Biodistribution of cerium dioxide and titanium dioxide nanomaterials in rats after single and repeated inhalation exposures.

BACKGROUND: Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation. The aim of the present study was therefore to acquire two comparable datasets to parametrize a physiologically-based kinetic model. METHOD: Rats were exposed to cerium dioxide (CeO2, 28.4 ± 10.4 nm) and titanium dioxide (TiO2, 21.6 ± 1.5 nm) ENMs in a single nose-only exposure to 20 mg/m3 or a repeated exposure of 2 × 5 days to 5 mg/m3. Different dose levels were obtained by varying the exposure time for 30 min, 2 or 6 h per day. The content of cerium or titanium in three compartments of the lung (tissue, epithelial lining fluid and freely moving cells), mediastinal lymph nodes, liver, spleen, kidney, blood and excreta was measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at various time points post-exposure. As biodistribution is best studied at sub-toxic dose levels, lactate dehydrogenase (LDH), total protein, total cell numbers and differential cell counts were determined in bronchoalveolar lavage fluid (BALF). RESULTS: Although similar lung deposited doses were obtained for both materials, exposure to CeO2 induced persistent inflammation indicated by neutrophil granulocytes influx and exhibited an increased lung elimination half-time, while exposure to TiO2 did not. The lavaged lung tissue contained the highest metal concentration compared to the lavage fluid and cells in the lavage fluid for both materials. Increased cerium concentrations above control levels in secondary organs such as lymph nodes, liver, spleen, kidney, urine and faeces were detected, while for titanium this was found in lymph nodes and liver after repeated exposure and in blood and faeces after a single exposure. CONCLUSION: We have provided insight in the distribution kinetics of these two ENMs based on experimental data and modelling. The study design allows extrapolation at different dose-levels and study durations. Despite equal dose levels of both ENMs, we observed different distribution patterns, that, in part may be explained by subtle differences in biological responses in the lung.

Physiologically-Based Kinetic Modeling of Intravenously Administered Gold (Au) Nanoparticles.

Physiologically-based kinetic (PBK) modeling is a valuable tool to understand the kinetics of nanoparticles (NPs) in vivo. However, estimating PBK parameters remains challenging and commonly requires animal studies. To develop predictive models to estimate PBK parameter values based on NP characteristics, a database containing PBK parameter values and corresponding NP characteristics is needed. As a first step toward this objective, this study estimates PBK parameters for gold NPs (AuNPs) and provides a comparison of two different NPs. Two animal experiments are conducted in which varying doses of AuNPs attached with polyethylene glycol (PEG) are administered intravenously to rats. The resulting Au concentrations are used to estimate PBK model parameters. The parameters are compared with PBK parameters previously estimated for poly(alkyl cyanoacrylate) NPs loaded with cabazitaxel and for LipImage 815. This study shows that a small initial database of PBK parameters collected for three NPs is already sufficient to formulate new hypotheses on NP characteristics that may be predictive of PBK parameter values. Further research should focus on developing a larger database and on developing quantitative models to predict PBK parameter values.

The Road to Achieving the European Commission's Chemicals Strategy for Nanomaterial Sustainability-A PATROLS Perspective on New Approach Methodologies.

The European Green Deal outlines ambitions to build a more sustainable, climate neutral, and circular economy by 2050. To achieve this, the European Commission has published the Chemicals Strategy for Sustainability: Towards a Toxic-Free Environment, which provides targets for innovation to better protect human and environmental health, including challenges posed by hazardous chemicals and animal testing. The European project PATROLS (Physiologically Anchored Tools for Realistic nanOmateriaL hazard aSsessment) has addressed multiple aspects of the Chemicals Strategy for Sustainability by establishing a battery of new approach methodologies, including physiologically anchored human and environmental hazard assessment tools to evaluate the safety of engineered nanomaterials. PATROLS has delivered and improved innovative tools to support regulatory decision-making processes. These tools also support the need for reducing regulated vertebrate animal testing; when used at an early stage of the innovation pipeline, the PATROLS tools facilitate the safe and sustainable development of new nano-enabled products before they reach the market.

