Neurotoxicity case studies

Schifano F (2000). Potential human neurotoxicity of MDMA ( Ecstasy ) Subjective self-reports, evidence from an Italian drug addiction centre and clinical case studies. 

Neurological Effects. The major public health concern regarding -hexane exposure is the potential for the development of neurotoxicity. Occupational studies have documented that human exposure to -hexane can result in a peripheral neuropathy that in severe cases can lead to paralysis (Altenkirch et al. 1977 Yamamura 1969 Wang et al. 1986). The dose-duration relationship has not been well characterized in humans, but concentrations of 500 ppm and above, and exposure for 2 months or more have been associated with human neurotoxicity. Brief exposure to extremely high concentrations of w-hexane may cause signs of narcosis in humans prostration and coma have been observed in animals exposed to a mixture of hexanes at concentrations of 70,000-80,000 ppm (Hine and Zuidema 1970). At these levels, however, explosion and fire would be the main concern. 

Intermediate-Duration Exposure. Case studies of occupational exposure to 77-hexane by the inhalation route show that neurotoxicity can develop in humans over this duration period (Altenkirch et... 

Information regarding health effects of fuel oils in humans and animals is available for the inhalation, oral, and dermal routes of exposure. Most of the information in humans is from cases of accidental ingestion of kerosene that resulted in respiratory, neurotoxic, and to a lesser extent, gastrointestinal effects. In addition, a few case studies have identified these effects as well as cardiovascular, hematological, and renal effects in humans after inhalation and/or dermal exposures to fuel oils. Fuel oils appear to be eye and skin irritants in both animals and humans following direct contact. Animal data exist for most systemic effects however, the data are inconclusive for many of the endpoints. Further, a number of the animal studies... 

Neurotoxicity in humans from dermal exposures has been reported in 1 case study in which anorexia was noted (Crisp et al. 1979) inhalation exposure may have also occurred. One animal study found no histopathological changes in the organs of the nervous system in mice following chronic and/or intermediate dermal exposures to marine diesel fuel and JP-5 (NTP/NIH 1986). However, increased response to tactile stimuli and hyperactivity occurred in mice from acute dermal exposures to kerosene (Upreti et al. 1989). 

In a few cases, studies to evaluate developmental neurotoxicity or other postnatal functions may have been conducted, and these can provide amore complete evaluation of potential developmental effects. In addition to the standard guideline studies, data from experimental studies on mechanisms of action, etc., can provide useful data for consideration in the risk assessment process. 

Poli, M.A., Musser, S.M., Dickey, R.W., Eilers, P.P., and Hall, S. 2000. Neurotoxic shellfish poisoning and brevetoxin metabolites a case study from Elorida. Toxicon 38, 981-993. 

An autopsy revealed purulent bronchopneumonia. It is unclear whether the respiratory effects were direct effects of the phenylmercuric acetate or secondary to the severe neurotoxicity also seen in this subject. A case study reported that no respiratory effects were observed in four men inhaling unspecified concentrations of methylmercury for several months (Hunter et al. 1940). Both of these studies are limited because exposure levels were unknown. 

Neurodegenerative diseases (NDDs) are those in which the irreversible deteriorization of neurons affects movement and/or memory. A number of these diseases have been associated with neurotoxic chemical exposures. These include Parkinson s disease, Alzheimer s disease, amyotrophic lateral sclerosis (also called motor neuron disease), and multiple sclerosis. NDDs and their associations with neurotoxic exposures are introduced here. Specific examples and case studies are discussed in the following sections. 

The case studies presented here are all from the published literature. In every study the neurotoxic effects found are related to exposures to chemical mixtures of lipophiles and hydrophiles that induced neurotoxic effects not anticipated from the individual chemicals. The Kovi/ values for each of the chemicals are given. If not listed in a column they follow the individual chemical names in parentheses. 

Neurotoxicity. Neurological effects including headache, nausea, vertigo, and confusion have been reported in case studies of humans exposed to nitrobenzene by inhalation. In orally exposed persons, apnea and coma have additionally been reported. No data are available in humans exposed via the dermal route. In animal studies, brain lesions have been observed in mice and rats exposed by inhalation and in rats that received a single oral dose. No data are available in animals exposed via the dermal route. Toxicokinetic studies in mice and rats provide evidence that nitrobenzene is distributed to brain tissue. Both the human and animal data provide clear evidence that nitrobenzene is a neurotoxic substance. Further studies in this area do not appear to be needed. In addition, results of the CUT two-year bioassay may provide further information on this end point. 

Slotkin TA (2005). Developmental neurotoxicity of organophosphorus a case study of chlorpyrifos. In Toxicology of Organophosphate and Carbamate Compounds (R Gupta, ed.), pp. 293-314. San Diego, CA, USA Academic Press. 

Another important ncunrtoxic sequel of OP exposure is developmental neurotoxicity. Since OP developmental neurotoxicity in both humans (Garry, 2004) and animal models (fzrael et ai. 2004) has been reviewed, we discuss only selected case studies to illustrate the conclusion that this neurotoxic effect of OPs can also occur independent of AChE inhibition. Initial studies indicated that the developing nervous system is far more sensitive to the acute cholinergic toxicity of OPs (Bushnell ei al, 1991 Pope and Chakraborti, 1992), most likely due to age-related differences in the hepatic detoxification of the AChE-active metabolites of OPs (Atierberry et ai, 1997 Benke and Murphy, 1975 Moitensen et ai, 1996). However, subsequent studies... 

Developmental Neurotoxicity of Organophosphates A Case Study of Chlorpyrifos... 

The overall schematic for quantified health risk estimates in the analysis of U.S. EPA (2007) entailed combining concentration—response functions with blood lead distributional statistics generated for each of the three case studies to produce distributions of IQ loss estimates for each study population. Before the quantitative analyses of health risk were done via using differing concentration—response functions, the health risk portion in U.S. EPA s full-scale health risk assessment was evaluated to produce several statistical modeling and assessment steps for the risk metric, IQ point loss, in young children sustaining developmental neurotoxicity effects at various PbB estimates. 

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