An exploratory quantitative risk assessment for high molecular weight sensitizers: wheat flour.

OBJECTIVE: Quantitative risk assessments have been made for wheat dust and allergen exposure and wheat sensitization using classical epidemiological approaches based on simple categorizations in exposure groups. Such analyses suggest the existence of an exposure threshold level for wheat specific sensitization and were used as input in recently conducted risk assessments for wheat flour by the American Conference of Governmental Industrial Hygienists and the Dutch Expert Committee on Occupational Standards. More advanced statistical analyses were applied using generalized additive modeling and smoothed plots to evaluate the shape of the exposure response relationship in greater detail and evaluate the presence of exposure thresholds. METHODS: Data were used from a recently conducted epidemiological study in bakery workers. Information was available on wheat sensitization (IgE antibodies), inhalable dust levels and wheat allergen levels. Initial analyses were based on simple exposure categorizations for inhalable dust and allergen exposure. A more detailed analysis using non-parametric generalized additive models (GAM models) and smoothing plots allowed inspection of the presence of an exposure threshold of evaluation of 'no' or 'lowest observed effect levels' (NOELs, LOELs) using exposure data on the individual level. RESULTS: All analyses showed an increasing sensitization risk with increasing exposure. The classical epidemiological analyses gave evidence for the existence of an exposure threshold or 'no observed effect level (NOEL)' for specific wheat sensitization between 0.5 and 1 mg/m3 of inhalable dust. The more advanced analyses did not suggest any evidence for the existence of an exposure threshold. However, estimates of a LOEL obtained by considering an arbitrary increase in sensitization risk between 1.5 and 2 as undesirable, were close to the NOEL from the classical analyses and would therefore not lead to an essentially different exposure limit. The criterion of an increase in wheat sensitization risk was based on the risk in non-wheat dust exposed populations. CONCLUSION: Exposure response modeling using different classical epidemiological approaches and advanced statistical methods resulted in health based LOEL or NOEL estimates within a relatively close range. But when sensitization accompanied by asthma or rhinitis symptoms was considered as critical endpoint, steeper exposure-response relationships were observed which would lead to lower LOEL values.

Individual-based and group-based occupational exposure assessment: some equations to evaluate different strategies.

Basically, two strategies can be considered for the analysis of hazardous pollutants in the work environment: group-based and individual-based strategies. This paper provides existing and recently derived equations for both strategies describing the influence of several factors on attenuation and on the standard error of an estimated linear regression coefficient relating a continuous exposure variable and a continuous health outcome via a simple linear regression model. We applied these equations using exposure variability information from industry-wide surveys over the past decade in order to gain more insight into the effects of various sources of exposure variability on choices among different analysis strategies. In general, for the modeling scenario considered here, there is not a straightforward criterion for choosing an optimal analysis strategy. Researchers have to decide between individual-based strategies generating precise, though biased, estimates or group-based strategies generating less precise but essentially unbiased estimates. For most exposure variability scenarios evaluated, an individual-based strategy yielded substantial attenuation. It is the authors' contention that the choice between individual-based and group-based strategies should be based on validity, rather than on precision, of the estimated exposure-response coefficient.

Wheat antigen exposure assessment for epidemiological studies in bakeries using personal dust sampling and inhibition ELISA.

BACKGROUND: Asthma in bakery workers caused by exposure to wheat flour proteins is an important occupational health problem. Until recently, gravimetric dust measurements were the only available technique for quantitative exposure assessment in bakeries. However, it is questionable whether dust levels are a good exposure parameter or only give a crude approximation of the actual flour allergen concentration. OBJECTIVE: In the present study we have investigated a method to measure wheat flour antigens with immunochemical methods. METHODS: Wheat flour antigens were measured in 449 personal dust samples taken in bakeries, using enzyme-linked immunosorbent assay (ELISA) inhibition and an anti-wheat IgG4 serum pool. Western-blotting was performed to compare the wheat flour proteins detected by IgE and IgG4. RESULTS: Electrophoresis and immunoblotting showed that many wheat flour proteins can bind IgG4 and IgE, but also a reasonable similarity in major allergens detected by our IgG4-serum pool and IgE-positive sera. Inhibition tests showed some cross-reactivity with some cereal species, but not with other ingredients used in bakeries. In bakeries, large differences in personal airborne flour levels were found between occupational titles. For several groups clear differences in wheat antigen exposure levels existed, where no differences in dust exposure levels could be found. The relationship between dust and wheat antigen exposure varied considerably, depending on the specific bakery occupation, the size of the bakery, and the type of product produced by the bakery. This study also shows that personal sampling of wheat antigens is possible on a large scale and can be used for epidemiological field studies. CONCLUSION: Measurement of airborne wheat antigens in bakeries is a more specific and sensitive measurement tool than measuring dust samples, and will probably be essential for epidemiologic field studies focusing on exposure-response relationships.

Enzyme immunoassays for total and allergen specific IgE in population studies.

OBJECTIVE: Extensive IgE serology in occupational or environmental health studies is often hampered by a lack of technical facilities and finance. The use in population studies of relatively simple and inexpensive enzyme immunoassays (EIAs) was therefore evaluated for the assessment of total serum immunoglobulin E (IgE), and of specific IgE reactions with various common (house dust mites, grass and birch pollen, and cat) or occupational (fungal alpha-amylase and rat urinary protein) allergens. METHODS: Total IgE was measured with a sandwich EIA, calibrated with commercially available IgE standards. Reproducibility was studied by testing pooled normal human serum samples in each of a large series of test plates. A panel of 156 children's serum samples with known IgE values was used to compare the assay with other total IgE assays. A previously developed EIA for anti-yeast IgE was adapted for the measurement of IgE reacting with various common and occupational allergens. Binding of IgE to microwells coated with commercially available allergen extracts, or allergen preparations from our own laboratory, was measured with a monoclonal anti-human IgE antibody and subsequent incubations with biotinylated rabbit anti-mouse Ig and avidin-peroxidase. Panels of serum samples from school children (n = 116), bakery workers (n = 126), and laboratory animal workers (n = 52) were used to study sensitivity and specificity, with reference to skin prick tests as the standard, and to compare the EIAs with commercially available test kits. RESULTS: The detection limit of the EIA for total IgE was 0.5-1 kU/l for undiluted serum samples, and the coefficient of variation between assays was less than 15% at serum concentrations between 1 and 150 kU/l. Results obtained with the panel of 156 children's serum samples were strongly correlated (r2 = 0.86) with IgE concentrations measured previously by radioimmunoassay. The results of the EIA for various occupational allergens correlated very well, both qualitatively and quantitatively, with the results of commercial test kits. Sensitivity and specificity of the EIA results as a predictor of skin prick test reactivity towards common allergens (house dust mite, grass pollen, birch pollen, and cat) were remarkably high (> 80%-90%) in the series of 116 children's serum samples. In a population of bakery workers the specificity of the EIAs was also very high (> 90%). The sensitivity was notably lower (30%-70%) in this adult population, which is, however, in agreement with results reported for conventional IgE tests. CONCLUSION: As the costs were estimated to be at least five to 10-fold lower than those of commercial test kits, the EIAs for total and specific IgE may be very useful tools in epidemiological studies of atopic respiratory or other disorders.