1-benzyl-5-phenylbarbituric acid

Skin irritation / corrosion

Administrative data

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-03-02 - 2018-03-14

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 430 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-benzyl-5-phenylbarbituric acid

EC Number:

276-940-2

EC Name:

1-benzyl-5-phenylbarbituric acid

Cas Number:

72846-00-5

Molecular formula:

C17H14N2O3

IUPAC Name:

1-benzyl-5-phenylpyrimidine-2,4,6(1H,3H,5H)-trione

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Molecular Formula:
C17H14N2O3
Molecular Weight:
294.31
Physical Appearance:
White powder
CAS No.:
72846-00-5
Batch Number:
170240
Purity:
99.5%

In vitro test system

Test system:

isolated skin discs

Source species:

rat

Cell type:

non-transformed keratinocytes

Cell source:

foreskin from multiple donors

Source strain:

Wistar

Details on animal used as source of test system:

Species:
Rat (Rattus norvegicus)
Strain:
Wistar
Justification of selection:
Rat is the rodent species and Wistar is the strain recommended by the test guideline.
Source:
Bred and reared at INTOX PVT. LTD.
Age at start of study:
22 days
No. of animals and sex:
5 males
Environmental conditions:
The experimental animal room was supplied with fresh and filtered air, with 10 to 15 air changes per hour. The room was air conditioned with temperature between 19 to 25 oC, relative humidity 30 to 70% and illumination cycle set to 12 hours light and 12 hours dark.

Vehicle:

water

Control samples:

yes, concurrent vehicle

yes, concurrent positive control

Amount/concentration applied:

150 mg + 150 μL analytical Grade Water

Duration of treatment / exposure:

24 hours

Number of replicates:

3

Test system

Amount / concentration applied:

150 mg + 150 μL analytical Grade Water

Duration of treatment / exposure:

24 hours

Number of animals:

three skin discs

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

transcutaneous electrical resistance (in kΩ)

Run / experiment:

test item

Value:

6.99

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the given experimental conditions of this study, it is concluded that the test item 1-Benzyl-5-Phenylbarbituric acid (BPBA) is considered non-corrosive to skin of the rat.

Executive summary:

1-Benzyl-5-Phenylbarbituric acid (BPBA), was evaluated for its corrosive potential by its ability to produce a loss of normal stratum corneum integrity and barrier function, which was measured as a reduction in the TER below the threshold level (cut-off value) of 5 k Ω for rat skin, and from any increase in the ionic permeability for sulforhodamine B dye.

The skin discs were taken from humanely sacrificed rats aged 28 days and were applied with 150 μL of test item, in triplicate. Concurrent triplicate sets of skin discs were applied either with analytical grade water (150 μl) as negative control or with 10M hydrochloric acid (150 μl) as positive control.

The test and control items were applied for up to 24 hours at 22 °C to the epidermal surfaces of skin discs in a two compartment test system in which the skin disc functioned as the separation between the compartments. The test / control items were then removed by washing with a jet of tap water until no further material could be removed. The skin impedance was measured as TER by using Aplab Autocompute LCR-Q meter 4910. The electrodes of LCR-Q meter were placed on either side of the skin disc to measure the resistance of skin disc at a frequency of 100 Hz and using series values. Following TER measurement, the skin was carefully examined for obvious damage. After visual examination, 10% (w/v) sulforhodamine B was applied to the epidermal surface of each skin disc for 2 hours, which was followed by the measurement of dye content in each skin disc.

The mean resistance of the skin in the negative control group was found to be 10.23 K Ω which was within the acceptable range of 10 to 25 k Ω and the mean dye content of skin disc was 39.13 μg/disc which was closer to the acceptable range of 15 to 35 μg/disc.

The mean resistance of the skin in the positive control group was found to be 1.00 K Ω which was within the acceptable range of 0.5 to 1.0 k Ω while the mean dye content of skin disc was 92.38 μg/disc, which was within the acceptable range of 40 to 100 μg/disc, thereby validating the experimental procedure.

The mean TER value obtained for 1-Benzyl-5-Phenylbarbituric acid (BPBA) was 6.99 K Ω which was greater than 5 k Ω, the skin discs showed no obvious damage (e.g. perforation) and mean disc dye content was found to be 29.84 μg/disc which was lesser than that observed in skin discs treated with the positive control item.

Under the given experimental conditions of this study, it is concluded that the test item 1-Benzyl-5-Phenylbarbituric acid (BPBA) is considered non-corrosive to skin of the rat.