2-(Hydroxyacetyl)-N-methylhydrazine-1-carboxamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27th June 2017 to 1st August 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:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: In Vitro classification based on Southee JA., 1998. Evaluation of the Prevalidation Process, Part 2, final report, Volume 2, The Bovine Corneal Opacity and Permeability (BCOP) Assay.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: "Bovine Corneal Opacity and Permeability Test: An In Vitro Assay of Ocular Irritancy, (1992)"; Gautheron, Pierre; Dukic, Martine; Alix, Danielle and Sina, Joseph F.; Fundamental and Applied Toxicology 18, 442-449.

Test guideline 3

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-N-[(methylcarbamoyl)amino]acetamide

EC Number:

815-593-9

Cas Number:

1613307-26-8

Molecular formula:

C4H10N3O3

IUPAC Name:

2-hydroxy-N-[(methylcarbamoyl)amino]acetamide

Test animals / tissue source

Species:

cattle

Strain:

not specified

Details on test animals or tissues and environmental conditions:

The bovine eyes were received from Spear Products on 27 Jun 2017 and transported to MB Research in Hank’s Balanced Salt Solution (HBSS) in a refrigerated container.
The eyes were examined and any eye with a cornea exhibiting evidence of vascularization, pigmentation, opacity or scratches was discarded.
Corneas from eyes that were free of defects were dissected from the surrounding tissues. A 2-3 mm rim of sclera was left attached to each cornea. The corneas were then placed in a container of fresh HBSS.

Test system

Vehicle:

other: Minimum Essential Media (MEM)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.75 ml of a 20% formulation of L-005313063-000D009

Duration of treatment / exposure:

Four hours (±10 minutes),

Details on study design:

Following the pretest observations, the MEM solution was removed from the anterior chamber and 0.75 ml of the test article mixture was applied to the epithelium of each of the five treated corneas.
The holders and corneas were then placed in the 32 (±2)°C incubator in a horizontal position to ensure contact of the test article with the corneas. After four hours (±10 minutes), the test article (or MEM solution in the controls) was removed from the epithelium of the cornea and anterior chamber of the holder by washing with MEM solution. The anterior and posterior chambers of the holders were then refilled with fresh MEM solution and opacity measurements were made taken with each treated cornea compared to each of the two control corneas. Opacity measurement of the cornea was made using an OP-KIT opacitometer.
Immediately following the four hour opacity measurement, the MEM solution was removed from the anterior chamber and replaced with 1.0 ml of 0.5% sodium fluorescein solution in Dulbecco's Phosphate Buffered Saline (DPBS). Each holder was then returned to the 32 (±2)°C incubator in a horizontal position ensuring contact of the fluorescein with the cornea.
After 90 minutes, the fluid from the posterior chamber was removed and the amount of dye that passed through the cornea was measured as the optical density at 490 nm by spectrophotometric analysis.

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Value:

-5.56

Negative controls validity:

valid

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The in vitro score was calculated as -5.56 and is classified as a non-irritant. (Southee,1998).

Executive summary:

Five corneas were dosed with 0.75 ml of a 20% formulation of L-005313063-000D009. Opacity measurements and sodium fluorescein permeability were determined.

The corrected mean opacity score was -5.5. The corrected mean optical density (permeability) score was -0.004.

The in vitro score was calculated as -5.56 and is classified as a non-irritant. (Southee,1998).