The pharmacokinetic profile of the antibacterial agent florfenicol was studied in plasma after intravenous (i.v.) injection and in plasma, muscle and liver following oral (p.o.) administration to cod Gadus morhua, held in seawater at 8 degrees C and weighing 100 to 200 g. Following i.v. injection, the plasma drug concentration-time profile showed 2 distinct phases. The plasma distribution half-life (t1/2alpha) was estimated to be 1.6 h, the elimination half-life (t1/2beta) to be 43 h, the total body clearance (ClT) to be 0.015 1 kg(-1) h(-1) and mean residence time (MRT) to be 74 h. The volume of distribution at steady state, Vd(ss), was calculated to be 1.1 l kg(-1). Following p.o. administration, the bioavailability was estimated to be 91%, the peak plasma concentrations (Cmax) to be 10.8 microg ml(-1) and the time to peak plasma concentrations (Tmax) to be 7 h. Corresponding Cmax and Tmax values were 13.0 microg g(-1) and 9 h, respectively, in muscle and 12.1 microg g(-1) and 9 h, respectively, in liver. The in vitro minimum inhibitory concentration (MIC) values of florfenicol against 3 Vibrio anguillarum strains isolated from diseased cod (A-21, HI-610, HI-618) were 0.5 microg ml(-1) for all 3 strains.

The pharmacokinetic properties of the antibacterial agent oxolinic acid and vetoquinol, the carbitol ester of oxolinic acid, were studied after intravenous (i.v.) and oral (p.o.) administration to 100-150 g cod, Gadus morhua L., held in sea water at 8 degreesC. Following i.v. injection, the plasma drug concentration-time profile showed two distinct phases. The distribution half-life (t(1/2)alpha) was estimated at 1.3 h, the elimination half-life (t(1/2)beta) as 84 h and the total body clearance (Cl-T) as 0.047 L kg(-1) h(-1). The volume of distribution at steady state, V-d(ss) was calculated to be 5.5 L kg(-1) , indicating good tissue penetration of oxolinic acid in cod. Following p.o. administration of oxolinic acid or vetoquinol, the peak plasma concentrations (C-max) of oxolinic acid and the time to peak plasma concentrations (T-max) were estimated to be 1.2 and 2.5 mug mL(-1), and 24 and 12 h, respectively. The bioavailabilities of oxolinic acid following p.o. administration of oxolinic acid and vetoquinol were calculated to be 55 and 72%, respectively. The in vitro minimum inhibitory concentration (MIC) values of oxolinic acid against three strains of Vibrio anguillarum isolated from diseased cod were 0.016 mug mL(-1) (HI-610), 0.250 mug mL(-1) (HI-618) and 0.250 mug mL(-1) (HI-A21). Based on a MIC value of 0.016 mug mL(-1) a single p.o. administration of 25 mg kg(-1) of oxolinic acid maintains plasma levels in excess of 0.064 mug mL(-1), corresponding to four times the MIC-value, for approximately 12 days. The analogous value for a single p.o. dose of 25 mg kg(-1) of oxolinic acid administered as vetoquinol was 13 days.

The efficacy of a single intraperitoneal injection of oxolinic acid to control an outbreak of atypical Aeromonas salmonicida infection in goldsinny wrasse (Ctenolabrus rupestris) and in the treatment of systemic vibriosis in corkwing wrasse (Symphodus melops) was examined. In addition a field study was performed to examine the effect of medication on the survival rate of goldsinny wrasse in Atlantic salmon cages. Four groups of wild caught goldsinny wrasse, each of 50 fish, were treated with an intraperitoneal injection of propylene glycol:saline (50:50) (control) or 50 mg/kg oxolinic acid at a concentration of 50 mg/mL. Three days after medication the fish in all groups were treated by an intraperitoneal injection of prednisolone acetate and an increase in seawater temperature from 9.0 to 11.5 degrees C. Cumulative mortalities were 18% in the two groups treated with oxolinic acid and 94 and 100% in the unmedicated control groups, giving a 'relative percentage survival' (RPS) value of 82%. A laboratory maintained population of originally wild caught corkwing wrasse experiencing high daily mortality was treated with oxolinic acid (50 mg/kg) or propylene glycol:saline (control). Cumulative mortalities were 84% (control) and 42% (oxolinic acid medicated group) giving an RPS value of 50%. In a field investigation using goldsinny wrasse approximately 30% were medicated with oxolinic acid (50 mg/kg) prior to stocking in cages with Atlantic salmon. In two of three cages the cumulative mortality was significantly lower (P = 0.025 and P < 0.001) in the medicated groups.

