We appreciate Lavigne-Robichaud et al`s critical remarks (1) to our systematic review addressing the epidemiological evidence for causal relations between job strain and the risk of ischemic heart disease (IHD) (2). Their main concern relates to the strength of the hypothesized association between job strain and IHD and, by extension, the magnitude of the population attributable fraction. They argue that our overall conclusion places too much emphasis on biases that inflate risk estimates and underrates biases that attenuate estimates towards the null. However, we believe it is premature to discuss in detail the strength of associations before a causal link is established with reasonable confidence. The main objective of our review was to evaluate the epidemiological evidence that observed associations are indeed causal. We concluded that the current evidence neither substantiates nor excludes a causal association for several reasons, including, but not limited to, the presence of inflating or deflating biases (2). That said, we appreciate the opportunity to discuss the sources of bias raised by Lavigne-Robichaud et al (1). First, it is argued that dichotomizing exposure into "high" and "no-high" job strain deflates risk estimates because a subgroup of the no-high job strain group (passive jobs with low demands and low control) might also be associated with increased risk. However, others have found that results are broadly similar when different non-strain groups are used as reference (3). Thus, at present, the evidence for effects of passive jobs is not strong enough to deviate from the parsimonious use of "all others" as reference. Second, the notion that the pooled risk estimate may be attenuated by sex because women develop IHD at older ages than men is supported by our review indicating slightly lower risk estimates among women. However, the confidence intervals substantially overlap [(2), table 4] and the small difference, if valid, may be due to several other factors and thus considered of minor importance. Third, the use of job-exposure matrices (JEM) is not associated with attenuated risk estimates if the average exposure in the job groups is close to the true average (4). This condition is probably violated in most instances and may lead to attenuated risk estimates if the exposure misclassification is non-differential. However, misclassification may depend on potential confounders (eg, sex, socioeconomic status and psychosocial and lifestyle factors) in ways that inflate or deflate risk estimates. Note also that the JEM studies do not provide the independent assessment of exposure that is needed for stronger conclusions to be drawn. This is because most studies are based on JEM established by population-based questionnaire studies. We consider the lack of independent exposure assessment a major obstacle for causal inference. Fourth, we agree that the prospective cohort study design in principle eliminates recall bias caused by later occurring manifest disease. But it is not obvious that subclinical or early stages of the disease cannot confound the association, potentially leading to inflated risk estimates even in prospective studies (3). Fifth, self-reported psychosocial work exposures are inherently vulnerable to respondents` individual interpretations, particularly when they are asked to rate the intensity or frequency of subjective experiences. We acknowledge the references provided by Lavigne-Robichaud et al, but these studies do not rule out potential confounding by personality (5, 6). The influence of social context, attitudes, life experiences and personality traits remains unresolved and likely constitute bias regardless of study design (7). We are aware that our review may be misused to discourage sound efforts to improve the psychosocial work environment. While this unfortunate risk is inherent to all critical appraisals of the literature, we believe it remains incumbent on researchers to provide the most evidence-based assessments possible so that we can collectively endeavor to improve science. References 1. Lavigne-Robichaud M, Landsbergis P, Brisson C, Sembajwe G, Gilbert-Ouimet M, Li J, Milot A, Trudel X. Job strain and ischemic heart disease: the balance of methodological bias and implications for prevention. Response to: Bonde JP et al. The demands-control-support work stress model and risk of ischemic heart disease: causal inference based on observational epidemiology. Scand J Work Environ Health. 2026;52(5):625-626. https://doi.org/10.5271/sjweh.4315. 2. Bonde JP, Skaaby S, Flachs EM, Dollard M, Keyes K, Rosengren A et al. The demands-control-support work stress model and risk of ischemic heart disease: causal inference based on observational epidemiology. Scand J Work Environ Health 2026 Jul;52(4):360-70. https://doi.org/10.5271/sjweh.4299. 3. Kivimäki M, Nyberg ST, Batty GD, Fransson EI, Heikkilä K, Alfredsson L et al.; IPD-Work Consortium. Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data. Lancet 2012 Oct;380(9852):1491-7. https://doi.org/10.1016/S0140-6736(12)60994-5. 4. Armstrong BG. Effect of measurement error on epidemiological studies of environmental and occupational exposures. Occup Environ Med 1998 Oct;55(10):651-6. https://doi.org/10.1136/oem.55.10.651. 5. Spector PE, O'Connell BJ. The contribution of personality traits, negative affectivity, locus of control and Type A to the subsequent reports of job stressors and job strains. J Occup Organ Psychol 1994;67:1-2. https://doi.org/10.1111/j.2044-8325.1994.tb00545.x. 6. Shipley BA, Weiss A, Der G, Taylor MD, Deary IJ. Neuroticism, extraversion, and mortality in the UK Health and Lifestyle Survey: a 21-year prospective cohort study. Psychosom Med 2007 Dec;69(9):923-31. https://doi.org/10.1097/PSY.0b013e31815abf83. 7. Kasl SV. Measuring job stressors and studying the health impact of the work environment: an epidemiologic commentary. J Occup Health Psychol 1998 Oct;3(4):390-401. https://doi.org/10.1037/1076-8998.3.4.390.

