Registration Dossier

Administrative data

Description of key information

There are no data available for Amines, C16-18 (even numbered)-alkyl , salts with phosphoric acid, mono- and di-C16-18 (even numbered) alkyl esters.

In a GLP compliant OECD TG 404 study, 0.5 ml hydrogenated tallow alkylamines were semi-occlusively applied to the shaved skin of three New Zealand White rabbits for 4 hours. Well-defined erythema and oedema were observed up to day 11 after removal of the patches. All signs of irritation were reversible.

Hydrogenated tallow alkylamines and octadecylamines caused severe eye irritation up to irreversible damage in the rabbit eye.

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:
weight of evidence
Study period:
1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study according to GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Pemberley Rabbits, Cottenham, Cambridgeshire
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: 2.0 to 2.2 kg
- Housing: individual housing in metal cages
- Diet (e.g. ad libitum): SDS Standard Rabbit Diet; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 19
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 19
- Photoperiod (hrs dark / hrs light): 12/12 (19:00-7:00 / 7:00-19:00)
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: Untreated skin areas of the test animals served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g (moistened with water)

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL distilled water
Duration of treatment / exposure:
4 h
Observation period:
approx. 30 min, 24, 48, 72 h, then every day up to day 11
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: The test substance was applied under a 2.5 square centimetre gauze pad moistened with 0.5 mL distilled water.
- Type of wrap if used: Each treatment site was occluded with Elastoplast elastic adhesive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treatment site was washed with distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: OECD Draize scoring system
Irritation parameter:
erythema score
Remarks:
overall
Basis:
mean
Remarks:
all animals
Time point:
other: 24h / 48h / 72h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: exposure 4 hours
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: exposure 4 hours
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: exposure 4 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: exposure 4 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24h / 48h / 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: exposure 4 hours
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: exposure 4 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: exposure 4 hours
Irritation parameter:
edema score
Remarks:
overall
Basis:
mean
Remarks:
all animals
Time point:
other: 24h / 48h / 72h
Score:
2.22
Max. score:
3
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: exposure 4 hours
Irritant / corrosive response data:
Approximately 30 minutes after removal of the dressing, slight oedema and very slight or well-defined erythema were observed in all animals. A slight increase in the level of reaction was seen in two animals during day 4 and day 5.
On day 5, hyperkeratinisation was seen in one animal which was no longer present thereafter.
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the study results, the test material Lilamin AC-HBG/P is considered to be irritating to skin.
Executive summary:

In a GLP compliant OECD TG 404 study, 0.5 g the test material Lilamin AC-HBG-P (hydrogenated tallow alkyl amine), a white granular solid (purity 95%), was applied semi-occlusively for 4 hours to the shaved skin of three New Zealand White Rabbits. The test substance was moistened with 0.5 ml water applied to a 2.5 cm2gauze patch. Examination of the treated skin was started approx. 30 minutes after patch removal and on days 2, 3 and 4. Additional observations were performed on days 5 through 11. Well-defined erythema and oedema were observed in all three animals. A slight increase in the level of reaction was noted in two animals during days 4 and 5. The reactions abated by the beginning of the second week and by day 11 all skins were normal. Hyperkeratinisation was seen in one animal on day 5. Average scores for erythema were 2.0 (24 hours), 2.0 (48 hours) and 2.0 (72 hours). Scores for oedema were 2.0, 2.3 and 2.3 for the same time points. Based on the study results, the test material Lilamin AC-HPG-P is considered to be irritating to skin.

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:
supporting study
Study period:
1989-06-06 to 1989-06-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guideline 405 and in compliance with GLP
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, conventional breed
- Weight at study initiation: 2.29 kg
- Age at study initiation: ca. 3 - 5 months
- Housing: fully air-conditioned rooms, cages on their own
- Diet (e.g. ad libitum): Altromin 2113 (supplied by Altromin GmbH Lage/Lippe)ad libitum and hey (ca. 15 g daily)
- Water (e.g. ad libitum): deionized, chlorinated water, ad libitum



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-3°C
- Humidity (%): 50 +-20 %
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL Genamin 18 R 100 D
Duration of treatment / exposure:
24 hrs
Observation period (in vivo):
1, 24, 48, 72 hrs, 7 days
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm (37°C) physiological saline solution
- Time after start of exposure: 24 hrs

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
0.01 % fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks:
corneal vascularisation after 7 days
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
1
Max. score:
1
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24h / 48h / 72h
Score:
3
Max. score:
3
Reversibility:
not reversible
Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Irritating [Xi] - R41- Risk of serious damage to eyes
Executive summary:

In an OECD TG 405 study, 0.1 ml of the test material Genamin 18 R 100 D (octadecylamine), a whitish waxy solid (purity approximately 100%), was applied to the eye of one New Zealand White rabbit. 24 hours after treatment, the eye was washed with 0.9% tepid NaCl solution. From 1 hour on, the conjunctiva showed red beefy discoloration and pronounced chemosis. Iris and cornea showed lesions. Additionally, a clear colourless to whitish-slimy discharge was noted. Due to progressed vascularisation of the eye, the study was terminated after 7 days. Mean Draize scores for conjunctiva redness and chemosis at 24, 48 and 72 hours were 3.0, 3.0 and 3.0. Mean scores for iris were 1.0, 1.0 and 1.0 and for cornea opacity were 2.0, 2.0 and 2.0 (same time points)

According to the results of the study the test substance Genamin 18 R 100 D has to be regarded as irritating (Xi – R41- Risk of serious damage to eyes) in compliance with the criteria laid down in 83/467/EWG.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Read across is made with hydrogenated tallow alkylamines inside the primary alkylamines category. There are no human data on acute toxicity for hydrogenated tallow alkylamines nor for any of the other primary alkylamines considered a chemical category with respect to chemical safety assessment. In animals, data from all alkylamines demonstrated a significant dermal irritative potential of this chemical category. C12 -18 -(even numbered)-alkylamines as well as tallow alkylamines and octadecenylamines were shown to be corrosive to rabbit skin, and, in consequence, not tested in rabbit eye. Hydrogenated tallow alkylamines and octadecylamines induced less severe effects in skin but caused severe eye irritation up to irreversible damage in the rabbit eye. For C12 -18 -(even numbered)-alkylamines, rat inhalation studies indicated irritative properties on the respiratory tract.

Justification for classification or non-classification

Read across is made with hydrogenated tallow alkylamines inside the primary alkylamines category

Hydrogenated tallow alkylamines fulfill the requirements for classification as Irritant with the designation R38 - irritating to skin and R41 - risk of serious damage to eyes. Based on the dermal corrosive properties no testing for eye irritation was performed.