Course Title: PSYC 661 Behavioral Effects of Environmental Contaminants
Instructor: M. Christopher Newland, Ph.D.
Department of Psychology, 110 Thach Hall, Auburn University. 844-6479 firstname.lastname@example.org
Meeting: Mondays and Wednesdays, 3:00 - 5:00 Room 210 Thach Hall.
Office Hours: 3:00-5:00 M. W. 9:00-10:30 or by appointment.
Text: Environmental Neurotoxicology. National Research Council, National Academy Press. 1992.
Background. The Toxic Substances Control Act (TSCA), Federal Insecticide, Fungicide, and Rodenticide act (FIFRA), and other pieces of legislation bearing on the health effects of chemicals in the workplace (OSHA), the home (Consumer Product Safety Commission), or the environment (EPA) specifically mention neurobehavioral toxicology as a regulatory concern. The inclusion of nervous system damage in general, and its behavioral manifestations in particular, represents a sea change in public concern over unintended exposure to chemicals. Where cancer has been (and still is) a major concern, the recognition that adverse behavioral effects follow certain types of chemical exposure is increasing.
The heightening public awareness that some toxic substances can act on the nervous system and produce detectable effects presents a major challenge to behavioral neuroscientists. Experimental psychologists and other neuroscientists are being asked to conduct both hazard assessment (are there neurobehavioral effects of some chemical at any dose?) and risk assessment (what is the risk to a population at a specific level of exposure?) for behavioral effects that are not always well understood. The heavy metal, lead, is a prototypical neurotoxicant. Concern over lead poisoning lies not in its carcinogenicity but rather in claims that it lowers scores on IQ tests, retards academic performance, and results in disruptive behavior. The issues that this pattern of effects raise include: Could lead's effects have been anticipated on the basis of studies with nonhuman species?
Can animal studies be conducted more economically while still being valid predictors of human effects?
What populations are most at risk to lead poisoning?
What are the health consequences of treatment for lead poisoning?
What is the actual risk at current levels of lead in the environment and is the cleanup worth the cost? Course Structure. The course will cover the basic issues in behavioral toxicology. Principles of behavior will be introduced as required to understand how to assess sensory or motor function, learning and memory, nonspecific behavioral effects, or the reinforcing or irritating properties of chemicals. Principles of toxicology will also be introduced as needed, and these will include the importance of dose-effect relationships, quantitative risk assessment with behavioral endpoints, hazard assessment, routes of exposure, and kinetics.
There are two ways to structure a course of this type: by chemical or by topic and functional domain. I have chosen the later approach so we will examine how neurotoxicants affect sensory function, motor function, learning and memory, and development. Having done this we will examine regulatory issues from two perspectives. First, we will examine how risk assessment has been conducted with behavior, and recommended improvements in the process. Second, we will examine the larger issue of making policy decisions and communicating hazard and risk to the public.
I have selected readings that will permit us to weave neurotoxicant-based threads as we wend our way through the course. Most of the papers pertain to heavy metals (lead, mercury, and manganese) and organic solvents (defined sufficiently broadly to include the alcohols) so we will focus on these important, and very different, neurotoxicants. This approach will acquaint you with the different ways in which we come to understand neurotoxic effects of chemical insult, and how we as a society make decisions resulting from that understanding. You can leave this course with the skills required to make intelligent decisions about how to assess, read about, or react to events (chemical or otherwise) that have adverse behavioral effects.
Evaluation will be based upon score on a take-home test administered in the beginning of the quarter (1/3 of your grade), class presentations of assigned papers and class participation (1/3) and the group project (1/3 of your grade). You will be responsible for presenting several papers through the quarter. These presentations will be about 20 to 40 minutes in length, depending on the nature of the paper you are assigned. Students not presenting are responsible for reading the paper and must be prepared to discuss it. We will cover the bolded readings attached to this syllabus.
