Decanedioic acid, compound with ethanolamine / Decanedioic acid, compound with 2-aminoethanol

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29th August -2017- 1st September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The study was conducted using approximately ten to twelve weeks old male rabbits obtained from Kuiper Rabbitry, Gary, Indiana. The rabbits weighed from 3.22 to 3.47 kilograms at the start of the study and were individually housed in stainless steel cages in a temperature (20 ± 3° C), humidity (30-70%), and (12 hour/cycle) light controlled room. Each rabbit was assigned a test animal number which appeared as an ear tag and also appeared on a cage card visible
on the front of each cage. The rabbits were nulliparous and non-pregnant. The rabbits were maintained according to the recommendations contained in the National Academy Press 2011: "Guide for the Care and Use of Laboratory Animals". They were conditioned for at least five days prior to study initiation. Purina Laboratory Rabbit Chow and water were available ad libitum. All animals used for this study were considered to be in good health at study initiation.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Moistened with water to assure good contact

Controls:

yes

Amount / concentration applied:

0.5g of neat test substance

Duration of treatment / exposure:

4 hours exposure to test substance

Observation period:

168 h0urs

Number of animals:

3 animals

Details on study design:

The day before study initiation, electric clippers were used to remove the hair from the left side of the
trunk, from the midline of the back to the abdomen. The following day a 0.5 g aliquot of the test
material, which was slightly moistened w/water to assure good skin contact, was then applied to an area
approximately 6 square centimeters on the side of the test animal. The application site is located
approximately 5-7 centimeters down from the backbone. The test substance was then covered with a
2.5 cm² - 2 layer gauze patch held in place with non-irritating Kendall Curity Standard Porous Tape and
the patch was then covered with a semi-occlusive plastic overwrap secured in place with Kendall Curity
Standard Porous Tape for the duration of the exposure period. At the end of the 4 hour contact period,
excess material was removed from the site; the site being observed and scored. Dermal irritation readings
for erythema and edema were performed approximately 4.5, 24, 48, 72 and168 hours after treatment.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: No erythema was observed

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: No erythema was observed

Interpretation of results:

GHS criteria not met

Conclusions:

Following exposure to test ubstance, the application sites were graded for indication of skin reactions at 4.5, 24, 48 and 72 hours. There were no skin irritation reactions in any of the test subjects. The maximum skin irritation score was 0. Therefore, In accordance with the criteria set forth in the CLP Guidiances, the test substance will not be classified for skin irritation.

Executive summary:

The Skin irritation potential of the test substance was conducted in accordance with the OECD 404 guildelines. The test substance an off white solid, was applied at a dose of 0.5 g to an unabraded site on a clipped area of each of three albino rabbits. The application sites were graded for indication of skin reactions at 4.5, 24, 48 and 72 hours after test substance application. There were no skin irritation reactions in any of the test subjects. The maximum skin irritation score was 0, and the primary skin irritation index was calculated to be 0. Therefore, In accordance with the criteria set forth in the CLP Guidiances, the test substance will not be classified for skin irritation.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 March 2017 - 17 March 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

Version / remarks:

26 July 2016

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU Method B40 Bis (In Vitro Skin Corrosion: Human Skin Model Test)

Version / remarks:

31 May 2018

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- No correction for purity was applied in this study.
- Stability at higher temperatures: no, maximum temperature: 25°C

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

skin obtained from plastic surgery from multiple donors

Justification for test system used:

Recommended test system in international guidelines (OECD and EC).

Vehicle:

unchanged (no vehicle)

Remarks:

Tissues were moistened with Milli-Q water to ensure close contact

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm Skin Model
- Tissue batch number(s): 25714
- Surface: 0.6 cm^2
- On the day of receipt the tissues were kept on agarose and stored in the refrigerator.

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 3 minute exposure: room temperature, 1 hour exposure: 36.7 - 37.5°C.
- Temperature of post-treatment incubation: 36.7 - 37.5°C.

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: the tissues were washed with phosphate buffered saline (one washing step)
- Observable damage in the tissue due to washing: no

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: TECAN Infinite® M200 Pro Plate Reader
- Wavelength: 570 nm

NUMBER OF REPLICATE TISSUES: 4 (2 tissues for the 3 minute exposure period, 2 tissues for the 1 hour exposure period) + 1 tissue for the negative and the positive control per exposure

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA (see table 1 in ''any other informatin on methods'')
A test item is considered corrosive in the in vitro skin corrosion test if:
a) The relative mean tissue viability obtained after 3-minute treatment compared to the negative control tissues is decreased below 50%.
b) In addition, a test item considered non-corrosive (viability ≥ 50%) after the 3-minute treatment is considered corrosive if the relative tissue viability after 1-hour treatment with the test item is decreased below 15%.

