Human biomonitoring data for several chemicals supported sufficiently low LOQs/LODs in HRMS to observe and even quantify average contamination levels for most target analytes. From the HRMS data, the LOQ of the air pollutant 1-OH-pyrene was determined as 1.4 ng/mL (c.f., 0.06 ng/mL for the QQQ). The reference value from the German human biomonitoring commission is 0.5 ng/mL in urine for non-smoking adults and twice this value in smokers . Thus, HRMS would only capture high-exposure levels above the reference value obtained biomonitoring data and thus this analyte was only detected in one measured urine sample. The intermediate in dye production, 2-naphthol was detected in all urine samples with both approaches indicating a LOQ (1.2 ng/mL in HRMS) that is sufficiently low to detect this compound in biological samples. According to the Fourth National Report on Human Exposures to Environmental Chemicals (CDC 2021), this LOQ is more than three times below the geometric mean urinary level of the industrial side product (4.2 ng/mL) in the U.S. American population (n=2,641). Urinary phytoestrogen levels that primarily originate from food and are typically regarded as beneficial exposures, were frequent, high, and dependent on the diet of the individual. In the US-American population (n>3,000), mean levels in urine were 65, 32 and 6.6 ng/mL for daidzein, genistein and equol, respectively . In our HRMS measurements, the LOQ value was 0.12 ng/mL (genistein, daidzein) to 0.41 ng/mL (equol), which are well below the mean levels obtained from large-scale biomonitoring data. In our urine samples, daidzein (24/24) and genistein (20/24) were detected in almost all samples with both instruments (HRMS/QQQ). At a lower concentration, equol was detected in only 50% of the samples by HRMS (n=9) compared to QQQ (n=18). Matairesinol was too low abundant to be detected in any urine samples with HRMS (LOQ: 0.85 ng/mL). The mean concentration value of this phytoestrogen was 0.6 ng/mL in Mexican women below the LOQ in HRMS . The personal care product ingredients methylparaben, ethylparaben, and propylparaben were frequently investigated in human urine. The mean urinary concentrations in the US population (n>2,600) were 32 ng/mL (methylparaben), 4 ng/mL (propylparaben) and the 75th percentile is 5.1 ng/mL for ethylparaben . A smaller Spanish study (n>200) reported slightly lower concentrations at 11.2 ng/mL (methylparaben), 1.1 ng/mL (ethylparaben), and 0.64 ng/mL (propylparaben) . Mean concentration levels in human biomonitoring studies were more than 30 times higher than the LOQ values (0.01 to 0.07 ng/mL) in this study. Nevertheless, only 46% (ethylparaben) to 84% (methylparaben) of the analytes were observed with both assays. If a paraben in urine was solely detected with QQQ, the abundance was usually very low (< LOQ). Thus, the LOQ determined by HRMS was sufficient to measure exposure far below the average contamination for this chemical class. The antibacterial/antifungal triclosan was described at a mean concentration of 5.8 ng/mL in the USA (CDC 2021) and 2.7 ng/mL in the Belgian population . The LOQ in HRMS was with 2.5 ng/mL (HRMS) slightly below the mean concentration in the biomonitoring studies, but this was still only detected (below the LOQ) in three urine samples in HRMS. The mycoestrogens, alternariol monomethyl ether (AME) and alternariol (AOH) were observed in the urine of Chinese at a mean concentration of 0.19 ng/mL alternariol and 0.065 ng/mL AME . The achieved LOQ in HRMS is below these mean urinary concentrations with 0.11 ng/mL (AME) and 0.20 ng/mL (AOH) and the analytes were also barely detected and not quantified in the urine samples. Despite a few analytes for which the LOQ and the LOD were not low enough to capture and quantify the analytes when present at mean concentrations reported in biomonitoring studies, HRMS detected exposures at, or even below, the population means for most compounds. With the QQQ, however, even extremely low levels of exposure were detected. The comparison of the achieved LOQ in our study with biomonitoring data revealed that the sensitivity required to measure chemical exposures in biospecimens strongly depends on the analyte of interest. The QQQ approach was superior in detecting and quantifying very low-abundance contaminants. The tolerable/acceptable daily intake (TDI, ADI) estimates the amount of an accidentally added compound or substance in general that can be daily consumed without health risk. These thresholds were available for thirteen target compounds, including bisphenol A, some phthalates, perfluorinated substances, several mycotoxins, parabens, methiocarb, and triclosan (Table ). The approximate urinary concentrations of chemicals, when absorbed at the exposure limit for negative health implications such as the TDI or ADI, were in most cases significantly higher than the reported LOQs. Independent of the instrument, the estimated urinary concentration at the TDI/ADI was typically more than 1,000 times higher than the LOQ, indicating a sufficient sensitivity for detecting harmful concentrations of chemicals. The LOQ of dibutyl phthalate and PFOS was 160 ng/mL and 3.5 ng/mL, respectively, only about half of the estimated concentration in urine at the TDI/ADI. Thus, a critical exposure level might not be detected depending on the actual urinary excretion rate and bioavailability of these substances. The urinary elimination was estimated to be 16% for PFOS and dibutyl phthalate was reported to be primarily excreted as mono butyl phthalate (over 70%) , consequently, toxicological relevant concentrations might not be observed with the achieved LOQ/LOD. The LOQ of the mycotoxins deoxynivalenol and nivalenol and BPA was also not sufficiently low for detecting relevant exposure levels with HRMS. However, the slightly lower LOQ in the QQQ approach was (except for nivalenol), also not in the required range. The BPA concentration estimation was based on the newly published EFSA draft opinion ) with a drastically lowered TDI of 0.01 ng/kg body weight per day. The LOQ was sufficiently low to observe concentrations at the previous TDI (0.4 µg/kg body weight per day) (EFSA 2015). In total, HRMS was suitable to detect and even quantify toxicologically relevant concentrations in urine for many analytes. The blank urine originated from a single individual, thus the impact of the matrix on the detectability of analytes was not evaluated in this study. Urine is highly influenced by inter-and intraindividual factors. Thus, results might vary depending on the precise urine matrix used. The sample pre-treatment, e.g. enzyme treatment, impacts the required LOQs for detecting toxicants as analytes might be masked from targeted analysis by biotransformation such as sulfation and glucuronidation. The urine samples were not pretreated with glucuronidase or sulfatase; therefore, except for a few analytes (zearalenone, zearalenol, estradiol), sulfated and glucuronidated metabolites of the target molecules were not captured in QQQ. Biotransformation products may be retrospectively discovered by HRMS, although these were not initially included in the target list. However, the search for biotransformation products was, although important , not conducted in this study as the main focus was on the comparison between both instrument platforms. Nevertheless, some compounds are known to be primarily present as glucuronides in urine ; therefore, with enzymatic pre-treatment, the concentration of the free analyte for the majority of toxicants should increase easing their detection and quantitation.