Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

Based on results available (see under Discussion), valeraldehyde does not meet classification criteria neither of Directive 67/548/EEC for heritable genetic damage or irreversible effects nor of Regulation (EC) No 1272/2008 (Annex I Sect. 3.5.2) for germ cell mutagenicity.

The genotoxic potential of valeraldehyde was tested in vitro with bacterial and mammalian cells (see table below). In vivo genotoxicity studies could not be identified. However, several in vivo test results are available for closely related aldehydes, i.e. isovaleraldehyde (structural isomer with a branched carbon chain) and isobutyraldehyde (branched chain aliphatic aldehyde reduced by one carbon atom) which can be used for read across. Structure, chain length, reactivity, physico-chemical properties, and metabolism of these aliphatic aldehydes are very similar, thus justifying cross reading of results from these substances to valeraldehyde.

 

The following table gives the available studies used in the genetic toxicity assessment of valeraldehyde, together with some basic information.

 

 

Study

Substance

Reliability

GLP

Test type/
Protocol

Guideline

Results

Remarks

In vitro tests;
gene mutation studies in bacteria

NTP
1988

Valeraldehyde

2

no data

Ames

similar
OECD 471

negative

tested up to 2000 µg/plate with and without metab. activ.

In vitro tests,
studies in mammalian cells

Brambilla
1989

Valeraldehyde

2

no

HPRT
gene mutation

similar
OECD 476

positive

V79 cells;
without metabolic activation;
3 concentrations
up to 2580 µg/mL;
cytotoxicity observed

Martelli 1994

Valeraldehyde

2

no

Gen. Tox.
 UDS

similar
OECD 482

positive

primary hepatocytes;
3 concentrations,
up to 2580 µg/mL
cytotoxicity observed

Marinari
1984

Valeraldehyde

2

no

DNA damage
(alkaline elution)

no TG

positive

single strand breaks,
no cross linking

BASF SE
1999

Read across;
Isobutyraldehyde

1

yes

HPRT
gene mutation

according
OECD 476

negative

CHO cells;
with and without metab. activ.;
5 concentrations,
up to 800 µg/mL
cytotoxicity observed with metabolic activation

In vivo tests;
somatic cell studies

BASF AG
2001

Read across;
Isovaleraldehyde

1

yes

MNT

Similar to
OECD 474

negative

Read across;
single ip injection;

3 concentrations up to
100 mg/kg bw (overt toxicity)

NTP
1999

Read across;
Isobutyraldehyde

2

no data

MNT

Similar to
OECD 474

negative

3 repeat single ip injections;
6 concentrations up to
1250 mg/kg bw (single dose)

NTP
1999

Read across;
Isobutyraldehyde

2

no data

Mammalian bone marrow
CA

Similar to
OECD 475

positive

Read across;
single ip injection;

5 concentrations up to
1750 mg/kg bw
significant CA associated with notable clinical signs of toxicity

NTP
1999

Read across
isobutyraldehyde

2

no data

Chronic cancer study

OECD 451

negative

mouse

NTP
1999

Read across
isobutyraldehyde

2

no data

Chronic cancer study

OECD 451

negative

rat

 

 

The Ames test is negative as is the case for other related aldehydes (e.g. isovaleraldehyde, butyraldehyde, isobutyraldehyde, propionaldehyde).

 

Results of in vitro tests with mammalian cell systems are predominantly positive e.g Brambilla (1989). In contrast HPRT test for isobutyraldehyde (BASF AG, 1999) the result was negative.

 

In vivo genotoxicity studies for valeraldehyde are not available, but data from closely related aldehydes can be read across.

 

Isovaleraldehyde was tested by BASF in an in vivo mammalian erythrocyte micronucleus test. The result was negative (no increase in polychromatic erythrocytes containing neither small nor large micronuclei). The study satisfies the requirements of OECD TG 474.

 

Further, isobutyraldehyde was thoroughly tested by NTP. A mouse bone marrow micronucleus test was negative, i.e. in two independent tests, there was no significant increase compared to controls of micronucleated polychromatic erythrocytes from animals treated with three repeat doses (24 h interval) of isobutyraldehyde up to the maximum (single) dose of 1250 mg/kg bw. In contrast, in two tests for induction of chromosomal aberrations in mouse bone marrow, results were clearly positive. After intraperitoneal injection of increasing isobutyraldehyde single doses up to a maximum of 1750 mg/kg bw, increasing frequencies of aberrant cells were observed. Significant increases in aberrant cells compared to controls was only seen at doses which caused notable toxicity (1500 and 1750 mg/kg bw). These doses were higher than the maximum single dose administered in the micronucleus test at a single day.

 

Given these conflicting results, NTP decided to perform long-term inhalation cancer studies in rats and mice similar to the OECD test guideline 451 (isobutyraldehyde concentrations 0, 1500, 3000, and 6000 mg/m³). There was no evidence of carcinogenic potential in males or females of either species.

 

Based on the above, it is concluded that valeraldehyde is not genotoxic.


Short description of key information:
In vitro genotoxicity tests with valeraldehyde gave negative results with bacterial cells but positive results with mammalian cells. No in vivo test was located. Closely related aldehydes gave the same results in vitro, but negative results in vivo. This result can be extrapolated to valeraldehyde. It is therefore concluded that valeraldehyde is not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on results available (see under Discussion), valeraldehyde does not meet classification criteria neither of Directive 67/548/EEC for heritable genetic damage or irreversible effects nor of Regulation (EC) No 1272/2008 (Annex I Sect. 3.5.2) for germ cell mutagenicity.