Evaluation of the EMA log kow trigger for fish BCF testing based on data for several human pharmaceuticals.

In the European Medicines Agency (EMA) "Guideline for Environmental Risk Assessment of Medicinal Products for Human Use," a fish bioconcentration factor (BCF) study is triggered in Phase I for pharmaceuticals having log Kow >4.5, to support Persistence, Bioaccumulation and Toxicity (PBT) screening, and in Phase II to assess secondary poisoning and bioaccumulation ('B') potential when log Kow ≥3. The standard sampling schedule outlined in OECD Test Guideline 305 (TG305) may require assessment of approximately 200 fish following exposure to low- and high-test concentrations and a negative control. We report experimental log Kow and BCF values for 64 human pharmaceuticals that were used to evaluate the current BCF testing trigger of log Kow ≥3, and whether a single BCF exposure concentration allows accurate classification of bioaccumulation potential. Our data support raising the BCF testing trigger to log Kow ≥4, and use of a single test concentration. The resulting reduction in the use of fish is consistent with the 3 R s principle and did not adversely affect classification accuracy. An assessment of potential risk of secondary poisoning was also conducted for three drugs classified as either B or vB, and no risks were identified.

Bioaccumulation and biomagnification of organochlorines in a marine food web at a pristine site in Iceland.

Organochlorine (OC) bioaccumulation and biomagnification were studied in a marine food web at a pristine site in Iceland. The species studied were the gastropod and grazer chink shell (Lacuna vincta), the filter feeding bivalve blue mussel (Mytilus edulis), the predators butterfish (Pholis gunnellus), and the seabird black guillemot (Cepphus grylle), all sampled and analysed in 1996-1997. Individual OC levels were generally low in chink shell and blue mussels, somewhat elevated in the fish, and an order of a magnitude higher in the top predator black guillemot, except for Sigma HCH (hexachlorocyclohexane isomers) and Sigma chlordane levels, which were similar in all organisms, ranging from 10 to 36 ng/g lipid weight (lw). In the molluscs and fish, mean concentrations of Sigma PCB (polychlorinated biphenyl) ranged from 111 to 377 ng/g lw, Sigma DDT (dichlorodiphenyltrichloroethane) ranged from 19 to 65 ng/g lw, and HCB (hexachlorobenzene) ranged from 21 to 30 ng/g lw. The levels of same OCs in the black guillemot were on average 2352, 361, and 283 ng/g lw, respectively. The OC tissue concentrations in blue mussel and black guillemot are comparable to levels in Arctic and sub-Arctic regions, but OC levels in blue mussel tissue were an order of magnitude lower than found in the North Sea and the Baltic Sea. The relative composition of OCs were generally similar among species with the PCB congeners emerging as the most abundant compounds with levels an order of magnitude higher than the other compounds in all species. Food web magnification factors (FWMFs) were determined for the OCs by using trophic levels determined from delta(15)N. FWMFs >1, indicating biomagnification, were found for Sigma PCB, penta- or higher chlorinated PCBs (e.g., PCB 101, 118, 138, 153, 180), beta-HCH, HCB, Sigma DDT, p,p-DDE, and transnonachlor. The highest FWMF was observed for PCB 180 at FWMF = 5.8.

Biomagnification of organic pollutants in benthic and pelagic marine food chains from the Baltic Sea.

The trophic transfer of organic pollutants with varying physical chemical properties was determined in both a pelagic and benthic food chain using delta 15N as a continuous variable for assessing trophic levels. The trophic transfer of organic pollutants through the entire food chain in terms of food chain magnification factors (FCMFs) was quantified from the slope of the regression between ln [concentration] and delta 15N. Organic pollutants with statistically significant FCMFs >1 were considered to biomagnify within the food chain, whereas those with FCMFs <1 were considered to trophically dilute. Statistically significant FCMFs >1 were found for PCB congeners and organochlorine pesticides in the Baltic food chains whereas statistically significant FCMFs <1 were found for PAHs and PCNs due to trophic dilution resulting from metabolism. FCMFs were generally greater in the pelagic food chain than in the benthic food chain. However, estimated FCMFs for the benthic food chain are likely in error, as the delta 15N method suggested a food chain structure which was not consistent with the known dietary patterns of the species. Biomagnification factors (BMFs) were additionally calculated as the ratio of the lipid normalized concentrations in the predator and prey species with adjustment for trophic level and were generally consistent with the FCMFs with BMF >1 for PCBs and organochlorines.

Modelling PCB bioaccumulation in a Baltic food web.

