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Papers by stefano caroldi

Arhiv za higijenu rada i toksikologiju, 1989

Dose-effect and dose-response relationships in occupational neurotoxicology are rarely studied by... more Dose-effect and dose-response relationships in occupational neurotoxicology are rarely studied by means of biochemical methods. Some biochemical markers are however available to extrapolate from animal to man and to use in monitoring human exposures. They might be framed in three categories exploring: the delivery of chemicals to the site of action, the modifications of the molecular target induced by chemicals, the biochemical consequences of these modifications. Estimation of absorbed doses in man is possible for virtually every neurotoxic chemical by means of analytical chemistry of body fluids. Protein adducts, as measured in cellular and other blood components, might assess more closely the delivery in vivo, to the site of action. In this way also in vivo comparisons across species will be more precise. Examples include haemoglobin adducts, plasma pseudocholinesterase inhibition etc. In addition measurements of blood enzymes involved in the detoxification (e.g. A-esterases and ...

Toxicology and Applied Pharmacology, 1987

Biochemical Pharmacology, 1984

The conversion of dopamine to noradrenaline, measured shortly after exposure to carbon disulphide... more The conversion of dopamine to noradrenaline, measured shortly after exposure to carbon disulphide, is reduced in the adrenals of rats. However, alongside this effect, carbon disulphide produces a gradual increase in the adrenal content of dopamine-beta-hydroxylase indicated by the increase of in vitro estimated enzyme activity and by the increased in vivo conversion of dopamine to noradrenaline observed 24 hr after the ninth exposure. Thus, after repeated exposures, the reduced rate of noradrenaline synthesis detectable immediately after the exposure alternates with the increased rate of synthesis.

Archives of Toxicology, 1995

Both disulfiram (tetraethylthiuram disulfide), an alcohol aversive drug, and thiram (tetramethylt... more Both disulfiram (tetraethylthiuram disulfide), an alcohol aversive drug, and thiram (tetramethylthiuram disulfide), a widely used pesticide, significantly increased the dopamine pool in the adrenal glands of dosed rats. The dopamine increase was detectable within 4 h of oral dosing with 100 mg/kg of either dithiocarbamate and peaked 24 h later at 10 times control values. In control rats the dopamine turnover was 0.51 h-1 as calculated by the assumed first order decline of dopamine after a single injection of ~-methylp-tyrosine (e-MT, 400 mg/kg i.p.) resulting in a dopamine-fi-hydroxylase (DBH) activity of 0.73 nmol/h per pair of adrenals. In the adrenals of rats pretreated with thiram and then injected with e-MT, the adrenal dopamine content did not significantly decline, indicating that thiram reduced the conversion ofdopamine to noradrenaline, eventually leading to the observed dopamine increase. Plasma DBH activity was significantly reduced 4 h and 24 h after dosing with thiram, but was unchanged after treatment with disulfiram. The determination of plasma DBH activity could be a marker to monitor the effect of thiram on catecholamine metabolism in occupationally exposed workers but not that of disulfiram in abstinent alcoholics.

Archives of Toxicology, 1984

Male rats were exposed for a maximum of 4 h to carbon disulphide at atmospheric levels of 1.0-4.0... more Male rats were exposed for a maximum of 4 h to carbon disulphide at atmospheric levels of 1.0-4.0 mg/1 and the turnover rates of adrenal dopamine was determined by injecting a-methyl-p-tyrosine and measuring the rate at which dopamine disappears. Although the level of exposure was significantly higher than the 30.0 ~tg/1 permissible limit, or the average occupational exposure, similar or even higher peak exposure values were reported from the viscose rayon industry. After inhibition of tyrosine hydroxylase by a-methyl-p-tyrosine, adrenal dopamine contents declined at a slower rate in rats exposed to carbon disulphide than in controls. The reduced rate of dopamine metabolism during exposure to carbon disulphide indicates inhibition of dopamine-fl-hydroxylase in vivo. The size of this effect, which could be detected as soon as 30 min after starting the exposure to carbon disulphide, was dose dependent. The rate of dopamine turnover was still reduced 2 h after the end of a single exposure. However at that time, because of the larger dopamine pool present in the adrenals, the amount of dopamine converted per unit of time was again at pre-exposure levels.

