The Conundrum of the PFOA human half-life, an international collaboration.

The Steering Committee of the Alliance for Risk Assessment (ARA) opened a call for scientists interested in resolving what appeared to be a conundrum in estimating of the half-life of perfluorooctanoate (PFOA) in humans. An Advisory Committee was formed from nominations received and a subsequent invitation led to the development of three small independent working groups to review appropriate information and attempt a resolution. Initial findings were shared among these groups and a conclusion developed from the ensuing discussions. Many human observational studies have estimated the PFOA half-life. Most of these studies note the likely occurrence of unmonitored PFOA exposures, which could inflate values of the estimated PFOA half-life. Also, few of these studies estimated the half-life of PFOA isomers, the branched chains of which likely have shorter half-lives. This could deflate values of the estimated linear PFOA half-life. Fortunately, several studies informed both of these potential problems. The majority opinion of this international collaboration is that the studies striking the best balance in addressing some of these uncertainties indicate the likely central tendency of the human PFOA half-life is less than 2 years. The single best value appears to be the geometric mean (GM) of 1.3 years (Zhang et al., 2013, Table 3), based on a GM = 1.7 years in young females (n = 20) and GM = 1.2 years in males of all ages and older females (n = 66). However, a combined median value from Zhang et al. (2013) of 1.8 years also adds value to this range of central tendency. While the Collaboration found this study to be the least encumbered with unmonitored PFOA exposures and branched isomers, more studies of similar design would be valuable. Also valuable would be clarification around background exposures in other existing studies in case adjustments to half-life estimates are attempted.

Assessment of ecological hazards and environmental fate of disinfectant quaternary ammonium compounds.

Disinfectant quaternary ammonium compounds (Quats) have diverse uses in a variety of consumer and commercial products, particularly cleaning products. With the emergence of the COVID-19 pandemic, they have become a primary tool to inactivate the SARS-CoV-2 virus on surfaces. Disinfectant Quats have very low vapor pressure, and following the use phase of the products in which they are found, disposal is typically "down-the-drain" to wastewater treatment systems. Consequently, the potential for the greatest environmental effect is to the aquatic environment, from treated effluent, and potentially to soils, which might be amended with wastewater biosolids. Among the earliest used and still common disinfectant Quats are the alkyl dimethyl benzyl ammonium chloride (ADBAC) compounds and the dialkyl dimethyl ammonium chloride (DDAC) compounds. They are cationic surfactants often found in consumer and commercial surface cleaners. Because of their biocidal properties, disinfectant Quats are heavily regulated for human and environmental safety around the world. Consequently, there is a robust database of information regarding the ecological hazards and environmental fate of ADBAC and DDAC; however, some of the data presented are from unpublished studies that have been submitted to and reviewed by regulatory agencies (i.e., EPA and European Chemicals Agency) to support antimicrobial product registration. We summarize the available environmental fate data and the acute and chronic aquatic ecotoxicity data for freshwater species, including algae, invertebrates, fish, and plants using peer-reviewed literature and unpublished data submitted to and summarized by regulatory agencies. The lower limit of the range of the ecotoxicity data for disinfectant Quats tends to be lower than that for other surface active agents, such as nonionic or anionic surfactants. However, ecotoxicity is mitigated by environmental fate characteristics, the data for which we also summarize, including high biodegradability and a strong tendency to sorb to wastewater biosolids, sediment, and soil. As a result, disinfectant Quats are largely removed during wastewater treatment, and those residues discharged in treated effluent are likely to rapidly bind to suspended solids or sediments, thus mitigating their toxicity.

Human health hazard assessment of quaternary ammonium compounds: Didecyl dimethyl ammonium chloride and alkyl (C12-C16) dimethyl benzyl ammonium chloride.