A high performance liquid chromatographic (HPLC) method was developed to determine the concentration of diflubenzuron, a delousing agent used in fish farming, in marine mud and shell sand. The recovery of diflubenzuron from mud was 100.8±1.1% and 105.5±4.3% for shell sand. The limit of quantitation was found to be 0.1 μg g−1. The stability of diflubenzuron was studied under laboratory conditions in marine sediments at different temperatures (4 and 14°C). No degradation of diflubenzuron occurred in the organic rich mud sediment or in the shell sand sediment during the experimental period of 204 days. Increasing the temperature from 4 to 14°C had no effect on the stability. Furthermore, diflubenzuron showed to be persistent in both mud and shell sand sediment since no detectable diffusion from the sediment to the water phase occurred during the experimental period of 204 days. Increasing the water current in the tanks had no effect on the persistence. Under field conditions, the concentrations of diflubenzuron found in the organic material from sediment traps placed 2 m from the bottom under the cage in a fish farm during medication were high and ranged from 71 to 259 μg g−1. The concentrations of diflubenzuron in the sediment under the fish farm were, however, low, with a maximum concentration of 5.4 μg g−1. The dispersion of diflubenzuron to the sediment was limited to less than 20 m from the edge of the cage in every direction. Fifteen months following the medication, only traces (<0.1 μg g−1) of diflubenzuron were detected in the sediment under the fish farm. Possible explanations for this decrease are resuspension and redistribution of sediment and/or oxic degradation of the drug.

This paper provides a critical review of the main issues regarding the scientific principles underlying environmental monitoring of marine aquaculture operations and makes recommendations relevant to the implementation of best practice for the management of aquaculture in Europe. Given that a variety of cultured species and approaches are adopted in Europe, it is not possible, or indeed desirable, to devise prescriptive guidelines. Instead, this paper reviews how science informs monitoring and provides a framework for the development of a monitoring strategy of marine aquaculture operations that is flexible enough to be applicable to a variety of locations, species and situations.Traditionally environmental monitoring has concentrated on a few key physical and chemical variables and organisms. The trend now, however, is towards whole-system environmental assessment (e.g. CEC 2000; Osparcom 1998), including considerations of the assimilative capacity of specific systems and their ability to absorb and dilute perturbations. Against this background this paper addresses the following specific objectives:review of the rationale and scientific principles underlying current environmental monitoring with specific reference to marine aquaculture;evaluation of the links between monitoring and regulatory criteria, specifically consideration of environmental quality objectives and environmental quality standards, and the role of environmental impact assessmentsassessment of the role of codes of best conduct and practice, and environmental management systems in the management of aquaculture operations.The paper concludes by proposing a set of recommendations which will contribute towards the sustainable management of aquaculture operations, through the implementation of a more focused approach to environmental monitoring.

A programme for monitoring the impact of organic waste from marine fish farms is presented. It consists of three types of investigation of increasing complexity and accuracy (A, B and C), which are applied more frequently with increasing environmental impact. The A-investigation is a simple measurement of sedimentation rate beneath the net cages; the B-investigation is a sediment investigation providing a trend monitoring of the sediment condition, and the C-investigation is a comprehensive investigation of the benthic macrofaunal community structure. The A- and B-investigations were designed specifically for fish farming and the latter utilises several parameters in order to make the investigation more robust. The C-investigation employs well-established methods and procedures, which have been used previously in monitoring programmes. Environmental quality standards (EQS) have been set for the B- and C-investigation. The monitoring programme is part of a larger management system in Norway called Modelling–Ongrowing fish farms–Monitoring (MOM).

