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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 to 22 January, 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 404 without deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2015

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

Council Regulation (EC) No. 440/2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Received from Robinson Services, Inc. on December 28, 2018 and January 9, 2019.
- Age: Young adult of 10-13 weeks
- Weight at study initiation: 2.118-2.506 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: 39-69 %
- Air Changes/Hour: 13
- Photoperiod: 12-hour light/dark cycle

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): The test substance was applied as received and mixed well prior to use.

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours.

Observation period:

0,5 h, 1 hour and then 24, 48, 72 hours and Days 7 after removal of the patch.

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure and type of wrap: Three dose sites, each approximately 6-cm², were delineated on this rabbit. Five tenths of a milliliter of the test substance was applied to the skin of each dose site and covered with a 1-inch x 1-inch, 4-ply gauze pad. The pads and entire trunk of the animal were then wrapped with semi-occlusive 3-inch Micropore™ tape to avoid dislocation of the patches.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: The pads were removed at the appropriate intervals (3 minutes, 1hour, and 4 hours).

OBSERVATION TIME POINTS
- Skin reactions were appreciated 30 minutes, 1 hour and then 24, 48, 72 hours and Days 7 after removal of the patch.

SCORING SYSTEM:
Individual dose sites were scored according to the Draize scoring system (Draize et al., 1944) at approximately 30-60 minutes, 24, 48, and 72 hours and at 7 days after patch removal
in addition to evaluation for corrosion at these intervals for the first animal only.
The classification of irritancy was obtained by adding the average erythema and edema scores for the 30-60 minute, 24, 48, and 72-hour scoring intervals and dividing by the number of evaluation
intervals. The resulting Primary Dermal Irritation Index (PDII) was classified as follows:

PDII: Classification:
0 Non-irritating
> 0 - 2.0 Slightly irritating
2.1 - 5.0 Moderately irritating
> 5.0 Severely irritating

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 30, 60 minutes, 24, 48 and 72 hours

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

Very slight erythema was observed at the 3-minute exposure site 30-60 minutes following patch removal which resolved by Day 7 for the first animal.
Very slight erythema was observed at the 1-hour exposure site 30-60 minutes following patch removal which resolved by 24 hours for the first animal.
Within 24 hours after patch removal, all three treated sites exhibited very slight to well-defined erythema and one treated site exhibited very slight edema. The overall incidence and severity of
irritation decreased gradually with time. All animals were free of dermal irritation by Day 7 (study termination).
No visible necrosis (corrosion) of the skin tissue was observed at the 3-minute, 1-hour and 4-hour dose sites during the study.
The Primary Dermal Irritation Index for the test item is 0.9.
See Table 7.3.1/1: Individual and average scores after 4 h exposure.

Other effects:

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

Any other information on results incl. tables

Table 7.3.1/1: Individual and average scores after 4 h exposure

Observations		Scores
Skin reactions	Observation time	Animal No. 3501	Animal No. 3502	Animal No. 3503
Erythema	1h	1	2	1
	24h	1	2	1
	48h	0	1	0
	72h	0	1	0
	Day 7	0	0	0
	Mean 24/48/72h	0.3	1.3	0.3
Oedema	1h	0	1	0
	24h	0	0	0
	48h	0	0	0
	72h	0	0	0
	Day 7	0	0	0
	Mean 24/48/72h	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance is classified as slightly irritating to the skin according to the criteria of the Primary Dermal Irritation Index but 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 a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, undiluted test substance was applied at the dose of 0.5 mL, under semiocclusive dressing during 4 hours on a clipped dorsal area of 3 females rabbits. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 h and Day 7 after the removal of the patch.

 

Within 24 hours after patch removal, all three treated sites exhibited very slight to well-defined erythema and one treated site exhibited very slight edema. The overall incidence and severity of irritation decreased gradually with time. All animals were free of dermal irritation by Day 7 (study termination).

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 0.3 / 1.3 / 0.3 for erythema and 0.0 / 0.0 / 0.0 for oedema. 

The Primary Dermal Irritation Index (PDII) calculated for this test substance was 0.9.

Under the test conditions, the test substance is classified as slightly irritating to the skin according to the criteria of the Primary Dermal Irritation Index but 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.