Relative neurotoxicological properties of five unsaturated aliphatic nitriles in rats

Gagnaire, François; Marignac, B.; Bonnet, Pierre

doi:10.1002/(sici)1099-1263(199801/02)18:1<25::aid-jat466>3.0.co;2-v

Cited by 33 publications

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“…While there were no differences in the body weights between the control and treated groups, the deficiencies in the electrophysiological parameters still persisted at the end of the recovery period. In a previous work, five related unsaturated aliphatic nitriles were studied in rats (Gagnaire et al 1998); only acrylonitrile had a toxic effect on the nervous system albeit different from the effects observed in the present study. The four other nitriles studied were methacrylonitrile, 3-methyl-2-butenenitrile, 4-pentenenitrile and trans-3-pentenenitrile.…”

Section: Discussioncontrasting

confidence: 73%

“…Furthermore, neurophysiological examination was carried out in rats treated likewise with 3,3'-iminodipropionitrile (NH(CH~-CHZCN)~) as a reference neurotoxic nitrile. The data of this study should complete those of a previous study on the relative neurotoxicological properties of five unsaturated aliphatic nitriles (acrylonitrile, methacrylonitrile, 3-methyl-2-butenenitrile, 4-pentenenitrile and trans-3-pentenenitrile) (Gagnaire et al 1998) and should help draw some conclusions about the possible structure activity relationship in this important chemical family.…”

mentioning

confidence: 66%

“…1991), and weakness in hindlimbs in cats or rats accompanied by decreases in sensory and motor conduction velocities and in the amplitudes of the sensory action potentials (Dudley et al 1942;Quast et a/. 1980;Gagnaire et al 1998). In addition to its central neurotoxicity, not fully understood, 3,3'-iminodipropionitrile shows high peripheral neurotoxicity characterized by axonal swelling due to accumulation of neurofilaments in the proximal portion of the axon (Chou & Hartman 1964& 1965Clark et al 1980;Griffin & Price 1981; Author for correspondence: FranCois Gagnaire, Department of Industrial and Experimental Toxicology, National Institut for Research and Safety, Avenue de Bourgogne, B.P.…”

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confidence: 99%

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Electrophysiological Deficiency in Peripheral Nerve Induced by Treatment for 12 Weeks with 2‐Butenenitrile, 3‐Butenenitrile, cis‐2‐Pentenenitrile and 3, 3′‐Iminodipropionitrile in Rats

Gagnaire

Marignac

1999

Pharmacology & Toxicology

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Motor and sensory conduction velocities and amplitudes of the sensory and motor action potentials of the tail nerve were studied in male Sprague-Dawley rats during subchronic oral treatment with three unsaturated aliphatic nitriles.The rats were given, by gastric intubation, doses of 10, 20 and 40 mg . kg-' 3-butenenitrile (ally1 cyanide) and 25, 50 and 100 mg . kg-' of either cis/trans-2-butenenitrile (crotononitrile) or cis-2-pentenenitrile once a day, 5 days per week for 12 weeks. Moreover, 3,3'-iminodipropionitrile was administered likewise at doses of 25, 50 and 100 mg . kg-' as reference neurotoxicant. Oral administration of the three unsaturated nitriles produced deafness and absence of reaction when the animals were subject to droptest. Moreover, rats exhibited both time-and concentration-dependent decreases in motor and sensory conduction velocities and amplitudes of the sensory action potentials. Nerve conduction velocities were partially reversible after 8 weeks of recovery. Rats receiving 3,3'-iminodipropionitrile developed deafness, head weaving and significant irreversive deficiencies in all the electrophysiological parameters studied. Further toxicological studies with related unsaturated nitriles should be carried out to determine the potential importance of the cis/trans isomerism in the observed neurotoxicity.

