Violence and Environmental Exposures

Karen RobinsonEnvironmental Health

Compiled by Dr. Jennifer Armstrong and Helen Neizgoda.

June, 2007

1. Books

Environmental Topics – Volume 7 – Environmental Toxicology:  Current Developments
Edited by John Rose
Published by: Gordon and Breach Science Publishers
ISBN – 905-6991-40X    1998
See Chapter 2, pages 13-48.
Environment Pollution, Neurotoxicity and Criminal Violence.  By Roger D. Masters

 

Is This Your Child’s World?  How You Can Fix the Schools and Homes that are making your Children Sick.
Doris J. Rapp, MD.
Bantam Books
October 1996
ISBN – 0 -553-10513-2

2. Video:

showing violent behaviour from children undergoing controlled exposures in medical facility:

Environmentally Sick Schools.  Dr. Doris Rapp. Available through CASLE or Halifax Regional Libraries or from Practical Allergy Research Foundation, PO Box 60, Buffalo NY, 14223.

 

3. Environmental Pollution, Neurotoxicity, and Criminal Violence. Roger D. Masters, Brian Hone, Anil Doshi, Environmental Toxicology, Gordon and Breach Publishers, 1997.

 

Here is a write up about Master’s publication.  This is taken from http://www.life.ca/nl/57/crime.html.

Toxic Pollutants
Cause Violent Crime
by Peter Montague

Pollution causes people to commit violent crimes – homicide, aggravated assault, sexual assault and robbery – according to new research by Roger D. Masters and co-workers at Dartmouth College. Sociologists have known for a long time that violent crimes occur more in some places than in others. Some U.S. counties have only 100 violent crimes per 100,000 people per year; other counties have rates of violent crime that are 30 times as high. The question is why some places have high crime rates and others don’t. Masters says pollution is part of the answer.

Masters has developed what he calls the neurotoxicity hypothesis of violent crime. According to this hypothesis, toxic pollutants – specifically the toxic metals lead and manganese – cause learning disabilities, an increase in aggressive behavior, and – most importantly – loss of control over impulsive behavior. These traits combine with poverty, social stress, alcohol and drug abuse, individual character, and other social factors to produce individuals who commit violent crimes.

Masters argues that, to be taken seriously, such a hypothesis must pass five tests. He then demonstrates how the neurotoxicity hypothesis meets all five, as follows:

1) It must be shown that individuals who engage in criminal behavior are more likely to have absorbed toxic chemicals than a comparable control population. Masters cites studies showing that low-level poisoning by lead, and by manganese, is associated with learning disabilities and attention deficit disorder, which are themselves associated with deviant behavior. Masters cites seven other studies showing that violent prisoners have significantly elevated levels of lead, manganese, cadmium, mercury or other toxic metals, compared to prisoners who are not violent.

2) If it is valid, the neurotoxicity hypothesis must be able to predict future violent behavior of young people exposed to toxins. Masters cites two prospective studies (and suggests we need more) showing that lead uptake at age seven is associated with juvenile delinquency and/or increased aggression in teenage and early adult years. The largest study, of 1,000 black children in Philadelphia, showed that both lead levels, and anemia, were predictors of the number of juvenile offenses, the seriousness of juvenile offenses, and the number of adult offenses, for males.

3) Is there a biological basis for believing that lead, manganese and other toxic metals could cause a person to lose control over impulsive and aggressive behavior?  Here Masters cites a wealth of studies showing how lead and manganese cause changes in the development of the brain, and in the functioning of neurotransmitters in the brain.

Different pollutants harm the brain differently. Lead in the brain damages glia, a kind of cell associated with inhibition and detoxification. Manganese has the effect of lowering levels of serotonin and dopamine, which are neurotransmitters associated with impulse control and planning. Masters notes that low levels of serotonin in the brain are known to cause mood disturbances, poor impulse control, and increases in aggressive behavior – effects that are increasingly treated with Prozac.

Masters emphasizes that children who are raised from birth on infant formula and who are not breast fed will absorb five times as much manganese as breast-fed infants. Calcium deficiency increases the absorption of manganese. A combination of manganese toxicity and calcium deficiency adds up to “reverse Prozac,” Masters says.

