Harvesting the promise of AOPs: An assessment and recommendations

The Adverse Outcome Pathway (AOP) concept is a knowledge assembly and communication tool to facilitate the transparent translation of mechanistic information into outcomes meaningful to the regulatory assessment of chemicals. The AOP framework and associated knowledgebases (KBs) have received significant attention and use in the regulatory toxicology community. However, it is increasingly apparent that the potential stakeholder community for the AOP concept and AOP KBs is broader than scientists and regulators directly involved in chemical safety assessment. In this paper we identify and describe those stakeholders who currently—or in the future—could benefit from the application of the AOP framework and knowledge to specific problems. We also summarize the challenges faced in implementing pathway-based approaches such as the AOP framework in biological sciences, and provide a series of recommendations to meet critical needs to ensure further progression of the framework as a useful, sustainable and dependable tool supporting assessments of both human health and the environment. Although the AOP concept has the potential to significantly impact the organization and interpretation of biological information in a variety of disciplines/applications, this promise can only be fully realized through the active engagement of, and input from multiple stakeholders, requiring multi-pronged substantive long-term planning an d strategies

Performance of juvenile turbot (Scophthalmus maximus) fed varying dietary L-carnitine levels at different stocking densities

Commercial farming of turbot (Scophthalmus maximus) at high stocking densities may lead to growth depression and increasing production costs. Moreover, the high levels of accumulated waste in an intensive system may cause rapid deterioration of water quality, which may undermine the production. L-carnitine is known as a growth-enhancer which shows promise as mitigator of crowding effects. The effects of stocking densities (4, 8, 11 and 14 kg m²) on growth performance, feed utilization and body composition were evaluated during 75 days on turbot (75.6 ± 2.8 g) fed two dietary L-carnitine levels (40 or 240 mg kg¹). At the end of the feeding trial, total ammonia excretion (TAN) was measured postprandially for 24h. Specific growth rate and weight gain decreased with increasing stocking density. Fish held at 4 kg m² had higher final body weight (94-96 g) than fish held at higher densities (80-87 g). Protein efficiency ratio was higher in fish held at 4 kg m² (1.33-1.36), in comparison to fish stocked at 8 kg m² (0.98) or 14 kg m² (0.45). Voluntary feed intake decreased from 0.70 to 0.56% BW with increasing stocking density. Dietary L-carnitine supplementation did not affect growth performance and body composition, except for body L-carnitine content which increased from 75 to 128 mg kg¹ BW with supplementation. Fish fed 240 mg L-carnitine supplements had lower TAN that the ones fed 40 mg L-carnitine (p A aquicultura de pregado (Scophthalmus maximus) utilizando elevadas densidades pode reduzir o crescimento e aumentar os custos de produção. Elevados níveis de metabolitos gerados nestes sistemas intensivos provocam rápida deterioração da qualidade da água, podendo também comprometer a performance da produção. A L-carnitina atua como potenciadora do crescimento parecendo ser promissora por atenuar alguns desses efeitos. Os efeitos de densidades (4, 8, 11 e 14 kg m²) no desempenho do crescimento, composição corporal foram avaliados em pregados (75,6 ± 2,8 g) alimentados durante 75 dias a dois níveis dietéticos de L-carnitina (40 ou 240 mg kg¹). Após esse período, determinou-se a excreção de amônia pós-prandial durante 24 horas. Os peixes cultivados na menor densidade, 4 kg m², apresentaram melhores taxas de crescimento e ganho de peso (94-96 g) em comparação aos mantidos em altas densidades (80-87 g). A taxa de eficiência proteica foi mais elevada a 4 kg m² (1,33-1,36), do que a densidades de 8 kg m² (0,98) ou 14 kg m² (0,45). A ingestão voluntária de alimento decresceu de 0,70 para 0,56% do peso corporal com o incremento da densidade. A suplementação de carnitina não afetou o crescimento e a composição corporal, com exceção do conteúdo de carnitine da carcaça que passou de 75 a 128 mg kg¹. Peixes alimentados com suplementos de 240 mg L-carnitina apresentam excreção de amônia mais baixa comparativamente aos alimentados com 40 mg L-carnitina (p < 0,05)

