Isovaleraldehyde

Endpoint summary

Additional information

As no valid studies on the mutagenic potential of isovaleraldehyde in bacterial mutation assays could be identified, other related aldehydes will be used as supporting substances for read across.tests are available for valeraldehyde, butyraldehyde, and isobutyraldehyde. These aldehydes are closely related to isovaleraldehyde (structural isomer with a linear carbon chain, linear and branched chain aliphatic aldehydes reduced in length by one carbon atom). Reactivity and physico-chemical properties as well as metabolism of these aldehydes are very similar to isovaleraldehyde, thus justifying the use of these substances for cross reading.

 

In the following table, the studies used in the genetic toxicity assessment of isovaleraldehyde are listed 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	Read across Valeraldehyde	2	no data	Ames	similar to OECD 471	negative	tested up to 2000 µg/plate with and without metab. activ.
Mortelmans 1986	Read across butyraldehyde	2	no data	Ames	similar to OECD 471	negative	tested up to 3333 µg/plate with and without metab. activ.
NTP 1999	Read across isobutyraldehyde	2	no data	Ames	similar to OECD 471	negative	tested up to 10,000 µg/plate with and without metab. activ.
Mortelmans 1986	Read across propylaldehyde	2	no data	Ames	similar to OECD 471	negative	tested up to 10,000 µg/plate with and without metab. activ.
In vitro tests, studies in mammalian cells
Obe/Tucker 1979/1993	isovaleraldehyde	2	no	SCE	similar to OECD 479	weak positive	human lymphcytes; without metabolic activation; 2 concentrations 16 and 24 µg/mL; only 2-fold increase in SCE frequencies per mitosis
In vivo test
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
BASF AG 2001	Isovaleraldehyde	1	yes	MNT	similar to OECD 474	negative	single ip injection; 3 concentrations up to 100 mg/kg bw (overt toxicity)

 

 

The Ames tests for the supporting aldehydes were all negative. It is concluded that an Ames test with isovaleraldehyde would be negative too.

 

The result of the SCE assay with human lymphocytes was weakly positive. For other aldehydes (e.g. valeraldehyde), it has been demonstrated that other in vitro mammalian cell assays (gene mutation HPRT, UDS, alkaline elution) showed positive results. It is very likely that isovaleraldehyde would test positive in similar in vitro tests using mammalian cell systems.

 

Isovaleraldehyde was tested in a valid mouse bone marrow micronucleus test in vivo according to OECD TG 474 with negative result (BASF, 2001). After intraperitoneal injection of increasing single doses of isovaleraldehyde up to 100 mg/kg bw, no increase in polychromatic erythrocytes containing neither small nor large micronuclei was observed. At the highest dose, overt toxicity were observed. There was no indication of a genotoxic potential of isovaleraldehyde in this in vivo micronucleus test.

 

Positive test results are often observed in in-vitro mammalian cell genotoxicity tests, whereas the respective in-vivo test results are negative. In vivo tests represent much more physiological conditions, i.e. absorption, distribution, and metabolism and excretion, and, therefore, are considered to rule out positive in-vitro test results. This is also supported by the observations with isobutyraldehyde, which was positive in mammalian cell tests, but which was negative in two rodent oncogenicity tests conducted by NTP.,

 

Taking into account the above information on mutagenic, genotoxic, and carcinogenic effects of isovaleraldehyde and supporting aldehydes, it is concluded that isovaleraldehyde is not genotoxic.

 

 

Short description of key information:
Isovaleraldehyde is considered to be negative in bacterial cell test systems, based on read across to related substances (valeraldehyde, butyraldehyde, propionaldehyde and isobutyraldehyde) which were all negative. Isovaleraldehyde was weakly positive in a sister chromatid exchange assay with human lymphocytes in vitro, but it was negative in an in vivo mammalian erythrocyte micronucleus test according to OECD TG 474. Overall, isovaleraldehyde is considered to lack genotoxic properties.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on results available (see under Discussion), isovaleraldehyde 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.