The Neurodevelopmental Impacts of Pesticides

December 16, 2005
4:00 pm US Eastern Time

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Call Transcript

1. Introduction: Eleni Sotos, MA, National Coordinator, Collaborative on Health and the Environment

Hi, I’d like to introduce myself—I am Eleni Sotos, the national coordinator of the Collaborative on Health and the Environment. The moderator for this call will be Elise Miller, Executive Director of the Institute for Children’s Environmental Health, and the coordinator of the CHE Learning and Developmental Disabilities Initiative. I would like to announce that the next month’s National Partnership Call has been scheduled, and that will be on Wednesday, January 18th at 9 am Pacific, noon Eastern. On this call, we will be discussing Thyroid Disease and Environmental Factors.

2. Welcome: Elise Miller, MEd, Coordinator, CHE Learning And Developmental Disabilities Initiative, and Executive Director of Institute for Children's Environmental Health

Thank you, Eleni. Welcome, everyone. I know it’s a busy time for the holidays, but I gather we have over 100 people on the call. So I really appreciate your interest, and I will now introduce all the speakers.

Ted Schettler, who is the Science Director of the Science and Environmental Health Network, will provide some framework and context for the discussion today. Then we will have Dr. Virginia Rauh, who is a Professor of Clinical Population and Family Health at Columbia University, and she’s going to be discussing her team’s study on neurobehavioral outcomes. Next will be Dr. Brenda Eskenazi – Director of the UC Berkeley Center for Children's Environmental Health Research, and she will discuss data on neurodevelopment in young children, focusing on exposure and birth weight. Finally, we will have Dr. Margaret Reeves, who is a Senior Scientist and Program Coordinator for the Pesticide Action Network of North America. She will discuss exposure, farm-workers’ poisoning, policy and activism. So, we have a great lineup, and I will now turn it over to Ted.

3. Call Framework and Context: Ted Schettler, MD, MPH, Science Director of the Science and Environmental Health Network

Thanks Elise. I just want to make a few brief comments to frame this conversation. Many of you on the call know this, but just as a reminder - pesticides are regulated by the EPA under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). When a pesticide is newly developed, the company that intends to market it must register it with the EPA. As part of that process, a battery of toxicological assays is required, as part of the application process.

Pre-market assays are done with the active ingredient - the pesticidal compound. In real life, active ingredients are often combined with other chemicals in the final formulation. Non-pesticidal substances in the final formulation are added as solvents, or surfactants – or for other purposes that influence the behavior of the pesticide in the environment where it’s applied. These “other” ingredients are usually labeled as, “inert,” on the package – although they may actually have their own biological activity and toxicity. That is, they may not really be inert, at all. The assays required are done in validated animal tests. They include looking for acute, sub-acute and chronic toxicity, genotoxicity, cancer and reproductive and developmental effects.

Earlier this year, a immune effects were added to mandated testing of newly proposed pesticides. The effects in fish and birds are also examined. One assay that is not mandated for pesticide registration is neurodevelopmental testing. That is, what’s the effect of the chemical on the developing brain? The EPA has the authority to require such testing, and they do so on a case-by-case basis. Several years ago, the EPA issued a data call-in for developmental neurotoxicity testing on a series of pesticides that have been on the market for a number of years. Those testing results are slowly coming in to the EPA – considerably behind schedule. Some, but not all, are publicly available.

There’s a lot of literature on the health effects of pesticides that includes not only the toxicological testing of the chemicals in laboratory animals, but also many epidemiologic studies in exposed populations. There’s a good summary of this literature that was compiled by the Ontario College of Family Physicians in 2004. It can be found on their website, http://www.cfpc.ca. A couple of comments on the principle findings in their review - they noted many positive associations between pesticide exposure and various kinds of cancers, which were outlined in their report. They also remarked about a consistency of findings of nervous-system effects from pesticide exposures. They also commented particularly on occupationally exposed populations, birth defects, fetal deaths, and intrauterine growth retardation.

Today’s call is going to focus on neurodevelopmental effects of, primarily, one group of pesticides. These are the organophosphates – a family of about 20-25 insecticidal chemicals widely used in agriculture. Organophosphates were first synthesized and used as nerve gas in World War II. Since then, their chemical structures and properties have been significantly modified to alter their toxicity and other physical/chemical properties. They’re all neurotoxic. That’s how they work as insecticides. Their impact on the developing brain has been a topic of intense interest, in recent years.

