Application of the threshold of toxicological concern approach to ingredients in personal and household care products

In the absence of chemical-specific data, the threshold of toxicological concern (TTC) provides a method to determine a conservative estimate of a chronic oral exposure below which there is a very low probability of risk. The TTC approach was originally developed to support exposures to indirect food additives and was based on linear low-dose risk estimates to assure protection in the event that the chemical was later determined to be a carcinogen. Subsequently, TTC values based on noncancer endpoints were proposed for chemicals without structural alerts for genotoxicity. The original database supporting the TTC values for noncancer endpoints includes >600 structurally diverse chemicals. The objectives of this work were to evaluate the applicability of the TTC database to ingredients used in consumer products based on a comparison of the diversity of chemical structures with those in the original TTC database and to confirm that the range of NOELs for these ingredients is consistent with the range of NOELs in the original database. The results show good coverage of the product ingredient structures and confirm that the NOELs for the ingredient chemicals are similar in range to the original dataset, supporting the use of the TTC for ingredients in consumer products.     

Exposure based waiving: The application of the toxicological threshold of concern (TTC) to inhalation exposure for aerosol ingredients in consumer products

The inhalation toxicology studies available in the public domain have been reviewed to establish a database for inhalation toxicology and derive thresholds of toxicological concern (TTC) for effects in the respiratory tract and systemically for Cramer class 1 and 3 chemicals. These TTCs can be used as the basis for developing an exposure based waiving (EBW) approach to evaluating the potential for adverse effects from exposure to ingredients in aerosol products, used by consumers. The measurement of consumer exposure in simulated product use is key to the application of an exposure based waiving approach to evaluating potential consumer risk. The detailed exposure evaluation for aerosol ingredients with defined use scenarios, in conjunction with an evaluation of the potential structure activity relationship for toxicity and the TTCs for inhalation exposure could be used to waive undertaking inhalation toxicology studies under REACH. Not all classes of chemicals are suitable for such an approach, but for chemicals with a predictable low potential toxicity, and very low levels of exposure, this approach, could reduce the amount of inhalation toxicology studies required for the implementation of the European REACH legislation. Such an approach is consistent with the concept of developing ‘intelligent testing strategies’ for REACH.     

Refining Aggregate Exposure: Example using Parabens

The need to understand and estimate quantitatively the aggregate exposure to ingredients used broadly in a variety of product types continues to grow. Currently aggregate exposure is most commonly estimated by using a very simplistic approach of adding or summing the exposures from all the individual product types in which the chemical is used. However, the more broadly the ingredient is used in related consumer products, the more likely this summation will result in an unrealistic estimate of exposure because individuals in the population vary in their patterns of product use including co-use and non-use. Furthermore the ingredient may not be used in all products of a given type. An approach is described for refining this aggregate exposure using data on (1) co-use and non-use patterns of product use, (2) extent of products in which the ingredient is used and (3) dermal penetration and metabolism. This approach and the relative refinement in the aggregate exposure from incorporating these data is illustrated using methyl, n-propyl, n-butyl and ethyl parabens, the most widely used preservative system in personal care and cosmetic products. When these refining factors were used, the aggregate exposure compared to the simple addition approach was reduced by 51%, 58%, 90% and 92% for methyl, n-propyl, n-butyl and ethyl parabens, respectively. Since biomonitoring integrates all sources and routes of exposure, the estimates using this approach were compared to available paraben biomonitoring data. Comparison to the 95th percentile of these data showed that these refined estimates were still conservative by factors of 2–92. All of our refined estimates of aggregate exposure are less than the ADI of 10 mg/kg/day for parabens.     

Application of the expanded Creme RIFM consumer exposure model to fragrance ingredients in cosmetic,personal care and air care products

As part of a joint project between the Research Institute for Fragrance Materials (RIFM) and Creme Global, a Monte Carlo model (here named the Creme RIFM model) has been developed to estimate consumer exposure to ingredients in personal care products. Details of the model produced in Phase 1 of the project have already been published. Further data on habits and practises have been collected which enable the model to estimate consumer exposure from dermal, oral and inhalation routes for 25 product types. . In addition, more accurate concentration data have been obtained which allow levels of fragrance ingredients in these product types to be modelled. Described is the use of this expanded model to estimate aggregate systemic exposure for eight fragrance ingredients. Results are shown for simulated systemic exposure (expressed as μg/kg bw/day) for each fragrance ingredient in each product type, along with simulated aggregate exposure. Highest fragrance exposure generally occurred from use of body lotions, body sprays and hydroalcoholic products. For the fragrances investigated, aggregate exposure calculated using this model was 11.5–25 fold lower than that calculated using deterministic methodology. The Creme RIFM model offers a very comprehensive and powerful tool for estimating aggregate exposure to fragrance ingredients.     

