N,2-dimethyl-N-phenylbutyramide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test material was examined for possible irritation and sensitisation activity in an experiment with guinea pigs. The Landsteiner/Draize method was used.
The test material was administered by intradermal injections. The test animals were treated repeatedly, the controls only once.

GLP compliance:

no

Remarks:

The study pre-dates the introduction of GLP

Type of study:

other: Landsteiner/Draize method

Justification for non-LLNA method:

LLNA not available at the time of testing.

Test material

Test material information

Constituent 1

Reference substance name:

N,2-dimethyl-N-phenylbutyramide

EC Number:

282-817-4

EC Name:

N,2-dimethyl-N-phenylbutyramide

Cas Number:

84434-18-4

Molecular formula:

C12H17NO

IUPAC Name:

N,2-dimethyl-N-phenylbutanamide

impurity 1

Reference substance name:

Unknown impurities

Molecular formula:

Unknown

IUPAC Name:

Unknown impurities

Test material form:

liquid

Specific details on test material used for the study:

Substance Identification: Gardamide

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Remarks:

albino

Sex:

male

Details on test animals and environmental conditions:

Sixteen male albino guinea pigs, weighing from 201 to 281 g, were divided into two groups of eight animals each, one test group and one control group.

Study design: in vivo (non-LLNA)

No. of animals per dose:

8 per group (test animals and control)

Details on study design:

The test material was administered by intradermal injections. The test animals were treated repeatedly, the controls only once.

PRELIMINARY INVESTIGATIONS
Preliminary observations showed that a concentration of 1 % of the test material induced moderate to severe skin irritation. Therefore, a 1 % dilution of the test material in propylene glycol was used for administration. The dilution was freshly prepared once every week.

A. INDUCTION EXPOSURE
For the induction exposure a 1 % aqueous suspension of the test material was used.
Some days before starting the treatment the right flank of the animals was shaved with electric clippers. Shaving was repeated before each injection and reading if necessary.
During the induction period, the test animals received a total of 10 intradermal injections, 3 times weekly for 3 weeks. The injections were given on different spots on the right flank, within an area of 3 to 4 square cm.
As the first injection, each animal received 0.05 mL of the 1 % dilution; for the 2nd to the 10th injections, 0.1 mL per animal was applied.

B. CHALLENGE EXPOSURE
For the challenge dose a 1 % aqueous suspension of the test material was used.
Two weeks after the 10th induction injection, the challenge dose was given in an amount of 0.05 mL of the 1 % aqueous suspension per animal.
The reaction sites were examined 24 hours after the injection. Diameter, colour and thickness were used as criteria for the intensity of the reaction.

Challenge controls:

At the same time as the challenge exposure in the test animals, the control animals were injected with 0.05 mL of the 1 % aqueous suspension of the test sample. The reaction sites were examined 24 hours after the injection. Diameter, colour and thickness were used as criteria for the intensity of the reaction.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

Table 1 shows the number of individual positive skin reactions observed during the induction and challenge period with the test material.

The test material caused mild to severe skin reactions upon repeated intradermal injections in all animals during the induction period. The challenge dose provoked moderate to severe reactions in all test animals and in all controls which were injected at the same time.

In general, the reactions in the controls were even more pronounced than in the test animals.

From these results it can be concluded that no sensitisation occurred after treatment with the test material.

 

Table 1: Individual Positive Reactions Observed During the Induction and Challenge Phase

Test Animals

Control Animals

Animal number

Individual direct reactions at each injection during the induction phase

Challenge

Animal number

Challenge

1

2

3

4

5

6

7

8

9

10

1836

++

++

++

++

+

++

+++

++

+++

++

++

1844

+++

1837

++

++

++

++

++

++

++

+++

+++

++

++

1845

+++

1838

+

+

++

++

++

++

+

+++

++

+++

+++

1846

+++

1839

++

+

++

+++

+

+

++

++

++

++

++

1847

++

1840

++

++

++

+

+

++

++

+

++

+++

++

1848

+++

1841

++

+

++

++

++

++

+++

+++

++

+++

++

1849

++

1842

++

++

++

++

++

+++

++

++

++

++

++

1850

+++

1843

++

+++

+++

+++

++

++

++

+++

+++

++

++

1851

+++

Degree of reaction:

+ = Mild

++ = Moderate

+++ = Severe

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Gardamide was concluded to be not sensitising in a guinea pig Landsteiner/Draize test. The study was conducted prior to the introduction of GLP or the applicable OECD test guideline.

Executive summary:

In an experiment with male albino guinea pigs, the test material was examined for sensitisation properties using the Landsteiner/Draize test.

The test material was administered by intradermal injections. The test animals were treated repeatedly, the controls only once. Preliminary observations showed that a concentration of 1 % of the test material induced moderate to severe skin irritation. Therefore, a 1 % dilution of the test material in propylene glycol was used for administration. For the challenge dose, a 1 % aqueous suspension of the test material was used.

During the induction period, the test animals received a total of 10 intradermal injections, 3 times weekly for 3 weeks. The injections were given on different spots on the right flank.

Two weeks after the 10th injection, the challenge dose was given. At the same time, the control animals were injected with the 1 % aqueous suspension of the test sample. The reaction sites were examined 24 hours after the injection. Diameter, colour and thickness were used as criteria for the intensity of the reaction.

The test material caused mild to severe skin reactions upon repeated intradermal injections in all animals during the induction period. The challenge dose provoked moderate to severe reactions in all test animals and in all controls which were injected at the same time. In general, the reactions in the controls were even more pronounced than in the test animals.

From these results, it can be concluded that no sensitisation occurred after treatment with the test material.