One of the perennial problems with epidemiologic research into the impact of pesticides or other chemicals is often the lack of good quantitative exposure data. On today’s call, we’re going to hear about two interesting, ongoing studies of developmental impacts of organophosphates in infants – where both exposure and outcome data have been carefully collected. These are the kinds of studies that will be necessary in order to examine neurodevelopmental impacts of pesticides and other industrial compounds in people. Finally, I should also just point out that there is now accumulating evidence suggesting that early life exposures to some pesticides also increased the risk of Parkinson’s disease later in life. There is considerable interest in how early life exposures may increase the risk of other neurodegenerative diseases such as Alzheimer’s or other forms of dementia.

4. First Speaker: Dr. Virginia Rauh, Professor of Clinical Population and Family Health at Columbia University

I am going to be presenting results from the Columbia Center for Children’s Environmental Health, which is part of the NIEHS EPA-funded network on National Centers for Children’s Environmental Health. In the Columbia study, we have focused on a cohort of about 700 mothers and their newborn infants - largely inner-city minority families. Approximately three quarters of the families are Latino, and approximately one quarter of the families are African-American. This is a cohort that has been followed currently, for approximately 7 years. We have plans to continue the prospective nature of this study.

This is a study that looked at the impact of ambient-pollutants on growth and development, and behavior through the early years of life. The exposure that was mentioned by Dr. Schettler is one of the exposures that were our principle focus - the organophosphate pesticides - in particular, Chlorpyrifos. We measured Chlorpyrifos exposure in pregnant women, during the second and early third trimester of pregnancy. It’s important to understand that during our period of study, Chlorpyrifos exposures actually changed in this cohort, due to the EPA ban, which took effect on 12/31/2001. At that time, the residential use of Chlorpyrifos and some other pesticides were banned, so our study participants were no longer able to purchase these products.

The good news is that following this period, we saw lower prenatal exposures in cord blood for Chlorpyrifos exposure. Several things prompted us to look at neurodevelopmental effects in the children with the prenatal exposures. The first is, we originally saw a significant effect – an adverse effect – on birth weight. This consisted of an approximately 150-gram deficit in birth weight among children who had high Chlorpyrifos exposure, prenatally. We were concerned that this type of growth retardation might translate into neurodevelopmental effects. As a result, we followed children over the next few years of life, using the Bailey’s Scale of Infant Development. This is a test, which is widely known and widely normed. It’s particularly useful for identifying children at the low end of the developmental range. That is, those children who may have some kind of developmental deficit.

In this case, we found that by 3 years of age, children with high Chlorpyrifos exposure prenatally had a developmental deficit in motor development. They also had an increased risk of motor delay at 3 years of age. This means that the odds of motor developmental delay among those kids who were exposed to Chlorpyrifos prenatally were approximately 5 times the risk of children who had very low Chlorpyrifos exposure. Similarly, the odds of mental developmental delay, according to the Bailey, revealed that approximately 2.5 times the number of children with high Chlorpyrifos exposure revealed developmental delay, which is scoring under the score of 80 on the Bailey developmental scale. In addition, we saw some neurobehavioral effects among those children who were highly exposed. Specifically, using the child-behavior checklist, we found that a significantly higher number of children at the age of 3 manifested symptoms of attentional disorders.

According to the DSM4, attentional disorders can be of the hyperactive or the inattentive type. In our particular cohort, it looked like the Chlorpyrifos-exposed children had higher rates of the inattentive type of attentional disorder. This is consistent with other studies of certain kinds of neurotoxicants. In particular, tobacco smoke and a range of other things such as lead, and other types of heavy-metal exposures that have been well studied. These findings are somewhat worrisome, in that they suggest that early developmental effects may persist, and may be come more apparent as children develop their repertoire of behaviors. We expect to follow this cohort of children for the next 4 years, to determine whether or not the early affect on motor development and the effect on mental development and the impact on behavioral functioning will persist into the early school years.

Elise Miller: Thank you Dr. Rauh. That was excellent. We next have Dr. Brenda Eskenazi.

5. Second Speaker: Dr. Brenda Eskenazi, Director of the UC Berkeley Center for Children's Environmental Health Research

Good morning, everyone. Or, good afternoon. I’m from the University of California at Berkeley. I’m going to be talking about our research for the Center for the Heath Assessment of Mothers and Children of Salinas – or the CHAMACOS Study – which is the key study of our Center for Children’s Environmental Health Research – funded by NIEHS and EPA – and a sister study to the Columbia study.

