p-phenetidine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No data provided on guidelines compliance and no GLP compliance.

Data source

Reference

Reference Type:

publication

Title:

The Immunogenicity of Phenacetin and some of its Metabolites in Guinea Pigs

Author:

Frey JR, Geleick H, Geczy A,de Weck AL

Year:

1974

Bibliographic source:

Int. Arch. Allergy 46: 571-583 (1974)

Report date:

1973

Materials and methods

Principles of method if other than guideline:

- Delayed type skin tests in vivo
-Specific stimulation of sensitized leukocytes in vitro

GLP compliance:

no

Type of study:

Freund's complete adjuvant test

Test material

Test material information

Constituent 1

Reference substance name:

p-phenetidine

EC Number:

205-855-5

EC Name:

p-phenetidine

Cas Number:

156-43-4

Molecular formula:

C8H11NO

IUPAC Name:

4-ethoxyaniline

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: White spotted Himalayan

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: closed colony (Bio, Fullinsdorf)
- Weight at study initiation: 400-500 g
- Diet (e.g. ad libitum): pellet diet with additional green vegetables ad libitum.
- Water (e.g. ad libitum): ad libitum

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: FCA (Freund's complete adjuvant) (i.d.) and water (e.c.)

Induction 2

Concentration / amount:

Sensitizing procedures:
(a) 10 x 0.1 mg in water, i.d., on alternate days
(b) 5 x 1 mg in FCA, i.d., every 2 or 3 days
(c) 5 x 1 mg in water, i.d., every 2 or 3 days
(d) 10 x 10, 3, 1% in PEG

Challenge

Concentration / amount:

Sensitizing procedures:
(a) 10 x 0.1 mg in water, i.d., on alternate days
(b) 5 x 1 mg in FCA, i.d., every 2 or 3 days
(c) 5 x 1 mg in water, i.d., every 2 or 3 days
(d) 10 x 10, 3, 1% in PEG

No. of animals per dose:

8 animals each group

Details on study design:

MAIN STUDY
INDUCTION EXPOSURE
- Exposure period: Induction of delayed hypersensitivity:
Epicutaneous tests: were performed 21-35 days after starting the sensitization course.The reactions were read after 24 h.
Intradermal tests: the tuberculine type reactions were read after 24 h.
- Test groups: phenacetin, N-acetyl-p-aminophenol, phenetidin HCl and 2-hydroxyphenetidin
- Control group: yes
- Site: clipped flank
- Frequency of applications: every 2 or 3 days
- Duration: until 21 days
- Concentrations:
Epicutaneous: 3, 1 and 0.3%
Intradermal: 1%

Results and discussion

Any other information on results incl. tables

Sensitization:

By injecting the four compounds intradermally at the rate of 5 times 1 mg in FCA, PT (phenetidine) and HPT induced contact and delayed hypersensitivity, whereas PA and NAPAP were inactive. In animals sensitized with HPT, epicutaneous cross-reactions with PT were elicited. In PT-sensitized animals, intradermal cross-reactions were elicited with PA and HPT and in HPT-sensitized animals with PT.

Similar results were obtained by injecting 10 times 0.1 mg of the four compounds in water on alternate days. The dose response curve established for PT showed that contact hypersensitivity was obtained with doses as low as 5 times 10 mcg..Doses of 1 mcg and less were inactive.

High degree of contact hypersensitivity to PT was also induced in all animals by epicutaneous application of PT in carbowaxat 10and 3°/o after 8-10 daily applications.

 

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

Sensitizing

Executive summary:

Guinea pigs were sensitized by p-phenetidin and 2-hydroxy p-phenetidin, two minor metabolites of phenacetin, as demonstrated by delayed type skin tests in vivo and by specific stimulation of sensitized leukocytes in vitro, phenacetin itself and the major metabolite N-acetyl-p-aminophenol being inactive. On the other hand, p-phenetidin as well as phenacetin itself induce immunological tolerance and desensitization of already sensitized animals. In this system, however, exclusively the oral route appears to be effective for induction of immunological tolerance and desensitization, in contrast to the intravenous route which is effective in other haptenic systems.