Assessing Human Exposure to SVOCs in Materials, Products, and Articles: A Modular Mechanistic Framework.

A critical review of the current state of knowledge of chemical emissions from indoor sources, partitioning among indoor compartments, and the ensuing indoor exposure leads to a proposal for a modular mechanistic framework for predicting human exposure to semivolatile organic compounds (SVOCs). Mechanistically consistent source emission categories include solid, soft, frequent contact, applied, sprayed, and high temperature sources. Environmental compartments are the gas phase, airborne particles, settled dust, indoor surfaces, and clothing. Identified research needs are the development of dynamic emission models for several of the source emission categories and of estimation strategies for critical model parameters. The modular structure of the framework facilitates subsequent inclusion of new knowledge, other chemical classes of indoor pollutants, and additional mechanistic processes relevant to human exposure indoors. The framework may serve as the foundation for developing an open-source community model to better support collaborative research and improve access for application by stakeholders. Combining exposure estimates derived using this framework with toxicity data for different end points and toxicokinetic mechanisms will accelerate chemical risk prioritization, advance effective chemical management decisions, and protect public health.

Linking Probabilistic Exposure and Pharmacokinetic Modeling To Assess the Cumulative Risk from the Bisphenols BPA, BPS, BPF, and BPAF for Europeans.

The bisphenols S, F, and AF (BPS, BPF, and BPAF) are used to replace the endocrine disrupting chemical bisphenol A (BPA) while exerting estrogenic effects of comparable potency. We assessed the cumulative risk for the aforementioned BPs in Europe and compared the risk before and after the year 2011, which was when the first BPA restrictions became effective. For this, we probabilistically modeled external exposures from food, personal care products (PCPs), thermal paper, and dust (using the tools MCRA and PACEM for exposures from food and PCPs, respectively). We calculated internal concentrations of unconjugated BPs with substance-specific PBPK models and cumulated these concentrations normalized by estrogenic potency. The resulting mean internal cumulative exposures to unconjugated BPs were 3.8 and 2.1 ng/kg bw/day before and after restrictions, respectively. This decline was mainly caused by the replacement of BPA by BPS in thermal paper and the lower dermal uptake of BPS compared to BPA. However, the decline was not significant: the selected uncertainty intervals overlapped (P2.5-P97.5 uncertainty intervals of 2.7-4.9 and 1.3-6.3 ng/kg bw/day before and after restrictions, respectively). The upper uncertainty bounds for cumulative exposure were higher after restrictions, which reflects the larger uncertainty around exposures to substitutes compared to BPA.

Pulmonary toxicity in rats following inhalation exposure to poorly soluble particles: The issue of impaired clearance and the relevance for human health hazard and risk assessment.

Intensive discussions are ongoing about the interpretation of pulmonary effects observed in rats exposed to poorly soluble particles. Alveolar clearance differs between rats and humans and becomes impaired in rats at higher exposure concentrations. Some have doubted the human relevance of toxic effects observed in rats under impaired clearance conditions and have suggested that experimental exposures should stay below concentrations inducing impaired clearance. However, for regulatory purposes, insight in potential health effects at relatively high concentrations is needed to fully understand the hazard. Many aspects of impaired particle clearance remain unclear, hampering human health hazard and risk assessment. For an adequate evaluation of the impact of impaired clearance on pulmonary toxicity, a clear definition of alveolar clearance is needed that enables to quantitatively relate the level of impairment to the induction of adverse pulmonary health effects. Also, information is needed on the mechanism of action and the appropriate dose metric for the pulmonary effects observed. In absence of these data, human hazard and risk assessment can only be performed in a pragmatic way. Unless available data clearly point out otherwise, rat pulmonary toxicity including lung inflammation and tumour formation, needs to be considered relevant for human hazard and risk assessment.

Direct and Air-Mediated Transfer of Labeled SVOCs from Indoor Sources to Dust.

