Neurotoxicity and

The demonstration that injected or force-fed neonatal rodents given extremely high doses of MSG showed evidence of brain lesions, has led to much additional research to determine any possible link between neurotoxicity and human use of MSG (33). However, no evidence from animal tests indicates that MSG in the diet causes brain damage in humans (34). 

The only prominent antitumor tetravalent platinum complex so far is iproplatin (102). In vitro it has been shown to cause interstrand DNA-breaking and cross linking. Free radical scavengers inhibit these effects. The complex is less neurotoxic and less nephrotoxic than cisplatin. Its synthesis begins with hydrogen peroxide oxidation of cis-dichlorobis(isopropvlamine) platinum (100) to the dimethylacetamide complex 101. The latter is heated in vacuum to liberate iproplatin [25]. 

Clinical trials showed therapeutic efficacy in a broad spectrum of tumors these include SCLC, testicular tumors, sarcomas, breast cancer, renal cell cancer, pancreatic tumors and lymphomas. Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. Therefore it is recommended that ifosfamide is coadministered with the thiol compound mesna to avoid hemorrhagic cystitis and to reduce the risk of developing bladder cancer. Other side effects include neurotoxicity and myelosuppression. 

Vinca alkaloids (vincristine, vinblastine, vindesine) are derived from the periwinkle plant (Vinca rosea), they bind to tubulin and inhibit its polymerization into microtubules and spindle formation, thus producing metaphase arrest. They are cell cycle specific and interfere also with other cellular activities that involve microtubules, such as leukocyte phagocytosis, chemotaxis, and axonal transport in neurons. Vincristine is mainly neurotoxic and mildly hematotoxic, vinblastine is myelosuppressive with veiy low neurotoxicity whereas vindesine has both, moderate myelotoxicity and neurotoxicity. 

Alkyl lead compounds are also highly neurotoxic and were implicated in large-scale kills of wading birds. 

Apart from the wide range of neurotoxic and behavioral effects caused by OPs, many of which can be related to inhibition of AChE, other symptoms of toxicity have been reported. These include effects on the immune system of rodents (Galloway and Handy 2003), and effects on fish reproduction (Cook et al. 2005 Sebire et al. 2008). In these examples, the site of action of the chemicals is not identified. Indirect effects on the immune system or on reproduction following initial interaction with AChE of the nervous system cannot be ruled out. It is also possible that OPs act directly on the endocrine system or the reproductive system, and phosphorylate other targets in these locations (Galloway and Handy 2003). 

CBs, like OPs, can cause a variety of sublethal neurotoxic and behavioral effects. In one study with goldfish Carrasius auratus), Bretaud et al. (2002) showed effects of carbofuran on behavioral end points after prolonged exposure to 5 pg/L of the insecticide. At higher levels of exposure (50 or 500 pg/L), biochemical effects were also recorded, including increases in the levels of norepinephrine and dopamine in the brain. The behavioral endpoints related to both swimming pattern and social interactions. Effects of CBs on the behavior of fish will be discussed further in Chapter 16, Section 16.6.1. 

This third part of the book will be devoted mainly to the problem of addressing complex pollution problems and how they can be studied employing new biomarker assays that exploit new technologies of biomedical science. Chapter 13 will give a broad overview of this question. The following three chapters, The Ecotoxicological Effects of Herbicides, Endocrine Disrupters, and Neurotoxicity and Behavioral Effects, will all provide examples of the study of complex pollution problems. 

RELATING NEUROTOXICITY AND BEHAVIORAL EFFECTS TO ADVERSE EFFECTS UPON POPULATIONS... 

Broadly speaking, the direct behavioral effects of neurotoxic pollutants on wild animals may be on feeding, breeding, or avoidance of predation (Beitinger 1990), or any combination of these. Any of these changes may have adverse effects on populations. Additionally, in the natural world, populations may be affected indirectly because of neurotoxic and behavioral effects on other species. Thus, a population decline of one species due to a behavioral effect of a pollutant may lead to a consequent decline of its parasites or predators, even though they are not themselves directly affected by the chemical. Direct effects will now be discussed before considering indirect ones. 

Iversen (1991) stresses the need for some in vivo testing for neurotoxicity and emphasizes the value of sensitive behavioral tests. Behavioral tests are described for mice and rats, which provide measures of mood, posture, CNS excitation, motor coordination, sedation, exploration, responsiveness, learning, and memory function. Such assays can function as primary screens for neurotoxicity before adopting a stepwise scheme of in vitro tests to discover more about the initial site of action of neurotoxic compounds. It is argued that the requirement for animal testing can be drastically reduced by adopting structured in vitro protocols such as these. 

Atterwill, C.K. et al. (1991). Alternative Methods and Their Application in Neurotoxicity Testing—Describes a range of in vitro tests for neurotoxicity and proposes a stepwise scheme for neurotoxicity testing. 

Lotti, M. (1992). Central neurotoxicity and behavioural effects of anticholinesterases. In B. Ballantyne and T.C. Marrs (Eds.) (1992). Clinical and Experimental Toxicology of Organophosphates and Carbamates 75-83. 

New chapters Endocrine-Disrupting Chemicals and Their Environmental Impacts and Neurotoxicity and Behavioral Effects of Environmental Chemicals, the first of which is co-authored by R.W. Goodhead and Charles Tyler... 

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