Archives of Toxicology, 1981

Levels of acetylcholinesterase and neurotoxic esterase were measured in brain autopsy material. I... more Levels of acetylcholinesterase and neurotoxic esterase were measured in brain autopsy material. In tissue from a fatal human poisoning and from hens given 4-8 x unprotected LDs0 AChE was highly inhibited and neurotoxic esterase uninhibited. The findings correlate with the inhibitory power of omethoate against these enzymes in vitro. It is concluded that omethoate has negligible potential to cause delayed neuropathy and a published report of human neuropathy due to omethoate is criticised.

Archives of Toxicology, 1991

Chlorpyrifos [0,0-diethyl 0-(3,5,6-trichloro-pyridyl) phosphorothioate] caused delayed polyneurop... more Chlorpyrifos [0,0-diethyl 0-(3,5,6-trichloro-pyridyl) phosphorothioate] caused delayed polyneuropathy in man. Contrary to previous studies, we report here that it also causes delayed polyneuropathy in the hen, the animal model for this toxicity. The minimal neuropathic dose was 60-90 mg/kg p.o., corresponding to 4-6 times the estimated LDs0. Consequently, pralidoxime (2-PAM) in conjunction with atropine was necessary to reverse acetylcholinesterase (ACHE) inhibition and cholinergic toxicity in hens given high enough doses of chlorpyrifos to cause neuropathy. Chlorpyrifos was slowly absorbed after single oral doses and the threshold of inhibition (>70%) of neuropathy target esterase (NTE), the putative target for delayed neuropathy, was reached within 5-6 days. High AChE inhibition (>90%), however, was measured within hours after dosing because of the higher potency of chlorpyrifos to inhibit this enzyme. In vitro studies showed that chlorpyrifos-oxon, the active metabolite of chlorpyrifos, was 10-20 times more active against AChE than against NTE, confirming the clinical observation. No differences were seen between human and hen enzymes in this respect. Hen and human brain homogenates contain A-esterases which hydrolysed chlorpyrifos to about the same extent in both species. In conclusion, chlorpyrifos causes delayed polyneuropathy in the hen, as was reported in man. The reasons for previous negative data in the hen are probably due to the relatively lower doses which were used. Judging from in vitro studies with hen and human enzymes, there are no differences in the two species as far as their relative sensitivity to delayed polyneuropathy. It is likely that delayed polyneuropathy would develop in both species only after severe cholinergic toxicity requiring aggressive antidotal treatment.

Archives of Toxicology, 1991

Methamidophos causes acute cholinergic toxicity in several species, including man, and organophos... more Methamidophos causes acute cholinergic toxicity in several species, including man, and organophosphate-induced delayed polyneuropathy which has been reported in man but not in the hen. Acetylcholinesterase (AChE) and neuropathy target esterase (NTE) are thought to be the molecular targets of acute and delayed toxicity, respectively. The rate constants of inhibition (ka) and reactivation (k + 3) of human and hen brain AChE and NTE by methamidophos resolved optical isomers are here reported. NTE inhibition was progressive and irreversible. Human and hen NTE ka (M-1.m-1) for D-(+) methamidophos was 88 and 59, respectively, and for L-(-) methamidophos 3.2 and 3.0, respectively. AChE spontaneously reactivates after inhibition. D-(+) methamidophos 10(-3).ka (M-1.m-1) for human and hen AChE was 0.24 and 0.13; 10(3).k+3 (m-1) was 0.83 and 0.69, respectively. L-(-) Methamidophos 10(-3).ka (M-1.m-1) for human and hen AChE was 5.7 and 2.8, whereas 10(3).k+3 (m-1) was 6.50 and 1.52, respectively. L-(-)-Inhibited AChE reactivated to about 60% for human and 30% for hen enzymes, respectively. D-(+)-Inhibited AChE reactivated to about 10-20% for both species. Maximal reactivation occurred within 4-6 h when a plateau was reached. The larger and faster reactivation of human AChE inhibited in vitro by L-(-) methamidophos suggests that a corresponding effect might be possible in vivo and therefore explain, in part, the relatively higher susceptibility of man to delayed polyneuropathy induced by racemic methamidophos which occurs, however, with doses always causing severe cholinergic toxicity.

