4 - Moderate edema (raised approximately 1 mm)

Conclusions:
Not corrosive, but possibly itrritating. Not suitable for EU classification.
Executive summary:

Berolamine AA15 was tested for primary irritation according to FDA - Fed.Reg. 37(244),27635, 1972. The substance was applied to the intact and abraded skin of 6 rabbits following 24 hour exposure from 0.5 ml on 1 square inch chromatography paper under occlusion. Scoring for erythema and eschar formation and oedema formation were performed on 24 and 72 hours after the start of the exposure. The primary irritation index resulted to 2.0 for the intact skin following FDA scoring system.

Based on the calculated primary irritation index, the susbstance would be classified as moderate skin irritant.

The iritation and oedema scoring for the intact skin was on average about 1 for each at 24 hour observation period as well as at 72 hour observation periode. As such, the level of rritation was less than following exposure to 10% aqueous sodium lauryl sulphate.

Although no evaluation according OECD/EU guideline, the exposure of 0.5 mL under occlusion for 24 hours, is expected to result to more severe dermal reactions compared to OECD guideline exposures of 0.5 ml for 4 hours under semi-occlusive conditions.

Results from this study indicate that the substance is not corrosive, but possibly irritating.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Berolamine 715. Guideline, GLP principles
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Remarks:
According to GLP principles (Statement SD, QA audit)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Cheshire Rabbit Farms
- Age at study initiation: no data
- Weight at study initiation: 2.5-3.0 kg
- Housing: housed individually in cages with a grid floor beneath which was a peat moss filled tray.
- Diet (e.g. ad libitum): Special Diet Services Standard Rabbit Diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 (15-19)
- Humidity (%): 46 (30-60)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml
Duration of treatment / exposure:
Single intillation, no flushing.
Observation period (in vivo):
The eyes were examined for irritation using standard illumination, unable to use fluorescein stain due to severe chemosis. The ocular reaction was recorded at one and 24 h at 24h it was decided to sacrifice the animals due to the severity of the observed effects.
Number of animals or in vitro replicates:
3 male and 3 female animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM: as described in OECD405

TOOL USED TO ASSESS SCORE: standard illumination, unable to use fluorescein stain due to severe chemosis
Irritation parameter:
overall irritation score
Time point:
other: 24h
Score:
> 2 - < 4
Max. score:
4
Reversibility:
not reversible
Remarks:
animals were killed after 24h for humane reasons
Irritant / corrosive response data:
Cornea
Dullness of the cornea was noted in all treated eyes 1 h and 24 h after instillation. Severe chemosis prevented the use of fluorescein stain to
assess opacity although it was noted that no obvious opacity was apparent.
Iris
Positive iridial responses (score 1-2) were noted in one treated eye at 1 h, and in all treated eyes at 24 h after instillation.

Conjunctivae
Redness
Positive redness (score 2) was noted in 5/6 treated eyes and the remaining animal showed slight redness (score 1) at 1 h post instillation. All treated eyes showed positive responses (score 2) at 24h.
Chemosis
Severe chemosis (score 3-4) was noted in all treated eyes at 1 h and 24 h.
Discharge
Moderate discharge was noted in all treated eyes at 1 h post instillation. Severe thick white discharge was noted in all treated eyes at 24 h.

No other non-ocular topical effects were noted at any time during the test.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The test substance was extremely irritant to the eye in the rabbit irritation test. The test was terminated after 24h for humane reasons.
Executive summary:

The test substance was extremely irritant to the eyes of 3 male and 3 female rabbits after single instillation of 0.1 ml. The test was terminated after 24h for humane reasons.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

All in vivo skin irritation/corrosion studies performed on other AAI substances all indicate them to be corrosive following 4 hour exposure.

As the substances within the AAI group show the same reactive groups, show similar composition of amide, imidazoline, and some dimer structures of both, with the length of original EA amines used for production as biggest difference. Inherent reactivity and toxicity is not expected to differ much between these substances.

Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-productsdiffers from other substances in the AAI group that are based on fatty acids with polyamines, in that it contains a high amount of hydroxylated polyethylene amines, causing it to display more neutral OH groups rather than basic primary amine groups. As toxicity is much related to the presence of free primary amine groups, it can be expected that in specifically in aspects of acute toxicity related to direct chemical interactions, this substance shows less effects compared to other AAI substances.

 

Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products was tested for primary irritation according to FDA - Fed.Reg. 37(244),27635, 1972. The intact and abraded skin of 6 rabbits was exposed to 0.5 mL of the test substance for 24 hour exposure under occlusion. Scoring for erythema and eschar formation and oedema formation were performed on 24 and 72 hours after the start of the exposure. The primary irritation index resulted to 2.0 for the intact skin following FDA scoring system. Based on the calculated primary irritation index, the substance would be classified as moderate skin irritant.

 

An indication for possible threshold effects for irritation comes from an available sensitisation study onFatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products: In a Guinea pig maximization study for dermal sensitisation, 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 2% in water. Epidermal concentrations of 5% were slightly irritating.

 

Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-productswas extremely irritant to the eyes of 3 male and 3 female rabbits after single instillation of 0.1 ml. The test was terminated after 24h for humane reasons.

 

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 ( 8.4 x 10 -8 Pa at 25°C).



Justification for selection of skin irritation / corrosion endpoint:
Only study available

Justification for selection of eye irritation endpoint:
Only study available

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-productstested for primary irritation according to FDA - Fed.Reg. 37(244),27635, 1972, and found to be a moderate skin irritant.

Tall oil + ammonia-ethanolamine reaction by-products was extremely irritant to the eyes of 3 male and 3 female rabbits after single instillation of 0.1 ml. The test was terminated after 24h for humane reasons.

Consequently, classification as skin irritant (GHS Cat.2) and corrosive to eyes (GHS Cat.1) is appropriate.

There is no data from inhalation studies. However, in view of the very low vapour pressure ofFatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products, exposure by inhalation is not likely.