Anger, W.K. (1986). Workplace exposures. In Z. Annau (Ed.), Neurobehavioral Toxicology. 7(331-347). Baltimore: Johns Hopkins University
Weiss, B. (1983). Behavioral Toxicology and Environmental Health Science: Opportunity and Challenge for Psychology. American Psychologist, 38, 1174-1187.
Weiss, B.& Cory-Slechta, D.A. (1994). Assessment of Behavioral Toxicity. In A.W. Hayes (Ed.), Principles and Methods of Toxicology. (1091-1155). New York: Raven Press
Julian, R.A. (1994) A Primer of Drug Action. New York: Freeman. Chapter 2, appendix.
Aschner, M.& Aschner, J.L. (1990). Mercury neurotoxicity: mechanisms of blood-brain barrier transport. Neuroscience and Biobehavioral Reviews, 14, 169-176.
Cox, C., Clarkson, T.W., Marsh, D.O., Amin-Zaki, L., Tikriti, S.& Myers, G.g. (1989). Dose-response analysis of infants prenatally exposed to methyl mercury: An application of a single compartment model to single-strand hair analysis. Environmental Research, 49, 318-332.
Newland, M.C., Cox, C., Oberdoerster, G.& Weiss, B. (1987). The clearance of manganese chloride in the primate. Fundamental and Applied Toxicology, 9, 314-328.
Newland, M.C., Ceckler, T.L., Kordower, J.H.& Weiss, B. (1989). Visualizing manganese in the primate basal ganglia with magnetic resonance imaging. Experimental Neurology., 106, 251-258.
Vahter, M., Mottet, N.K., Friberg, L., Lind, B., Shen, D.D.& Burbacher, T. (1994). Speciation of mercury in the primate blood and brain following long-term exposure to methyl mercury. Toxicology and Applied Pharmacology, 124, 221-229.
Weiss, B., Cory-Slectha, D.A.& Cox, C. (1990). Modification of lead distribution by diethyldithiocarbamate. Fundamental and Applied Toxicology, 15, 791-799.
Pryor, G.T., Uyeno, E.T., Tilson, H.A.& Mitchell, C.L. (1983). Assessment of chemicals using a battery of neurobehavioral tests: A comparative study. Neurotoxicology and Teratology, 5, 91-117.
Tegeris, J.S.& Balster, R.L. (1994). A comparison of the acute behavioral effects of alkylbenzenes using a functional observationsl battery in mice. Fundamental and Applied Toxicology, 22, 240-250.
Wood, R.W.& Colotla, V.A. (1990). Biphasic changes in mouse motor activity during exposure to toluene. Fundamental and Applied Toxicology, 14, 6- 14.
Rees, D.C., Knisely, J.S., Breen, T.J.& Balster, R.L. (1987). Toluene, halothane, 1,1,1-trichloroethane, and oxazepam produce ethanol-like discriminative stimulus effects in mice. Journal of Pharmacology and Experimental Therapeutics, 243, 931-937.
Wood, R.W.& Coleman, J.B. (1995). Behavioral evaluation of the irritant properties of formaldehyde. Toxicology and Applied Pharmacology, 130, 67-72.
Maurissen, J.P.J. (1995). Neurobehavioral methods for the evaluation of sensory functions. In L.W. Chang & W. Slikker (Eds.), Neurotoxicology: Approaches and Methods. (239-264). San Diego: Academic Press
Pryor, G.T., Rebert, C.S., Dickinson, J.& Feeney, E.M. (1984). Factors affecting toluene-induced ototoxicity in rats. Neurotoxicology and Teratology, 6, 223-238.
Rice, D.C.& Gilbert, S.G. (1990). Effects of developmental exposure to methyl mercury on spatial and temporal visual function in monkeys. Toxicology and Applied Pharmacology, 102, 151-163.
Rice, D.C.& Gilbert, S.G. (1992). Exposure to methyl mercury from birth to adulthood impairs high-frequency hearing in monkeys. Toxicology and Applied Pharmacology, 115, 6-10.
Stern, S.& Laties, V.G. (1985). 60-Hz electric fields: detection by female rats. Bioelectromagnetics, 6, 99-103.