Archives of Environmental Health: An International Journal, 1985

Measurement of neuropathy target esterase activity (NTE) in blood lymphocytes has been suggested ... more Measurement of neuropathy target esterase activity (NTE) in blood lymphocytes has been suggested as a possible biomonitor for organophosphate-induced delayed polyneuropathy. Human lymphocyte NTE was characterized in vitro according to the sensitivity to several organophosphate inhibitors, which was found similar to that of the nervous system enzyme. Methods for collection, storage, and processing of blood and the NTE assay are described (averaged coefficient of variation of the method is 8%). The mean (± SO) value of lymphocyte NTE activity in a caucasian population (108 healthy subjects) was 11.5 ± 2.5 nMoles/min • mg of protein. No sex or age differences were detected. The averaged intraindividual coefficient of variation was 1().1%. These results suggest the feasibility of the test in clinical conditions, a sufficient reproducibility of the test, and a large interindividual variation. Appropriate baseline values are advisable when using the test to evaluate the effects of an occupational exposure to organophosphorus esters which may cause delayed polyneuropathy.

Jat Journal of Applied Toxicology, Mar 1, 1994

... Stefan0 Caroldi,* Paola De Paris,* Sergio Zotti,S Ilia ZanellaS and Francesco BrugnoneO *Isti... more ... Stefan0 Caroldi,* Paola De Paris,* Sergio Zotti,S Ilia ZanellaS and Francesco BrugnoneO *Istituto di Medicina del Lavoro, University of Padova, Italy $Divisione Medica 111. ULSS 21, Padova. ... L. Magos, The clinical and experimental aspects of carbon disulphide intoxication. ...

Hum Exp Toxicol, 1994

1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals su... more 1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals such as zinc, ferrum and manganese but not that of copper. 2 We studied the effect of CaNa2EDTA injection on serum dopamine-β-hydroxylase, a copper-dependent enzyme, in three male lead welders hospitalized for suspected lead poisoning. 3 injection of CaNa 2EDTA (1000 mg i.v.) resulted in rapid reduction of serum dopamine-β-hydroxylase activity which returned to normal level within 24 hours. 4 Copper sulphate (8 μM) but not ethylmaleimide (10 mM) restored in vitro serum dopamine-β-hydroxylase activity to pre-dosing values which indicates that CaNa2EDTA inhibits dopamine-β-hydroxylase by removing copper from the enzyme. 5 An inverse dose effect relationship between injected CaNa2EDTA and residual serum dopamine-β-hydroxylase activity was observed. 6 In spite of the reported lack of changes in copper serum concentration, CaNa2EDTA significantly affects the activity of a copper-dependent enzyme in the serum. 7 As CaNa 2EDTA is currently the drug of choice for the treatment of asymptomatic lead poisoning in children, the effect of CaNa2EDTA on copper-enzymes requires further investigation.

Toxicology letters, 1988

Some organophosphorous esters cause a polyneuropathy which becomes clinically evident 2 weeks aft... more Some organophosphorous esters cause a polyneuropathy which becomes clinically evident 2 weeks after a single dose. The pathogenesis involves modifications of a target protein, neuropathy target esterase, in the axons and a selective inhibition of retrograde axonal transport. It was suggested that copper metabolism might also be involved because of increased levels of plasma copper and ceruloplasmin in animals developing this polyneuropathy. Our results do not confirm this observation; treatment of hens with highly neuropathic single doses of two organophosphates (dihexyl-2,2-dichlorovinyl phosphate and mono-o-cresyl diphenyl phosphate) does not affect total and plasma free copper when measured several times during the development of polyneuropathy. We concluded that copper homeostasis is not affected and that copper changes are unlikely to be involved in the pathogenesis of this polyneuropathy.

Toxicology Letters, 1981

A moderate neuropathic response was obtained in hens 2 weeks after being given a single massive S... more A moderate neuropathic response was obtained in hens 2 weeks after being given a single massive S.C. dose of dichtorvos (100 mg/kg of active ingredient in a commercial 50% formulation). I day after dosing inhibition of neurotoxic esterase in peripheral nerve was 79-90%, ~1. spinal cord 7041% and in brain 89-92%. It is unlikely that repeated exposure of man to dichlorvos could cause neuropathy except at doses causing severe cholinergic effects at every exposure.

Toxicology and Applied Pharmacology, 1982

The potential neurotoxicity of organophosphate esters is usually evaluated by measuring neurotoxi... more The potential neurotoxicity of organophosphate esters is usually evaluated by measuring neurotoxic esterase (NTE) inhibition in brains taken from dosed birds. An improved method to measure NTE in peripheral nerve has been developed and used to compare brain, spinal cord, and peripheral nerve NTE inhibition both in vitro and in vivo after a single dose of several organophosphates. Brain and spinal cord NTE activities are a good mirror of NTE activity of the sciatic nerve. The rate of resynthesis of NTE in peripheral nerves after inhibition with an effective dose of a neurotoxic organophosphate was similar to that in other nervous tissues.

Scandinavian Journal of Work, Environment & Health, 1980

The investigation evaluates the efficiency attributed to some measures (improvements in environme... more The investigation evaluates the efficiency attributed to some measures (improvements in environment, individual health habits) in reducing the risk of lead poisoning in the ceramics industry. The evaluation of the average levels of lead in the blood of 154 exposed workers was carried out in four plants at a time interval of six to eight months. The study considers the variations in relation to possible measures brought about during the interval. A reduction of environmental risk was in effect shown by a clear improvement in the blood lead levels, which still, however, exceeded the internationally recommended limits in many of the subjects. It was concluded that further improvements can only be made by reducing the lead content of the glazes used.

Scandinavian Journal of Work, Environment & Health, 1980

The ceramics industry and lead poisoning. Lead poisoning in relation to technology and jobs.

Occupational and Environmental Medicine, 1992

Assay of free and acid labile carbon disulphide (free and total CS2 respectively) in human blood ... more Assay of free and acid labile carbon disulphide (free and total CS2 respectively) in human blood was performed by gas chromatography/ spectrometry. The method used a large dynamic head space volume and a "cryogenic trap". Blood CS2 concentration was measured in 42 subjects not occupationally exposed to CS2 (group A) and in 11 alcoholic subjects (group B) treated with disulfiram. Free CS2 658 copyright.

Journal of Applied Toxicology, 1987

In agreement with the inhibition of dopamine-beta-hydroxylase by exposure to CS2, the extension o... more In agreement with the inhibition of dopamine-beta-hydroxylase by exposure to CS2, the extension of exposure time from 4 to 16 h increased dopamine concentrations in the hypothalmus and adrenals, and decreased noradrenaline concentration in the hypothalmus. The extension of exposure time also increased the toxicity of amphetamine. In conscious animals the stereotypic activity produced by 6.0 mg/kg and even that of 3.0 mg/kg amphetamine sulphate was suppressed by severe hyperthermia resulting in exhaustion, prostration and eventually death. A 16 h exposure to CS2 did not increase the lethal or hyperthermic effects of amphetamine in rats anaesthetized with 60 mg/kg sodium pentobarbitone. In fact the CS2 exposed rats became more hypothermic than non-exposed rats.

Journal of Applied Toxicology, 1994

... Stefan0 Caroldi,* Paola De Paris,* Sergio Zotti,S Ilia ZanellaS and Francesco BrugnoneO *Isti... more ... Stefan0 Caroldi,* Paola De Paris,* Sergio Zotti,S Ilia ZanellaS and Francesco BrugnoneO *Istituto di Medicina del Lavoro, University of Padova, Italy $Divisione Medica 111. ULSS 21, Padova. ... L. Magos, The clinical and experimental aspects of carbon disulphide intoxication. ...

Human & Experimental Toxicology, 1994

1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals su... more 1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals such as zinc, ferrum and manganese but not that of copper. 2 We studied the effect of CaNa2EDTA injection on serum dopamine-β-hydroxylase, a copper-dependent enzyme, in three male lead welders hospitalized for suspected lead poisoning. 3 injection of CaNa 2EDTA (1000 mg i.v.) resulted in rapid reduction of serum dopamine-β-hydroxylase activity which returned to normal level within 24 hours. 4 Copper sulphate (8 μM) but not ethylmaleimide (10 mM) restored in vitro serum dopamine-β-hydroxylase activity to pre-dosing values which indicates that CaNa2EDTA inhibits dopamine-β-hydroxylase by removing copper from the enzyme. 5 An inverse dose effect relationship between injected CaNa2EDTA and residual serum dopamine-β-hydroxylase activity was observed. 6 In spite of the reported lack of changes in copper serum concentration, CaNa2EDTA significantly affects the activity of a copper-dependent enzym...

