cis-N-methyl-N-(1H-pyrrolo[2,3-d]pyrimidin4-yl)cyclobutane-1,3-diamine phosphate (1:1)

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 03 Dec 2018 to 07 Dec 2018.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: EC Guideline No. 440/2008. Part B: Methods for the Determination of Toxicity and other health effects, Guideline B.40BIS:"In Vitro Skin Corrosion: Human Skin Model Test". Official Journal of the European Union No. L142, 31 May 2008.

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

(1s,3s)-N1-methyl-N1-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}cyclobutane-1,3-diamine; phosphoric acid

EC Number:

951-920-2

Molecular formula:

C11H15N5* H3PO4

IUPAC Name:

(1s,3s)-N1-methyl-N1-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}cyclobutane-1,3-diamine; phosphoric acid

In vitro test system

Test system:

human skin model

Source species:

human

Cell type:

other: human-derived epidermal keratinocytes

Cell source:

other: not specified

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

50 µL Milli-Q water (negative control)
50 µL 8N KOH (positive control)

Duration of treatment / exposure:

3 minutes and 1 hour

Duration of post-treatment incubation (if applicable):

42 hr +/- 1 hours at 37°C.

Number of replicates:

Triplicate

Test system

Details on study design:

The test is based on the experience that corrosive chemicals show cytotoxic effects following short-term exposure to the stratum corneum of the epidermis. The test is designed to predict
and classify the skin corrosion potential of a test item by assessment of its effect on a threedimensional human epidermis model (1-4).
The test consists of topical application ofPF-03817968-09 on the skin tissue for 3-minute and 1-hour. After exposure the skin tissue is thoroughly rinsed to remove the test item followed by immediate determination of the cytotoxic (corrosive) effect.
Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) at the end of the treatment.

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

% tissue viability

Value:

ca. 4.2

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

the mean tissue viability of the positive control

Any other information on results incl. tables

In the range of 20 - 100% viability the Coefficient of Variation between tissue replicates was <_ 16%, indicating that the test system functioned properly

Applicant's summary and conclusion

Interpretation of results:

other: Non-corrosive

Conclusions:

In conclusion,PF-03817968-09 is not corrosive in the in vitro skin corrosion test under the experimental conditions described in this report.