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Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects. We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics. We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008–2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection. Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4′-methylenedianiline, and a composite of o-toluidine and m-toluidine (99–100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4′-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: −11; 95% CI: −19, −1) or time of day, seasonal, and geographic variability. Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects. [Display omitted] • Measured four melamine derivatives and 41 aromatic amines in ECHO pregnant women. • Melamine, cyanuric acid, and ten aromatic amines detected in >60% of women. • Concentrations higher in non-Hispanic Black or Hispanic women for several compounds. • Most chemicals positively associated with the tobacco biomarker cotinine. • Annual, within-day, seasonal, and geographic variability observed. [ABSTRACT FROM AUTHOR]

It has long been known that bladder cancer (BC) incidence is approximately four-fold higher in men than in women in the United States, and a similar disparity also exists in other countries. The reason for this phenomenon is not known, which impedes progress in BC prevention. However, BC incidence is also significantly higher in male animals than in their female counterparts after treatment with aromatic amines, which are principal human bladder carcinogens. These animal studies and related studies in the context of available human data provide significant insight into what may drive the excessive BC risk in men, which is the focus of this article. The carcinogenicity and biotransformation of bladder carcinogens as well as the impact of sex hormones on these processes are discussed, highlighting the novel concept that the gender disparity in BC risk may result primarily from the interplay of androgen, estrogen, and liver, with the liver functioning via its metabolic enzymes as the main decider of bladder exposure to carcinogens in the urine and the male and female hormones exerting opposing effects on carcinogenesis in the bladder and likely also on liver enzymes handling bladder carcinogens. The findings may facilitate further investigation into the mechanism of gender disparity in BC risk and may also have important implications for BC prevention. [ABSTRACT FROM AUTHOR]

Abstract: o-Toluidine is a monocyclic aromatic amine present in the formulation of some materials that contact drinking water. NSF/ANSI 61 Annex A (2011) and US EPA (2005a) risk assessment guidelines were used to determine an acceptable drinking water level. Occupational exposure to o-toluidine is associated with an increased risk of bladder cancer but human disease rates could not be used to establish risk values due to inadequate exposure data and coexposures in the epidemiology cohorts. Chronic dietary exposure to o-toluidine hydrochloride was associated with benign and malignant tumors in both sexes of F344 rats and B6C3F1 mice. o-Toluidine is genotoxic in vitro and in vivo. A 10−5 cancer risk level was extrapolated from the human equivalent BMDL10 of 13mg/kg-day for the combined incidence of papillomas and carcinomas of the bladder transitional epithelium in female rats. Considering varying susceptibility to tumor development at different life stages, the unit risk was modified to incorporate potency adjustments for early-life exposures. A framework for lifestage adjustment is presented that makes assumptions evident. For this assessment, the lifetime unit risk derived was ∼2-fold greater than the unadjusted adult lifetime unit risk, and the resulting Total Allowable Concentration in drinking water is 20μg/L. [Copyright &y& Elsevier]

Benzidine has been marked as a priority chemical on the National Priorities List by the U.S. Environmental Protection Agency because of its carcinogenic nature. Benzidine sorbs to the sediment matrix after entering water-sediment ecosystems and undergoes at least three different fate processes, including cation exchange, hydrophobic partitioning, and covalent binding. Sediment samples taken from Lake Macatawa (MI, USA) were used after drying and grinding treatments in this study. Sorption experiments were conducted in the buffered deionized water-sediment slurries with a pH range of approximately 3 to 7. Experimental results indicated that low pH conditions (e.g., pH 3.2) favored sorption of benzidine onto sediment, where a large proportion of benzidine species protonated and sorbed predominantly through the fast cation exchange process. Sorption kinetics data suggested that reactions between protons and carbonate components residing in the sediment matrices led to a shift of sorption mechanisms from cation exchange to hydrophobic partitioning, covalent binding, or both when the slurry pH increased from 3 to 7. A sorption mechanism- based model is presented to describe benzidine sorption behavior in the sediment-water systems at different pH values. This model comprises three components mathematically: the linear hydrophobic partitioning, Langmuir-type covalent binding, and quadratic cation exchange. On the basis of nonlinear regression, this model fits the experimental data well. The organic carbon-normalized distribution coefficient value calculated from this model (1,914 L/kg at pH 6.9), and the available covalent binding sites in the sediment matrices were 27 to 52 mmol/kg organic carbon in the pH range of 5.0 to 6.9. The predicted model parameters are in good agreement with the reported literature values. By this model, the individual contribution from each sorption mechanism can be quantified with a wide pH range (e.g., from pH 3 to 7). This model strategy could provide an alternative way to predict the complex sorption processes of aromatic amines containing one or two amino groups in the aqueous-sediment environment. [ABSTRACT FROM AUTHOR]

