Health and Toxicology Studies

Krieger S; Day B; Kuhl A; Spence M 
Suitability of the Direct Peptide Reactivity Assay (DPRA) for assessing chemical sensitization potential of aromatic polymeric polyisocyanate pre-polymer (P3) substances     
Poster presented at the 62nd Annual Meeting of the Society of Toxicology (SOT), Nashville, Tennessee, USA, 19-23 Mar., 2023


Plehiers PM
Letter to the editor regarding Tiwari and Raghavan, Indian J Occup Environ Med 2022;26:189-92
Indian J Occup Environ Med, 27, (2), 2023, 190-1


Plehiers PP; Skoglund R; Spence MW; Kiorpes AL
Toxicol Ind Health, Vol. 38, (9), 2022, 493-4


Plehiers PP; Skoglund R; Spence MW; Kiorpes AL
Concluding remarks
Toxicol Ind Health, Vol. 38, (9), 2022, 653-4


Chappelle AH
Letter to the editor concerning “Risk assessment for toluene diisocyanate and respiratory disease human studies”
Saf Health Work, Vol. 13, (1), 2022, 129-30


Spence MW; Plehiers PM
Letter to the editor concerning Gui et al. Inception cohort study of workers exposed to toluene diisocyanate at a polyurethane foam factory
Am J Ind Med, Vol. 64, (12), 2021, 1053-4


Spence MW; Plehiers PP
A brief overview of properties and reactions of diisocyanates
Toxicol Ind Health, Vol. 38, (9), 2022, 495-9


West RJ; Burleson S; Gulledge T; Miller JW; Chappelle AH; Krieger S; Graham C; Snyder S; Simon G; Plehiers PM
Exploring structure/property relationships to health and environmental hazards of polymeric polyisocyanate prepolymer substances-2. Dermal sensitization potential in the mouse local lymph node assay
Toxicol Ind Health, Vol. 38, (9), 2022, 556-77


Antoniou EE; Zeegers MP
The relationship between toluene diisocyanate exposure and respiratory health problems: a meta-analysis of epidemiological studies
Toxicol Ind Health, Vol. 38, (9), 2022, 595-605


Dekant W; Colnot T
Evaluation of animal toxicity studies with diisocyanates regarding presence of thresholds for induction and elicitation of respiratory allergy by quantitative weight of evidence
Toxicol Ind Health, Vol. 38, (9), 2022, 578-94


Schupp T; Plehiers PM
Absorption, distribution, metabolism, and excretion of methylene diphenyl diisocyanate and toluene diisocyanate: many similarities and few differences
Toxicol Ind Health, Vol. 38, (9), 2022, 500-28


Unterberger-Henig, E
Comparative evaluation of three methylene dianiline isomers in the bacterial reverse mutation assay, the in vitro gene mutation test, and the in vitro chromosomal aberration test
Toxicol Ind Health, Vol. 38, (9), 2022, 529-43


Bartels M; van Osdol W; Le Merdy M; Chappelle A; Kuhl A; West R
In silico predictions of absorption of MDI substances after dermal or inhalation exposures to support a category based read-across assessment
Regul Toxicol Pharmacol, 129, 2022, 105117


Ji Z; Koehler MW; Scott AB; LeBaron MJ
Assessment of cellular and molecular metrics for dose selection in an in vivo comet assay: a case study with MDI
Environ Mol Mutagen, Vol. 62, (8), 2021, 446-57


Wisnewski AV; Liu J; Nassar AF
LC-UV-MS and MS/MS characterize glutathione reactivity with different isomers (2,2’ and 2,4’ vs. 4,4’) of methylene diphenyl-diisocyanate
EC Pharmacol Toxicol, Vol. 7, (3), 2019, 205-19


Prueitt RL; Lynch HN; Mohar I; Goodman JE
Critical evaluation of threshold for respiratory effects of toluene diisocyanate
Poster presented at EUROTOX 2018: 54th Congress of the European Societies of Toxicology,  Brussels, Belgium, 2-5 Sep., 2018