Aggregate exposure modelling of zinc pyrithione in rinse-off personal cleansing products using a person-orientated approach with market share refinement

Realistic estimates of chemical aggregate exposure are needed to ensure consumer safety. As exposure estimates are a critical part of the equation used to calculate acceptable “safe levels” and conduct quantitative risk assessments, methods are needed to produce realistic exposure estimations. To this end, a probabilistic aggregate exposure model was developed to estimate consumer exposure from several rinse off personal cleansing products containing the anti-dandruff preservative zinc pyrithione. The model incorporates large habits and practices surveys, containing data on frequency of use, amount applied, co-use along with market share, and combines these data at the level of the individual based on subject demographics to better estimate exposure. The daily-applied exposure (i.e., amount applied to the skin) was 3.79 mg/kg/day for the 95th percentile consumer. The estimated internal dose for the 95th percentile exposure ranged from 0.01–1.29 μg/kg/day after accounting for retention following rinsing and dermal penetration of ZnPt. This probabilistic aggregate exposure model can be used in the human safety assessment of ingredients in multiple rinse-off technologies (e.g., shampoo, bar soap, body wash, and liquid hand soap). In addition, this model may be used in other situations where refined exposure assessment is required to support a chemical risk assessment.     

Novel database for exposure to fragrance ingredients in cosmetics and personal care products

Exposure of fragrance ingredients in cosmetics and personal care products to the population can be determined by way of a detailed and robust survey. The frequency and combinations of products used at specific times during the day will allow the estimation of aggregate exposure for an individual consumer, and to the sample population. In the present study, habits and practices of personal care and cosmetic products have been obtained from market research data for 36,446 subjects across European countries and the United States in order to determine the exposure to fragrance ingredients. Each subject logged their product uses, time of day and body application sites in an online diary for seven consecutive days. The survey data did not contain information on the amount of product used per occasion or body measurements, such as weight and skin surface area. Nevertheless, this was found from the literature where the likely amount of product used per occasion or body measurement could be probabilistically chosen from distributions of data based on subject demographics. The daily aggregate applied consumer product exposure was estimated based on each subject’s frequency of product use, and Monte Carlo simulations of their likely product amount per use and body measurements. Statistical analyses of the habits and practices and consumer product exposure are presented, which show the robustness of the data and the ability to estimate aggregate consumer product exposure. Consequently, the data and modelling methods presented show potential as a means of performing ingredient safety assessments for personal care and cosmetics products.     

Potential exposure of German consumers to engineered nanoparticles in cosmetics and personal care products

Abstract

The rapid increase in the number of consumer products containing engineered nanoparticles (ENP) raises concerns about an appropriate risk assessment of these products. Along with toxicological data, exposure estimates are essential for assessing risk. Currently, cosmetics and personal care products (C&PCP) represent the largest ENP-containing consumer product class on the market. We analyzed factors influencing the likelihood that ENP-containing products are available to consumers. We modelled potential external exposure of German consumers, assuming a maximum possible case where only ENP-containing products are used. The distribution of exposure levels within the population due to different behavior patterns was included by using data from an extensive database on consumer behavior. Exposure levels were found to vary significantly between products and between consumers showing different behavior patterns. The assessment scheme developed here represents a basis for refined exposure modelling as soon as more specific information about ENPs in C&PCP becomes available.     

Relationship Between the Primary Dermal Irritation Index and Ocular Irritation

Abstract

The hypothesis that a chemical or product found to be irritating to animal skin need not be tested in the Draize Eye Irritancy Test but simply assumed to be eye irritant is reviewed. A comparison of the Primary Irritation Index (PII) and the ocular irritation scores of chemicals reported in the literature and until now unpublished data on petrochemicals, neat product ingredients, household and cosmetic products indicates that this hypothesis is often invalid. The indiscriminate use of such an hypothesis can lead to both the loss of consumer products and increased consumer cost due to the potential for liability.     