Two small-scale field studies were conducted to investigate the transfer of substances from products into dust due to direct and air-mediated transfer. The project focused on semivolatile organic compounds (SVOCs), which are frequently found in and re-emitted from dust. For the field studies, four artificial products containing deuterium-labeled SVOCs (eight phthalates and adipates) were installed in residential indoor environments. Two plastic products were installed vertically to investigate substance transfer due to evaporation into air. One plastic product and a carpet were installed horizontally to investigate the direct transfer from source to dust. A pyrethroid was intentionally released by spraying a commercial spray. Dust samples were collected from the floor, elevated surfaces in the room and the surfaces of the horizontally installed products. We observed that the dust concentrations of substances exclusively transferred via air were similar at different collection sites, but the concentrations of chemicals present in horizontal products were up to 3 orders of magnitude higher in dust deposited on the source. We conclude that direct transfer from source into dust substantially increases the final SVOC concentration in dust in contact with the source, regardless of the vapor pressure of investigated SVOCs, and may lead to larger human exposure.

Tracking SVOCs' Transfer from Products to Indoor Air and Settled Dust with Deuterium-Labeled Substances.

Semivolatile organic compounds (SVOCs) can be released from products and distributed in the indoor environment, including air and dust. However, the mechanisms and the extent of substance transfer into air and dust are not well understood. Therefore, in a small-scale field study the transfer of nine SVOCs was investigated: Four artificial consumer products were doped with eight deuterium-labeled plasticizers (phthalates and adipates) and installed in five homes to investigate the emission processes of evaporation, abrasion, and direct transfer. Intentional release was studied with a commercial spray containing a pyrethroid. During the 12 week study, indoor air and settled dust samples were collected and analyzed. On the basis of our measurement results, we conclude that the octanol-air partitioning coefficient Koa is a major determinant for the substance transfer into either air or dust: A high Koa implies that the substance is more likely to be found in dust than in air. The emission process also plays a role: For spraying, we found higher dust and air concentrations than for evaporation. In contrast, apartment parameters like air exchange rate or temperature had just a minor influence. Another important mechanistic finding was that although transfer from product to dust currently is postulated to be mostly mediated by air, direct transport from product to dust on the product surface was also observed.

Human exposure to conventional and nanoparticle--containing sprays-a critical review.

The release of pesticides from conventional spray products has been investigated in depth, and suitable analytical techniques detecting the mass of the released substances are available. In contrast, nanoparticle-containing sprays are less studied, although they are perceived as critical for consumers because inhalation exposure can occur to potentially toxic nanoparticles. A few recent studies presented analytical concepts for exposure experiments and generated data for exposure assessment. This study attempts to review and compare the current approaches to characterize nanosprays and to identify challenges for future research. Furthermore, experimental setups used for exposure assessment from conventional sprays are reviewed and compared to setups used for nanoparticle-containing sprays. National and international norms dealing with nanoparticle characterization, spray characterization and exposure are inspected with regard to their usefulness for standardizing exposure assessment. Different approaches in the field of exposure modeling are reviewed and compared. The conclusion is that due to largely varying experimental setups to date exposure values for nanosprays are difficult to compare. All studies are only conducted with a limited set of sprays, and no systematic evaluation of the study conditions is available. A suitable set of experimental setups as well as minimum reporting requirements should be agreed upon to enable the systematic evaluation of consumer sprays in the future. Indispensable features of such experimental setups are developed in this review.

A rapid micro chamber method to measure SVOC emission and transport model parameters.