Chronic exposure to work-related mental stressors has been linked to higher risk of disease, possibly mediated by effects on the normal diurnal cortisol concentration pattern due to allostatic overload. The purpose of this study was to examine if the diurnal cortisol pattern changed with exposure to work-related stressors according to the demand-control-support (DCS) and the effort-reward-imbalance (ERI) stress models. In 2007, 4467 Danish public service employees participated in a study on job stress and mental health, and 3217 were reexamined in 2009, using identical methods. DCS and ERI-exposures were assessed from self-administered questionnaires. Cortisol concentrations were assessed from saliva samples, one in the morning and one in the evening. Saliva sampling time distributions enabled us to estimate exposure effects on cortisol concentration patterns for the first two hours after awakening and for nine hours in the evening, and on the peak-to-nadir slope. Associations between the exposures and the diurnal cortisol pattern were examined by linear mixed model analyses, separately for DCS- and ERI-exposures, with mutual adjustment for main and composite variables of the stress model and a large set of potential confounders. DCS- and ERI-exposures were not associated with changes in the diurnal cortisol pattern. In contrast, many associations between potential confounders and cortisol were statistically significant, including the diurnal slope pattern assessed from saliva sampling times. We found no support for the hypothesis that DCS- or ERI- exposures are associated with changes of the diurnal pattern of cortisol concentrations in saliva samples.

The aim of this study was to investigate the association between long-term exposure to ambient air pollution at the residential address and the risk of acute myocardial infarction (AMI) in a younger working population. The study population included all Danish residents aged 35–50 in 1995 with employment and no previous diagnosis of AMI. Information on AMI was obtained through national registries. We estimated the exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), elemental carbon (EC) and primary organic aerosols (POA) from 1979 onwards based on the Danish integrated multi-scale air pollution modeling system. Poisson regression models were used to estimate incidence rate ratios (IRR) with 95

OBJECTIVE:Reviews consistently suggest an association between job strain and ischemic heart disease (IHD), but causality remains uncertain. This study aimed to critically assess causal inference using the most informative epidemiological studies. METHODS:A systematic search in PubMed and Embase up to 15 November 2024 identified observational studies reporting quantitative estimates of associations between job strain (defined by job demands and control) and IHD. Eligible studies were cohort or case-control designs with exposure data obtained independently by medically verified IHD (ICD-8/9: 410-414; ICD-10: I20-I25) and risk estimates adjusted at least for age, sex, and socio-economic status. One estimate per study was included in inverse-variance weighted random-effects meta-analyses. We evaluated main sources of upward and downward bias, potential confounding, and key criteria for causal inference including outcome specificity, exposure-response, and consistency. RESULTS:This review comprised 25 cohort and 1 case-control study (122 risk estimates). The fully adjusted pooled relative risk estimate (RRE) for job strain and all IHD outcomes combined was 1.14 [95% confidence interval (CI) 1.06-1.23; 21 studies]. For myocardial infarction, the RRE was 1.08 (95% CI 1.00-1.15; 11 studies), and, in studies using job-exposure matrices, it was 1.06 (95% CI 0.99-1.13; 7 studies). Strong heterogeneity, small effect sizes, limited exposure-response evidence, net bias in unpredictable directions, and lack of confirmation of findings in studies using alternatives to self-reported exposure assessment preclude causal inference. CONCLUSION:Evidence for a causal relationship between job strain and IHD is limited. At most, any true effect appears to be small.

