Acute and chronic aquatic toxicity of ammonium perfluorooctanoate (APFO) to freshwater organisms.

Recent concerns have been raised concerning the widespread distribution of perfluorinated compounds in environmental matrices and biota. The compounds of interest include ammonium perfluorooctanoate (APFO, the ammonium salt of perfluorooctanoic acid, PFOA). APFO is used primarily as a processing aid in the production of fluoropolymers and fluoroelastomers. The environmental presence of perfluorooctanoate (PFO(-), the anion of APFO) and its entry into the environment as APFO make quality aquatic toxicity data necessary to assess the aquatic hazard and risk of APFO. We conducted acute and chronic freshwater aquatic toxicity studies with algae, Pseudokirchneriella subcapitata, the water flea, Daphnia magna, and embryo-larval rainbow trout, Oncorhynchus mykiss, using OECD test guidelines and a single, well-characterized sample of APFO. Acute 48-96 h LC/EC(50) values were greater than 400mg/l APFO and the lowest chronic NOEC was 12.5mg/l for inhibition of the growth rate and biomass of the freshwater alga. Un-ionized ammonia was calculated to be a potential significant contributor to the observed toxicity of APFO. Based on environmental concentrations of PFO(-) from various aquatic ecosystems, the PNEC value from this study, and unionized ammonia contributions to observed toxicity, APFO demonstrates little or no risk for acute or chronic toxicity to freshwater and marine aquatic organisms at relevant environmental concentrations.

Dichloromethane marine risk assessment with special reference to the OSPARCOM region: North Sea.

This risk assessment on dichloromethane was carried out specifically for the marine environment, following methodology given in the EU risk assessment Regulation (1488/94) and Guidance Document of the EU New and Existing Substances Regulation (TGD, 1997). The study consists of collection and evaluation of data on effects and environmental concentrations from analytical monitoring programs in large rivers and estuaries in the North Sea area. The risk is indicated by the ratio of 'predicted environmental concentrations' (PEC) to 'predicted no-effect concentrations' (PNEC) for the marine aquatic environment. In total, 23 studies for fish, 17 studies for invertebrates and 6 studies for algae were evaluated. Both acute and chronic toxicity studies were taken into account and appropriate assessment factors used to define a PNEC value of 830 microg/l. Most of the available monitoring data apply to rivers and estuaries and were used to calculate PECs. The most recent data (1983--1995) support a typical PEC for dichloromethane lower than 0.2 microg/l and a worst case PEC of 13.6 microg/l. Dichloromethane is not a 'toxic, persistent and liable to bioaccumulate' substance sensu the Oslo and Paris Conventions for the Prevention of Marine Pollution (OSPAR-DYNAMEC). The calculated PEC/PNEC ratios give margins of 60 to 4000 between the PNEC and PEC, dilution within the sea would further increase these margins. It can be concluded that the present use of dichloromethane does not present a risk to the marine aquatic environment.

Carbon tetrachloride marine risk assessment with special reference to the OSPARCOM region: North Sea.

This risk assessment on carbon tetrachloride was carried out specifically for the marine environment, according to the methodology laid down in the European Union (EU) risk assessment Regulation (1488/94) and the Technical Guidance Documents for New and Existing Substances (TGD, 1996). The Montreal Protocol on ozone depleting substances scheduled a phase-out of carbon tetrachloride except for some essential and feedstock uses. This study consisted of the collection and evaluation of data on effects and environmental concentrations from analytical monitoring programs in large rivers and estuaries in the North Sea area. The risk is indicated by the ratio of the Predicted Exposure Concentration (PEC) and the Predicted No-Effect Concentration (PNEC) for the marine aquatic environment. In total 16 studies for fish, 7 studies for invertebrates and 5 for algae have been evaluated. The appropriate assessment factor has been used to calculate a PNEC of 7 microg/l based on long-term exposure for three trophic levels. For coastal waters and estuaries a typical and worst case PEC of 0.003 and 0.31 microg/l are derived. For river waters a typical and worst case PEC of 0.02 and 0.12 microg/l are derived, respectively. These ratios, which do not take into account any dilution within the sea, correspond to safety margins from 25 to 2500 between the aquatic effect and the exposure concentration. Carbon tetrachloride does not meet the criteria of 'toxic, persistent and liable to bioaccumulate' substances as mentioned by the Oslo and Paris Conventions for the Prevention of Marine Pollution (OSPAR-DYNAMEC). It can be concluded that the present use of carbon tetrachloride does not present a risk to the marine aquatic environment.

