Cancer risk from chronic exposures to chemicals and radiation: a comparison of the toxicological reference value with the radiation detriment.

This article aims at comparing reference methods for the assessment of cancer risk from exposure to genotoxic carcinogen chemical substances and to ionizing radiation. For chemicals, cancer potency is expressed as a toxicological reference value (TRV) based on the most sensitive type of cancer generally observed in animal experiments of oral or inhalation exposure. A dose-response curve is established by modelling experimental data adjusted to apply to human exposure. This leads to a point of departure from which the TRV is derived as the slope of a linear extrapolation to zero dose. Human lifetime cancer risk can then be assessed as the product of dose by TRV and it is generally considered to be tolerable in a 10-6-10-4 range for the public in a normal situation. Radiation exposure is assessed as an effective dose corresponding to a weighted average of energy deposition in body organs. Cancer risk models were derived from the epidemiological follow-up of atomic bombing survivors. Considering a linear-no-threshold dose-risk relationship and average baseline risks, lifetime nominal risk coefficients were established for 13 types of cancers. Those are adjusted according to the severity of each cancer type and combined into an overall indicator denominated radiation detriment. Exposure to radiation is subject to dose limits proscribing unacceptable health detriment. The differences between chemical and radiological cancer risk assessments are discussed and concern data sources, extrapolation to low doses, definition of dose, considered health effects and level of conservatism. These differences should not be an insuperable impediment to the comparison of TRVs with radiation risk, thus opportunities exist to bring closer the two types of risk assessment.

A long-term copper exposure in a freshwater ecosystem using lotic mesocosms: Invertebrate community responses.

A lotic mesocosm study was carried out in 20-m-long channels, under continuous, environmentally realistic concentrations of copper (Cu) in low, medium, and high exposures (nominally 0, 5, 25, and 75 µg L-1 ; average effective concentrations <0.5, 4, 20, and 57 µg L-1 respectively) for 18 mo. Total abundance, taxa richness, and community structure of zooplankton, macroinvertebrates, and emerging insects were severely affected at Cu treatment levels of 25 and 75 µg L-1 . Some taxa were sensitive to Cu, including gastropods such as Lymnaea spp. and Physa sp., crustaceans such as Chydorus sphaericus, Gammarus pulex, and Asellus aquaticus, rotifers such as Mytilina sp. and Trichocerca sp., leeches such as Erpobdella sp., and the emergence of dipteran insects such as Chironomini. Other taxa appeared to be tolerant or favored by indirect effects, as in Chironimidae larvae, the emergence of Orthocladiinae, and the zooplankter Vorticella sp., which increased in the 25 and 75 µg L-1 treatments. After approximately 8 mo of Cu exposure, the macroinvertebrate community in the high treatment was decimated to the point that few organisms could be detected, with moderate effects in the medium treatment, and very slight effects in the low-Cu treatment. Subsequently, most taxa in the high-Cu exposure began a gradual and partial recovery. By the end of the study at 18 mo, macroinvertebrate taxa richness was similar to control richness, although overall abundances remained lower than controls. After 18 mo of copper exposure, a no-observed-effect concentration at the community level for consumers was set at 5 µg L-1 (4 µg L-1 as average effective concentration), and a lowest-observed-effect concentration at 25 µg L-1 (20 µg L-1 as average effective concentration). Environ Toxicol Chem 2017;36:2698-2714. © 2017 SETAC.

Identification of synthetic steroids in river water downstream from pharmaceutical manufacture discharges based on a bioanalytical approach and passive sampling.