The aims of our study were to estimate the sources, pathways and levels of in-utero and postnatal pesticide exposure of children living in an agricultural community. We were to determine the relationship of pesticide exposure, and neurodevelopment growth and respiratory disease. We aimed to also understand the mechanisms of how pesticides might affect children and human health. We also have, as a part of our center – which I will not be talking about today – interventions to reduce exposure to children. Whether or not we find positive health effects, we also want to clean-up children’s environment. We are working with our communities to develop interventions - to reduce take-home exposure from farm workers to the homes of children.

The area that we’re studying is about 2 hours south of the Bay Area in California. It is an area of intense agricultural spraying. Many of you probably are aware of the Central Valley. The Central Valley is a much larger area than the area that we’re studying. But the intensity – that is, the concentration – of pesticides, is actually less than in the Salinas Valley. The Salinas Valley is also an area where farming occurs about 11 months a year. So we were able to include in our population a fairly mobile farm-worker population that’s relatively stable, compared to the Central Valley – and where we can follow the children. In terms of the kinds of pesticides that are applied, organophosphate pesticides, that is, in the Salinas Valley, there are about half a million pounds of OP pesticides used in any given year. Some of these pesticides are known endocrine disrupters. They therefore could affect neurodevelopment through multiple mechanisms. Probably the leading number of pounds used – in terms of OP pesticides – is Diazenon, at about 130,000 pounds in 2001, during the year that our children were born. Malathion was also leading.

One thing I’d like to say, in regards to what Ginny just talked about in NYC… When Chlorpyrifos and Diazenon were banned for home use, they were not banned for agricultural use. We actually saw an increase of Diazenon during the period after they home-banned, in terms of agricultural use. What pertains to what Ginny talked about does not pertain to the agricultural setting. Also, the pesticides that we’re talking about are more than 25 different pesticides - probably 40 different pesticides, where we have a considerable number of pounds of application.

Our study population comprised 600 pregnant women, who were living in the Salinas Valley. They were MediCal-eligible, and we were trying to get primarily the mobile farm-worker family population, so they’re mostly Latina, and they plan to deliver at a community clinic or community hospital. We’re seeing them at community clinics. In California, you do receive prenatal care – even if you’re undocumented. In terms of our longitudinal birth cohort study, women were interviewed multiple times during their pregnancy. We did neurodevelopmental assessment at the time, in the first two months after – with the neonatal assessment tools using the Brazelton Scale. We’d also assess the children at 6, 12, 24, 42 – and currently our children are 5 years old. We hope to follow them to 7 years. We also did home inspections, and collected dust samples. So we know what the exposures were in the dust as well. We are currently doing respiratory sporometry functioning, and we’ll be looking at school performance. We’ve also collected about 50,000 biological and ambient specimens from urine, blood, the children and the mother’s breast milk samples, saliva samples, as well as environmental samples. And of course, many of those samples have not been analyzed. So I’ll be talking about just a fraction of those samples. As I said, there are about 50,000 in storage. Characteristics of our mothers: Most of them, 92 percent of them, are Spanish-speaking. Almost all of them were born in Mexico. They are living in poverty. About half of the women worked in agriculture during pregnancy, and 84 percent had agricultural workers in the home.

I will now be talking about the exposure measurements. Unlike the study at Columbia, our primary exposure measurement was using dialkylphosphate metabolite levels. There are 6 dialkylphosphate metabolites that are supposed to represent most of the OP’s - something like 80 percent of the OP's that are used. We’re in a different exposure scenario than in New York City, where they primarily focused on a couple of pesticides. In an agricultural community, we’ve got multiple pesticides. This was a way to get at the final common pathway of all of these different exposures. However, exposure measurement of OP's is problematic, which I hope to get into, in a little bit.

In terms of our exposures of our pregnant women, the exposures during pregnancy were considerably higher – statistically significantly higher – than the National Health and Nutrition Examination Survey. CDC also did a random sample, at the same time, of women, not necessarily pregnant women around the United States, and levels in our agricultural community are significantly higher. We have found – unlike the study at Columbia, and another study at Mount Sinai – no relationship with our pesticide measurements and birth weights. We did, however, find that women with higher levels of organophosphate metabolites – particularly dimethyls… For example, a dimethyl pesticide might be Malathion or Oxydemeton-methyl, and shortened gestational duration. However, there was no relationship with birth weight.

