A microbial identification framework for risk assessment.

Micro-organisms are increasingly used in a variety of products for commercial uses, including cleaning products. Such microbial-based cleaning products (MBCP) are represented as a more environmentally-friendly alternative to chemically based cleaning products. The identity of the micro-organisms formulated into these products is often considered confidential business information and is not revealed or it is only partly revealed (i.e., identification to the genus, not to the species). That paucity of information complicates the evaluation of the risk associated with their use. The accurate taxonomic identification of those micro-organisms is important so that a suitable risk assessment of the products can be conducted. To alleviate difficulties associated with adequate identification of micro-organisms in MBCP and other products containing micro-organisms, a microbial identification framework for risk assessment (MIFRA) has been elaborated. It serves to provide guidance on a polyphasic tiered approach, combining the data obtained from the use of various methods (i.e., polyphasic approach) combined with the sequential selection of the methods (i.e., tiered) to achieve a satisfactory identity of the micro-organism to an acceptable taxonomic level. The MIFRA is suitable in various risk assessment contexts for micro-organisms used in any commercial product.

Assessment of workers' exposure to microorganisms when using biological degreasing stations.

Biological degreasing stations (BDSs) are used by mechanics. These BDSs use a water-based solution with a microbial degradation process. Occupational exposure during the use of BDSs has not been reported and few studies have identified the bacteria present. The objectives were to measure the concentration of microorganisms during BDSs' use and monitor the bacterial community in the liquid over time. Five mechanical workshops were studied. Six 30-min samples were taken at each workshop over one year. Bioaerosols in the ambient air samples were collected with Andersen impactors near the BDS Bioaerosols in the workers' breathing zone (WBZ) were collected on filters. Fresh bio-degreasing fluids were collected from unopened containers, and used bio-degreasing fluids were collected in the BDS. The results show that the use of BDSs does not seem to increase bioaerosols concentrations in the WBZ (concentrations lower than 480 CFU/m3) and that the bacterial communities (mainly yeasts, Bacillus subtilis and Pseudomonas aeruginosa) in the bio-degreasing fluids change through time and differ from the original community (B. subtilis). This study established that workers using BDSs were exposed to low levels of bioaerosols. No respiratory protection is recommended based on bioaerosols concentrations, but gloves and strict personal hygiene practices are essential.

Safety assessment of the use of Bacillus-based cleaning products.

Non-pathogenic Bacillus species used in cleaning products produce the appropriate enzymes to degrade stains and soils. However, there is little scientific data regarding the human exposure by inhalation of Bacillus spores during or after use of microbial-based cleaning products. Herein, air samples were collected at various locations in a ventilated, carpeted, residential room to determine the air concentration of viable bacteria and spores during and after the application of microbial-based carpet cleaning products containing Bacillus spores. The influence of human activities and vacuuming was investigated. Bioaerosol levels associated with use and post-application activities of whole room carpet treatments were elevated during post-application activity, but quickly returned to the indoor background range. Use of trigger spray spot applications generated aerosolized spores in the immediate vicinity, however, their use pattern and the generation of mostly non-respirable particles suggest minimal risks for pulmonary exposure from their use. The aerosol counts associated with use of these microbial-based cleaners were below the recommendation for safe exposure levels to non-pathogenic and non-toxigenic microorganisms except during application of the spot cleaner. The data presented suggest that carpet cleaning products, containing non-pathogenic Bacillus spores present a low potential for inhalation exposure and consequently minimal risk of adverse effects.

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.

Socio-environmental risk factors for medically-attended agricultural injuries in Wisconsin dairy farmers.

