Screening for drinking water contaminants of concern using an automated exposure-focused workflow.

BACKGROUND: The number of chemicals present in the environment exceeds the capacity of government bodies to characterize risk. Therefore, data-informed and reproducible processes are needed for identifying chemicals for further assessment. The Minnesota Department of Health (MDH), under its Contaminants of Emerging Concern (CEC) initiative, uses a standardized process to screen potential drinking water contaminants based on toxicity and exposure potential. OBJECTIVE: Recently, MDH partnered with the U.S. Environmental Protection Agency (EPA) Office of Research and Development (ORD) to accelerate the screening process via development of an automated workflow accessing relevant exposure data, including exposure new approach methodologies (NAMs) from ORD's ExpoCast project. METHODS: The workflow incorporated information from 27 data sources related to persistence and fate, release potential, water occurrence, and exposure potential, making use of ORD tools for harmonization of chemical names and identifiers. The workflow also incorporated data and criteria specific to Minnesota and MDH's regulatory authority. The collected data were used to score chemicals using quantitative algorithms developed by MDH. The workflow was applied to 1867 case study chemicals, including 82 chemicals that were previously manually evaluated by MDH. RESULTS: Evaluation of the automated and manual results for these 82 chemicals indicated reasonable agreement between the scores although agreement depended on data availability; automated scores were lower than manual scores for chemicals with fewer available data. Case study chemicals with high exposure scores included disinfection by-products, pharmaceuticals, consumer product chemicals, per- and polyfluoroalkyl substances, pesticides, and metals. Scores were integrated with in vitro bioactivity data to assess the feasibility of using NAMs for further risk prioritization. SIGNIFICANCE: This workflow will allow MDH to accelerate exposure screening and expand the number of chemicals examined, freeing resources for in-depth assessments. The workflow will be useful in screening large libraries of chemicals for candidates for the CEC program.

Current Breast Milk PFAS Levels in the United States and Canada: After All This Time, Why Don't We Know More?

BACKGROUND: Despite 20 y of biomonitoring studies of per- and polyfluoroalkyl substances (PFAS) in both serum and urine, we have an extremely limited understanding of PFAS concentrations in breast milk of women from the United States and Canada. The lack of robust information on PFAS concentrations in breast milk and implications for breastfed infants and their families were brought to the forefront by communities impacted by PFAS contamination. OBJECTIVES: The objectives of this work are to: a) document published PFAS breast milk concentrations in the United States and Canada; b) estimate breast milk PFAS levels from maternal serum concentrations in national surveys and communities impacted by PFAS; and c) compare measured/estimated milk PFAS concentrations to screening values. METHODS: We used three studies reporting breast milk concentrations in the United States and Canada We also estimated breast milk PFAS concentrations by multiplying publicly available serum concentrations by milk:serum partitioning ratios for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Measured and estimated breast milk concentrations were compared to children's drinking water screening values. DISCUSSION: Geometric means of estimated breast milk concentrations ranged over approximately two orders of magnitude for the different surveys/communities. All geometric mean and mean estimated and measured breast milk PFOA and PFOS concentrations exceeded drinking water screening values for children, sometimes by more than two orders of magnitude. For PFHxS and PFNA, all measured breast milk levels were below the drinking water screening values for children; the geometric mean estimated breast milk concentrations were close to-or exceeded-the children's drinking water screening values for certain communities. Exceeding a children's drinking water screening value does not indicate that adverse health effects will occur and should not be interpreted as a reason to not breastfeed; it indicates that the situation should be further evaluated. It is past time to have a better understanding of environmental chemical transfer to-and concentrations in-an exceptional source of infant nutrition. https://doi.org/10.1289/EHP10359.

Potential for Manganese-Induced Neurologic Harm to Formula-Fed Infants: A Risk Assessment of Total Oral Exposure.

BACKGROUND: High oral exposure and biological vulnerabilities may put formula-fed infants at risk for manganese-induced neurotoxicity. OBJECTIVES: We sought to characterize manganese concentrations in public drinking water and prepared infant formulas commonly purchased in the United States, integrate information from these sources into a health risk assessment specific to formula-fed infants, and examine whether households that receive water with elevated manganese concentrations avoid or treat the water, which has implications for formula preparation. METHODS: Manganese was measured in 27 infant formulas and nearly all Minnesota community public water systems (CPWS). The risk assessment produced central tendency and upper-end exposure estimates that were compared to a neonatal animal-based health reference dose (RfD) and considered possible differences in bioavailability. A survey study assessed esthetic concerns, treatment, and use of water in a Twin Cities community with various levels of manganese in drinking water. RESULTS: Ten percent of CPWSs were estimated to exceed the EPA health advisory level of 300 µg/L. Manganese concentrations in formula ranged from 69.8 to 741 µg/L, with amino acid>soy>cow's milk formula concentrations. Central tendency estimates of soy and amino acid formula reconstituted with water at the CPWS 95th percentile manganese concentration exceeded the neonatal-based RfD. Upper-end estimates of manganese intake from formula alone, independent of any water contribution, equaled or exceeded the neonatal-based RfD. In the survey study, we observed increased awareness of esthetic issues and water avoidance at higher manganese concentrations, but these concentrations were not a reliable consumption deterrent, as the majority of households with inside tap drinking water results above 300 µg/L reported drinking the water. DISCUSSION: Excessive exposure to manganese early in life can have long-lasting neurological impacts. This assessment underscores the potential for manganese overexposure in formula-fed infants. U.S. agencies that regulate formula and drinking water must work collaboratively to assess and mitigate potential risks. https://doi.org/10.1289/EHP7901.

