Ecotoxicological assessment of galaxolide and tonalide as contaminants of emerging concern in marine ecosystems

The polycyclic musk compounds Galaxolide (HHCB) and Tonalide (AHTN) are the most frequently consumed fragrance materials applied in many household and personal care products. These substances have been detected in all environmental compartments and, due to their inherent lipophilicity, they easily bioaccumulate in aquatic organism. The aim of this PhD thesis was to assess the risk of environmental concentrations of HHCB and AHTN in the marine environments. In order to provide a more complete assessment on marine biota, empirical approach based on data of ecotoxicological assays was explored based on environmental risk assessment (ERA) scheme. In this case, it was intended to employ organisms from different trophic levels like microalgae, echinoderms, bivalves, shrimps, and fish. This diversification in the species allows assessing how organisms with different biological complexity can be affected. In addition, different endpoints were used for each species, taking as basis the sensitivity and relevance of the endpoints. Another important aspect considered to select the endpoints was their level of biological organization, so that the responses measured were based on acute and chronic exposure, focusing on growth, survival, development, behaviour, and biomarkers at the biochemical and molecular levels. The results obtained in this thesis show that environmental concentrations of both compounds are detrimental to microalgae growth posing significant risk to Phaeodactylum tricornutum and Isochrysis galbana. It was also observed that environmental concentrations of HHCB and AHTN significantly altered the early life stages endpoints such as fertilization, larval development, and survival in tested species. Furthermore, this thesis has proven that in a scenario of heterogenous pollution where lethality is not expected to occur, HHCB and AHTN may trigger spatial avoidance, which might reduce the local biodiversity of ecosystems due to emigration to safer environments. Sublethal effects assessed in bivalves after chronic exposure to HHCB and AHTN showed that these substances are bioavailable to marine organisms and they have the potential to induce oxidative stress, genotoxicity, neurotoxicity and alter the health status of marine organisms. It was also observed that both compounds modulated endocrine disruption biomarkers in small fish. Despite the significant alterations in endocrine disruption biomarkers induced by both compounds, AHTN appeared to be a more potent inhibitor of endocrine activity in the marine environments. This PhD Thesis has demonstrated the adverse effects of environmental concentrations of HHCB and AHTN in marine ecosystems. Therefore, the data presented in this study should be integrated with other available data required for policy actions that will aid the conservation and management of the sea

Nitromusk and Polycyclic Musk Compounds as Long-Term Inhibitors of Cellular Xenobiotic Defense Systems Mediated by Multidrug Transporters

Synthetic musk compounds, widely used as fragrances in consumer products, have been detected in human tissue and, surprisingly, in aquatic organisms such as fish and mollusks. Although their persistence and potential to bioaccumulate are of concern, the toxicity and environmental risks of these chemicals are generally regarded as low. Here, however, we show that nitromusks and polycyclic musks inhibit the activity of multidrug efflux transporters responsible for multixenobiotic resistance (MXR) in gills of the marine mussel Mytilus californianus. The IC(10) (concentration that inhibits 10%) values for the different classes of musks were in the range of 0.09–0.39 μM, and IC(50) values were 0.74–2.56 μM. The immediate consequence of inhibition of efflux transporters is that normally excluded xenobiotics will now be able to enter the cell. Remarkably, the inhibitory effects of a brief 2-hr exposure to musks were only partially reversed after a 24- to 48-hr recovery period in clean seawater. This unexpected consequence of synthetic musks—a long-term loss of efflux transport activity—will result in continued accumulation of normally excluded toxicants even after direct exposure to the musk has ended. These findings also point to the need to determine whether other environmental chemicals have similar long-term effects on these transporters. The results are relevant to human health because they raise the possibility that exposure to common xenobiotics and pharmaceuticals could cause similar long-term inhibition of these transporters and lead to increased exposure to normally excluded toxicants

Effects and Risk Assessment of the Polycyclic Musk Compounds Galaxolide (R) and Tonalide (R) on Marine Microalgae, Invertebrates, and Fish

The current research investigated the potential environmental risk of the polycyclic musk compounds, Galaxolide (R) (HHCB) and Tonalide (R) (AHTN), in the marine environments. These substances are lipophilic, bioaccumulated, and potentially biomagnified in aquatic organisms. To understand the toxicity of HHCB and AHTN, acute toxicity tests were performed by exposing marine microalgae (Phaeodactylum tricornutum, Tretraselmis chuii, and Isochrysis galbana), crustaceans (Artemia franciscana), echinoderms (Paracentrotus lividus), bivalves (Mytilus galloprovincialis), fish (Sparus aurata), and a candidate freshwater microalga (Raphidocelis subcapitata) to environmentally relevant concentrations (0.005-5 mu g/L) following standardized protocols (US EPA, Environment Canada and OECD). P. tricornutum and I. galbana were sensitive to both substances and for P. tricornutum exposed to HHCB and AHTN, the IC10 values (the inhibition concentration at which 10% microalgae growth inhibition was observed) were 0.127 and 0.002 mu g/L, respectively, while IC10 values calculated for I. galbana were 5.22 mu g/L (a little higher than the highest concentration) and 0.328 mu g/L, for HHCB and AHTN, respectively. Significant (p < 0.01) concentration dependent responses were measured in P. lividus and M. galloprovincialis larvae developments, as well as S. aurata mortality tested with HHCB. The effect of HHCB on P. lividus larvae development was the most sensitive endpoint recorded, producing an EC50 value (the effect concentration at which 50% effect was observed) of 4.063 mu g/L. Considering the risk quotients both substances seem to represent high environmental risk to P. tricornutum and M. galloprovincialis in marine environments