The pharmacokinetic properties of the antibacterial agents oxolinic acid and flumequine were studied in corkwing wrasse (Symphodus melops) after either intraperitoneal injection or bath treatment. Following intraperitoneal administration the peak plasma concentrations (Cmax) and the time to peak plasma concentrations (Tmax) were estimated to be 2.0 microg/mL and 12 h, respectively, for oxolinic acid and 2.6 microg/mL and 12 h, respectively, for flumequine. In muscle, Cmax and Tmax were estimated to 6.7 microg/g and 12 h, respectively, for oxolinic acid with corresponding values of 8.5 microg/g and 13 h, respectively, for flumequine. In liver, Cmax and Tmax were calculated to 7.0 microg/g and 12 h, respectively, for oxolinic and 12.2 microg/g and 11 h, respectively, for flumequine. Elimination half-lives (t1/2 beta) of 26, 24 and 29 h, respectively, for plasma, muscle and liver were calculated for flumequine. For oxolinic acid two distinct elimination phases were found and calculated to be 16 h (t1/2 beta) and 57 h (t1/2 gamma) in plasma, 15 and 59 h, respectively, in muscle and 20 and 72 h, respectively, in liver. Bath treatment using 150 mg/L of flumequine or 200 mg/L of oxolinic acid for 72 h resulted in flumequine concentrations of 1.0 microg/mL in plasma, 5.0 microg/g in muscle and 12.4 microg/g in liver. Corresponding values for oxolinic acid were 1.0 microg/g in plasma, 2.5 microg/g in muscle and 4.9 microg/g in liver.

The pharmacokinetic properties of the antibacterial agent oxolinic acid and its carbitol ester (Vetoquinol) were studied after intravenous (oxolinic acid) and oral (oxolinic acid and Vetoquinol) administration to Atlantic salmon (Salmo salar) held in seawater at 10 degrees C. Following intravenous injection of oxolinic acid, the plasma drug concentration-time profile showed two distinct phases, The distribution half life (t(1/2) alpha) was calculated to be 1 h and the elimination half life (t(1/2)beta) to be 15 h. Total body clearance (Cl-T) was determined to be 0.40 l/kg h and the volume of distribution at steady state, V-d(SS) to be 5.7 l/kg indicating good tissue penetration of oxolinic acid in Atlantic salmon. The peak plasma concentrations (C-max) and the time to peak plasma concentrations (T-max) for oxolinic acid were estimated to be 0.5 mu g/ml and 19 h, respectively, when administrating oxolinic acid and 3.8 mu g/ml and 7 h, respectively, following oral administration of Vetoquinol. A bioavailability of 25% was calculated following oral administration of oxolinic acid whereas a total bioavailability of 93% (oxolinic acid + Vetoquinol) where oxolinic acid accounted for 71% was calculated following oral administration of Vetoquinol. In muscle, C-max and T-max were estimated to 3.2 mu g/g and 17 h, respectively, following oral administration of oxolinic acid with corresponding values of 4.6 mu g/g and 14 h for oxolinic acid following oral administration of Vetoquinol. Following oral administration of oxolinic acid, C-max and T-max were estimated to 5.6 mu g/g and 10 h, respectively, in liver with corresponding values of 11.5 mu g /g and 9 h following oral administration of Vetoquinol. The in vitro minimum inhibitory concentration (MIC) values for oxolinic acid and Vetoquinol against 20 strains of Aeromonas salmonicida ranged from 0.0625 to > 8 mu g/ml for oxolinic acid and from 2 to > 516 mu g/ml for Vetoquinol. (C) 2000 Elsevier Science B.V. All rights reserved.

The pharmacokinetic properties of the antibacterial agent oxolinic acid were studied after intravenous, intraperitoneal and oral administration to 1.5–3.0 kg Atlantic halibut, Hippoglossus hippoglossus L., held in sea water at 9 °C. Following intravenous injection, the plasma drug concentration‐time profile showed two distinct phases. The terminal elimination half‐life was estimated to be 52 h, whereas total body clearance (ClT) was determined to be 0.044 L kg–1 h–1. The volume of distribution at steady state, Vd(ss), was calculated to be 3.0 L kg–1, indicating good tissue penetration of oxolinic acid in Atlantic halibut. The peak plasma concentration (Cmax) and the time to peak plasma concentration (Tmax) were estimated to be 1.2 and 2.7 μg mL–1, and 21.5 and 80 h, respectively, following oral administration of medicated feed or intraperitoneal injection. The corresponding bioavailabilities were calculated to be 15% and 92%, respectively. Oral administration of vetoquinol, the carbitol ester of oxolinic acid, increased the bioavailability of oxolinic acid to 64% and the total bioavailability (oxolinic acid + vetoquinol) to 82%, whereas Cmax and Tmax values of 6.7 μg mL–1 and 14.5 h, respectively, for oxolinic acid, and 1.0 μg mL–1 and 6.3 h, respectively, for vetoquinol were obtained. Based on a minimum inhibitory concentration (MIC) of 0.0625 μg mL–1 for susceptible strains, a single intraperitoneal injection of 25 mg kg–1 of oxolinic acid maintains plasma levels in excess of 0.25 μg mL–1, corresponding to four times the MIC value, for ≈12 days. The corresponding values for a single oral dose of 25 mg kg–1 of oxolinic acid and vetoquinol were 5 and 10 days, respectively. For resistant strains with a MIC of 1 μg mL–1, a single oral dose of vetoquinol (25 mg kg–1) maintained plasma levels in excess of 4 μg mL–1 for 34 h.

