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EC number: 204-683-8 | CAS number: 124-13-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- publication dated 1994
- Reliability:
- 2 (reliable with restrictions)
Data source
Reference
- Reference Type:
- publication
- Title:
- Cytotoxic and genotoxic effects of five n-alkanals in primary cultures of rat and human hepatocytes
- Author:
- Martelli A, Canonero R, Cavanna M, Ceradelli M & Marinari UM
- Year:
- 1 994
- Bibliographic source:
- Mutation Research 323 (1994) 121-126
- Report date:
- 1993
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
- GLP compliance:
- not specified
- Type of assay:
- unscheduled DNA synthesis
Test material
- Reference substance name:
- Nonanal
- EC Number:
- 204-688-5
- EC Name:
- Nonanal
- Cas Number:
- 124-19-6
- Molecular formula:
- C9H18O
- IUPAC Name:
- nonanal
- Details on test material:
- One of five n-alkanals - propanal, butanal, pentanal, hexanal and nonanal.
More than 300 aldehydes have been identified in foods and some chemicals of this family have been found to constitute the terminal non-radical products of the free radical induced peroxidative breakdown of biomembrane polyunsaturated fatty acids. Due to the electrophilic nature of the carbonyl carbon, aldehydes have been shown to react with thiols and amines and to form protein-protein, DNA-protein and DNA-DNA cross-links.
Propanal (98% pure), butanal (99% pure), pentanal (98% pure), hexanal (98% pure), nonanal (98% pure) and N-nitrosodimethylamine (NOMA) were purchased from E. Merck, Darmstadt, Germany.
Other materials used in the assay were collagenase type IV from Sigma Chimica, Italy; Williams' E medium from Flow Laboratories, Milan, Italy and [methyl-3H] thymidine (specific activity 23-25 Ci/mmole) from Amersham International (UK). All other chemicals, reagent grade, were obtained from E. Merck.
Constituent 1
Test animals
- Species:
- other: rat and human hepatocytes
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- The liver has the most comprehensive metabolic activity, the highest exposure to aldehydes ingested with foods, and the greatest susceptibility to lipid peroxidation, it was considered of interest to examine the five above mentioned n-alkanals in primary cultures of hepatocytes for both cytotoxicity and capability of inducing unscheduled DNA synthesis (UDS). Due to the known species differences in the activity of aldehyde dehydrogenases responsible for the oxidation to carboxylic acids of the functional group of these compounds a comparison has been carried out between rat and human hepatocytes.
Rat hepatocytes were isolated from Sprague-Dawley male albino rats (200-250 g) by collagenase perfusion. Cell suspensions less than 80% viable, as evaluated by the trypan blue exclusion test, were discarded.
Human hepatocyte suspensions were prepared from apparently healthy fragments of human liver discarded during the course of prescribed surgery from two human subjects. As checked by both macroscopic and histological examinations, these fragments were devoid of appreciable alterations. The proportion of viable hepatocytes after perfusion was 65% in case 1 and 83% in case 2.
Administration / exposure
- Route of administration:
- other: cell culture exposure
- Vehicle:
- Isolated rat or human hepatocytes were suspended in William's E supplemented with 10% calf serum and gentamicin (50µg/mI), and plated at a concentration of 1 x 10E6 in 35-mm Petri dishes coated with rat tail collagen. After 3 h attachment, dishes were washed with WE and refed with serum-free WE supplemented with half-log-spaced concentrations of the n-alkanals.
