## 1 Introduction
### Traditional Approaches to Establishing the Relationship between Benzene Exposure and AML  
The Bradford Hill criteria [9; 10] have been extensively used to evaluate causation when human epidemiologic relationships are found between exposure to a contaminant such as benzene and the disease outcome, such as AML or other hematopoietic and pulmonary diseases [10]. Despite its extensive use, this method is still debated among epidemiologists, as they question, among many arguments, its scope of application and the possibility of ruling out causality in some specific scenarios. The assessment of the potential relationship between environmental benzene exposure and childhood AML includes studying exposures prior to conception, during pregnancy, or while breastfeeding [5]. Parental exposure to benzene, for instance, has been studied as a potential risk factor for infant AML, with conflicting results among researchers. [PERSON] et al. [11] and [PERSON] et al. [12] did not find any association between parental exposure and childhood AML. On the other hand, [PERSON] et al. [13] and [PERSON] et al. [14] reported elevated rates of childhood AML associated with benzene, solvents, and paternal petroleum occupational exposure (prenatal). Households' exposures to benzene have also been investigated, showing no increases in childhood AML related to home use of solvents [15; 16]. Nevertheless, cigarette smoke, the main non-occupational source of benzene, is associated with an increased risk of developing this disease, even at low-level exposure to benzene, through parental smoking during pregnancy [17; 18]. Other exposure surrogates for benzene as an air pollutant are traffic density and proximity to chemical plants, refineries, and gas stations. While several air pollutants are typically present in different concentrations, their risks are ranked by odds ratios. [PERSON] and [PERSON] [19] observed an increase in childhood AML related to car density with an incidence greater than 20 cars/km\({}^{2}\), possibly attributable to benzene in the gasoline. [PERSON] [20] reported correlations between traffic density between benzene and butadiene air concentrations. The corresponding odds ratios for children reveal a relationship with the incidence rate of childhood AML. Similarly, [PERSON] et al. [21] also reported an association between elevated rates of childhood AML to traffic density, attributable to high benzene exposure. [PERSON] et al. [22] reported an increased risk of this disease in proximity to gas stations, while [PERSON] et al. [23] found no association. These opposing results have also been reported when analyzing the risks of nearby petrochemical plants [5]. The discrepancies found in the literature may be due to the method of estimating exposures, potential confound from correlated pollutants, and the intrinsically anisotropic nature of the control volumes defined for the studies. For instance, air measurements in outdoor volumes, show considerable variability in space and time, compared to values reported for indoor control volumes. Benzene has undoubtedly been classified as a human carcinogen causing AML in adults when exposed to relatively high concentrations at work. Nevertheless, it is not clear if low concentrations of this compound in outdoor air cause childhood AML, although some studies reveal some association [24]. Previous studies involving benzene exposure and childhood AML statistically reported their results as odds ratio (OR) and/or risk ratio (RR). OR stands for the ratio of an event's odds in one group (for example, the exposed group) to its odds in the other group (for example, the nonexposed group); the risk ratio (RR) stands for the ratio of the risk of an event in one group to the risk of an event in the other group. An OR or RR greater than 1.0 indicates an increase in odds or risk among the exposed group compared to the unexposed one. Conditional and unconditional logistic regressions are typically used to fit the data of these studies, hence estimating the ORs, and RRs [25; 26; 27].