The paper describes the concept of a management system called MOM (Modelling-Ongrowing fish farms-Monitoring) which may be used to adjust the local environmental impact of marine fish farms to the holding capacity of the sites. The concept is based on integrating the elements of environmental impact assessment, monitoring of impact and environmental quality standards (EQS) into one system. The amount of monitoring is dependent on the level of the environmental impact. Two terms are introduced: (1) the degree of exploitation, which is an expression of how much the site is being utilised, and (2) the level of monitoring, which determines the amount of monitoring depending on the environmental impact. For Norwegian conditions, a monitoring programme, including EQS, has been developed concerning the impact on the sediment under fish farms. It consists of three types of investigations of increasing elaboration and accuracy. A model, which simulates the environmental impact on a site given information about the farm's size and production and the hydrodynamic conditions and topography of the site, has been developed but not yet tested. The model and the monitoring programme with EQS are only briefly described, but will be published later. The MOM system should help to maintain satisfactory environmental conditions in and around fish farms and may be a valuable tool in site selection and coastal zone management.

The tissue distribution and depletion of ormethoprim (OMP, 5 mg kg−1 day−1) and sulphadimethoxine (SDM, 25 mg kg−1 day−1) were studied in Atlantic salmon (Salmo salar) after oral administration of Romet30 in feed for 5 consecutive days. The seawater temperature was 10.0 ± 0.5 °C and the salinity 33%. The concentrations of the drugs in plasma and the tissues were determined by high performance liquid chromatography. The plasma and tissue levels of OMP and SDM reached steady state levels between 3 and 8 days following initiation of medication. The highest average concentration of OMP in plasma, muscle, liver and kidney were 1.50, 3.67, 9.10 and 166.0 μg ml−1 (g−1), respectively. The corresponding values for SDM were 14.30, 17.72, 7.42 and 6.80 μg ml−1 (g−1), respectively. The elimination half-lives (t12β) for SDM in plasma, muscle liver, and kidney were 20, 19, 62 and 45 h, respectively. The corresponding values for OMP were 63, 143, 95 and 410 h for plasma, muscle, liver and kidney respectively. The mean ratios of OMP:SDM at steady state concentrations in the various organs were 1:10, 1:5, 1:0.8 and 1:0.06 for plasma, muscle, liver and kidney, respectively. The in vitro minimum inhibitory concentration values (MIC) for Romet30 and various OMP: SDM ratios against selected strains of Aeromonas salmonicida were 1–2 μg ml−1 for Romet30 and for the ratios of 1:5 and 1:1. For the OMP: SDM ratios of 1:0, 1:10 and 1:20, the MICs were 2–4 μg ml−1.

The pharmacokinetic properties of the antibacterial agent flumequine were studied after intravenous, intraperitoneal and oral administration to Atlantic halibut (Hippoglossus hippoglossus) held in seawater at 9 °C and weighing 1.5-2.5 kg. Following intravenous injection the plasma drug concentration-time profile showed three distinct phases. The distribution half life (t12 α) was estimated to be 0.8 h and the terminal elimination half life (t12 γ) to be 43 h. Total body clearance (ClT) was determined to be 0.052 1/kg h−1. The volume of distribution at steady state, Vd(ss), was estimated to be 2.3 1/kg indicating good tissue penetration of flumequine in Atlantic halibut. The peak plasma concentration (Cmax) and the time to peak plasma concentrations (Tmax) were estimated to be 2.7 and 6.1 μg/ml and 20 and 10 h, respectively, following oral administration of medicated feed or intraperitoneal injection. The bioavailabilities were calculated to be 31 and 69%, respectively, following oral or intraperitoneal administration. Only traces (< 10 ng/ml) of the metabolite 7-hydroxy-flumequine were found in a few of the plasma samples. Based on a minimum inhibitory concentration (MIC) of 0.0625 μg/ml for susceptible strains, a single intraperitoneal injection of 25 mg/kg of flumequine maintain plasma levels in excess of 0.25 μg/ml corresponding to 4 times the MIC-value, for approximately 10 d. The corresponding value for a single oral dose of 25 mg/kg of flumequine given as medicated feed, was 5 d.