The third study, which is not being represented today, also did not find an association with either birth weight or gestational age. One of the curiosities, which we have discussed in past calls – not necessarily with this group – why there are differences in relationship of different measurements of OP's, and fetal growth and length of gestation. It may have something to do with not only the types of measurements – blood versus urine – as well as the particular mixture of pesticides that are being used in the different communities that we’re discussing. Again, we find a relationship with shortened gestation.

We are particularly interested in the relationship with neurodevelopment. We did find that there was a relationship on a neonatal – Brazelton Neonatal Behavior Assessment Scale – with newborns having more abnormal reflexes as the prenatal DAP metabolite levels increased; particularly, again, the dimethyl metabolites. Again, we see a dose-related increase in neonates having abnormal reflexes. We are currently looking at the relationship of both prenatal and post-natal dialkylphosphate metabolite levels in the mothers and in the children, in relationship to neurodevelopment at later ages. And we are also looking at the relationship of different genotypes. For example, the PON-1 genotype and how it might modify the susceptibility and the relationship of exposure and neurodevelopmental outcome. We are also looking at thyroid toxicity, because the ways in which pesticides may affect neurodevelopment may be via thyroid. I think I would like to wrap up by saying one more thing. That is, we are seeing new studies of actual exposure measurements. The exposure measurements are difficult to interpret, and they may reveal little about chronic exposures of children or of pregnant women, whether you use blood or you use urine, the same problem lies. The other thing is, there is a growing number of animal studies, which are beginning to look at complex mixtures. We are seeing very high levels of organochlorine exposures in our population, too. The combination of exposures, I think, is really where our research should be headed, in the near future. Thank you.

Elise Miller: Thank you so much, Dr. Eskenazi. It’s very useful to have these emerging studies – both in urban environments, as well as in farming communities. Let’s turn to Dr. Margaret Reeves.

6. Third Speaker: Dr. Margaret Reeves, Senior Scientist and Program Coordinator for Pesticide Action Network North America (PANNA)

Thank you. I’m one of the staff scientists at Pesticide Action Network North America, in San Francisco. I will talk just briefly about some of the work we’re doing regarding exposure – mostly among the farm-worker communities.

As Dr. Eskenazi pointed out, she mentioned both acute versus chronic exposure. So that’s important to keep in mind, in terms of what we’re looking at. At any rate, I’ll just make 4 brief points. About 1/3 of the reported cases of acute pesticide-related illnesses amongst California farm-workers are associated with exposure to organophosphates (OP’s) or organocarbamate neurotoxic pesticides. But, we know that under-reporting is a huge problem. And we know that many – perhaps, most – cases never get reported. As long as doctors, workers, other affected individuals fail to report, the problem essentially doesn’t exist. Hence, there is little incentive to eliminate pesticide use and exposure. In other words, I’m speaking on behalf of the opponents for reductions of pesticides. We don’t hear about cases, so it’s not a problem – so why all the fuss?

One of the big focuses that we have is reporting. It’s essential that acute exposures get reported. Along those lines, the people and the pieces are lining up in California for a legislative push to require laboratory reporting of all cholinesterase tests to a centralized authority. Cholinesterase testing -- which is one of the only easily available tests for relatively high levels of acute exposure to OP pesticides and carbamates to some extent – has actually been mandated by the California legislature for the past 30 years. But the system is quite non-functional, because there’s essentially no access to that information.

Following Washington State’s implementation of a similar cholinesterase-testing program – called “Medical Monitoring,” they actually had tremendous results in terms of access to information that could then be used to evaluate what’s happening, in terms of exposure. That, I think, is part of the initiative for behind moving forward on something like that in California. It’s still in the very, very preliminary stages. We’re not sure who and where and what and how it’s going to move forward. But that’s in the works.

Also at the national level, it’s important to remember that EPA’s OP risk assessments are not yet complete. So there’s still opportunity for input. As was pointed out, Chlorpyrifos, for example – although it’s been banned for most domestic uses – is still used very widely in agriculture. It also is a big focus of Pesticide Action Network’s drift-catching projects. We have created a tool called the drift-catcher, which is an air-monitoring tool that we can actually put into the hands of community members who are interested in not only documenting airborne exposure to Chlorpyrifos or other pesticides, but are actually interested and willing to do something about that, in terms of policy change. So Chlorpyrifos has, in fact, been a focus of some of that.