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Section: Discussioncontrasting

confidence: 73%

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confidence: 66%

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Electrophysiological Deficiency in Peripheral Nerve Induced by Treatment for 12 Weeks with 2‐Butenenitrile, 3‐Butenenitrile, cis‐2‐Pentenenitrile and 3, 3′‐Iminodipropionitrile in Rats

Gagnaire

Marignac

1999

Pharmacology & Toxicology

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“…also demonstrated that administration of AN to rats by inhalation, produced electrophysiological changes in the tail nerves. 13 The chronic neurobehavioral effects of AN in rats are unknown, although Quast described behavioral changes in a long-term carcinogenicity study, reporting that Á 'During the study an occasional control and treated rat exhibited clinical signs of erratic movements, trembling, circling and limb weakness suggestive of nervous system dysfunction'. 12 However, these studies were grossly descriptive in nature, and the potential neurobehavioral effects of AN have not been quantitated objectively.…”

Section: Introductionmentioning

confidence: 99%

Neurobehavioral alterations in rats exposed to acrylonitrile in drinking water

Suhua²,

Xing

et al. 2007

Hum Exp Toxicol

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This study was carried out on rodents, to explore the neurobehavioral effects of acrylonitrile (AN) administered in drinking water. Thirty, male, Sprague-Dawley rats were randomly divided into three groups: two exposure groups (50 and 200 ppm AN), and one control group (tap water without AN). Three tests, including the open field test, rotarod test and spatial water maze, were applied to evaluate locomotor activities, motor co-ordination and learning and memory, respectively, prior to initiation of the treatment, and at Week 4, 8 and 12 postexposure. There were no consistent changes in the open field test, except for locomotion and grooming episodes. In the rotarod test, AN significantly decreased the latencies to fall in a dose and time-dependent manner. In the spatial water maze test, rats exposed to AN for 12 weeks had significantly more training times and longer escape latencies than control animals. These findings indicate that oral exposure to AN induces neurobehavioral alterations in rats.

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“…study. 3 . The panel agreed with the use of an uncertainty factor of 1.8 for human variability in toxicokinetics, based on the ratio of the 95th percentile to the mean for acrylonitrile in blood; 4 a factor of 3.2 for human variability in toxicodynamics; a factor of 3.2 for toxicodynamic differences between rats and humans; and a factor of 10 for subchronic to chronic extrapolation.…”

Section: Hazard Characterizationmentioning

confidence: 99%

Report of an independent peer review of an acrylonitrile risk assessment

Haber¹,

Patterson

2005

Hum Exp Toxicol

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A peer review panel made up of experts in toxicology, epidemiology, cancer mode of action (MOA), cancer mechanisms, carcinogenicity, genotoxicity, dose–response, US Environmental Protection Agency (EPA) cancer and noncancer methods, pharmacokinetic modeling and acrylonitrile, met on 22–23 September 2003 in Cincinnati, OH. The purpose of the meeting was to provide an independent review of a risk assessment of acrylonitrile that had been prepared by the Acrylonitrile Group (AN Group). Toxicology Excellence for Risk Assessment (TERA) organized the peer review and selected the panel. The panel discussed the toxicity and epidemiology literature of acrylonitrile and MOA information, and reached conclusions regarding its MOA, weight of evidence (WOE) for carcinogenicity, preferred approach for dose-response assessment and risk values. This paper summarizes the discussion and conclusions of the panel regarding the acrylonitrile assessment. Subsequent to the peer review, the authors of the acrylonitrile assessment revised their report and the panel reviewed the revised report. A manuscript of the revised assessment is being published in Regulatory Toxicology and Pharmacology.

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Relative neurotoxicological properties of five unsaturated aliphatic nitriles in rats

Cited by 33 publications

References 0 publications

Electrophysiological Deficiency in Peripheral Nerve Induced by Treatment for 12 Weeks with 2‐Butenenitrile, 3‐Butenenitrile, cis‐2‐Pentenenitrile and 3, 3′‐Iminodipropionitrile in Rats

Electrophysiological Deficiency in Peripheral Nerve Induced by Treatment for 12 Weeks with 2‐Butenenitrile, 3‐Butenenitrile, cis‐2‐Pentenenitrile and 3, 3′‐Iminodipropionitrile in Rats

Neurobehavioral alterations in rats exposed to acrylonitrile in drinking water

Report of an independent peer review of an acrylonitrile risk assessment

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