Valeraldehyde

Endpoint summary

Description of key information

No skin sensitisation tests could be identified for n-valeraldehyde. But there is information available from a reliable LLNA with the structural similar 2-methylbutanal. Based on the information with the source substance 2-methylbutanal it is concluded that n-valerladehyde is a weak skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For details on endpoint specific justification please see read-across justification report attached to this endpoint study record.

Reason / purpose for cross-reference:

read-across source

Parameter:

SI

Value:

4.4

Test group / Remarks:

100%, 6 animals

Parameter:

SI

Value:

0.9

Test group / Remarks:

25%, 6 animals

Parameter:

SI

Value:

1

Test group / Remarks:

5%, 6 animals

Parameter:

SI

Remarks on result:

other: See table below. For the 5% and 25% group no significant response was observed. For the 100% group, the radioactivity count was increased about 4 fold. A SI of 4.4 was calculated. EC3 was calculated to be 70%.

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: See Table below

Results of the local lymph node assay with source substance (mean ± sd)

 

Concentration	DPM	SI
Solvent control	550.50 ± 351.43	1.0 ±0.6
5%	546.83 ± 399.41	1.0 ± 0.6
25%	494.17 ± 212.05	0.9 ± 0.4
100%	2466.4 ± 803.88*	4.4 ± 1.4
Positive control	4073.8 ± 1325.3*	7.4 ± 2.4

 

* statistically different; α = 0.05

 

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

In this LLNA, a positive response was only obtained after application of the highest dose (100% test substance). At this dose, local irritation reaction was observed. Test groups exposed to 5% and 25% test substance solution did not show any reaction. The 50% solution was not tested. Thus there is no information about an effect in the concentration range between 25% and 100% (additional value in dose-response-plot).

Executive summary:

The study used as source investigated the effect of 2-methylbutyraldehyde on skin sensitisation. The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross reference “assessment report”.

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no individual caging, test substance concentrations were not in consecutive order)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

no individual caging, test substance concentrations were not in consecutive order

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan, Indianapolis, IN, USA
- Age at study initiation: approx. 10 - 11 weeks
- Weight at study initiation:
- Housing: up to 6 per cage in filter tubs containing corncob bedding
- Diet (e.g. ad libitum): LabDiet Certified Rodent Diet #5002 (PMI Nutrition International, St. Louis, MO, USA) in pelleted form, ad libitum
- Water (e.g. ad libitum): municipal drinking water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 40 - 70
- Air changes (per hr): 12 - 15 times/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

5, 25, and 100 % test substance in vehicle

No. of animals per dose:

6

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: soluble in vehicle
- Application: one female mouse was used per concentration (1%, 5%, 25%, 50%, 75%, and 100% of test substance). Animals received one application of test solution on three consecutive days spread on the dorsal surface of each ear (25µL/ear) in a manner to prevent material loss
- Irritation: pure (100%) test substance caused slight erythema at day 3 which resolved by day 6
- Lymph node proliferation response: no data

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: local lymph node assay
- Criteria used to consider a response positive: a stimulation index (SI) of ≥ 3 (i.e., 3-fold greater proliferation than control animals) is considered positive for dermal sensitization potential of the test substance

TREATMENT PREPARATION AND ADMINISTRATION
- Test solutions:Test solutions were prepared daily just prior to dosing. Concentrations were not verified analytically.
- Administration: test material (25 µL/ear) was administered once daily for three consecutive days on the dorsal surface of both ears using an adjustable pipette as for the range finding test.

OBSERVATIONS
- Visual control of ears, evaluation of erythema: prior to application and on day 2, 3 and 6
- Weighing: on day 1 and 6

TREATMENT WITH 3H-THYMIDINE AND PREPARATION OF LYMPH NODE CELL SUSPENSION
- 3H-Thymidine treatment: on day 6 five hours prior to sacrifice, all mice received a 250 µL intravenous injection via the lateral tail vein containing 20 µCi of 3H-thymidine (specific activity 2Ci/mmol) diluted in phosphate buffered saline (PBS).
- Isolation of lymph nodes: both of the auricular lymph nodes per mouse were excised. Single cell suspensions in PBS were prepared by gentle mechanical disaggregation using a tissue homogenizer. Cells were washed twice and suspended in trichloroacetic acid for approx. 18 h. The resulting precipitate was separated by centrifugation and the radioactivity in each precipitate was measured using ß-scintillation counting.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Means and standard deviation (SD) were generated for body weight data (absolute and gain) and the LLNA response (dpm & SI values).
Body weight and dpm data were analyzed by a one-way analysis of variance. When differences were indicated by the ANOVA, a comparison of treated vs. control groups was done using a Dunnett’s t-test. The alpha level at which all tests were conducted was 0.05.