BACKGROUND:Polychlorinated biphenyls (PCBs) are industrial chemicals commonly used in building materials before their ban decades ago. PCBs are immunotoxic and childhood exposure may impair the developing immune system. We examined the risk of asthma, allergic rhinoconjunctivitis, atopic eczema, and respiratory infections among children exposed to lower-chlorinated PCBs in indoor air. METHODS:The study included 13 633 children residing in one of two partly PCB contaminated residential areas in Greater Copenhagen, Denmark at least one day before their 15th birthday during the period 1970-2018. Exposure was quantified using indoor air measurements combined with register-based relocation dates (ng/m3 PCBtotal × years at the address). Register-based hospital discharges and medication claims defined the outcomes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression with time-varying cumulated exposure lagged six months, adjusted for child sex, ancestry, and calendar year. RESULTS:We identified 890 (7%) asthma cases, 1379 (10%) allergic rhinoconjunctivitis cases, 46 (<1%) atopic eczema cases, and 2058 (16%) respiratory infections cases. We observed no association between PCB and any of the outcomes: adjusted HR per interquartile range increase in PCByear for asthma: 1.00 (95% CI: 0.99-1.01); allergic rhinoconjunctivitis: 1.00 (95% CI: 1.00-1.00); atopic eczema: 1.02 (95% CI: 1.00-1.04); respiratory infections: 1.00 (95% CI: 0.99-1.00). CONCLUSION:We found no evidence in support of changes to risk of developing asthma, allergic rhinoconjunctivitis, atopic eczema, and respiratory infections among children exposed to PCBs in indoor air.

BACKGROUND:Fetal exposure to endocrine-disrupting chemicals (EDCs) has been associated with reduced male fecundity, but with few studies considering chemical mixtures. OBJECTIVES:We assessed the association between fetal exposure to a mixture of EDCs and biomarkers of male fecundity in young adulthood. MATERIALS AND METHODS:The study population comprised 841 young adult males enrolled in the Fetal Programming of Semen Quality cohort, established as a male offspring sub-cohort within the Danish National Birth Cohort. Maternal blood samples were analyzed for concentrations of per- and polyfluoroalkyl substances (PFAS), phthalate metabolites, and triclosan. We used quantile g-computation to estimate the change in semen characteristics, testicular volume, and reproductive hormone levels with 95% confidence intervals (CI) per one-quartile increase in all chemicals within three chemical mixtures; an overall chemical mixture, a PFAS mixture, and a non-persistent chemical mixture. RESULTS:Fetal exposure to a one-quartile increase in the overall chemical mixture was associated with 4.0 million/mL lower sperm concentration (95% CI: -9.1, 1.1), 16.1 million lower total sperm count (95% CI: -33.8, 1.6), 0.5 mL smaller testicular volume (95% CI: -1.2, 0.3), 5% higher proportion of non-progressive and immotile spermatozoa (95% CI: 0.99, 1.11), and 7% higher concentration of FSH (95% CI: 0.99, 1.16), but with limited precision. Effect sizes were greatest in magnitude for sperm concentration and total sperm count. We observed somewhat similar associations for the PFAS mixture and no associations for the non-persistent chemical mixture. DISCUSSION:Results suggest that fetal exposure to an overall mixture of EDCs may be adversely associated with several biomarkers of male fecundity, but findings are also compatible with null associations. These associations, if true, appeared to be driven by PFAS, but misclassification due to a single measurement of the phthalate metabolites and triclosan may have attenuated the results.

