Jobs in many modern settings, including manufacturing, service, agriculture and construction, are variable in their content and timing. This prompts the need for exposure assessment methods that do not assume regular work cycles. A scheme is presented for classifying levels of routinization to inform development of an appropriate exposure assessment strategy for a given occupational setting. Five levels of routinization have been defined based on the tasks of which the job is composed: 1) a single scheduled task with a regular work cycle; 2) multiple cyclical tasks; 3) a mix of cyclical and non-cyclical tasks; 4) one non-cyclical task; 5) multiple non-cyclical tasks. This classification, based primarily on job observation, is illustrated through data from a study of automobile manufacturing workers (n = 1200), from which self-assessed exposures to physical and psychosocial stressors were also obtained. In this cohort, decision latitude was greater with higher routinization level (p < 0.0001), and the least routinized jobs showed the lowest self-reported exposure to physical ergonomic stressors. The job analysis checklist developed for non-routinized jobs is presented, and limitations of the task analysis method utilized in the study are discussed. A work sampling approach to job analysis is recommended as the most efficient way to obtain a comparable unbiased exposure estimate across all routinization levels.

This study examined the agreement of subjective ratings of upper extremity exposures with corresponding direct measurements obtained simultaneously from workers. Psychophysical ratings of exposure, based on the Borg CR-10 scale, were obtained for the period of time in which direct measurements were acquired using electrogoniometers (wrist), electroinclinometers (shoulder) and electromyography (grip force). Subjects were selected from workers at two automobile manufacturing plants. Significant relationships between subjective ratings of wrist position and measured wrist posture or motion and between ratings of shoulder position and measured shoulder posture were not found. Ratings of manual effort were significantly correlated with directly measured grip force (% maximum voluntary contraction). Ratings of pace were significantly correlated with directly measured wrist motion and this relationship was strengthened with the addition of relative grip force as a covariate. Workers with hand/wrist symptoms provided ratings that were more strongly related to the directly measured exposures than those without symptoms. Self-report by workers is an alternative to more resource-intensive and invasive exposure assessment methods. However, the validity of workers' self-reported exposure assessments has been questioned. The objective of this study was to examine the agreement of selected questionnaire items with corresponding direct measurements from bioinstrumentation and to provide a better understanding of worker self-reports.

No abstract

Ticlopidine is a first-generation thienopyridine antiplatelet drug that prevents adenosine 59-diphosphate (ADP)-induced platelet aggregation. We identified the enzymes responsible for the two-step metabolic bioactivation of ticlopidine in human liver microsomes and plasma. Formation of 2-oxo-ticlopidine, an intermediate metabolite, was NADPH dependent and cytochrome P450 (CYP) 1A2, 2B6, 2C19, and 2D6 were involved in this reaction. Conversion of 2-oxo-ticlopidine to thiol metabolites was observed in both microsomes (M1 and M2) and plasma (M1). These two metabolites were considered as isomers, and mass spectral analysis suggested that M2 was a thiol metabolite bearing an exocyclic double bond, whereas M1 was an isomer in which the double bond was migrated to an endocyclic position in the piperidine ring. The conversion of 2-oxo-ticlopidine to M1 in plasma was significantly increased by the addition of 1 mM CaCl 2 . In contrast, the activity in microsomes was not changed in the presence of CaCl 2 . M1 formation in plasma was inhibited by EDTA but not by other esterase inhibitors, whereas this activity in microsomes was substantially inhibited by carboxylesterase (CES) inhibitors such as bis-(p-nitrophenyl)phosphate (BNPP), diisopropylphosphorofluoride (DFP), and clopidogrel. The conversion of 2-oxo-ticlopidine to M1 was further confirmed with recombinant paraoxonase 1 (PON1) and CES1. However, M2 was detected only in NADPHdependent microsomal incubation, and multiple CYP isoforms were involved in M2 formation with highest contribution of CYP2B6. In vitro platelet aggregation assay demonstrated that M2 was pharmacologically active. These results collectively indicated that the formation of M2 was mediated by CYP isoforms whereas M1, an isomer of M2, was generated either by human PON1 in plasma or by CES1 in the human liver.

No abstract