Assessing exposure to semivolatile organic compounds (SVOCs) that are emitted from consumer products and building materials in indoor environments is critical for reducing the associated health risks. Many modeling approaches have been developed for SVOC exposure assessment indoors, including the DustEx webtool. However, the applicability of these tools depends on the availability of model parameters such as the gas-phase concentration at equilibrium with the source material surface, y0, and the surface-air partition coefficient, Ks, both of which are typically determined in chamber experiments. In this study, we compared two types of chamber design, a macro chamber, which downscaled the dimensions of a room to a smaller size with roughly the same surface-to-volume ratio, and a micro chamber, which minimized the sink-to-source surface area ratio to shorten the time required to reach steady state. The results show that the two chambers with different sink-to-source surface area ratios yield comparable steady-state gas- and surface-phase concentrations for a range of plasticizers, while the micro chamber required significantly shorter times to reach steady state. Using y0 and Ks measured with the micro chamber, we conducted indoor exposure assessments for di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP) and di(2-ethylhexyl) terephthalate (DEHT) with the updated DustEx webtool. The predicted concentration profiles correspond well with existing measurements and demonstrate the direct applicability of chamber data in exposure assessments.

Quantitative Microbial Risk Assessment of Contracting COVID-19 Derived from Measured and Simulated Aerosol Particle Transmission in Aircraft Cabins.

BACKGROUND: SARS-CoV-2 can be effectively transmitted between individuals located in close proximity to each other for extended durations. Aircraft provide such conditions. Although high attack rates during flights were reported, little was known about the risk levels of aerosol transmission of SARS-CoV-2 in aircraft cabins. OBJECTIVES: The major objective was to estimate the risk of contracting COVID-19 from transmission of aerosol particles in aircraft cabins. METHODS: In two single-aisle and one twin-aisle aircraft, dispersion of generated aerosol particles over a seven-row economy class cabin section was measured under cruise and taxi conditions and simulated with a computational fluid dynamic model under cruise conditions. Using the aerosol particle dispersion data, a quantitative microbial risk assessment was conducted for scenarios with an asymptomatic infectious person expelling aerosol particles by breathing and speaking. Effects of flight conditions were evaluated using generalized additive mixed models. RESULTS: Aerosol particle concentration decreased with increasing distance from the infectious person, and this decrease varied with direction. On a typical flight with an average shedder, estimated mean risk of contracting COVID-19 ranged from 1.3×10-3 to 9.0×10-2. Risk increased to 7.7×10-2 with a super shedder (<3% of cases) on a long flight. Risks increased with increasing flight duration: 2-23 cruise flights of typical duration and 2-10 flights of longer duration resulted in at least 1 case of COVID-19 due to onboard aerosol transmission by one average shedder, and in the case of one super shedder, at least 1 case in 1-3 flights of typical duration cruise and 1 flight of longer duration. DISCUSSION: Our findings indicate that the risk of contracting COVID-19 by aerosol transmission in an aircraft cabin is low, but it will not be zero. Testing before boarding may help reduce the chance of a (super)shedder boarding an aircraft and mask use further reduces aerosol transmission in the aircraft cabin. https://doi.org/10.1289/EHP11495.

PACEMweb: a tool for aggregate consumer exposure assessment.

BACKGROUND: To ascertain the safe use of chemicals that are used in multiple consumer products, the aggregate human exposure, arising from combined use of multiple consumer products needs to be assessed. OBJECTIVE: In this work the Probabilistic Aggregate Consumer Exposure Model (PACEM) is presented and discussed. PACEM is implemented in the publicly available web tool, PACEMweb, for aggregate consumer exposure assessment. METHODS: PACEM uses a person-oriented simulation method that is based on realistic product usage information obtained in surveys from several European countries. PACEM evaluates aggregate exposure in a population considering individual use and co-use patterns as well as variation in product composition. Product usage data is included on personal care products (PCPs) and household cleaning products (HCPs). RESULTS: PACEM has been implemented in a web tool that supports broad use in research as well as regulatory risk assessment. PACEM has been evaluated in a number of applications, testing and illustrating the advantage of the person-oriented modeling method. Also, PACEM assessments have been evaluated by comparing its results with biomonitoring information. SIGNIFICANCE: PACEM enables the assessment of realistic aggregate exposure to chemicals in consumer products. It provides detailed insight into the distribution of exposure in a population as well as products that contribute the most to exposure. This allows for better informed decision making in the risk management of chemicals. IMPACT: Realistic assessment of the total, aggregate exposure of consumers to chemicals in consumer products is necessary to guarantee the safe use of chemicals in these products. PACEMweb provides, for the first time, a publicly available tool to assist in realistic aggregate exposure assessment of consumers to chemicals in consumer products.

