Urinary and fecal excretion of aromatic amines in pet dogs and cats from the United States

Chinthakindi, Sridhar; Kannan, Kurunthachalam

doi:10.1016/j.envint.2022.107208

Cited by 14 publications

(11 citation statements)

References 39 publications

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“…Despite the limitation, the daily urinary excretion of 6PPD and 6PPD-Q in these populations should be of concern because it largely reflects their internal exposure dose. Given that a portion of 6PPD and 6PPD-Q may also be excreted through feces and exhaled air like some other pollutants, , the actual exposure dose of 6PPD and 6PPD-Q may even be higher than our estimates. Although the dose is unlikely to exceed a proposed reference dose (RfD) of 26000 (ng/kg bw)/day calculated for 6PPD, the potential health risk posed by long-term exposure to 6PPD-Q requires considerable attention, as 6PPD-Q has been proven to be more toxic to aquatic organisms than 6PPD from the individual species to the tissue levels. − ,, In future studies, additional biomonitoring investigations on 6PPD and 6PPD-Q are needed to better elucidate their internal exposure in humans.…”

Section: Resultsmentioning

confidence: 68%

First Report on the Occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as Pervasive Pollutants in Human Urine from South China

Liang

et al. 2022

Environ. Sci. Technol. Lett.

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-N′-phenyl-p-phenylenediamine (6PPD) and its quinone derivative, 6PPD-quinone (6PPD-Q), have been found to be prevalent in the environment, but there are currently no data on their presence in humans. Herein, we conducted the first human biomonitoring study of 6PPD and 6PPD-Q by measuring 150 urine samples collected from three different populations (general adults, children, and pregnant women) in South China. Both 6PPD and 6PPD-Q were detected in the urine samples, with detection frequencies between 60% and 100%. Urinary 6PPD-Q concentrations were significantly higher than those of 6PPD and correlated well with those of 6PPD (p < 0.01), indicating coexposure to 6PPD and 6PPD-Q in humans. In vitro metabolic experiments demonstrated rapid depletion of 6PPD by human liver microsomes, which should be responsible for the lower concentrations of 6PPD in human urine. Additionally, pregnant women exhibited apparently higher concentrations of 6PPD and 6PPD-Q (median 0.068 and 2.91 ng/mL, respectively) than did adults (0.018 and 0.40 ng/mL) and children (0.015 and 0.076 ng/mL). The high daily urinary excretion of 6PPD-Q in pregnant women was estimated to be 273 (ng/kg bw)/day. Considering that 6PPD-Q was a lethal toxicant to multiple aquatic species, the potential human health risks posed by its long-term exposure require urgent attention.

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Section: Resultsmentioning

confidence: 68%

First Report on the Occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as Pervasive Pollutants in Human Urine from South China

Liang

et al. 2022

Environ. Sci. Technol. Lett.

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“…Pet dogs and cats share a common living environment with humans and can serve as sentinels of human exposure to environmental contaminants ( https://factor.niehs.nih.gov/2022/1/feature/3-feature-sentinels/index.htm ). Exposure of pet dogs and cats to various environmental chemicals has been reported through the analysis of urine, feces, blood, hair, and silicone tags ( Ali et al, 2013 ; Brits et al, 2019 ; Brits et al, 2018 ; Chinthakindi and Kannan, 2022 ; Gonzalez-Gomez et al, 2018 ; Karthikraj and Kannan, 2019 ; Mizukawa et al, 2016 ; Poutasse et al, 2019 ; Wise et al, 2020 ; Wise et al, 2022 ; Zhang et al, 2019 ). Positive correlations were found between exposure levels in humans and dogs from the same homes to several classes of environmental chemicals ( Wise et al, 2020 ; Wise et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

An assessment of exposure to several classes of pesticides in pet dogs and cats from New York, United States