Prueitt RL; Lynch HN; Zu K; Shi L; Goodman, JE
Dermal exposure to toluene diisocyanate and respiratory cancer risk
Environ.Int., Vol. 109, 2017, 181-92


American Chemistry Council (ACC) Diisocyanates Panel; Bernstein DI
A guide for the primary care physician in evaluating diisocyanate exposed workers
Infographic, 2017, 


Bernstein DI; Jolly A; Spence M
A guide for the primary care physician in evaluating diisocyanate exposed workers
Presentation, American College of Occupational and Environmental Medicine (ACOEM) American Occupational Health Conference (AOHC), Denver, Colorado, USA, 23-6 Apr., 2017


Goodman JE; Zu K; Loftus CT; Prueitt R
Dermal TDI exposure is not associated with lung cancer risk
Am.J.Ind.Med., Vol. 60, (2), 2017, 221-2


Prueitt R; Rhomberg LR; Guan N; Goodman JE; Xiaowei J
Evaluation of the carcinogenicity of toluene diisocyanate
Asian.J.Ecotoxicol., Vol. 11, (4), 2016, 26-60


Chappelle AH; Spence M; Tury B
Letter to the editor RE: Wolf et al. 
Crit.Rev.Toxicol., Vol. 46, (10), 2016, 911-2


Pauluhn J
Interrelationship of TDI- and HDI-induced respiratory tract irritation and allergy in rats
Poster, Society of Toxicology (SOT) 54th Annual Meeting & ToxExpo, San Diego, California, USA, 22-26 Mar., 2015


Guan N
A hypothesis-based weight-of-evidence approach to evaluate the human carcinogenicity of TDI
Presentation, International Summit on Health and Environmental Risk Assessment, the First Training Course on Regulatory Toxicology and Risk Assessment, Guangzhou, China, 11 Mar., 2015


Hughes MA; Carson M; Collins MA; Jolly AT; Molenaar DM; Steffens W; Swaen GM
Does diisocyanate exposure result in neurotoxicity?
Clin.Toxicol., Vol. 52, (4), 2014, 242-57


Luna LG; Green BJ; Zhang F; Arnold SM; Siegel PD; Bartels MJ
Quantitation of 4,4'-methylene diphenyl diisocyanate human serum albumin adducts
Toxicol.Rep., Vol. 1, 2014, 743-751


Luna LG; Markham DA; Bartels MJ; Brzak KA
Feasibility of biomonitoring methylene diphenyl diisocyanate adducted to lysine amino acids in rat urine
Poster, 62nd ASMS Conference on Mass Spectrometry and Allied Topics, Baltimore, Maryland, USA, 15-19 Jun., 2014


Pauluhn J.
Development of a respiratory sensitization/elicitation protocol of toluene diisocyanate (TDI) in Brown Norway rats to derive an elicitation-based occupational exposure level
Toxicol., Vol. 319, 2014, 10-22


Prueitt RL; Rhomberg LR; Goodman JE 
Hypothesis-based weight-of-evidence evaluation of the human carcinogenicity of toluene diisocyanate
Crit.Rev.Toxicol., Vol. 43, (5), 2013, 391-435


Poole A; Chappelle AH; Collins MA 
Mechanisms for the development of rat lung tumors following inhalation exposures to MDI 
Poster, Society of Toxicology 53 rd Annual  Meeting and ToxExpo, Phoenix, AZ, 23-27 March, 2014


Prueitt RL; Goodman JE; Rhomberg LR 
Hypothesis-based weight-of-evidence evaluation of the human carcinogenicity of toluene diisocyanate
Poster, Society of Toxicology 52 nd Annual Meeeting and ToxExpo, San Antonio, TX, 10-14 March, 2013


Luna LG; Green BJ; Zhang F; Siegel PD; Bartels MJ 
Enrichment and measurement of a signature MDI HSA peptide adduct
Poster, CIRPD Conference on Isocyanates and Health: Past, Present and Future, 3-4 April, 2013


Arnold SM; Collins MA; Graham C; Jolly AT; Parod RJ; Poole A; Schupp T; Shiotsuka RN; Woolhiser MR 
Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from polyurethane flexible foam
Reg.Toxicol.Pharmacol., Vol. 64, (3), Dec., 2012, 504-15