Arhiv za higijenu rada i toksikologiju, 1989

Dose-effect and dose-response relationships in occupational neurotoxicology are rarely studied by... more Dose-effect and dose-response relationships in occupational neurotoxicology are rarely studied by means of biochemical methods. Some biochemical markers are however available to extrapolate from animal to man and to use in monitoring human exposures. They might be framed in three categories exploring: the delivery of chemicals to the site of action, the modifications of the molecular target induced by chemicals, the biochemical consequences of these modifications. Estimation of absorbed doses in man is possible for virtually every neurotoxic chemical by means of analytical chemistry of body fluids. Protein adducts, as measured in cellular and other blood components, might assess more closely the delivery in vivo, to the site of action. In this way also in vivo comparisons across species will be more precise. Examples include haemoglobin adducts, plasma pseudocholinesterase inhibition etc. In addition measurements of blood enzymes involved in the detoxification (e.g. A-esterases and ...

Toxicology and Applied Pharmacology, 1987

Biochemical Pharmacology, 1984

The conversion of dopamine to noradrenaline, measured shortly after exposure to carbon disulphide... more The conversion of dopamine to noradrenaline, measured shortly after exposure to carbon disulphide, is reduced in the adrenals of rats. However, alongside this effect, carbon disulphide produces a gradual increase in the adrenal content of dopamine-beta-hydroxylase indicated by the increase of in vitro estimated enzyme activity and by the increased in vivo conversion of dopamine to noradrenaline observed 24 hr after the ninth exposure. Thus, after repeated exposures, the reduced rate of noradrenaline synthesis detectable immediately after the exposure alternates with the increased rate of synthesis.

Archives of Toxicology, 1995

Both disulfiram (tetraethylthiuram disulfide), an alcohol aversive drug, and thiram (tetramethylt... more Both disulfiram (tetraethylthiuram disulfide), an alcohol aversive drug, and thiram (tetramethylthiuram disulfide), a widely used pesticide, significantly increased the dopamine pool in the adrenal glands of dosed rats. The dopamine increase was detectable within 4 h of oral dosing with 100 mg/kg of either dithiocarbamate and peaked 24 h later at 10 times control values. In control rats the dopamine turnover was 0.51 h-1 as calculated by the assumed first order decline of dopamine after a single injection of ~-methylp-tyrosine (e-MT, 400 mg/kg i.p.) resulting in a dopamine-fi-hydroxylase (DBH) activity of 0.73 nmol/h per pair of adrenals. In the adrenals of rats pretreated with thiram and then injected with e-MT, the adrenal dopamine content did not significantly decline, indicating that thiram reduced the conversion ofdopamine to noradrenaline, eventually leading to the observed dopamine increase. Plasma DBH activity was significantly reduced 4 h and 24 h after dosing with thiram, but was unchanged after treatment with disulfiram. The determination of plasma DBH activity could be a marker to monitor the effect of thiram on catecholamine metabolism in occupationally exposed workers but not that of disulfiram in abstinent alcoholics.

Archives of Toxicology, 1984

Male rats were exposed for a maximum of 4 h to carbon disulphide at atmospheric levels of 1.0-4.0... more Male rats were exposed for a maximum of 4 h to carbon disulphide at atmospheric levels of 1.0-4.0 mg/1 and the turnover rates of adrenal dopamine was determined by injecting a-methyl-p-tyrosine and measuring the rate at which dopamine disappears. Although the level of exposure was significantly higher than the 30.0 ~tg/1 permissible limit, or the average occupational exposure, similar or even higher peak exposure values were reported from the viscose rayon industry. After inhibition of tyrosine hydroxylase by a-methyl-p-tyrosine, adrenal dopamine contents declined at a slower rate in rats exposed to carbon disulphide than in controls. The reduced rate of dopamine metabolism during exposure to carbon disulphide indicates inhibition of dopamine-fl-hydroxylase in vivo. The size of this effect, which could be detected as soon as 30 min after starting the exposure to carbon disulphide, was dose dependent. The rate of dopamine turnover was still reduced 2 h after the end of a single exposure. However at that time, because of the larger dopamine pool present in the adrenals, the amount of dopamine converted per unit of time was again at pre-exposure levels.

