Dataset Information

Respiratory symptoms, sensitization, and exposure response relationships in spray painters exposed to isocyanates.

ABSTRACT:

Rationale

Associations between oligomeric isocyanate exposure, sensitization, and respiratory disease have received little attention, despite the extensive use of isocyanate oligomers.

Objectives

To investigate exposure-response relationships of respiratory symptoms and sensitization in a large population occupationally exposed to isocyanate oligomers during spray painting.

Methods

The prevalence of respiratory symptoms and sensitization was assessed in 581 workers in the spray-painting industry. Personal exposure was estimated by combining personal task-based inhalatory exposure measurements and time activity information. Specific IgE and IgG to hexamethylene diisocyanate (HDI) were assessed in serum by ImmunoCAP assay and enzyme immunoassays using vapor and liquid phase HDI-human serum albumin (HDI-HSA) and HSA conjugates prepared with oligomeric HDI.

Measurements and main results

Respiratory symptoms were more prevalent in exposed workers than among comparison office workers. Log-linear exposure-response associations were found for asthmalike symptoms, chronic obstructive pulmonary disease-like symptoms, and work-related chest tightness (prevalence ratios for an interquartile range increase in exposure of 1.2, 1.3 and 2.0, respectively; P ConclusionsThe results provide evidence of exposure-response relationships for both work-related and non-work-related respiratory symptoms and specific sensitization in a population exposed to oligomers of HDI. Specific IgE was found in only a minority of symptomatic individuals. Specific IgG seems to be merely an indicator of exposure.

SUBMITTER: Pronk A

PROVIDER: S-EPMC2176099 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Isocyanates are respiratory and skin sensitizers that are one of the main causes of occupational asthma globally. Genetic and epigenetic markers are associated with isocyanate-induced asthma and, before asthma develops, we have shown that genetic polymorphisms are associated with variation in plasma and urine biomarker levels in exposed workers. Inter-individual epigenetic variance may also have a significant role in the observed biomarker variability following isocyanate exposure. Therefore, we determined the percent methylation for CpG islands from DNA extracted from mononuclear blood cells of 24 male spray-painters exposed to 1,6-hexamethylene diisocyanate (HDI) monomer and HDI isocyanurate. Spray-painters' personal inhalation and skin exposure to these compounds and the respective biomarker levels of 1,6-diaminohexane (HDA) and trisaminohexyl isocyanurate (TAHI) in their plasma and urine were measured during three repeated industrial hygiene monitoring visits. We controlled for inhalation exposure, skin exposure, age, smoking status, and ethnicity as covariates and performed an epigenome-wide association study (EWAS) using likelihood-ratio statistical modeling. We identified 38 CpG markers associated with differences in isocyanate biomarker levels (Bonferroni < 0.05). Annotations for these markers included 18 genes: ALG1, ANKRD11, C16orf89, CHD7, COL27A, FUZ, FZD9, HMGN1, KRT6A, LEPR, MAPK10, MED25, NOSIP, PKD1, SNX19, UNC13A, UROS, and ZFHX3. We explored the functions of the genes that have been published in the literature and used GeneMANIA to investigate gene ontologies and predicted protein-interaction networks. The protein functions of the predicted networks include keratinocyte migration, cell-cell adhesions, calcium transport, neurotransmitter release, nitric oxide production, and apoptosis regulation. Many of the protein pathway functions overlap with previous findings on genetic markers associated with variability both in isocyanate biomarker levels and asthma susceptibility, which suggests there are overlapping protein pathways that contribute to both isocyanate toxicokinetics and toxicodynamics. These predicted protein networks can inform future research on the mechanism of allergic airway sensitization by isocyanates and aid in the development of mitigation strategies to better protect worker health.