Occupational Asthma Reference

Heederik D, Houba R, An exploratory quantitative risk assessment for high molecular weight sensitizers: wheat flour, Ann Occup Hyg, 2001;45:175-185,


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Dick Heederik, Institute of Risk Assessment Sciences, Utrecht Dick Heederik

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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.

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.

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.

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.

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