Then finally, the fourth point I want to make is that biomonitoring, of course, is an important component. Efforts to document exposure, already mentioned, were the extensive CDC biomonitoring program. PAN has provided analysis of the pesticide-specific part of the CDC data, with emphasis including neurotoxic pesticides. Including Chlorpyrifos, lindane and others.

We also have a current community-based project, doing both drift catching as I’ve mentioned – air monitoring - and analysis of Chlorpyrifos metabolite in urine in a farm-worker community in California’s Central Valley. That has been a bit problematic in some of the logistics, but we are optimistic that it’ll move forward. This bio-drift project is a project of PAN, Commonweal, the California Coalition - Californians for Pesticide Reform - which represents about 180 groups around the state, and a community group in the small town of Lindsay, California, called El Quinto Sol. In part, this project was designed as a model – how could other communities, if they’re interested in doing this kind of biomonitoring, learn from our attempts to put this project together. I think I’m just going to leave it at that, mentioning some of the things that we’re working on, and perhaps in the Q-and-A period, there’ll be more opportunity to expand.

Elise Miller: Thank you. That’s excellent, Dr. Reeves. So now we are going to turn to the Q-and-A period.

7. Questions / Comments/ Discussion

Sandra Steingraber: This is Sandra Steingraber at Ithaca College. I’m going to ask a question on behalf of [anonymous person], who is on this call. He is an environmental activist living in Galesburg, Illinois. He also has ALS. So he communicates through written word rather than spoken word. He has e-mailed me a question, which keep in mind, he formulated before having had a chance to hear this.

I’m going to read his question. I think it’s probably directed at any one of you, as it involves a biomonitoring question. His question is, “What do the speakers think about using the CDC report on human exposure to environmental chemicals as a model to investigate the levels of over 100 chemicals in patients with specific conditions, such as Parkinson’s or ALS?”

He has calculated that a minimal study with 200 patients and 200 controls -- $3,200 per person – would total $1.28 million for the lab analysis. To lower the cost of a study like this, he asks, as sort of Part 2 of the question – “Could the existing CDC data for over 2000 people serve as the control group?” Another cost-lowering option might be only to investigate a subset of the CDC list of chemicals. That’s it.

Brenda Eskenazi: I could respond, somewhat. This is Brenda. I think that what he is proposing is a case-controlled study of ALS and controls. Is that what I’m hearing?

Sandra Steingraber: Or Parkinson’s, he suggests.

Brenda Eskenazi: Or Parkinson’s. The problem, again, is the exposure. We’re not talking about… I’m well aware of the measurements that CDC does, since they do our measurements, as well. The problem is that except for the organochlorines, you’re talking about transient exposures that may not be correlated, over time. Even in a community like an agricultural community, where there’s steady pesticide usage. Or, even in home environments, because that will be seasonal, as well.

So you’ll be getting current levels of exposure to transient chemicals, which may not reflect the exposure during the critical period, when the disease began, or if one knew it. I think that’s the problem. I think it’s a noble attempt, but I think it’s not like working with dioxins or organochlorines, where their half-lives are very long.

Elise Miller: Thank you. And thank you for that question, as well. Other questions, please?

Suzanne Wuerthele: This is Suzanne Wurerthele with EPA’s regional office in Denver. I’d like to ask our speakers to comment on the fact that EPA has so far made its decisions on organophosphate pesticides, primarily on the basis of cholinesterase, under the assumption that this is the endpoint that’s the most sensible. I’m wondering if our speakers could comment on the possibility that developmental neurotoxicity might occur at levels of exposure that do not cause cholinesterase, or even by a different mechanism?

Virginia Rauh: This is Virginia. I would defer to Brenda, if she has some thoughts about this. Certainly, Ted Slotkins has suggested that some of the damage may occur by at least 2 different mechanisms. So I think the jury is out on that. I would definitely agree that we should be looking at levels that are considerably lower than have been offered in the past.

Brenda Eskenazi: Yes. I would concur that there are probably multiple mechanisms that are involved, here. As I mentioned, I think some of these chemicals are endocrine-disruptors that may work through the thyroid. When we’re dealing with developing mechanisms and developing organisms, we may not see a fetal cholinesterase inhibition to the levels that would produce neurobehavioral effects in adults. So I’m not sure that those should be the only markers.

Elise Miller: Just as a reminder – on our next call in January, on January 18th – we will be focusing on thyroid. I suspect that this question about the impact of pesticides on thyroid will come up on that call, as well. Other questions?