Masters says toxic metals affect individuals in complex ways. For example, because lead diminishes a person’s normal ability to detoxify poisons, lead may heighten the effects of alcohol and drugs.

4) For the neurotoxicity hypothesis to hold up, individuals must receive doses of toxic metals sufficient to be associated with violent behaviour. Masters argues that, despite recent significant decreases in lead in the environment (because leaded gasoline and lead paint have been banned in the U.S.), in neighborhoods where automobile traffic has historically been high, and in towns where industries have released large quantities of toxic metals for years, many local soils still contain toxic quantities of lead, cadmium, and manganese sufficient to poison children who play in the dirt. He also argues that aging water delivery systems very likely contribute lead and manganese because lead pipes and even iron pipes contain these toxins.

Masters argues that (a) children absorb up to 50 percent of the lead they ingest (compared to 8 percent for adults); (b) even low exposures in the womb and in early childhood can have permanent effects on intelligence and behavior; (c) current lead levels are known to have direct effects on neurotransmitters that are known to affect cognition and to influence impulse control; and (d) the highest levels of lead uptake are reported in precisely the demographic groups most likely to commit violent crimes (inner city minority youths).

Masters emphasizes the importance of studies showing a synergistic effect (multiplier effect) between toxic metals and poor diet. For example, it has been thoroughly documented that uptake of lead is greatly increased among individuals who have a diet low in calcium, zinc, and essential vitamins. Similarly, as noted above, calcium deficiency greatly increases one’s absorption of manganese. Thus, Masters argues, amounts of lead and manganese that wouldn’t harm a well-nourished individual may poison undernourished children.

Masters cites federal studies of nutrition to make the point that black teenage males consume, on average, only about 65 percent as much calcium as whites. The calcium needs of pregnant or breast-feeding women are higher than average, which creates a particular problem for minority women. And non-Hispanic black women get only 467 milligrams of calcium per day (mg/d), compared to 642 mg/d for white women, government studies show.

Because of increased manganese absorption by babies who drink infant formula and who are not breast fed, Masters considers infant formula toxic. He emphasizes that poor mothers tend not to breast-feed their babies. By 1986-87, 73 percent of infants born to mothers with more than 12 years of education were breastfed compared with 49 percent of infants born to mothers with 12 years of education, and 31 percent of mothers with less than 12 years of education. Furthermore, white infants are more than three times as likely to be breast fed as black infants. “The effects of manganese toxicity associated with infant formula are thus greatest for the poor, for ethnic minorities, and for those with little education,” Masters says.

Masters cites studies showing that alcohol increases the uptake of toxic metals, at least in laboratory animals, and probably has a similar effect on humans.

5) If the neurotoxicity hypothesis is valid, then measures of environmental pollution should correlate with higher rates of violent crime.

To test his hypothesis, Masters acquired data from the FBI for violent crimes in all counties of the U.S. He correlated this with data on industrial releases of lead and manganese into the environment of each county, using data from the U.S. Environmental Protection Agency’s (EPA) TRI [toxic release inventory] database. He also examined other variables for each county – population size, population density, housing built before 1950, number of police officers per person, number of school dropouts and high school dropouts, educational achievement, unemployment rate, race and ethnicity [white, black, hispanic], persons below the poverty level, number of people on welfare, infant deaths per 1,000 live births, all alcohol-related causes of death, and all causes of death with explicit mention of alcohol.

The EPA’s recorded releases of toxic metals are not predicted by these demographic or socio-economic variables. In fact, less than 5 percent of the variance of reported releases of lead is accounted for by 19 socio-economic factors (many of them listed in the previous paragraph).

Masters split all U.S. counties into six groups – those with and without industrial lead releases; those with and without industrial manganese releases; and those with higher-than-average or lower-than-average rates of alcohol-related deaths. After controlling for all the conventional measures of social deterioration (poverty, school dropouts, etc.), Masters found that counties having all three measures of neurotoxicity – lead, manganese, and high alcohol – have rates of violent crime three times the national average.

In other words, environmental pollution and alcohol have a strong effect on violent crimes, completely independent of any of the “traditional” predictors of violent crime (poverty, poor education, etc.)

