Detailed aggregate exposure analysis shows that exposure to fragrance ingredients in consumer products is low: Many orders of magnitude below thresholds of concern.

The Research Institute for Fragrance Materials (RIFM) and Creme Global Cremeglobal.com partnered to develop an aggregate exposure model for fragrance ingredients. The model provides a realistic estimate of the total exposure of fragrance ingredients to individuals across a population. The Threshold of Toxicological Concern (TTC) and Dermal Sensitization Threshold (DST) were used to demonstrate the magnitude of low exposure to fragrance materials. The total chronic systemic, inhalation, and dermal 95th percentile exposures on approximately 3000 fragrance ingredients in RIFM's inventory were compared to their respective TTC or DST. Additionally, representative fragrance ingredients were randomly selected and analyzed for exposure distribution by product type (i.e., cosmetic/personal care, household care, oral care, and air care) and route of exposure. It was found that 76 % of fragrance ingredients fall below their respective TTC limits when compared to 95th percentile systemic exposure, while 99 % are below inhalation TTC limits. The lowest 95th percentile aggregate exposure by product type was from household care products, then air care, and oral care products. The highest exposure was from personal care/cosmetic products. The volume of use for most fragrance ingredients (63 %) was <1 metric ton, estimating that environmental exposure to fragrance ingredients is likely low.

Consumer knowledge and awareness of the toxicity and handling of household products at a tertiary care center in Beirut, Lebanon.

Household products intoxication is a common and preventable problem. Household product hazard awareness is lacking among consumers in Lebanon, posing a public health hazard. A cross-sectional observational study was conducted at the American University of Beirut Medical Center by administering surveys to 176 adult participants. The surveys focused on demographics, awareness of product toxicity, practices used to avoid intoxication, and sources of information. Each participant was given a score for behavior and awareness. Informative brochures were handed to increase awareness among consumers. We surveyed 176 patients, of whom (84.7%) were females with a mean age of 42.2 ± 13.5 years. Most were married (77.3%), had a college education (76.7%), were employed (62.5%), and were in charge of household cleaning (76.7%). Toilet cleaners were the substances most perceived to be toxic (94.0%). Most people (86.4%) had low to medium scores on behavior, while most (77.3%) had high scores on awareness. Male gender and using product labels as sources of information were associated with higher behavior scores, while referring to a friend or a relative as a source of information on product intoxication was associated with a lower behavior score. Greater awareness scores were strongly associated with being married, having a higher monthly income, and referring to warning signs presented on the labels as a source of knowledge. Unsafe handling and storage of household products are common among consumers in our population. Therefore, it may be necessary to launch education campaigns to improve consumer handling of household products.

Risk assessment to human health: Consumer exposure to ingredients in air fresheners.

Ingredient chemicals like fragrances may cause adverse health effects. Frequent health risk assessments and stringent management of consumer products are of paramount importance to reduce these serious occurrences. In this study, the respiratory and dermal health effects were assessed in relation to air fresheners. Twenty six fragrance ingredients, thirty four biocidal ingredients, and sixteen hazardous ingredients were analyzed and assessed according to their risk to human health on five groups by application type in eighty two air fresheners. For hazard characterization of ingredients, toxicological information on the intrinsic properties of the ingredients was collected, and reference values were determined as chronic NOAEL. Exposure assessment was performed in two steps. The 95th exposure factor values were used to estimate exposure to assume the worst-case scenario and the maximum concentration determined by the product purpose and application type was used type in tiered 1 assessment. The values input into the exposure algorithms were developed via the exposure route. In the tiered 2 assessment, the 75th exposure factor values were used to estimate the assumed reasonable exposure to ingredients. Six ingredients for the inhalation and twelve ingredients for the dermal route were conducted for tiered 2 assessment. This study showed that the assessed ingredients have no health risks at their maximum concentrations in air fresheners. The approach should be used to establish improved guidelines for specific ingredients that may pose inhalation and dermal hazard.

Consumer products as sources of chemical exposures to children: case study of triclosan.

PURPOSE OF REVIEW: Consumer products are often overlooked as sources of children's exposures to toxic chemicals. Various regulatory bodies have developed lists of chemicals of concern that can be found in products contacted by children. However, this information has not been summarized for health practitioners. This review organizes such chemicals and products into four categories, with the antibacterial agent triclosan used to illustrate the potential risks to children from a common ingredient in consumer products. RECENT FINDINGS: Biomonitoring, house dust, indoor air, and product testing document children's exposures to a wide variety of chemicals. An increasing number of epidemiology studies have shown associations between these exposures and health effects in children. Triclosan is an example of a chemical contained in high contact products (e.g., soaps, lotions, and toothpaste) not necessarily designed for children. Triclosan exposure in children has been associated with increased responsiveness to airway allergens, with it also capable of endocrine disruption. However, the utility and necessity of this chemical in consumer products has not been demonstrated in most cases. SUMMARY: Triclosan and the other examples provided show that a changing marketplace with little regulatory oversight of chemical uses can lead to unanticipated exposures and potential health risks to children.

Pregnant Women's perceptions of exposure to brominated flame retardants.

BACKGROUND: Recent media reports on human studies associating brominated flame retardants (BFRs) in household products in pregnancy with urogenital anomalies in boys and endocrine disruption in both sexes. We sought to explore the perceptions of pregnant women of brominated flame retardant (BFR) exposure, in light of recent media reports on the adverse health effects of BFR exposure prenatally. METHODS: Pregnant women were recruited for interviews through posters and pamphlets in prenatal clinics, prenatal fairs and community centres. Interviews were audiotaped and transcribed verbatim for Charmaz-based qualitative analysis supported by NVIVO 10™. RESULTS: Theoretical sufficiency was reached after analyzing the interviews of 23 pregnant women. Themes co-constructed were: I-Lack of Awareness of BFRs; II-Factors Influencing BFR Exposure; III-Responsibility; IV-Informed Choice. Almost all participants felt it was difficult to make informed choices to avoid BFRs, and wanted communication from clinicians and regulation from governments regarding decreasing BFR exposure. CONCLUSION: Pregnant women in Canada may be unaware of the potential risks of exposure to BFRs. Professional organizations and governments should further study risk associated with BFR exposure in pregnancy and provide educational materials for pregnant women and clinicians regarding BFR exposure.

Dose-response behavior of the bacterium Vibrio fischeri exposed to pharmaceuticals and personal care products.

The presence of pharmaceuticals and personal care products (PPCPs) in the environment has become a real and widespread concern in recent years. Therefore, the primary goal of this study was to investigate 20 common and widely used PPCPs to assess their individual and combined effect on an important species in one trophic level, i.e., bacteria. The ecotoxicological effects of PPCPs at two different concentration ranges were determined in the bacterium Vibrio fischeri using Microtox(®) and were statistically analyzed using three models in the GraphPad Prism 6 program for Windows, v.6.03. A four-parameter model best fit the majority of the compounds. The half maximal effective concentration (EC50) of each PPCP was estimated using the best-fitting model and was compared with the results from a recent study. Comparative analysis indicated that most compounds showed the same level of toxicity. Moreover, the stimulatory effects of PPCPs at environmental concentrations (low doses) were assessed. These results indicated that certain compounds have traditional inverted U- or J-shaped dose-response curves, and 55% of them presented a stimulatory effect below the zero effect-concentration point. Effective concentrations of 0 (EC0), 5 (EC5) and 50% (EC50) were calculated for each PPCP as the ecotoxicological points. All compounds that presented narcosis as a mode of toxic action at high doses also exhibited stimulation at low concentrations. The maximum stimulatory effect of a mixture was higher than the highest stimulatory effect of each individually tested compound. Moreover, when the exposure time was increased, the hormetic effect decreased. Hormesis is being increasingly included in dose-response studies because this may have a harmful, beneficial or indifferent effect in an environment. Despite the results obtained in this research, further investigations need to be conducted to elucidate the behavior of PPCPs in aquatic environments.

Ecological risks of home and personal care products in the riverine environment of a rural region in South China without domestic wastewater treatment facilities.

Home and personal care products (HPCPs) including biocides, benzotriazoles (BTs) and ultraviolet (UV) filters are widely used in our daily life. After use, they are discharged with domestic wastewater into the receiving environment. This study investigated the occurrence of 29 representative HPCPs, including biocides, BTs and UV filters, in the riverine environment of a rural region of South China where no wastewater treatment plants were present, and assessed their potential ecological risks to aquatic organisms. The results showed the detection of 11 biocides and 4 BTs in surface water, and 9 biocides, 3 BTs and 4 UV filters in sediment. In surface water, methylparaben (MeP), triclocarban (TCC), and triclosan (TCS) were detected at all sites with median concentrations of 9.23 ng/L, 2.64 ng/L and 5.39 ng/L, respectively. However, the highest median concentrations were found for clotrimazole (CLOT), 5-methyl-1H-benzotriazole (MBT) and carbendazim (CARB) at 55.6 ng/L, 33.7 ng/L and 13.8 ng/L, respectively. In sediment, TCC, TCS, and UV-326 were detected with their maximum concentrations up to 353 ng/g, 155 ng/g, and 133 ng/g, respectively. The concentrations for those detected HPCPs in surface water and sediment were generally lower in the upper reach (rural area) of Sha River than in the lower reach of Sha River with close proximity to Dongjiang River (Pt-test<0.05), indicating other input sources of HPCPs in the lower reach. Biocides showed significantly higher levels in surface water in the wet season than in the dry and intermediate seasons. Preliminary risk assessment demonstrated that the majority of HPCPs monitored represented low risk in surface waters. There are potentially greater risks to aquatic organisms from the use of TCS and TCC in the wet season than in dry and intermediate seasons in surface waters. This preliminary assessment also indicates potential concerns associated with TCC, TCS, DEET, CARB, and CLOT in sediments, although additional data should be generated to assess this fully. Thus future research is needed to investigate ecological effects of these HPCPs on benthic organisms in sediment of rural rivers receiving untreated wastewater discharge.

Ending the use of animals in toxicity testing and risk evaluation.

This article discusses the use of animals for the safety testing of chemicals, including pharmaceuticals, household products, pesticides, and industrial chemicals. It reviews changes in safety testing technology and what those changes mean from the perspective of industrial innovation, public policy and public health, economics, and ethics. It concludes that the continuing use of animals for chemical safety testing should end within the decade as cheaper, quicker, and more predictive technologies are developed and applied.

Particle size distribution of aerosols sprayed from household hand-pump sprays containing fluorine-based and silicone-based compounds.

Japan has published safety guideline on waterproof aerosol sprays. Furthermore, the Aerosol Industry Association of Japan has adopted voluntary regulations on waterproof aerosol sprays. Aerosol particles of diameter less than 10 µm are considered as "fine particles". In order to avoid acute lung injury, this size fraction should account for less than 0.6% of the sprayed aerosol particles. In contrast, the particle size distribution of aerosols released by hand-pump sprays containing fluorine-based or silicone-based compounds have not been investigated in Japan. Thus, the present study investigated the aerosol particle size distribution of 16 household hand-pump sprays. In 4 samples, the ratio of fine particles in aerosols exceeded 0.6%. This study confirmed that several hand-pump sprays available in the Japanese market can spray fine particles. Since the hand-pump sprays use water as a solvent and their ingredients may be more hydrophilic than those of aerosol sprays, the concepts related to the safety of aerosol-sprays do not apply to the hand pump sprays. Therefore, it may be required for the hand-pump spray to develop a suitable method for evaluating the toxicity and to establish the safety guideline.

[ORGANOPHOSPHORUS FLAME RETARDANTS - TOXICITY AND INFLUENCE ON HUMAN HEALTH]. / FOSFOROWE ZWIAZKI ORGANICZNE ZMNIEJSZAJACE PALNOSC - TOKSYCZNOSC I WPLYW NA ZDROWIE LUDZI.

Organophosphorus flame retardants (flame retardants, FRs) have been used for several decades in many industries, including the production of dyes, varnishes, adhesives, synthetic resins, polyvinyl chloride, hydraulic fluids, plastics and textiles. Their importance in recent times has increased due to i.a., significantly reduced use of polybrominated diphenyl ethers (PBDEs) - persistent organic pollutants, dangerous for the environment. The aim of this study was to review the available literature data concerning phosphorous FRs primarily for neurotoxic, fertility, reproductive and carcinogenic effects. The analysis concerned the following most commonly used substances: tris(2-ethylhexyl)phosphate (TEHP), tris(2-butoxyethyl)phosphate (TBEP), triphenyl phosphate (TPP), tris(2-chloroethyl)phosphate (TCEP), tetrakis(hydroxymethyl)-phosphonium chloride (THPC), tributyl phosphate (TBP), tricresyl phosphate (TCP), tris(2-chloroisopropyl)phosphate (TCPP), tris(1,3-dichloroisopropyl)phosphate (TDCP) and tetrakis(hydroxymethyl)phosphonium sulphate (THPS). In animal studies neurotoxic effects were found after exposure to TBEP, THPC, TBP and TCP, while in humans they were observed only after exposure to TCP. TCEP, THPS, TBP, TCP and TDCP caused disorders in fertility and/or fetal development of animals. Adverse effects on reproduction in humans may be caused by TPP, TCP, and TDCP. In laboratory animals the development of tumors was observed after high doses of TEHP, TCEP, TBP and TDCP. None of these compounds is classified as a human carcinogen. The environmental toxicity of phosphate FRs is low (except for TPP, TCEP and TBEP). They are not stable compounds, in living organisms they are metabolised and quickly excreted. Therefore, they can be used as an alternative to PBDEs.

The hapten-atopy hypothesis III: the potential role of airborne chemicals.

One explanation for the large increase in the prevalence of atopic disease in developed countries during the last 50 years is the 'hygiene hypothesis'. This proposes that a reduced exposure to pathogenic microorganisms at a key period(s) during development results in the maintenance or acquisition of an atopic phenotype. Alternatively, or additionally, we have postulated that increased exposure to chemicals generally, and to irritant/haptenic chemicals in particular, during critical windows of maternal pregnancy/early life have also contributed to changes in the prevalence of atopic disease. Having previously reviewed the potential roles of oral and cutaneous exposure to chemicals on the subsequent diagnosis of atopic disease, we here consider possible evidence of a role for exposure to airborne chemicals as a contributory factor in acquired susceptibility to atopic allergy. After controlling for known confounders, five specific maternal occupations during pregnancy have been implicated as being associated with subsequent atopic disease in the offspring. Each of these occupations is characterized by high and persistent exposure to airborne chemicals. High-level exposure to volatile organic compounds in the domestic environment, either during pregnancy or in early life, is also associated with development of childhood atopic disease. Similarly, sustained exposure to airborne chlorinated chemicals from swimming pools during childhood has been associated with the development of atopic allergy. A possible immunological basis for these associations is that exposure to certain airborne chemicals, even at low levels, can result in the delivery of 'danger' signals that, in turn, bias the immune response towards the selective induction or maintenance of preferential T helper 2-type immune responses consistent with the acquisition of allergic sensitization.

Perinatal exposure to solvents and wheezing, eczema and food allergies at age 2.

OBJECTIVES: The time from the prenatal period through early childhood is an important window of vulnerability for the developing immune and respiratory systems, both sensitive to environmental chemicals such as solvents. This study sought to examine the effects of solvent exposure during the prenatal and postnatal periods on wheezing, eczema and food allergies in early childhood. METHODS: This study, based on the PELAGIE cohort, included 1505 mother-child pairs with measurements of prenatal and postnatal solvent exposures and data on wheezing, eczema or food allergies. The maternal occupation reported at inclusion, in early pregnancy allowed us to define prenatal occupational solvent exposure (by three specific job-exposure matrices). Data on prenatal and postnatal domestic solvent exposure, that is exposure to products that contain solvents, were obtained from self-administered questionnaires, once at inclusion and again when the child was 2 years old. Outcome data was collected at the 2-year follow-up. Associations between exposures and outcomes were estimated by logistic regression models, after adjustment for potential confounders. RESULTS: No association was observed between prenatal exposure to solvents and the outcomes studied. Postnatal exposure was associated with an increased risk of wheezing (OR=1.80 (95% CI 1.25 to 2.59)) which persisted after adjustment for prenatal exposure. No significant association was observed with eczema or food allergies. CONCLUSIONS: Postnatal exposure to solvent-containing products in the home may increase the risk of wheezing in early childhood. Follow-up studies are needed to determine if the health effects observed at age 2 persist at later ages.

Exposure characteristics of familial cases of lung injury associated with the use of humidifier disinfectants.

