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Administrative data

Description of key information

For the endpoint skin irritation/corrosion there is an in vitro study available (Bisini, 2017) indicative of the fact that Neopentyl Glycol Dipelargonate is a non-corrosive substance. In addition there is an acute dermal toxicity study (Salvador, 2014) on the analogue TMP Pelargonate from which there were no indications of skin irritating effects. Based on these studies the substance Neopentyl Glycol Dipelargonate can be regarded as non-irritating to the skin.

With regard to the eye irritation effects, there are also two studies available. An in vitro ( Geitlinger, 2018) on the substance itself and an in vivo study (Salvador, 2014) on the analogue TMP Pelargonate indicate that the test item, Neopentyl Glycol Dipelargonate, has no eye irritating properties.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)
other:
Endpoint:
skin irritation: in vitro / ex vivo
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
Adopted on 28 July 2015
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test system:
human skin model
Source species:
other: Reconstructed Human Epidermis TestMethod: EPISKIN™
Cell type:
other: epidermis keratinocytes as cell source and use of representative tissue and cytoarchitecture
Cell source:
other: Reconstructed Human Epidermis TestMethod: EPISKIN™ - Batch 18-EKIN-002
Source strain:
not specified
Vehicle:
unchanged (no vehicle)
Details on test system:
In the Main Assay, alive tissues were treated with the test item (20 microliters), positive and negative controls.
D-BPS was used as negative control and 5% (w/v) of sodium dodecyl sulphate (SDS) solution was instead used as positive control.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
20 microliters of test item; 20 microliters of the solution as positive control; 20 microliters of D-PBS.
Duration of treatment / exposure:
15 +/- 0.5 minutes in a ventilated cabinet at room temperature
Duration of post-treatment incubation (if applicable):
A 42 ± 1 hour recovery period was allowed by incubation at 37°C, 5% CO2 and saturated humidity.
Number of replicates:
3 replicated for each tested item
Irritation / corrosion parameter:
other: Colour observation
Run / experiment:
Preliminary test - Direct MTT reduction test
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Colourless drops, no colour change (no interaction)
Irritation / corrosion parameter:
other: Colour observation
Run / experiment:
Colouring potential test
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Colourless solution (no interaction)
Irritation / corrosion parameter:
other: Optical Density
Run / experiment:
Main assay
Value:
0.718
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
The test item did not induce cell death in any replicate, the mean cell viability after the blank subtraction was 110% when compared to the negative control
Other effects / acceptance of results:
The negative control gave the expected baseline value (Optical Density values of the three replicates higher than 0.6) and variability [Standard Deviation (SD) of % viability lower or equal to 18], in agreement with the guideline indications. According to the method, the
negative control mean value is considered the baseline value of the experiment and thus represents 100% of cell viability. The positive control caused the expected cell death (2% of cell viability when compared to the negative control) and variability (SD of % viability equal to 0.5). Based on the stated criteria
(mean viability ≤ 40% and SD of % viability ≤ 18), the assay was regarded as valid. The test item did not induce cell death in any replicate, the mean cell viability after the blank subtraction was 110% when compared to the negative control. Intra-replicate variability was acceptable with a SD of % viability value equal to 16.6 (lower than 18, as stated in the Study Protocol).

MAIN ASSAY

BLANK              Negative Control

 

OD

 

 

OD

OD-blank                                             Viability(%)

0.0043

N1 -1

 

0.742

0.7023                           0.6988             109.1

0.041

N1 -2

 

0.735

0.6453

0.035

N2 -1

 

0.685

0.6453                        0.6453              102 .1

0.041

N2 -2

 

0.703

0.6633

0.038

N3 -1

 

0.609

0.5693                         0.5693                 88.8

0.040

N3 -2

 

0.609

0.5693

Mean

0.040

Mean

0.681

Mean

0.6

100

SD

0.003

SD

0.1

SD

0.07

10.3

CV(%)

7.1

CV(%)

8.7

CV(%)

10.3

10.3

 

Positive Control

 

 

OD

 

 

OD-blank

 

 

Viability(%)

 

0.0108                         1.7  

 

  0.0083 1.3

                        

  0.0143 2.2

 

P1-1

0.052

0.0123

P1-2

0.049

0.0093

P2-1

0.044

0.0043

P2-2

0.052

0.0123

P3-1

0.053

0.0133

P3-2

0.055

0.0153

Mean

0.051

 

Mean

0.011

2

SD

0.004

 

SD

0.003

0.2

CV(%)

7.6

 

CV(%)

27.0

27.0

 

Test Item

 

 

OD

 

 

OD-blank

 

 

Viability(%)

 

0.6363                          99.3

 

 

0.7918                        123.6

 

 

0.6078                        94.9

B1-1

0.671

0.6313

B1-2

0.681

0.6413

B2-1

0.824

0.7843

B2-2

0.839

0.7993

B3-1

0.641

0.6013

B3-2

0.654

0.6143

Mean

0.718

 

Mean

0.7

106

SD

0.09

 

SD

0.10

15.5

CV(%)

12.4

 

CV(%)

14.6

14.6

DISCUSSION

The mean Optical Density of Blank Controls was 0.040, lower than the maximum acceptable value (0.1). The negative control gave the expected baseline value (Optical Density values of the three replicates higher than 0.6) and variability (Standard Deviation of the % viability lower or equal to 18), in agreement with guideline indications. According to the method, the mean value is considered the baseline value of the experiment and thus represents 100% of cell viability.