Archives of Toxicology, 1981

Levels of acetylcholinesterase and neurotoxic esterase were measured in brain autopsy material. I... more Levels of acetylcholinesterase and neurotoxic esterase were measured in brain autopsy material. In tissue from a fatal human poisoning and from hens given 4-8 x unprotected LDs0 AChE was highly inhibited and neurotoxic esterase uninhibited. The findings correlate with the inhibitory power of omethoate against these enzymes in vitro. It is concluded that omethoate has negligible potential to cause delayed neuropathy and a published report of human neuropathy due to omethoate is criticised.

Archives of Toxicology, 1991

Chlorpyrifos [0,0-diethyl 0-(3,5,6-trichloro-pyridyl) phosphorothioate] caused delayed polyneurop... more Chlorpyrifos [0,0-diethyl 0-(3,5,6-trichloro-pyridyl) phosphorothioate] caused delayed polyneuropathy in man. Contrary to previous studies, we report here that it also causes delayed polyneuropathy in the hen, the animal model for this toxicity. The minimal neuropathic dose was 60-90 mg/kg p.o., corresponding to 4-6 times the estimated LDs0. Consequently, pralidoxime (2-PAM) in conjunction with atropine was necessary to reverse acetylcholinesterase (ACHE) inhibition and cholinergic toxicity in hens given high enough doses of chlorpyrifos to cause neuropathy. Chlorpyrifos was slowly absorbed after single oral doses and the threshold of inhibition (>70%) of neuropathy target esterase (NTE), the putative target for delayed neuropathy, was reached within 5-6 days. High AChE inhibition (>90%), however, was measured within hours after dosing because of the higher potency of chlorpyrifos to inhibit this enzyme. In vitro studies showed that chlorpyrifos-oxon, the active metabolite of chlorpyrifos, was 10-20 times more active against AChE than against NTE, confirming the clinical observation. No differences were seen between human and hen enzymes in this respect. Hen and human brain homogenates contain A-esterases which hydrolysed chlorpyrifos to about the same extent in both species. In conclusion, chlorpyrifos causes delayed polyneuropathy in the hen, as was reported in man. The reasons for previous negative data in the hen are probably due to the relatively lower doses which were used. Judging from in vitro studies with hen and human enzymes, there are no differences in the two species as far as their relative sensitivity to delayed polyneuropathy. It is likely that delayed polyneuropathy would develop in both species only after severe cholinergic toxicity requiring aggressive antidotal treatment.

Archives of Toxicology, 1991

Methamidophos causes acute cholinergic toxicity in several species, including man, and organophos... more Methamidophos causes acute cholinergic toxicity in several species, including man, and organophosphate-induced delayed polyneuropathy which has been reported in man but not in the hen. Acetylcholinesterase (AChE) and neuropathy target esterase (NTE) are thought to be the molecular targets of acute and delayed toxicity, respectively. The rate constants of inhibition (ka) and reactivation (k + 3) of human and hen brain AChE and NTE by methamidophos resolved optical isomers are here reported. NTE inhibition was progressive and irreversible. Human and hen NTE ka (M-1.m-1) for D-(+) methamidophos was 88 and 59, respectively, and for L-(-) methamidophos 3.2 and 3.0, respectively. AChE spontaneously reactivates after inhibition. D-(+) methamidophos 10(-3).ka (M-1.m-1) for human and hen AChE was 0.24 and 0.13; 10(3).k+3 (m-1) was 0.83 and 0.69, respectively. L-(-) Methamidophos 10(-3).ka (M-1.m-1) for human and hen AChE was 5.7 and 2.8, whereas 10(3).k+3 (m-1) was 6.50 and 1.52, respectively. L-(-)-Inhibited AChE reactivated to about 60% for human and 30% for hen enzymes, respectively. D-(+)-Inhibited AChE reactivated to about 10-20% for both species. Maximal reactivation occurred within 4-6 h when a plateau was reached. The larger and faster reactivation of human AChE inhibited in vitro by L-(-) methamidophos suggests that a corresponding effect might be possible in vivo and therefore explain, in part, the relatively higher susceptibility of man to delayed polyneuropathy induced by racemic methamidophos which occurs, however, with doses always causing severe cholinergic toxicity.