A test item is considered non corrosive in the in vitro skin corrosion test if:
a) The relative mean tissue viability obtained after the 3-minute treatment compared to the negative control tissues is not decreased below 50%.
b) In addition, the relative tissue viability after the 1-hour treatment is not decreased below 15%.

ACCEPTABILITY CRITERIA:
a) The absolute mean OD570 of the two tissues of the negative control should reasonably be within the acceptance limits of OECD 431 (lower acceptance limit ≥0.8 and upper acceptance limit ≤2.8)
b) The mean relative tissue viability following 1-hour exposure to the positive control should be <15 %.
c) In the range 20 - 100% viability, the Coefficient of Variation (CV) between tissue replicates should be ≤ 30%.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount applied: 32.9 - 40.2 mg on tissues moistened with 25 μl Milli-Q water

NEGATIVE CONTROL
- Amount applied: 50 μl Milli-Q water

POSITIVE CONTROL
- Amount: 50 μl 8N KOH

Duration of treatment / exposure:

- 3 minutes
- 1 hour

Duration of post-treatment incubation (if applicable):

3 hours

Number of replicates:

4 in total; 2 per exposure period

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1 hour exposure period (mean of replicates)

Value:

75

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks:

7%

Remarks on result:

other: Coefficient of variation between tissue repl.: 6.2%

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 minutes exposure period (mean of replicates)

Value:

90

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks:

20%

Remarks on result:

other: Coefficient of variation between tissue repl.: 6.1%

Other effects / acceptance of results:

- OTHER EFFECTS:
- Visible damage on test system: no
- Direct-MTT reduction: no
- Colour interference with MTT: no

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes, the absolute mean OD570 was between the acceptance limits (i.e., a mean of 1.708 ± 0.073 and 1.874 ± 0.071 for the 3-minute and the 1-hour application, respectively).
- Acceptance criteria met for positive control: yes, the mean relative tissue viability following 1 hour exposure was <15% (i.e., 7%).
- Acceptance criteria met for variability between replicate measurements: yes, CV between tissue replicates was ≤30% (i.e., 6.1% for the 3 minute exposure period and 6.2% for the 1 hour exposure period).

- Because the mean relative tissue viability for Sebacic MEA salt was not below 50% after 3 minutes treatment and not below 15% after 1 hour treatment Sebacic MEA salt is considered to be not corrosive.

Table 2 Historical control data

	Negative control		Positive control		Positive control
	3-minute treatment (OD570)	1-hour treatment (OD570)	3-minute treatment (OD570)	1-hour treatment (OD570)	3-minute treatment (% viability)	1-hour treatment (% viability)
Range	1.324 – 2.615	1.361 – 2.352	0.0172 – 0.56	0.046 – 0.339	6 – 25	3 – 13
Mean	1.84	1.85	0.19	0.14	11.03	7.45
SD	0.26	0.22	0.09	0.06	4.39	2.51
n	81	83	80	77	38	38

SD = Standard deviation

n = Number of observations

The above mentioned historical control data range of the controls were obtained by collecting all data over the period of November 2013 to November 2016.

Interpretation of results:

GHS criteria not met

Remarks:

Not classified according to Regulation (EC) 1272/2008

Conclusions:

The resuls of a skin corrosion test, performed according to OECD guideline 431, showed that Sebacic MEA salt was not corrosive to the skin. The test substance is therefore not classified according to GHS and Regulation (EC) 1272/2008.

Executive summary:

The resuls of a skin corrosion test, performed according to OECD guideline 431, showed that Sebacic MEA salt was not corrosive to the skin. The test substance is therefore not classified according to GHS and Regulation (EC) 1272/2008.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5th October 2017- 8th October 2017.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline 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:

The Study was conducted using rabbits obtained from Kuiper Rabbitry, Gary, Indiana. The rabbits weighed from 2.74 to 2.83
kilograms at the start of the study and were individually housed in stainless steel cages in a
temperature (63-73°F), humidity (30-70%), and light controlled room. Each rabbit was assigned a
test animal number which appeared on a cage card visible on the front of each cage. The
females were nulliparous and non-pregnant. The rabbits were maintained according to the
recommendations contained in the National Academy Press 2011: "Guide for the Care and Use
of Laboratory Animals". They were conditioned for at least five days prior to study initiation.
Purina Rabbit chow and water were available ad libitum. All animals used for this study were
considered to be in good health at the study initiation.

