Background: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks.Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens.Methods: The authors participated in a workshop held 4–8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development “hot spots,” exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options.Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental “hot spot” compartments; and c) modifying traditional dose–response approaches to address doses of ARB for various health outcomes and pathways.Conclusions: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.Citation: Ashbolt NJ, Amézquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, Coors A, Finley R, Gaze WH, Heberer T, Lawrence JR, Larsson DG, McEwen SA, Ryan JJ, Schönfeld J, Silley P, Snape JR, Van den Eede C, Topp E. 2013. Human health risk assessment (HHRA) for environmental development and transfer of antibiotic resistance. Environ Health Perspect 121:993–1001; http://dx.doi.org/10.1289/ehp.1206316

No abstract

No abstract

Antibiotics and their metabolized products in human and animal waste are the major cause of antibiotic resistance in bacteria. Understanding what happens to drugs after their use could improve methods to remove antibiotics from rivers and soils and reduce the prevalence of resistance in bacterial populations in the environment.

European regulatory frameworks for chemicals (i.e. registered under REACH, plant protection products (PPPs), biocides, human and veterinary medicinal products) require that substances undergo an assessment to identify whether they are persistent (P), bioaccumulative (B) and toxic (T), or very persistent (vP) and very bioaccumulative (vB), i.e. to identify them as PBT substances or vPvB substances according to their properties. We screened current practices, evaluated possibilities and made a proposal for a harmonised assessment. Our proposal assumes that it should be possible to identify PBT and vPvB substances on the basis of the data available according to the requirements of the respective legal frameworks. For substances registered as PPPs and mostly also biocides and medicinal products, a 'definitive assessment' is often possible. Within REACH, the registrant has to provide all information necessary for PBT assessment regardless of the yearly tonnage of chemicals. But in cases of limited data availability, we suggest using a weight of evidence approach to account for such differences in data availability and type of data across different frameworks and to make use of valuable additional information. We propose to base the evaluation of persistence on degradation half-lives and to normalise a number of parameters (e.g. type of kinetics used, temperature). But further work is needed, e.g. for deriving DegT 50 for water and sediment compartments. For the B-criterion, information other than BCF in fish could be considered and more information related to bioaccumulation processes should be gathered (e.g. in species other than fish, different uptake routes). Testing for T identification is focused on standard aquatic species but could also be complemented by e.g. information from other species. Information such as those read-across from structurally related substances and QSAR are often of importance for screening assessments. The aim of PBT and vPvB identification is to reliably target the problematic substances, with as few false negatives or positives as possible, regardless of the regulatory framework. Each aspect was thus considered in the context of the others for a final balanced decision. As the need for conservatism is interpreted differently under the various frameworks, harmonizing this identification is a challenging task.