"Objective:The aim of this study was to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for the threshold number of years of alternating shift work associated with a relative increase in serum total cholesterol level (T-Cho), as an index of lipid metabolism.Methods: We conducted a 14-year prospective cohort study among male workers (N=6886) at a Japanese steel company who had received annual health check-ups between 1991 and 2005. The endpoints were either a 20, 25, 30, 35, 40 or 45% increase in T-Cho levels during the observation period, compared to T-Cho at baseline. We investigated the associations between the years of alternating shift work and the relative increases in T-Cho using pooled logistic regression, adjusted for other potential covariates. Results: We estimated the BMDL and BMD for years of alternating shift work among 40-, 50-, or >50-year old subjects using benchmark responses (BMR) of 5 or 10% and parameters for the duration of alternating shift work and other covariates. Assuming a mean age of 44 years among workers in their 40s, the BMDL/BMD for years of alternating shift work with a BMR of 5% were 21.0/28.0 (=20%), 21.3/26.1 (=25%), 24.1/28.8 (=30%), 25.6/29.8 (=35%), 27.1/31.5 (=40%), and 27.7/32.1 (=45%).Conclusions:The threshold number of years of alternating shift work that caused a 5% increase in T-Cho was shown to be =21 years among middle-aged workers. Special attention should be paid to influence the process at an earlier stage and not when the risk has already materialized."

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