Anne Greenlee: This is Anne Greenlee, calling from La Grande, Oregon, with Oregon Health & Sciences University. My question is for Margaret Reeves, concerning the bio-drift program that you have, and the issue that Brenda brought up about the inability to capture those exposures that happen close to the exposure. I’m wondering if you’re adding that to your study, where the community members are able to collect information on the drifts. But, then what about the exposures to the people? Are they providing blood or urine close to the time of that drift exposure?

Margaret Reeves: Yes. The idea for the project is actually a couple of things. One is that we also collect food, to exclude if that’s the case, that source of exposure, Food-borne of exposures. The idea that we collect air samples during a week period, near the end of which we do a urine sample. The idea is – the question is – is it possible to actually correlate airborne levels and metabolites in the urine? Frankly, we’ve had problems. It’s a very small sample size, so it’s very much a pilot project with limited funds, of course, and all the rest. We had an issue with the lab results, in that the minimum level of detection was substantially higher than what the CDC lab was, for example. But even there, comparing several studies, the null result seems that we got from the lab seems very questionable. We’re working on some of that. The idea is that yes, we do both air monitoring and metabolite-sampling at the exact same time.

Anne Greenlee: Once you have those findings, then what sorts of community action are you thinking about, as far as interventions or political sway?

Margaret Reeves: That’s the next big step. There’s an important component of this project, which is working with the community organizations to identify what their priorities are – and what the possible scenarios are. The kinds of things that people are looking at are buffer zones and neighbor-notification. Some of the first steps are plans to meet with the local or county agricultural commissioner. There’s an organized program of migrant families at the school system. That’s one way around which they can get the knowledge to the communities. It’s impossible, at this point, to figure out what it is the community wants to do about it. But we are working with an organized group, and helping them to be organized around it. We’ll see what the outcomes will be.

Anne Greenlee: Good luck.

Margaret Reeves: Thank you.

Loren Vanderlin: Hi, this is Loren Vanderlin from Toronto Public Health. I have a question for either Dr. Rauh or Dr. Eskenazi. Thank you very much for your wonderful studies. We’ve relied on them a lot here in Toronto, in making the case about health impacts and needing pesticide by-laws. I wonder if there are any plans for any similar studies that would look at impacts from exposure to pyrethroids as being kind of the new frontier of insecticides that are more widely available for residential use in lice treatment.

Brenda Eskenazi: We do have measurements of pyrethroids in house dust. We’re hoping to get pyrethroids measurements, as well, in biological specimens. We are expanding to pyrethroids. But again, we also are looking at organochlorines because of the high levels of exposure.

Virginia Rauh: I would just add that we also have a number of pesticides that we haven’t analyzed, yet. We are doing our lab work in conjunction with CDC. We have a little bit of a backlog. But we will also be taking a look at the impact of some of these other pesticides.

Lynne Cannon: This is Lynne Cannon, from the Learning Disabilities Association. As I understand it, both Dr. Rauh’s project and Dr. Eskenazi’s project only look at children up to the age of 5. I wondered if your work at that age correlated with the work of pesticide studies in Mexico. Also, whether there would be any possibility that your work could be extended, for example, to age 10 – to look more closely at the cognitive impacts it could have on school-aged children.

Virginia Rauh: I’ll take that question, Lynne. We’re currently following, in the New York sample, the children until 8 years of age. I may not have made that clear. We do hope to continue following them until at least 10 years of age, so that we would have access to more of the early school-age kinds of measures. With respect to the Mexico study – that’s the Gillett study…?

Lynne Cannon: Yes.

Virginia Rauh: I don’t know, exactly, what their ranges of exposure were. We had a range of exposure to Chlorpyrifos – ranging from non-detect, which was about 6.2 picograms per gram, up to 63 picograms per gram. We were looking at the highest quartile of exposure, and that is the place where we saw the most-significant effects. We think that with respect to neurocognitive impacts, there are many other areas of attentional disorders and learning disabilities that we can expand our work into. As the children become older, of course, it’s a cohort study. So we have completed published findings by the age of 3. But we have considerable numbers of children who’ve already matured through the age of 5. We’re expecting to do more clinical assessments of attentional deficit – and maybe some additional physiological assessments of attentional problems. We are hopeful that by looking at more detailed aspects of the neurodevelopmental deficits, we’ll have a clearer idea about hypothesizing mechanisms, and could propose additional studies in the future.

