2-amino-2-(hydroxymethyl)propane-1,3-diol hydrochloride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 1, 2016 - January 6, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-2-(hydroxymethyl)propane-1,3-diol hydrochloride

EC Number:

214-684-5

EC Name:

2-amino-2-(hydroxymethyl)propane-1,3-diol hydrochloride

Cas Number:

1185-53-1

Molecular formula:

C4H11NO3.ClH

IUPAC Name:

2-amino-2-(hydroxymethyl)propane-1,3-diol hydrochloride

Test material form:

solid

Specific details on test material used for the study:

Designation: Art. 108219
Synonym: Tris(hydroxymethyl)-aminomethananhydrochlorid
Trade name: TRIS-HCL Emprove Bio Bulk
CAS-No.: 1185-53-1
Batch: TD16007119
Purity: 100.2% (Titration with perchloric acid)
Appearance: Colourless crystals
Expiry date: June 30, 2021
Storage: +15 to +25°C, store in tightly closed containers, protected from moisture


PREPARATION OF THE TEST MATERIAL
The test item Art. 108219 (TRIS-HCL Emprove Bio Bulk) was prepared as a 20% (w/v) solution in a 0.9% sodium chloride solution. The stability in the vehicle was not investigated. The test item preparation was administered within <1 hour after preparation.

Test system

Vehicle:

physiological saline

Controls:

yes, concurrent vehicle

yes, concurrent positive control

Amount / concentration applied:

TEST MATERIAL: 750 µL (i.e. 150mg/750µL)

NEGATIVE / VEHICLE CONTROL: 750 µL

Designation: 0.9% sodium chloride solution
Supplier: B. Braun Melsungen AG, Germany
Batch: 15464012
Released until: October 2018


POSITIVE CONTROL: 750 µL

Designation: Art. 814223
Synonym: Imidazole
Supplier: Merck KGaA, Germany
Batch: S6746923
Purity (GC) 99.8% (a/a)
Released until: August 31, 2018
Imidazole was dissolved with 0.9% sodium chloride solution to a concentration of 20% (w/v)

Duration of treatment / exposure:

240 minutes

Number of animals or in vitro replicates:

in vitro: triplicate design

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Run / experiment:

Run 1 / Experiment 1

Value:

0.8

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: No observations (e.g. tissue peeling, residual test chemical, non-uniform opacity patterns) were seen in a visually inspection of the corneas after treatment.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was 0.4 and, thus, within three standard deviations of the current historical mean of the negative control (IVIS: -1.4 – 3.4).
- Acceptance criteria met for positive control: After treatment with the positive control (20% Imidazole) the calculated IVIS was 111.4 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS 78.8 – 134.7). Therefore, the study fulfilled the acceptance criteria.

Any other information on results incl. tables

		Opacity	Permeability	IVIS
				per cornea	per group (mean value)	SD
Negative control	0.9% NaCl Solution	0.5	0.000	0.500	0.4	0.2
		0.2	0.001	0.515
		0.2	-0.002	0.170
Positive control	20% Imidazole solution	76.1	2.854	118.910	111.4	9.5
		80.6	2.270	114.650
		54.2	3.102	100.730
Test item	Art. 108219	1.8	-0.001	1.785	0.8	0.9
		0.1	-0.001	0.085
		0.4	0.001	0.415

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, the test itemTRIS-HCL did not show an eye hazard potential. The test item is not requiring classification for eye irritation or serious eye damage (UN GHS: No Category).

Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 437. Under the conditions of the present study, the test itemTRIS-HCL did not show an eye hazard potential. The test item is not requiring classification for eye irritation or serious eye damage (UN GHS: No Category).