Sielken RL; Bretzlaff RS; Valdez-Flores C; Parod R
Statistical comparison of carcinogenic effects and dose-response relationships in rats and mice for 2,4-toluene diamine to those ascribed to toluene diisocyanate
Hum.Ecol.Risk Assess., Vol. 18, (6), Nov., 2012, 1315-37


Schupp T and Collins MA
Toluene diisocyanate (TDI) airway effects and dose-responses in different animal models
EXCLI J., Vol.11, 24 Jul., 2012, 416-35


Pauluhn J 
Interrelating the acute and chronic mode of action of inhaled methylenediphenyldiisocyanate (MDI) in rats assisted by computational toxicology.
Reg.Toxicol.Pharmacol., Vol. 61, 2011, 351-64


Pauluhn J and Poole A
Brown Norway rat asthma model of diphenylmethane-4,4'-diisocyanate (MD): determination of the elicitation threshold concentration of after inhalation sensitization
Toxicol., Vol. 281, 2011, 15-24


Hoffman HD; Leibold E; Ehnes C; Fabian E; Landsiedel R; Gamer A; Poole A
Dermal uptake and excretion of 14C-toluene diisocyanate (TDI) and 14C-methylene diphenyl diisocyanate (MDI) in male rats.
Clinical signs and histopathology following dermal exposure of male rats to TDI

Toxicol.Lett., Vol 199, 2010, 364-71


Pauluhn J
Brown Norway rat asthma model of diphenylmethane - 4,4'- diisocyanate (MDI): analysis of the elicitation dose-response relationship
Toxicol.Sci. Vol.104 (2) Aug, 2008, 320-31


Ott MG; Jolly AT; Burkert AL; Brown WE 
Issues in diisocyanate antibody testing 
Critical Reviews in Toxicology, Vol. 37, 2007, 567-585


Zeiger E and Woolhiser M
The genetic toxicity of diisocyanates in humans and laboratory animals
Poster presented at Society of Toxicology 46 th Annual Meeting, Charlotte , NC , 25-29 March 2007


Bernstein DI; Ott MG; Woolhiser M; Lummus Z; Graham C
Evaluation of antibody binding to diisocyanate protein conjugates in a general population
Ann. Allergy Asthma Immunol., Vol. 97, Sept., 2006, 357-64


Malo J-L; L’Archevéque J; Lummus Z; Bernstein D
Changes in specific IgE and IgG and monocyte chemoattractant protein-1 in workers with occupational asthma caused by diisocyanates and removed from exposure
J.Allergy Clin.Immunol., Vol. 118, (2), Aug., 2006, 530-3


Pauluhn J; Brown WE; Hext P; Leibold E; Leng G
Analysis of biomarkers in rats and dogs exposed to polymeric methylenediphenyl diisocyanate (pMDI) and its glutathione adduct 
Toxicology, Vol. 222, (3), 2006, 202-12


Bernstein DI; Ott MG; Koke M; Graham C; Woolhiser M; Lummus ZL
Diisocyanate antigen specific antibodies are detectable in a non-worker population without diisocyanate exposure
Poster presented at American Thoracic Society 100th International Conference, San Diego, 20-25 May, 2005


Gledhill A; Wake A; Hext P; Leibold E; Shiotsuka R
Absorption, distribution, metabolism and excretion of an inhalation dose of [14C] 4,4'-methylenediphenyl diisocyanate in the male rat
Xenobiotica, Vol.35, (3), Mar., 2005, 273-92


Pauluhn J
Concentration-dependence of stability of aerosols of monomeric diphenyl-methane-4,4'-diisocyanate (MDI) 
Poster presented at Society of Toxicology 44th Annual Meeting, New Orleans, 6-10 March, 2005


Pauluhn J; Woolhiser MR; Bloemen L
Repeated inhalation challenge with diphenylmethane-4,4’-diisocyanate in Brown Norway rats leads to time-related increase of neutrophils in bronchoalveolar lavage after topical induction 
Inhal.Toxicol., Vol.17, 2005, 67-78


