On December 13, 1999, the National Institute for Occupational Safety and Health (NIOSH) received a request for Technical Assistance (TA) from the Massachusetts Department of Public Health, Occupational Health Surveillance Program (OHSP). OHSP asked NIOSH to conduct a health hazard evaluation (HHE) at ChemDesign Corporation in Fitchburg, Massachusetts, to investigate a cluster of eight occupational asthma cases which had been reported to OHSP. The chemicals associated with the cases were identified as AMT (3-amino-5-mercapto-1,2,4-triazole) and DE-498 (Flumetsulam). AMT was raw material used in the production of DE-498 and AMT-based product two (AMTBP2). In response to the request, NIOSH investigators, accompanied by an OHSP industrial hygienist, conducted an initial site visit to ChemDesign on February 1-3, 2000. The NIOSH industrial hygienist returned on June 5-9 to conduct air sampling at four routine operations where employees could be exposed to AMT or DE-498: (1) charging AMT powder into a reactor vessel, (2) discharging DE-498 "wet cake" from a centrifuge, (3) charging DE-498 into the dryer, and (4) discharging DE-498 from the dryer. On July 6-7, the NIOSH Project Officer and medical team visited ChemDesign to recruit workers for participation in a medical survey. On June 12-16, the team conducted a medical evaluation of volunteer production workers. The onsite medical evaluation consisted of a questionnaire interview, lung function testing, and a blood sample collection. A methacholine challenge test was administered at Burbank Hospital in Fitchburg, Massachusetts. In August 2000, NIOSH obtained copies of company medical records for the workers who signed a medical records release form. Environmental monitoring found quantifiable concentrations of AMT or DE-498 in personal breathing zone (PBZ) air samples during tasks where these materials were manually added to or discharged from the closed system in Building 16. The greatest potential for exposure to these materials existed during these specific tasks. Although use of respiratory protection and other personal protective equipment (PPE) appeared to provide substantial protection, reports of upper respiratory symptoms by several employees with occupational asthma (OA) indicate that PPE may not provide adequate protection for these individuals. Visible airborne dust during AMT and dryer charges, indicates a need for improved engineering controls (local exhaust ventilation) to reduce the potential for worker exposures. AMT and DE-498 in area air samples collected at the boundaries of restricted areas established during reactor and dryer charging, ranged from below the limit of detection to barely quantifiable levels. Changes in work practices, PPE, and engineering controls during the various production campaigns preclude assessment of the nature and extent of previous exposures to AMT and DE-498. A total of 41 employees and four former employees participated in the medical survey; the participation rate was 41% in production workers with a potential for AMT exposure. The medical survey identified 12 cases of physician-diagnosed asthma that were diagnosed after the cases started working at ChemDesign. In 11 of these, the onset corresponded with periods when AMT was used in the company. The physician's diagnosis of OA was mostly made on the basis of the presence of nonspecific bronchial hyperreactivity (NSBH), work-related respiratory symptoms, and in some cases work-related serial peak flow changes. The NSBH occurred after a latency period; allergy to common allergens was not a risk factor for the development of OA in these cases. Laboratory studies were undertaken to assess whether the respiratory symptoms observed in ChemDesign workers could be due to an allergic response to AMT and DE-498. Studies done on human blood of employees exposed to AMT were not able to clearly demonstrate that AMT or DE-498 exposures were associated with an allergic response to those agents. However, animal studies clearly show that AMT, but not DE-498, is capable of causing an allergic response. The results from the animal studies support the original complaints that AMT caused occupational asthma. However, the possible role of DE-498 cannot be excluded from negative animal studies. A large percentage of employees reported respiratory symptoms that started during 1998, when two new campaigns using AMT were started in ChemDesign. However, apart from AMT, other agents were reported as causing or making the respiratory symptoms worse. Chronic lung function effects were also found. A high percentage of the participants (18%) had mild airflow obstruction according to the American Thoracic Society (ATS) criteria. The cross-sectional analysis of the lung function measurements done by NIOSH showed significant decrease in Forced Expiratory Volume in one second (FEV1) and in the ratio of FEV1 and Forced Vital Capacity (FVC), FEV1/FVC: this pattern is suggestive of airway obstruction. The data analysis of company yearly lung function data confirmed that the study participants had a higher mean decline in FEV1 and FEV1/FVC with age, than would be expected from the reference equations. In summary, the results of the medical and laboratory investigation provide evidence that the incidence of OA was associated with exposure to AMT. There was an association between AMT exposure and asthma onset, NSBH associated with AMT exposure improved after withdrawal from AMT exposure, and AMT was found to be a sensitizer in animal studies. The findings show that ChemDesign employees are exposed to agents that can lead to occupational asthma and steeper decline in lung function with age than would be expected. Respiratory symptoms and lung function monitoring currently done at ChemDesign provide an opportunity to utilize the data for the protection of employees' respiratory health. Active workers' participation in the respiratory health protection program should be encouraged. Investigators examined changes in yearly thyroid hormone (T4) measurements in relation to working on the AMT campaigns. The possibility that AMT was associated with the decrease in thyroid hormone production could not be ruled out because of insufficient data. The investigation provides strong evidence that AMT (3-Amino-5-mercapto-1,2,4-triazole) was the causal agent responsible for the cluster of occupational asthma that occurred in ChemDesign. AMT has a potential for causing allergic response in experimental animals. Environmental monitoring found quantifiable concentrations of AMT in personal breathing zone air samples collected during routine production. Study participants had a high frequency of work-related respiratory symptoms whose onset corresponded with the use of AMT. The group of study participants had decreased mean pulmonary function values suggestive of airflow obstruction, identified from cross-sectional and longitudinal data. The findings of this study show that ChemDesign employees are exposed to chemical agents that can lead to occupational asthma and to COPD. Therefore effective exposure controls and a pulmonary function monitoring program need to be implemented and maintained to prevent further occurrence of respiratory disease in the employees.