N-methylformanilide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

THE SENSITIZATION POTENTIAL OF SOME PERFUME INGREDIENTS TESTED USING A MODIFIED DRAIZE PROCEDURE

Author:

D.W. SHARP

Year:

1978

Bibliographic source:

Toxicology, 9 (1978) 261-271

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Modified Draize Technique

Principles of method if other than guideline:

Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical

GLP compliance:

not specified

Type of study:

other: Modified Draize Technique

Justification for non-LLNA method:

Not specified

Test material

Test material information

Constituent 1

Reference substance name:

Benzyl formate

EC Number:

203-214-4

EC Name:

Benzyl formate

Cas Number:

104-57-4

Molecular formula:

C8H8O2

IUPAC Name:

Benzyl formate

Test material form:

liquid

Details on test material:

Details on test material
-Name of the test material : benzyl formate
-Substance type : Organic
-Physical state : colorless liquid
- Molecular formula: C8H8O2
- Molecular weight : 136.14792 g/mol
- Smiles notation: C1=CC=C(C=C1)COC=O
- Purity : No data available
- Impurities (identity and concentrations): No data available

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 350 g
- Housing: Housed in wire mesh cages in pairs of the same sex
- Diet (e.g. ad libitum): Pelleted guinea pig diet, cabbage and hay ad libitum
- Water (e.g. ad libitum): water ad libitum

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

Induction concentration: 0.1 mL at 2.5 X 0.25%(ICC) : 10 guinea pigs

Adequacy of induction:

other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC).

Challenge

Challenge 1

No.:

#1

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

Challenge concentration: 0.1 mL at 0. 25% (ICC) and 20% (ACC): 10 guinea pigs
Re- challenge concentration: 0.1 mL at 0.25%(ICC) and 20% (ACC): 10 guinea pigs

Day(s)/duration:

24 hours

Adequacy of challenge:

other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC). The highest concentration which caused no irritation was selected as the application challenge concentration (ACC).

Challenge 2

No.:

#1

Route:

epicutaneous, open

Vehicle:

not specified

Concentration / amount:

Challenge concentration: 0.1 mL at 0. 25% (ICC) and 20% (ACC): 10 guinea pigs
Re- challenge concentration: 0.1 mL at 0.25%(ICC) and 20% (ACC): 10 guinea pigs

Day(s)/duration:

24 hours

Adequacy of challenge:

other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC). The highest concentration which caused no irritation was selected as the application challenge concentration (ACC).

No. of animals per dose:

10: 4 males and 6 females

Details on study design:

MAIN STUDY
RANGE FINDING TESTS: For each test material preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing.


A. INDUCTION EXPOSURE: Intradermal
- No. of exposures:4
- Exposure period: No Data Available
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: 4 sites, 2 auxillary and 2 inguinal lymph nodes
- Frequency of applications:1
- Duration: No Data Available
- Concentrations: 0.1 mL at 2.5 X 0.5% (ICC)

B. CHALLENGE EXPOSURE: Intradermal and Epicutaneous
- No. of exposures:1
- Day(s) of challenge: Fourteen days later, challenge test was performed
- Exposure period:24 hours
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: onto the shaved flank in a small circular area
- Concentrations: 0.1 mL at 0.5% (ICC) and 10%(ACC).
- Evaluation (hr after challenge):24 hours

C. RECHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: 7 Days Later , rechalleange test was performed.
- Exposure period: No Data Available
- Test groups:10 animal
- Control group: 4 animal (same sex)
- Site: Intradermally and topically on opposite flanks
- Concentrations: 0.1 mL at 0.5% (ICC) and 10% (ACC).
- Evaluation (hr after challenge): No Data Available

-Other:

Observations and scoring –
Each injection reaction was given a total score based on size (2 largest diameters), erythema and oedema. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale. Reactions were examined under a Philips colour-matching unit with 3 Philips 40 W Actinic Blue 05 fluorescent tubes and 3 Philips 40 W White 35 fluorescent tubes.

Challenge controls:

At each challenge with controls, 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively

Positive control substance(s):

not specified

Results and discussion

Positive control results:

no data

In vivo (non-LLNA)

Results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 mL at 0.25% (ICC) and 20 (ACC).

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Negative results were observed in treated groups.

Remarks on result:

no indication of skin sensitisation

In vivo (LLNA)

Cellular proliferation data / Observations:

No skin sensitization reaction were observed.

Any other information on results incl. tables

SENSITIZATION POTENTIAL OF SYNTHETIC PERFUME INGREDIENTS

Non-sensitizer = no evidence of sensitization

Test chemical	ICC(%)	ACC(%)	Results
test chemical	0.25	20	Not sensitizer

 

Applicant's summary and conclusion

Interpretation of results:

other: Not sensitizing

Conclusions:

 
No signs of contact sensitization were observed at 0. 25% ICC and 20% ACC concentrations. Hence, the test chemical was considered to be non-sensitizingto the skin of albino Hartley guinea pigs.

Executive summary:

Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical.

Hartley strain albino guinea pigs bred were used for the study. Four guinea pigs of same sex were used for the preliminary irritation study and 10 guinea pigs were used for the main sensitization studyand 4 previously untreated animals of the same sexwere used as challenge controls.

The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC) ]

The ICC and ACC for the test chemical was determined to be 0.25% and 20% respectively

In the induction phase, 0.1 ml aliquots of test substance at 2.5 times the ICC were injected intradermally at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes. After a rest period of 14 days, each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC: the topical application was made by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.At each challenge with controls, 4 previously untreated animals of the same sex were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively.

 

Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls.

 

No signs of contact sensitization were observed at 0. 25% ICC and 20% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.