Metallothionein induction and condition index of dogwhelks <i>Nucella lapillus</i> (L.) exposed to cadmium and hydrogen peroxide

It has been suggested that metallothionein (MT) not only can regulate essential metals and detoxify toxic metals, but that MT can also play a significant role as an antioxidant and can be induced by oxidative stresses other than metals. This study is aimed at investigating the effect of hydrogen peroxide (H2O2), and the combined effect of H2O2 and cadmium (Cd) on MT induction and condition index (CI) in dogwhelks Nucella lapillus. Adult male dogwhelks (27 +/- 1 mm in shell length) were exposed for 20 days to (1) control (filtered natural seawater only); (2), 0.50 ppm Cd; (3) 2.0 ppm H2O2 + 0.50 PPm Cd; (4) 1.0 ppm H2O2 + 0.25 ppm Cd: (5) 2.0 ppm H2O2; (6) 1000 ppm H2O2 or (7) 1000 ppm H2O2 + 0.50 ppm Cd. The concentration of MT in the Leiblein gland of N. lapillus was quantified using the silver saturation method. MT or MT-like proteins in the animals were induced by Cd (0.5 ppm), H2O2 (2.0 ppm) or Cd + H2O2, indicating that MT in this gastropod species can be induced by either metal or oxidative stresses. Exposure to high H2O2 (1000 ppm) alone or combined with Cd, and exposure to Cd (0.50 ppm) or H2O2 (2.0 ppm), resulted in significant weight loss? indicated by a reduction of CI. However, CIs of groups (3) and (4) were similar to that of the control suggesting that Cd antagonistically reduces toxicity caused by H2O2 since Cd- induced MT may have a protective function against hydroxyl radicals

Field validation, in Scotland and Iceland, of the artificial mussel for monitoring trace metals in temperate seas

The artificial mussel (AM), a novel chemical sampling device, has been developed for monitoring dissolved trace metals in marine environments. The AM consists of Chelex-100 suspended in artificial seawater within Perspex tubing and enclosed with semi-permeable polyacrylamide gel at both ends. To validate the field performance of the AM in temperate waters, we deployed AMs alongside transplanted blue mussels Mytilus edulis in coastal environments in Scotland (Holy Loch, Loch Fyne, Loch Striven and Millport) and Iceland (Reykjavikurhofn, Gufunes, South of [thorn]erney, Hofsvik, Hvalfjorethur and Sandgerethi) for monitoring trace metals. While uptake patterns of Cd between the AM and M. edulis were highly comparable, discrepancies were found in the accumulation profiles of the other metals (Cu, Cr, Pb and Zn), in particular Zn. Nonetheless, the AMs gave a better resolution to accurately reveal the spatial difference in dissolved metal contamination when compared with M. edulis. AMs complement the use of mussels since AMs indicate dissolved metals in seawater, whereas uptake by mussels indicates a mixture of dissolved and particulate metals. Our results also indicated that historical metal exposure of the transplanted M. edulis could significantly confound their metal concentrations especially when the deployment period was short (i.e. lt 34 d). This study suggested that the AM can overcome problems associated with variable biological attributes and pre-exposure history in the mussel, and provides a standardized and representative time-integrated estimate of dissolved metal concentrations in different marine environment

Growth rate as a factor confounding the use of the dogwhelk <i>Nucella lapillus </i>as biomonitor of heavy metal contamination