Archives of Environmental Health: An International Journal, 1985

Measurement of neuropathy target esterase activity (NTE) in blood lymphocytes has been suggested ... more Measurement of neuropathy target esterase activity (NTE) in blood lymphocytes has been suggested as a possible biomonitor for organophosphate-induced delayed polyneuropathy. Human lymphocyte NTE was characterized in vitro according to the sensitivity to several organophosphate inhibitors, which was found similar to that of the nervous system enzyme. Methods for collection, storage, and processing of blood and the NTE assay are described (averaged coefficient of variation of the method is 8%). The mean (± SO) value of lymphocyte NTE activity in a caucasian population (108 healthy subjects) was 11.5 ± 2.5 nMoles/min • mg of protein. No sex or age differences were detected. The averaged intraindividual coefficient of variation was 1().1%. These results suggest the feasibility of the test in clinical conditions, a sufficient reproducibility of the test, and a large interindividual variation. Appropriate baseline values are advisable when using the test to evaluate the effects of an occupational exposure to organophosphorus esters which may cause delayed polyneuropathy.

Jat Journal of Applied Toxicology, Mar 1, 1994

... Stefan0 Caroldi,* Paola De Paris,* Sergio Zotti,S Ilia ZanellaS and Francesco BrugnoneO *Isti... more ... Stefan0 Caroldi,* Paola De Paris,* Sergio Zotti,S Ilia ZanellaS and Francesco BrugnoneO *Istituto di Medicina del Lavoro, University of Padova, Italy $Divisione Medica 111. ULSS 21, Padova. ... L. Magos, The clinical and experimental aspects of carbon disulphide intoxication. ...

Hum Exp Toxicol, 1994

1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals su... more 1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals such as zinc, ferrum and manganese but not that of copper. 2 We studied the effect of CaNa2EDTA injection on serum dopamine-β-hydroxylase, a copper-dependent enzyme, in three male lead welders hospitalized for suspected lead poisoning. 3 injection of CaNa 2EDTA (1000 mg i.v.) resulted in rapid reduction of serum dopamine-β-hydroxylase activity which returned to normal level within 24 hours. 4 Copper sulphate (8 μM) but not ethylmaleimide (10 mM) restored in vitro serum dopamine-β-hydroxylase activity to pre-dosing values which indicates that CaNa2EDTA inhibits dopamine-β-hydroxylase by removing copper from the enzyme. 5 An inverse dose effect relationship between injected CaNa2EDTA and residual serum dopamine-β-hydroxylase activity was observed. 6 In spite of the reported lack of changes in copper serum concentration, CaNa2EDTA significantly affects the activity of a copper-dependent enzyme in the serum. 7 As CaNa 2EDTA is currently the drug of choice for the treatment of asymptomatic lead poisoning in children, the effect of CaNa2EDTA on copper-enzymes requires further investigation.

Toxicology letters, 1988

Some organophosphorous esters cause a polyneuropathy which becomes clinically evident 2 weeks aft... more Some organophosphorous esters cause a polyneuropathy which becomes clinically evident 2 weeks after a single dose. The pathogenesis involves modifications of a target protein, neuropathy target esterase, in the axons and a selective inhibition of retrograde axonal transport. It was suggested that copper metabolism might also be involved because of increased levels of plasma copper and ceruloplasmin in animals developing this polyneuropathy. Our results do not confirm this observation; treatment of hens with highly neuropathic single doses of two organophosphates (dihexyl-2,2-dichlorovinyl phosphate and mono-o-cresyl diphenyl phosphate) does not affect total and plasma free copper when measured several times during the development of polyneuropathy. We concluded that copper homeostasis is not affected and that copper changes are unlikely to be involved in the pathogenesis of this polyneuropathy.

Toxicology Letters, 1981

A moderate neuropathic response was obtained in hens 2 weeks after being given a single massive S... more A moderate neuropathic response was obtained in hens 2 weeks after being given a single massive S.C. dose of dichtorvos (100 mg/kg of active ingredient in a commercial 50% formulation). I day after dosing inhibition of neurotoxic esterase in peripheral nerve was 79-90%, ~1. spinal cord 7041% and in brain 89-92%. It is unlikely that repeated exposure of man to dichlorvos could cause neuropathy except at doses causing severe cholinergic effects at every exposure.

