Research gaps and priorities for quantitative microbial risk assessment (QMRA).

The coronavirus disease 2019 pandemic highlighted the need for more rapid and routine application of modeling approaches such as quantitative microbial risk assessment (QMRA) for protecting public health. QMRA is a transdisciplinary science dedicated to understanding, predicting, and mitigating infectious disease risks. To better equip QMRA researchers to inform policy and public health management, an Advances in Research for QMRA workshop was held to synthesize a path forward for QMRA research. We summarize insights from 41 QMRA researchers and experts to clarify the role of QMRA in risk analysis by (1) identifying key research needs, (2) highlighting emerging applications of QMRA; and (3) describing data needs and key scientific efforts to improve the science of QMRA. Key identified research priorities included using molecular tools in QMRA, advancing dose-response methodology, addressing needed exposure assessments, harmonizing environmental monitoring for QMRA, unifying a divide between disease transmission and QMRA models, calibrating and/or validating QMRA models, modeling co-exposures and mixtures, and standardizing practices for incorporating variability and uncertainty throughout the source-to-outcome continuum. Cross-cutting needs identified were to: develop a community of research and practice, integrate QMRA with other scientific approaches, increase QMRA translation and impacts, build communication strategies, and encourage sustainable funding mechanisms. Ultimately, a vision for advancing the science of QMRA is outlined for informing national to global health assessments, controls, and policies.

Application of Effect-Based Methods to Water Quality Monitoring: Answering Frequently Asked Questions by Water Quality Managers, Regulators, and Policy Makers.

Effect-based methods (EBM) have great potential for water quality monitoring as they can detect the mixture effects of all active known and unknown chemicals in a sample, which cannot be addressed by chemical analysis alone. To date, EBM have primarily been applied in a research context, with a lower level of uptake by the water sector and regulators. This is partly due to concerns regarding the reliability and interpretation of EBM. Using evidence from the peer-reviewed literature, this work aims to answer frequently asked questions about EBM. The questions were identified through consultation with the water industry and regulators and cover topics related to the basis for using EBM, practical considerations regarding reliability, sampling for EBM and quality control, and what to do with the information provided by EBM. The information provided in this work aims to give confidence to regulators and the water sector to stimulate the application of EBM for water quality monitoring.

Effect-based monitoring to integrate the mixture hazards of chemicals into water safety plans.

Water safety plans (WSPs) are intended to assure safe drinking water (DW). WSPs involve assessing and managing risks associated with microbial, chemical, physical and radiological hazards from the catchment to the consumer. Currently, chemical hazards in WSPs are assessed by targeted chemical analysis, but this approach fails to account for the mixture effects of the many chemicals potentially present in water supplies and omits the possible effects of non-targeted chemicals. Consequently, effect-based monitoring (EBM) using in vitro bioassays and well plate-based in vivo assays are proposed as a complementary tool to targeted chemical analysis to support risk analysis, risk management and water quality verification within the WSP framework. EBM is frequently applied to DW and surface water and can be utilised in all defined monitoring categories within the WSP framework (including 'system assessment', 'validation', 'operational' and 'verification'). Examples of how EBM can be applied within the different WSP modules are provided, along with guidance on where to apply EBM and how frequently. Since this is a new area, guidance documents, standard operating procedures (SOPs) and decision-making frameworks are required for both bioassay operators and WSP teams to facilitate the integration of EBM into WSPs, with these resources being developed currently.

Quantitative chemical risk assessment for mixtures: Application to alkylphenol mixtures and phthalate mixtures in tap and bottled water.

The occurrence and hazard risks of mixtures of Contaminants of Emerging Concern (CECs) in drinking water (DW) lead to serious consideration regarding the possible impacts on public health. Consequently, there is ongoing research, development and empowerment of risk assessment procedures to get more toxicological insight. For instance, alkylphenols and phthalates have been frequently reported to be present both in bottled and tap water, affecting different human endpoints. Currently, deterministic chemical risk assessment (CRA) is used to evaluate the compounds' mixture health risk. However, CRA deals just qualitatively with sources of uncertainty, which may lead to erroneous assessment of risks. Here, a new procedure for quantitative chemical risk assessment of CEC mixtures (QCRAMIX) is proposed. Its potential is illustrated by a case study where the risks related to the presence of mixtures of alkylphenols or phthalates in tap versus bottled DW are compared. Uncertainties in both exposure and hazard assessment steps of the procedure are included to calculate a probabilistic mixture Benchmark Quotient (BQMIX). The QCRAMIX procedure highlighted the non-negligible health risks posed by those compounds in both DW sources based on overall water consumption. In fact, DW consumers' behaviour in 13 different countries, in terms of total DW consumption and fraction of bottled and tap water consumed, were considered to evaluate the influence on health risk. For alkylphenols, the total water consumption was found to be the most relevant factor in increasing the health risk, while for phthalates the risk was found to be mainly influenced by the percentage of bottled water consumed. Hence, the proposed QCRAMIX procedure can be a valuable tool for prioritization of CECs to be included in DW regulations which aim to minimize the overall risk, accounting for actual DW consumption.

