Octanal

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

other: validation data generation for two methods of assessing sensitisation potential and predictivity for humans

Adequacy of study:

weight of evidence

Study period:

No data provided

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Findings are presented for 271 substances to determine the relatively predictivity of the methods of Klecak compared with human patch test results. Octanal is mentioned as one of these substances. The methods used in this assay became the standard basis for regulatory test guidelines and the conclusion on octanal sensitising potential determined by these methods is considered reliable, in conjunction with supporting negative human data

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

The Freund's Complete Adjuvant Test was conducted on male and female guinea pigs, in which a group of 268 test substances were tested for their ability to cause skin sensitisation. Intradermal induction and open epicutaneous challenge doses were applied and skin reactions were observed 24, 48 and 72 hours following challenge application.

GLP compliance:

not specified

Type of study:

Freund's complete adjuvant test

Justification for non-LLNA method:

This data is submitted alongside an existing LLNA method as weight of evidence.

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: No information provided
- Age at study initiation: Not documented
- Weight at study initiation: 300 - 450g
No further information available in publication

Route:

intradermal

Vehicle:

no data

Concentration / amount:

For the FCAT study
0.1ml of the test material in a 5% Freund's Complete Adjuvant (FCA) solution - the induction concentration for n-octanal is not specified
For the challenge application concentrations of 100, 30, 10, 3, 1 or 0.3% were selected- based on the non-irritant levels identified in the preliminary phase

Route:

epicutaneous, open

Vehicle:

no data

Concentration / amount:

For the FCAT study
0.1ml of the test material in a 5% Freund's Complete Adjuvant (FCA) solution - the induction concentration for n-octanal is not specified
For the challenge application concentrations of 100, 30, 10, 3, 1 or 0.3% were selected- based on the non-irritant levels identified in the preliminary phase

No. of animals per dose:

For the FCAT assay:
2 groups of 10 - 20 guinea pigs per group.
An additional 4 guinea pigs were used to determine the primary irritation concentrations of the test substance so that non-irritating concentrations were chosen for the challenge.

Details on study design:

RANGE FINDING TESTS:
4 guinea pigs were used to determine the primary irritation concentrations of the test substance so that non-irritating concentrations were chosen for the challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 times (on days 1, 5 and 9) during the exposure period of 9 days.
- Exposure period: 9 days
- Test groups: 0.1 ml of the test material in FCA was intradermally administered into the scapula region on an area of 6 x 2 cm.
- Control group: The animals of the control group were treated with 0.1ml of FCA only
- Site: Scapula region, on a shaved area approximately 6 x 2 cm.
- Frequency of applications: Once on each of the exposure days
- Duration: Not documented
- Concentrations: The final concentrations of the emulsion are 5%.

B. CHALLENGE EXPOSURE
- No. of exposures: 2 exposures on Days 21 and 35.
- Day(s) of challenge: Days 21 and 35
- Exposure period: 24 hours
- Test groups: On the contralateral flank, 0.025ml of the test compound was applied at the minimal irritating and some lower nonirritating concentrations. The applications were made using a pipette to skin areas measuring 2cm2.
- Control group: On the contralateral flank, 0.025ml of the test compound was applied at the minimal irritating and some lower nonirritating concentrations. The applications were made using a pipette to skin areas measuring 2cm2.
- Site: The contralateral flank
- Concentrations: 10%
- Evaluation (hr after challenge): The reactions were read at 24, 48 and 72 hours after challenge application.

OTHER:

Challenge controls:

No information provided

Positive control substance(s):

not specified

Positive control results:

No information

Reading:

other:

Clinical observations:

At the test concentration used in this study, the test substance did not elicit any allergenic responses.

Remarks on result:

other: Reading: other:. Clinical observations: At the test concentration used in this study, the test substance did not elicit any allergenic responses..

The FCAT assay is significantly more sensitive than HRIPT in predicting sensitisation. 157 substances were correlated for positive or negative results for human RIPT and the FCAT assay but 106 negative HRIPT tests gave positive FCAT results. The false negative rate was lower with 5 positive HRIPT tests not detected by FCAT. Of the 290 test substances 271 were negative in both the OET and HRIPT, a further 12 were positive in both tests and only 7 materials gave false positive or false negative responses. The maximum user concentration for Aldehyde C-8 was 0.06%, the concentration tested in HRIPT was 0.25% giving a negative result. The range of concentrations used in FCAT and OET also gave negative results.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test substance under examination was not considered to be a potential allergen and as such, was not considered to be a skin sensitiser.

