Maturational differences in chlorpyrifos-oxonase activity may contribute to age-related sensitivity to chlorpyrifos

Mortensen, Spencer R.; Chanda, Sushmita; Hooper, Michael J.; Padilla, Stephanie

doi:10.1002/(sici)1522-7146(1996)11:6<279::aid-jbt3>3.0.co;2-h

Cited by 118 publications

(42 citation statements)

References 21 publications

(30 reference statements)

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“…Young animals may be more susceptible to the toxic effects of organophosphates due to lower activity of detoxifying enzymes such as paraoxonase that deactivate active OP metabolites (e.g., paraoxon, chlorpyrifos-oxon) (123,(126)(127)(128)(129)(130)(131). For example, Mortensen et al (126) reported markedly lower plasma and liver chlorpyrifos-oxonase levels in neonate compared to adult rat tissue.…”

Section: Potential Respiratory Health Effectssupporting

confidence: 92%

“…In summary, young children may be especially vulnerable to pesticides because of the sensitivity of their developing organ systems combined with a limited ability to enzymatically detoxify these chemicals (13,123,(126)(127)(128)(129)(130)(131). According to the National Academy of Sciences (13), children's OP exposures are of special concern because "exposure to neurotoxic compounds at levels believed to be safe for adults could result in permanent loss of brain function if it occurred during the prenatal and early childhood period of brain development" (13).…”

Section: Potential Respiratory Health Effectsmentioning

confidence: 98%

“…For example, Mortensen et al (126) reported markedly lower plasma and liver chlorpyrifos-oxonase levels in neonate compared to adult rat tissue. They concluded that the higher sensitivity of young rats to acute chlorpyrifos toxicity may not be explained by increased sensitivity of the target enzyme, brain AChE, but it may be partially explained by a deficiency of chlorpyrifos-oxonase activity (126).…”

Section: Potential Respiratory Health Effectsmentioning

confidence: 99%

See 2 more Smart Citations

Exposures of children to organophosphate pesticides and their potential adverse health effects.

Eskenazi

Bradman

Castorina

1999

Environ Health Perspect

582

326

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Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children's exposure to pesticides and other environmental agents, and thereby reduce the incidence of environmentally related disease.

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Section: Potential Respiratory Health Effectssupporting

confidence: 92%

Section: Potential Respiratory Health Effectsmentioning

confidence: 98%

Section: Potential Respiratory Health Effectsmentioning

confidence: 99%

See 1 more Smart Citation

Exposures of children to organophosphate pesticides and their potential adverse health effects.

Eskenazi

Bradman

Castorina

1999

Environ Health Perspect

582

326

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“…This may not be the case for organophosphorus pesticide toxicity because both the activation and detoxification potential in young animals usually is less than in adults (156), producing increased toxicity in the young (157). This increased toxicity stems mainly from an agerelated deficiency in detoxification enzymes in the young (158)(159)(160).…”

Section: Practical Considerations In the Experimental Design Of Pharmmentioning

confidence: 89%

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

DORMAN

Allen

Byczkowski

et al. 2001

Environ Health Perspect

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We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic.

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“…Considerable evidence suggests that immature detoxification mechanisms in the young account for much of the reported age-related differences in sensitivity (e.g., Atterberry et al 1997;Benke and Murphy 1975;Chanda et al 1997;Mendoza 1976;Mortensen et al 1996;Sterri et al 1985). All of these chemicals are detoxified through a combination of P450 microsomal enzymes, carboxylesterases, and/or A-esterases, but the metabolic patterns differ greatly (Chambers et al, 2010).…”

Section: Kineticsmentioning

confidence: 99%

Age-Related Differences in Acetylcholinesterase Inhibition Produced by Organophosphorus and N-Methyl Carbamate Pesticides

Moser¹

2011

Pesticides in the Modern World - Pests Control and Pesticides Exposure and Toxicity Assessment

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Maturational differences in chlorpyrifos-oxonase activity may contribute to age-related sensitivity to chlorpyrifos

Cited by 118 publications

References 21 publications

Exposures of children to organophosphate pesticides and their potential adverse health effects.

Exposures of children to organophosphate pesticides and their potential adverse health effects.

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

Age-Related Differences in Acetylcholinesterase Inhibition Produced by Organophosphorus and N-Methyl Carbamate Pesticides

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