A steady state model is developed to describe the bioaccumulation of organic contaminants by 14 species in a Baltic food web including pelagic and benthic aquatic organisms. The model is used to study the bioaccumulation of five PCB congeners of different chlorination levels. The model predictions are evaluated against monitoring data for five of the species in the food web. Predicted concentrations are on average within a factor of two of measured concentrations. The model shows that all PCB congeners were biomagnified in the food web, which is consistent with observations. Sensitivity analysis reveals that the single most sensitive parameter is log K(OW). The most sensitive environmental parameter is the annual average temperature. Although not identified amongst the most sensitive input parameters, the dissolved concentration in water is believed to be important because of the uncertainty in its determination. The most sensitive organism-specific input parameters are the fractional respiration of species from the water column and sediment pore water, which are also difficult to determine. Parameters such as feeding rate, growth rate and lipid content of organism are only important at higher trophic levels.

Interpreting time trends and biomagnification of PCBs in the Baltic region using the equilibrium lipid partitioning approach.

Multi-year monitoring data for PCBs in abiotic media and biota collected from the Baltic region were compiled into a database and analyzed using the equilibrium lipid partitioning (ELP) approach to study temporal trends as well as to investigate food web biomagnification. Statistically significant reductions in ELP concentrations between 1987 and 2001 were observed in guillemots, air, and some fish species and a general, but not always statistically significant decline in concentrations was observed throughout the Baltic ecosystem. Estimated clearance half-lives ranged from 2.7-10.7 years. The database contained concentrations for a range of different Baltic species, which comprise a well-known Baltic food web. It was possible to derive the trophic position of the species in this food web and relate them to ELP concentrations. A significant positive correlation between ELP concentrations and trophic position was obtained. Estimated food web magnification factors ranged between 1.9 and 5.1 for selected congeners.

Development of a dynamic model for estimating the food web transfer of chemicals in small aquatic ecosystems.

A dynamic combined fate and food web model was developed to estimate the food web transfer of chemicals in small aquatic ecosystems (i.e. ponds). A novel feature of the modeling approach is that aquatic macrophytes (submerged aquatic vegetation) were included in the fate model and were also a food item in the food web model. The paper aims to investigate whether macrophytes are effective at mitigating chemical exposure and to compare the modeling approach developed here with previous modeling approaches recommended in the European Union (EU) guideline for risk assessment of pesticides. The model was used to estimate bioaccumulation of three hypothetical chemicals of varying hydrophobicity in a pond food web comprising 11 species. Three different macrophyte biomass densities were simulated in the model experiments to determine the influence of macrophytes on fate and bioaccumulation. Macrophytes were shown to have a significant effect on the fate and food web transfer of highly hydrophobic compounds with log KOW>=5. Modeled peak concentrations in biota were highest for the scenarios with the lowest macrophyte biomass density. The distribution and food web transfer of the hypothetical compound with the lowest hydrophobicity (log KOW=3) was not affected by the inclusion of aquatic macrophytes in the pond environment. For the three different hypothetical chemicals and at all macrophyte biomass densities, the maximum predicted concentrations in the top predator in the food web model were at least one order of magnitude lower than the values estimated using methods suggested in EU guidelines. The EU guideline thus provides a highly conservative estimate of risk. In our opinion, and subject to further model evaluation, a realistic assessment of dynamic food web transfer and risk can be obtained using the model presented here.

Trophodynamics of mercury and other trace elements in a pelagic food chain from the Baltic Sea.

Mercury (Hg) and 13 other trace elements (Al, Ti, V, Cr, Fe, Mn, Co, Ni, Cu, Zn, As, Cd, and Pb) were measured in phytoplankton, zooplankton, mysis and herring in order to examine the trophodynamics in a well-studied pelagic food chain in the Baltic Sea. The fractionation of nitrogen isotopes (delta(15)N) was used to evaluate food web structure and to estimate the extent of trophic biomagnification of the various trace elements. Trophic magnification factors (TMFs) for each trace element were determined from the slope of the regression between trace element concentrations and delta(15)N. Calculated TMFs showed fundamental differences in the trophodynamics of the trace elements in the pelagic food chain studied. Concentrations of Al, Fe, Ni, Zn, Pb and Cd showed statistically significant decreases (TMF<1) with increasing trophic levels and thus these trace elements tropically dilute or biodilute in this Baltic food chain. Cu, As, Cr, Mn, V, Ti and Co showed no significant relationships with trophic levels. Hg was unique among the trace elements studied in demonstrating a statistically significant increase (TMF>1) in concentration with trophic level i.e. Hg biomagnifies in this Baltic food chain. The estimated TMF for Hg in this food chain was comparable to TMFs observed elsewhere for diverse food chains and locations.