Propazine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17th March 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Contains sufficient detail to suggest GLP-like characteristics even though no statement of certification is reported (reasonably thorough description of authors, dates, design, results, and interpretation).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: "apprisal of the safety of chemicals in foods, drugs and cosmetics (1959), the US Association of food and drug officials (AFDO).

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Maurer, Th., Thomann, P., Weirich, E.G. and Hess, R. (1975) The optimization test in the guinea pig. A method for the predictive evaluation of the contact allergenicity of chemicals. Agents and Actions Vol. 5 (2), 174 - 179, 1975

Deviations:

not specified

GLP compliance:

no

Type of study:

Freund's complete adjuvant test

Test material

Test material information

Constituent 1

Reference substance name:

Propazine

EC Number:

205-359-9

EC Name:

Propazine

Cas Number:

139-40-2

Molecular formula:

C9H16ClN5

IUPAC Name:

6-chloro-N2,N4-bis(propan-2-yl)-1,3,5-triazine-2,4-diamine

Details on test material:

Product designation: propazine
batch No. Lot. 368

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Pirbright white strain

Sex:

male/female

Details on test animals and environmental conditions:

The test was performed on groups of 10 male and 10 female guinea pigs of the Pirbright white strain bred on our premises and weighing between 400 to 450 grams. The animals were housed individually in Macrolon cages, type. 3, kept at a constant room temperature of 22 ± 10 °C, at a relative humidity of 55 ± 5 % and on a 10 hours light cycle day. The animals received ad libitum standard guinea pig pellets NAFAG, No. 830, Gossau SG and water.

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

polyethylene glycol

Induction 2

Concentration / amount:

Both during the induction period and the challenge test has been used a solution of 0.1 % dilution of the test substance in polyethylene glycol (PEG 400) + saline (70 : 30 parts)

Challenge

Challenge 1

Route:

intradermal and epicutaneous

Vehicle:

polyethylene glycol

Challenge 2

Concentration / amount:

Both during the induction period and the challenge test has been used a solution of 0.1 % dilution of the test substance in polyethylene glycol (PEG 400) + saline (70 : 30 parts)

No. of animals per dose:

20 animals

Details on study design:

During the induction period the animals received one injection every second day (except weekends) to a total of 10 intracutaneous injections of a freshly prepared 0.1 % dilution of G 30028 in polyethylene glycol (PEG 400) + saline (70 : 30 parts)
On the first day, injections of 0.1 ml were administered into the shaven skin of the right flank and the back, while on the following days a single intracutaneous injection was given into the back.
During the second and third week of the induction period the test material was .incorporated in a mixture of the normal vehicle with complete Bacto Adjuvant ( Bacto Adjuvant, complete Freud (difco, Michigan, USA) (vehicle : adjuvant = 1 : 1)
Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1 % dilution of the test substance in polyethylene glycol (PEG 400) + saline (70 : 30 parts) was administered into the skin of the left flank.
Twentyfour hours after each injection during the first week of the induction period and 24 hours after the challenge injection the reactions were recorded. Before examination, the reaction sites were depilated chemically (Butoquick®, 5 minutes).

Challenge controls:

Fourteen days after the last sensitizing injection, a challenge injection of 0.1 ml of a freshly prepared 0.1 % dilution of the test substance in polyethylene glycol (PEG 400) + saline (70 : 30 parts) was administered into the skin of the left flank

Positive control substance(s):

no

Study design: in vivo (LLNA)

Positive control substance(s):

not specified

Statistics:

The two largest perpendicular diameters (in mm) and the increase in the skin fold thickness (in mm) were measured and by multiplication of these values reaction vo1ume was obtained (in id) for each reading from each animal. The mean volume plus one standard deviation of the induction reactions observed in the individual animal in the first week was taken as representing the skin irritation threshold for each animal. Any challenge reaction greater than this threshold value in the induction period was graded as an allergic reaction and the animal termed positive. The number of positive animals in the test group was compared with the number of animals in the control group (treated with the vehicle alone) that showed a nonspecific reaction of at least the same magnitude negative control (The exact Fisher test for comparison of the basic probability of two binominal distributions, L. Sachs, Statistische Auswertungsmethoden, Thieme Verlag, Stuttgart, 1971. A probability of less or equal to 0.01 was considered to indicate a significant difference).

Ten days after the intracutaneous challenge injection a subirritant dose of the test compound was applied epicutaneously under occlusive dressings which were left in place for 24 hours.

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

other: control group

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

see statistics

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control group. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: see statistics.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

15

Total no. in group:

20

Clinical observations:

see statistics

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 15.0. Total no. in groups: 20.0. Clinical observations: see statistics.

Results 3

Reading:

other: challenge reactions after occlusive epicutaneous administration of the test compound

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: other: challenge reactions after occlusive epicutaneous administration of the test compound. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Under the experimental conditions employed, significant differences between the test group and the vehicle treated controls were only seen after intradermal challenge administration of. Test solution, i.e. when the skin barrier was intentionally bypassed.

No difference between the test and the control group was seen after epidermal challenge administration. The negative results upon epidermal challenge demonstrate that, in artificially sensitized guineapigs, exposure of the intact skin to the test compound does not provoke contact dermatitis.