Nonadditive effects of PAHs on Early Vertebrate Development: mechanisms and implications for risk assessment

Health Canada, Health Products and Food Branch, Bureau of Chemical Safety, Ottawa, Ontario K1A0L2, Canada.
Toxicological Sciences (Impact Factor: 4.48). 06/2008; 105(1):5-23. DOI: 10.1093/toxsci/kfm303
Source: PubMed

ABSTRACT Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants. Traditionally, much of the research has focused on the carcinogenic potential of specific PAHs, such as benzo(a)pyrene, but recent studies using sensitive fish models have shown that exposure to PAHs alters normal fish development. Some PAHs can induce a teratogenic phenotype similar to that caused by planar halogenated aromatic hydrocarbons, such as dioxin. Consequently, mechanism of action is often equated between the two classes of compounds. Unlike dioxins, however, the developmental toxicity of PAH mixtures is not necessarily additive. This is likely related to their multiple mechanisms of toxicity and their rapid biotransformation by CYP1 enzymes to metabolites with a wide array of structures and potential toxicities. This has important implications for risk assessment and management as the current approach for complex mixtures of PAHs usually assumes concentration addition. In this review we discuss our current knowledge of teratogenicity caused by single PAH compounds and by mixtures and the importance of these latest findings for adequately assessing risk of PAHs to humans and wildlife. Throughout, we place particular emphasis on research on the early life stages of fish, which has proven to be a sensitive and rapid developmental model to elucidate effects of hydrocarbon mixtures.