As Masters says, neurotoxicity is only one of many factors contributing to violence, but he believes it may be especially important in explaining why violent crime rates differ so widely between geographic areas and by ethnic group. Masters says that traditional sociological approaches to crime cannot explain why the availability of handguns or drugs triggers violent behavior in only a small proportion of the population, a proportion that varies greatly from place to place. Part of the explanation may be the way the physical environment affects brain chemistry and behavior, Masters says.

“The presence of pollution is as big a factor as poverty,” Masters said in an interview in the May 31, 1997 edition of New Scientist magazine. “It’s the breakdown of the inhibition mechanism that’s the key to violent behavior,” he says. When our brain chemistry is altered by exposure to toxins, we lose the natural restraint that holds our violent tendencies in check, Masters believes.

Former U.S. Surgeon General C. Everett Koop has said, “Regarding violence in our society as purely a sociologic matter, or one of law enforcement, has led to an unmitigated failure. It is time to test further whether violence can be amenable to medical/public health interventions.”

For decades, researchers have focused on the human health consequences of toxic metals – mainly asking, do they cause cancer?  This new research seems to be telling us that we should also be looking at the way these pollutants are affecting human behaviour.

Peter Montague is the Editor of Rachel’s Environment & Health Weekly, where this article first appeared (Issue 551). The report he cites is Environmental Pollution, Neurotoxicity, and Criminal Violence by Roger D. Masters, Brian Hone, and Anil Doshi, published in Environmental Toxicology (Gordon and Breach Publishers, 1997).

 

4.Research Links Lead Exposure, Criminal Activity

Data May Undermine Giuliani’s Claims

By Shankar Vedantam
Washington Post Staff Writer
Sunday, July 8, 2007; A02
http://www.washingtonpost.com/wp-dyn/content/article/2007/07/07/AR2007070701073_pf.html

Rudy Giuliani never misses an opportunity to remind people about his track record in fighting crime as mayor of New York City from 1994 to 2001.

“I began with the city that was the crime capital of America,” Giuliani, now a candidate for president, recently told Fox’s Chris Wallace. “When I left, it was the safest large city in America. I reduced homicides by 67 percent. I reduced overall crime by 57 percent.”

Although crime did fall dramatically in New York during Giuliani’s tenure, a broad range of scientific research has emerged in recent years to show that the mayor deserves only a fraction of the credit that he claims. The most compelling information has come from an economist in Fairfax who has argued in a series of little-noticed papers that the “New York miracle” was caused by local and federal efforts decades earlier to reduce lead poisoning.

The theory offered by the economist, Rick Nevin, is that lead poisoning accounts for much of the variation in violent crime in the United States. It offers a unifying new neurochemical theory for fluctuations in the crime rate, and it is based on studies linking children’s exposure to lead with violent behavior later in their lives.

What makes Nevin’s work persuasive is that he has shown an identical, decades-long association between lead poisoning and crime rates in nine countries.

“It is stunning how strong the association is,” Nevin said in an interview. “Sixty-five to ninety percent or more of the substantial variation in violent crime in all these countries was explained by lead.”

Through much of the 20th century, lead in U.S. paint and gasoline fumes poisoned toddlers as they put contaminated hands in their mouths. The consequences on crime, Nevin found, occurred when poisoning victims became adolescents. Nevin does not say that lead is the only factor behind crime, but he says it is the biggest factor.

Giuliani’s presidential campaign declined to address Nevin’s contention that the mayor merely was at the right place at the right time. But William Bratton, who served as Giuliani’s police commissioner and who initiated many of the policing techniques credited with reducing the crime rate, dismissed Nevin’s theory as absurd. Bratton and Giuliani instituted harsh measures against quality-of-life offenses, based on the “broken windows” theory of addressing minor offenses to head off more serious crimes.

Many other theories have emerged to try to explain the crime decline. In the 2005 book “Freakonomics,” Steven D. Levitt and Stephen J. Dubner said the legalization of abortion in 1973 had eliminated “unwanted babies” who would have become violent criminals. Other experts credited lengthy prison terms for violent offenders, or demographic changes, socioeconomic factors, and the fall of drug epidemics. New theories have emerged as crime rates have inched up in recent years.