For protection of elastomeric materials against ageing, antioxidants such as UV-stabilizers and antiozonants are used. Although historically N-phenyl-N′-(1,3-dimethylbutyl)-p-phenylenediamine (6PPD) was the only approved antiozonant in Germany, a range of other phenylene diamine antiozonants (excluding 6PPD) are permitted for use in rubber articles intended for repeat food-contact use in the US (FDA regulations chapter 21 Part 177.2600). The biggest disadvantage of 6PPD is its partial decomposition during the vulcanization leading to the formation of toxic primary aromatic amines (PAA), such as aniline and secondary aromatic amines (SAA). A number of new PPDs have been developed and patented, that due to their chemical structures, are far less soluble in aqueous solutions but a lot more soluble within the rubber matrix. They therefore show significantly less migration of PAA and SAA. These new antiozonants were investigated and compared to 6PPD using commercial rubber materials with a certain content of antiozonant with regard to their migration of PAA and SAA into three different food simulants. The lowest concentration of PAA and SAA in all food simulants was measured in the RU 997 stabilized elastomer. Due to this fact RU 997 was permitted as a new antiozonant for commodities based on rubber according to the Recommendation XXI ‘Articles based on natural and synthetic rubber’ of the Federal Institute for Risk Assessment (BfR). RU 997 therefore represents an alternative for 6PPD with less migration of aromatic amines. [ABSTRACT FROM AUTHOR]

Several primary aromatic amines (AAs) are known or suspected carcinogens. Despite this, the exposure of pet animals to this class of chemicals is unknown. In this study, we investigated the occurrence of 30 AAs and two tobacco chemical markers (nicotine and cotinine) in 63 pet urine (42 dog and 21 cat) and 77 pet feces (37 dog and 40 cat) samples collected from the Albany area of New York State. Eight of the 30 AAs (∑ 8 AAs) were found in > 38% of dog and cat urine samples, at median concentrations of 7.99 (range: 0.42-52.3 ng/mL) and 31.4 (2.63-75.9) ng/mL, respectively. Nine of the 30 AAs (∑ 9 AAs) were found in > 73% of dog and cat feces samples, at median concentrations of 278 (range: 61.7-613 ng/g) and 240 (55.4-645) ng/g dry wt, respectively. Among the 30 AAs, 2,6-dimethylaniline (2,6-DMA) accounted for the highest median concentrations in both urine and fecal samples. Median concentrations of nicotine and cotinine were below 0.92 ng/mL in urine and below 3.86 ng/g in feces of both dogs and cats. No significant relationship was found between AA concentrations and pet age or gender. The lack of significant Spearman's rank correlation between the concentrations of AA and nicotine in pet urine/feces suggested that sources other than tobacco smoke contributed to AA exposure in pets. Furthermore, the calculated fecal excretion rates of AAs were higher than the intake rates (estimated through reverse dosimetry), which indicates that cats and dogs are exposed to AA precursors such as azo dyes. Concentrations in urine and feces reflected exposure to direct and indirect exposure sources, respectively, of AAs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)