BACKGROUND: This study describes 17 families with 38 lung injury patients (14 males, 24 females; 22 preschool-age children less than six years of age and 16 individuals of 13-50 years) who used disinfectant added to humidifiers in the home. METHODS: Clinical examination and humidifier disinfectant-use histories were taken, and a thorough home investigation was performed to assess exposure to humidifier disinfectant. RESULTS: Nine of the patients (three pregnant females, six preschool-age children) died soon after they first developed lung damage. Six (16%) were pregnant females and 22 (58%) were preschool-aged children younger than six years. The patients used humidifier disinfectant products containing either polyhexamethylene guanidine phosphate (PHMG, n = 36) or oligo(2-(2-ethoxy)ethoxyethyl guanidinium chloride (PGH, n = 2). Twenty-six patients (68%) used the brand "Oxy"®, which contains PHMG. Of the ten patients with fatal lung injury, nine were found to have used PHMG. CONCLUSIONS: Our findings suggest that the use of humidifier disinfectant products containing either PGH or PHMG can cause lung injury, especially in preschool-age children younger than six years and pregnant women.

Presence in, and release of, nanomaterials from consumer products.

Widespread use of engineered nanomaterials (ENMs) in consumer products has led to concerns about their potential impact on humans and the environment. In order to fully assess the impacts and release of ENMs from consumer products, this chapter provides an overview of the types of consumer products that contain nanomaterials, the potential release mechanisms of these ENMs from consumer products, and the associated human exposure. Information from two large datasets on consumer goods associated with ENMs, namely, the U.S.-based Project for Emerging Nanotechnologies from the Woodrow Wilson International Center, and the European-based National Institute for Public Health and the Environment of Netherlands, have been summarized. These databases reveal that silver, titanium, carbon-based ENMs are the major nanomaterials associated with consumer products. The presence and potential release of silver, titanium, carbon-based, and other nanomaterials from consumer goods available in published literature are also summarized, as well as the potential human exposure scenarios of inhalation, ingestion, dermal, and combination of all means. The prospecting of nanomaterial in water and biosolids provides further evidence of ENM occurrence, which could be linked to the use of nanomaterials containing consumer goods. Finally, this overview provides guidelines on toxicity studies, which calls for further efforts to analyze the biological effects of ENMs on human beings and their exposure pathways in consumer products.

Inhalation Toxicity Screening of Consumer Products Chemicals using OECD Test Guideline Data-based Machine Learning Models.

This study aimed to screen the inhalation toxicity of chemicals found in consumer products such as air fresheners, fragrances, and anti-fogging agents submitted to K-REACH using machine learning models. We manually curated inhalation toxicity data based on OECD test guideline 403 (Acute inhalation), 412 (Sub-acute inhalation), and 413 (Sub-chronic inhalation) for 1709 chemicals from the OECD eChemPortal database. Machine learning models were trained using ten algorithms, along with four molecular fingerprints (MACCS, Morgan, Topo, RDKit) and molecular descriptors, achieving F1 scores ranging from 51 % to 91 % in test dataset. Leveraging the high-performing models, we conducted a virtual screening of chemicals, initially applying them to data-rich chemicals generally used in occupational settings to determine the prediction uncertainty. Results showed high sensitivity (75 %) but low specificity (23 %), suggesting that our models can contribute to conservative screening of chemicals. Subsequently, we applied the models to consumer product chemicals, identifying 79 as of high concern. Most of the prioritized chemicals lacked GHS classifications related to inhalation toxicity, even though they were predicted to be used in many consumer products. This study highlights a potential regulatory blind spot concerning the inhalation risk of consumer product chemicals while also indicating the potential of artificial intelligence (AI) models to aid in prioritizing chemicals at the screening level.

Ranking of concern, based on environmental indexes, for pharmaceutical and personal care products: an application to the Spanish case.

A wide range of Pharmaceuticals and Personal Care Products (PPCPs) are present in the environment, and many of their adverse effects are unknown. The emergence of new compounds or changes in regulations have led to dynamical studies of occurrence, impact and treatment, which consider geographical areas and trends in consumption and innovation in the pharmaceutical industry. A Quantitative study of Structure-Activity Relationship ((Q)SAR) was performed to assess the possible adverse effects of ninety six PPCPs and metabolites with negligible experimental data and establish a ranking of concern, which was supported by the EPA EPI Suite™ interface. The environmental and toxicological indexes, the persistence (P), the bioaccumulation (B), the toxicity (T) (extensive) and the occurrence in Spanish aquatic environments (O) (intensive) were evaluated. The most hazardous characteristics in the largest number of compounds were generated by the P index, followed by the T and B indexes. A high number of metabolites has a concern score equal to or greater than their parent compounds. Three PBT and OPBT rankings of concern were proposed using the total and partial ranking method (supported by a Hasse diagram) by the Decision Analysis by Ranking Techniques (DART) tool, which was recently recommended by the European Commission. An analysis of the sensibility of the relative weights of these indexes has been conducted. Hormones, antidepressants (and their metabolites), blood lipid regulators and all of the personal care products considered in this study were at the highest levels of risk according to the PBT and OPBT total rankings. Furthermore, when the OPBT partial ranking was performed, X-ray contrast media, H2 blockers and some antibiotics were included at the highest level of concern. It is important to improve and incorporate useful indexes for the predicted environmental impact of PPCPs and metabolites and thus focus experimental analysis on the compounds that require urgent attention.