Quaternary ammonium compounds (Quats) are a large class of permanently charged cationic chemicals that are used in a variety of consumer and industrial products for their antimicrobial properties. Didecyl dimethyl ammonium chloride (DDAC) and alkyl (C12, C14, C16) dimethyl benzyl ammonium chloride (C12-C16 ADBAC) are frequently used as active ingredients in antimicrobials and are the focus of the current hazard assessment. Robust toxicology databases exist for both DDAC and C12-C16 ADBAC; however, the majority of available studies for DDAC and C12-C16 ADBAC are unpublished, but have been submitted to and reviewed by regulatory agencies (i.e., EPA and European Chemicals Agency) to support antimicrobial product registration. With the objective of contributing to public understanding of the robust and complete toxicology database available for DDAC and C12-C16 ADBAC, a comprehensive review was conducted using available peer-reviewed literature and unpublished data submitted to and summarized by regulatory agencies. A review of available literature indicates that DDAC and C12-C16 ADBAC have similar hazard profiles. Both DDAC and C12-C16 ADBAC are poorly absorbed via the oral and dermal exposure routes (≤10%), are not systemically distributed, and are primarily excreted in feces. DDAC and C12-C16 ADBAC are not dermal sensitizers, are not specific developmental or reproductive toxicants, are not carcinogenic or genotoxic, and do not cause systemic toxicity. DDAC and C12-C16 ADBAC are irritating/corrosive to skin at high concentrations, and are acutely toxic via the oral, dermal (C12-C16 ADBAC only), and inhalation exposure routes; however, both DDAC and C12-C16 ADBAC are considered non-volatile and are not readily aerosolized. Both DDAC and C12-C16 ADBAC can cause toxicity in repeated dose oral toxicity studies with no-observed-adverse-effect levels ranging from 10 to 93.1 mg/kg-day for DDAC and 3.7-188 mg/kg-day for C12-C16 ADBAC in subchronic and chronic studies conducted with beagles, mice, and rats. The toxicological effects associated with reported lowest-observed-adverse-effect levels for both DDAC and C12-C16 ADBAC are consistently characterized by reduced food consumption, reduced mean body weight, reduced body weight gain, and local irritation. These effects are consistent with the mode of action of an irritating/corrosive chemical. Based upon currently available data, the main concern associated with exposure to DDAC and C12-C16 ADBAC is local effects through irritation.

Description and evaluation of a peracetic acid air sampling and analysis method.

Peracetic acid (PAA) is a corrosive chemical with a pungent odor, which is extensively used in occupational settings and causes various health hazards in exposed workers. Currently, there is no US government agency recommended method that could be applied universally for the sampling and analysis of PAA. Legacy methods for determining airborne PAA vapor levels frequently suffered from cross-reactivity with other chemicals, particularly hydrogen peroxide (H2O2). Therefore, to remove the confounding factor of cross-reactivity, a new viable, sensitive method was developed for assessment of PAA exposure levels, based on the differential reaction kinetics of PAA with methyl p-tolylsulfide (MTS), relative to H2O2, to preferentially derive methyl p-tolysulfoxide (MTSO). By quantifying MTSO concentration produced in the liquid capture solution from an air sampler, using an internal standard, and utilizing the reaction stoichiometry of PAA and MTS, the original airborne concentration of PAA is determined. After refining this liquid trap high-performance liquid chromatography (HPLC) method in the laboratory, it was tested in five workplace settings where PAA products were used. PAA levels ranged from the detection limit of 0.013 parts per million (ppm) to 0.4 ppm. The results indicate a viable and potentially dependable method to assess the concentrations of PAA vapors under occupational exposure scenarios, though only a small number of field measurements were taken while field testing this method. However, the low limit of detection and precision offered by this method makes it a strong candidate for further testing and validation to expand the uses of this liquid trap HPLC method.

Acute toxicity of peroxy sulfonated oleic acids (PSOA) to freshwater aquatic species and sludge microflora as observed in laboratory environments.