BACKGROUND: Accidents are common in the agricultural industry, particularly among dairy farmers. How said farmers get hurt is well established, but far less is known about how distal, socio-environmental factors influence injuries. This study examined associations between medically-attended agricultural injuries and: (1) personal sociodemographic characteristics, and (2) farm environment features and general safety practices. METHODS: A cross-sectional survey was implemented with linked data from electronic health records on prior agricultural injuries that occurred between 01/01/2002-12/31/2015. The sample included adult dairy producers who resided in north-central Wisconsin (USA) and were medically-homed to the Marshfield Clinic Health System. Multiple logistic regression was used to analyze associations between socio-environmental characteristics and agricultural injuries. RESULTS: There were 620 dairy farmers in the analytical sample, with 50 medically-attended agricultural injuries observed during the 14-year study time period (5.7 injuries per 1000 dairy farmers per year). In the multivariable model, the odds of agricultural injury were significantly greater among farmers who have private individually-purchased health insurance (OR=4.25; 95% CI: 1.31, 13.84), do not live at their dairy operation (OR=2.91; CI: 1.27, 6.67), and do not provide safety training to their workers (OR=4.27; CI: 1.00, 18.21). CONCLUSIONS: Dairy farmers in this analysis who did not live at their dairy operation, did not provide safety training to all their workers, or had individually-purchased health insurance were more apt to get injured, but more research is needed to confirm these findings in prospectively designed studies. How these factors can be directly addressed or otherwise used to better focus farm injury prevention initiatives should also be explored.

Trends in Occupations and Work Sectors Among Patients With Work-Related Asthma at a Canadian Tertiary Care Clinic.

BACKGROUND: Work-related asthma (WRA) is the most common chronic occupational lung disease in the developed world. Several factors including sociodemographic status and occupation/industry increase the risks of developing WRA. In this study, we sought to identify changes in patterns and characteristics among patients with WRA over a 15-year period in an occupational lung disease clinic. METHODS: We performed a retrospective analysis of patients with WRA charts at the Occupational Lung Disease Clinic of a University Hospital in Toronto, Canada. Patients were divided into two periods classified by first attendance at the clinic 2000 through 2007 and 2008 through 2015. Comparisons between the two periods included: sociodemographic characteristics, smoking status, occupations, exposures, and submitted workers' compensation claims. RESULTS: Fewer occupational asthma cases were seen in the more recent period vs the earlier period (40 vs 74 cases), with a smaller reduction in work-exacerbated asthma cases (40 vs 58). The recent period included a significantly smaller proportion employed in the manufacturing industry and isocyanate-induced cases compared with the earlier period. An increased proportion were employed in health-care and education industries (primarily cleaners and teachers) in the recent period, consistent with a corresponding increased frequency of cleaning agents and dust exposures. CONCLUSIONS: The changes observed in work sectors in the patients with WRA in this clinic in Toronto are consistent with reductions reported in Ontario workers' compensation claims for occupational asthma and may relate to preventive measures. Cleaners and teachers should be a focus of further intervention measures for work-related asthma.

Occupational skin disease in Victoria, Australia.

OBJECTIVES: To describe the characteristics of patients with occupational skin disease (OSD) in a tertiary referral clinic in Victoria, Australia. METHODS: A retrospective review was conducted of records from patients seen at the Occupational Dermatology Clinic in Melbourne, Australia between 1 January 1993 and 31 December 2010. RESULTS: Of the 2894 people assessed in the clinic during the 18-year period, 44% were women and 56% were men. In all, 2177 (75%) were diagnosed with occupational skin disease (OSD). Of the patients with a work-related skin condition, 45% (n = 979) were considered to be atopic. The most common diagnosis in those with OSD was irritant contact dermatitis (ICD) (44%), followed by allergic contact dermatitis (33%) and endogenous eczema (11%). Women were significantly more likely to have soaps and detergents (P < 0.001) and water/wet work (P < 0.001) as causes of their ICD than men. Men were significantly more likely to have oils and coolants (P < 0.001) and solvent exposures (P < 0.001) as causes of their ICD. Occupational groups with the highest incidence of OSD were the hair and beauty professions (70 per 100 000), followed by machine and plant operators (38 per 100 000) and health-care workers (21 per 100 000). CONCLUSION: We confirm the importance of occupational contact dermatitis as the most common cause of OSD, with ICD being the most common diagnosis. There are differences in the causes of ICD between our group of male and female workers. For the first time in Australia, rates of OSD in certain industries have been calculated.

Implementing the Use of Chemical-Free Products in a Perinatal Unit.

OBJECTIVE: To develop a process to identify, adopt, and increase individual awareness of the use of chemical-free products in perinatal hospital units and to develop leadership skills of the fellow/mentor pair through the Sigma Theta Tau International Maternal-Child Health Nurse Leadership Academy (STTI MCHNLA). DESIGN: Pretest/posttest quality improvement project. SETTING: Tertiary care 80-bed perinatal unit. PATIENTS: Mothers and newborns on perinatal unit. INTERVENTIONS/MEASUREMENTS: The chemical hazard ratings of products currently in use and new products were examined and compared. Chemical-free products were selected and introduced to the hospital system, and education programs were provided for staff and patients. We implemented leadership tools taught at the STTI MCHNLA to facilitate project success. Pre- and postproject evaluations were used to determine interest in the use of chemical-free products and satisfaction with use of the new products. Cost savings were measured. RESULTS: Products currently in use contained potentially harmful chemicals. New, chemical-free products were identified and adopted into practice. Participants were interested in using chemical-free products. Once new products were available, 71% of participants were positive about using them. The fellow and mentor experienced valuable leadership growth throughout the project. CONCLUSIONS: The change to chemical-free products has positioned the organization and partner hospitals as community leaders that set a health standard to reduce environmental exposure for patients, families, and staff. The fellow and mentor learned new skills to assist in practice changes in a large organization by using the tools shared in the STTI MCHNLA.

Self-reported occupational skin contact with cleaning agents and the risk of disability pension.

BACKGROUND: Occupational skin diseases often affect the hands and can lead to consequences at both the individual and the social level. OBJECTIVES: To investigate and quantify the association between self-reported occupational skin contact with cleaning agents and subsequent transition to disability pension. METHODS: A sample of 8337 employees between 18 and 59 years of age participated in the Danish Work Environment Cohort Study in 1990, 1995, or 2000. They were followed up regarding disability pension until 2006 using the DREAM register on social transfer payments for all inhabitants in Denmark. The Cox proportional hazards model was used to estimate the impact of occupational exposure to cleaning agents on subsequent disability pension. RESULTS: Among women, 11% of the disability pension cases were attributable to exposure to cleaning agents and/or disinfectants. CONCLUSIONS: The study suggests a potential for prevention of work-related disabilities among job groups exposed to cleaning agents.

Comparative assessment of the acute skin irritation potential of detergent formulations using a novel human 4-h patch test method.

Predictive skin irritation test methods, which do not require use of animals, are needed for the pre-market assessment of detergent formulations. The utility of a novel and ethical human acute skin irritation patch test method, originally developed for chemical skin irritation assessment, was evaluated. In this IRB-approved method, subjects were patched under occlusion for increasing periods of time up to 4h in duration. The total incidence of positive skin reactions for test products was compared to a positive control (20% aqueous sodium dodecyl sulfate [SDS]). Acutely irritating formulas were defined as those showing a significantly increased or equal incidence of positive responders compared with that of SDS. The time of exposure required for 50% of subjects to show a positive skin reaction (TR50 value) was calculated for each product and enabled test product comparisons within and between studies. Using this approach, 24 detergent formulations of various types were tested in seven individual studies. The skin irritation profiles were generally consistent within product types, which could be categorized as follows (by decreasing irritancy): mold/mildew removers (average TR50 = 0.37 h) > disinfectants/sanitizers (0.64 h) > fabric softener concentrate (1.09 h) = aluminum wash (1.20 h) > 20% SDS (1.81 h) > liquid laundry detergents (3.48 h) > liquid dish detergents (4.16 h) = liquid fabric softeners (4.56 h) = liquid hand soaps (4.58 h) = shampoos (5.40 h) = hard surface cleaners (6.34 h) > powder automatic dish detergents (>16 h) = powder laundry detergents (>16 h). In addition to formulation effects, some seasonal effects were noted; particularly greater winter-time reactivity to 20% SDS and the hard surface cleaner and liquid laundry formulations. These results demonstrate the utility of this patch test method for the comparative skin irritation assessment of these different product types.

Functional assessment of a washing emulsion for sensitive skin: mild impairment of stratum corneum hydration, pH, barrier function, lipid content, integrity and cohesion in a controlled washing test.

