title: Toxicogenomics in vitro as an alternative tool for safety evaluation of petroleum substances and PAHs with regard to prenatal developmental toxicity.
abstract: The REACH legislation requires chemicals - including petroleum substances - that are put on the EU market in quantities greater than 1000 tonnes/year, to be tested for prenatal developmental toxicity. This will require large numbers of animals since prenatal development toxicity testing is animal-intensive. The application of toxicogenomic technologies might reduce the number of animals to study prenatal developmental toxicity of petroleum substances by allowing their grouping into categories with the same toxicological properties. This substance categorization may be supported by similarities in molecular fingerprints. The developmental toxicity effects observed in some oil products are most likely related to polycyclic aromatic hydrocarbons (PAHs) with high-molecular weight. However, the current review indicates that even though the available studies provide clues regarding the HOX, FOX, SHH and PAX family genes, which regulate functions in skeleton development, single individual genes cannot be used as biomarkers of PAHs exposure and subsequent prenatal developmental toxicity. Furthermore, it should be considered that toxicogenomic technologies applied to specific tissues/organs testing might lead to unreliable results regarding developmental toxicity due to induction of tissue-specific pathways. Thus, an approach which applies a battery of in vitro tests including the zebrafish embryo test, embryonic stem cells, and the whole embryo culture is suggested as it would be more relevant for studying developmental effects in the terms of substances categorization.
authors.affiliation: Shell Health, Shell International bv, P.O. Box 162, 2501 AN The Hague, The Netherlands; Division of Toxicology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Tsitou
authors.affiliation: Shell Health, Shell International bv, P.O. Box 162, 2501 AN The Hague, The Netherlands.
authors.forename: Marjoke
authors.initials: M
authors.lastname: Heneweer
authors.affiliation: Shell Health, Shell International bv, P.O. Box 162, 2501 AN The Hague, The Netherlands. Electronic address: peter.boogaard@shell.com.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Boogaard
mesh_terms: D023401:Animal Use Alternatives; D000818:Animals; D047108:Embryonic Development; D006801:Humans; D010578:Petroleum / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D043922:Toxicogenetics
chemical_list: D010578:Petroleum; D011084:Polycyclic Aromatic Hydrocarbons
keywords: Developmental toxicity; Oil; Polycyclic aromatic hydrocarbons; REACH; Reprotoxicity; Toxicogenomics