Lee Y-M; Kim H-A; Park H-S; Lee S-K; Nahm D-H
Exposure to toluene diisocyanate (TDI) induces IL-8 production from bronchial epithelial cells: effect of pro-inflammatory cytokines
J.Kor.Med.Sci., Vol. 18, (6), Dec., 2003, 809-12


Lummus ZL; Park HS; Brown WE; Jolly AT; Biagini RE; Wanner MA; Lewis DM; Burkert AL; Daftarian H; Bernstein DI
Interlaboratory agreement of toluene diisocyanate (TDI)-specific serum antibody results are strongly influenced by antigen characteristics
J.Allergy Clin.Immunol., Vol.111, (2), Suppl., Feb., 2003, S193, Abs.501


Collins MA
Toxicology of toluene diisocyanate
Appl.Occup.Environ.Hyg., Vol.17, (12), Dec., 2002, 846-55


Kilgour JD; Rattray NJ; Foster J; Soames A; Hext PM
Pulmonary responses and recovery following single and repeated inhalation exposure of rats to polymeric methylene diphenyl diisocyanate aerosols
J.Appl.Toxicol., Vol.22, 2002, 371-85


Lemière C; Romeo P; Chaboillez S; Tremblay C; Malo J-L
Airway inflammation and functional changes after exposure to different concentrations of isocyanates
J.Allergy Clin.Immunol., Vol.110, (4), Oct., 2002, 641-6


Reisser M; Schmidt BF; Brown WE 
Synthesis, characterization, and solvolysis studies of mono- and bis-S-(glutathionyl) adducts of methylene-bis-phenylisocyanate (MDI)
Chem.Res.Toxicol., Vol.15, (10), 2002, 1235-41


Gledhill A; Wake A; Hext P; Leibold E; Shiotsuka R
Absorption, distribution, metabolism and excretion of an inhalation dose of [14C]-MDI in the male rat 
Poster presented at Eurotox 2002 Congr., Budapest, 15-18 Sept., 2002


Park H-S; Lee S-K; Kim H-Y; Nahm D-H; Kim S-S 
Specific immunoglobulin E and immunoglobulin G antibodies to toluene diisocyanate-human serum albumin conjugate: useful markers for predicting long-term prognosis in toluene diisocyanate-induced asthma
Clin.Exp.Allergy, Vol.32, (4), 2002, 551-5


Park H-S; Cho S-H; Hong C-S; Kim Y-Y
Isocyanate-induced occupational asthma in far-east Asia: pathogenesis to prognosis
Clin.Exp.Allergy, Vol.32, (2), 2002, 198-204


Nakashima K; Takeshita T; Morimoto K
Diagnosis and prevention of diseases induced by isocyanate
Environ.Health Prevent.Med., Vol.7, (2), 2002, 40-6


Bernstein DI; Cartier A; Côté J; Malo J-L; Boulet L-P; Wanner M; Milot J; L'Archevéque J; Trudeau C; Lummus Z
Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test efficiency than specific antibodies for identification of diisocyanate asthma
Amer.J.Respir.Crit.Care Med., Vol.166, 2002, 445-50


Feron VJ; Kittel B; Kuper CF; Ernst H; Rittinghausen S; Muhle H; Koch W; Gamer A; Mallett AK; Hoffmann HD
Chronic pulmonary effects of respirable methylene diphenyl diisocyanate (MDI) aerosol in rats: combination of findings from two bioassays
Arch.Toxicol., Vol. 75, (3), May, 2001, 159-75


Pauluhn J; Gollapudi B; Hammond T; Linscombe A, Thiel A; Zischka-Kuhbier D
Bone marrow micronucleus assay in Brown-Norway rats exposed to diphenyl-methane 4,4'-diisocyanate
Arch.Toxicol., Vol. 75, 2001, 234-42


Park H-S; Kim H-Y; Lee S-K; Kim S-S; Nahm D-H
Diverse profiles of specific IgE response to toluene diisocyanate (TDI)-human serum albumin conjugate in TDI-induced asthma patients
J.Kor.Med.Sci., Vol. 16, (1), Feb., 2001, 57-61


