Caroline H Hemmingsen

Air force ground crew personnel are potentially exposed to fuels and lubricants, as raw materials, vapours and combustion exhaust emissions, during operation and maintenance of aircrafts. This study investigated exposure levels and biomarkers of effects for employees at a Danish air force military base. We enrolled self-reported healthy and non-smoking employees (n = 79) and grouped them by exposure based on job function, considered to be potentially exposed (aircraft engineers, crew chiefs, fuel operators and munition specialists) or as reference group with minimal occupational exposure (avionics and office workers). We measured exposure levels to polycyclic aromatic hydrocarbons (PAHs) and organophosphate esters (OPEs) by silicone bands and skin wipes (PAHs only) as well as urinary excretion of PAH metabolites (OH-PAHs). Additionally, we assessed exposure levels of ultrafine particles (UFPs) in the breathing zone for specific job functions. As biomarkers of effect, we assessed lung function, plasma levels of acute phase inflammatory markers, and genetic damage levels in peripheral blood cells. Exposure levels of total PAHs, OPEs and OH-PAHs did not differ between exposure groups or job functions, with low correlations between PAHs in different matrices. Among the measured job functions, the UFP levels were higher for the crew chiefs. The exposure level of the PAH fluorene was significantly higher for the exposed group than the reference group (15.9 ± 23.7 ng/g per 24 h vs 5.28 ± 7.87 ng/g per 24 h, p = 0.007), as was the OPE triphenyl phosphate (305 ± 606 vs 19.7 ± 33.8 ng/g per 24 h, p = 0.011). The OPE tris(1,3-dichlor-2-propyl)phosphate had a higher mean in the exposed group (60.7 ± 135 ng/g per 24 h) compared to the reference group (8.89 ± 15.7 ng/g per 24 h) but did not reach significance. No evidence of effects for biomarkers of systemic inflammation, genetic damage or lung function was found. Overall, our biomonitoring study show limited evidence of occupational exposure of air force ground crew personnel to UFPs, PAHs and OPEs. Furthermore, the OH-PAHs and the assessed biomarkers of early biological effects did not differ between exposed and reference groups.

BACKGROUND: Studies have suggested increased risks of childhood leukaemia after prenatal exposure to antibiotics, particularly nitrofurantoin. However, these findings may be related to the underlying maternal infection. This multinational study aimed to investigate the association between prenatal nitrofurantoin exposure and childhood leukaemia while accounting for maternal infection. METHODS: In a population-based cohort study of children born in Denmark, Finland, Norway or Sweden from 1997 to 2013, prenatal exposure to nitrofurantoin or pivmecillinam (active comparator) was ascertained from national Prescription Registries. Childhood leukaemia was identified by linkage to national Cancer Registries. Poisson regression was used to estimate incidence rate ratios (IRRs) and incidence rate differences (IRDs) with inverse probability of treatment weights applied to account for confounding. RESULTS: We included 44 091 children prenatally exposed to nitrofurantoin and 247 306 children prenatally exposed to pivmecillinam. The children were followed for 9.3 years on average (standard deviation 4.1). There were 161 cases of childhood leukaemia. The weighted IRR for prenatal nitrofurantoin exposure when compared with pivmecillinam was 1.34 (95% confidence interval 0.88, 2.06), corresponding to an IRD of 15 per million person-years. Higher point estimates were seen for first- and third-trimester exposure. There was no evidence of a dose-response relationship. CONCLUSIONS: Prenatal exposure to nitrofurantoin was not substantially associated with childhood leukaemia, although a slightly elevated IRR with confidence intervals including the null was observed, corresponding to a small absolute risk. The lack of a dose-response relationship and a clear biological mechanism to explain the findings suggests against a causal association.

Cancer is an important cause of childhood mortality, yet the etiology is largely unknown. A combination of pre- and postnatal factors is thought to be implicated, including maternal medication use. We aimed to provide: 1) a systematic review of peer-reviewed publications on associations between maternal medication use and childhood cancer, with a focus on study design and methodology; and 2) suggestions for how to increase transparency, limit potential biases, and improve comparability in studies on maternal medication use and childhood cancer. We conducted a systematic search in the PubMed, Embase, Scopus, Cochrane, and Web of Science databases to June 8, 2020. Altogether, 112 studies were identified. The reviewed studies were heterogeneous in study design, exposure, and outcome classification. In 21 studies (19%), the outcome was any childhood cancer. Of the 91 papers that reported on specific types of cancer, 62% did not report the cancer classification system. The most frequently investigated medication groups were sex hormones (46 studies, excluding fertility medications), and antiinfectives (37 studies). Suggestions for strengthening future pharmacoepidemiologic studies on maternal medication use and childhood cancer relate to choice of cancer classification system, exposure windows, and methods for identification of, and control for, potential confounders.