Application of in vitro skin penetration measurements to confirm and refine the quantitative skin sensitization risk assessment of methylisothiazolinone

Use of quantitative risk assessment (QRA) for assessing the skin sensitization potential of chemicals present in consumer products requires an understanding of hazard and product exposure. In the absence of data, consumer exposure is based on relevant habits and practices and assumes 100% skin uptake of the applied dose. To confirm and refine the exposure, a novel design for in vitro skin exposure measurements was conducted with the preservative, methylisothiazolinone (MI), in beauty care (BC) and household care (HHC) products using realistic consumer exposure conditions. A difference between measured exposure levels (MELs) for MI in leave-on versus rinse-off BC products, and lower MELs for MI in HHC rinse-off compared to BC products was demonstrated. For repeated product applications, the measured exposure was lower than estimations based on summation of applied amounts. Compared to rinse-off products, leave-on applications resulted in higher MELs, correlating with the higher incidences of allergic contact dermatitis associated with those product types. Lower MELs for MI in rinse-off products indicate a lower likelihood to induce skin sensitization, also after multiple daily applications. These in vitro skin exposure measurements indicate conservatism of default exposure estimates applied in skin sensitization QRA and might be helpful in future risk assessments.     

Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals

Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions “What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?” and “Are there correlations between oral toxicity data for amphibians and data for mammals or birds?” Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations.     

Human health safety evaluation of cosmetics in the EU: A legally imposed challenge to science

As stated in the European legislation, cosmetic products present on the European market must be safe for the consumer. Safety evaluation of the products is carried out by a qualified safety assessor who needs to consider potential exposure scenarios next to the physicochemical and toxicological profiles of all composing ingredients. Whereas, until recently, the tools to determine the toxicological profile of cosmetic ingredients mainly consisted of animal experiments, they have now been narrowed down substantially by the legally imposed animal testing ban on cosmetic ingredients, taken up in the Cosmetic Products Directive (76/768/EEC). This Directive, however, is not a stand-alone piece of European legislation, since as well directly as indirectly it is influenced by a complex web of related legislations. Vertical legislations deal with different categories of chemicals, including dangerous substances, biocides, plant protection products, food additives, medicinal products, and of course also cosmetics. Horizontal legislative texts, on the contrary, cover more general fields such as protection of experimental animals, consumer product safety, misleading of consumers, specific provisions for aerosols, and others. Experience has learnt that having a general overview of these related legislations is necessary to understand their impact on the cosmetic world in general terms and on cosmetic safety evaluation in particular. This goes for a variety of concerned parties, including national and European regulators/agencies, contract laboratories, raw material suppliers, cosmetic companies, research and educational centers. They all deal with a number of aspects important for the quality and toxicity of cosmetics and their ingredients.This review summarises the most relevant points of the legislative texts of different types of product categories and emphasises their impact on the safety evaluation of cosmetics.     

Perspectives on trace chemical safety and chemophobia: risk communication and risk management

Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia (i.e., the fear of chemicals). Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.     

Perspectives on trace chemical safety and chemophobia: risk communication and risk management

Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia, i.e., the fear of chemicals. Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.     

Cleaning and asthma: A systematic review and approach for effective safety assessment

Research indicates a correlative relationship between asthma and use of consumer cleaning products. We conduct a systematic review of epidemiological literature on persons who use or are exposed to cleaning products, both in occupational and domestic settings, and risk of asthma or asthma-like symptoms to improve understanding of the causal relationship between exposure and asthma. A scoring method for assessing study reliability is presented. Although research indicates an association between asthma and the use of cleaning products, no study robustly investigates exposure to cleaning products or ingredients along with asthma risk. This limits determination of causal relationships between asthma and specific products or ingredients in chemical safety assessment. These limitations, and a lack of robust animal models for toxicological assessment of asthma, create the need for a weight-of-evidence (WoE) approach to examine an ingredient or product's asthmatic potential. This proposed WoE method organizes diverse lines of data (i.e., asthma, sensitization, and irritation information) through a systematic, hierarchical framework that provides qualitatively categorized conclusions using hazard bands to predict a specific product or ingredient's potential for asthma induction. This work provides a method for prioritizing chemicals as a first step for quantitative and scenario-specific safety assessments based on their potential for inducing asthmatic effects. Acetic acid is used as a case study to test this framework.     

