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Proposal for a tiered dietary bioaccumulation testing strategy for engineered nanomaterials using fish

Handy, Richard D., Ahtiainen, Jukka, Navas, José María, Goss, Greg, Bleeker, Eric A. J., von der Kammer, Frank·2018·Environmental Science: Nano
DOI 10.1039/c7en01139c
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Abstract

The scientific community has invested effort into standardising methodologies for the regulatory ecotoxicity testing of engineered nanomaterials (ENMs), but the practical requirements for bioaccumulation testing of ENMs have been given less attention.

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Fig. 1 A tiered approach to the dietary bioaccumulation testing strategy. The first tier uses dissolution in water or in lipids as an environmental chemistry trigger(s) for concern, but where these triggers do not work for a particular ENM, then an alternative settling rate test is proposed or similar measures that quantifies removal from the water column. This tier uses a weight of evidence from these tests plus existing data sets from the literature. A positive result of the trigger test and/or evidence of concern from literature will move investigations to the next tier. In tier 2 new data generation occurs using in silico models and supported by evidence from soils, microbial or invertebrate tests that might suggest a bioaccumulation potential. A likely risk from this tier will move work to tier 3 where in chemico studies are done to determine the bioaccessible fractions of ENMs in the gut lumen environment of fish. If the digestibility assay is positive, then gut sacs can be used to confirm accumulation by the gut mucosa of fish tissue. Only if both these tests are positive would the work proceed to the final in vivo test (tier 4). The latter test is essentially the OECD TG 305 dietary bioaccumulation method, with some additional caveats and guidance for ENMs.
Fig. 1 A tiered approach to the dietary bioaccumulation testing strategy. The first tier uses dissolution in water or in lipids as an environmental chemistry trigger(s) for concern, but where these triggers do not work for a particular ENM, then an alternative settling rate test is proposed or similar measures that quantifies removal from the water column. This tier uses a weight of evidence from these tests plus existing data sets from the literature. A positive result of the trigger test and/or evidence of concern from literature will move investigations to the next tier. In tier 2 new data generation occurs using in silico models and supported by evidence from soils, microbial or invertebrate tests that might suggest a bioaccumulation potential. A likely risk from this tier will move work to tier 3 where in chemico studies are done to determine the bioaccessible fractions of ENMs in the gut lumen environment of fish. If the digestibility assay is positive, then gut sacs can be used to confirm accumulation by the gut mucosa of fish tissue. Only if both these tests are positive would the work proceed to the final in vivo test (tier 4). The latter test is essentially the OECD TG 305 dietary bioaccumulation method, with some additional caveats and guidance for ENMs.CC-BY-NC · From the PDF
Fig. 2 Chemistry triggers for an ENM of concern in tier 1 of the testing strategy, using Degussa P25 titanium dioxide nanoparticles (open circles) compared to a TiO2 bulk material of similar composition with a primary particle diameter of 147 nm (closed circle) and unexposed controls (triangles). (A) Particle settling from a 1 mg L -1 exposure measured by the decrease in total Ti concentration in the water column over time in a 20 L fish tank containing aerated Plymouth freshwater (Handy and Ramsden, unpublished observations). (B) Particle settling in unstirred Krebs physiological saline from initial 10 mg L -1 stock dispersions of each TiO2 material (Handy and Butcher unpublished observations). Note in panel A and B that the bulk material settles faster than the equivalent ENM in both freshwater and saline. (C) Dissolution curves for TiO2 materials measured by dialysis in a fish gut saline. The cumulative appearance of total Ti metal through the dialysis tubing into the external medium is shown with curves fitted to a rectangular hyperbola. The dialysis bag contained a total of 800 μ g of Ti metal, thus only 5% or less of the materials dissolved. The unexposed saline was at or below the detection limit. Redrawn from Al-Jubory and Handy. 11 All values are means ± S.E. of triplicate measurements. Note, the error bars are often too small to visualise.
Fig. 2 Chemistry triggers for an ENM of concern in tier 1 of the testing strategy, using Degussa P25 titanium dioxide nanoparticles (open circles) compared to a TiO2 bulk material of similar composition with a primary particle diameter of 147 nm (closed circle) and unexposed controls (triangles). (A) Particle settling from a 1 mg L -1 exposure measured by the decrease in total Ti concentration in the water column over time in a 20 L fish tank containing aerated Plymouth freshwater (Handy and Ramsden, unpublished observations). (B) Particle settling in unstirred Krebs physiological saline from initial 10 mg L -1 stock dispersions of each TiO2 material (Handy and Butcher unpublished observations). Note in panel A and B that the bulk material settles faster than the equivalent ENM in both freshwater and saline. (C) Dissolution curves for TiO2 materials measured by dialysis in a fish gut saline. The cumulative appearance of total Ti metal through the dialysis tubing into the external medium is shown with curves fitted to a rectangular hyperbola. The dialysis bag contained a total of 800 μ g of Ti metal, thus only 5% or less of the materials dissolved. The unexposed saline was at or below the detection limit. Redrawn from Al-Jubory and Handy. 11 All values are means ± S.E. of triplicate measurements. Note, the error bars are often too small to visualise.CC-BY-NC · From the PDF