Toxicology and Applied Pharmacology, 1982

The potential neurotoxicity of organophosphate esters is usually evaluated by measuring neurotoxi... more The potential neurotoxicity of organophosphate esters is usually evaluated by measuring neurotoxic esterase (NTE) inhibition in brains taken from dosed birds. An improved method to measure NTE in peripheral nerve has been developed and used to compare brain, spinal cord, and peripheral nerve NTE inhibition both in vitro and in vivo after a single dose of several organophosphates. Brain and spinal cord NTE activities are a good mirror of NTE activity of the sciatic nerve. The rate of resynthesis of NTE in peripheral nerves after inhibition with an effective dose of a neurotoxic organophosphate was similar to that in other nervous tissues.

Scandinavian Journal of Work, Environment & Health, 1980

The investigation evaluates the efficiency attributed to some measures (improvements in environme... more The investigation evaluates the efficiency attributed to some measures (improvements in environment, individual health habits) in reducing the risk of lead poisoning in the ceramics industry. The evaluation of the average levels of lead in the blood of 154 exposed workers was carried out in four plants at a time interval of six to eight months. The study considers the variations in relation to possible measures brought about during the interval. A reduction of environmental risk was in effect shown by a clear improvement in the blood lead levels, which still, however, exceeded the internationally recommended limits in many of the subjects. It was concluded that further improvements can only be made by reducing the lead content of the glazes used.

Scandinavian Journal of Work, Environment & Health, 1980

The ceramics industry and lead poisoning. Lead poisoning in relation to technology and jobs.

Occupational and Environmental Medicine, 1992

Assay of free and acid labile carbon disulphide (free and total CS2 respectively) in human blood ... more Assay of free and acid labile carbon disulphide (free and total CS2 respectively) in human blood was performed by gas chromatography/ spectrometry. The method used a large dynamic head space volume and a "cryogenic trap". Blood CS2 concentration was measured in 42 subjects not occupationally exposed to CS2 (group A) and in 11 alcoholic subjects (group B) treated with disulfiram. Free CS2 658 copyright.

Journal of Applied Toxicology, 1987

In agreement with the inhibition of dopamine-beta-hydroxylase by exposure to CS2, the extension o... more In agreement with the inhibition of dopamine-beta-hydroxylase by exposure to CS2, the extension of exposure time from 4 to 16 h increased dopamine concentrations in the hypothalmus and adrenals, and decreased noradrenaline concentration in the hypothalmus. The extension of exposure time also increased the toxicity of amphetamine. In conscious animals the stereotypic activity produced by 6.0 mg/kg and even that of 3.0 mg/kg amphetamine sulphate was suppressed by severe hyperthermia resulting in exhaustion, prostration and eventually death. A 16 h exposure to CS2 did not increase the lethal or hyperthermic effects of amphetamine in rats anaesthetized with 60 mg/kg sodium pentobarbitone. In fact the CS2 exposed rats became more hypothermic than non-exposed rats.

Journal of Applied Toxicology, 1994

... Stefan0 Caroldi,* Paola De Paris,* Sergio Zotti,S Ilia ZanellaS and Francesco BrugnoneO *Isti... more ... Stefan0 Caroldi,* Paola De Paris,* Sergio Zotti,S Ilia ZanellaS and Francesco BrugnoneO *Istituto di Medicina del Lavoro, University of Padova, Italy $Divisione Medica 111. ULSS 21, Padova. ... L. Magos, The clinical and experimental aspects of carbon disulphide intoxication. ...

Human & Experimental Toxicology, 1994

1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals su... more 1 In humans CaNa 2EDTA increases urinary excretion of lead as well as that of essential metals such as zinc, ferrum and manganese but not that of copper. 2 We studied the effect of CaNa2EDTA injection on serum dopamine-β-hydroxylase, a copper-dependent enzyme, in three male lead welders hospitalized for suspected lead poisoning. 3 injection of CaNa 2EDTA (1000 mg i.v.) resulted in rapid reduction of serum dopamine-β-hydroxylase activity which returned to normal level within 24 hours. 4 Copper sulphate (8 μM) but not ethylmaleimide (10 mM) restored in vitro serum dopamine-β-hydroxylase activity to pre-dosing values which indicates that CaNa2EDTA inhibits dopamine-β-hydroxylase by removing copper from the enzyme. 5 An inverse dose effect relationship between injected CaNa2EDTA and residual serum dopamine-β-hydroxylase activity was observed. 6 In spite of the reported lack of changes in copper serum concentration, CaNa2EDTA significantly affects the activity of a copper-dependent enzym...