A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study

The US Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a tiered screening approach to determine the potential for a chemical to interact with estrogen, androgen, or thyroid hormone systems and/or perturb steroidogenesis. Use of high-throughput screening (HTS) to predict hazard and exposure is shifting the EDSP approach to (1) prioritization of chemicals for further screening; and (2) targeted use of EDSP Tier 1 assays to inform specific data needs. In this work, toxicology data for three triazole fungicides (triadimefon, propiconazole, and myclobutanil) were evaluated, including HTS results, EDSP Tier 1 screening (and other scientifically relevant information), and EPA guideline mammalian toxicology study data. The endocrine-related bioactivity predictions from HTS and information that satisfied the EDSP Tier 1 requirements were qualitatively concordant. Current limitations in the available HTS battery for thyroid and steroidogenesis pathways were mitigated by inclusion of guideline toxicology studies in this analysis. Similar margins (3–5 orders of magnitude) were observed between HTS-predicted human bioactivity and exposure values and between in vivo mammalian bioactivity and EPA chronic human exposure estimates for these products’ registered uses. Combined HTS hazard and human exposure predictions suggest low priority for higher-tiered endocrine testing of these triazoles. Comparison with the mammalian toxicology database indicated that this HTS-based prioritization would have been protective for any potential in vivo effects that form the basis of current risk assessment for these chemicals. This example demonstrates an effective, human health protective roadmap for EDSP evaluation of pesticide active ingredients via prioritization using HTS and guideline toxicology information.     

Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients

Based on chemical, cellular, and molecular understanding of dermal sensitization, an exposure-based quantitative risk assessment (QRA) can be conducted to determine safe use levels of fragrance ingredients in different consumer product types. The key steps are: (1) determination of benchmarks (no expected sensitization induction level (NESIL)); (2) application of sensitization assessment factors (SAF); and (3) consumer exposure (CEL) calculation through product use. Using these parameters, an acceptable exposure level (AEL) can be calculated and compared with the CEL. The ratio of AEL to CEL must be favorable to support safe use of the potential skin sensitizer. This ratio must be calculated for the fragrance ingredient in each product type. Based on the Research Institute for Fragrance Materials, Inc. (RIFM) Expert Panel's recommendation, RIFM and the International Fragrance Association (IFRA) have adopted the dermal sensitization QRA approach described in this review for fragrance ingredients identified as potential dermal sensitizers. This now forms the fragrance industry's core strategy for primary prevention of dermal sensitization to these materials in consumer products. This methodology is used to determine global fragrance industry product management practices (IFRA Standards) for fragrance ingredients that are potential dermal sensitizers. This paper describes the principles of the recommended approach, provides detailed review of all the information used in the dermal sensitization QRA approach for fragrance ingredients and presents key conclusions for its use now and refinement in the future.     

A risk assessment process for allergic contact sensitization

This review describes an approach that has been used to assess the skin sensitization risk of new chemicals and product formulations prior to launching the new chemical or product on the market. The risk assessment process utilizes a comparative toxicological approach, in which data on the inherent toxicity of a material, and the exposure to it through manufacturing or consumer use or foreseeable misuse, are integrated and compared with data generated by 'benchmark' materials of similar chemistry or product application, or both. This approach has been valuable in providing an accurate assessment of the skin sensitization potential for a wide range of consumer products and pharmaceuticals, ranging from products with a very transient skin exposure (e.g. some paper products), to cosmetics, to products whose ingredients may be deposited on fabrics and thus result in chronic skin exposure. The risk assessment process described includes both guinea-pig (Buehler) and human skin sensitization test methodologies to evaluate inherent toxicity under relevant epicutaneous exposure conditions. Alternative guinea-pig test methods have been reported to be more sensitive than the Buehler method, particularly those employing intradermal injection of the test material in Freund's complete adjuvant (e.g. maximization test). However, by bypassing the skin barrier at induction, these methods can overstate the sensitization risk of epicutaneous exposure to weak sensitizers (Andersen and Hamann, 1983 and 1984; Matsushita et al., 1975a,b), and can understate the risk to very strong sensitizers possibly through tolerance induction (Buehler, 1985). In addition, materials are tested and classified at concentrations that may not be relevant to anticipated human exposure. The Buehler guinea-pig test data are important in assessing skin sensitization risk in the early phases of product development, where human exposure can be limited, controlled and monitored (e.g. manufacturing employees). The Buehler test can often define consumer skin sensitization risk; however, the ultimate consumer skin safety assessment should in general be developed through a series of controlled human tests; the human repeat insult patch test and, when necessary, the provocative or extended product use tests. Post-market monitoring of skin-related consumer comments is the final phase of the data gathering process. These results can be used to assess further each product and to provide valuable feedback to confirm the validity of the overall risk assessment process. Risk assessment for skin sensitization potential is seldom a simple process.(ABSTRACT TRUNCATED AT 400 WORDS)     

Undeclared formaldehyde levels in patient consumer products: formaldehyde test kit utility

Purpose: Formaldehyde allergic contact dermatitis (ACD) may be due to products with free formaldehyde or formaldehyde-releasing agents; however, assessment of formaldehyde levels in such products is infrequently conducted. The present study quantifies total releasable formaldehyde from “in-use” products associated with formaldehyde ACD and tests the utility of commercially available formaldehyde spot test kits.

