On October 14, 1997, the National Institute for Occupational Safety and Health (NIOSH) received a Health Hazard Evaluation (HHE) request from the Union of Needle trades, Industrial and Textile Employees (UNITE!) Local 1871 on behalf of employees at the Woodbridge Corporation in Brodhead, Wisconsin. The request indicated that five Woodbridge employees had been diagnosed with cancer over the last four years, and employees were concerned that these cancers might be caused by workplace exposures at Woodbridge Corporation, namely exposure to toluene diisocyanate (TDI), the primary chemical constituent used to make the flexible foam used for automotive seat cushions. The HHE requestor later noted that 83 employees had recently completed a health and safety survey, and various health symptoms were reported which were consistent with exposure to diisocyanates. On November 19 - 20, 1998, NIOSH investigators conducted an initial site visit, which included an opening conference, employee interviews, interviews with Woodbridge health and safety personnel, medical records review, and a walk-through inspection of the Woodbridge foam-production facility. During March 3 - 5, 1999, NIOSH investigators returned to the Woodbridge facility to conduct environmental air sampling for hydrocarbon solvents (naphthas). Based on the findings from the first two site visits, NIOSH investigators conducted a combined medical and industrial hygiene study at the plant during the week of May 24, 1999, which was designed to evaluate employees' exposures to TDI, and to determine the relationship between TDI exposure and the prevalence of occupational asthma, airway hyper responsiveness, allergic sensitization to TDI, and diisocyanate-related allergic contact dermatitis. NIOSH investigators also conducted an evaluation of the five reported cancers. One hundred fourteen (39%) of the 290 Woodbridge employees completed medical questionnaires, 100 provided blood samples for measuring TDI-specific antibodies, 65 provided serial peak flow records for assessing airway hyper responsiveness, and 26 participated in skin patch testing to assess allergic contact dermatitis. Asthma and work-related asthma were defined from questionnaire responses using standard epidemiologic definitions; cases defined in this way may not meet standard clinical definitions of asthma. Twenty-two percent (25/114) of the participants met the case definition for asthma, and 18% (20/114) met the case definition for work-related asthma. Production work [prevalence rate ratio (PRR)=3.40; 95% confidence interval (CI)= 0.92-39.52] and ever working with TDI (PRR=2.31; 95% CI 0.34-123.20) were both associated with asthma. Production work (PRR=2.66; 95% CI=0.65-29.16) and ever working with TDI (PRR=1.83; 95% CI 0.25-92.75) were also associated with work-related asthma. However, these associations were not statistically significant (p<0.05). Of the 59 peak flow participants whose peak flow records were suitable for analysis, 25 (42%) met the definition for airway hyper responsiveness. Of the 25, 8 had a work-related pattern, 5 had a non-work related pattern, and no pattern could be discerned for the remaining 12. Eighty-two (72%) of participants met the case definition for work-related mucous membrane (nose and eye) irritation symptoms. Production line work (PRR=1.57; 95% CI 1.05-10.05) and ever working with TDI (PRR=1.88; 95% CI 0.97-23.08) were associated with mucous membrane symptoms (p<0.05). Antibody test and skin patch testing results did not show an immune response to TDI, or the presence of TDI related allergic contact dermatitis. Of the 100 individuals providing blood for antibody testing, two had an elevated TDI-specific immunoglobulin class G (IgG) antibody level, and none had an elevated TDI-specific immunoglobulin class E (IgE) antibody level. Of the 26 individuals participating in skin patch testing, none developed skin reactions to any of the test allergens either 48 or 96 hours after patch test application. Personal breathing zone (PBZ) air samples were calculated for each worker participating in the medical evaluation. Additionally, PBZ samples were obtained for a random sample of workers who did not participate in the medical evaluation. TDI area air sampling was also conducted. Workers who participated were also asked to provide an end-of-shift urine sample, which was analyzed for a metabolite of TDI exposure, toluene diamine (TDA). The highest TDI (2,4-, 2,6- and total TDI) exposures were found among production line workers. Demold workers had the highest mean total TDI exposures (2.75 micrograms per cubic meter [microg/m3]), followed by insert workers (2.37 microg/m3), mechanics (1.49 microg/m3), and utility (1.40 microg/m3) workers. However, TDI concentrations for all PBZ and area samples were below the current American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) of 36 microg/m3. A sample stability problem arose when TDI air samples collected in May 1999 underwent storage for a 3-month period; a 12-14% decline in TDI concentration between analysis in September and October 1999 was identified in these samples. However, reanalysis of the samples did not support a continuous sample stability problem, and only minor concentration declines were identified between the initial and subsequent TDI analyses. Analysis of urine TDA concentrations in workers demonstrated that production line workers (primarily demold and insert workers) had the highest TDA levels; creatinine-corrected mean urine total TDA levels among demold workers and insert workers were 1.77 micrograms per liter (microg/l) and 1.74 microg/l, respectively. Statistically significant correlations were found between total TDI exposure and both uncorrected (r=0.30, p=0.007) and creatinine-corrected (r=0.35, p=0.002) urine 2,4-TDA levels. PBZ and area air samples were collected for formaldehyde on May 22, 1999, (during the cold blast mold cleaning operation) and on May 24, 1999, (during typical operation). PBZ and area samples were also collected for hydrocarbon solvents (naphthas), as well as for bis (2-dimethylaminoethyl) ether (DMAEE) on March 4, 1999, and May 24, 1999, respectively. All concentrations of formaldehyde and hydrocarbon solvents (naphthas) were below applicable exposure limits. One of 8 PBZ DMAEE concentrations exceeded the ACGIH TLV of 0.33 mg/m3. Although airborne exposures to TDI were below recommended exposure limits, respiratory, mucous membrane, and skin problems were noted in this worker population and these symptoms were associated with indicators of TDI exposure. The strength of this association, however, was limited by the low participation rate of the study. Insert and demold workers had higher environmental TDI exposure levels compared with offline workers and non-production personnel, and subsequently demonstrated higher urine TDA levels. Exposures to formaldehyde and hydrocarbon solvents were also below the applicable exposure criteria. DMAEE was measured in excess of the TLV in one PBZ sample. The reported cancers among Woodbridge employees are not consistent with a work-related etiology, due to the variety of cancers noted, the limited carcinogenic potential of the compounds identified, and the low exposure levels measured for each compound. Recommendation include following proper medical surveillance procedures for employees exposed to TDI, improving ventilation, improving the availability and usage of personal protective equipment, and following existing health and safety guidelines.