Biological monitoring of exposure to 1,5–naphthalene diisocyanate and 4,4’-methylenediphenyl diisocyanate

Sennbro, Carl Johan; Lindh, Christian; Mattsson, Christian; Jönsson, Bo; Tinnerberg, Håkan

doi:10.1007/s00420-006-0096-5

Cited by 21 publications

(10 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Available studies on MDI ( Table 4 ) are mostly from the PUR sector with five papers classified under PUR production/use ( Rosenberg et al , 2002 ; Sennbro et al , 2006 ; Robert et al , 2007 ; Cocker et al , 2009 ; Keen et al , 2012 ). Exposures reported in studies from France ( Robert et al , 2007 ) and Sweden ( Sennbro et al , 2006 ) are in reasonable agreement; urine levels of MDA up to 33.7 µg g −1 creatinine (19.2 µmol mol −1 creatinine) in the Robert et al (2007) study and 78 µg l −1 (~32.6 µmol mol −1 creatinine) in the Sennbro et al (2006) study. Low levels were reported in the UK PUR elastomer industry with only 6 of the 71 workers sampled having detectable exposures (<0.5–0.7 µmol mol −1 creatinine) in one study ( Cocker et al , 2009 ) and a reported 90th percentile of 0.5 µmol mol −1 creatinine in a second study ( Keen et al , 2012 ).…”

Section: Resultsmentioning

confidence: 99%

Biomonitoring for Occupational Exposure to Diisocyanates: A Systematic Review

Scholten

Kenny

Duca

et al. 2020

Annals of Work Exposures and Health

View full text Add to dashboard Cite

Abstract Diisocyanates are a group of chemicals that are widely used in occupational settings. They are known to induce various health effects, including skin- and respiratory tract sensitization resulting in allergic dermatitis and asthma. Exposure to diisocyanates has been studied in the past decades by using different types of biomonitoring markers and matrices. The aim of this review as part of the HBM4EU project was to assess: (i) which biomarkers and matrices have been used for biomonitoring diisocyanates and what are their strengths and limitations; (ii) what are (current) biomonitoring levels of the major diisocyanates (and metabolites) in workers; and (iii) to characterize potential research gaps. For this purpose we conducted a systematic literature search for the time period 2000–end 2018, thereby focussing on three types of diisocyanates which account for the vast majority of the total isocyanate market volume: hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), and 4,4′-methylenediphenyl diisocyanate (MDI). A total of 28 publications were identified which fulfilled the review inclusion criteria. The majority of these studies (93%) investigated the corresponding diamines in either urine or plasma, but adducts have also been investigated by several research groups. Studies on HDI were mostly in the motor vehicle repair industry [with urinary hexamethylene diamine result ranging from 0.03 to 146.5 µmol mol−1 creatinine]. For TDI, there is mostly data on foam production [results for urinary toluene diamine ranging from ~0.01 to 97 µmol mol−1 creatinine] whereas the available MDI data are mainly from the polyurethane industry (results for methylenediphenyl diamine range from 0.01 to 32.7 µmol mol−1 creatinine). About half of the studies published were prior to 2010 hence might not reflect current workplace exposure. There is large variability within and between studies and across sectors which could be potentially explained by several factors including worker or workplace variability, short half-lives of biomarkers, and differences in sampling strategies and analytical techniques. We identified several research gaps which could further be taken into account when studying diisocyanates biomonitoring levels: (i) the development of specific biomarkers is promising (e.g. to study oligomers of HDI which have been largely neglected to date) but needs more research before they can be widely applied, (ii) since analytical methods differ between studies a more uniform approach would make comparisons between studies easier, and (iii) dermal absorption seems a possible exposure route and needs to be further investigated. The use of MDI, TDI, and HDI has been recently proposed to be restricted in the European Union unless specific conditions for workers’ training and risk management measures apply. This review has highlighted the need for a harmonized approach to establishing a baseline against which the success of the restriction can be evaluated.

show abstract

Section: Resultsmentioning

confidence: 99%

Biomonitoring for Occupational Exposure to Diisocyanates: A Systematic Review

Scholten

Kenny

Duca

et al. 2020

Annals of Work Exposures and Health

View full text Add to dashboard Cite

show abstract

“…However, the detectable limit of the immunoassay appeared to be confounded by non-specific human serum protein binding to solid phase IgM mAb 15D4 as reported values were outside the range of dNCO plasma concentrations reported in workers (8-hour shift). (28,34) Previous studies have reported non-specific binding of HSA and dNCO-HSA conjugates with serum immunoglobulins including IgE (35) and IgG. (36) Nonspecific binding of murine IgM to other human proteins and lipid antigens has also been reported.…”

