Effects of low‐dose chlorpyrifos on neurobehavior and potential mechanisms: A review of studies in rodents, zebrafish, and <scp><i>Caenorhabditis elegans</i></scp>

Silva, Marilyn H.

doi:10.1002/bdr2.1661

Cited by 48 publications

(23 citation statements)

References 220 publications

(444 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Organophosphates' primary reported MoA, especially for acute neurotoxicity, is inhibition of acetylcholinesterase (AChE). However, behavioral studies in rodents, zebrafish and C. elegans suggest adverse effects of organophosphates on brain development after perinatal exposure already below concentrations inhibiting AChE, yet with some uncertainties (Silva 2020). Specific mechanisms for organophosphate-induced DNT in general have not been identified.…”

Section: Organophosphatesmentioning

confidence: 99%

Establishment of an a priori protocol for the implementation and interpretation of an in‐vitro testing battery for the assessment of developmental neurotoxicity

Masjosthusmann

Blum

Bartmann

et al. 2020

EFS3

156

View full text Add to dashboard Cite

In this project we set up a human cell-based DNT in vitro testing strategy that is based on test methods with high readiness and data generated therefrom. The methods underwent a fit-for-purpose evaluation that considered four key elements: 1. The test system, 2. the exposure scheme, 3. the assay and analytical endpoint(s) and 4. the classification model. This testing battery was challenged with 119 chemicals for which rich toxicological information was available (for some of them also on their DNT hazard). Testing was performed in 5 test systems measuring 10 DNT-specific endpoints and additional 9 viability/ cytotoxicity-related parameters. For approximately half of the compounds, additional and complementary data from DNT in vitro tests was added by the US-EPA. This extended battery was also evaluated. Testing results revealed that the test methods of this current DNT in vitro battery are reliable and reproducible. The endpoints had to a large extent low redundancy. Battery performance, as assessed with compounds well-characterized for DNT hazard had a sensitivity of 82.7 % and a specificity of 88.2 %. Gap analyses suggested that radial, astro-and microglia as well as myelination endpoints may be added to the battery. Two case studies, one for screening and prioritization of 14 flame retardants, and one on hazard characterization of 2 pesticides, were presented. Hypothetical AOPs were developed based on the latter case study. In conclusion, the DNT testing strategy explored here is a very promising first approach for DNT hazard identification and characterization. The performance is encouraging and may be improved by inclusion of further tests. Some uncertainties in DNT in vitro battery testing outcomes could be reduced by incorporating test data and modelling approaches related to in vitro and in vivo toxicokinetics of test compounds.

show abstract

Section: Organophosphatesmentioning

confidence: 99%

Establishment of an a priori protocol for the implementation and interpretation of an in‐vitro testing battery for the assessment of developmental neurotoxicity

Masjosthusmann

Blum

Bartmann

et al. 2020

EFS3

156

View full text Add to dashboard Cite

show abstract

“…Both human and rodent studies have found interesting links between exposure to these various pesticides and ASD diagnosis or ASD-like behaviors [ 24 , 25 ]. However, results differ depending on the agent, the dose, the time of exposure, age of behavioral assessment, and the outcomes measured.…”

Section: Introductionmentioning

confidence: 99%

Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models

Biosca-Brull

Pérez-Fernández

Mora

et al. 2021

IJERPH

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.

show abstract

“…Sex differences in this study can be attributed to various factors that require further investigation (reviewed in [72]. ASD is more common in males than in females [73,74], as observed in some genetic mouse models of the disorder [66].…”

Section: Discussionmentioning

confidence: 89%

Developmental and social deficits and enhanced sensitivity to prenatal chlorpyrifos in PON1-/- mouse pups and adults

et al. 2020

View full text Add to dashboard Cite

The levels and activity of the enzyme paraoxonase 1 affect the vulnerability to the teratogenic effects of organophosphate pesticides. Mutant mice lacking the gene for paraoxo-nase1 (PON1-/-) are more susceptible to the toxic effects of chlorpyrifos, and were hypothesized to be more vulnerable to social behavior deficits induced by exposure to chlorpyrifos during gestation. Three experiments were performed comparing PON1-/mice to PON1 +/+ mice born to dams treated with 0.5 mg/kg chlorpyrifos or cornoil vehicle on gestational days 12-15. Chlofpyrifos-exposed male PON1-/mouse pups had delayed development of reflexes in in the first experiment. In the second experiment, adult male and female PON1-/mice and the female PON1 +/+ mice all displayed lower social preference than the male vehicle-treated PON1 +/+ mice. The PON1-/mice and the female PON1 +/+ mice displayed lower social preference compared to the PON1 +/+ male mice. Male adult mice that had been exposed in utero to chlorpyrifos showed less conditioned social preference regardless of genotype. In the third study, the delayed reflex development was replicated in male and female PON1-/mice, but chlorpyrifos did not augment this effect. Nest Odor Preference, a test of early social attachment to dam and siblings, was lower in PON1-/mouse pups compared to PON1 +/+ pups. This study shows for the first time that PON1-/mice have a behavioral phenotype that indicates impaired reflex development and social behavior. Chlorpyrifos exposure during gestation tended to augment some of these effects.

show abstract

Effects of low‐dose chlorpyrifos on neurobehavior and potential mechanisms: A review of studies in rodents, zebrafish, and Caenorhabditis elegans

Cited by 48 publications

References 220 publications

Establishment of an a priori protocol for the implementation and interpretation of an in‐vitro testing battery for the assessment of developmental neurotoxicity

Establishment of an a priori protocol for the implementation and interpretation of an in‐vitro testing battery for the assessment of developmental neurotoxicity

Relationship between Autism Spectrum Disorder and Pesticides: A Systematic Review of Human and Preclinical Models

Developmental and social deficits and enhanced sensitivity to prenatal chlorpyrifos in PON1-/- mouse pups and adults

Contact Info

Product

Resources

About