Valeraldehyde

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Valeraldehyde

EC Number:

203-784-4

EC Name:

Valeraldehyde

Cas Number:

110-62-3

Molecular formula:

C5H10O

IUPAC Name:

pentanal

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): n-Valeraldehyde
- Test substance No.: 06/0576-1
- Batch No.: Verkaufstank B533 v. 05.09.06
- Purity: >99%
- Homogeneity: given
- Stability: The stability will be verified by reanalysis after completion of the administration period of the subsequent guideline study
- Date of production September 05, 2006
- Physical state / Appearance: Liquid/colorless, clear
- Storage conditions: Refrigerator (KS), under N2, under light exclusion

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 d

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

5

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes


DETAILED CLINICAL OBSERVATIONS: Yes


BODY WEIGHT: Yes


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: on days 7, 14 and 29


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on days 7, 14 and 29

Other examinations:

The plasma metabolome was examined by metanomics GmbH after appropriate sample work up using GC/MS and LC/MS techniques. Test substance related changes in the metabolome were compared to typical metabolite profiles (up- and down-regulations of the analytes) of known toxicological modes of action. Based on these evaluations, the toxicological mode of action (including target organs and toxic mechanisms) of the test substance was assessed.

Results and discussion

Results of examinations

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Details on results:

1000 mg/kg bw:
- N-VALERALDEHYDE showed almost no changes in the metabolite profile compared to the control in both sexes (p < 0.05; based on 290 metabolites).
- The metabolite profile of N-VALERALDEHYDE in both sexes did not match with the specific metabolite profiles of a number of modes of action in the MetaMapTox database: males: the best matches were with compounds that did not indicate a clear spectrum of toxicity (up to 28 % concordance). females: the best matches were also with compounds that did not indicate a clear spectrum of toxicity (up to 17 % concordance).
- N-VALERALDEHYDE did not match established metabolite profiles for specific toxicity in both males and females.

300 mg/kg bw:
- N-VALERALDEHYDE showed almost no changes in the metabolite profile compared to the control in both sexes (p < 0.05; based on 290 metabolites).
- The metabolite profile of N-VALERALDEHYDE in both sexes did not match with the specific metabolite profiles of a number of modes of action in the MetaMapTox database: males: the best matches were with compounds that did not indicate a clear spectrum of toxicity (up to 25 % concordance).
females: the best matches were also with compounds that did not indicate a clear spectrum of toxicity (up to 29 % concordance).
- N-VALERALDEHYDE did not match established metabolite profiles for specific toxicity in both males and females.

Effect levels

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: clinical signs; body weight; food consumption haematology; clinical chemistry; organ weights

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Results:

- N-VALERALDEHYDE showed almost no changes in the metabolite profile compared to the control in both sexes (p<0.05; based on 290 metabolites):

dose group	sex	Change compared to control	d 7	d 14	d 28
1000 mg/kg bw	males	up	2	9	7
		down	2	0	2
	females	up	14	2	5
		down	1	6	3
300 mg/kg bw	males	up	3	1	0
		down	3	1	5
	females	up	11	9	3
		down	3	7	3

Applicant's summary and conclusion

Conclusions:

Based on the metabolome analysis it is concluded that n-valeraldehyde is unlikely to have a significant systemic toxicological potential in oral studies in rats.

Executive summary:

5 male and female Wistar rats were treated with valeraldehyde via oral gavage for 28 days at doses of 300 and 1000 mg/kg bw. There were signs of toxicity during clinical observations. No changes in food consumption, body or organ weights was observed.

n-valeraldehyde showed almost no changes in the metabolite profile compared to the control in both sexes (p<0.05; based on 290 metabolites). The metabolite profile of n-valeraldehyde in plasma does not match well with any of the reference compounds or established toxicological modes of action at the dose levels tested. Based on the metabolome analysis it is concluded that v-valeraldehyde is unlikely to have a significant systemic toxicological potential in oral studies in rats.