3-(2-chloroethyl)(1H,3H)quinazoline-2,4-dione

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2006-02-09 to 2006-02-10

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Well documented non-GLP study performed according to OECD Guideline for testing of Chemicals, Draft OECD Guideline 430, In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER), 27 March 2002.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Draft OECD Guideline 430, In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER), 27 March 2002

Deviations:

no

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-chloroethyl)(1H,3H)quinazoline-2,4-dione

EC Number:

225-795-3

EC Name:

3-(2-chloroethyl)(1H,3H)quinazoline-2,4-dione

Cas Number:

5081-87-8

Molecular formula:

C10H9ClN2O2

IUPAC Name:

3-(2-CHLOROETHYL)QUINAZOLINE-2,4(1H,3H)-DIONE

Details on test material:

- Name of test material (as cited in study report): T 1201
- Substance type: white to pale beige solid
- Physical state: solid
- Analytical purity: no data
- Purity test date: no data
- Lot/batch No.: 00464885 RT001201G1A251
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature, protected from moisture; kept away from direct sunlight
- Other:
Solubility:
0.09 g/L in water
26.7 g/L in acetone
7.9 g/L in ethanol

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, 33178 Borchen
- Age at study initiation: 29 days
- Weight at study initiation: not applicable
- Housing: single, Makrolon Type II cage, with wire mesh top
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): artificial light 12h dark/12h light (6:00 am - 6:00 pm light)

Test system

Type of coverage:

other: not applicable

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: concurrent negative control (deionised water) and positive control (hydrochloric acid (36% ~ 10 M) Reag. Ph Eur

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1305 g, 0.1105 g, and 0.1248 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 150 µL

Duration of treatment / exposure:

24 hours

Observation period:

not applicable

Number of animals:

Three skin discs were used for each test group

Details on study design:

- The test material was applied for 24 hours to the epidermal surfaces of rat skin discs. Corrosive materials are identified by their ability to produce a loss of normal stratum corneum integrity and barrier function, which is measured as a reduction in the inherent TER below a certain threshold level (5 kOhm). Irritant and non-corrosive materials do not reduce the TER below the threshold level. A dye-binding step is incorporated into the test procedure to verify the TER results, if the TER values of the test item are less than 5 kOhm. Surfactants and neutral organics may produce faltse positive artefacts in the TER assay due to enhanced permeability of the skin sample towards ions.

- TER measurements:
The TER was measured by using a low-voltage, alternating current impedance meter (WTW LF 330). Prior to measuring the electrical resistance, the surface tension of the skin was reduced by adding a sufficient volume of 70% ethanol to cover the epidermis. After a few seconds the ethanol was removed by inverting the tube, and the tissue was then hydrated by the addition of 3 mL magnesium sulphate solution (154 mM). The electrodes were placed on either side of the skin disc to take the conductivity measurement in µS/skin disc. The resistance values were calculated from conductivity by the following equation:
resistance (Ohm) = 1/conductivity (S)
The mean TER results are accepted on condition that concurrent positive and negative control values fall within the acceptable ranges for the method.The control substances and their associated resistance ranges for the methodology and apparatus used in this test are:
Positive control (10 M hydrochloric acid (36%)): 0.5 - 1 kOhm*
Negative control (deionised water): 8 - 25 kOhm*
*: values reflect the laboratory's historical data and - for the negative control - differ from the range given in the OECD Guideline. Since the range given in the guideline is only a suggestion, the acceptance range was established by the facility based on the own historical data. This does not affect the validity of the test system.

If the mean TER value obtained for the test item is greater than 5 kOhm, then it is classified as non-corrosive. If the TER value is less than or equal to 5 kOhm it is classified as corrosive.

Results and discussion

In vitro

Results

Results 1

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Value:

12.59

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: mean, SD: 1.49

Results 2

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Run / experiment:

1

Value:

11.98

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Results 3

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Run / experiment:

2

Value:

11.49

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Results 4

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Run / experiment:

3

Value:

14.29

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

Impedance measurement of all three skin discs treated with the test substance indicated no corrosive effect. The skin discs appeared macroscopically intact after treatment. An appropriate reference substance was used as positive control and showed a distinct increase in conductivity indicating that the test was sensitive and valid. The actual impedance values remained in the range given by the guideline and were far below the general threshold of 5 kOhm indicating a substantial corrosive potential of the positive control substance. The mean TER-value of the negative control of the experiment remained well within the acceptance range.

Summary TER-results:
Negative control: mean: 13.08 kOhm (SD: 4.67) - not corrosive
Negative control 1: 11.36 kOhm
Negative control 2: 10.64 kOhm
Negative control 3: 17.24 kOhm

Positive control: mean: 0.76 kOhm (SD: 0.07) - corrosive
Positive control 1: 0.83 kOhm
Positive control 2: 0.75 kOhm
Positive control 3: 0.69 kOhm

T 1201: mean: 12.59 kOhm (SD: 1.49) - not corrosive
T 1201 1: 11.98 kOhm
T 1201 2: 11.49 kOhm
T 1201 3: 14.29 kOhm

Any other information on results incl. tables

Sulforhodamine B Dye application and removal:

The assessment of dye penetration was not necessary, because the TER values of the test item T 1201 were greater than 5 kOhm.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

It was concluded that the test item did not corrode rat skin under the experimental conditions used. Both positive control and negative control reached typical impedance values as stated in the guideline and in the range of the laboratory's historical controls. Therefore, the test substance is considered to be non-corrosive in this TER test.