Most of the theories have been long on intuition and short on evidence. Nevin says his data not only explain the decline in crime in the 1990s, but the rise in crime in the 1980s and other fluctuations going back a century. His data from multiple countries, which have different abortion rates, police strategies, demographics and economic conditions, indicate that lead is the only explanation that can account for international trends.

Because the countries phased out lead at different points, they provide a rigorous test: In each instance, the violent crime rate tracks lead poisoning levels two decades earlier.

“It is startling how much mileage has been given to the theory that abortion in the early 1970s was responsible for the decline in crime” in the 1990s, Nevin said. “But they legalized abortion in Britain, and the violent crime in Britain soared in the 1990s. The difference is our gasoline lead levels peaked in the early ’70s and started falling in the late ’70s, and fell very sharply through the early 1980s and was virtually eliminated by 1986 or ’87.

“In Britain and most of Europe, they did not have meaningful constraints [on leaded gasoline] until the mid-1980s and even early 1990s,” he said. “This is the reason you are seeing the crime rate soar in Mexico and Latin America, but [it] has fallen in the United States.”

Lead levels plummeted in New York in the early 1970s, driven by federal policies to eliminate lead from gasoline and local policies to reduce lead emissions from municipal incinerators. Between 1970 and 1974, the number of New York children heavily poisoned by lead fell by more than 80 percent, according to data from the New York City Department of Health.

Lead levels in New York have continued to fall. One analysis in the late 1990s found that children in New York had lower lead exposure than children in many other big U.S. cities, possibly because of a 1960 policy to replace old windows. That policy, meant to reduce deaths from falls, had an unforeseen benefit — old windows are a source of lead poisoning, said Dave Jacobs of the National Center for Healthy Housing, an advocacy group that is publicizing Nevin’s work. Nevin’s research was not funded by the group.

The later drop in violent crime was dramatic. In 1990, 31 New Yorkers out of every 100,000 were murdered. In 2004, the rate was 7 per 100,000 — lower than in most big cities. The lead theory also may explain why crime fell broadly across the United States in the 1990s, not just in New York.

The centerpiece of Nevin’s research is an analysis of crime rates and lead poisoning levels across a century. The United States has had two spikes of lead poisoning: one at the turn of the 20th century, linked to lead in household paint, and one after World War II, when the use of leaded gasoline increased sharply. Both times, the violent crime rate went up and down in concert, with the violent crime peaks coming two decades after the lead poisoning peaks.

Other evidence has accumulated in recent years that lead is a neurotoxin that causes impulsivity and aggression, but these studies have also drawn little attention. In 2001, sociologist Paul B. Stretesky and criminologist Michael Lynch showed that U.S. counties with high lead levels had four times the murder rate of counties with low lead levels, after controlling for multiple environmental and socioeconomic factors.

In 2002, Herbert Needleman, a psychiatrist at the University of Pittsburgh, compared lead levels of 194 adolescents arrested in Pittsburgh with lead levels of 146 high school adolescents: The arrested youths had lead levels that were four times higher.

“Impulsivity means you ignore the consequences of what you do,” said Needleman, one of the country’s foremost experts on lead poisoning, explaining why Nevin’s theory is plausible. Lead decreases the ability to tell yourself, “If I do this, I will go to jail.”

Nevin’s work has been published mainly in the peer-reviewed journal Environmental Research. Within the field of neurotoxicology, Nevin’s findings are unsurprising, said Ellen Silbergeld, professor of environmental health sciences at Johns Hopkins University and the editor of Environmental Research.

“There is a strong literature on lead and sociopathic behavior among adolescents and young adults with a previous history of lead exposure,” she said.

Two new studies by criminologists Richard Rosenfeld and Steven F. Messner have looked at Giuliani’s policing policies. They found that the mayor’s zero-tolerance approach to crime was responsible for 10 percent, maybe 20 percent, at most, of the decline in violent crime in New York City.