OBJECTIVES:The objective was to investigate if high physical workload during pregnancy is associated with adverse pregnancy outcomes. METHODS:The register-based cohort, DOC*X-Generation included employed pregnant women in Denmark (1977-2018). A summary score of physical workloads, based on a job exposure matrix with eight physical work activities, was linked to the job held during pregnancy (coded by DISCO-88). The exposure was divided into five groups from low to high exposure. Data on miscarriages were retrieved from the Danish National Patient Register. Preterm birth (PTB) and small for gestational age (SGA) were determined by gestational age and birth weight from the Danish Medical Birth Register. Other nationwide registers provided data on potential confounders. RESULTS:We included pregnancies for approximately 1 million unique women where 13% terminated in miscarriages (of ~1.9 million pregnancies), 5% were PTB (of ~1.5 million pregnancies) and 13% were SGA (of ~1.6 million pregnancies). Employment in occupations with high physical workload was associated with increased risk of all three outcomes in a dose-dependent manner. For the highest compared with the lowest exposed group, adjusted ORs were 1.24 (95% CI 1.22 to 1.27) for miscarriage, 1.15 (95% CI 1.12 to 1.19) for overall PTB and 1.12 (95% CI 1.10 to 1.14) for SGA. CONCLUSIONS:This study, based on an unselected cohort of employed women over a 40-year period, corroborates previous findings of an increased risk of adverse pregnancy outcomes due to high physical workload during pregnancy. A general recommendation to decrease the overall occupational workload of pregnant women might prevent adverse pregnancy outcomes.

OBJECTIVES:Occupational physical activity (OPA) during pregnancy has been linked to adverse pregnancy outcomes, but crude exposure assessment remains an issue in causal inference. We aimed to develop a quantitative trimester-specific job exposure matrix (JEM) for standing, walking, and forward bending among pregnant workers. METHODS:Accelerometer measurements from 403 female workers across 109 DISCO-08 job codes were obtained in Denmark between January 2023 and June 2024. Full workdays were measured during two weeks among pregnant workers and one week among non-pregnant workers. We used linear mixed-effects models to estimate exposure levels of occupational standing, walking, and forward bending for all 1171 DISCO-08 codes, including age, trimester, and expert ratings as fixed effects, and job codes and workers as random effects. RESULTS:The between-job variances relative to total variances were 56% for standing, 51% for walking, and 45% for forward bending. The fixed effect trimester reduced standing time by 0.38 hours during the 3rd trimester compared to non-pregnant participants, whereas no differences were observed for walking or forward bending. Based on the trimester-specific JEM for occupational standing time, bakers had the highest exposure (range from non-pregnant to 3rd trimester, 5.41-5.03 hours/workday). For walking and forward bending, the highest exposed jobs from the pregnancy-specific JEM were waiters (1.76 hours/workday) and livestock/dairy producers (1.24 hours/workday), respectively. CONCLUSIONS:The JEM enhances independent objective exposure assessment in epidemiological studies of OPA and pregnancy outcomes and may advance guidelines and potentially prevent adverse pregnancy outcomes.

Polychlorinated biphenyls (PCBs) are industrial chemicals commonly found in food and building materials. PCBs are immunotoxic and may disturb the fetal programming of the immune and respiratory systems. We evaluated the association between maternal PCB exposure in indoor air and asthma, allergic rhinitis, atopic eczema, and respiratory infections in the offspring in the Health Effects of PCBs in Indoor Air (HESPAIR) cohort. This register-based study examined 7982 children born to mothers residing in two partially PCB contaminated residential areas in Greater Copenhagen before and/or during pregnancy. Children were included if their mothers at any point had lived in a contaminated or uncontaminated apartment in the period from 3.6 years prior to conception until the date of birth. PCB exposure was defined as mothers’ number of years in an apartment prior to birth of the child multiplied with the PCB concentration in indoor air based on air measurements. Information on the outcomes was retrieved from the Danish health registers from 1977 to 2018. We estimated adjusted hazard ratios using Cox regression. Our main analyses revealed no association between maternal exposure to PCBs in indoor air and any of the studied allergic and respiratory outcomes. Findings of sensitivity analyses were consistent with main analyses. While these findings may appear reassuring for the considerable number of people living or working in PCB contaminated indoor environments, they should be interpreted with caution due to the indirect measure of exposure, incomplete registration of diagnoses, and lack of supporting evidence from comparable studies.

