Accepted: 21 December 2017
Occupational asthma risk from exposures to toluene
diisocyanate: A review and risk assessment
Robert D. Daniels PhD
National Institute for Occupational Safety
and Health (NIOSH), Cincinnati, Ohio
Robert D. Daniels, National Institute for
Occupational Safety and Health (NIOSH),
1090 Tusculum Avenue, Mailstop C-15,
Cincinnati 45226, OH.
Background: Toluene Diisocyanate (TDI) is a known respiratory sensitizer linked to
occupational asthma (OA). To better manage worker risks, an appropriate characteri-
zation of the TDI-OA dose-risk relationship is needed.
Methods: The literature was reviewed for data suitable for dose-response modeling.
Previous study data were fit to models to derive prospective occupational exposure
limits (OELs), using benchmark dose (BMD) and low-dose extrapolation approaches.
Results: Data on eight TDI-exposed populations were suitable for analysis. There were
118 OA cases in a population contributing 13 590 person-years. The BMD-based OEL
was 0.4 ppb. The OEL based on low-dose extrapolation to working lifetime extra risk of
1/1000 was 0.3 ppb.
Conclusions: This study synthesized epidemiologic data to characterize the TDI-OA
dose-risk relationship. This approach yielded prospective OEL estimates below recent
recommendations by the American Conference of Governmental Industrial Hygienists,
but given significant study limitations, this should be interpreted with caution.
Confirmatory research is needed.
dose-response, epidemiology, isocyanates, occupational asthma, risk assessment
Asthma is a complex heterogeneous respiratory disease characterized
by variable airflow limitation and/or airway hyperresponsiveness.
disease is among the most common chronic illnesses in the human
experience, affecting about 300 million people worldwide.
incidence of new-onset adult asthma appears on the rise in
industrialized countries, with estimates ranging from <1 to 11 cases
per 1000 person-year among published reports,
but settling on
about 2 per 1000 person-years among persons aged 20-50 years in
large prospective studies.
The broad category of work-related asthma
comprises adult onset asthma cases that are either caused by
workplace exposures (ie, occupational asthma) or are a preexisting
disease that is worsened by work factors (work-exacerbated asthma).
Estimates of the fraction of adult asthma that is work-related have
widely varied, but typically range between 10 and 25% in industrialized
De novo occupational asthma (OA) is induced via sensitization to a
specific substance in the workplace, or by exposure to an inhaled
irritant at work.
There are over 300 causal agents for OA, which are
broadly separated into proteinaceous substances (eg, natural rubber
latex, enzymes, and animal-derived antigens), and low-molecular
weight (LMW) chemicals (eg, isocyanates and acid anhydrides).
Among known LMW agents, isocyanates, such as methylene diphenyl
diisocyanate (MDI), hexamethylene diisocyanate (HDI), and toluene
diisocyanate (TDI), are widely used in the manufacture of flexible and
rigid polyurethane (PUR) foams, sealants, elastomers, adhesives,
and coatings. In particular, TDI (usually a mixture of toluene-2,
4-diisocyanate and toluene-2,6-diisocyanate) is a highly volatile and
Institution at which the work was performed: The National Institute for Occupational
Safety and Health (NIOSH).
Published 2018. This article is a U.S. Government work and is in the public domain in the
wileyonlinelibrary.com/journal/ajim Am J Ind Med. 2018;61:282–292.