Brenda Eskenazi: One thing I guess I didn’t make clear, as well – these are both birth-cohort studies, where the children are aging – as we are. So also, our children are 7 years. We have money to follow the children up to 7 years of age. They are now 5 years old. We just haven’t finished the data analysis for the biomonitoring analysis as far as 5, at this point. The children are currently 5 years of age.

A new, exciting study we’re about to begin is a parallel study in Mexico. The children from our community in Salinas come from a few different states in Mexico. We’ll be recruiting children from those same states, at the same age, at 5 years of age, looking at neurodevelopment and pesticide exposure in Mexico, given that our children are mostly Mexican-American. One of the things I didn’t mention is that we’re also not only looking at cognitive functioning and behavior, but we’re also looking at autonomic nervous system functioning, because we’re concerned about the effects of pesticides – not just in cognition, but also on respiration and cardiac reactivity, and reaction to stressors that involve the autonomic nervous system. We have developed mechanisms and ways of studying the autonomic nervous system.

Lynne Cannon: Thank you. We look forward to seeing the results of your study.

Michael Lerner: A question that probably includes Ted Schettler, but for any of the speakers: where could a policymaker or an interested lay person find a summary of not only what is known, but what we are concerned about, about the broad impact of pesticide exposures on human health, both in terms of developmental conditions, degenerative conditions, just the whole range of them? This has been a wonderful description of the challenges of the real research. But for a policymaker or for an interested person, what could we say in sort of a broad sweep, about what our concerns are on broad impacts of pesticide exposures on human health?

Ted Schettler: I would just refer, again, to the summary that was provided by the Ontario College of Family Physicians in 2004 (http://www.cfpc.ca) as one place to go for a summary and a bibliography and a description of some of the challenges in drawing conclusions – from the epidemiologic studies – which include adequacy of exposure assessment, as well as controlling for confounders and a variety of other things that make this kind of work extraordinarily difficult. I think that implied in your question is this notion that when you begin to see the signals that really do stand out in the epidemiologic literature, they’re probably very real. Because there are a lot of issues that are conspiring to find false-negatives. So, I think that that summary is probably as good as any, to lay out for the case in the literature as it is. There may be some updates to particular parts of it since then, but that’s a place to start.

Michael Lerner: Ted, just one follow-up question. You distinguish between the efforts to assess what happens with individual’s health – why one of us gets ill with Parkinson’s or whatever – and then the public health questions that are addressed through epidemiology, and then you distinguish ecological health as a third level of analysis. If you look at the issue of pesticides from the third level of ecological health analysis, are there people who are trying to put together the totality of the animal experiments, the wildlife observations, the human health observations in a synthesis about what all of those literatures tell us about the effects of pesticide exposures?

Ted Schettler: I think you find attempts at that in a couple of places. But probably in the sustainable agriculture literature and activities, you will find that system’s overview represented, as well as anywhere else. You can find, in that literature, critiques of the industrial-agricultural model. You can find critiques of ecological impacts, economic considerations. But I think that’s probably where one would look.

Margaret Reeves: This is Margaret. I think Ted did a fine job. I don’t have anything else to add. There’s a lot out there, but I think that what you’re looking for are concise summaries. I think those are probably the best places.

Claudia Miller: This is Claudia Miller, from the University of Texas. I wanted to know a little bit more about the use of the PON-screening. I think Dr. Eskenazi mentioned that they were examining that. I mention the fact that Dr. Clement Furlong’s work, looking at some of the alleles, that if one is homozygous for those particular alleles and they put them in a rodent, that the rodent might as well be known for paraoxonase - it just has no ability to metabolize the stuff, and this was actually the chlorpyrifos-oxonase. The question really is - and concern is - what about people in the population that may be especially susceptible because of the inability to metabolize these things. Are we then seeing increases in some of the neurobehavioral problems that people are very much concerned about, whether it’s autism or things that were mentioned earlier, ALS and Parkinson’s? I think we really need to be looking at this simultaneously.

Brenda Eskenazi: I absolutely agree. In fact, we have a grant to do just exactly that. We have just analyzed with Dr. Clem Furlong, and Dr. Nina Holland in our group. We’ve looked at a number of different polymorphisms, as well as five different enzymes in both the fetal cord blood, as well as the maternal blood. We’ve got two papers – one’s in-press and one is under review. We have seen a very wide range of potential susceptibility to OP’s, with the children being, of course, more vulnerable, because they have lower levels of the paraoxonase. Therefore, they’re going to be potentially more susceptible to pesticides. This remains to be seen, by looking at it in relationship to exposure, and health outcomes such as neurodevelopment. But we are about to look at that.

