Registration Dossier

Administrative data

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 November 2017 to 27 November 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-{2-[2-(3-azaniumylpropoxy)ethoxy]ethoxy}propan-1-aminium di[(2Z)-3-carboxyprop-2-enoate]
Cas Number:
1629579-82-3
Molecular formula:
C18H32N2O11
IUPAC Name:
3-{2-[2-(3-azaniumylpropoxy)ethoxy]ethoxy}propan-1-aminium di[(2Z)-3-carboxyprop-2-enoate]
Test material form:
liquid
Details on test material:
CAS Number: 1629579-82-3
EC Number: 818-033-1
Molecular formula: C18H32N2O11
Specific details on test material used for the study:
Identification: Bis-Aminopropyl Diglycol Dimaleate
Appearance: Clear to transparent yellow liquid
Test item storage: At room temperature
Purity/Composition correction factor: Contains 74% water
Stability at higher temperatures Yes, maximum temperature: 40°C, maximum duration: 60 minutes
Chemical name (IUPAC), synonym or trade name: Bis-Aminopropyl Diglycol Dimaleate
CAS Number: 1629579-82-3

In vitro test system

Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: SkinEthic Laboratories
Vehicle:
unchanged (no vehicle)
Control samples:
not required
Amount/concentration applied:
The liquid test item was applied undiluted (25 µl) directly on top of the tissue.
Duration of treatment / exposure:
15 mins
Number of replicates:
3

Results and discussion

In vitro

Results
Irritation / corrosion parameter:
% tissue viability
Value:
> 50
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
In conclusion, Bis-Aminopropyl Diglycol Dimaleate is non-irritant in the in vitro skin irritation test under the experimental conditions described in this report and should not be classified.
Conclusions:
Bis-Aminopropyl Diglycol Dimaleate was checked for color interference in aqueous conditions and possible direct MTT reduction by adding the test item to MTT medium. Because no color changes were observed it was concluded that the test item did not interact with the MTT endpoint. 

Skin irritation is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the test item compared to the negative control tissues was 98%. Since the mean relative tissue viability for the test item was above 50% the test item is considered to be non-irritant.

The positive control had a mean cell viability after 15 ± 0.5 minutes exposure of 16%. The absolute mean OD570of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was ≤ 8%, indicating that the test system functioned properly.

The mean relative tissue viability for the test item was above 50% the test item is considered to be non-irritant.
Executive summary:

The objective of this study was to evaluate Bis-Aminopropyl Diglycol Dimaleate for its ability to induce skin irritation on a human three-dimensional epidermal model (EPISKIN Small model (EPISKIN-SMTM)). The possible skin irritation potential of the test item was tested through topical application for 15 minutes.

 

The study procedures described in this report were based on the most recent OECD and EC guidelines. Batch 11_13_17_1 of the test item was a clear to transparent yellow liquid. The test item was applied undiluted (25 µl), directly on top of the skin tissue for 15 ± 0.5 minutes. After a 42-hour post-incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

 

Skin irritation is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the test item compared to the negative control tissues was 98%. Since the mean relative tissue viability for the test item was above 50% after 15 ± 0.5 minutes treatment the test item is considered to be non-irritant.

 

The positive control had a mean cell viability of 16% after 15 ± 0.5 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was ≤ 8%, indicating that the test system functioned properly.

 

In conclusion, Bis-Aminopropyl Diglycol Dimaleate is non-irritant in the in vitro skin irritation test under the experimental conditions described in this report and should not be classified according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations.