Amines, N'-[3-[(3-aminopropyl)amino]propyl]-N,N-di-C16-18-alkyltrimethylenedi-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 03, 2016 - October 04, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2012

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

May 2008, including most recent amendments.

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998.

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147.

Version / remarks:

November 2000; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[3-({3-[(3-aminopropyl)amino]propyl}amino)propyl](hexadecyl)octadecylamine; [3-({3-[(3-aminopropyl)amino]propyl}amino)propyl]dihexadecylamine; [3-({3-[(3-aminopropyl)amino]propyl}amino)propyl]dioctadecylamine

EC Number:

941-593-4

Cas Number:

1623405-26-4

Molecular formula:

Not applicable UVCB

IUPAC Name:

[3-({3-[(3-aminopropyl)amino]propyl}amino)propyl](hexadecyl)octadecylamine; [3-({3-[(3-aminopropyl)amino]propyl}amino)propyl]dihexadecylamine; [3-({3-[(3-aminopropyl)amino]propyl}amino)propyl]dioctadecylamine

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): di-C16-C18 (evennumbered) alkyl tripropylenetetramine
- Purity: 100% (UVCB substance)
- Purity test date: 08 July 2016
- Batch No.: 1330539
- Expiration date of the batch: 04 August 2018
- Appearance: Viscous liquid
- Storage condition of test material: At room temperature container flushed with nitrogen
- pH: 8.5-10.5 at concentration of 1%
- Specific gravity/density: 0.864 at 20°C

Specific details on test material used for the study:

pH: 8.5-10.5 at concentration of 1%

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Charles River France, L’Arbresle, France.
- Age at study initiation: Animal used withihn the study was 13 weeks old .
- Weight at study initiation: 2636 gram.
- Housing: Individually housed in cages with perforated floors and shelter.
- Diet: Approximately 100 g/day pelleted diet for rabbits (Global Diet 2030 Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS set to maintain
- Temperature (°C): 40 – 70
- Humidity (%): 18 - 24
- Air changes (per hr): approx 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 03 October 2016 to 04 October 2016

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of the animal were examined approximately 5 minutes and 1 hour after instillation of the test item.
An extra observation was done at 6 minutes after instillation of the test item.

Number of animals or in vitro replicates:

One male animal

Details on study design:

STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). No other animals were treated, after considering the degree of eye irritation observed in the first animal.

TREATMENT
The animal was treated by instillation of 0.1 mL of the test item, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test item. The other eye remained untreated and served as the reference control.

REMOVAL OF TEST SUBSTANCE
-Washing (if done): No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation).
- Necropsy: No necropsy was performed on the animal sacrificed for severe irritation/corrosion of the eye.
- Irritation:
The eyes of the animal were examined approximately 5 minutes and 1 hour after instillation of the test item.

SCORING SYSTEM
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to OECD 405.

TOOL USED TO ASSESS SCORE: ophthalmic examination lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal #1

Time point:

other: 6 minutes

Score:

2

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal #1

Time point:

other: 1 hour

Score:

4

Max. score:

4

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 6 minutes

Score:

1

Max. score:

2

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour

Max. score:

2

Remarks on result:

not determinable

Remarks:

due to the severe corneal damage

Results 5

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

other: 6 minutes

Score:

2

Max. score:

3

Results 6

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

other: 1 hour

Score:

2

Max. score:

3

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 6 minutes

Score:

2

Max. score:

4

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour

Score:

4

Max. score:

4

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(Discharge)

Basis:

animal #1

Time point:

other: 6 minutes

Score:

3

Max. score:

3

Results 10

Irritation parameter:

conjunctivae score

Remarks:

(Discharge)

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Max. score:

3

Irritant / corrosive response data:

Instillation of test item into one eye of one rabbit resulted in severe effects on the eye and signs of pain and stress (restless behaviour, closing of the eye). Due to these immediate severe effects an extra observation was done at 6 minutes after instillation. At one hour after instillation the effects worsened and blood in the lacrimal fluid was seen. The iris could not be scored at this point due to the severe corneal damage.
The animal was sacrificed for humane reasons approximately 1 hour after application of the test item. The other animals assigned to the study were not treated.

Other effects:

Remnants of the test item were present in the eye shortly after application but not at one hour after application.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In an eye irritation study with one rabbit, performed according to OECD/EC test guidelines, severe effects were observed including opacity of the cornea (grade 4/4) and chemosis of the conjunctivae (grade 4/4). Based on the results di-C16-C18 (evennumbered) alkyl tripropylenetetramine should be classified as Irreversible effects on the eye (Category 1) and labeled as H318: Causes serious eye damage.

Executive summary:

An acute eye irritation/corrosion study was performed with di-C16-C18 (evennumbered) alkyl tripropylenetetramine in the rabbit according to OECD/EC guidelines and in compliance with GLP principles. Instillation of approximately 0.1 mL of di-C16-C18 (evennumbered) alkyl tripropylenetetramine into one eye of one rabbit resulted in severe effects on the eye and signs of pain and stress (restless behaviour, closing of the eye). At 6 minutes after installation opacity of the cornea (grade 2/4) and injury of the iris (grade 1/2) were observed. The injury of the conjunctivae included redness (grade 2/3), chemosis (grade 2/4) and discharge (grade 3/3). At one hour after installation the effects worsened into opacity of the cornea (grade 4/4) and chemosis of the conjunctivae (grade 4/4). Blood was seen in the lacrimal fluid and the iris could not be scored due to the severe corneal damage. Remnants of the test item were present in the eye shortly after application but not at one hour after application. The animal was sacrificed for humane reasons approximately 1 hour after application of the test item. The other animals assigned to the study were not treated.

Based on these severe effects:

- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments), di-C16-C18 (evennumbered) alkyl tripropylenetetramine should be classified as : having irreversible effects on the eyes (Category 1).

- according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), di-C16-C18 (evennumbered) alkyl tripropylenetetramine should be classified as Irreversible effects on the eye (Category 1) and labeled as H318: Causes serious eye damage.