Nevin acknowledges that crime rates are rising in some parts of the United States after years of decline, but he points out that crime is falling in other places and is still low overall by historical measures. Also, the biggest reductions in lead poisoning took place by the mid-1980s, which may explain why reductions in crime might have tapered off by 2005. Lastly, he argues that older, recidivist offenders — who were exposed to lead as toddlers three or four decades ago — are increasingly accounting for much of the violent crime.

Nevin’s finding may even account for phenomena he did not set out to address. His theory addresses why rates of violent crime among black adolescents from inner-city neighborhoods have declined faster than the overall crime rate — lead amelioration programs had the biggest impact on the urban poor. Children in inner-city neighborhoods were the ones most likely to be poisoned by lead, because they were more likely to live in substandard housing that had lead paint and because public housing projects were often situated near highways.

Chicago’s Robert Taylor Homes, for example, were built over the Dan Ryan Expressway, with 150,000 cars going by each day. Eighteen years after the project opened in 1962, one study found that its residents were 22 times more likely to be murderers than people living elsewhere in Chicago.

Nevin’s finding implies a double tragedy for America’s inner cities: Thousands of children in these neighborhoods were poisoned by lead in the first three quarters of the last century. Large numbers of them then became the targets, in the last quarter, of Giuliani-style law enforcement policies.

 

 


5. Article on the Internet:

 

Environmental Issues –  School Environment – Healthy or Hazardous?
by Rose Marie Williams

Taken from http://www.tldp.com/issue/11_00/environ.html.  1983-2002 Townsend Letter for Doctors and Patients

We like to think schools are safe, healthy places that create an atmosphere conducive to learning, creativity and mind broadening experiences. In some cases, quite the opposite is true.

Modern construction materials, toxic chemical exposure and poor indoor air quality can impede learning, dull mental acuity, induce behavior disorders, and contribute to myriad health problems, not the least of which is asthma.

Parents, educators, and physicians need to become more aware of these environmental issues in order to act as true advocates for children’s health. Administrators, teachers, custodial and cafeteria staff need to learn more about the products they are exposed to in the workplace.

It is naive to expect government regulatory agencies to always act on our behalf. There are too many reasons why this often does not work. This column will highlight a few problems affecting children’s health in the school environment.

Pesticides in Schools

Schools use toxic chemicals for pest and termite control in buildings; on lawns, trees, and athletic fields; as disinfectants and deodorizers; and as wood preservatives on “treated lumber” in playground equipment.

Synthetic pesticides, largely derived from petroleum products, include insecticides, fungicides, herbicides and rodenticides. The United States Environmental Protection Agency (EPA) registers these products because they are harmful to all living creatures.

It is a federal offense to advertise registered products as safe. Registration merely implies that the active ingredient will do what the label claims – kill or diminish some life form. Using a registered product in a manner not consistent with the directions is also a breach of law.

Pesticides are poisons that not only kill the target pest, but pose a serious threat to other organisms. Repeated exposures to small doses can be very harmful to humans and wildlife.

Some pesticides pose an additional threat because they are long lasting in an indoor environment. Dursban (active ingredient – chlorpyrifos) is one such chemical found to linger on furniture and release vapors into the air weeks after being sprayed.1

Chlorpyrifos, associated with numerous toxic health effects in children and birth defects in newborns, has finally been restricted by the EPA as of June, 2000, following years of lobbying efforts by health advocacy groups.

Pesticides and Children

The two major classes of pesticides – organophosphate and carbamate insecticides – kill insects by disrupting nerve transmission. The nervous systems of humans are similarly affected by these neurotoxins.

Pesticides and children are a dangerous mix. Children are not merely miniature adults. They are more susceptible to exposure to pesticides for several reasons. Children play closer to the ground where pesticides are directly sprayed, and on floors or rugs where pesticides are tracked in on shoes.

Children’s unique eating patterns and hand to mouth behavior expose them to more pesticides than adults. They take in more food, water, and air per body weight than adults. Their skin is more absorbent to lipophilic agents than adults.2

Children’s decreased ability to detoxify and excrete pesticides, and the rapid growth, development, and differentiation of their vital organ systems compounds their risks of exposure to chemicals. Children’s underdeveloped immune systems make them more vulnerable to the toxic effects of pesticides.3

Pesticide Testing

 

Some 70,000 chemicals are in the marketplace, the great majority of which came into use before any testing was mandated. When EPA was created their testing protocol did not even consider the effects of pesticides on children.