A bioanalytical approach was used to identify chemical contaminants at river sites located downstream from a pharmaceutical factory, where reproductive alterations in wild fish have been previously observed. By using polar organic compound integrative samplers (POCIS) at upstream and downstream sites, biological activity profiles based on in vitro bioassays revealed the occurrence of xenobiotic and steroid-like activities, including very high glucocorticoid, antimineralocorticoid, progestogenic and pregnane X receptor (PXR)-like activities (µg standard-EQ/g of sorbent range), and weak estrogenic activity (ng E2-EQ/g of sorbent range). Chemical analyses detected up to 60 out of 118 targeted steroid and pharmaceutical compounds in the extracts. In vitro profiling of occurring individual chemicals revealed the ability of several ones to act as agonist and/or antagonist of different steroids receptors. Mass balance calculation identified dexamethasone, spironolactone, and 6-alpha-methylprednisolone as major contributors to corticosteroid activities and levonorgestrel as the main contributor to progestogenic activities. Finally, RP-HPLC based fractionation of POCIS extracts and testing activity of fractions confirmed identified compounds and further revealed the presence of other unknown active chemicals. This study is one of the first to report environmental contamination by such chemicals; their possible contribution to in situ effects on fish at the same site is suggested.

Adverse effects in wild fish living downstream from pharmaceutical manufacture discharges.

A set of biochemical and histological responses was measured in wild gudgeon collected upstream and downstream of urban and pharmaceutical manufacture effluents. These individual end-points were associated to fish assemblage characterisation. Responses of biotransformation enzymes, neurotoxicity and endocrine disruption biomarkers revealed contamination of investigated stream by a mixture of pollutants. Fish from sampled sites downstream of the industrial effluent exhibited also strong signs of endocrine disruption including vitellogenin induction, intersex and male-biased sex-ratio. These individual effects were associated to a decrease of density and a lack of sensitive fish species. This evidence supports the hypothesis that pharmaceutical compounds discharged in stream are involved in recorded endocrine disruption effects and fish population disturbances and threaten disappearance of resident fish species. Overall, this study gives argument for the utilisation of an effect-based monitoring approach to assess impacts of pharmaceutical manufacture discharges on wild fish populations.

(Tri)butyltin biotic degradation rates and pathways in different compartments of a freshwater model ecosystem.

Experiments were conducted in controlled temperate freshwater ecosystems (microcosms) to determine the persistence and biogeochemical dynamic of tributyltin (TBT) and its degradation products. TBT and its derivatives were monitored simultaneously for 23 days (552 h) in sediment-water systems, with or without macroorganisms (macrophytes: Elodea canadensis and gastropods: Lymnaea stagnalis). Biphasic TBT removal from the water column was significantly enhanced by the presence of biota. The persistence of TBT in biota was assessed by a kinetic approach of the different bioaccumulation pathways and associated metabolisms adopted by the snails and the macrophytes in response to the TBT contamination. Furthermore, sediment acted for the final sink for butyltins in both types of microcosms, with more than 70% of TBT and its metabolites recovered in this compartment after two weeks of exposure. Degradation pathways in sediments of both biotic and abiotic microcosms appeared to represent a key process in TBT cycle and were characterized by half-lives in the range of one month. Specific transformation and transfer pathways of TBT as reactional mechanisms are discussed and modelled assessing in detail the role of each compartment with regards to the fate of TBT in the model aquatic ecosystems.

Evaluation of an in vitro hsp70 induction test for toxicity assessment of complex mixtures: comparison with chemical analyses and ecotoxicity tests.

The aim of this study was to assess the potential of a human cell line containing the hsp70 promoter linked to the chloramphenicol acetyltransferase reporter gene in evaluating the toxic potential of complex mixtures. Cells were exposed to eluates of industrial wastes and the cellular responses were compared with the metal contents of the samples and with standardized aquatic (microalgal growth inhibition, daphnia Immobilization, bacterial luminescence inhibition, Ceriodaphnia dubia reproduction inhibition) and terrestrial (earthworm lethality, plant growth inhibition) tests. The hsp70 promoter was significantly induced by 11 of 14 samples, with different dose-response patterns. Significant correlations of in vitro induction potency with aquatic ecotoxicity, especially with chronic tests, and with the metal contents of the samples were observed. Our study provides new information on the relevance of hsp70 gene induction as a criterion of toxicity and suggests its usefulness for the detection of toxicity associated with metallic pollution in complex mixtures.