Physiologically based pharmacokinetic modeling of intravenously administered nanoformulated substances.

The use of nanobiomaterials (NBMs) is becoming increasingly popular in the field of medicine. To improve the understanding on the biodistribution of NBMs, the present study aimed to implement and parametrize a physiologically based pharmacokinetic (PBPK) model. This model was used to describe the biodistribution of two NBMs after intravenous administration in rats, namely, poly(alkyl cyanoacrylate) (PACA) loaded with cabazitaxel (PACA-Cbz), and LipImage™ 815. A Bayesian parameter estimation approach was applied to parametrize the PBPK model using the biodistribution data. Parametrization was performed for two distinct dose groups of PACA-Cbz. Furthermore, parametrizations were performed three distinct dose groups of LipImage™ 815, resulting in a total of five different parametrizations. The results of this study indicate that the PBPK model can be adequately parametrized using biodistribution data. The PBPK parameters estimated for PACA-Cbz, specifically the vascular permeability, the partition coefficient, and the renal clearance rate, substantially differed from those of LipImage™ 815. This emphasizes the presence of kinetic differences between the different formulations and substances and the need of tailoring the parametrization of PBPK models to the NBMs of interest. The kinetic parameters estimated in this study may help to establish a foundation for a more comprehensive database on NBM-specific kinetic information, which is a first, necessary step towards predictive biodistribution modeling. This effort should be supported by the development of robust in vitro methods to quantify kinetic parameters.

A physiologically based pharmacokinetic model to predict pegylated liposomal doxorubicin disposition in rats and human.

The use of nanoparticles (NPs) can support an enhancement of drug distribution, resulting in increased drug penetration into key tissues. Experimental in vitro data can be integrated into computational approaches to simulate NP absorption, distribution, metabolism and elimination (ADME) processes and provide quantitative pharmacokinetic predictions. The aim of this study is to develop a novel mechanistic and physiologically based pharmacokinetic (m-PBPK) model to predict the biodistribution of NPs focusing on Doxil. The main processes underpinning NPs ADME were represented considering molecular and cellular mechanisms such as stability in biological fluids, passive permeability and uptake activity by macrophages. A whole-body m-PBPK rat and human models were designed in Simbiology v. 9.6.0 (MATLAB R2019a). The m-PBPK models were successfully qualified across doxorubicin and Doxil® in both rat and human since all PK parameters AUC0-inf, Cmax, t1/2, Vd and Cl were within twofold, with an AUC0-inf absolute average-fold error (AAFE) value of 1.23 and 1.16 and 1.76 and 1.05 for Doxorubicin and Doxil® in rat and human, respectively. The time to maximum concentration in tissues for doxorubicin in both rat and human models was before 30 min of administration, while for Doxil®, the tmax was after 24 h of administration. The organs that accumulate most NP are the spleen, liver and lungs, in both models. The m-PBPK represents a predictive platform for the integration of in vitro and formulation parameters in a physiological context to quantitatively predict the NP biodistribution. Schematic diagram of the whole-body m-PBPK models developed for Doxil® in rat and human physiology.

A comparative biodistribution study of polymeric and lipid-based nanoparticles.

Biodistribution of nanoencapsulated bioactive compounds is primarily determined by the size, shape, chemical composition and surface properties of the encapsulating nanoparticle, and, thus, less dependent on the physicochemical properties of the active pharmaceutical ingredient encapsulated. In the current work, we aimed to investigate the impact of formulation type on biodistribution profile for two clinically relevant nanoformulations. We performed a comparative study of biodistribution in healthy rats at several dose levels and durations up to 14-day post-injection. The studied nanoformulations were nanostructured lipid carriers incorporating the fluorescent dye IR780-oleyl, and polymeric nanoparticles containing the anticancer agent cabazitaxel. The biodistribution was approximated by quantification of the cargo in blood and relevant organs. Several clear and systematic differences in biodistribution were observed, with the most pronounced being a much higher (more than 50-fold) measured concentration ratio between cabazitaxel in all organs vs. blood, as compared to IR780-oleyl. Normalized dose linearity largely showed opposite trends between the two compounds after injection. Cabazitaxel showed a higher brain accumulation than IR780-oleyl with increasing dose injected. Interestingly, cabazitaxel showed a notable and prolonged accumulation in lung tissue compared to other organs. The latter observations could warrant further studies towards a possible therapeutic indication within lung and conceivably brain cancer for nanoformulations of this highly antineoplastic compound, for which off-target toxicity is currently dose-limiting in the clinic.

Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030.

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally.

Modelling Exposure by Spraying Activities-Status and Future Needs.

Spray applications enable a uniform distribution of substances on surfaces in a highly efficient manner, and thus can be found at workplaces as well as in consumer environments. A systematic literature review on modelling exposure by spraying activities has been conducted and status and further needs have been discussed with experts at a symposium. This review summarizes the current knowledge about models and their level of conservatism and accuracy. We found that extraction of relevant information on model performance for spraying from published studies and interpretation of model accuracy proved to be challenging, as the studies often accounted for only a small part of potential spray applications. To achieve a better quality of exposure estimates in the future, more systematic evaluation of models is beneficial, taking into account a representative variety of spray equipment and application patterns. Model predictions could be improved by more accurate consideration of variation in spray equipment. Inter-model harmonization with regard to spray input parameters and appropriate grouping of spray exposure situations is recommended. From a user perspective, a platform or database with information on different spraying equipment and techniques and agreed standard parameters for specific spraying scenarios from different regulations may be useful.

Exposure-based waiving under REACH.

Within the REACH framework, but also within OECD, there is understanding that for reasons of animal welfare, costs and logistics, it is important to limit the number of tests to be conducted. Exposure-based waiving (EBW) is a potentially important element in testing strategies. This publication describes criteria for exposure-based waiving as foreseen in the REACH regulation and gives more detail to the REACH requirements for exposure-based waiving The principle behind any EBW is that there are situations when human or environmental exposures are so low or infrequent that there is a very low probability that the acquisition of additional effect information may lead to an improvement in the ability to manage risk. EBW therefore is risk-based and needs thorough knowledge on exposure as well as on effects criteria. Both elements are discussed: exposure models are analysed and the uncertainty in their predictions discussed as well as no-effect criteria such as the threshold of toxicological concern. Examples of EBW are provided for environmental, consumer and worker exposure. REACH only allows EBW in a limited number of cases with constraints on tonnage levels, types of tests to be waived and the need for a thorough ES and exposure assessment throughout the life cycle of a chemical and for all human exposure routes and environmental pathways. EBW will only be considered a real option by industry if a cost-benefit analysis shows an advantage, which may heavily depend on the weighing factor one applies for the non-use of experimental animals.

Modeling consumer exposure to spray products: an evaluation of the ConsExpo Web and ConsExpo nano models with experimental data.

To ensure safe use of chemical substances in consumer products, the exposure of consumers to these substances needs to be evaluated. For this purpose, generally consumer exposure modeling tools are used. To build confidence in such tools, evaluation of their performance with experimental data is indispensable. This work describes the evaluation of two consumer exposure modeling tools: ConsExpo Web and ConsExpo nano. Both models contain a module to estimate exposure of substances released as an aerosol during the use of spray products. This particular model was tested by comparing measured exposure data with model simulations. Experimental data were obtained from the public literature. These typically provide measured air concentrations under simulated use conditions of spray products. ConsExpo Web and ConsExpo nano were used to simulate experimental settings of the different studies. The resulting simulated air concentrations were compared with the reported ones. Overall, good agreement between modeled and measured data was observed. However, a significant proportion of the studies considered, did not provide sufficient detail in the specification of the experimental conditions to make them suitable for model evaluation. Critical information that was often lacking was on product composition, the mass sprayed during usage, and the generated aerosol size distribution.