Stern, S.& Laties, V.G. (1989). Comparison of 60-Hz electric fields
and incandescent light as aversive stimuli controlling the behavior of
rats. Bioelectromagnetics, 10, 99-109.
Chia, S.E., Goh, J., Lee, G., Foo, S.C., Gan, S.L., Bose, K., Jeyaratnam, J. (1993). Use of a computerized postural sway measurement system for assessing workers exposed to manganese. Clin-Exp-Pharmacol-Physiol. 20, 549-53.
Chia, S.E., Gan, S.L.,Chua, L.H.; Foo, S.C., Jeyaratnam, J. (1995) Postural stability among manganese exposed workers. Neurotoxicology. 16, 519-26.
Newland, M.C. (1995). Motor function and the physical properties of the operant: applications to screening and advanced techniques. In L.W. Chang & W. Slikker (Eds.), Neurotoxicology: Approaches and Methods. (265-299). San Diego: Academic Press
Newland, M.C. (1997) Neural, behavioral, and measurement considerations in the detection of motor impairment. In Reuhl, K.R., and Lowndes, H.E. (Eds). Comprehensive Toxicology: Vol 11: Nervous System and Behavioral Toxicology. Elsevier pp 247-269.
Newland, M.C.& Weiss, B. (1991). Ethanol's effects on tremor and positioning in squirrel monkeys. Journal of Studies on Alcohol, 52, 492-499.
Newland, M.C.& Weiss, B. (1992). Persistent effects of manganese on effortful responding and their relationship to manganese accumulation in the primate globus pallidus. Toxicology and Applied Pharmacology, 113, 87-97.
Peele, D.B., and Crofton, K.M. (1987). Pyrethroid effects on schedule-controlled behavior: time and dosage relationships. Neurotoxicology and Teratology, 9, 387-394.
Pryor, G.T. (1991). A toluene-induced motor syndrome in rats resembling that seen in some human solvent abusers. Neurotoxicology and Teratology, 13, 387-400.
Tepper, J.L., Weiss, B.& Cox, C. (1982). Microanalysis of ozone depression of motor activity. Toxicology and Applied Pharmacology, 64, 317- 326.
van Emmerik, R.E.A., Sprague, R.L.& Newell, K.M. (1993). Finger tremor and tardive dyskinesia. Experimental and Clinical Psychopharmacology, 1, 259-268.
Weiss, B., Ferin, J., Merigan, W., Stern, S.& Cox, C. (1981). Modification of rat operant behavior by ozone exposure. Toxicology and Applied Pharmacology, 58, 244-251.
Weiss, B.& Laties, V.G. (1964). Effects of amphetamine, chlorpromazine, pentobarbital, and ethanol on operant response duration. Journal of Pharmacology and Experimental Therapeutics, 144, 17-23.
Wood, R.W., Weiss, A.B., Weiss, B. (1973) Hand tremor induced by industrial exposure to inorganic mercury. Archives of Environmental Health, 26, 249-252.
Allen, A.R.& MacPhail, R.C. (1991). Effects of triadimefon on a multiple schedule of fixed-interval performance: comparison with methylphenidate, d-amphetamine, and chlorpromazine. Pharmacology, Biochemistry, and Behavior, 40, 775-780.
Cory-Slechta, D.A., Weiss, B.& Cox, C. (1985). Performance and exposure indices of rats exposed to low concentrations of lead. Toxicology and Applied Pharmacology, 78, 291-295.
Perkins, A.N., Eckerman, D.A.& MacPhail, R.C. (1991). Discriminative stimulus properties of triadimefon: comparison with methylphenidate. Pharmacology, Biochemistry, and Behavior, 40, 757-761.
Rees, D.C., Wood, R.W.& Laties, V.G. (1989). Evidence of tolerance following repeated exposure to toluene in the rat. Pharmacology, Biochemistry, and Behavior, 32, 283-291.
Rice, D.C. (1988). Schedule-controlled behavior in infant and juvenile monkeys exposed to lead from birth. NeuroToxicology, 9, 75-88.