Section: Discussionmentioning

confidence: 99%

A Murine Monoclonal Antibody with Broad Specificity for Occupationally Relevant Diisocyanates

Lemons¹,

Siegel²,

Mhike³

et al. 2013

Journal of Occupational and Environmental Hygiene

View full text Add to dashboard Cite

Diisocyanates (dNCOs) used in industrial applications are well known low molecular weight allergens. Occupational exposure is associated with adverse health outcomes including allergic sensitization and occupational asthma. In this study, we report the production and initial characterization of a dNCO-hapten specific murine IgM monoclonal antibody (mAb). Female BALB/c mice were immunized intraperitoneally with 25 µg of 4,4′-methylene diphenyl diisocyanate (MDI)-keyhole limpet hemocyanin. Following six biweekly booster immunizations, splenocytes were recovered and fused to Sp2/0-Ag14 murine myeloma cell line for hybridoma production. Hybridomas were then screened in a solid-phase indirect enzyme-linked immunosorbent assay (ELISA) against 40:1 4,4′-MDI– human serum albumin (HSA). mAb reactivity to dNCO-HSA conjugates and dNCO-HSA spiked human serum were characterized using a sandwich ELISA. One hybridoma produced a multimeric IgM mAb (15D4) that reacted with 4,4′-MDI-HSA. Sandwich ELISA analysis demonstrated comparable reactivity with other occupationally relevant dNCO-HSA adducts, including 2,4-toluene diisocyanate (TDI)-HSA, 2,6-TDI-HSA, and 1,6-hexamethylene diisocyanate (HDI)-HSA, but not other electrophilic chemical HSA conjugates. The limit of quantification (LOQ) of 4,4′-MDI-HSA, 2,4-TDI-HSA, 2,6-TDI-HSA, and 1,6-HDI-HSA sandwich ELISAs were 567.2, 172.7, 184.2, and 403.5 ng/mL (8.67, 2.60, 2.77, and 6.07 pmol/mL), respectively. In contrast, experiments using dNCO-supplemented human sera showed an increase in the detectable limit of the assay. A mAb has been produced that has potential utility for detecting mixed diisocyanate exposures in occupational environments. The mAb may have additional utility in the standardization of specific IgE detection immunoassays as well as chromatographic-mass spectrometric methods to enrich dNCO adducted HSA in the plasma of occupationally exposed workers.

show abstract

“…Exposure to MDI can be demonstrated by determining MDA in hydrolysed urine or hydrolysed protein (plasma, erythrocytes) Kääriä et al 2001;Schütze et al 1995;Sennbro et al 2006;Skarping et al 1994Skarping et al , 1995Skarping et al , 1996. Hydrolysis is necessary to dissolve the binding of MDI to biological materials, for example protein.…”

Section: Biological Monitoringmentioning

confidence: 99%

4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

2015

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

The article contains sections titled: Toxic Effects and Mode of Action Mechanism of Action Toxicokinetics and Metabolism Absorption, distribution, elimination Metabolism Binding to macromolecules/biological monitoring Effects in Humans Single exposures Repeated exposure Local effects on skin and mucous membranes Allergenic effects Reproductive and developmental toxicity Genotoxicity Carcinogenicity Animal Experiments and in vitro Studies Acute toxicity Subacute, subchronic and chronic toxicity Local effects on skin and mucous membranes Allergenic effects Reproductive toxicity Genotoxicity Carcinogenicity Manifesto (MAK value, classification)

show abstract

Biological monitoring of exposure to 1,5–naphthalene diisocyanate and 4,4’-methylenediphenyl diisocyanate

Cited by 21 publications

References 27 publications

Biomonitoring for Occupational Exposure to Diisocyanates: A Systematic Review

Biomonitoring for Occupational Exposure to Diisocyanates: A Systematic Review

A Murine Monoclonal Antibody with Broad Specificity for Occupationally Relevant Diisocyanates

4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

Contact Info

Product

Resources

About