Phthalate metabolites in paired human serum and whole blood

Li, Zhenming; Wu, Dexin; Yu, Xiao‐Qi; Mao, Weili; Zhao, Nan; Zhao, Meirong; Jin, Hangbiao

doi:10.1016/j.scitotenv.2022.153792

Cited by 22 publications

(14 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found a species-specific difference between humans and mice, where hTRPA1 was at least 100-fold more susceptible to PA monoesters than mTRPA1. An important finding was that the EC50 value of hTRPA1 activation by MEHP was within the range reported in previous epidemiological studies (maximum serum levels of 39-1700 ng/mL) 54,55) . These findings imply that PA esters may exert TRPA1-dependent adverse effects on humans, which have never been demonstrated in experimental animals.…”

Section: Conclusive Remarkssupporting

confidence: 81%

Species-Specific Activation of Transient Receptor Potential Ankyrin 1 by Phthalic Acid Monoesters

Mori

Aoki

Okamoto

et al. 2022

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Phthalic acid (PA) diesters are widely used in consumer products, as plasticizers, and are ubiquitous environmental pollutants. There is a growing concern about their adjuvant effect on allergic diseases. Although its precise mechanism remains unknown, possible involvement of TRPA1 has been suggested. Hence, in this study, the activation of human and mouse TRPA1s by a series of PA di-and monoesters was investigated using a heterologous expression system in vitro.Consequently, it was found that monoesters activated human TRPA1, where EC50 values were in the order of mono-hexyl > mono-heptyl > mono-n-octyl > mono-2-ethylhexyl > mono-isononyl and mono-isodecyl esters. Significant species differences in TRPA1 activation by PA monoesters were also discovered; PA monoesters activated human TRPA1 but not mouse TRPA1 in a concentrationdependent manner up to 50 μM. These findings suggest that PA esters may exert TRPA1-dependent adverse effects on humans, which have never been demonstrated in experimental animals.

show abstract

Section: Conclusive Remarkssupporting

confidence: 81%

Species-Specific Activation of Transient Receptor Potential Ankyrin 1 by Phthalic Acid Monoesters

Mori

Aoki

Okamoto

et al. 2022

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Moreover, phthalate metabolites were detected more frequently in whole human blood (83–100%) than in serum (79–100%), with concentrations ranging from 1.6 to 33 ng/mL . All whole blood samples had detectable concentrations of MEP, MBP, MMP, MEHP, MECPP, and MEHHP (>99%), in which MMP, MBP, and MEHP were the most common . In contrast to phthalates, DINCH has less potential to leach from PVC films into medical devices .…”

Section: Resultsmentioning

confidence: 99%

“…Nine phthalate metabolites were detected in 100% of serum samples from 69 women in Quzhou, southern China, and almost all serum samples contained detectable MMP, MEP, MBP, MEHP, and MECPP (concentration range of 0.70–61 ng/mL). Moreover, phthalate metabolites were detected more frequently in whole human blood (83–100%) than in serum (79–100%), with concentrations ranging from 1.6 to 33 ng/mL . All whole blood samples had detectable concentrations of MEP, MBP, MMP, MEHP, MECPP, and MEHHP (>99%), in which MMP, MBP, and MEHP were the most common .…”

Section: Resultsmentioning

confidence: 99%

“…71 All whole blood samples had detectable concentrations of MEP, MBP, MMP, MEHP, MECPP, and MEHHP (>99%), in which MMP, MBP, and MEHP were the most common. 71 In contrast to phthalates, DINCH has less potential to leach from PVC films into medical devices. 72 Therefore, the current research on levels of exposure to phthalate alternatives focuses on monitoring urine samples.…”

Section: Levels Of Phthalates and Their Alternatives Inmentioning

confidence: 99%

See 1 more Smart Citation

Cumulative Exposure to Phthalates and Their Alternatives and Associated Female Reproductive Health: Body Burdens, Adverse Outcomes, and Underlying Mechanisms

Weng

Zhu

Liao

et al. 2023

Environ. Sci. Technol.