Maternal prenatal exposures to per- and polyfluoroalkyl substances (PFAS) have been linked to adverse birth outcomes. However, few investigations have considered paternal PFAS exposure. We estimated the parent-specific associations of prenatal PFAS exposures with adverse birth outcomes. This study included 498 couples from the INUENDO cohort recruited at antenatal care visits in Greenland, Poland, and Ukraine during 2002–2004. We measured five major types of PFAS in parental serum during pregnancy. We analyzed three birth outcomes ascertained from medical records, including gestational age, birth weight, and birth length. We used weighted least squares linear regression to evaluate parent-specific associations of serum PFAS with the birth outcomes, adjusting for parental co-exposures and covariates. We also used quantile g-computation for mixture modeling of the birth outcomes of paternal and/or maternal exposures to multiple PFAS. No associations were found between maternal and paternal PFAS exposures and gestational age. However, after adjusting for paternal PFOA, a higher level of maternal serum perfluorooctanoate (PFOA) was linked to a tendency towards lower birth weight and shorter birth length. Paternal exposure to several PFAS was also associated with a tendency for shorter birth length, but the estimated effect sizes were small. We found no joint exposure effects in the mixture analyses. While the evidence was inconclusive, maternal PFOA and paternal PFAS exposures seemed to be associated with lower offspring birth weight and shorter birth length, respectively. Parent-specific effects of PFAS exposures on offspring growth and development warrant further research.

We aimed to investigate the association between occupational exposure to respirable crystalline quartz (RCQ) and acute myocardial infarction (AMI) in a Danish register-based cohort (DOC*X Dust, n = 903,415). Through 1976-2017, information on occupation was linked to quantitative exposure estimates of RCQ, obtained from the job-exposure matrix of SYN-JEM. The follow-up period (1996-2018) counted 19,357,326 person-years, where 35,511 first-time AMIs occurred, according to register-based hospital contacts. Incidence rate ratios (IRRs) for AMI based on cumulative, recent, and maximum exposure were computed using Poisson regression adjusted for socio-economic factors, comorbidities, air pollution, and other occupational exposures such as noise, physically demanding work, exposure to diesel exhaust, and job strain. For cumulative exposure, the IRR for AMI in the unadjusted model was highest in the two lowest exposed quartiles (IRR for Q1 = 1.19 (95%CI: 1.13-1.25), IRR for Q2 = 1.12 (95%CI: 1.06, 1.17)). However, in the fully adjusted model, these associations were no longer significant and even inverse for exposed above 25th percentile. The lowest IRR was observed in the highest RCQ exposure quartile (IRR = 0.87, (95%CI: 0.83-0.92)). In general, the RCQ exposure levels in the DOC*X Dust cohort were presumed to be lower than in countries that - contrary to Denmark - have an active mining industry. In conclusion, no increased risk of AMI due to RCQ exposure was observed, but cautious interpretation is warranted because of potential bias from the healthy worker survivor effect.

BACKGROUND:Tattoo inks are mixtures of organic and inorganic color pigments and having a tattoo may be adversely associated with biomarkers of male fecundity. OBJECTIVE:To examine the association between tattoo exposure and biomarkers of male fecundity. METHODS:Participants were young adult Danish males (aged 18-21 years) sampled from the Danish National Birth Cohort. Upon recruitment in 2017-2019, participants answered a comprehensive questionnaire including information on tattoo exposure and provided a semen and blood sample. We applied a negative binomial regression model to estimate percentage differences (95 % confidence intervals [CI]) in semen characteristics, testicular volume, and reproductive hormone levels between tattooed and non-tattooed participants. RESULTS:Among the 1045 participants included in this study, 174 (17 %) had at least one tattoo and most tattooed participants (84 %) had tattoo(s) in only black color. About half (53 %) had one tattoo, 21 % had two tattoos, and 26 % had three or more tattoos. We observed no association between either number or color scheme of tattoo(s) relative to semen characteristics or reproductive hormone levels. Having a tattoo was associated with 6 % (95 % CI: 0, 12) larger testicular volume, but since testicular volume was measured by the participants themselves, this finding may be due to differential misclassification bias. Across all outcomes the crude and adjusted models were comparable. CONCLUSION:Overall, we found no support for adverse associations between tattoo exposure and biomarkers of male fecundity, but studies with more details on tattoo exposure and longer follow-up of participants are needed before firm conclusions can be drawn.

