1,6-Hexandiammonium dihydroxide, N,N'-bis-(2-hydroxypropyl)-N,N,N',N'-tetramethyl

Skin irritation / corrosion

Administrative data

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 20 SEP 2017 to 12 OCT 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)

Version / remarks:

28 July 2015

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

442-730-6

EC Name:

-

Cas Number:

35132-93-5

Molecular formula:

C16H38N202.2H0

IUPAC Name:

(2-hydroxypropyl)({6-[(2-hydroxypropyl)dimethylazaniumyl]hexyl})dimethylazanium propane-1,2-diol dihydroxide

impurity 1

Reference substance name:

Propane-1,2-diol

EC Number:

200-338-0

EC Name:

Propane-1,2-diol

Cas Number:

57-55-6

Molecular formula:

C3H8O2

IUPAC Name:

propylene glycol

impurity 2

Reference substance name:

N,N,N',N'-tetramethylhexamethylenediamine

EC Number:

203-842-9

EC Name:

N,N,N',N'-tetramethylhexamethylenediamine

Cas Number:

111-18-2

Molecular formula:

C10H24N2

IUPAC Name:

N,N,N',N'-tetramethylhexane-1,6-diamine

Test material form:

liquid

Details on test material:

Water added up to 100 %.

In vitro test system

Test system:

artificial membrane barrier model

Justification for test system used:

The CORROSITEX™ Assay is a standardized, quantitative in vitro test for skin corrosivity and has been validated by the ECVAM for testing acids, bases and their derivatives. The bio-barrier membrane is constructed to have physico-chemical properties similar to rat skin.
This in vitro method is permitted by the UN GHS tiered testing and evaluation strategy for the assessment and classification of skin corrosivity. Substances classified as non-corrosive shall undergo additional testing in accordance with the tiered testing strategy

Vehicle:

unchanged (no vehicle)

Details on test system:

SOURCE AND COMPOSITION OF MEMBRANE BARRIER USED
- Was the Corrositex® test kit used: yes
- Components: One vial containing BIOBARRIER matrix and a micro stirbar, One vial containing BIOBARRIER diluent, Racks of seven vials filled with CDS, One tray of membrane discs plus one additional membrane disc, Qualify test tubes, Categorize test tubes and one bottle of CONFIRM reagent

WAS THE COMPATIBILITY TEST PERFORMED: yes

WAS THE TIMESCALE CATEGORY TEST PERFORMED: yes

METHOD OF DETECTION
- Indicator solution: CDS (no further information available)
- Dye(s) used: no information available

METHOD OF APPLICATION: undiluted atop the biobarrier membrane

NUMBER OF REPLICATES: 4

NUMBER OF INDEPENDENT EXPERIMENTS TO DERIVE FINAL PREDICTION:

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)

Category Time [min.] Time [min.] Time [min.] Time [min.]
1 0 – 3 > 3 - 60 > 60 - 240 > 240
2 0 - 3 > 3 - 30 > 30 - 60 > 60
UN GHS Subcategory 1A 1B 1C non corrosive
Packing Group 1 2 3 not applicable
Risk-Phrase R35 R34 R34 no label
Hazard Statement H314 H314 H314 no label

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 µL

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 500 µL
- Concentration (if solution): 10 %

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 500 µL
- Concentration (if solution): 85 %

Duration of treatment / exposure:

Treatment until color change was observed.

Duration of post-treatment incubation (if applicable):

not applicable

Number of replicates:

4

Results and discussion

In vitro

Results

Results 1

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

1

Value:

44.08

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Results 2

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

2

Value:

44.03

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Results 3

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

3

Value:

32.83

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Results 4

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

4

Value:

43.33

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

Any other information on results incl. tables

Table2:  Results of the Test Item Dispersogen SPS

	CORROSITEX™ Time [min]	Colour Change	Consistency Change
Replicate 1	44.08	yes	no
Replicate 2	44.03	yes	no
Replicate 3	32.83	yes	no
Replicate 4	43.33	yes	no
Mean ± SD	41.07±5.50
Positive control	25.83	yes	no
Negative control	> 60	no	no

The mean time, required to activate the CDS was 41.07± 5.50 min.

Result of the Categorization test:

A direct change was observed in tube A and B and the category was read from the CORROSITEX colour chart. The chemical has been categorized to category 2 (materials with low acid/alkaline reserves).

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

In this in vitro study according to OECD TG 435 (membrane barrier test) the test substance showed corrosive effects. The mean time to activate the CDS was >30-60 min. (41.07 ± 5.50 min.).

Executive summary:

The potential of the test substance to induce skin corrosion was analysed by using the “In VitroMembrane Barrier Test (CORROSITEX™ Assay)” according to OECD TG 425 and under GLP conditions.

The test substance proved its ability to activate the CDS (chemical detection system) and was subsequently subjected to the timescale category test. The test substance was applied undiluted atop the bio-barrier membrane and the time required to activate the CDS was measured in four replicates. The mean time was compared to the given thresholds. The test substance was compatible with the CORROSITEX™ Assay, as assessed in the qualification step. The categorization step and the classification step could be performed.

In this study under the given conditions the test substance showed corrosive effects (mean time to activate the CDS: 41.07 +- 5.5 min).

The controls confirmed the validity of the study. The positive control activated the CDS between 3 - 60 min. (25.83 min.), the negative control did not activate the CDS before 60 min.