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Administrative data

Description of key information

The substance did not turn out to be irritant to skin in an in vitro skin irritation test.

The substance did not turn out to be irritant to eye in a BCOP test; moreove, it is predicted not to be eye irritant by an expert system.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 08, 2018 - Septembre 15, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD 439
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Justification for test system used:
The test item is applied topically to a three-dimensional RhE model, comprised of non-transformed, human-derived epidermal keratinocytes, which have been cultured to form a multi-layered, highly differentiated model of the human epidermis.
The RhE test method is based on the premise that irritant chemicals are able to penetrate the stratum corneum and damage the underlying layers of keratinocytes and other skin cells. Cell viability is measured by enzymatic conversion of the vital dye MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Thiazolyl blue], into a blue formazan salt that is quantitatively measured after extraction from tissues.
Irritant chemicals are identified by their ability to decrease cell viability below defined threshold levels.
Vehicle:
unchanged (no vehicle)
Details on test system:
The test system used for the in vitro skin irritation test was reconstructed human epidermis (SkinEthicTM RHE) as recommended by the OECD 439 guideline. The SkinEthicTM RHE model consists of normal human keratinocytes cultured for 17-days on an insert of 0.5 cm2 polycarbonate filter at the air-liquid interface in a chemically defined growth medium. The cells form a multilayered, highly differentiated and stratified epidermis model of the human epidermis that consists of main basal, supra basal, spinous and granular layers and a functional stratum corneum.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
For the treatment of 11-Methyldodecyl Laurate, negative control tissues and positive control tissues, 16 µL/0.5 cm2 of test item, 16 µL/0.5 cm2 of sterile dulbecco’s phosphate buffered saline (DPBS) and 16 µL/0.5 cm2 of 5% sodium dodecyl sulphate (5% aq.) were applied for 42 minutes at room temperature, respectively. Nylon mesh was used for uniform spreading of liquid materials.
Duration of treatment / exposure:
Tissues were exposed to 11-Methyldodecyl Laurate, negative and positive control for 42 minutes.
Duration of post-treatment incubation (if applicable):
After washing and drying, tissues were incubated in 6-well plate containing 2 mL growth medium at 37± 1°C in 5± 1% CO2 in a humidified incubator for 42 hours.
Number of replicates:
Three replicates were used for the test item, positive control and negative control.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Experiment 1
Value:
95.13
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Experiment 2
Value:
94.28
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Experiment 3
Value:
94.35
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Mean
Value:
94.59
Negative controls validity:
valid
Positive controls validity:
not valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
The negative and positive controls gave acceptable results and the study was accepted as valid.

TABLE1: Data Summary of Percent Viability

Treatment

Tissue Replicate

O.D. at 570 nm

Blank Corrected O.D.

Mean of Corrected O.D.

Mean O.D. of Three Tissues

% Viability/

Tissue

Mean % Viability

S.D. of % Viability

C.V. of % Viability

Corrosivity Class

Negative Control

(Dulbecco’s Phosphate Buffered Saline (DPBS))

1

1.346

1.302

1.296

1.293

100

100

0.01

0.77

NA

1.329

1.285

1.346

1.302

2

1.332

1.288

1.296

1.346

1.302

1.342

1.298

3

1.318

1.274

1.287

1.325

1.281

1.349

1.305

11-Methyldodecyl Laurate

1

1.293

1.250

1.23

1.223

95.13

94.59

0.47

0.50

No Category

1.266

1.223

1.260

1.217

2

1.259

1.216

1.219

94.28

1.265

1.222

1.262

1.219

3

1.257

1.214

1.22

94.35

1.262

1.219

1.269

1.226

Positive control

(Sodium dodecyl sulphate (5% aq.))

1

0.064

0.020

0.019

0.02

1.47

1.52

0.09

5.92

Category 2

0.063

0.019

0.063

0.019

2

0.065

0.021

0.021

1.62

0.064

0.020

0.066

0.022

3

0.062

0.018

0.019

1.47

0.064

0.020

0.064

0.020

Key     : O.D. = Optical Density, S.D. = Standard Deviation, C.V. = Coefficient of Variation, NA = Not Applicable.

Note      :              For Negative control, SD and CV of % viability was calculated using corrected OD at 570 nm; For the test item and positive control SD and CV of %           viability was calculated using % viability/tissue.

Interpretation of results:
GHS criteria not met
Conclusions:
The negative and positive controls gave acceptable results and the study was accepted as valid. Based on the results obtained, the test item 11-Methyldodecyl Laurate is classified as non-irritant to skin (UN GHS No Category).
Executive summary:

This study was performed to evaluate the non-irritant and irritant potential of 11-Methyldodecyl Laurate using reconstructed human epidermis (RHE) tissue in accordance with the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS).

Tissues were exposed tothenegative control (Dulbecco’s Phosphate Buffered Saline (DPBS)), positive control (sodium dodecyl sulfate,5% aqueous (SDS)) and11-Methyldodecyl Lauratein triplicate for 42 minutes at room temperature.

The mean cell viability in tissues treated with the test item was 94.59% after 42 minutes exposure. A significant reduction in percent cell viability was not observed in treated tissues when compared with that of the concurrent negative control.

The Optical density (OD) values for the negative control replicates were between 1.274 and 1.305, against the guideline requirement of ≥ 0.8 and ≤ 3.0 (≥ 1.2 as per SkinEthic SOP). The OD of the blankwasbetween0.042and0.053which met the guideline requirement of OD< 0.1.The positive control showed a 1.52% cell viability, against the acceptance criteria of <40% for the SkinEthic RHE model, when compared with that of the concurrent negative control. Variation between tissue replicates (i.e., CV% value) was 0.50% for the test item group, 5.92% for positive control and 0.77% for negative control against the guideline requirement of ≤ 18%, which demonstrate the efficiency of the test system, SkinEthicTMRHE model. All criteria for a valid study were met as describe in the study plan.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
December 14, 2018 - December 15, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD 437
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Test System : Isolated cornea from the eyes of freshly slaughtered cattle
Source : Deonar Abattoir slaughter house, Mumbai, Maharashtra
Bovine Age : Between 1 to 5 years (the age of the animals was determined based on the teeth count and horn ring count in addition to the Horizontal Diameter of corneas and central corneal thickness)
Transportation Condition : Transported (in a sealed plastic container) under cold condition in Hanks’ Balanced Salt Solution containing antibiotics [e.g., penicillin at 100 IU/mL and streptomycin at 100 μg/mL]
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
yes, concurrent positive control
Amount / concentration applied:
750 μL test item (undiluted)
Duration of treatment / exposure:
Corneas were exposed for approximately 10 minutes ± 30 seconds at 32 ± 1 °C
Duration of post- treatment incubation (in vitro):
2 hours ± 10 minutes at 32 ± 1ºC
Number of animals or in vitro replicates:
three replicate for each condition (Normal saline, N,N-Dimethylformamide, 11-methyldodecyl laurate)
Irritation parameter:
other: Final Opacity Value
Run / experiment:
Mean
Value:
0.74
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
other: Final OD490 Value
Run / experiment:
Mean
Value:
-0.009
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
other: IVIS
Run / experiment:
Mean
Value:
0.61
Negative controls validity:
valid
Positive controls validity:
valid

Normal Saline (0.75 mL)

Cornea Holder N°

Io

 (LUX)

I (Initial)

(LUX)

Initial Opacity Value

I

(Post Treatment)

(LUX)

Post Treatment Opacity

Value

Corr. Opacity

Value

OD490

Value

Corr. OD490

Value

IVIS

18

1090

1025

2.95

1021

3.11

0.16

0.077

0.038

0.73

20

1116

1033

3.62

1038

3.42

-0.20

0.084

0.045

0.48

26

1073

1015

2.70

1013

2.78

0.08

0.079

0.04

0.68

Mean

0.01

-

0.041

0.63

SD

0.19

-

0.004

0.13

 

N,N-Dimethylformamide (0.75 mL)

Cornea holder N°

Io

(LUX)

I (Initial)

(LUX)

Initial Opacity Value

I

(Post

Treatment)

(LUX)

Post Treatment Opacity

Value

Corr. Opacity

Value

Final Opacity

Value

OD490

Value

Corr. OD490

Value

Final OD490

Value

IVIS

19

1117

1075

1.98

305

106.49

104.51

104.50

1.293

1.254

1.213

122.70

23

1142

1063

3.38

297

113.77

110.39

110.38

1.526

1.487

1.446

132.07

27

1137

1085

2.33

327

99.11

96.78

96.77

1.871

1.832

1.791

123.64

Mean

103.88

-

1.524

1.483

126.14

SD

6.83

-

0.291

0.291

5.16

 

11-Methyldodecyl Laurate(0.75 mL)

Cornea holder N°

Io

 (LUX)

I (Initial)

(LUX)

Initial Opacity Value

I

(Post

Treatment)

(LUX)

Post Treatment Opacity Value

Corr. Opacity Value

Final Opacity Value

OD490

Value

Corr. OD490Value

Final OD490

Value

IVIS

21

1099

1039

2.72

1030

3.09

0.37

0.36

0.073

0.034

-0.007

0.26

25

1245

1159

3.38

1128

4.55

1.17

1.16

0.063

0.024

-0.017

0.91

28

1107

1054

2.43

1036

3.15

0.72

0.71

0.076

0.037

-0.004

0.65

Mean

0.74

-

0.032

-0.009

0.61

SD

0.40

-

0.007

0.007

0.33

Keys: IVIS = In Vitro Irritation Score, Io =Baseline Reading (With medium but without cornea), I = LUX Reading with Medium and Cornea, OD490= Optical Density at 490 Wave Length, - = Not Applicable,
Corr. = Corrected. Blank OD490value = 0.039.


 

Interpretation of results:
GHS criteria not met
Conclusions:
The mean IVIS score for the corneas, treated with 11-methyldodecyl laurate, was found to be 0.61.
Based on results from this study, the classification for 11-methyldodecyl laurate is as follows:
Classification (OECD 437 UN GHS): No Category
Executive summary:

This study was conducted to evaluate theocular irritancy of11-methyldodecyl laurate,in compliance with the OECD test guideline437 for theBCOP test.

Three sets, each consisting of three corneas were tested. The first set was treated with750 μLof normal saline (control), the second set was treated with750 μL ofdimethylformamide (positive control), and thethird set wastreated with750 μLof the test item,11-methyldodecyl laurate.Post application, corneas were incubated for approximately 10 minutes,after which the test item was washed-off. Corneas were then incubated for approximately 2 hat32 ± 1 ºC. At theend of incubation opacity readings were taken.

The post opacity permeability reading was measured by applying1 mL of fluorescein sodium solution
(4 mg/mL)
on to the anterior surface of the cornea followed by incubation for approximately90 min at
32 ºC. At the end of incubation, the Optical Density (OD) was measured at 490 nm, from fluid collected from the posterior chamber.

The mean in-vitroIrritancy Score(IVIS) ofnormal saline (control)anddimethylformamide(positive control)treated corneaswere found to be 0.63 and 126.14 which confirmed the reliability of the test procedure. The IVIS score for corneas, treated with11-methyldodecyl laurate was found to be 0.61.Based on results of this study, the classification for11-methyldodecyl laurateis as follows:

Classification (OECD 437UN GHS)   :          No Category

Endpoint:
eye irritation, other
Remarks:
in silico method
Type of information:
(Q)SAR
Remarks:
expert system
Adequacy of study:
weight of evidence
Study period:
2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Remarks:
Toxic Hazard Estimation by decision tree approach
Justification for type of information:
Documentation about the justification is provided in attachment.

This endpoint study record provides an expert system prediction (based on the chemical structure). Data are deemed to be sufficient to fulfil the information requirements.
Qualifier:
according to
Guideline:
other: Guidance on information requirements and chemical safety assessment. Chapter R.6: QSARs and grouping of chemicals.
Version / remarks:
May 2008.
Deviations:
no
Remarks on result:
no indication of irritation
Remarks:
predicted by in silico model
Interpretation of results:
GHS criteria not met
Conclusions:
The substance has been predicted as non-irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the study results, 11-Methyldodecyl Laurate should not be classified as irritant to skin and eye.