Neurotoxicity chronic

Burchfiel, J.L. and F.H. Duffy. 1982. Organophosphate neurotoxicity chronic effects of sarin on die electroencephalogram of monkey and man. Neurobehav. Toxicol. Teratol. 4 767-778. 

Due to a lack of sufficient scientific evidence regarding safety, further tests are needed to evaluate geno-toxicity, reproductive toxicity, neurotoxicity, chronic and carcinogenicity. 

In a cross-sectional study, exposure and effect are studied simultaneously. This approach contains an inherent problem because exposure must precede the effect. However, it can he used to investigate acute effects and also mild chronic effects (which do not force people to leave their jobs) if exposure has remained rather stable for a long time. When the prevalence of the effects studied are compared with the prevalence in other worker groups (controls or references) which correspond otherwise with the study group but are not exposed to the agent investigated, indicative evidence of possible causality may be obtained. For example, cross-sectional studies have been applied successfully to reveal the associations between mild neurotoxic effects and exposure to organic solvents. ... 

European Centre for the Validation of Alternative Methods (ECVAM), six in vitro systems for chronic neurotoxicity testing are recommended for further consideration (Worth and Balls 2002). These are described as in vitro models that may be suitable for long-term toxicity testing. The systems are... 

Recently much interest has been shown in the possible neuroproctive effects of adenosine but the responses are complex. Thus A3 agonists can offer some protection given chronically before ischaemic challenge but given acutely post-challenge they can be neurotoxic (see Jacobsen 1998). 

Chronic toxicity Mammalian systems Carcinogenicity Neurotoxicity De ve 1 opm e nta l/rep rod u cti ve toxicity Aquatic vertebrates and invertebrates Plants Mutagenicity, increased tumours Reproduction and growth Cancer slope factors Reference doses, and so on IC50, EC50... 

Finocchio DV, Luschei ES, Mottet NK, Body RL. 1980. Effects of methylmercury on the visual system of the rhesus macaque (Macaca mulatto). I. Pharmacokinetics of chronic methylmercury related to changes in vision and behavior. In Merigan WH, Weiss B, editors. Neurotoxicity of the visual system. New York Raven Press, p. 113-122. 

In contrast, a similar injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) produced a zone of total 5-HT denervation at least 2 to 3 mm in diameter. These chronic intracerebral micro injection experiments lend further support to the view that the parent compound is not itself neurotoxic (Berger 1989 Berger et al., in preparation Molliver et al. 1986). 

After a single dermal exposure to waste from the reclamation of a Fyrquel hydraulic fluid that may have been contaminated with tri-or/7 o-cresyl phosphate (TOCP), no apparent signs of neurotoxicity were observed in calves of 10 cows that manifested neurotoxicity just after the birth of the calves. The cows were apparently also exposed orally concurrent to the dermal exposure (Julian et al. 1976). No intermediate- or chronic-duration dermal studies examining developmental effects in animals were located. 

No data were located regarding toxic effects in humans following oral exposure to polyalphaolefin hydraulic fluids. No deaths or body weight changes occurred in rats in a series of acute lethality studies with nine polyalphaolefin hydraulic fluids at doses ranging from 4,250 to 5,000 mg/kg. One of these fluids was also tested for neurotoxicity in chickens, and did not produce effects at 4,250 mg/kg. The available data have not identified a target organ or effect for these fluids. The data are inadequate for MRL derivation. No intermediate or chronic oral MRLs for polyalphaolefin hydraulic fluids were derived due to the lack of data. 

Mineral Oil Hydraulic Fluids. There is limited information on the toxicity of mineral oil hydraulic fluids in humans. A single case report of a child accidentally ingesting a single dose of automotive transmission fluid provides limited information on death and systemic effects. A case-control study provides some information on the carcinogenicity of mineral oil hydraulic fluids. The study population was exposed via inhalation and dermal routes. An occupational exposure study provides information on neurotoxicity following chronic dermal exposure. Information on the toxicity of mineral oil hydraulic fluids is limited to a series of inhalation, oral, and dermal acute-duration exposures. These studies provide information on death, systemic effects, and neurotoxicity by inhalation, oral, and dermal routes, and immunotoxicity following dermal exposure. 

Intake can be expressed either as a pollutant mass per unit time, as discussed above, or as a mass per kg of body weight per unit time. The latter expression facilitates comparison to health effects data, especially laboratory animal data, which are commonly reported in equivalent units. Similarly, depending on the route of exposure, intake may be estimated on an annual basis to address chronic effects, or on a smaller time scale for addressing acute effects including lethality, teratogenesis, reproductive and neurotoxic effects. 

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