Rice, D.C.& Gilbert, S.G. (1985). Low lead exposure from birth produces behavioral toxicity (DRL) in monkeys. Toxicology and Applied Pharmacology, 80, 421-426.
Rice, D.C., Gilbert, S.G.& Willes, R.F. (1979). Neonatal low-level lead exposure in monkeys: locomotor activity, schedule- controlled behavior, and the effects of amphetamine. Toxicology and Applied Pharmacology, 51, 503-513.
Cohn, J, Cox, C, Cory-Slechta, D.A. (1993) The effects of lead exposure on learning in a multiple repeated acquisition and performance schedule. Neurotoxicolgy, 14, 329-346.
Cohn, J.& Cory-Slechta, D.A. (1994). Lead exposure potentiates the effects of NMDA on repeated learning. Neurotoxicology and Teratology, 16, 455-465.
Newland, M.C., Sheng, Y., Logdberg, B.& Berlin, M. (1994). Prolonged behavioral effects of in utero exposure to lead or methylmercury: reduced sensitivity to changes in reinforcing stimuli during behavioral transitions and in steady state. Toxicology and Applied Pharmacology. 126, 6-15.
Rice, D.C. (1985). Chronic low-lead exposure from birth produces deficits in discrimination reversal in monkeys. Toxicology and Applied Pharmacology, 77, 201-210.
Wood, R.W., Rees, D.C., Laties, V.G. (1983). Behavioral effects of toluene are modulated by stimulus control. Toxicology and Applied Pharmacology, 68, 462-472.
Bushnell, P.J. (1989). Behavioral effects of acute p-xylene inhalation in rats: autoshaping, motor activity, and reversal learning. Neurotoxicology and Teratology, 10, 569-577.
Gilbert, S.G.& Rice, D.C. (1987). Low-level lifetime lead exposure produces behavioral toxicity (spatial discrimination reversal) in adult monkeys. Toxicology and Applied Pharmacology, 91, 484-490.
Heise, G.A.& Hudson, J.D. (1985). Effects of pesticides and drugs on working memory in rats: continuous delayed response. Pharmacology, Biochemistry, and Behavior, 23, 591-598.
Levin, E.D., Schantz, S.L.& Bowman, R.E. (1988). Delayed spatial alternatio deficits resulting form perinatal PCB exposure in monkeys. Archives of Toxicology, 62, 267-273.
Rice, D.C. (1984). Behavioral deficit (delayed matching to sample) in monkeys exposed from birth to low levels of lead. Toxicology and Applied Pharmacology, 75, 337-345.
\ Baker, E.L., Letz, R.E., Eisen, E.A., Pothier, L.J., Plantamura, D.L., Larson, M.& Wolford, R. (1988). Neurobehavioral effects of solvents in construction painters. Journal of Occupational Medicine, 30, 116-123.
Bellinger, D., Leviton, A., Waternaux, C., Needleman, H.& Rabinowitz, M. (1987). Longitudinal analyses of prenatal and postnatal lead exposure and early cognitive development. New England Journal of Medicine, 316, 1037-1043.
Bellinger, D., Leviton, A., Waternaux, C., Needleman, H.& Rabinowitz, M. (1989). Low-level lead exposure, social class, and infant development. Neurotoxicology and Teratology, 10, 497-503.
Dick, R.B., Setzer, J.V., Taylor, B.J.& Shukla, R. (1989). Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone. British Journal of Industrial Medicine, 46, 111-121.
Echeverria, D., Heyet, N.J., Martin, M., Naleway, C.A., Woods, J.S.& Bittner, A.C. (1995). Behavioral effects of low-level exposure to Hg0 among dentists 1995. Neurotoxicology and Teratology, 17, 161-168.
Iregren, A. (1990). Psychological test performance in foundry workers exposed to low levels of manganese. Neurotoxicol. Teratol., 12, 673-675.