The stability and activity of eight antibacterial agents dissolved in seawater were determined using UV-spectroscopy, high-performance liquid chromatography and microbiological assays. The samples were illuminated by daylight at sea level and submerged to a depth of 1 meter in the sea. Oxytetracycline, furazolidone, oxolinic acid and flumequine were degraded and lost their antibacterial activity during the experimental period of 21 days at sea level. Some degradation was found for sulfadiazine and sulfadimethoxine, while trimethoprim and ormethoprim were found to be stable. However, no significant decrease in antibacterial activity was observed for these substances. When exposed to underwater light intensities, only oxytetracycline, furazolidone and to a certain extent flumequine were decomposed. All other substances were found to be stable, Only oxytetracycline and furazolidone showed reduced antimicrobial activity when exposed to underwater light intensities.

We reviewed the biological and oceanographic data used to help decide on the siting of salmon farms in Canada (British Columbia and New Brunswick), Norway, Scotland, Ireland, Iceland, United State (Washington and Maine). The LENKA program in Norway and a ranking technique based on biophysical features in British Columbia are examples of semi-quantitative approaches. A zoning system partially based on detailed data on fjord oceanography has been initiated in Scotland. Guidelines to protect critical fish habitat, especially for wild salmon, have been developed in each of the jurisdictions. Models to help predict sedimentation, hypernutrification, and dissolved oxygen levels have been used in Norway and Washington. Siting criteria need to be supplemented with these models, which consider cumulative effects and predict the carrying capacity of key fjord areas where farms are likely to cluster. Coordinated and comprehensive research programs are needed which consider salmon production in the context of the oceanographic regimes within fjords. For site-specific evaluations and as communication methods, referral systems and guidelines are relied on extensively in site evaluations in the various jurisdictions.

1. Uptake, bioavailability, tissue disposition and elimination of sulphadimethoxine (SDM) and ormetoprim (OMP) were examined in Atlantic salmon (Salmo salar) following intravenous and oral administration of Romet(30) at a dose of 5 mg OMP and 25 mg SDM kg(-1) fish.2. Plasma clearance was rapid for both drugs following a single i.v. dose, characterized by t(1/2)alpha = 0.48 and 0.54 h, t(1/2)beta = 9.9 and 25.6 h for SDM and OMP respectively with a volume of distribution (V-ss) = 0.389 and 2.4781 kg(-1).3. Following oral administration, peak plasma concentrations of 1.13 and 9.99 mu g ml(-1) were achieved after 1.76 and 20.3 h for OMP and SDM respectively. Bioavailabilities were 85% for OMP and 39% for SDM.4. Oral administration revealed the highest concentration of OMP in kidney and liver whereas the highest concentrations of SDM were found in muscle and bile.5. High concentrations of N-4-acetylated SDM were found in the bile indicating significant metabolism of SDM.

High-performance liquid chromatography was used to quantify residues of oxolinic acid and flumequine in muscle of wild fish caught in the vicinity of fish farms using the LiftUp feed collector system or a hydroacoustic feed detector during medication. Both systems are designed to minimise feed waste and thereby the amount of medicated feed entering the surroundings. The result indicates that both systems decrease the supply of medicated pellets to the wild fish during medication, since the mean and maximum concentrations of drugs in muscle of wild fish were reduced compared to fish farms not using this equipment. Therefore, the equipment will reduce the environmental impact of antibacterial agents used in fish farming.

Applying high-performance liquid chromatography (HPLC) and microbiological assays, various antibacterial agents were tested for their stability in an artificial marine aquaculture sediment under laboratory conditions. HPLC analysis revealed that oxolinic acid (OXA), flumequine (FLU), oxytetracycline (OTC) and sulfadiazine (SUL) were stable, while sulfadimethoxine (SMX) decreased by ca. 20% during the experimental period of 180 days. Ormethoprim (OMP) and trimethoprim (TMP) were unstable and could not be detected after 1 and 2 months, respectively. Microbiological test-systems measured no decrease in the antimicrobial activity of sediments to which OXA, FLU, SUL and SMX were added. In the OTC- and OMP-treated sediments, no antibacterial activity was found 1 month after addition of the antibacterial agents. Two months following administration the antibacterial activity in the TMP-treated sediment was considerably reduced and after 3 months no antibacterial activity could be observed.