1,1,1-trichloroethane marine risk assessment with special reference to the OSPARCOM region: North Sea.

This risk assessment on 1,1,1-trichloroethane was carried out specifically for the marine environment, accordingly to the methodology laid down in the EU risk assessment Regulation (1488/94) and the Guidance Document of the EU New and Existing Substances Regulation (TGD, 1996). 1,1,1-trichloroethane is being phased out of most uses because of its ozone depletion potential (ODP) under the Montreal Protocol. Production for emissive uses has already been phased out end 1995 in Europe and 1996 in the United States, Japan and other industrial countries. The risk assessment study consists of the collection and evaluation of data on effects and environmental concentrations from analytical monitoring programmes in large rivers and estuaries in the North Sea area. The risk is indicated by the ratio of the Predicted Environmental Concentration (PEC) and the Predicted No-Effect Concentration (PNEC) for the marine aquatic environment. In total 14 studies for fish, 7 studies for invertebrates and 9 studies for algae have been evaluated. Both acute and chronic studies have been taken into account and the appropriate assessment factors have been used to calculate a PNEC value of 21 microg/l based on long term exposure. The PEC was derived from monitoring data. The PEC was set at 0.206 microg/l (worst case) and 0.024 microg/l (typical case) for coastal waters and estuaries and 0.6 microg/l (worst case) and <0.1 microg/l (typical case) for river waters. The calculated PEC/PNEC ratios, which do not take into account any dilution factor within the sea, correspond to a safety margin of 35 to 1000 between the aquatic effect and the exposure concentration. 1,1,1-trichloroethane is not a 'toxic, persistent and liable to bioaccumulate' substance according to the criteria as mentioned by the Oslo and Paris Conventions for the Prevention of Marine Pollution (OSPAR-DYNAMEC). It can be concluded that the present use of 1,1,1-trichloroethane does not present a risk to the marine aquatic environment.

Vinyl chloride marine risk assessment with special reference to the OSPARCOM region: North Sea.

This risk assessment on vinyl chloride was carried out specifically for the marine environment, according to the methodology laid down in the European Union (EU) risk assessment Regulation (1488/94) and the Technical Guidance Documents for New and Existing Substances (TGD, 1996). Vinyl chloride is used for the production of polyvinyl chloride (PVC). The study consisted of the collection and evaluation of data on effects and environmental concentrations from analytical monitoring programmes in large rivers and estuaries in the North Sea area. The risk is indicated by the ratio of the Predicted Exposure Concentration (PEC) and the Predicted No-Effect Concentration (PNEC) for the marine aquatic environment. In total 6 studies for fish, 3 studies for invertebrates and one for algae have been evaluated. The appropriate assessment factors have been used to calculate a PNEC of 210 microg/l based on short-term exposure. For coastal waters and estuaries a worst case PEC of 0.15 microg/l is derived. For river waters a typical and worst case PEC of <0.008 and 0.4 microg/l is derived, respectively. These concentrations, which do not take into account any dilution within the sea, correspond to safety margins from 500 to 250,000 between the aquatic effect and the exposure concentration. Vinyl chloride is not a 'toxic, persistent and liable to bioaccumulate' substance sensu the Oslo and Paris Conventions for the Prevention of Marine Pollution (OSPAR-DYNAMEC). It can be concluded that the present use of vinyl chloride does not present a risk to the marine aquatic environment.

Monochlorobenzene marine risk assessment with special reference to the OSPARCOM region: North Sea.

This risk assessment on monochlorobenzene was carried out for the marine environment, following methodology given in the EU risk assessment Regulation (1488/94) and Guidance Document of the EU New and Existing Substances Regulation (TGD, 1996). Data from analytical monitoring programmes in large rivers and estuaries in the North Sea area were collected and evaluated for effects and environmental concentrations. Risk is indicated by the ratio of predicted environmental concentration (PEC) to predicted no-effect concentration (PNEC) for the marine aquatic environment. In total, 27 data for fish, 24 data for invertebrates and 13 data for algae were evaluated. Acute and chronic toxicity studies were taken into account and appropriate assessment factors used to define a final PNEC value of 32 micro/l. Recent monitoring data indicate that monochlorobenzene levels in surface waters are below determination limits of 0.1, 0.2, 0.5 microg/l used in monitoring programs. Assuming that half of the lowest determination (0.1 microg/l) is typical, a PEC of 0.05 microg/l was derived. A worst case of 0.5 microg/l is assumed. PEC/PNEC ratios give safety factors of 60 to over 500, taking no account of dilution in the sea. Monochlorobenzene is not a 'toxic, persistent and liable to bioaccumulate' substance sensu the Oslo and Paris Conventions for the Prevention of Marine Pollution (OSPAR-DYNAMEC) criteria. Environmental fate and effects data indicate that current use of monochlorobenzene poses no unacceptable risk to the aquatic environment.