Needleman, H.L., Gunnoe, C., Leviton, A., Reed, R., Peresie, H., Maher, C.& Barrett, P. (1979). Deficits in psychologic and classroom performance of children with elevated dentine lead levels. New England Journal of Medicine, 300, 689-695.
Paule, M.G. (1990). Use of the NCTR operant test batery in nonhuman primates. Neurotoxicology and Teratology, 12, 413-418.
Paule, M.G., Forrester, T.M., Maher, M.A., Cranmer, J.M.& Allen, R.R. (1990). Monkey versus human performance in the NCTR operant test battery. Neurotoxicology and Teratology, 12, 503-507.
Weiss, B.& Reuhl, K. (1994). Delayed neurotoxicity: A silent toxicity. In L.W. Chang (Ed.), Principles of Neurotoxicology. (765- 784). New York: Marcel Dekker
Clarren, S.K.& Bowden, D.M. (1982). Fetal alcohol syndrome: a new primate model for binge drinking and its relevance to human ethanol teratogenesis. The Journal of Pediatrics, 101, 819-824.
Gilbert, S.G., Burbacher, T.M.& Rice, D.C. (1993). Effects of in utero methylmercury exposure on a spatial delayed alternation task in monkeys. Toxicology and Applied Pharmacology, 123, 130-136.
Gilbert, S.G.& Rice, D.C. (1994). In utero caffeine exposure affects feeding pattern and variable ratio performance in infant monkeys. Fundamental and Applied Toxicology, 22, 41-50.
Goodwin, G.A., Heyser, C.J., Moody, C.A., Rajachandran, L, Molina, V.A., Arnold, H.M., McKinzie, D.L., Spear, N.E., Spear, L.P. (1992) A fostering study of the effects of prenatal cocaine exposure: II. Offspring behavioral measures. 14, 423-432.
Heyser, C.J., Molina, V.A., and Spear, L.P. (1992) A fostering study of the effects of prenatal exposure: I. Maternal behaviors. Neurotoxicology and Teratology, 14, 415-421.
Kellog, C., Ison, J.R.& Miller, R.K. (1983). Prenatal diazepam exposure: effects on auditory temporal resolution in rats. Psychopharmacology, 79, 332-337.
Rice, D.C. (1989) Delayed neurotoxicity in monkeys exposed developmentally to methylmercury. NeuroToxicology, 10, 645-650.
Streissguth, A.P., Barr, H.M., Sampson, P.D., Parrish-Johnson, J.C., Kirchner, G.L.& Martin, D.C. (1986). Attention, distraction and reaction time at age 7 years and prenatal alcohol exposure. Neurotoxicology and Teratology, 8, 717-725.
Streissguth, A.P., Clarren, S.K.& Jones, K.L. (1985). Natural history of the fetal alcohol syndrome: a 10-year follow-up of eleven patients. The Lancet, 85-91.
Streissguth, A.P., Sampson, P.D., Barr, H.M., Darby, B.L.& Martin, D.C. (1989). IQ at age 4 in relation to maternal alcohol use and smoking during pregnancy. Developmental Psychology, 25, 3-11.
Streisguth, A.P., Barr, H.M., Olson, H.C., Sampson, P.D., Bookstein, F.L., Burgess, D.M. (1994) Drinking during pregnancy decreases word attack and srithmetic scores on standardized tests: Adolescent data from a population-based prospective study. Alcoholism: Clinical and Experimental Research, 18, 248-254.
Weiss, B., Williams, J.H., Margen, S., Abrams, B., Caan, B., Citron, L.J., Cox, C.& McKibben, J. (1980). Behavioral responses to artificial food colors. Science, 207, 1487-1489.
Fox, D.K., Hopkins, B.L., Anger, W.K. (1987) The long-term effects of a token economy on safety performance in open-pit mining. Journal of Applied Behavior Analysis, 20, 215-224.
Hopkins, B.L., Conard, R.J., Dangel, R.F., Fitch, H.G., Smith, M.J.& Anger, W.K. (1986). Behavioral technology for reducing occupational exposures to styrene. JABA, 19, 3-11.
