Exposure-response relationships for hexahydrophthalic and methylhexahydrophthalic anhydrides with total plasma protein adducts as biomarkers.
OBJECTIVE
This study investigated the exposure-response relationships of hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA) and evaluated the applicability of the total plasma protein adducts (TPPA) of these anhydrides as biomarkers of exposure and risk.


METHODS
In a cross-sectional study of 139 workers in a plant manufacturing electrical capacitors, the long-term exposure to HHPA and MHHPA was assessed through the quantification of TPPA using gas chromatography-mass spectrometry. Smoking and medical histories were obtained through questionnaires. Work-related symptoms of the eyes and airways were recorded. Specific immunoglobulin (Ig) E (radioallergosorbent test) and IgG (enzyme-linked immunosorbent assay) were determined in serum.


RESULTS
The mean level of the TPPA of HHPA was 840 fmol/ml and that of the TPPA of MHHPA was 1700 fmol/ml. There was no correlation between the TPPA of HHPA and the TPPA of MHHPA. Of all the workers, 19% were found to be positive for specific IgE and 17-19% for IgG. Positive associations were observed between HHPA exposure and specific IgE and IgG and between MHHPA exposure and specific IgG. Regarding work-related symptoms, 27% of the workers had symptoms of the nose, 21% had symptoms of the eyes, 11% had symptoms of the lower airways, and 8% had nose bleeding. There were significant exposure-response relationships for symptoms of the eyes and nose for HHPA exposure.


CONCLUSIONS
The results show that there is an exposure-response relationship for HHPA both with specific antibodies and with work-related symptoms and down to adduct levels of 40 fmol/ml plasma. In addition, the results elucidate the potential power of TPPA as a relevant index of exposure and risk.
Rosqvist
Seema
S
Department of Occupational and Environmental Medicine, Institute of Laboratory Medicine, University Hospital, Lund, Sweden.
Nielsen
Jörn
J
Welinder
Hans
H
Rylander
Lars
L
Lindh
Christian H
CH
Jönsson
Bo A G
BA
D000328:Adult; D000395:Air Pollutants, Occupational / Q000737:chemistry / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D004853:Epoxy Resins / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D010795:Phthalic Acids / Q000737:chemistry / Q000633:toxicity*; D010796:Phthalic Anhydrides / Q000737:chemistry / Q000633:toxicity*; D013548:Sweden
D000395:Air Pollutants, Occupational; D015415:Biomarkers; D001798:Blood Proteins; D004853:Epoxy Resins; D010795:Phthalic Acids; D010796:Phthalic Anhydrides; C005752:araldite; C106919:methylhexahydrophthalic acid