OBJECTIVES:Firefighters face a range of hazards, including strenuous tasks in high-temperature environments and exposure to chemicals. These hazards may increase the risk of kidney diseases. However, limited evidence supports this hypothesis within this occupational group. Hence, this study aimed to assess the relationship between firefighting and kidney diseases. METHODS:A cohort comprising 10 094 male Danish firefighters was analysed, including 3455 full-time and 6639 part-time/volunteer firefighters. Diagnoses of kidney disease from 1994 to 2014 were retrieved from the Danish National Patient Registry. Morbidity among firefighters was compared with that of a sample of the male working population, and standardised incidence ratios (SIR) were used to estimate relative risks. RESULTS:The results indicated a positive association between full-time firefighting and urolithiasis (SIR 1.36; 95% CI 1.13 to 1.63). Shorter employment (<5 years) was associated with a higher risk of glomerulonephritis and chronic kidney disease, whereas longer employment (≥5 years) was linked to lower risks for most outcomes, except for urolithiasis, which remained elevated regardless of employment duration. Full-time specialised smoke divers were indicated to have a higher risk of glomerulonephritis, renal failure and chronic kidney disease. Urolithiasis risk was associated with an elevated risk in both regular and specialised full-time firefighters. Risk estimates for the assessed kidney diseases among part-time/volunteer firefighters generally reflected a lower risk. CONCLUSIONS:This study provides evidence for elevated risks of certain kidney diseases in full-time firefighters, especially urolithiasis. Awareness of sufficient hydration in relation to extreme heat exposures may be particularly important among firefighters.

ABSTRACT Background Atopic dermatitis (AD) may be associated with male reproductive health. However, epidemiological studies are yet to explore this hypothesis. Objectives To investigate whether AD in childhood is associated with poorer reproductive health in young men from the general population. Methods This study is based on the Danish National Birth Cohort (DNBC) and its sub‐cohort, the Fetal Programming of Semen Quality cohort (FEPOS), which consists of young men born between 1998 and 2000 and whose mothers were included in the DNBC. In total, 5697 young men were invited during the recruitment period from 2017 to 2019, where 1058 were enroled and completed a comprehensive questionnaire regarding health and lifestyle, provided semen and blood samples and self‐measured their testicular volume. Information on maternal‐reported doctor‐diagnosed AD was obtained from the DNBC during childhood. The associations of semen characteristics, testicular volume and reproductive hormone levels with the occurrence of AD were analyzed using negative binomial and linear regression models. Results In total, 220 (21%) young men had childhood AD. Men with childhood AD had slightly higher sperm concentration compared to those without (17%, 95% confidence intervals (CI): 3% to 33%), and lower FSH (−9%, 95% CI: −17% to 0%) and LH (−8%, 95% CI: −14% to −1%). Testosterone and estradiol levels and the remaining reproductive health outcomes were comparable between men with and without childhood AD. Conclusions This study indicates that childhood AD might not have a clinically significant negative association with semen quality or reproductive hormone levels in young adulthood.