Image 3
CC-BY-NC · From the PDF
Fig. 3 (A) Summary of the step-wise in chemico digestibility assay simulating digestion in fish gut. The first three steps can be done with simple shaking at room temperature for 1 hour, followed by 12 h ( e.g. , overnight) for the enzymatic digestion and a final strong acid digestion of the remainder. * The enzyme mix is simplified from Carter et al. 71 as trypsin 0.8 mg mL -1 , chymotrypsin 1.6 mg mL -1 , protease 0.7 mg mL -1 at pH 8 in 0.9% NaCl. (B) Example in chemico digestibility data for 1 g samples of fish pellets loaded with Ag or Ag2S ENMs (Handy and Teape, unpublished observations from the EU Nanofase project materials). Only a few percent of the total silver are extracted by NaCl, EDTA or HCl extractions respectively, suggesting low oral bioavailability of these materials from fish food. Values are means ± S.E., n = 6 digestions each. Different letters indicate a significant difference between substances with extraction method (Kruskal Wallis or ANOVA, P < 0.05, note the controls had < 0.1% extractable silver).
Fig. 3 (A) Summary of the step-wise in chemico digestibility assay simulating digestion in fish gut. The first three steps can be done with simple shaking at room temperature for 1 hour, followed by 12 h ( e.g. , overnight) for the enzymatic digestion and a final strong acid digestion of the remainder. * The enzyme mix is simplified from Carter et al. 71 as trypsin 0.8 mg mL -1 , chymotrypsin 1.6 mg mL -1 , protease 0.7 mg mL -1 at pH 8 in 0.9% NaCl. (B) Example in chemico digestibility data for 1 g samples of fish pellets loaded with Ag or Ag2S ENMs (Handy and Teape, unpublished observations from the EU Nanofase project materials). Only a few percent of the total silver are extracted by NaCl, EDTA or HCl extractions respectively, suggesting low oral bioavailability of these materials from fish food. Values are means ± S.E., n = 6 digestions each. Different letters indicate a significant difference between substances with extraction method (Kruskal Wallis or ANOVA, P < 0.05, note the controls had < 0.1% extractable silver).CC-BY-NC · From the PDF
Fig. 4 Example data on TiO2 for tier 3 (panel A) and tier 4 (panel B) of the testing strategy. (A) Total Ti metal concentrations in the mucosa of whole gut sacs from rainbow trout exposed to 1 mg L -1 TiO2 in the gut lumen for 4 h (data from Al-Jubory and Handy 11 ). Control (grey bars), bulk TiO2 (black bars), P25 TiO2 ENMs (white bars). The mucosa accumulates Ti indicating some potential for bioaccumulation. (B) In vivo results from trout fed diets containing no added TiO2 (control, grey bars), or 10 (stippled bars), or 100 mg P25 TiO2 ENMs kg -1 food (white bars) for six weeks. Data redrawn from Ramsden et al. 34 Note, like the gut sac studies, the intestine in vivo shows Ti accumulation, but not the liver. In both panels, data are means ± S.E., n = 6. * Significantly different from the control (ANOVA or Kruskal Wallis, P < 0.05). The in vivo studies were performed at Plymouth University with ethical approval from the local ethics committee and authorisation by a project license (under the UK Home Office Scientific Procedures Act) held by R. D. Handy.
Fig. 4 Example data on TiO2 for tier 3 (panel A) and tier 4 (panel B) of the testing strategy. (A) Total Ti metal concentrations in the mucosa of whole gut sacs from rainbow trout exposed to 1 mg L -1 TiO2 in the gut lumen for 4 h (data from Al-Jubory and Handy 11 ). Control (grey bars), bulk TiO2 (black bars), P25 TiO2 ENMs (white bars). The mucosa accumulates Ti indicating some potential for bioaccumulation. (B) In vivo results from trout fed diets containing no added TiO2 (control, grey bars), or 10 (stippled bars), or 100 mg P25 TiO2 ENMs kg -1 food (white bars) for six weeks. Data redrawn from Ramsden et al. 34 Note, like the gut sac studies, the intestine in vivo shows Ti accumulation, but not the liver. In both panels, data are means ± S.E., n = 6. * Significantly different from the control (ANOVA or Kruskal Wallis, P < 0.05). The in vivo studies were performed at Plymouth University with ethical approval from the local ethics committee and authorisation by a project license (under the UK Home Office Scientific Procedures Act) held by R. D. Handy.CC-BY-NC · From the PDF
Image 6
CC-BY-NC · From the PDF

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Metadata

Authors
Handy, R. D., Ahtiainen, J., Navas, J. M., Goss, G., Bleeker, E. A. J., & von der Kammer, F.
Venue
Environmental Science: Nano
Publisher
Royal Society of Chemistry (RSC)
Published
2018
Volume
5
Issue
9
Pages
2030-2046
ISSN
  • 2051-8153
  • 2051-8161
DOI
10.1039/c7en01139c
Cited by
18
References
1
Language
en
Licence
creativecommons.org/licenses/by-nc/3.0/ (vor, 213 d)

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Handy, R. D., Ahtiainen, J., Navas, J. M., Goss, G., Bleeker, E. A. J., & von der Kammer, F. (2018). Proposal for a tiered dietary bioaccumulation testing strategy for engineered nanomaterials using fish. Environmental Science: Nano. https://doi.org/10.1039/c7en01139c