1,2-dichlorobenzene marine risk assessment with special reference to the OSPARCOM region: North Sea.

This risk assessment on 1,2-dichlorobenzene was carried out for the marine environment, following methodology given in the EU risk assessment Regulation (1488/94) and Guidance Document of the EU New and Existing Substances Regulation (TGD, 1996). Data from analytical monitoring programmes in large rivers and estuaries in the North Sea area were collected and evaluated on effects and environmental concentrations. Risk is indicated by the ratio of predicted environmental concentration (PEC) to predicted no-effect concentration (PNEC) for the marine aquatic environment. In total, 26 data for fish, 24 data for invertebrates and 17 data for algae were evaluated. Acute and chronic toxicity studies were taken into account and appropriate assessment factors used to define a final PNEC value of 37 microg/l. All available monitoring data indicate that 1,2-dichlorobenzene levels in estuaries are below 0.1 microg/l. Worst case concentrations in rivers are below 0.45 microg/l. With this value, calculated PEC/PNEC ratios give safety margins of 100 to 300, taking no account of dilution in the sea. 1,2-dichlorobenzene is not a 'toxic, persistent and liable to bioaccumulate' substance sensu the Oslo and Paris Convention for the Prevention of Marine Pollution (OSPAR-DYNAMEC) criteria. Environmental fate and effects data indicate that current use of 1,2-dichlorobenzene poses no risk to the aquatic environment.

1,4-dichlorobenzene marine risk assessment with special reference to the OSPARCOM region: North Sea.

This risk assessment on 1,4-dichlorobenzene was carried out for the marine environment, following methodology given in the EU risk assessment Regulation (1488/94) and Guidance Document of the EU New and Existing Substances Regulation (TGD, 1996). Data from analytical monitoring programs in large rivers and estuaries in the North Sea area were collected and evaluated on effects and environmental concentrations. Risk is indicated by the ratio of predicted environmental concentration (PEC) to predicted no-effect concentration (PNEC) for the marine aquatic environment. In total, 17 data for fish, 9 data for invertebrates and 7 data for algae were evaluated. Acute and chronic toxicity studies were taken into account and appropriate assessment factors used to define a final PNEC value of 20 microg/l. Recent monitoring data indicate that 1,4-dichlorobenzene levels in coastal waters and estuaries are below the determination limit of 0.1 microg/l used in monitoring programs. The worst case value recorded in river water is below 0.45 microg/l. Using these values, calculated PEC/PNEC ratios give safety margins of about 40-200, taking no account of dilution in the sea. Environmental fate and bioaccumulation data indicate that current use of 1,4-dichlorobenzene poses no risk to the aquatic environment.

A strategy to reduce the numbers of fish used in acute ecotoxicity testing of pharmaceuticals.

The pharmaceutical industry gives high priority to animal welfare in the process of drug discovery and safety assessment. In the context of environmental assessments of active pharmaceutical ingredients (APIs), existing U.S. Food and Drug Administration and draft European regulations may require testing of APIs for acute ecotoxicity to algae, daphnids, and fish (base-set ecotoxicity data used to derive the predicted no-effect concentration [PNECwater] from the most sensitive of three species). Subject to regulatory approval, it is proposed that testing can be moved from fish median lethal concentration (LC50) testing (typically using > or = 42 fish/API) to acute threshold tests using fewer fish (typically 10 fish/API). To support this strategy, we have collated base-set ecotoxicity data from regulatory studies of 91 APIs (names coded for commercial reasons). For 73 of the 91 APIs, the algal median effect concentration (EC50) and daphnid EC50 values were lower than or equal to the fish LC50 data. Thus, for approximately 80% of these APIs, algal and daphnid acute EC50 data could have been used in the absence of fish LC50 data to derive PNECwater values. For the other 18 APIs, use of an acute threshold test with a step-down factor of 3.2 is predicted to give comparable PNECwater outcomes. Based on this preliminary scenario of 91 APIs, this approach is predicted to reduce the total number of fish used from 3,822 to 1,025 (approximately 73%). The present study, although preliminary, suggests that the current regulatory requirement for fish LC50 data regarding APIs should be succeeded by fish acute threshold (step-down) test data, thereby achieving significant animal welfare benefits with no loss of data for PNECwater estimates.