Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat

Kristensen, David M.; Hass, Ulla; Lesné, Laurianne; Lottrup, Grete; Jacobsen, Peter; Desdoits-Lethimonier, Christèle; Boberg, Julie; Petersen, Jørgen Holm; Toppari, Jorma; Jensen, Tina Kold; Brunak, Søren; Skakkebæk, Niels E.; Nellemann, Christine; Main, Katharina M.; Jégou, Bernard; Leffers, Henrik

doi:10.1093/humrep/deq323

Cited by 222 publications

(254 citation statements)

References 39 publications

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“…Reasons for the intake of OTC analgesics were mainly headache (66.5%) followed by muscle ache (8.7%) and other types of pain (8.7% in sum). Fever, inflammation, and cold accounted for 6.9% (Kristensen et al 2010).…”

Section: Na4ap In Human Nsaidsmentioning

confidence: 99%

“…There is also an influence based on whether the inquiry was realized through self-administered questionnaires or by telephone interviews. In a study carried out in a Danish cohort (Kristensen et al 2010), 285 mothers completed both a questionnaire and a telephone interview. In the questionnaire, 30.9% (88 of 285) of the mothers reported the use of analgesics as opposed to 57.2% in the telephone interview (163 of 285).…”

Section: Na4ap In Human Nsaidsmentioning

confidence: 99%

“…PGs are supposed to be involved, inter alia, in processes such as early male sexual development and masculinization and hormone regulation (Gupta 1989, Amateau & McCarthy 2004. Kristensen et al (2010) showed that intrauterine exposure of Wistar rats to NA4AP led to a significant reduction in the anogenital distance of male offspring. In the same study, the authors reported a reduced production of PGD2 and testosterone in ex vivo fetal rat testes (Kristensen et al 2010).…”

Section: Evidence For the Developmental Toxicity Of Na4apmentioning

confidence: 99%

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Ubiquitous presence of paracetamol in human urine: sources and implications

Modick¹,

Weiß²,

Dierkes³

et al. 2014

Reproduction

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N-acetyl-4-aminophenol (acetaminophen/paracetamol, NA4AP) is one of the most commonly used over-the-counter analgesic and antipyretic drugs. Recent studies have reported anti-androgenic effects of NA4AP in vitro and possible associations between intrauterine exposure to NA4AP and the development of male reproductive disorders in humans. NA4AP is also a major metabolite of aniline (phenylamine), representing 75-86% of the aniline dose excreted in urine. Aniline is an important large-volume intermediate in several industrial processes. Besides individuals in various occupational settings with aniline exposure, the general population is also known to be ubiquitously exposed to aniline. In this article, we provide an overview of the recent literature concerning the intake of NA4AP during pregnancy and the possible anti-androgenic effects of NA4AP as well as literature concerning its known metabolic precursor aniline. We also present new research data, including the first human biomonitoring data on NA4AP excretion in urine, showing ubiquitous NA4AP body burdens in the general population at a wide range of concentrations. We found a small but significant impact of smoking on urinary NA4AP concentrations. We further present preliminary data on NA4AP excretion after therapeutic acetaminophen use, after aniline exposure in an occupational setting, and during a controlled fasting study (excluding oral exposure to both aniline and acetaminophen). Our findings indicate exposure to aniline (or aniline-releasing substances) as well as nutrition (next to the direct use of acetaminophen as medication) as possible sources of internal body burdens of NA4AP.Reproduction (2014) 147 R105-R117

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Section: Na4ap In Human Nsaidsmentioning

confidence: 99%

Section: Na4ap In Human Nsaidsmentioning

confidence: 99%

Section: Evidence For the Developmental Toxicity Of Na4apmentioning

confidence: 99%

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Ubiquitous presence of paracetamol in human urine: sources and implications

Modick¹,

Weiß²,

Dierkes³

et al. 2014

Reproduction

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show abstract

“…Because acetaminophen is known to freely cross the placenta (2,11), the effects on fetus are needed to be considered for use during pregnancy. To date, several different birth cohort studies have associated maternal use of acetaminophen with increasing risk for reproductive disorders in male offspring (12)(13)(14).…”

mentioning

confidence: 99%

A risk assessment of a common drug using xenograft model

Kodama

Kurokawa

2017

Ann. Transl. Med.

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“…Durant la décennie 1990, les données sur l'action des PEE étaient éparses et insuffisamment structurées, donnant prise à des controverses. Depuis les années pendant les deux premiers trimestres) exposerait aussi à un risque accru de cryptorchidie [16]. L'expérimentation animale a permis de démontrer le lien causal entre l'exposition aux perturbateurs endocriniens (antiandrogène et/ou estrogénomimétique) et le syndrome de dysgénésie testiculaire (Tableau I).…”

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