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1ml

Duration of treatment / exposure:

The test article was ground into a fine powder prior to dosing and 0.1 ml packed volume was instilled into one eye holding the eye lids together for one second
to prevent loss of the material. The contralateral eye served as the untreated control for each rabbit

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

24 hours before the start of the study both eyes of the experimental animals were examined for
pre-existing ocular lesions. Only those animals with no pre-existing ocular lesions were used for
test purposes. The test article was ground into a fine powder prior to dosing and the powdered
test article was used for dosing. Five minutes prior to dosing, the eyes were anesthetized with
Tetracaine HCL solution. Three animals were dosed by instilling 0.1 ml. packed volume of the
test article into one eye and then holding the eye lids together for one second to prevent loss of
the material. The contralateral eye served as the untreated control for each rabbit.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no observed effect

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no observed effect

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no observed effect

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

other: no observed effect

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was instilled into the eyes of rabbits and the eyes were observed and scored at 1, 24, 48 and 72 hours. There were minimal eye irritation reactions in all of the test subjects which cleared by the 1 hour observation. Therefore, in accordance with the CLP guidance, the test substance does not meet the classification criteria for eye irritation.

Executive summary:

The test substance potential to induce eye irritation was conducted in the OECD guidelines 405. 24 hours before the start of the study both eyes of the experimental animals were examined for pre-existing ocular lesions. Only those animals with no pre-existing ocular lesions were used for test purposes.The test substance was instilled into the eyes of rabbits and the eyes were observed and scored at 1, 24, 48 and 72 hours. The eyes were examined at 1, 24, 48 and 72 hours after treatment. There were minimal eye irritation reactions in all of the test subjects which cleared by the 1 hour observation. Therefore, in accordance with the CLP guidance, the test substance does not meet the classification criteria for eye irritation.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 March 2017 - 21 March 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Version / remarks:

26 July 2013

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Purity correction factor: 1.136
- Stability at higher temperatures: No, maximum temperature: 25°C

Species:

cattle

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: young cattle, obtained from the slaughterhouse Vitelco, 's-Hertogenbosch, The Netherlands.
- Storage, temperature and transport conditions of ocular tissue: eyes were excised by a slaughterhouse employee as soon as possible after slaughter. Subsequently, eyes were collected an transported in physiological saline in a suitable container under cooled conditions.
- The eyes were checked for unacceptable defects and those exhibiting defects were discarded.
- Isolated corneas were stored in a petri dish with cMEM containing 1% (v/v) L-glutamine and 1% (v/v) Fetal Bovine Serum.

Vehicle:

physiological saline

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Concentration in vehicle: 20% (w/v) solution
- Amount(s) applied: 750 µL

NEGATIVE CONTROL: Physiological saline
- Amount(s) applied: 750 µL

POSITIVE CONTROL: Imidazole solution
- Amount(s) applied: 750 µL

Duration of treatment / exposure:

240 ± 10 minutes

Duration of post- treatment incubation (in vitro):

In cMEM for opacity measurements and subsequently 90 ±5 minutes in sodium-fluorescein for permeability determinations

Number of animals or in vitro replicates:

3 for the negative control, the positive control and the treatment group each.

Details on study design:

Two experiments were performed since the individual in vitro irritancy scores of the test item were spread over two categories in the first experiment and the results were therefore inconclusive.
TREATMENT METHOD: The medium from the anterior compartment was removed and 750 µL of either the negative control, positive control or test item was introduced onto the epithelium of the cornea. The holders were slightly rotated, with the corneas maintained in a horizontal position, to ensure uniform distribution of the control or the test item over the entire cornea. Corneas were incubated in a horizontal position for 240 ± 10 minutes at 20-24°C in the first experiment and at 25°C in the second experiment.

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: After the incubation the solutions were removed and the epithelium was washed at least three times with MEM with phenol red (Earle’s Minimum Essential Medium, Life Technologies).

- POST-EXPOSURE INCUBATION: refilled with fresh cMEM for opacity measurements and subsequently 90 ±5 minutes incubation in sodium-fluorescein for permeability determinations

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: opacity meter (OP-KIT)
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of a microtiter plate reader (TECAN Infinite® M200 Pro Plate Reader, OD490). OD490 values of less than 1.500 were used in the permeability calculation.
- Other: possible pH effects of the test substance on the corneas were recorded. Each cornea was inspected visually for dissimilar opacity patterns.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA (see table 1):
A test substance that induces an IVIS ≤ 3 is not classified for eye irritancy (UN GHS: no category);
A test substance that induces IVIS >55 is defined as a corrosive or severe irritant (UN GHS: category 1);
For a test substance that induces an IVIS >3 and ≤55, no prediction on irritant potency can be made.