Development of a quantitative chemical risk assessment (QCRA) procedure for contaminants of emerging concern in drinking water supply.

The uncertainties on the occurrence, fate and hazard of Contaminants of Emerging Concern (CECs) increasingly challenge drinking water (DW) utilities whether additional measures should be taken to reduce the health risk. This has led to the development and evaluation of risk-based approaches by the scientific community. DW guideline values are commonly derived based on deterministic chemical risk assessment (CRA). Here, we propose a new probabilistic procedure, that is a quantitative chemical risk assessment (QCRA), to assess potential health risk related to the occurrence of CECs in DW. The QCRA includes uncertainties in risk calculation in both exposure and hazard assessments. To quantify the health risk in terms of the benchmark quotient probabilistic distribution, the QCRA estimates the probabilistic distribution of CECs concentration in DW based on their concentration in source water and simulating the breakthrough curves of a granular activated carbon (GAC) treatment process. The model inputs and output uncertainties were evaluated by sensitivity and uncertainty analyses for each step of the risk assessment to identify the most relevant factors affecting risk estimation. Dominant factors resulted to be the concentration of CECs in water sources, GAC isotherm parameters and toxicological data. To stress the potential of this new QCRA approach, several case studies are considered with focus on bisphenol A as an example CEC and various GAC management options. QCRA quantifies the probabilistic risk, providing more insight compared to CRA. QCRA proved to be more effective in supporting the intervention prioritization for treatment optimization to pursue health risk minimization.

Optimizing the performance of conventional water treatment system using quantitative microbial risk assessment, Tehran, Iran.

The performance of conventional drinking water treatment plants (WTPs) can be improved using quantitative microbial risk assessment (QMRA). A QMRA study on Cryptosporidium using actual pathogen density was conducted to examine the performance of Jalaliyeh WTP in Tehran, Iran. The infection risk and the burden of disease attributed to the parasite presence in finished water were estimated incorporating physical and chemical log reduction values (LRVs), using stochastic modeling and disinfection profiling. The risk and burden of disease were compared with health-based targets, i.e. one case of infection per 10,000 people or 10-6 DALYs per person per year. The parasite's LRVs were 2.31 and 0.034 log provided by physico-chemical treatment and disinfection processes, respectively. The mean of estimated risk (111 cases per 104 people per year) and the burden of disease (11.7 DALYs per 106 people per year) both exceeded the targets. To control the excess risk, three QMRA-based disinfection scenarios were examined including: (1) employing chlorine dioxide (ClO2) instead of chlorine (2) ozonation with a concentration of 0.75 mg/L (Ct = 22.5 min mg/L) and (3) UV irradiation with a dose of 10 mJ/cm2. The LRV of parasite may be increased to 3.0, 5.1 and 4.9 log by employing ClO2, ozonation and UV irradiation, respectively. The use of ozone or UV as alternative disinfectants, could enhance the disinfection efficacy and provide sufficient additional treatment against the excess risk of parasite. QMRA could make it easier applying appropriate improvement to conventional WTPs in order to increase the system performance in terms of health-based measures.

Using QMRA-based regulation as a water quality management tool in the water security challenge: experience from the Netherlands and Australia.

Innovation in the water sector is at play when addressing the global water security challenge. This paper highlights an emerging role for Quantitative Microbial Risk Assessment (QMRA) and health-based targets in the design and application of robust and flexible water quality regulation to protect public health. This role is especially critical as traditional supply sources are subject to increased contamination, and recycled wastewater and stormwater become a crucial contribution to integrated water supply strategies. Benefits and weaknesses of QMRA-based regulation are likely to be perceived differently by the multiple stakeholders involved. The goal of the current study is to evaluate the experience of QMRA-based regulation implementation in the Netherlands and Australia, and to draw some lessons learned for regulators, policy makers, the industry and scientists. Water experts from regulatory bodies, government, water utilities, and scientists were interviewed in both countries. This paper explores how QMRA-based regulation has helped decision-making in the Netherlands in drinking water safety management over the past decade. Implementation is more recent in Australia: an analysis of current institutional barriers to nationally harmonized implementation for water recycling regulation is presented. This in-depth retrospective analysis of experiences and perceptions highlights the benefits of QMRA-based regulation and the challenges of implementation. QMRA provides a better assessment of water safety than the absence of indicators. Setting a health target addresses the balance between investments and public safety, and helps understand risks from alternative water sources. Challenges lie in efficient monitoring, institutional support for utilities, interpretation of uncertainty by regulators, and risk communication to consumers.