Growth rate of individually tagged dogwhelks Nucella lapillus (L.) was measured in free-living individuals at 3 sites of differing heavy metal contamination in the Firth of Clyde, west Scotland. Condition index (CI), concentrations of metals (Cd, Cu, Pb and Zn), metallothionein (NIT), RNA (the RNA/protein ratio) and glycogen were also measured. In general, the marine environments of Gourock and Largs were contaminated with significantly higher tributyltin, Pb and Zn than Loch Fyne, as indicated by the results of imposex indices, and metal concentrations in transplanted polymer-ligands (Chelex (R) 100) and Mytilus edulis. Further, metal concentrations of native M. edulis (Pb and Zn) and Semibalanus balanoides (Cu) from Gourock were significantly higher than those from Loch Fyne. However, metal accumulation in the dogwhelks displayed a very different pattern. At a standard size (0.5 g wet soft-body weight), N. lapillus from Largs showed higher Cd, Cu and MT in their tissues than individuals from the other 2 populations. Levels of Pb and Zn were similar among the populations despite different concentrations in Chelex and mussels. Gourock dogwhelks showed similar levels of Cu and NIT but lower Cd compared to those of Loch Fyne. These differences can be attributed primarily to differences in dogwhelk growth rate between sites. Gourock individuals had a higher Cl and RNA/protein ratio in the foot muscle and grew faster (especially at small sizes), resulting in a tissue-dilution effect on metal and NIT concentrations, In contrast, higher levels of Cd, Cu and NIT in dogwhelks from Largs can be attributed to their growth rate being relatively slow compared to the rate of metal accumulation, Slow-growing individuals in Loch Fyne had relatively high Cd, Pb Zn and NIT, although Loch Fyne has been regarded as a clean reference site, Among populations, differences in growth rate may be due to differences in prey availability, predation pressure, and/or genotype. The present results demonstrate that inter-site differences in growth rate can confound the use of the dogwhelks as a biomonitor of metal

Can saltwater toxicity be predicted from freshwater data?

The regulation of substances discharged to estuarine and coastal environments relies upon data derived from ecotoxicity tests. Most such data are generated for freshwater rather than saltwater species. If freshwater toxicity data are related to saltwater toxic effects in a systematic and predictable way, the former can be used to predict the latter. This would have economic advantages due to a reduction in toxicity testing of saltwater species. If toxicity data are plotted as species sensitivity distributions, four theoretical relationships between freshwater and saltwater can be envisaged. Examples show that each one of these relationships is supported by empirical data. These examples show that although there is considerable potential for freshwater to saltwater prediction, species parity and representativeness need to be examined for each chemical substance to avoid bias

Sediment metal enrichment and ecological risk assessment of ten ports and estuaries in the World Harbours Project

Ten global harbours were assessed for sediment quality by quantifying the magnitude of anthropogenic change and ecological risk. Anthropogenic change (enrichment) was high for Derwent River and Sydney estuary, moderate for Santander Harbour, Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin. All 10 enrichment indices used showed similar results. Derwent River sediment was rated at high ecological risk, followed by Sydney and Santander estuaries with moderate risk. Auckland and Darwin sediments exhibited minimal ecological risk and sediment in the remaining harbours (Dublin, Hong Kong, Ravenna, Ria de Vigo and Rio de Janeiro) were assessed at slight ecological risk. The extraordinary variety of environments and types/quantities/qualities of data investigated resulted in as much a critique and development of methodology, as an assessment of human impact, including unique techniques for elemental normalisation and contaminant classification. Recommendations for an improved technical framework for sediment quality assessment are provided

Sediment metal enrichment and ecological risk assessment of ten ports and estuaries in the World Harbours Project

Ten global harbours were assessed for sediment quality by quantifying the magnitude of anthropogenic change and ecological risk. Anthropogenic change (enrichment) was high for Derwent River and Sydney estuary, moderate for Santander Harbour, Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin. All 10 enrichment indices used showed similar results. Derwent River sediment was rated at high ecological risk, followed by Sydney and Santander estuaries with moderate risk. Auckland and Darwin sediments exhibited minimal ecological risk and sediment in the remaining harbours (Dublin, Hong Kong, Ravenna, Ria de Vigo and Rio de Janeiro) were assessed at slight ecological risk. The extraordinary variety of environments and types/quantities/qualities of data investigated resulted in as much a critique and development of methodology, as an assessment of human impact, including unique techniques for elemental normalisation and contaminant classification. Recommendations for an improved technical framework for sediment quality assessment are provided