RIFM fragrance ingredient safety assessment, cis-3-hexenyl methyl carbonate, CAS Registry Number 67633-96-9.

The following paper presents the method of determination of the percolation threshold in cement composites with expanded graphite by impedance spectroscopy. Most of the applications of cement composites with conductive additives require exceeding the percolation threshold. The ionic conductivity of cement matrix below the percolation threshold has a major impact on the conductivity of the composite, as a result, it significantly hinders the exploitation of these composites. The electric properties of cement composites with expanded graphite were evaluated by DC measurements and impedance spectroscopy (IS). Based on Nyquist plots, two equivalent circuits were adopted for the composites. Next, the values of capacitance and inductance of cement composites with expanded graphite were calculated from the fitted equivalent circuits. The analysis of the results shows that the percolation threshold occurs when the reactance of the composite changes from captative to inductive. Comparison between the values of percolation threshold obtained from DC measurements and IS shows that the method is effective for cement composites with conductive additives.

Toxicological properties and risk assessment of the anionic surfactants category: Alkyl sulfates, primary alkane sulfonates, and α-olefin sulfonates.

The category of the anionic surfactants (ANS) consisting of 46 alkyl sulfates, 6 primary alkane sulfonates, and 9 α-olefin sulfonates has been assessed under the high production volume (HPV) chemicals program of the Organisation for Economic Cooperation and Development (OECD) in 2007. In this review the toxicological properties of these chemicals are summarized. The chemicals of this category are used predominantly in detergents, household cleaning products, and cosmetics. These chemicals show low acute and repeat dose toxicity. There was no evidence of genetic or reproductive toxicity, or carcinogenicity. There also was no indication for sensitizing properties. Skin and eye irritating effects in consumers are not to be expected. For consumers, the calculated body burden is about 10,000 times lower than the lowest NOAEL value in experimental animals, so that adverse effects caused by substances of the ANS category can be excluded.

Assessment of sensitization risk of a laundry pre-spotter containing protease.

When proteolytic enzymes were first introduced to common laundry detergents in the 1960s, their ability to cause hypersensitivity due to exposure by inhalation was soon recognized as a problem, especially for production workers. Subsequently, formulations and manufacturing methods were developed to minimize exposure to enzymes via inhaled dust particles. Although detergents containing proteases are now considered safe for consumers, the experience with laundry pre-spotter products is not as extensive. Two studies were undertaken to examine the risk of sensitization to protease (i.e. Savinase(®)) used in a trigger-spray laundry pre-spotter product. The first was a laboratory study simulating a very heavy-use scenario in a controlled environment cubical chamber (14.5 m(3)). The product was applied to a series of fabric targets held vertically over a standard washing machine. Eight replicates of the experiment were done, using 30 sprays for each replicate. Airborne particle distributions in the breathing zone were characterized using a TSI particle analyzer. Enzyme concentrations in air were measured using PTFE membrane filters that were frozen until analyzed by an enzyme linked immunosorbent assay (ELISA). Results indicated that aerosol concentrations returned to baseline within 10 min, during which the average enzyme concentration in air was 17 ± 1.6 and 12 ± 0.92 ng/m(3) using low- and high-volume samplers, respectively. The corresponding amount of enzyme that could be inhaled was significantly less than allowed in occupational situations. The second study was a 6-month, controlled-use study involving approximately 100 subjects with confirmed atopic status by skin prick testing with common aeroallergens. The study involved daily exaggerated use of the pre-spotter product for 6 months, with prick testing for the protease carried out at baseline, 3 and 6 months. Results from the clinical study indicated that none of the subjects exhibited reactions that would indicate sensitization to the protease by inhalation. The principal limitations of the study were the relatively small number of subjects and the limited duration (96 completed the entire 6-month exposure program).