View full text Add to dashboard Cite

The global birth rate has recently shown a decreasing trend, and exposure to environmental pollutants has been identified as a potential factor affecting female reproductive health. Phthalates have been widely used as plasticizers in plastic containers, children's toys, and medical devices, and their ubiquitous presence and endocrine-disrupting potential have already raised particular concerns. Phthalate exposure has been linked to various adverse health outcomes, including reproductive diseases. Given that many phthalates are gradually being banned, a growing number of phthalate alternatives are becoming popular, such as di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) adipate (DEHA), and di(2-ethylhexyl) terephthalate (DEHTP), and they are beginning to have a wide range of environmental effects. Studies have shown that many phthalate alternatives may disrupt female reproductive function by altering the estrous cycle, causing ovarian follicular atresia, and prolonging the gestational cycle, which raises growing concerns about their potential health risks. Herein, we summarize the effects of phthalates and their common alternatives in different female models, the exposure levels that influence the reproductive system, and the effects on female reproductive impairment, adverse pregnancy outcomes, and offspring development. Additionally, we scrutinize the effects of phthalates and their alternatives on hormone signaling, oxidative stress, and intracellular signaling to explore the underlying mechanisms of action on female reproductive health, because these chemicals may affect reproductive tissues directly or indirectly through endocrine disruption. Given the declining global trends of female reproductive capacity and the potential ability of phthalates and their alternatives to negatively impact female reproductive health, a more comprehensive study is needed to understand their effects on the human body and their underlying mechanisms. These findings may have an important role in improving female reproductive health and in turn decreasing the number of complications during pregnancy.

show abstract

“…In the first phase, the ester bonds are hydrolyzed to monoesters by lipase or esterase, and in the second phase, phthalates are converted into sulpho- or glucuro-conjugates [ 18 , 19 , 20 ]. Epidemiological studies have confirmed that phthalate metabolites (mPAEs) are more toxic than their parent phthalate, based on their pharmacokinetic properties [ 21 , 22 ]. Mono(2-ethylhexyl) phthalate (MEHP) is one of the primary metabolites of DEHP; it is excreted in urine within 48 h after exposure to the phthalate in humans [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Risk Assessment of Phthalates and Their Metabolites in Hospitalized Patients: A Focus on Di- and Mono-(2-ethylhexyl) Phthalates Exposure from Intravenous Plastic Bags

Saab

Oueis

Mehanna

et al. 2022

Toxics

View full text Add to dashboard Cite

Phthalate esters (PAEs) are plasticizers associated with multiple toxicities; however, no strict regulations have been implemented to restrict their use in medical applications in Lebanon. Our study aimed at assessing the potential risks correlated with phthalate exposure from IV bags manufactured in Lebanon. GC–MS analysis showed that di-(2-ethylhexyl) phthalate (DEHP) is the predominant phthalate found in almost all samples tested with values ranging from 32.8 to 39.7% w/w of plastic. DEHP concentrations in the IV solutions reached up to 148 µg/L, as measured by SPME-GC–MS/MS, thus resulting in hazard quotients greater than 1, specifically in neonates. The toxicity of DEHP is mainly attributed to its metabolites, most importantly mono-(2-ethylhexyl) phthalate (MEHP). The IV bag solution with the highest content in DEHP was therefore used to extrapolate the amounts of urinary MEHP. The highest concentrations were found in neonates having the lowest body weight, which is concerning, knowing the adverse effects of MEHP in infants. Our study suggests that the use of IV bags manufactured in Lebanon could pose a significant risk in hospitalized patients, especially infants in neonatal care. Therefore, Lebanon, as well as other countries, should start imposing laws that restrict the use of phthalates in medical IV bags and substitute them with less toxic plasticizers.

show abstract

Phthalate metabolites in paired human serum and whole blood

Cited by 22 publications

References 56 publications

Species-Specific Activation of Transient Receptor Potential Ankyrin 1 by Phthalic Acid Monoesters

Species-Specific Activation of Transient Receptor Potential Ankyrin 1 by Phthalic Acid Monoesters

Cumulative Exposure to Phthalates and Their Alternatives and Associated Female Reproductive Health: Body Burdens, Adverse Outcomes, and Underlying Mechanisms

Risk Assessment of Phthalates and Their Metabolites in Hospitalized Patients: A Focus on Di- and Mono-(2-ethylhexyl) Phthalates Exposure from Intravenous Plastic Bags

Contact Info

Product

Resources

About