Nonanoic acid, mixed diesters, with oxybis[propanol] and dodecanoic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 to 24 January 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 405 without deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2017

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Commission regulation (EU) No. 2017/735

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Nonanoic acid, mixed diesters, with oxybis[propanol] and dodecanoic acid

EC Number:

946-682-1

Cas Number:

2166089-27-4

Molecular formula:

Non applicable (UVCB)

IUPAC Name:

Nonanoic acid, mixed diesters, with oxybis[propanol] and dodecanoic acid

Test material form:

liquid

Details on test material:

- Appearance: Limpid liquid
- Storage condition of test material: Keep container tightly closed. Preferably store in the original packaging. Store at room temperature, protect from humidity.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Received from Robinson Services, Inc. on January 9, 2019.
- Age: Young adult of 11 weeks
- Weight at study initiation: 2.149-2.598 kg
- Housing: Each animal was singly housed in suspended stainless steel caging. Enrichment (e.g., toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least
three times per week.
- Diet: Certified RSI 5025 High Fiber Rabbit Diet (Rowe Nutrition, LLC). A designated amount of diet (approximately 150 grams/day) and Alfalfa Timothy Hay Cubes (Standlee Premium Western Forage) were available to each rabbit.
- Water: Filtered tap water was supplied ad libitum.
- Acclimation period: 6-11 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 48-69 %
- Air Changes/Hour: 13
- Photoperiod: 12-hour light/dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye serving as control

Amount / concentration applied:

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

Duration of treatment / exposure:

No washing was done

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1, 24, 48, 72 h following treatment, according with the Draize method of scoring (Draize et al., 1944).

Number of animals or in vitro replicates:

3 females

Details on study design:

TREATMENT
Prior to instillation, 1-2 drops of ocular anesthetic (Tetracaine Hydrochloride Ophthalmic Solution USP, 0.5%) were placed into both the treated and control eye of each animal. One-tenth of a milliliter of the test substance was then instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance.
The other eye of each rabbit remained untreated with the test substance and served as a control.
The rabbits were then returned to their designated cages.

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM:
According to OECD guideline 405, ocular irritation was evaluated using a white light source in accordance with the Draize method of scoring (Draize et al., 1944).
The time interval with the highest mean score (Maximum Mean Total Score - MMTS) for all rabbits was used to classify the test substance by the system of Kay and Calandra (Kay & Calandra, 1962).

MMTS Irritation classification Requirement For Maintenance of Classification
0.0 - 0.5 Non Up to 0.5 at 1 hour with zeros at 24 hours; otherwise, increase one 0.0 - 0.5 non level
0.6 - 2.5 practically non with zeros at 24 hours; otherwise, increase one level
2.6- 15.0 minimally with zeros at 48 hours; otherwise, increase one level
15.1 -25.0 mildly with zeros at 96 hours; otherwise, increase one level
25.1 - 50.0 moderately with 7 day mean <=20 and individual total scores <=10 in at least 60% of the rabbits with no total score >30; otherwise, increase one level
50.1 - 80.0 severely with 7 day mean <=40 and individual total scores <=30 in at least 60% of the rabbits with no total score >60; otherwise, increase one level
80.1 - 100.0 extremely with 7 day mean <=80 and individual total scores <=60 in at least 60% of the rabbits with no total score >100; otherwise, increase one level
100.1 - 110 maximally with 7 day mean >80 and individual total scores >60 in at least 60% of the rabbits; otherwise, decrease one level

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

other:

Remarks:

animal #1, animal #2 and animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

other:

Remarks:

animal #1, animal #2 and animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of mild irritation

Results 6

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 9

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24/48/72 h

Score:

6

Max. score:

110

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

One hour after test substance instillation, minimal conjunctivitis was noted for all three treated eyes. There was no corneal opacity or iritis observed in any treated eye during this study. The
overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation by 72 hours (study termination).
The Maximum Mean Total Score (MMTS) of of test material is 6.0.
See Table 7.3.2/1: Individual and mean scores of conjunctivae, iris and cornea.

Other effects:

All animals appeared active and healthy and gained body weight during the study. Apart from the eye irritation noted, there were no other signs of gross toxicity, adverse clinical effects,
or abnormal behavior.

Any other information on results incl. tables

Table 7.3.2/1: Individual and mean scores of conjunctivae, iris and cornea

Time / Animal	Cornea			Iris			Conjunctivae
							redness			chemosis
	1 (3401)	2 (3402)	3 (3403)	1 (3401)	2 (3402)	3 (3403)	1 (3401)	2 (3402)	3 (3403)	1 (3401)	2 (3402)	3 (3403)
1 h	0	0	0	0	0	0	1	1	1	1	1	1
24 h	0	0	0	0	0	0	1	1	1	1	1	1
48 h	0	0	0	0	0	0	0	0	0	1	1	1
72 h	0	0	0	0	0	0	0	0	0	0	0	0
Mean 24/48/72 h	0	0	0	0	0	0	0.3	0.3	0.3	0.6	0.6	0.6

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance is classified as mildly irritating to the eye according with the time interval with the highest mean score (Maximum Mean Total Score - MMTS) for all
rabbits using to classify the test substance by the system of Kay and Calandra.
However, the test substance is not classified according to the criteria of the Draize score system, the Regulation EC No. 1272/2008 (CLP) and to the GHS.
This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

Executive summary:

In an eye irritation study conducted according to OECD 405 Guideline and in compliance with GLP, test substance was instilled as supplied, into the eye of 3 New Zealand rabbits at the dose of 0.1 mL, the other eye remained untreated serving as control. The lids were then gently held together for about one second in order to prevent loss of the test substance. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method and by the system of Kay and Calandra.

 

All animals appeared active and healthy and gained body weight during the study. Apart from the eye irritation noted below, there were no other signs of gross toxicity, adverse clinical effects, or abnormal behavior. One hour after test substance instillation, minimal conjunctivitis was noted for all three treated eyes. There was no corneal opacity or iritis observed in any treated eye during this study. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation by 72 hours (study termination).

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.0, 0.0 for cornea score; 0.0, 0.0, 0.0 for iris score; 1.0, 0.0, 0.0 for conjunctivae score and 1.0, 1.0, 0.0 for chemosis score. The Maximum Mean Total Score (MMTS) of of test material is 6.0.

Under the test conditions, the test substance is classified as mildly irritating to the eye according with the time interval with the highest mean score (Maximum Mean Total Score - MMTS) for all rabbits using to classify the test substance by the system of Kay and Calandra.

However, the test substance is not classified according to the criteria of the Draize score system, the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.