Developmental toxicity study of chlorpyrifos in rats

Farag, Ahmed A.; Okazy, Ahmed M El; El-Aswed, Ahmed F

doi:10.1016/s0890-6238(02)00121-1

Cited by 77 publications

(48 citation statements)

References 37 publications

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“…In the present study, high dose (15 mg/kg/d) of chlorpyrifos also induced fetal death and minor insignificant malformations. Similar observations in rats exposed to chlorpyrifos at 15 mg/kg/d dose were also reported (Breslin et al, 1996;Farag et al, 2003). Transfer and compartmentalization of chemical from mother to Table 5.…”

Section: Discussionsupporting

confidence: 80%

Transplacental Disposition and Teratogenic Effects of Chlorpyrifos in Rats

2006

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-Rats were orally fed with different doses viz. 9.6, 12 and 15mg/kg/d from GD 0-20 and examined for evidence of fetotoxicity and teratogenecity to evaluate the potential effects of technical chlorpyrifos (97%). Fetotoxic effects were not observed at tested dose levels as evidenced by number of implantations, number of corpora lutea and live fetuses/dam, but significant alterations were noted in percent δ resorption and fetal weight. There were no major malformations, but some minor anomalies such as reduced parietal ossification and absence of phalanges found significant in high dose were not considered as compound-related effects. On the other hand the accumulation of chlorpyrifos residue in dams was more in brain (0.0328 μg/g) than in liver (0.0071 μg/g).The level of residue in fetuses was in the following order : liver (0.0531 μg/g) > brain (0.0364 μg/g) >placenta (0.040 μg/g) > amniotic fluid (0.0010 μg/g). Although, the total residue was higher in fetuses (0.0447 μg/g) than in dams (0.0120 μg/g), the absence of abnormalities in fetal gross morphology, visceral and skeleton suggest that technical chlorpyrifos at tested dose levels is non-teratogenic in rats.

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Section: Discussionsupporting

confidence: 80%

Transplacental Disposition and Teratogenic Effects of Chlorpyrifos in Rats

2006

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“…When rabbits were given 0, 1, 9, 81, or 140 mg/kg/day on gestation days 7-19, slightly decreased fetal weights and crown-rump lengths, an increased incidence of unossified xiphisternum and/or fifth sternebra occurred at 140 mg/kg/day; however, this dose was also maternally toxic (202). More recent studies reporting no fetal effects in rats given up to 15 mg/kg/day via gavage from day 0 to 20 of pregnancy (216), or up to 25 mg/kg/day via gavage on days 6-15 of pregnancy are consistent with these observations (217). Maternal brain cholinesterase activity was significantly reduced at 15 and 25 mg/kg/day when dosed on days 6-15 of pregnancy.…”

Section: Reproductive and Developmentalsupporting

confidence: 70%

Organophosphorus Pesticides

Storm¹

2012

Patty's Toxicology

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Most organophosphorus compounds today fall into two general groups: the so‐called nerve agents, that are very acutely toxic and organophosphorus pesticides that are less toxic. Nerve agents were generally the first toxic organophosphorus developed, and were the original basis for organophosphorus pesticides. Interest about nerve agents has increased lately given concerns about their potential use in terrorist acts. Organophosphate nerve agents and pesticides are a highly diverse group of chemicals. They are all characterized by their ability to inhibit the enzyme acetylcholinesterase (AChE) that deactivates the neurotransmitter acetylcholine (ACh). At present, the widest use of organophosphorus compounds is as pesticides, although they have also been used as therapeutic agents, gasoline additives, hydraulic fluids, cotton defoliants, fire retardants, plastic components, growth regulators, and industrial intermediates to a much smaller extent. Compounds in this class are numerous and have been categorized in many ways according to the nature of the substituents. Gallo and Lawryk (1991) [2], for example, categorized them into four main groups I–IV based on the characteristics of the leaving group (X). Group I compounds, phosphorylcholines, have a leaving group that contains a quaternary nitrogen and are among the most potent organophosphates (e.g., Shradan). Group II compounds, fluorophosphates, have a fluoride leaving group and are also generally highly toxic (e.g., diisopropyl fluorophosphate). Group III compounds have leaving groups that contain cyanide or a halogen other than fluoride and are generally less potent than group I or II (e.g., Parathion). Group IV contains most of the organophosphates used as insecticides today. These compounds have alkoxy, alkylthio, aryloxy, arylthio, or heterocyclic leaving groups and a wide variety of other substituents. Another classification scheme is based on the nature of the atoms that immediately surround the central phosphorus atom and results in 14 different categories. According to this scheme, phosphates are the prototype for the entire class and are those compounds where all four atoms that surround the phosphorus atom are oxygen (e.g., dichlorvos, mevinphos). Sulfur‐containing organophosphate compounds (phosphorothioates, phosphorothiolates, phosphorodithioates, and phosphorodithiolates) are far more numerous than phosphates and include well‐recognized organophosphate insecticides such as parathion, diazinon, chlorpyrifos, etc. Other groups contain nitrogen (phosphoramides and phosphorodiamides), nitrogen and sulfur (phosphoramidothionates and phosphoramidothiolates), carbon (phosphonates and phosphinates), or carbon and sulfur (phosphonothionates, phosphonothionothiolates, and phosphinothionates). All aspects of organophosphate chemistry, toxicity, analysis, and exposure potential have been previously and comprehensively reviewed. In addition, information regarding the toxicity of organophosphorus pesticides in particular has expanded greatly in recent years as a result of toxicity data supplied by registrants to the U.S. EPA's Office of Pesticides to support reregistration. These data have been made publicly available by the U.S. EPA on its Internet Web site ( www.epa.gov/pesticides ). The following discussion draws heavily from recent reviews and also includes summaries of relevant toxicity data submitted to, and made available by, the U.S. EPA.

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“…The negative findings of the previous reports are supported by an additional study in which Fischer 344 rats were given 0, 5, 15, 25 mg/kg by gavage on days 6-15 of pregnancy (Farag et al, 2003). Fetuses were evaluated on prenatal day 21.…”

Section: Iiic1 General Teratogenic and Reproductive Toxicity Assaymentioning

confidence: 81%