Positive control results indicated an appropriate cell death with an acceptable relative cell viability (2% of the negative control value). Variability between replicates gave also the expected value (SD of%viability = 0.5). Based on the stated criteria, mean viability, expressed as percentage of the negative control, lower or equal to 40% and standard deviation of % viability equal or lower than 18, the study was accepted as valid.

The test item did not induce cell death in any replicate, the mean cell viability after the blank subtraction was 106% when compared to the negative control. Intra-replicate variability was acceptable with a SD of % viability value equal to 15.5 (lower than 18, as stated in the Study Protocol).

Interpretation of results:
GHS criteria not met
Conclusions:
Neopentyl Glycol Dopelargonate is considered as "not corrosive in the human Skin Model Test"
Executive summary:

The study was followed in according to OECD guideline and GLP without significate deviations.

The potential of the test item Neopentyl Glycol Dipelargonate to be irritant to the skin was investigated through an in vitro skin irritation study, using a commercial reconstructed human epidermis (RhE) model named EPISKIN™.

The blank, negative and positive controls gave acceptable results and the study was accepted as valid.

The mean cell viability of the test item treated tissues, after the blank subtraction, was 106%. Based on the results obtained, the test item Neopentyl Glycol Dipelargonate is classified as non-irritant to the skin (UN GHS No Category).

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
other: three-dimensional human cornea tissue
Strain:
other: Commercially available EpiOcularTM kit.
Details on test animals or tissues and environmental conditions:
The EpiOcularTM tissue consists of normal, human-derived keratinocytes which have been cultured to form a stratified squamous epithelium similar to that found in the human cor-nea. It consists of highly organized basal cells. These cells are not transformed or trans-fected with genes to induce an extended life span. The EpiOcularTM tissues are cultured in specially prepared cell culture inserts with a porous membrane through which nutrients can pass to the cells. The tissue surface is 0.6 cm2.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
50 microliters to two tissue replicates
Duration of treatment / exposure:
28 minutes
Number of animals or in vitro replicates:
two in vitro replicates
Details on study design:
This study was performed in order to evaluate the potential of Neopentyl Glycol Dipelargonate to evoke eye irritation in a Reconstructed human Cornea-like Epithelium (RhCE) model in an in vitro study.
The EpiOcularTM Eye Irritation Test (EIT) predicts the acute ocular irritation potential of chemicals by measurement of its irreversible tissue damage caused by cytotoxic effects in the human cornea model. Within a testing strategy, the EpiOcularTM EIT is used as a re-placement of the Draize Eye Irritation Test.
It is utilized for the classification and labelling of chemicals concerning their eye irritation potential. The EpiOcularTM EIT is intended to differentiate substances that are “not eye irritant” from those that require labelling as either GHS category 1 or 2 for serious eye damage resp. eye irritation potential.
Eye irritant materials are identified by their ability to produce a decrease in cell viability as determined. The cell viability is measured by dehydrogenase conversion of MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide), present in cell mitochondria, into a blue formazan salt that is quantitatively measured after extraction from tissues. The per-centage reduction of cell viability in comparison of untreated negative controls is used to predict the eye irritation potential. The formazan production was evaluated by measuring the optical density (OD) of the resulting solution.
Irritation parameter:
other: Optical density at 570 nm
Remarks:
Corrected medium value
Run / experiment:
Tissue 1
Value:
2.064
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation parameter:
other: Optical density at 570 nm
Remarks:
Corrected medium value
Run / experiment:
Tissue 2
Value:
2.046
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation

Comparison of Tissue Viability

For the test item and the positive control, the following percentage values of tissue viability were calculated in comparison to the negative control:

Designation

Positive Control

Neopentyl Glycol Dipelargonate

% Viability (Tissue 1)

37.2%

94.8%

% Viability (Tissue 2)

34.2%

94.0%

% Viability Mean

35.7%

94.4%

 


Assessment

Eye irritation is assessed using the criteria given in the following table (source: MatTek Corporation):

% Viability

Assessment

UN GHS classification

> 60 %

Non eye irritant

No category

60 %

At least eye irritant

No prediction can be made (category 1 or 2)

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the test, Neopentyl Glycol Dipelargonate was considered non-eye irritant in the EpiOcularTMEye Irritation Test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

For read across justification see at section 13

Justification for classification or non-classification

Skin irritation:

As no skin irritating properties are expected based on the available results, a the substance is not to be classified according to the criteria described in EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of substance and mixtures (CLP).

Eye irritation

As no effects of eye irritation or eye damage are observed in any of the available studies), the substance is not to be classified according to the criteria described in EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP).