developmental neurotoxicity
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Environmental health perspectives. Supplements, ISSN 1078-0475 Vol.. 102, suppl. 2, 1994
164 s. : il., tab. ; 28 cm
- MeSH
- environmentální zdraví MeSH
- neurotoxické syndromy MeSH
- Publikační typ
- sborníky MeSH
- Konspekt
- Hygiena. Lidské zdraví
- NLK Obory
- environmentální vědy
- toxikologie
Cyanobacterial blooms are increasing in frequency and intensity globally, and impacting recreational waters as well as waters used for drinking water provisioning. They are sources of bioactive metabolites including retinoids and the neurotoxin anatoxin-a. Here, we investigated the effects of anatoxin-a on a differentiating in vitro human neural stem cell model previously characterised with retinoic acids. Effects on protein and gene expression upon exposure for 9 or 18 days to anatoxin-a alone or in co-exposure with all-trans retinoic acid were evaluated using a panel of neural and glial differentiation biomarkers. Anatoxin-a did not cause distinct developmental neurotoxicity alone, or in co-exposure with retinoic acid. However, in line with its excitotoxicity, in co-exposure with 200 nM all-trans retinoic acid it reduced the differentiation of acetylcholinergic neuron subtypes in the culture at 1000 nM (highest tested concentration). While this could have substantial functional implications for the developing nervous system, there is no indication for developmental neurotoxicity beyond its (excito-)toxicity to acetylcholinergic neurons, which only occurred in co-exposure to all-trans retinoic acid.
- MeSH
- exprese genu MeSH
- lidé MeSH
- neurotoxické syndromy * etiologie MeSH
- retinoidy metabolismus MeSH
- sinice * MeSH
- toxiny kmene Cyanobacteria MeSH
- tretinoin toxicita MeSH
- tropany * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
... CONTENTS -- ENVIRONMENTAL HEALTH CRITERIA FOR NEUROTOXICITY RISK ASSESSMENT FOR HUMAN HEALTH: PRINCIPLES ... ... INTRODUCTION 7 -- 2.1 Purpose of the publication 7 -- 2.2 General principles of neurotoxicity risk assessment ... ... 17 -- 2.4.1 Neurotoxicity versus adverse effects 17 -- 2.4.2 Direct versus indirect effects 18 -- 2.4.3 ... ... BASIC PRINCIPLES FOR NEUROTOXICITY RISK -- ASSESSMENT 25 -- 3.1 Neurobiological principles 25 -- 3.1.1 ... ... neurotoxicity 137 -- 5.4 In vitro methods 141 -- 5.5 Testing strategies for neurotoxicity 144 -- 5.6 ...
Environmental health criteria, ISSN 0250-863X 223
xxi, 223 s. : tab. ; 24 cm
- MeSH
- hodnocení rizik metody MeSH
- nervový systém účinky léků MeSH
- neurotoxické syndromy etiologie MeSH
- vystavení vlivu životního prostředí MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- neurologie
- toxikologie
- environmentální vědy
- NLK Publikační typ
- publikace WHO
BACKGROUND: Pyrethroid metabolites are widely detectable in urine from the general population, including pregnant women and children. Pyrethroids are neurotoxic and suggested endocrine disruptors. Exposure during vulnerable developmental time windows may have long-term impacts on neurodevelopment. OBJECTIVE: To evaluate the epidemiological evidence for neurodevelopmental effects related to prenatal and childhood pyrethroid exposure in a systematic review and to assess biological plausibility by evaluating mechanistic evidence. METHODS: We searched PubMed and Web of Science up to September 1, 2021 and included original studies published in English in which pyrethroid exposure was measured or estimated during pregnancy or childhood and associations with neurodevelopmental outcomes in the children were investigated. The Navigation Guide Systematic Review Methodology was used to evaluate the epidemiological evidence. For mechanistic evidence, we focused on relevant key events (KEs) suggested in Adverse Outcome Pathways (AOPs) using the OECD-supported AOP-wiki platform. A systematic search combining the KEs with pyrethroids, including 26 individual compounds, was performed in the ToxCast database. RESULTS: Twenty-five epidemiological studies met the inclusion criteria, 17 presented findings on prenatal exposure, 10 on childhood exposure and two on both exposure windows. The overall body of evidence was rated as "moderate quality" with "sufficient evidence" for an association between prenatal pyrethroid exposure and adverse neurodevelopment. For childhood exposure, the overall rating was "low quality" with "limited evidence" because of cross-sectional study design. Regarding mechanistic evidence, we found that pyrethroids are able to interfere with neurodevelopmental KEs included in established AOPs for adverse neurodevelopmental. The evidence was strongest for interference with thyroid hormone (TH) function. CONCLUSION: Pyrethroids are probably human developmental neurotoxicants and adverse impacts of pyrethroid exposure on neurodevelopment are likely at exposure levels occurring in the general population. Preventive measures to reduce exposure among pregnant women and children are warranted.
- MeSH
- dítě MeSH
- epidemiologické studie MeSH
- hormony štítné žlázy MeSH
- insekticidy * toxicita MeSH
- lidé MeSH
- průřezové studie MeSH
- pyrethriny * metabolismus toxicita MeSH
- těhotenství MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- systematický přehled MeSH
Neurotoxic properties of quinolinic acid following intracerebroventricular application were investigated in the hippocampal formation of 12- and 30-day-old rats. Quinolinic acid neurodegenerative potency was found to depend on the survival time, the dose applied and the developmental stage of the animal. Pretreatment with kynurenic acid and ketamine as well as the transection of the perforant path were noted to protect major parts of the hippocampal cell layers from quinolinic acid-induced degenerative effects. The results are interpreted in view of a putative dependence of quinolinic acid neurotoxicity on the presence of established synaptic, in particular glutamatergic, processes which play a major role in the hippocampal formation and mature during the first postnatal weeks. For comparison, we studied local effects of quinolinic acid on superior cervical and dorsal root ganglia in which glutamate inputs obviously do not occur; no signs of neuronal vulnerability were seen.
- MeSH
- glutamáty * fyziologie MeSH
- hipokampus * patologie růst a vývoj účinky léků MeSH
- inbrední kmeny potkanů MeSH
- injekce intraventrikulární MeSH
- ketamin * farmakologie MeSH
- krysa rodu rattus MeSH
- kyselina chinolinová MeSH
- kyselina glutamová MeSH
- kyselina kynurenová farmakologie MeSH
- kyseliny chinolinové antagonisté a inhibitory toxicita MeSH
- neurotoxiny farmakologie MeSH
- pyridiny * toxicita MeSH
- věkové faktory MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Záměr: Práce shrnuje neuropsychologické sledování zaměstnanců exponovaných TCDD při hromadné průmyslové intoxikaci v letech 1965-1968 v závodě vyrábějícím herbicidy. Soubor a metody: Asi 350 osob bylo exponovaných, u 80 dělníků se projevily známky otravy. V letech 1996 a 2001 bylo vyšetřeno vždy 13 mužů, v r. 2004 14 mužů, v roce 2008 10 mužů. Byly hodnoceny 1. základní kognitivní výkonnost (WAIS-R), 2. paměť, pozornost, exekutivní funkce (WMS, HRNB, WCST a další), 3. sebeposouzení vyšetřovaných osob, 4. symptomová validita (TOMM, Retest Consistency Index –RCI a vzorec výkonů v subtestech Opakování čísel a Slovník). Statistická analýza: Použity byly deskriptivní metody a Spearmanova pořadová korelace. Výsledky: I čtyřicet let po intoxikaci byla ve skupině vyšetřovaných hladina TCDD v tuku 100x vyšší než v obecné populaci. Po celou dobu sledování byly v souboru doklady neuropsychologického oslabení především exekutivních fukcí. Byly zjištěny významné korelace mezi hladinami TCDD a neuropsychologickými výkony. Omezení studie: Malý rozsah souboru omezuje možnost zobecnění výsledků. Nicméně jsou v souladu s řadou citovaných prací.
- Klíčová slova
- neuropsychologické oslabení, TCDD,
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy statistika a číselné údaje MeSH
- neuropsychologie metody statistika a číselné údaje MeSH
- polychlorované dibenzodioxiny škodlivé účinky MeSH
- pracovní expozice statistika a číselné údaje škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- MeSH
- neuropsychologické testy MeSH
- neurotoxiny MeSH
- noxy MeSH
- toxikologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
Ochratoxin A (OTA) is nephrotoxic, hepatotoxic, reprotoxic, embryotoxic, teratogenic, neurotoxic, immunotoxic, and carcinogenic for laboratory and farm animals. Male and female reproductive health has deteriorated in many countries during the last few decades. A number of toxins in environment are suspected to affect reproductive system in male and female. OTA is one of them. OTA has been found to be teratogenic in several animal models including rat, mouse, hamster, quail, and chick, with reduced birth weight and craniofacial abnormalities being the most common signs. The presence of OTA also results in congenital defects in the fetus. Neither the potential of OTA to cause malformations in human nor its teratogenic mode of action is known. Exposure to OTA leads to increased embryo lethality manifested as resorptions or dead fetuses. The mechanism of OTA transfer across human placenta (e.g., which transporters are involved in the transfer mechanism) is not fully understood. Some of the toxic effects of OTA are potentiated by other mycotoxins or other contaminants. Therefore, OTA exposure of pregnant women should be minimized. OTA has been shown to be an endocrine disruptor and a reproductive toxicant, with abilities of altering sperm quality. Other studies have shown that OTA is a testicular toxin in animals. Thus, OTA is a biologically plausible cause of testicular cancer in man.
- MeSH
- blokátory kalciových kanálů toxicita MeSH
- endokrinní disruptory toxicita MeSH
- karcinogeny toxicita MeSH
- křečci praví MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- ochratoxiny toxicita MeSH
- rozmnožování účinky léků MeSH
- spermie abnormality MeSH
- těhotenství MeSH
- teratogeneze účinky léků MeSH
- teratogeny toxicita MeSH
- testikulární nádory chemicky indukované MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH