Bis[2-(diethylamino)ethyl] adipate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in chemico

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))

Version / remarks:

10.2 Deviations from the Guideline
Due to a programming error (the UV-lamp was not on) the peptide calibration samples and Co-elution controls for the Lys-peptide assay were measured after the incubated samples.
This was considered uncritical because the applicability of the calibration and stability of samples was verified using reference controls A and B.

Deviations:

yes

Remarks:

The deviation was considered uncritical

GLP compliance:

yes (incl. QA statement)

Type of study:

direct peptide reactivity assay (DPRA)

Justification for non-LLNA method:

The direct peptide reactivity assay (DPRA) is an in chemico assay to quantify the reactivity of the test item towards cysteine and lysine containing peptides. This reactivity is related to the skin sensitisation potential.
This study was performed in order to estimate the skin sensitisation potential of Bis[2-(diethylamino)ethyl]adipate using a peptide model.
To quantify the sensitisation potential, the depletion of the cysteine and lysine containing peptides caused by known amounts of the test item was measured using HPLC.
The assay was used for supporting the discrimination between skin sensitizers (i.e. UN GHS Category 1) and non-sensitizers in accordance with the UN GHS. A categorization in the sub-categories 1 A and 1 B is not possible.

Test material

Test material information

Constituent 1

Reference substance name:

Bis[2-(diethylamino)ethyl] adipate

EC Number:

240-610-6

EC Name:

Bis[2-(diethylamino)ethyl] adipate

Cas Number:

16545-00-9

Molecular formula:

C18H36N2O4

IUPAC Name:

1,6-bis[2-(diethylamino)ethyl] hexanedioate

impurity 1

Reference substance name:

2-diethylaminoethanol

EC Number:

202-845-2

EC Name:

2-diethylaminoethanol

Cas Number:

100-37-8

Molecular formula:

C6H15NO

IUPAC Name:

2-(diethylamino)ethanol

Test material form:

liquid

Results and discussion

In vitro / in chemico

Results

Key result

Run / experiment:

mean

Parameter:

other: Mean peptide depletion [%]

Value:

3

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

valid

Any other information on results incl. tables

According to the test guideline, the reactivity is classified as “high”, “moderate”, “low” or “minimal” using the Cysteine 1:10/Lysine 1:50 prediction model shown in Table8.4–a.

 

Table8.4–a         Evaluation of results according to the Cysteine 1:10/Lysine 1:50 prediction model

Mean peptide depletion [%]	Reactivity Class	DPRA Prediction
0 – ≤ 6.38	Minimal	Negative
> 6.38 – ≤ 22.62	Low	Positive
> 22.62 – ≤ 42.47	Moderate
> 42.47 - ≤ 100	High

 

The mean peptide depletion in the Lys-peptide and Cys-peptide assay was 3.00 %, therefore the test item was classified with:

 

DPRA Prediction: Negative

Reactivity class: Minimal

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

All acceptance criteria were fulfilled, therefore the test was considered valid. The DPRA prediction for the test item Bis[2-(diethylamino)ethyl]adipate was negative with reactivity class minimal according to the Cysteine 1:10/Lysine 1:50 prediction model.
According to the test guideline, a second run should be considered to verify the result if the mean percent depletion falls in the range of 3 % to 10 % for the cysteine 1:10/lysine 1:50 prediction model or the cysteine percent depletion falls in the range of 9 % to 17 % for the cysteine 1:10 prediction model. This was considered not necessary because the mean depletion was exactly at the lower border where a second run is recommended, but well below the limit regarding the cysteine depletion alone evaluated with the Cysteine 1:10 model (measured depletion: 5.05 % compared to recommended repetition of the experiment in the range 9 % to 17 %).
No observations arousing doubts concerning the accuracy of the results and the validity of the study were made.

Executive summary:

The study was performed in order to evaluate the reactivity of the test itemBis[2-(diethylamino)ethyl]adipatetowards cysteine (Cys-) and lysine (Lys-) containing peptides. A test item solution in acetonitrile was incubated 24 ± 2 h at 24.6 - 24.8 °C together with cysteine and lysine peptides, respectively, and the peptide concentration after the incubation was measured using HPLC-UV.

Three replicates were prepared using 1:10 and 1:50 molar ratio of the test item with the Cys- and Lys-peptide, respectively. Triplicate samples of the solvent without test item were incubated and measured in parallel.

The peptide depletion values after incubation are shown in Table 3-a:

Table3-a              Results

Cys-peptide depletion [%]	Lys-Peptide depletion [%]	Mean peptide depletion [%]
5.05	0.96	3.00

 

The DPRA predicition is “negative” with minimal reactivity according to the Cysteine 1:10/Lysine 1:50 prediction model.