BACKGROUND/PURPOSE: Sensitive skin has been described as a skin type with higher reactivity than normal skin and exaggerated reactions to external irritants. Washing with soaps is harmful for barrier-related parameters. Cutaneous irritation induced by cleansing products under exaggerated test conditions, e.g. patch testing, is not necessarily predictive of the irritation occurring under standardized daily use conditions. The purpose of the study was to assess the effect of an improved washing solution for sensitive skin in a half-site comparison on barrier-related parameters. METHODS: Thirty healthy volunteers with self-reported sensitive and so-called problematic skin performed standardized washings with a soap-free washing emulsion with mild acidity (pH 5.5) for 3 weeks. Test areas were both forearms and the cheek. Non-invasive biophysical measurements of the following skin parameters, epidermal permeability barrier function measured as transepidermal water loss (TEWL), stratum corneum (SC) hydration, pH value, skin surface lipids, skin temperature and SC integrity/cohesion, were assessed prior to the first washing, on days 7, 14 and 21 after beginning the washing procedure. SC cohesion was quantified using two independent methods on D-Squame tapes: optical spectroscopy measuring the absorbance and a protein assay assessing the total protein (Bradford). Both methods showed a good correlation. SC integrity was quantified by measuring TEWL after sequential stripping with D-Squame tapes. RESULTS: The use of the washing emulsion led to a mild damage of the epidermal permeability barrier function with no marked difference to water application. Furthermore, a mild but significant dehydration was assessed after 21 days vs. baseline without any differences between the water-treated and the washing emulsion-treated forearm. On the cheek no dehydration was detectable but the lipid content was reduced under the washing emulsion. The pH value increased in all three test areas after 21 days, again without significant differences between water and the washing solution. SC cohesion was quantified using two independent methods on D-Squame tapes: optical spectroscopy measuring the absorbance and a protein assay assessing the total protein (Bradford). Both methods showed a good correlation. The SC cohesion decreased after 21 days on the water-treated as well as on the washing emulsion-treated arm. The decrease over time was significant when used the optical spectroscopy measuring. A standardized questionnaire revealed positive characteristics of the washing emulsion and good acceptance. CONCLUSION: The investigated standardized washing model with the endpoints epidermal barrier function, SC hydration, surface pH, skin surface lipids, skin temperature and SC integrity/cohesion showed only mild damage comparable to washing with water.

Cosmetic allergy: incidence, diagnosis, and management.

A recent epidemiologic survey in the UK revealed that 23% of women and 13.8% of men experience some sort of adverse reaction to a personal care product over the course of a year. Although most of these reactions may be due to subjective sensory irritation, various studies reveal that up to 10% of dermatologic patients who are patch tested are allergic to cosmetic products or their constituent ingredients. Causative products include deodorants and perfumes, skin care products, hair care products, and nail cosmetics. Allergic contact dermatitis mainly results from fragrance chemicals and preservatives. Recent work has suggested that additional fragrance chemicals may need to be tested in order to identify those patients 'missed' by the current fragrance mix; in particular, hydroxy-isohexyl-3-cyclohexene carboxaldehyde (HMPPC Lyral) has been singled out as an important sensitizing agent. The increased usage of natural fragrances and botanic extracts can also cause problems in their own right or through co-reactivity. The preservative methyldibromo glutaronitrile has also been recognized as an increasingly important sensitizer in Europe, which has led to the recent recommendation that it should be prohibited from 'leave-on' products until information on 'safe' consumer levels becomes available. Other emerging allergens include UV filters, tosylamide/formaldehyde resin, and nail acrylates. The diagnosis of cosmetic allergy should be confirmed with patch testing, including testing of 'whole' products, when necessary, and repeat open application tests can be used to confirm the relevance of reactions in cases of doubt.

Environmental risk assessment of phosphonates, used in domestic laundry and cleaning agents in The Netherlands.

