Nonanoic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1965

Report date:

1965

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Principles of method if other than guideline:

delayed contact hypersensitivity in the guinea pig

GLP compliance:

no

Type of study:

Buehler test

Justification for non-LLNA method:

there is no justification why in the past (1981) the study was performed using Buehler test.

Test material

Test material information

Constituent 1

Reference substance name:

Nonanoic acid

EC Number:

203-931-2

EC Name:

Nonanoic acid

Cas Number:

112-05-0

Molecular formula:

C9H18O2

IUPAC Name:

nonanoic acid

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): C-182

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: males 302 to 396 grams; females 303 to 367 grams
- Housing: singly in suspended stainless steel cages
- Diet: Charles River Vitamin-C fortified Guinea pig diet, ad libitum
- Water: automatic watering system, ad libitum
- Acclimation period: 16 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 65-75°F
- Photoperiod (hrs dark / hrs light): 12/12 hours

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: 80 % Ethanol and Acetone (induction); acetone (challenge)

Induction 2

Concentration / amount:

Induction: 100%
Challenge: 10%;
Re-challenge: 25%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: 80 % Ethanol and Acetone (induction); acetone (challenge)

Challenge 2

Concentration / amount:

Induction: 100%
Challenge: 10%;
Re-challenge: 25%

No. of animals per dose:

20 (10 male, 10 females) in the definitive experiment received the test substance

Details on study design:

RANGE FINDING TESTS:
- No. of animals: 16
- Vehicle: acetone
- Concentrations: 5, 10, 25, 50, 75, and 100%
- Application of test material: each animal was dosed with two to four different concentrations, at different sites of the clipped dorsal skin.
- Application of test material: 0.2 mL of test material mixture was applied beneath a surgical gauze square, placed directly to the test site. The gauze was covered with plastic sheeting and held in place with an elastic adhesive bandage.
- Evaluation of skin reactions: observation for signs of skin irritation were made approx. 24 and 48 hours after dosing. Evaluation was made according to OECD TG 406, paragraph 23.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9 expoures in total; 3 exposures per week
- Exposure period: 3 weeks
- Test groups: 20 animals (10 m, 10 f)
- Control group:
-- Positive control; DCNB; 12 animals (6 m, 6 f)
-- Irritation control (challenge only): pelargonic acid 8 animals; DCNB 8 animals (4m, 4f each)
- Site: dorsal skin, right side of the midline
- Frequency of applications: 3 exposures per week
- Duration: 6 hours each
- Concentrations:
-- pelargonic acid: 100% inductions 1-5; 75% from the 6th induction onwards, due to severe skin irritation
-- DCNB: 0.5 and 0.75% during inductions 1 through 8; ninth induction was omitted due to severe skin irritation


B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 1
- Exposure period: 6 hours
- Test groups: as above
- Control group: as described above
- Site: dorsal skin, sites left of the midline
- Concentrations:
--pelargonic acid: 10% (challenge); 25% (re-challenge, 7 days after first challenge))
-- DCNB: 0.1% at challenge and at re-challenge
- Evaluation (hr after challenge): 24 and 48 after challenge dosing (and after re-challnge dosing)


OTHER: Re-challenge was made 7 days after the challenge treatment

Challenge controls:

yes

Positive control substance(s):

yes

Remarks:

2,4-dinitrochlorbenzene

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Remarks on result:

not measured/tested

Results 2

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

other: irritation controls, DCNB (or pelargonic acid) only

No. with + reactions:

0

Total no. in group:

16

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: irritation controls, DCNB (or pelargonic acid) only. No with. + reactions: 0.0. Total no. in groups: 16.0.

Results 3

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

other: irritation controls, DCNB (or pelargonic acid) only

No. with + reactions:

0

Total no. in group:

16

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: irritation controls, DCNB (or pelargonic acid) only. No with. + reactions: 0.0. Total no. in groups: 16.0.

Results 4

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 5

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 6

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

other: test group, re-challenge

Dose level:

25%

No. with + reactions:

3

Total no. in group:

20

Clinical observations:

barely perceptible erythema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: test group, re-challenge. Dose level: 25%. No with. + reactions: 3.0. Total no. in groups: 20.0. Clinical observations: barely perceptible erythema.

Results 7

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

other: test group, re-challenge

Dose level:

25%

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

barely perceptible erythema

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: test group, re-challenge. Dose level: 25%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: barely perceptible erythema.

Results 8

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1%

No. with + reactions:

10

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 20.0.

Results 9

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.1%

No. with + reactions:

10

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 20.0.

Any other information on results incl. tables

 

Pelargonic acid:

0/20 test animals challenged with 10-% test substance exhibited any dermal response, 3/20 showed barely perceptible erythema (+/-) after challenge with 25% test substance at 24 h, and 1/20 at 48 h. No irritation responses were noted in the corresponding controls with the 10- and 25-% solutions. Scores of +/- are considered equivocal.

Positive control, DCNB:
9/12 animals challenged with the positive control, 0.1% 2,4-dinitrochlorobenzene, had a score of 1 and greater. No responses for the irritation controls for this treatment were observed. This means 9/12 animals showed positive results (because of a dermal score of 1 or greater, in the absence of a dermal response in irritation control animals).

 

 

 

Materials	Hr	Erythema evaluation scores					Total No. of animals
		0	+/-	1	2	3
DCNB, 0.1%	24	2	1	3	6	0	12
	48	2	2	4	4	0
Irritation control	24	8	0	0	0	0	8
	48	8	0	0	0	0
Pelargonicacid10%	24	20	0	0	0	0	20
	48	20	0	0	0	0
Re-challenge, 25%	24	17	3	0	0	0	20
	48	19	1	0	0	0
Irritation control	24	8	0	0	0	0	8
	48	8	0	0	0	0
Re-challenge irritationcontrol	24	7	1	0	0	0	7
	48	7	1	0	0	0

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance exhibited no potential to produce dermal sensitization in a Buehler test using guinea pigs.

Executive summary:

A dermal sensitisation study was performed according to OECD TG 406 (Buehler) using Hartley guinea pigs. During induction, pelargonoic acid was applied at a concentration of 100% ( at 75% beginning with the 6th treatment due to severe dermal irritation) to a surgical gauze which was directly placed onto the dorsal skin under occlusive conditions for 6 hours. 9 induction treatments were performed within 3 weeks. No dermal sensitisation reaction was seen at 24 and 48 hours after a challenge (patch technique; 14 days after the last induction insult; concentration 10%). Following a re-challenge (patch technique; 7 days after the first challenge; concentration 25%), 3 out of 20 animals exhibited barely perceptible erythema after 24 and 48 h, which were stated to be ambiguous concerning the sensitisation potential of the test substance. Hence the test item elicited no skin sensitisation potential.