Gamer A; Hellwig J; Doe JE; Tyl RW
Prenatal toxicity of inhaled polymeric methylenediphenyl diisocyanate (MDI) aerosols in pregnant Wistar rats
Toxicol.Sci., Vol. 54, 2000, 431-40


Brown WE; Gamaluddin S; Kennedy AL
Antibody testing: analysis of the specificity of antibody detection in a non-diisocyanate-exposed population
Paper, Symposium on Isocyanates: Sampling, Analysis and Health Effects, Orlando, 26-27 Oct., 2000. ASTM STP 1408, Lesage J et al. eds.


Chappelle AH; Shiotsuka RN; Bartels MJ
Some limitations in the use of urine biomonitoring for measuring TDI exposure
Paper, Symposium on Isocyanates: Sampling, Analysis and Health Effects, Orlando, 26-27 Oct., 2000. ASTM STP 1408, Lesage J et al. eds.


Jolly A; Bramann D; Hoffarth H-P
Patch testing for isocyanates
Paper, Symposium on Isocyanates: Sampling, Analysis and Health Effects, Orlando, 26-27 Oct., 2000. ASTM STP 1408, Lesage J et al. eds.


Aul DJ; Bhaumik A; Kennedy AL; Brown WE; Lesage J; Malo J-L
Specific IgG response to monomeric and polymeric diphenylmethane diisocyanate conjugates in subjects with respiratory reactions to isocyanates
J.Allergy Clin.Immunol., Vol. 103, (5), Pt. 1, May, 1999, 749-55


Bernstein DI; Jolly A
Current diagnostic methods for diisocyanate induced occupational asthma
Amer.J.Ind.Med., Vol. 36, 1999, 459-68


Gamaluddin S; Kennedy AL; Malo J-L; Brown WE
Analysis of the specificity of antibody detection in relation to diisocyanate asthma
Toxicol.Sci., Vol. 48, (1-S), Mar., Suppl., 1999, Abstr. 1962


Pauluhn J; Dearman R; Doe J; Hext P; Landry TD
Respiratory hypersensitivity to diphenylmethane-4,4'-diisocyanate in guinea pigs: comparison with trimellitic anhydride
Inhal.Toxicol., Vol. 11, 1999, 187-214


Pauluhn J; Emura M; Mohr U; Popp A; Rosenbruch M
Two-week inhalation toxicity of polymeric diphenylmethane-4,4'-diisocyanate (PMDI) in rats: analysis of biochemical and morphological markers of early pulmonary response
Inhal.Toxicol., Vol. 11, 1999, 1143-63


Park H-S; Jung K-S; Kim H-Y; Nahm D-H; Kang K-R
Neutrophil activation following TDI bronchial challenges to the airway secretion from subjects with TDI-induced asthma
Clin.Exp.Allergy, Vol. 29, (10), 1999, 1395-401


Park H-S
New advances in the pathogenesis of isocyanate-induced occupational asthma
Med.Prog., May, 1999, 21-4


Tyl RW; Fisher LC; Dodd DE; Pritts IM; Kubena MF; Losco PE; Troup CM; Lyon JP; Landry TD
Developmental toxicity evaluation of inhaled toluene diisocyanate vapor in CD rats
Toxicol.Sci., Vol. 52, 1999, 248-57


Tyl RW; Neeper-Bradley TL; Fisher LC; Dodd DE; Pritts IM; Losco PE; Lyon JP; Landry TD
Two-generation reproductive toxicity study of inhaled toluene diisocyanate vapor in CD rats
Toxicol.Sci., Vol. 52, 1999, 258-68


Wester RC; Hui X; Landry T; Maibach HI
In vivo skin decontamination of methylene bisphenyl isocyanate (MDI): soap and water ineffective compared to propylene glycol, polyglycol-based cleanser, and corn oil
Toxicol.Sci., Vol. 48, 1999, 1-4


Desrosiers M; Nguyen B; Ghezzo H; Leblanc C; Malo JL
Nasal response in subjects undergoing challenges by inhaling occupational agents causing asthma through the nose and mouth
Allergy, Vol. 53, 1998, 840-8.