Modeling explicitly and mechanistically median lethal concentration as a function of time for risk assessment.

A mechanistic model that explains how toxic effects depend on the duration of exposure has been developed. Derived from the dynamic energy budget (DEB)tox model, it expresses the hazard rate as a function of the toxic concentration in the organism. Using linear approximations in accordance with the general simplifications made in DEBtox, the concentration that induces x% of lethality (LCx) and in particular the lethal concentration 50% (LC50) are expressed explicitly as functions of time. Only three parameters are required: an asymptotic effect concentration, a time constant, and an effect velocity. More sophisticated (but still analytic) models are possible, describing more complex toxicity patterns such as an increase of sensitivity with time or, conversely, an adaptation. These models can be fitted to the common and widespread LC50 endpoints available from the literature for various aquatic species and chemicals. The interpretation of the values assigned to the parameters will help explain the toxicity processes and standardize toxicity values from different sources for comparisons.

Ecotoxicity of ethylene glycol monomethyl ether and its acetate.

Ethylene glycol monomethyl ether (EGME) and ethylene glycol monomethyl ether acetate (EGMEA) have been tested for their acute and chronic toxicity to various organisms occupying different trophic levels in the aquatic ecosystems. The results obtained in this study and those collected from the literature clearly reveal that EGME does not present short- or long-term ecotoxic effects in the ranges of concentrations likely to be found in aquatic environments. Indeed, in general, concentrations of 1000 to 10,000 mg/L of EGME are necessary before significant adverse effects can be observed in aquatic species. Conversely, acute toxicity occurs in fish at about 50 mg/L of EGMEA, and reproduction of Ceriodaphnia dubia is affected by 0.06 mg/L of this chemical. A teratogenic effect-with a specific malformation of the eyes-occurs in Xenopus laevis in the presence of 75 mg/L of EGMEA. This study was partially supported by the French Ministry of the Environment as part of the PNETOX program (1998).

Ecotoxicity of ethylene glycol monobutyl ether and its acetate.

Ethylene glycol monobutyl ether (EGBE) and ethylene glycol monobutyl ether acetate (EGBEA) were tested for their acute and chronic toxicity to various organisms occupying different trophic levels in the aquatic ecosystems. The obtained results and those collected from the literature clearly show that EGBE affects the survival, growth, and reproduction of aquatic organisms only at concentrations of approximately 100 mg/L or more. EGBEA appears to be slightly more ecotoxic to aquatic species. At 1000 and 10,000 mg/L, both chemicals strongly affect the early stages of development of the Japanese oyster, but such concentrations are too high to be found in aquatic environments. Micronucleus tests on Xenopus laevis show that EGBE and EGBEA are not genotoxic in the range of concentrations tested. Consequently, neither chemical presents a risk to the aquatic environment. EGBE does affect the gonadosomatic index of adult male zebra fish (Danio rerio); however, these are preliminary results and must be confirmed by additional experiments. This study was partially supported by the French Ministry of the Environment as part of the PNETOX program (1998).

An index of effluent aquatic toxicity designed by partial least squares regression, using acute and chronic tests and expert judgements.

The evaluation of the ecotoxicity of effluents requires a battery of biological tests on several species. In order to derive a summary parameter from such a battery, a single endpoint was calculated for all the tests: the EC10, obtained by nonlinear regression, with bootstrap evaluation of the confidence intervals. Principal component analysis was used to characterize and visualize the correlation between the tests. The table of the toxicity of the effluents was then submitted to a panel of experts, who classified the effluents according to the test results. Partial least squares (PLS) regression was used to fit the average value of the experts' judgements to the toxicity data, using a simple equation. Furthermore, PLS regression on partial data sets and other considerations resulted in an optimum battery, with two chronic tests and one acute test. The index is intended to be used for the classification of effluents based on their toxicity to aquatic species.