Correction to: A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction: A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance.

Minnesota has been grappling with extensive per- and polyfluoroalkyl substances (PFASs) groundwater contamination since 2002, in a major metropolitan setting. As toxicological information has accumulated for these substances, the public health community has become increasingly aware of critically sensitive populations. The accumulation of some PFAS in women of childbearing age, and the placental and breastmilk transfer to their offspring, require new risk assessment methods to protect public health. The traditional water guidance paradigm is inadequate to address maternal-to-infant transfer of accumulated levels of perfluorooctanoate (PFOA), in particular. Even short exposures during infancy have dramatic impacts on serum levels for many years. In addition, developmental effects are the critical effects anchoring recent risk assessments. In response, the Minnesota Department of Health created an Excel-based model that incorporates chemical-specific properties and exposure parameters for early life stages. Serum levels were assessed in both formula-fed and breastfed infants, with placental transfer in both scenarios. Peak breastfed infant serum levels were 4.4-fold higher than in formula-fed infants, with both of these scenarios producing serum levels in excess of the adult steady-state level. The development and application of this model to PFOA are described.

A Method for Developing Rapid Screening Values for Active Pharmaceutical Ingredients (APIs) in Water and Results of Initial Application for 119 APIs.

Americans fill upward of four billion prescriptions for pharmaceuticals each year, and many of those pharmaceuticals eventually make their way into the environment. Hundreds of different active pharmaceutical ingredients (APIs) are detected in ambient waters and source water used for drinking water in the U.S. Very few of these drugs have health-based guidance values that suggest a safe level for individuals exposed in the ambient environment through drinking water. The Minnesota Department of Health (MDH) has developed a novel method to derive screening-level human health guidance values for APIs. This method was designed for rapid evaluation and relies on Food and Drug Administration (FDA)-approved drug labels and limited additional public data resources for necessary information. MDH developed an analytical framework using traditional and novel uncertainty and adjustment factors specific to the information available for APIs. This framework, along with an estimated lowest therapeutic dose (LTD), was used to derive screening reference dose (sRfD) values. Water screening values (WSV) were then derived using the sRfD, a relative source contribution factor (RSC), and a water intake rate for infants to represent a highly exposed population. MDH used this new method to derive water screening values for 119 APIs that are commonly prescribed and/or commonly monitored in Minnesota waters, including antibiotics, antidepressants, steroids, and other classes of drugs. The derived WSVs can be used to provide context to environmental detections, prioritize APIs for further health-based guidance development, prioritize APIs for future environmental monitoring studies, and inform the development or refinement of analytical methods.

Focus on Chronic Exposure for Deriving Drinking Water Guidance Underestimates Potential Risk to Infants.

In 2007, the Minnesota Department of Health (MDH) developed new risk assessment methods for deriving human health-based water guidance (HBG) that incorporated the assessment of multiple exposure durations and life stages. The methodology is based on US Environmental Protection Agency recommendations for protecting children's health (US EPA 2002). Over the last 10 years, the MDH has derived multiple duration (e.g., short-term, subchronic, and chronic) water guidance for over 60 chemicals. This effort involved derivation of multiple duration reference doses (RfDs) and selection of corresponding water intake rates (e.g., infant, child, and lifetime). As expected, RfDs typically decreased with increasing exposure duration. However, the corresponding HBG frequently did not decrease with increasing duration. For more than half of the chemicals, the shorter duration HBG was lower than chronic HBG value. Conventional wisdom has been that chronic-based values will be the most conservative and will therefore be protective of less than chronic exposures. However, the MDH's experience highlights the importance of evaluating short-term exposures. For many chemicals, elevated intake rates early in life, coupled with short-term RfDs, resulted in the lowest HBG. Drinking water criteria based on chronic assessments may not be protective of short-term exposures in highly exposed populations such as formula-fed infants.