We want to thank Drs. Burstyn & Luta (1) for their recognition of our recent study (2) suggesting that estimates of breast cancer risk following retrospective self-reported night shift work are inflated by recall bias. The main strength of the study was a gold standard based on individual, prospective, objective and detailed information on night shift work that allowed validation of self-reported night shift work obtained after breast cancer was diagnosed - the usual situation for case-control studies (3). The study confirmed what textbooks have long taught but rarely documented empirically (4-6). We also want to thank Drs. Burstyn & Luta for their advice on how we could have utilized this precious dataset not only for simple but also probabilistic and Bayesian quantitative bias analyses. Even if highly instructive, this may still require strong statistical involvement. Using data provided in our paper, Drs. Burstyn & Luta's bias-corrected odds ratio (OR) estimate of breast cancer following night shift work was centered around 1.0 (95% credible interval 0.3-1.7) and suggests that recall bias could completely, and not only partly as in our analysis (OR 1.05; correctly computed 95% confidence interval 0.88-1.27), explain the observed associations between night shift work and breast cancer found in case-control studies with retrospective self-reported exposure information. This finding strengthens our concern that breast cancer studies based on retrospective self-reports of night shifts may not provide convincing evidence. The gold standard of this validation study was based on a cohort of healthcare workers with day-by-day night shift information from a pay roll register and has earlier been used for breast cancer risk assessment showing no increased risk (7). A recent Swedish study using comparable data neither showed an overall increased risk (8). However, these studies included only information on recent night shift work. The next step should be a follow up of the cohorts when information on more distant night shift work becomes available with an emphasis on analyses that explore the timing of shift work on breast cancer risk. References 1. Burstyn I, Luta G. Advice on better utilization of validation data to adjust odds ratios for differential exposure misclassification (recall bias). Scand J Work Environ Health - online first. https://doi.org/10.5271/sjweh.4226 2. Vestergaard JM, Haug JN, Dalbøge A, Bonde JP, Garde AH, Hansen J et al. Validity of self-reported night shift work among women with and without breast cancer. Scand J Work Environ Health. 2024;50(3):152-7. https://doi.org/10.5271/sjweh.4142. 3. Cordina-Duverger E, Menegaux F, Popa A, Rabstein S, Harth V, Pesch B et al. Night shift work and breast cancer: a pooled analysis of population-based case-control studies with complete work history. Eur J Epidemiol. 2018; 33(4):369-79. https://doi.org/10.1007/s10654-018-0368-x. 4. Berrington de González A, Richardson DB, Schubauer-Berigan MK. Statistical methods in cancer research, Volume V. Bias assessment in case-control and cohort studies for hazard identification. Lyon, France: International Agency for Research on Cancer; 2024. 5. Checkoway H, Pearce N, Kriebel D. Research Methods in Occupational Epidemiology. New York: Oxford University Press 2004. p372. 6. Rothman KJ. Modern Epidemiology. Boston/Toronto: Little, Brown and Company; 1986. p358. 7. Vistisen HT, Garde AH, Frydenberg M, Christiansen P, Hansen AM, Hansen J et al. Short-term effects of night shift work on breast cancer risk: a cohort study of payroll data. Scand J Work Environ Health. 2017;43(1):59-67. https://doi.org/10.5271/sjweh.3603. 8. Gustavsson P, Bigert C, Andersson T, Kader M, Härmä M, Selander J et al. Night work and breast cancer risk in a cohort of female healthcare employees in Stockholm, Sweden. Occup Environ Med. 2023;80(7):372-6. https://doi.org/10.1136/oemed-2022-108673. Henrik Albert Kolstad, MD,1, 2 Jesper Medom Vestergaard, MIT,1 Jens Peter Bonde, MD,3 Sadie Costello, PhD,4 Annett Dalbøge, PhD,1 Åse Marie Hansen, PhD,5, 6 Ann Dyreborg Larsen, PhD,6 Anne Helene Garde, PhD 5, 6 1 Occupational and Environmental Medicine, Danish Ramazzini Centre, Aarhus University Hospital, Aarhus, Denmark. 2 Department of Clinical Medicine, Aarhus University, Denmark. 3 Department of Occupational and Environmental Medicine, Bispebjerg and Frederiksberg Hospital, Denmark. 4 Environmental Health Science, School of Public Health, University of California, Berkeley, USA. 5 The National Research Centre for the Working Environment, Denmark. 6 Department of Public Health, University of Copenhagen, Denmark. Correspondence to: Henrik Kolstad, Occupational and Environmental Medicine, Danish Ramazzini Centre, Aarhus University Hospital, Aarhus, Denmark. [E-mail: kolstad@clin.au.dk].