Margaret Reeves: I just actually wanted to add one comment that was brought up much earlier as sort of a reminder to us all, that much of the studies are focused on – especially with regulatory assessments – active ingredients, missing the inerts and “inerts.” Another issue I wanted to bring up is that of the metabolites, themselves. Some of the metabolites being even more toxic, apparently. Can anybody address that issue, as well? So there are both chemical mixtures, and metabolites.

Brenda Eskenazi: I can just say something about the metabolites – there’s been a recent study, which has suggested that we are exposed to the metabolites, the dialkylphosphate metabolites. That it’s not just that urine levels that we’re getting in humans may not just reflect their metabolism of a parent compound, but actually exposure to metabolites. I don’t know of any study that has specifically looked at the relationship of exposure to metabolites in health outcomes. But, maybe in animal studies.

Michael Lerner: Two questions – one for Elise. Elise, as the director of the Learning & Developmental Disabilities Initiative, many of the developmental issues are concerns of partners in the initiative. To what degree in the LDDI calls and process, have you addressed pesticide issues specifically, and to what degree have your partner organizations of the Learning Disabilities Association and others, formulated responses, either collectively or individually to the pesticide issue, in terms of policy concerns or other initiatives?

Elise Miller: Thank you, Michael. We did actually have Dr. Eskenazi on one of our Learning Development & Disabilities Initiative calls. I believe it was in September. We focused on some of the research that she’s undertaking on that call. We also have responded – at least to those members in LDDI who have been interested. We wrote a letter regarding lindane, with the help of Pesticide Action Network, in drafting that letter. A number of LDDI members – including the Learning Disabilities Association and the American Association on Mental Retardation, signed on – basically recommending and encouraging lindane to not only be phased out of agricultural use, but out of pharmaceutical use – because it’s used for lice on children’s heads, still. I’ll also mention that Lynne Cannon from the Learning Disabilities Association, who asked a question earlier, developed as the head of the LDA of Iowa, showed a video on thyroid conditions and their links to learning disabilities, and that also highlighted some of the pesticide issues. So, there has been a number of different ways that we’ve gotten into this subject, but clearly there are more opportunities we’d like to bring up in 2006.

Lynne Cannon: We do have a resolution that was passed in 2003/2004, on endocrine disruptors, pesticides, et cetera.

Elise Miller: You mean the Learning Disabilities Association of America?

Lynne Cannon: Yes. And we distribute this freely to anybody and everybody who will take it. I would be happy to mail some copies to CHE, so that they can use it at their discretion, and respond to it in any way that might need updating. I believe it is on the website, but I will send you a copy and I will request that it be put on the LDA website if it is not already on it.

Sandra Steingraber: I’ll throw out one of my own questions, quickly. One of the most common questions I get from the public is evidence for harmful for exposures occurring in school-aged children. Apart from the question of following cohorts of kids whose prenatal and perinatal exposures we’ve documented – and then looking at their outcomes, I think that the spirit of this question is that of parents who couldn’t deal with thinking about environmental harm when they were pregnant. But now that their kids are in school, they’re interested in thinking about these things. They might want to get organic food in the schools, or get their kids’ playgrounds to stop spraying the soccer fields. Could anyone tell me if we have some exposure studies, looking at school-aged children and OP pesticides? But is there evidence for harm for kids who are exposed at that age?

Margaret Reeves: With nothing concrete to add, it seems there is a lot coming out around asthma, especially in California’s Central Valley. Apparently, there are lots of links to chemical exposure and others. Not just pesticides, but pesticides are included in the mix. I don’t know who to connect you to, but that’s one body of literature that’s being developed.

Elise Miller: We’re going to have to actually wrap up, here. I just want to thank all of our presenters and the excellent questions that people asked. I want to now turn it over to Eleni for wrap-up, and a reminder about our next call. Thank you to everyone, and happy holidays!

Eleni Sotos: Thanks, Elise. I just want to quickly remind folks that our next call is scheduled for Wednesday, January 18th at 9 am PT, noon ET. We will be looking at Thyroid Disease and Environmental Factors. I’d like to thank everyone, and happy holidays! We look forward to our call in January. Take care, everyone!