BACKGROUND: Peroxy sulfonated oleic acids (PSOA) is a novel surfactant peracid. The commercial applications of PSOA result in the chemical primarily being disposed of via industrial waste water effluent. Given this manner of disposal, it is important to understand the aquatic hazards of the chemical to better assess the risk posed to aqueous environments. Acute aquatic toxicity laboratory experiments were performed to evaluate aquatic hazards and were conducted according to standard OECD test guidelines with rainbow trout (Oncorhynchus mykiss), water fleas (Daphnia magna) and algae (Pseudokirchneriella subcapitata). In addition, microbial toxicity was evaluated in activated sludge obtained from a domestic sewage treatment facility. RESULTS: Lethal concentration in 50 % of test species (LC50) and effect concentration in 50 % of test species (EC50) values for PSOA ranged from 0.75 to 5.44 mg/L, representing a relatively small range spanning less than an order of magnitude. No observed effect concentration (NOEC) and lowest observed effect concentration (LOEC) ranges were also relatively small, with ranges of 0.25-1.66 and 0.5-3.6 mg/L, respectively. The EC50, LOEC and NOEC values for microbial toxicity were 216, 60 and 20 mg/L, respectively. Predicted no effect concentrations (PNEC) for aqueous media were based on the 96-h LC50 (0.75 mg/L) for O. mykiss, the organism displaying the greatest sensitivity to PSOA. These values were derived for freshwater, marine water and intermittent releases to water and ranged from 7.5 × 10-5 to 7.5 × 10-3 mg/L. A sewage treatment plant PNEC of 2 mg/L was derived based on an activated sludge 3-h NOEC of 20 mg/L. CONCLUSION: These values, along with the anticipated environmental fate and transport for PSOA, were considered in assessing the overall aquatic risk posed by this chemical. Despite the relatively high acute aquatic hazards for PSOA, environmental modeling suggests the overall risk of PSOA to aqueous environments is low based on its anticipated uses. This conclusion is consistent with the significant processing of industrial wastewater by onsite or municipal wastewater treatment facilities prior to release to the environment.

Evaluation of the toxicity data for peracetic acid in deriving occupational exposure limits: a minireview.

Peracetic acid (PAA) is a peroxide-based chemistry that is highly reactive and can produce strong local effects upon direct contact with the eyes, skin and respiratory tract. Given its increasing prominence in industry, attention has focused on health hazards and associated risks for PAA in the workplace. Occupational exposure limits (OEL) are one means to mitigate risks associated with chemical hazards in the workplace. A mini-review of the toxicity data for PAA was conducted in order to determine if the data were sufficient to derive health-based OELs. The available data for PAA frequently come from unpublished studies that lack sufficient study details, suffer from gaps in available information and often follow unconventional testing methodology. Despite these limitations, animal and human data suggest sensory irritation as the most sensitive endpoint associated with inhalation of PAA. Rodent RD50 data (the concentration estimated to cause a 50% depression in respiratory rate) were selected as the critical studies in deriving OELs. Based on these data, a range of 0.36-0.51mg/m(3) (0.1-0.2ppm) was calculated for a time-weighted average (TWA), and 1.2-1.7mg/m(3) (0.4-0.5ppm) as a range for a short-term exposure limit (STEL). These ranges compare favorably to other published OELs for PAA. Considering the applicable health hazards for this chemistry, a joint TWA/STEL OEL approach for PAA is deemed the most appropriate in assessing workplace exposures to PAA, and the selection of specific values within these proposed ranges represents a risk management decision.

Toxicological evaluation of peroxy sulfonated oleic acid (PSOA) in subacute and developmental toxicity studies.

Peroxy sulfonated oleic acid (PSOA) is a new coupler used in sanitizing solutions primarily for the food and beverage industry. The toxicity of PSOA was evaluated in a 28-day repeat dose study according to OECD 407 guidelines with a 14-day recovery period and a developmental toxicity study according to OECD 414 guidelines. In both studies, PSOA was administered once daily via gavage at 0, 5, 15 and 50 mg/kg/day to Sprague-Dawley rats. Due to its corrosive properties, the highest test concentration was restricted to 0.5%. No findings related to PSOA administration were observed for the 28-day repeat-dose study and the NOEL is 50 mg/kg/day. Additionally, no impairment of the mucous membranes of the gastrointestinal tract was observed up to 0.5%, which is considered the NOEC in terms of local toxicity. For the developmental study, an embryo-fetal NOEL of 50 mg/kg/day was identified and the maternal NOEL is considered to be 15 mg/kg/day, based on slight reductions in maternal body weight and food consumption, as well as a modest increase in the incidence of clinical observations at the high dose. These findings demonstrate that PSOA appears to have minimal potential to induce toxicity associated with repeat-dose or developmental exposures.