Materials and Methods: Personal care products from 2 patients with ACD to formaldehyde were initially screened at the clinic for formaldehyde using a formaldehyde spot test kit. Formaldehyde positive products were sent to the laboratory for confirmation by gas chromatography-mass spectrometry. In addition, 4 formaldehyde spot test kits were evaluated for potential utility in a clinical setting.

Results: Nine of the 10 formaldehyde spot test kit positive products obtained from formaldehyde allergic patients had formaldehyde with total releasable formaldehyde levels ranging from 5.4 to 269.4?µg/g. Of these, only two shampoos tested listed a formaldehyde-releasing agent in the ingredients or product literature. Subsequently, commercially available formaldehyde spot test kits were evaluated in the laboratory for ability to identify formaldehyde in personal care products.

Conclusions: Chemical based formaldehyde spot test were more reliable than the enzymatic based test in identifying product releasable formaldehyde content. It is concluded that product labeled ingredient lists and available information are often inadequate to confirm the potential for formaldehyde exposure and chemical based spot test kits may have utility for identification of potential formaldehyde exposure from personal care products.     

Driving safer products through collaborative innovation Lessons learned from the Green Chemistry & Commerce Council’s collaborative innovation challenge for safe and effective preservatives for consumer products

Whether responding to retailer, government, consumer, or advocacy pressures to eliminate chemicals of concern from their products or position themselves in the growing sustainable products space, many brands are on the constant lookout for new safe, effective chemical ingredients for their products. Increasingly brands are willing to set aside their competitive instincts to collaboratively search for, develop, evaluate, and push to market new green chemicals for which they share a common need. This article analyzes “collaborative innovation” initiatives of the Green Chemistry & Commerce Council (GC3), a business organization focused on accelerating the commercialization of green chemistry solutions. In particular, the article explores in detail lessons learned from the GC3's Collaborative Innovation Challenge on Safe and Effective Preservatives, which convened two retailers, eleven brands, and six chemical suppliers to identify new, sustainable preservative options for consumer products. These efforts have found that collaborative innovation is most effective when there are strong market or policy signals to act and solutions do not confer any particular competitive advantage. They have shown that companies see benefit in collaboration to solve chemistry challenges as such collaboration can accelerate innovation by providing a strong demand signal, sharing knowledge to overcome development challenges, de-risking investment and ultimately lowering costs.     

Categorization framework to aid exposure assessment of nanomaterials in consumer products

Exposure assessment is crucial for risk assessment for nanomaterials. We propose a framework to aid exposure assessment in consumer products. We determined the location of the nanomaterials and the chemical identify of the 580 products listed in the inventory maintained by the Woodrow Wilson International Center for Scholars, of which 37% used nanoparticles suspended in liquids, whereas <1% contained "free airborne nanoparticles". C(60) is currently only used as suspended nanoparticles in liquids and nanosilver is used more as surface bound nanoparticles than as particles suspended in liquids. Based on the location of the nanostructure we were able to further group the products into categories of: (1) expected, (2) possible, and (3) no expected exposure. Most products fall into the category of expected exposure, but we were not able to complete a quantitative exposure assessment mainly due to the lack of information on the concentration of the nanomaterial in the products--a problem that regulators and industry will have to address if we are to have realistic exposure assessment in the future. To illustrate the workability of our procedure, we applied it to four product scenarios using the best estimates available and/or worst-case assumptions. Using the best estimates available and/or worst-case assumptions we estimated the consumer exposure to be 26, 15, and 44 microg kg(-1) bw year(-1) for a facial lotion, a fluid product, and a spray product containing nanoparticles, respectively. The application of sun lotion containing 2% nanoparticles result in an exposure of 56.7 mg kg(-1) bw d(-1) for a 2-year-old child, if the amounts applied correspond to the European Commission recommendations on use of sunscreen.