BACKGROUND:Reports of low semen quality have led to investigations of potential risk factors, including cannabis use. Cannabis affects the endocannabinoid system, which in part regulates spermatogenesis and hormonal balance, but evidence on its impact on male reproductive health remains inconsistent. OBJECTIVE:This study examined the associations between ever cannabis use and biomarkers of male fecundity in a large cohort of young Danish men incorporating detailed information on their concurrent health behaviors and potential confounding factors during fetal life, a key limitation of previous studies. METHODS:We used data from the Fetal Programming of Semen Quality cohort, a sub cohort of 1058 young men born to women enrolled in the Danish National Birth Cohort. Cannabis use was self-reported via an online questionnaire before a clinical examination. Semen samples were collected and analyzed for volume, concentration, total count, motility, morphology, and DNA fragmentation. Hormone levels were measured from venous blood samples. Testicular volume was self-assessed using a Prader Orchidometer. RESULTS:Among participants included in the analytical sample, 324 (31 %) had never used cannabis and 721 (59 %) had used cannabis at least once. We observed no association between ever cannabis use and male fecundity biomarkers, except for a slight indication of higher follicle-stimulating hormone (FSH) levels among ever cannabis users (8 % [95 % CI: -2, 20]). CONCLUSION:While we found no associations between ever cannabis use and most biomarkers of fecundity in young men, the higher FSH levels among ever cannabis users could suggest early signs of impaired testicular function. However, this needs to be confirmed in studies with a more comprehensive assessment of cannabis exposure.

Firefighters face numerous occupational hazards that raise concerns regarding adverse health effects and mortality. Therefore, we conducted an updated evaluation of mortality in a cohort of Danish firefighters by adding 7 years of follow-up. The updated cohort comprised 11,888 male Danish firefighters, and the assessment of mortality spanned from 1970 through 2021. Data on vital status, emigration and mortality was retrieved from the Danish Civil Registration System and the Danish Register of Causes of Death. Standardized Mortality Ratios (SMRs) were calculated for the cohort, along with 95

BACKGROUND:Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may influence lung and immune system development, but previous epidemiological studies are inconclusive and have not extended into young adulthood. OBJECTIVE:To examine associations between prenatal exposure to a mixture of PFAS and respiratory and immune-related outcomes in a cohort of males. METHODS:We studied 866 males with maternal pregnancy plasma measured for 15 PFAS, triclosan, and 10 phthalate metabolites used as a proxy for prenatal exposure. Spirometry was measured at approximately age 19 years. Asthma in young adulthood was reported in questionnaires at age 18 years. Asthma, hay fever, and eczema at 7 and 11 years of age were based on parental reports. We estimated the difference in spirometry measures and odds ratios (ORs) for questionnaire outcomes per one-interquartile range (IQR) increase in a mixture of seven well-detected PFAS using quantile g-computation models. Subsequently, we examined a mixture of seven PFAS, two phthalate metabolites and triclosan, and ran single-pollutant analyses. RESULTS:A one-IQR increase in the PFAS mixture was associated with lower forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) (milliliter difference [95 % CI]: 85 [-160;-9], -88 [-173;-3], respectively), but not FEV1/FVC. Higher concentration of the PFAS mixture was also associated with lower odds of a history of and current hay fever (OR [95 % CI]: 0.52 [0.34; 0.80], 0.49 [0.30; 0.81], respectively), but not asthma or eczema. Associations did not change substantially when including phthalate metabolites and triclosan to the PFAS mixture and single-pollutant analyses were overall consistent with the mixture analyses. CONCLUSION:Prenatal PFAS exposure was associated with lower FEV1 and FVC in a cohort of young adult males, suggesting an impact on lung development. Associations with reduced hay fever in childhood may suggest influences on immune maturation. Potential sex-specific effects should be addressed in future studies.