cis-N-hydroxy-3-[methyl(1H-pyrrolo[2,3-d]pyrimidin- 4-yl)amino]cyclobutanecarboxamide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5th Feb 2019 to 25th Feb 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

cis-N-hydroxy-3-[methyl(1H-pyrrolo[2,3-d]pyrimidin- 4-yl)amino]cyclobutanecarboxamide

EC Number:

951-622-2

Molecular formula:

C12H15N5O2

IUPAC Name:

cis-N-hydroxy-3-[methyl(1H-pyrrolo[2,3-d]pyrimidin- 4-yl)amino]cyclobutanecarboxamide

In vivo test system

Test animals

Species:

mouse

Strain:

CBA:J

Sex:

female

Details on test animals and environmental conditions:

20 Females (nulliparous and non-pregnant). Five females per group. Age at the Initiation of Dosing: Young adult animals (approximately 12 weeks old) were selected.
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 22°C with an
actual daily mean relative humidity of 42 to 47%. A 12-hour light/12-hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation)
were maintained in the animal rooms.

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

0%, 5%, 10%, 25%

No. of animals per dose:

5

Details on study design:

Three groups of five animals were treated with one test item concentration per group. The highest test item concentration was selected from the pre-screen test. One group of five
animals was treated with the vehicle.

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

ca. 1

Variability:

+/- 0.1

Test group / Remarks:

0%

Remarks on result:

other: Vehicle Control

Results 2

Key result

Parameter:

SI

Value:

ca. 1.2

Variability:

+/-0.3

Test group / Remarks:

5%

Remarks on result:

not determinable

Remarks:

No indication of skin sensitisation was detected

Results 3

Key result

Parameter:

SI

Value:

ca. 1.2

Variability:

+/-0.1

Test group / Remarks:

10%

Remarks on result:

not determinable

Remarks:

No indication of skin sensitisation was detected

Results 4

Key result

Parameter:

SI

Value:

ca. 0.9

Variability:

+/-0.1

Test group / Remarks:

25%

Remarks on result:

not determinable

Remarks:

No indication of skin sensitisation was detected

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Since there was no indication that the test item elicits a SI ≥ 3 when tested up to 25%, PF07085579 was not considered to be a skin sensitizer.
It was established that the EC3 value (the estimated test item concentration that will give a SI =3) (if any) exceeds 25%. The six-month reliability check with Alpha-hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at Charles River Den Bosch is an appropriate model for testing for contact hypersensitivity. Based on these results, PF-07085579 would not be regarded as a skin sensitizer according to the recommendations made in the test guidelines. The test item does not have to be classified and has no obligatory labelling requirement for sensitization by skin contact according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).