Executive summary:

In a study conducted by Klecak (1985), test substances under examination were tested for their ability to induce skin sensitisation in a Freund's Complete Adjuvant Test. The test substances were applied to an area of the scapula region measuring 6 x 2 cm of 10 to 20 male and female guinea pigs per test and control group at a concentration of 5% solution in Freund’s Complete Adjuvant. The control animals were treated with 0.1ml of FCA only. The test was applied intradermally 3 times during the 9 day induction, specifically on days 1, 5 and 9. Following a range-finding test to determine the maximal irritating and minimal irritating test substance concentrations in which the test substance was tested at 3, 10, 30 and 100%, a concentration of 10% was chosen as the challenge concentration. On days 21 and 35 of the study, the challenge dose of 10% of test solution was applied to the contralateral flank of each test and control animal. The site was left uncovered. Skin reactions were examined 24, 48 and 72 hours after application.  At the test concentrations used in this study, octanal did not elicit any allergenic responses and as such, was not considered to be a skin sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a study conducted by Klecak (1985), the test substances under examination were tested for their ability to induce skin sensitisation in a Freund's Complete Adjuvant Test. The test substances were applied to an area of the scapula region measuring 6 x 2 cm of 10 to 20 male and female guinea pigs per test and control group at a concentration of 5% solution in Freund’s Complete Adjuvant. The control animals were treated with 0.1ml of FCA only. The test was applied intradermally 3 times during the 9 day induction, specifically on Days 1, 5 and 9. Following a range-finding test to determine the maximal irritating and minimal irritating test substance concentrations in which the test substance was tested at 3, 10, 30 and 100%, a concentration of 10% was chosen as the challenge concentration. On Days 21 and 35 of the study, the challenge dose of 10% of test solution was applied to the contralateral flank of each test and control animal. The site was left uncovered. Skin reactions were examined 24, 48 and 72 hours after application. At the test concentrations used in this study, the test substance did not elicit any allergenic responses and as such, was not considered to be a skin sensitiser.

The paper authored by Klecak based on the FCAT results also provides a comparison of FCAT responses with human repeat insult patch test results, but it does not provide sufficient detail relating to the octanal response in this comparison. The paper also provides results for the Open epicutaneous test and again compares octanal response in the OET and HRIPT. In this case it is reported that octanal gave a negative response in both assays. However, the method details are omitted, a full description of results and methods of assessing reactions are all presented in minimal detail. 

In a study conducted by Watanabe (2001), octanal was tested for its ability to induce skin sensitisation. Guinea pigs were sensitised intracutaneously on both sides of the abdomen for 7 days at a concentration of 0.1 mL of 1% n-octanal/day. Three weeks later n-octanal was injected intracutaneously to 12 male guinea pigs per test and control group at a concentration of 0.1%, 0.5% and 1.0% of n-octanal. Control animals received 0.1 ml of saline-I % Tween 80 solution intracutaneously instead of the n-octanal solution. At the test concentrations used in this study, the test substance did elicit allergenic responses and as such, was considered to be a potential skin sensitiser. However this single result was not consistent with other investigations or human exposure experiences.

As the two reported studies provide both a positive and negative response it is considered appropriate keep the classification of octanal as a non-sensitiser based on the classification provided in the IFRA/IOFI Labelling Manual 2010, Attachment III.

Migrated from Short description of key information:

Two studies are available for evaluation of skin sensitisation.  In the first, an intracutaneous test, octanal was identified as having sensitising potential. In the second, a comparison of results from two complementary assays - the FCAT and OET tests, octanal is not identified as eliciting sensitisation in either guinea pig study, nor in the human repeat insult patch test used for comparative purposes.

Justification for selection of skin sensitisation endpoint:

The methods of Klecak and others set out in this publication formed the basis of standard regulatory test guidelines and the conclusions drawn from these results in realtion to octanal are considered valid, with supporting results from other investigations

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin Sensitisation:

Classification as a skin sensitiser according to Regulation EC No. 1272/2008 is not considered appropriate for octanal. One study indicated the potential to elicit a sensitisation response was present but two further studies indicated that potential was not expressed in humans or guinea pigs. Refer to section 7.10.4 for human sensitisation RIPT results.