Perspectives on the relevance of the circadian time structure to workplace threshold limit values and employee biological monitoring

Abstract

The circadian time structure (CTS) and its disruption by rotating and nightshift schedules relative to work performance, accident risk, and health/wellbeing have long been areas of occupational medicine research. Yet, there has been little exploration of the relevance of the CTS to setting short-term, time-weighted, and ceiling threshold limit values (TLVs); conducting employee biological monitoring (BM); and establishing normative reference biological exposure indices (BEIs). Numerous publications during the past six decades document the CTS substantially affects the disposition - absorption, distribution, metabolism, and elimination - and effects of medications. Additionally, laboratory animal and human studies verify the tolerance to chemical, biological (contagious), and physical agents can differ extensively according to the circadian time of exposure. Because of slow and usually incomplete CTS adjustment by rotating and permanent nightshift workers, occupational chemical and other contaminant encounters occur during a different circadian stage than for dayshift workers. Thus, the intended protection of some TLVs when working the nightshift compared to dayshift might be insufficient, especially in high-risk settings. The CTS is germane to employee BM in that large-amplitude predictable-in-time 24h variation can occur in the concentration of urine, blood, and saliva of monitored chemical contaminants and their metabolites plus biomarkers indicative of adverse xenobiotic exposure. The concept of biological time-qualified (for rhythms) reference values, currently of interest to clinical laboratory pathology practice, is seemingly applicable to industrial medicine as circadian time and workshift-specific BEIs to improve surveillance of night workers, in particular. Furthermore, BM as serial assessments performed frequently both during and off work, exemplified by employee self-measurement of lung function using a small portable peak expiratory flow meter, can easily identify intolerance before induction of pathology.

Does the compromised sleep and circadian disruption of night and shiftworkers make them highly vulnerable to 2019 coronavirus disease (COVID-19)?

“…It is well known that the circadian time structure substantially affects the pharmacokineticsabsortion, distribution, metabolism, and eliminationas well as the pharmacodynamics of medications according to the biological time of their administration (Smolensky et al 2017). In the same way, the handling of and tolerance to chemical, physical, and biological agents, including infectious ones, can differ, often markedly, according to the circadian time of exposure (Smolensky et al 2017).…”

“…It is well known that the circadian time structure substantially affects the pharmacokineticsabsortion, distribution, metabolism, and eliminationas well as the pharmacodynamics of medications according to the biological time of their administration (Smolensky et al 2017). In the same way, the handling of and tolerance to chemical, physical, and biological agents, including infectious ones, can differ, often markedly, according to the circadian time of exposure (Smolensky et al 2017). This can be explained by the staging of the circadian system, alone or in combination with the immune system, that based on past evolutionary determinants anticipate environmental challenges and additionally facilitate beneficial adjustment to changes associated with the pro-inflammatory state during nighttime sleep and anti-inflammatory state during daytime activity (Moldofsky 1995).…”

Working Time Society consensus statements: Circadian time structure impacts vulnerability to xenobiotics—relevance to industrial toxicology and nonstandard work schedules

“…The American Conference of Governmental Industrial Hygienists defines a TLV as the level of a chemical, physical, or biological agent to which nearly all workers may be repeatedly exposed, day after day, without adverse health effects. Three types of TLVs regulate industrial exposures–time-weighted average ones applicable to typical 8 h/d, 40 h/wk exposures; short-term exposure limit ones applicable to brief (≤15 min) encounters of ≤4 times/d with ≥60 min between each; and ceiling limit, i.e., maximum allowed exposures ones—and industrial hygienists or other trained specialists are responsible for ensuring compliance24 ) . A major theoretical construct underlying TLVs is homeostasis, i.e., the unsubstantiated assumption of constancy of biological functions and processes, implying the time or shift during the 24 h when workplace contaminants are experienced is inconsequential.…”

Variations in exposure to carcinogens among shift workers and non‐shift workers

“…Being exposed to other carcinogens in addition to shift work might place these workers at greater risk of developing cancer. For instance, being exposed to hazardous workplace substances when circadian rhythms are disturbed as a result of shift work may have greater toxicity effects and lower rates of clearance compared to when exposure occurs during undisturbed circadian rhythms Thus, it is important to know whether shift workers are more likely to be exposed to carcinogens at work compared to non‐shift workers.…”