In the long-term cooperative project Voluntary Plan of Action (1990) between the Dutch Soap and Detergent Association (NVZ) and the Dutch Ministry of Housing, Spatial Planning and the Environment (VROM) environmental risk assessments of several main components of laundry cleaning formulations were completed. As a part of that project the environmental risk assessment of HEDP, ATMP, EDTMP and DTPMP phosphonates used in detergent applications has been carried out according to the EU Technical Guidance Document for Environmental Risk Assessment for New and Existing Chemicals. All PEC/PNEC ratios were well below 1. Results of this assessment based on the total industry volumes from 1995 and 1998 indicate that the environmental risk of these phosphonates is low in The Netherlands with properly functioning sewage treatment plants.

A skin sensitization safety assessment of a new bleach activator technology in detergent applications.

A new chemical called nonanoyl amido caproylacid oxybenzenesulphonate (NACAOBS) is being developed for use as a bleach activator in laundry detergents. Bleach activators, like NACAOBS, are typically used at levels between 2% and 6% in laundry detergents. NACAOBS is stable in aqueous solutions, but undergoes rapid perhydrolysis when combined with water and peroxygen bleach in laundry detergents. Animal testing demonstrated that NACAOBS, as a raw material, is a weak skin sensitizer. Clinical testing, including extended simulated laundry pretreatment, human repeat insult patch testing and home use testing was then undertaken, following sufficient reassurance of 1) the weak sensitization potential of the substance, 2) its rapid degradation in laundry wash solutions and, consequently, 3) low-to-negligible consumer dermal exposures to the native substance. Results confirmed the skin sensitization safety profile of laundry detergents containing NACAOBS, namely the absence of any reaction suggestive of contact sensitization (even under exaggerated dermal exposure conditions in a detergent matrix), and a skin compatibility profile comparable to that of current detergents. Further confirmation of the skin safety profile was obtained from a successful 12-month market test of a granular detergent containing 3.6% of the new substance, during which not a single adverse skin reaction was reported. In addition, NOBS (an oxybenzenesulphonate structural analogue to NACAOBS) has similar toxicological properties and has been safely marketed in detergents at similar levels for many years. It can be concluded that the likelihood of NACAOBS to induce skin sensitization or even elicit allergic reactions in consumer detergent use scenarios is negligible.

Including transformation products into the risk assessment for chemicals: the case of nonylphenol ethoxylate usage in Switzerland.

A method for applying the risk assessment approach using ratios of predicted environmental concentrations (PECs) and predicted no-effect concentrations (PNECs) to mixtures of parent compounds and their environmental transformation products is presented. Nonylphenol ethoxylates (NPnEOs) and a selection of their most relevant transformation products are investigated as a case study illustrating the method. The PEC values of NPnEO and its transformation products are calculated with a regional multimedia fate model including the transformation kinetics of the NPnEO degradation cascade. PNEC values are derived from a selection of toxicity data on NPnEO and its transformation products. The toxicity of the emerging mixture of NPnEO and its transformation products is then estimated under the assumption of concentration addition (similar mode of action). On this basis, PEC-to-PNEC ratios for the aquatic environment and the sediment are calculated for the individual components of the mixture and the mixture itself. For this purpose, average release rates of NPnEO and its transformation products from Swiss sewage treatment plants were used. While the PEC values of the individual components do not exceed the corresponding PNEC values, the risk quotient of the mixture in water is greater than 1. In sediment, the mixture does not exceed a risk quotient of 1. A combination of sensitivity and scenario analyses is employed to identify the upper and lower bounds of the results.

Current best practice for the health surveillance of enzyme workers in the soap and detergent industry.

This study defines current best practice for the health surveillance of workers who are potentially exposed to enzymes in the manufacture of enzymatic detergent products. It is recommended that health surveillance is performed 6-monthly for the first 2 years and annually thereafter. The health surveillance programme should include a respiratory questionnaire to detect symptoms, assessment of lung function to detect pre-symptomatic changes and an immunological test to detect specific immunoglobulin E (IgE) to enzymes. The International Union Against Tuberculosis and Lung Disease respiratory questionnaire should be used since it has been validated extensively for detecting asthma. Operators should observe the American Thoracic Society performance criteria for spirometers and standardized procedures for conducting spirometry. Since current airborne monitoring techniques for enzymes do not detect short-duration peak exposures, the incidence of employee sensitizations remains the most reliable measure of the integrity of environmental control. The Pepys skin prick test has been validated as a sensitive, specific and practical test for detecting specific IgE to many inhalant allergens including enzymes. For newly sensitized workers, a multi-cause investigation should be conducted to identify potential sources of exposure. Group results of immunological test results assist in the evaluation of workplace control measures, and should be used to monitor the effectiveness of hygiene and engineering programmes and to help prioritize areas for improvement. Positive responses to a questionnaire or abnormal spirometry should be assessed further. Occupational asthma should be excluded in any case of adult-onset asthma that starts or deteriorates during working life. This is particularly important because an accurate diagnosis of occupational asthma with early avoidance of exposure to its cause can result in remission of symptoms and restoration of lung function.

