Fatty acids, tall-oil, reaction products with formaldehyde and (Z)-N-9-octadecenyl-1,3-propanediamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 10 December 2012 to 25 December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well documented GLP study performed according to OECD Guideline 405, EU Method B5, EPA OPPTS 870.2400 and JMAFF guidelines (2011). The only deviation of the study guidelines is that the observation period was limited to 7 days instead of 21 days according to the guideline, however the effects were fully reversible wihtin 7 days

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Observation period limited to 7 days instead of 21 days according to the guideline, however the effects were fully reversible wihtin 7 days

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

Observation period limited to 7 days instead of 21 days according to the guideline, however the effects were fully reversible wihtin 7 days

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines (2011)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, tall-oil, reaction products with formaldehyde and (Z)-N-9-octadecenyl-1,3-propanediamine

EC Number:

272-789-1

EC Name:

Fatty acids, tall-oil, reaction products with formaldehyde and (Z)-N-9-octadecenyl-1,3-propanediamine

Cas Number:

68911-83-1

Molecular formula:

C40H76N2O

IUPAC Name:

Fatty acids, tall-oil, reaction products with formaldehyde and (Z)-N-9-octadecenyl-1,3-propanediamine

Details on test material:

- Name of test material (as cited in study report): Reaction product of oleic acid, N1-(9Z)-9-octadecen-1-yl-1,3-propanediamine and paraformaldehyde
- Substance type: Dark brown liquid
- Physical state: Liquid
- Analytical purity: > 99%
- Composition of test material, percentage of components: 0.10% H2O
- Lot/batch No.: 8351213508
- Expiration date of the lot/batch: 05 May 2014
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark
- Other: specific gravity: 0.896 at 20°C; pH: 10.7 in aqueous solution (50% extract)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L'Arbresle Cedex, France
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: at least 1.0 kg
- Housing: Animals were individually housed in labeled cages with perforated floors and shelters.
- 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 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): 15 room air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye remained untreated and served as the reference control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

The eye lids were gently held together for about one second to prevent loss of the test substance.

Observation period (in vivo):

Mortality/viability: twice daily
Toxicity: at least once daily
Body weight: day of treatment (prior to instillation) and after the final observation
Necropsy: no necropsy was performed according to the protocol
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance. The irritation scores and a description of all other (local)effects were recorded.

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

SCORING SYSTEM:
Scoring of corneal irritation (score 0 to 4), area of cornea involved (score 0 to 4), iris (score 0 to 2), conjunctival irritation (score 0 to 3), chemosis (score 0 to 4), discharge (score 0 to 3)

TOOL USED TO ASSESS SCORE: Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.

Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Instillation of 0.1 mL of Reaction Product of Oleic acid, N1-(9Z)-9-octadecen-1-yl-1,3-propanediamine and paraformaldehyde into one eye of each of three rabbits resulted in effects on the conjunctivae for all animals and an effect on the cornea for one animal.
The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in all animals. Mean scores of redness following grading at 24, 48 and 72 hours after instillation were 1.3 for all animals and mean scores of chemosis following grading at 24, 48 and 72 hours after instillation were 1.3 for all animals and mean scores of chemosis following grading at 24, 48 and 72 hours after instillation were 0.3 for two animals and 0.0 for the other animal.
One animal showed sight dulling of the normal luster of the cornea which resolved within 24 hours, but no corneal opacity was observed.

No iridial irritation was observed and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion:
There was no evidence of ocular corrosion.

Coloration/remnants:
No staining of (peri)ocular tissues by the test substance was observed and no test substance remnants were seen.

Other effects:

Toxicity/mortality:
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this test, reaction product of oleic acid, N1-(9Z)-9-octadecen-1-yl-1,3-propanediamine and paraformaldehyde does not have to be classified and has no obligatory labelling requirements for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No 1272/2008 of the European Parliament and the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures including all amendments.