Parameter:

SI

Value:

4.4

Test group / Remarks:

100%, 6 animals

Parameter:

SI

Value:

0.9

Test group / Remarks:

25%, 6 animals

Parameter:

SI

Value:

1

Test group / Remarks:

5%, 6 animals

Parameter:

SI

Remarks on result:

other: See table below. For the 5% and 25% group no significant response was observed. For the 100% group, the radioactivity count was increased about 4 fold. A SI of 4.4 was calculated. EC3 was calculated to be 70%.

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: See Table below

Results of the local lymph node assay (mean ± sd)

 

Concentration	DPM	SI
Solvent control	550.50 ± 351.43	1.0 ±0.6
5%	546.83 ± 399.41	1.0 ± 0.6
25%	494.17 ± 212.05	0.9 ± 0.4
100%	2466.4 ± 803.88*	4.4 ± 1.4
Positive control	4073.8 ± 1325.3*	7.4 ± 2.4

 

* statistically different; α = 0.05

 

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

In this LLNA, a positive response was only obtained after application of the highest dose (100% test substance). At this dose, local irritation reaction was observed. Test groups exposed to 5% and 25% test substance solution did not show any reaction. The 50% solution was not tested. Thus there is no information about an effect in the concentration range between 25% and 100% (additional value in dose-response-plot).

Executive summary:

In a local lymph node assay with 2-methylbutyraldehyde (2-methylbutanal) (purity 98.2%), adult female CBA/J mice (6 animals per group) were tested using concentrations of 5, 25, and 100% test substance in vehicle (4:1 acetone/olive oil). Hexyl cinnamic aldehyde (30% in vehicle) was used as positive control material.

 

The positive control substance displays the appropriate response. For 2-methylbutyraldehyde, there was no effect of treatment on body weight development. Skin irritation, which resolved in all mice by day 6, was only observed on day 3 in mice dosed with 100% test substance (slight to well-defined erythema, 4 and 2 of 6 mice respectively). Increases in lymph cells were only observed in the 100% test group. For this group a SI of 4.4 was determined. EC3 was 70%.

 

In this study, 2-methylbutanal is a weak dermal sensitizer (categorized according to the expert ECETOC panel - Technical Report No. 87, 2003) (Dow 2008).

 

This study is classified as acceptable. It was performed according to OECD test guideline 429 with some restrictions (no individual caging, test substance concentrations were not in consecutive order).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

No skin sensitisation tests could be identified for valeraldehyde.

Results from a Local-Lymph-Node Assay with the structural similar 2-methylbutanal are used for the assessment of the skin sensitising potency of n-valeraldehyde in a read across approach.

To cover the data requirement for the target substance concerning skin sensitisation a study according to OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay) conducted with the source substance was regarded as adequate and reliable and therefore suitable for read-across. The reliability of the study is evaluated with Klimisch score 2 (reliable with restrictions), since the study was well conducted with acceptable restrictions (no individual caging, test substance concentrations with a remarkable gap between 25% and 100%) and compliant to GLP.

The study was performed using the preferred animal species (adult female CBA/J mice; 6 animals per group). Sufficient dose levels in adequate spacing were administered during the dose range finding study [1%, 5%, 25%, 50%, 75%, and 100% of test substance in vehicle (4:1 acetone/olive oil); one application of test solution on three consecutive days spread on the dorsal surface of each ear (25µL/ear)], where pure test substance caused slight erythema at day 3 which resolved by day 6. In the main study, concentrations of 5%, 25% and 100% test substance in vehicle (4:1 acetone/olive oil) were tested. A positive response was only obtained after application of the highest dose (100% test substance). At this dose, local irritation reaction was observed. Test groups exposed to 5% and 25% test substance solution did not show any reaction, nor did the 50% and 75% concentration during the dose range finding study. Hexyl cinnamic aldehyde (30% in vehicle) was used as positive control and the treated animals displayed the appropriate response. For 2-methylbutanal (source substance), there was no effect of treatment on body weight development. Skin irritation, which resolved in all mice by day 6, was only observed on day 3 in mice dosed with 100% test substance (slight to well-defined erythema, 4 and 2 of 6 mice respectively). Increases in lymph cells were only observed in the 100% test group. For this group a stimulation index (SI) of 4.4 was determined. An estimated concentration needed to produce a stimulation index of 3 (EC3) of 70% has been calculated. In this study, 2-methylbutanal is a weak dermal sensitizer (categorized according to the expert ECETOC panel - Technical Report No. 87, 2003) and skin sensitiser under Regulation (EC) No. 1272/2008 of Category 1B.

 

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on read-across to data with the structural similar 2-methylbutanal it is concluded that valeraldehyde is a weak skin sensitiser and requires classification as skin sensitiser - Category 1B under Regulation (EC) No. 1272/2008.