A hand immersion test under laboratory-controlled usage conditions: the need for sensitive and controlled assessment methods.

Exaggerated test conditions were frequently used to investigate the cutaneous tolerance of detergent products in the past. As the sensitivity of newly designed biometric methods is steadily improving, the trend towards more realistic test conditions should be encouraged. A hand immersion test under laboratory-controlled usage conditions is presently described, fulfilling such principles. Panelists soaked their hands in 2 different hand dishwashing liquids, 2x daily for 10 min each (with successive in-solution/out-of-solution cycles) for 4 consecutive days. Products were at usual dilution for dishwashing liquids and were randomized between the dominant and non-dominant hands of panelists. Visual scoring of erythema and dryness developing on the whole hands (scoring scales including interdigital areas and joints) during the week did not allow discrimination between the 2 products. However the dominant hands were significantly more susceptible to alterations than the non-dominant hands, regardless of product attribution. In contrast, skin electrical measurements (Corneometer CM800 and Skicon 200) on the dorsum of the hands (muscle mass between thumb and index) and squamometry analysis of tape stripping (harvested from the same site) yielded significant differences between the 2 products. In conclusion, a hand immersion test under realistic conditions has been described, which discriminates between products when sensitive assessment methods are used to explore skin sites partially protected from daily-life skin aggressions.

Safety assessment of enzyme-containing personal cleansing products: exposure characterization and development of IgE antibody to enzymes after a 6-month use test.

BACKGROUND: Enzyme-containing personal cleansing products were being considered for the consumer market. Although enzymes have been marketed safely for many years as ingredients in laundry products, their use in a personal cleansing application represented a new type of exposure for consumers that was not supported by the historical safety data. An exposure assessment and additional safety data would be needed before marketing to ensure consumer safety. OBJECTIVE: The work in this paper was designed to evaluate the potential for inhalation exposure to the enzyme during use of this new product while showering. Then a clinical trial was conducted to determine whether or not the level, duration, and routes of exposure encountered during use of this product would induce a Type I sensitization response to the enzyme. METHODS: Exposure was assessed during normal showering activities by collecting air samples with both high volume and personal samplers and quantitating enzyme levels with an ELISA. To assess the potential for sensitization, panelists were asked to use a prototype protease-containing bar product for all personal cleansing tasks and to keep a use diary reporting any associated symptoms. Physical and dermatologic examinations and skin prick tests with enzyme were conducted before the test commenced and at 2-month intervals. RESULTS: Exposure assessment results showed that airborne enzyme levels were primarily dependent on the concentration of the enzyme in the personal cleansing product. Mean values for total airborne enzyme protein ranged from 5.7 to 11.8 ng/m3 when enzyme concentration, time of use, and measurement technique remained constant. After 6 months of at-home product use, four of 61 test subjects using the enzyme-containing bar had positive skin prick test responses when tested with the enzyme. The skin prick test data were supplemented with serologic analyses, which detected IgE specific for the protease enzyme. None of these subjects showed any clinical symptoms indicative of allergic reaction. CONCLUSION: The ability of enzymes to induce development of allergic antibodies in this study led to the conclusion that this prototype enzyme-containing personal cleansing bar would represent an inappropriate use of enzymes in a consumer product application. The likelihood of both induction of an immunologic response and subsequent elicitation of allergy symptoms in a small but significant fraction of the user population was high. This finding resulted in the decision to halt further development of this prototype.