Vock EH; Vamvakas S; Gahlmann R; Lutz WK
Investigation of the induction of DNA double-strand breaks by methylenediphenyl-4,4'-diisocyanate in cultured human lung epithelial cells
Toxicol.Sci., Vol. 46, 1998, 83-9.


Vamvakas S; Vock EH; Lutz WK
On the role of DNA double-strand breaks in toxicity and carcinogenesis
Crit.Rev.Toxicol., Vol. 27, (2), 1997, 155-74.


Lemière C; Cartier A; Dolovich J; Chan-Yeung M; Grammer L; Ghezzo H; L'Archeveque L; Malo JL
Outcome of specific bronchial responsiveness to occupational agents after removal from exposure
Amer.J.Resp.Crit.Care Med., Vol. 154, 1996, 329-33.


Doe JE; Hoffmann HD
Toluene diisocyanate: an assessment of carcinogenic risk following oral and inhalation exposure
Toxicol.Ind.Health, Vol. 11, (1), 1995, 13-32


Kennedy AL; Lastbom L; Skarping G; Dalene M; Ryrfeldt A; Moldeus P; Brown WE
Analysis of the reactivity of [14-C]toluene diisocyanate (TDI) in an isolated, perfused lung model
Chemico-Biol.Interac., Vol. 98, 1995, 167-83.


Kennedy AL; Wilson TR; Stock MF; Alarie Y; Brown WE
Distribution and reactivity of inhaled 14C-labeled toluene diisocyanate (TDI) in rats
Arch.Toxicol., Vol. 68, (7), 1994, 434-43.


Reuzel PGJ; Kuper CF; Feron VJ; Appelman LM; Löser E
Acute, subacute and subchronic inhalation toxicity studies of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats
Fund.Appl.Toxicol., Vol. 22, 1994, 186-94.


Reuzel PGJ; Arts JHE; Lomax LG; Kuijpers MHM; Kuper CF; Gembardt C; Feron VJ; Löser E
Chronic inhalation toxicity and carcinogenicity study of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats
Fund.Appl.Toxicol., Vol. 22, 1994, 195-210.


Kennedy AL; Stock MF; Alarie Y; Brown WE
Uptake and distribution of 14C during and following inhalation exposure to radioactive toluene diisocyanate
Toxicol.Appl.Pharmacol., Vol. 100, 1989, 280-92.


Ader AW; Carney IF; Loeser E
Risk evaluation of chronic exposure to toluene diisocyanate based on long-term animal studies
SPI/FSK Polyurethanes World Congress, Aachen, 29 Sept. -2 Oct., 1987, 188-92.


Thorne PS; Hillebrand JA; Lewis GR; Karol MH
Contact sensitivity by diisocyanates: potencies and cross-reactivities
Toxicol.Appl.Pharmacol., Vol. 87, 1987, 155-65.


Karol MH
Hypersensitivity to isocyanates
In, Dean J et al., eds. Immunotoxicology and Immunopharmacology, Raven Press, 1985, 475-488.


Rampy LW; Loeser E; Lyon JP; Carney I
Two carcinogenicity studies of toluene diisocyanate
Proc. SPI 6th Int.Tech./Marketing Conf., San Diego, California, 2-4 Nov., 1983, 413-415.


Loeser E
Long-term toxicity and carcinogenicity studies with 2,4/2,6-toluene-diisocyanate (80/20) in rats and mice
Toxicol.Letters, Vol. 15, 1983, 71-81


O'Brien IM; Harries MG; Burge PS; Pepys J 
Toluene di-isocyanate-induced asthma. I. Reactions to TDI, MDI, HDI and histamine 
Clin.Allergy, Vol. 9, 1979, 1-6.


O'Brien IM; Newman-Taylor AJ; Burge PS; Harries MG; Fawcett IW; Pepys J
TDI-induced asthma. II. Inhalation challenge tests and bronchial reactivity studies
Clin.Allergy, Vol. 9, 1979, 7-15.