Hopkins, B.L., Conard, R.J.& Smith, M.J. (1986). Effective and reliable behavioral control technology. American Industrial Hygiene Association Journal, 47, 785-791.
Weiss, B.& Clarkson, T.W. (1986). Toxic chemical disasters and the implication of Bhopal for technology transfer. The Milbank Quarterly, 64, 216-240.
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Students will present papers from the primary literature. Structure this as a "platform presentation" that might be delivered at a scientific meeting. In your presentation you must describe clearly the reason that the author(s) gave for conducting the research, the methods used, their strengths and weaknesses, the conclusions drawn, and the degree to which these conclusions are supported by the data and the extant literature. The following list contains some of the criteria that I use in grading:
1. Clear description of the research question.
2. Clear description of the methods (with diagrams if that helps).
3. Graphical presentation of the results. You may use the blackboard, transparencies (I will have an overhead projector available) or handouts.
4. Presentation of the authors' conclusions, coupled with a critical assessment of the degree to which they are supported. This presentation should be fair to the authors and critical. After all, no single experiment is perfect. Discuss logical inconsistencies, gaps that remain in the literature, the presence (or absence) of information on dose-effect relationships, time-courses of action, and control procedures. Discuss the wider importance (if any) of this paper. To do this you should place the paper into a broader context by drawing from the general readings, lecture, and the literature.
5. Is a mechanism of action identified, and what is it?
6. What, if any, are the public health implications of the findings?
7. What, if any, are the implications for testing or screening strategies?
8. Do the results pertain to hazard identification of risk assessment?
9. Was the experimental design appropriate?
a. Are dose-effect data presented?
b. Are time course data presented?
c. Were appropriate controls used?
d. Are the data pertinent to the behavior of individual subjects?
e. Were appropriate measures of variability presented, and how to they bear on the conclusions?
We will leave time for group projects at the end of the term. Depending on the class size, we will have two or three projects, with groups comprising three or four members. Each group can select its topic from the list of suggestions below or can come up with one of its own (subject to the instructor's approval).
The project will entail providing an evaluation of the risk associated with a putative neurotoxicant. Provide the background for a decision and arrive at a conclusion based upon the data that you present. Evidence should come from the animal laboratory and human epidemiology studies. Be aware of important issues such as dose and mechanisms for neurotoxicity. I would like for the emphasis to be on behavioral work, but that may be supplemented with other studies related to the neurotoxicity of the compound. Each group should describe the population at risk for toxicity (young?, old?), the populations exposed, levels of exposure, and conditions of exposure. You should broaden the question, where appropriate, to describe such issues as the use of the substance and why it is present where it is, the social and political dimensions of risk, whether safety measures can reasonably be applied to limit exposure, why the population exposed is exposed (i.e., is this an environmental justice issue?), wildlife or agricultural animals that might be exposed, or other related areas. This latter list is not meant to be exhaustive, nor is it intended that all those issues be covered. The class is a diverse one so it should be possible to draw from different members to broaden the basis of coverage.
Divide up the chores and present what you have learned at the end of the quarter. Meet with me before Thanksgiving to tell me what your plans are and so I can know what to expect. Turn in a written report when you give your presentation. Clearly state who did which parts of the report as you will receive a group and individual grade on this. The group's report should be concise and complete (perhaps 30 to 50 pages, plus references).
-- Methylmercury exposure through fish (you may limit it to Alabama, if you like, or you may feel like taking on the tuna industry).
-- Behavioral consequences of exposure to PCB's or dioxins.
-- Algal blooms as a potential neurotoxic risk.
-- Identify a superfund site or some other site of concern and summarize the neurotoxic potential. (information about chemicals is available on the Web).
-- Risk associated with adding manganese to the nation's gasoline supply.
-- Hazard and risk associated with pesticide use. You should limit yourself to a type of pesticide (e.g. organophosphates, pyrethroids, carbamates, . . .) and you will need to decide whether to focus on occupation exposure or public health issues.
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