NOMA was used at a dose of 5 mM as the positive control to verify the metabolic competence of hepatocytes. At the end of a 20-h exposure
the cytotoxic effect of each concentration tested was immediately evaluated by washing the dishes with saline (0.85% NaCO and adding 0.8 mI/dish of a 0.4% trypan blue solution in saline; the percentage of viable cells was calculated by counting in duplicate 1000 cells/dish. - Details on exposure:
- Cultures were exposed simultaneously for 20 h to n-alkanals and 10µCi/ml [methyl³H] thymidine and were processed immediately after treatment for the autoradiographic evaluation of UDS. Each dose of n-alkanals was evaluated in two independent experiments carried out using cultures prepared from two rat or two human donors. Data are expressed as the mean ± SD of the 200 net nuclear counts obtained from four autoradiographs
(two from each donor). Silver grains over the nucleus minus the grains over a randomly chosen equal-sized area in the cytoplasm were defined as net grains per nucleus. Cytoplasmic labeling was also considered in order to assess a possible effect of the five n-alkanals on mitochondrial
DNA. - Duration of treatment / exposure:
- 20 hour culture exposure
- Frequency of treatment:
- Single treatment, experiments were replicated
- Post exposure period:
- No data
- No. of animals per sex per dose:
- Not applicable - in vitro cultures used
- Positive control(s):
- No data
Examinations
- Tissues and cell types examined:
- Cultures were exposed simultaneously for 20 h to n-alkanals and 10µCi/ml [methyl³H] thymidine and were processed immediately after treatment for the autoradiographic evaluation of UDS. Each dose of n-alkanals was evaluated in two independent experiments carried out using cultures prepared from two rat or two human donors. Data are expressed as the mean ± SD of the 200 net nuclear counts obtained from four autoradiographs
(two from each donor). Silver grains over the nucleus minus the grains over a randomly chosen equal-sized area in the cytoplasm were defined as net grains per nucleus. Cytoplasmic labeling was also considered in order to assess a possible effect of the five n-alkanals on mitochondrial
DNA. - Details of tissue and slide preparation:
- Cultures were exposed simultaneously for 20 h to n-alkanals and 10µCi/ml [methyl³H] thymidine and were processed immediately after treatment for the autoradiographic evaluation of UDS. Each dose of n-alkanals was evaluated in two independent experiments carried out using cultures prepared from two rat or two human donors. Data are expressed as the mean ± SD of the 200 net nuclear counts obtained from four autoradiographs
(two from each donor). Silver grains over the nucleus minus the grains over a randomly chosen equal-sized area in the cytoplasm were defined as net grains per nucleus. Cytoplasmic labeling was also considered in order to assess a possible effect of the five n-alkanals on mitochondrial
DNA. - Evaluation criteria:
- No information
- Statistics:
- No information
Results and discussion
Test results
- Sex:
- not specified
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- After 20 h exposure, cytotoxicity was similar in cells of the two species, and increased with the length of the carbon chain. In rat hepatocytes, propanal (10-100 mM), butanal (10 -100 mM), pentanal (0 -30 mM) and hexanal (3-30 mM) induced a modest but significant and dose-dependent increase of net nuclear grain counts, while in human hepatocytes this effect was not detected. Nonanal (3-30 mM), which showed the highest cytotoxic effect, failed to induce UDS in both cell types. These results seem to suggest that at the concentrations which are presumably attained after ingestion with food or generated by lipid peroxidation processes the five n-alkanals tested are presumably unable to induce genotoxic effects in the human liver.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
The alkanals propanal, butanal, pentanal, hexanal and nonanal: (a) produce a cytotoxic effect in primary cultures of both rat and human
hepatocytes which is similar in both species and which increases with the length of the carbon chain (b) induce, with the exception of nonanal, a modest but significant and dose-dependent amount of DNA repair synthesis in rat, but not in human, hepatocytes.
In conclusion, the following considerations suggest that the probability of occurrence in humans of genotoxic effects produced by the five n-alkanals considered in this study is negligible. In the first place, even if they were weak inducers of mutations and DNA repair in rodent cells, their active concentrations were far higher than those which can be attained in vivo as a consequence of ingestion with food or generation by lipid peroxidation processes. In the second place, human cells seem to be less sensitive to n-alkanal genotoxicity than rodent cells under normal conditions of efficiency of detoxification systems - Executive summary:
Five n-alkanals were examined for cytotoxicity, as evaluated by the trypan blue exclusion test, and for genotoxicity, as evaluated by the induction of unscheduled DNA synthesis (UDS), in primary cultures of rat and human hepatocytes. After a 20 hour exposure, cytotoxicity was similar in cells of the two species, and increased with the length of the carbon chain. In rat hepatocytes, propanal (10-100 mM), butanal (10 -100 mM), pentanal (0 -30 mM) and hexanal (3-30 mM) induced a modest but significant and dose-dependent increase of net nuclear grain counts, while in human hepatocytes this effect was not detected. Nonanal (3-30 mM), which showed the highest cytotoxic effect, failed to induce UDS in both cell types. These results seem to suggest that at the concentrations which are presumably attained after ingestion with food or generated by lipid peroxidation processes the five n-alkanals tested are presumably unable to induce genotoxic effects in the human liver.
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