Robinson

Kannan

2022

Environment International

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“…Aromantic amines, such as aniline and 2,6-dimethylaniline, are often used as industrial intermediates and in the production of textile dyes, cosmetics, and several pharmaceutical drugs (Pauluhn, 2004;Bugosen et al, 2020;Stabbert et al, 2003;Chinthakindi and Kannan, 2021. Aniline itself is produced globally on a large scale (e.g., 8.4 million tons in 2020) (Chinthakindi and Kannan, 2022a;Bugosen et al, 2020), although it reportedly has carcinogenic potential in humans. Nonetheless, the tolerable daily intake (TDI) value of aniline has been set by the United States Environmental Protection Agency at 7.0 µg/kg/day (Chinthakindi and Kannan, 2022b).…”

Section: Introductionmentioning

confidence: 99%

“…Aromatic amines, including aniline and 2,6-dimethylaniline, have been detected in indoor Correspondence: Hiroshi Yamazaki (E-mail: hyamazak@ac.shoyaku.ac.jp) air, cigarette smoke, and indoor dust collected in several countries (Chinthakindi and Kannan, 2021;Stabbert et al, 2003;Zhang et al, 2017;Palmiotto et al, 2001;Kannan, 2022b, 2022a). These aromatic amines can migrate from food contact materials such as containers, packaging, cutlery, and kitchen equipment (Chinthakindi and Kannan, 2022a;Perez et al, 2019). Among several aromatic amines, aniline and 2,6-dimethylaniline have been commonly detected in urine samples from humans (Chinthakindi and Kannan, 2022b), dogs, and cats (Chinthakindi and Kannan, 2022a) and in feces from dogs and cats (Chinthakindi and Kannan, 2022a).…”

Section: Introductionmentioning

confidence: 99%

“…These aromatic amines can migrate from food contact materials such as containers, packaging, cutlery, and kitchen equipment (Chinthakindi and Kannan, 2022a;Perez et al, 2019). Among several aromatic amines, aniline and 2,6-dimethylaniline have been commonly detected in urine samples from humans (Chinthakindi and Kannan, 2022b), dogs, and cats (Chinthakindi and Kannan, 2022a) and in feces from dogs and cats (Chinthakindi and Kannan, 2022a).…”

Section: Introductionmentioning

confidence: 99%

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Forward and reverse dosimetry for aniline and 2,6-dimethylaniline in humans extrapolated from humanized-liver mouse data using simplified physiologically based pharmacokinetic models

et al. 2022

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Although human urinary aniline and 2,6-dimethylaniline were unexpectedly detected in biomonitoring data, little is known about the daily intake doses of aniline and 2,6-dimethylaniline in the living environment or their relation to tolerable daily intake (TDI) values in humans. In the current study, to evaluate the daily oral intake of aniline and 2,6-dimethylaniline in humans, forward and reverse dosimetry was carried out using simplified in silico physiologically based pharmacokinetic (PBPK) modeling established using in vivo experimental pharmacokinetic data. These data were from humanized-liver mice after single oral doses of 100 mg/kg aniline (previously determined) and 116 mg/kg 2,6-dimethylanine (currently investigated). The in vivo elimination rates of 2,6-dimethylaniline from plasma in humanized-liver mice were generally slow compared with those of aniline. Faster in vitro metabolic elimination rates of aniline mediated by liver 9000 × g supernatant fractions from rats than those from humans may suggest the existence of higher first-pass effects in rats than in humanized-liver mice. In silico aniline and 2,6-dimethylaniline concentration curves in human urine after virtual oral administrations were estimated by human PBPK models created with data from humanized-liver mice. Reverse dosimetry analysis using human PBPK models estimated the daily intake of aniline, based on reported human urinary concentrations in biomonitoring data, to be roughly similar to the aniline TDI level. These results suggest that forward and reverse dosimetry using simplified human PBPK models founded on data from humanized-liver mice can be used to evaluate possible higher than expected exposures of aniline and 2,6-dimethylaniline in humans.

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Urinary and fecal excretion of aromatic amines in pet dogs and cats from the United States

Cited by 14 publications

References 39 publications

First Report on the Occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as Pervasive Pollutants in Human Urine from South China

First Report on the Occurrence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and 6PPD-Quinone as Pervasive Pollutants in Human Urine from South China

An assessment of exposure to several classes of pesticides in pet dogs and cats from New York, United States

Forward and reverse dosimetry for aniline and 2,6-dimethylaniline in humans extrapolated from humanized-liver mouse data using simplified physiologically based pharmacokinetic models

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