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean of 3 replicates

Value:

2.4

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Remarks:

IVIS: 0.3 - 1.3

Positive controls validity:

valid

Remarks:

IVIS: 96.2 - 103.3

Remarks on result:

other: First experiment

Irritation parameter:

in vitro irritation score

Run / experiment:

Mean of 3 replicates

Value:

1.4

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Remarks:

IVIS: -0.4 - 2.1

Positive controls validity:

valid

Remarks:

IVIS: 70.8 - 126.3

Remarks on result:

other: Second experiment

Other effects / acceptance of results:

- The corneas treated with Sebacic MEA salt showed opacity values between 1.3 and 3.7 in the first experiment and between -1.4 and 4.1 for the second experiment.
- Permeability values were ranging from -0.009 to -0.018 in the first experiment and ranging from -0.002 to 0.011 for the second experiment.
- IVIS scores were 1.2, 2.5 and 3.4 (n=3) in the first experiment and -1.2, 1.1 and 4.2 (n=3) in the second experiment.

Since the individual in vitro irritancy scores were spread over 2 categories in both experiments, the tests were inconclusive.

OTHER EFFECTS:
- No pH effect of the test item was observed on the rinsing medium in both experiments.
- In the first experiment, the corneas treated with sebacic MEA salt were slightly turbid and treaded after 240 minutes of treatment. In the second experiment, the corneas treated with sebacic MEA salt were slightly turbid after 240 minutes of treatment.
- In the first experiment, one of the negative control eyes was slightly turbid. In the second experiment two of the negative control eye were slightly turbid. This had no effect on the validity of the experiment since the opacity and permeability values were within the historical data range.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes, results were within historical range (IVIS ranging from 0.3 to 1.3 in the first experiment and ranging from -0.4 to 2.1 in the second experiment).
- Acceptance criteria met for positive control: yes, results were within historical range (IVIS ranging from 96.2 to 103.3 in the first experiment and ranging from 70.8 to 126.3 in the second experiment). Corneas were turbid after 240 minutes of treatment (in both experiments). In the second experiment, the corneas treated with the positive control also had a fleck after 240 minutes of treatment.

Table 2 Historical Control Data for the BCOP Studies

	Negative control			Positive control
	Opacity	Permeability	In vitro Irritancy Score	In vitro Irritancy Score
Range	-5.4 – 5.2	-0.010 – 0.205	-5.3 – 5.3	86.5 - 211.4
Mean	0.40	0.02	0.60	137.01
SD	1.72	0.02	1.76	27.54
n	101	101	104	102

SD = Standard deviation

n = Number of observations

The above mentioned historical control data range of the controls were obtained by collecting all data over the period of February 2014 to February 2017.

Interpretation of results:

study cannot be used for classification

Remarks:

Based on inconclusive results.

Conclusions:

Based on the outcome of a Bovine Corneal Opacity and Permeability test (BCOP) performed according to OECD guideline 437 and GLP principles, no conclusion can be drawn for eye irritation or serious eye damage of sebacic MEA salt since two experiments provided inconclusive results.

Executive summary:

Based on the outcome of a Bovine Corneal Opacity and Permeability test (BCOP) performed according to OECD guideline 437 and GLP principles, no conclusion can be drawn for eye irritation or serious eye damage of sebacic MEA salt since two experiments provided inconclusive results.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

In vitro study was conducted to determine the skin corrosion potential of tests substance in accordance to OECD 431 guideline. After 3 minutes exposure, 90% tissue viability and after 1hour exposure, 75% tissue viability, therefore, in accordance with the CLP guidance, the test substance does not meet the classification criteria for skin corrosion.In addition, in vivo study confirmed maximum skin irritation score was 0. Therefore, In accordance with the criteria set forth in the CLP Guidance’s, the test substance will not be classified for skin irritation.

In vitro study was conducted to determine the eye damage potential of Bovine Corneal Opacity and Permeability test (BCOP) performed according to OECD guideline 437 and GLP principles, no conclusion can be drawn for eye irritation or serious eye damage of the test substance since two experiments provided inconclusive results. In addition, in vivo study confirmed minimal eye irritation reactions in all of the test subjects which cleared by the 1 hour observation. Therefore, in accordance with the CLP guidance, the test substance does not meet the classification criteria for eye irritation.