Assessment of consumer exposure to boron in cleaning products: a case study of Canada.

Boron is an essential mineral for plants, and as such, is a normal dietary constituent for humans. Humans may be naturally exposed to boron through food and drinking water, or via anthropogenic sources such as consumer products. The World Health Organisation established an acceptable safe range of population mean intakes for boron of 1-13 mg/day. Most studies of dietary boron intake show a range of 1-2 mg/day. Consumer products have been estimated to contribute a geometric mean daily intake of 0.1 mg to total boron exposure; however, there are few published surveys of consumer exposure to boron from use of cleaning products. The Government of Canada published a draft screening assessment report of boric acid, its salts and precursors that included estimates of consumer exposure to boron found as ingredients in consumer products. The manufacturers of consumer cleaning products conducted a survey of boron content of current products and estimated exposure using the publicly available exposure tool ConsExpo Web. Dermal exposures to boron during cleaning product use were estimated to result in annual internal exposures ranging from ≪0.001 to 0.36 µg/kg bw/day based on dermal absorption of 0.5%. Using a conservative point of departure for hazard assessment (2,900 µg boron/kg bw/day), estimated margins of exposure for dermal exposures to boron from cleaning product use range from 8,056 to >1,000,000. This work demonstrates that exposure to boron from cleaning product use is very low and essentially insignificant when compared to other (e.g. dietary) sources of boron intake by Canadian consumers.

Development of a physiologically-based pharmacokinetic model of 2-phenoxyethanol and its metabolite phenoxyacetic acid in rats and humans to address toxicokinetic uncertainty in risk assessment.

2-Phenoxyethanol (PhE) has been shown to induce hepatotoxicity, renal toxicity, and hemolysis at dosages ≥ 400 mg/kg/day in subchronic and chronic studies in multiple species. To reduce uncertainty associated with interspecies extrapolations and to evaluate the margin of exposure (MOE) for use of PhE in cosmetics and baby products, a physiologically-based pharmacokinetic (PBPK) model of PhE and its metabolite 2-phenoxyacetic acid (PhAA) was developed. The PBPK model incorporated key kinetic processes describing the absorption, distribution, metabolism and excretion of PhE and PhAA following oral and dermal exposures. Simulations of repeat dose rat studies facilitated the selection of systemic AUC as the appropriate dose metric for evaluating internal exposures to PhE and PhAA in rats and humans. Use of the PBPK model resulted in refinement of the total default UF for extrapolation of the animal data to humans from 100 to 25. Based on very conservative assumptions for product composition and aggregate product use, model-predicted exposures to PhE and PhAA resulting from adult and infant exposures to cosmetic products are significantly below the internal dose of PhE observed at the NOAEL dose in rats. Calculated MOEs for all exposure scenarios were above the PBPK-refined UF of 25.

A strategy for safety assessment of chemicals with data gaps for developmental and/or reproductive toxicity.

Alternative methods for full replacement of in vivo tests for systemic endpoints are not yet available. Read across methods provide a means of maximizing utilization of existing data. A limitation for the use of read across methods is that they require analogs with test data. Repeat dose data are more frequently available than are developmental and/or reproductive toxicity (DART) studies. There is historical precedent for using repeat dose data in combination with a database uncertainty factor (UF) to account for missing DART data. We propose that use of the DART decision tree (Wu et al., 2013), in combination with a database UF, provides a path forward for DART data gap filling that better utilizes all of the data. Our hypothesis was that chemical structures identified by the DART tree as being related to structures with known DART toxicity would potentially have lower DART NOAELs compared to their respective repeat dose NOAELs than structures that lacked this association. Our analysis supports this hypothesis and as a result also supports that the DART decision tree can be used as part of weight of evidence in the selection of an appropriate DART database UF factor.