Hexanoic acid

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Relative irritancy of free fatty acids of different chain length

Author:

Stillman, M.A. et al.

Year:

1975

Bibliographic source:

Contact Dermatitis 1:65 - 69

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

skin irritation / corrosion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Hexanoic acid and further fatty acids in 0.5 M and 1 M concentrations were applied daily under occlusive patch tests to human skin until detectable erythema appeared or until the experiment terminated after 10 consecutive days of applications. In addition intradermal injections of hexanoic acid in 0.01 M and 0.1 M concentrations were performed; each site was evaluated at 24 h and 48 h for erythema and induration.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexanoic acid

EC Number:

205-550-7

EC Name:

Hexanoic acid

Cas Number:

142-62-1

Molecular formula:

C6H12O2

IUPAC Name:

hexanoic acid

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 35 in total: 20 volunteers for patch test (10 volunteers for 0.5 M fatty acids and 10 volunteers for 1.0 M fatty acids) and 15 volunteers for intradermal injections (5 volunteers for 0.01 M fatty acids and 10 volunteers for 0.01 M and 0.1 M of each fatty acid).
- Demographic information: white men, not further specified

Route of exposure:

other: dermal (occlusive) and intradermal

Reason of exposure:

intentional

Exposure assessment:

not specified

Details on exposure:

The irritant potential of the test substance in human volunteers was evaluated after (A) dermal and (B) intradermal exposure.

A) For the dermal route, A1-test ® patches (Imeco, Astra Agency, Stockholm, Sweden) were saturated with 0.04 mL test solution (0.5 M and 1 M hexanoic acid in propanol) and applied on the interscapular area of the volunteers. The patch was held in place via occlusive coverage with a Blenderm® tape (Minnesota Mining and Manufacturing Company, St. Paul, MN, USA). After 24 h, the patches were removed and the skin reactions were evaluated 30 min later. If no erythema were visible, the volunteers were re-exposed for a maximum of 10 consecutive days. If erythema were present over the entire patch area, no further application occurred on the respective volunteer and the number of days needed to induce the erythema was recorded. Propanol saturated patches served as vehicle control and were applied to each volunteer.

B) For the intradermal route, 0.1 mL of the test solution (0.01 M and 0.1 M hexanoic acid in olive oil) were injected into the back of the volunteers. After 24 h and 48 h, each site was evaluated for erythema and induration. As vehicle control, olive oil was injected in all volunteers.

Examinations:

A) Dermal application:
After 24 h exposure, the patches were removed and the skin reactions (erythema) were evaluated 30 min later.

B) Intradermal exposure:
24 h and 48 h after intradermal exposure, each site was evaluated for erythema and induration.

Results and discussion

Clinical signs:

A) Dermal application
0.5 M hexanoic acid induced erythema in 1 out of 10 volunteers after re-exposure for 7 consecutive days.
1 M hexanoic acid resulted in the formation of erythema in 7 out of 10 volunteers after a distinct number of treatments at consecutive days: 1 volunteer reacted after re-exposure for 2 days; 1 volunteer after 3 and and another volunteer after 7 days; 4 volunteers showed erythema after re-exposure for 8 days. The vehicle propanol did not induce erythema formation.

B) Intradermal injection
All volunteers showed slight indurations of 5 mm and mild erythema after injection of hexanoic acid (0.01 M and 0.1 M) and the vehicle control (olive oil). No difference between the test and control sites was visible.

Any other information on results incl. tables

Table 1: Cumulative number of subjects responding to 0.5 M and 1 M hexanoic acid (total of 10 subjects each)

Day	0.5 M (5.8% w/v)	1.0 M (11.6% w/v)
1	0	0
2	0	1
3	0	2
4	0	2
5	0	2
6	0	2
7	1	3
8	1	7
9	1	7
10	1	7

 

Applicant's summary and conclusion

Conclusions:

Daily dermal application of 1 M hexanoic acid (11.6% (w/v)) resulted in erythematous responses in 7 out of 10 subjects till the termination of the study on day 10. One out of 10 volunteers showed erythema after daily dermal application of 0.5 M hexanoic acid (5.8% (w/v)). No differences between control and test sites have been noted after intradermal injections of 0.01 M or 0.1 M hexanoic acid.
Based on these results, hexanoic acid is considered to produce skin irritation in humans after chronic exposure in a concentration dependent manner.