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    • "We must keep in mind that BaA might induce toxic effect on fish early life stage at concentration below the LOEC value. Moreover, in the field, PAHs generally occur as mixtures and therefore additive and synergistic effects with other compounds can take place (Billiard et al., 2008). This was not taken into consideration in this single compound study. "
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    ABSTRACT: Benz[a]anthracene (BaA) is a ubiquitous polycyclic aromatic hydrocarbon found in numerous aquatic ecosystems. However, ecotoxicological data in aquatic organisms are scarce. To remedy this lack of data, Japanese medaka (Oryzias latipes) embryos were exposed to BaA and toxic effects were investigated at multiple toxicological endpoints. Japanese medaka embryos were incubated onto BaA-spiked artificial sediment for 9 days at low or moderate environmental concentrations ranging from 0.9 to 12µgg(-1) dw. BaA-exposed embryos exhibited significant tachycardia. BaA exposure was also shown to increase CYP1A activity in the hepato-biliary tissue as well as craniofacial deformities and DNA damage in pro-larvae. The photomotor response of BaA-exposed larvae was reduced in comparison to the control group. According to this set of tests, the lowest tested and observed effect concentration (LOEC) for Japanese medaka early life stages was equivalent to 0.92µgg(-1) dw of BaA. This concentration fall into the range of concentrations frequently encountered in sediments of polluted aquatic ecosystems. Taking into consideration these results, BaA represents a threat for fish early life stages in particular those developing onto or into contaminated sediments. Copyright © 2014 Elsevier Inc. All rights reserved.
    Ecotoxicology and Environmental Safety 12/2014; 113C:321-328. DOI:10.1016/j.ecoenv.2014.12.011 · 2.48 Impact Factor
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    • "Based on their embryo-larval toxicity, an alkyl-phenanthrene model was recently developed on methylated-phenanthrene from two to four carbons to better evaluate the complex toxicity of PAH mixtures (Barron et al. 2004). Alkyl-phenanthrene toxicity can be explained (1) by indirect toxicity due to reactive oxygen species production and (2) by direct toxicity of the compound itself or its metabolites (Billiard et al. 2008). Indeed, biotransformation of alkyl-phenanthrenes generates highly toxic metabolites by hydroxylation on double bonds of rings or on the alkyl side chains. "
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    ABSTRACT: A new gravel-contact assay using rainbow trout, Oncorhynchus mykiss, embryos was developed to assess the toxicity of polycyclic aromatic hydrocarbons (PAHs) and other hydrophobic compounds. Environmentally realistic exposure conditions were mimicked with a direct exposure of eyed rainbow trout embryos incubated onto chemical-spiked gravels until hatching at 10 °C. Several endpoints were recorded including survival, hatching delay, hatching success, biometry, developmental abnormalities, and DNA damage (comet and micronucleus assays). This bioassay was firstly tested with two model PAHs, fluoranthene and benzo[a]pyrene. Then, the method was applied to compare the toxicity of three PAH complex mixtures characterized by different PAH compositions: a pyrolytic extract from a PAH-contaminated sediment (Seine estuary, France) and two petrogenic extracts from Arabian Light and Erika oils, at two environmental concentrations, 3 and 10 μg g−1 sum of PAHs. The degree and spectrum of toxicity were different according to the extract considered. Acute effects including embryo mortality and decreased hatching success were observed only for Erika oil extract. Arabian Light and pyrolytic extracts induced mainly sublethal effects including reduced larvae size and hemorrhages. Arabian Light and Erika extracts both induced repairable DNA damage as revealed by the comet assay versus the micronucleus assay. The concentration and proportion of methylphenanthrenes and methylanthracenes appeared to drive the toxicity of the three PAH fractions tested, featuring a toxic gradient as follows: pyrolytic < Arabian Light < Erika. The minimal concentration causing developmental defects was as low as 0.7 μg g−1 sum of PAHs, indicating the high sensitivity of the assay and validating its use for toxicity assessment of particle-bound pollutants.
    Environmental Science and Pollution Research 12/2014; 21(24). DOI:10.1007/s11356-014-2804-0 · 2.76 Impact Factor
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    • "This area has long been a concern because the developed agriculture and heavy industry have caused a serious pollution problem in the sediment, water and soil of some persistent organic pollutants, especially polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) (Zhang et al., 2004; Shi et al., 2005; Tao et al., 2007). As typical persistent toxic substances (PTSs), PAHs and OCPs are of great concern worldwide due to their toxic, mutagenic, and carcinogenic (Mehlman et al., 1997; Reynaud and Deschaux, 2006; Billiard et al., 2008) or endocrine disruptive potentials (Snedeker, 2001; Turusov et al., 2002). These chemicals have become a major threat to the ecological system also due to their high input (Neamtu et al., 2009). "
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    ABSTRACT: A novel platform, named the Bayesian matbugs calculator (BMC), was developed to select the best SSD model, assess ecological risk at high-, mid- and low-levels of the 95% credible interval (CI), and to set the priority of toxic substances. The BMC platform was applied to the ecological risk assessment and priority setting of 32 toxic substances, including polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs), in the water from the Beijing-Tianjin-Bohai (BTB) area of northern China. The results showed that most of the studied PAH and OCP compounds have a high-level ecological risk with potential affected fraction (PAF) > 10 - 3 except for benzo(a)anthracene, pyrene, chrysene and β-hexachlorocyclohexane (β-HCH). The Yongdinghe River, Yongdingxinhe River, and Guanting Reservoir had the highest multiple substance combined PAF (msPAF) at mid-level, whereas the Qingshuihe River had the lowest msPAF, ranging from 2.91 × 10 -7 to 1.15 × 10 -1 at various levels. On the basis of ecological risk at the high level of 95% CI, the priorities for PAHs and OCPs were anthracene, chrysene, benzo(a)pyrene, δ-HCH, p,p ′ -dichlorodiphenyldichloroethane (p,p ′ -DDD), heptachlor epoxide, endosulfan sulfate, methoxychlor, and endosulfan II. The BMC platform can be concluded to be a friendly, accessible, efficient tool to select the best SSD model, calculate relevant indicators, assess ecological risks with uncertainty, and to set the priority of toxic substances.
    Ecological Indicators 10/2014; 45:209–218. DOI:10.1016/j.ecolind.2014.04.008 · 3.23 Impact Factor
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