Research of chemical toxicity on lab specimens was extrapolated to consider health effects on an adult male weighing 170 pounds. No thought was given to the toxic effects these chemicals would have on a 60 pound child or 30 pound toddler.

Testing is only done on the active ingredient which may compose as little as 1% to 10% of the total product. The other ingredients are listed as “inert,” when they often contain active compounds, some more toxic than the active ingredient listed on the label.4

Little or no testing is done on the synergistic activity of all ingredients in a marketed product, nor is there any government or industry testing on the adverse or long range effects, or from exposure to multiple products as exist in real life situations.

Carpeting in the Classroom

In an effort to modernize and quiet down classroom noise many schools now use rugs. However, there is more to carpeting than meets the eye. Volatile organic compounds (VOCs) emitted by carpet backings and adhesives have been blamed for health problems ranging from nausea to skin irritation.

Synthetic glues and fibers release toxic chemical fumes contributing to indoor air problems. Studies involving carpet installation workers have determined higher levels of leukemia, central nervous system damage, lung, oral, and testicular cancers.

Even small amounts of fumes can cause serious health problems. One study of mice exposed to carpet fumes developed abnormalities of their respiratory, neuromuscular and neurological systems. Many died, and autopsies found kidney damage and lesions in the liver and brain. It didn’t matter if the carpeting was brand new, or twelve years old!5

To further illustrate the serious health risks associated with carpeting, insurance companies are reluctant to grant life insurance to rug installers, who must first sign a release against future cancers developed down the road.

There are several things to be aware of concerning carpeting: 1) the glues, latex backings, and rubber padding are all toxic and off-gas, 2) pesticides used to control carpet beetles may include arsenic and benzene, 3) carpets become reservoirs for tracked in pesticides, heavy metals, and other toxins.6

Symptoms of Pesticide Exposure

Some pesticides used in school buildings and on playing fields may damage the kidneys or liver, and cause tumors or cancer. It is mind boggling to think about young folks engaging in heavy exercise, breathing heavily, and rolling around on pesticide treated turf at schools, parks, and playing fields.

Additional symptoms of acute pesticide exposure may include headaches, nausea, dizziness, diarrhea, vomiting, confusion, memory loss, moodiness, learning problems, hyperactivity, fatigue, sleep disorders, loss of coordination, weakness, skin rashes, and respiratory problems.7

Asthma

Asthma is the 3rd leading cause of hospitalization for children in the United States. It is the largest single cause of school absenteeism, according to the Centers for Disease Control and Prevention. Asthma deaths among young adults and children have increased an alarming 118% between 1980 and 1993.8 Meanwhile the incidence of asthma nationwide has increased 73% between 1982 and 1994, according to the American Lung Association of New York.9

A recently passed law in New York State now requires all schools to permit children with asthma to carry their inhalers while in school, with permission from a parent and physician. That this became necessary points to a serious indoor air problem in the school setting.10

Aggressive Behavior

As mentioned previously, there is very little research looking at the cumulative effects of chemical exposure. However a new five-year study at the University of Wisconsin looked at the effects on mice exposed to a mixture of commonly used carbamate insecticides, the triazine herbicides and nitrogen at levels typically found in drinking water.

Findings showed detrimental effects on the nervous, immune, and endocrine (hormone) systems which has direct implications for humans. If any of these three closely connected systems is damaged, or degraded, it may have an adverse effect on the others.

Observations included interference in thyroid hormone levels, reduced body weight, immune dysfunction and increased aggressive behavior.11

A recent study of four and five year old Yaqui Indian children in Mexico noted impaired mental and physical ability and increased aggression among children exposed to pesticides in the lowland farming district. Yaqui children residing in the upland ranching area with no pesticide exposure did not demonstrate any impairment of developmental skills.12

We are asking why there is an increase in childhood cancer, asthma and violent behavior. Thus far modern science has produced unsatisfactory answers. Like the song about love, perhaps scientists are looking in all the wrong places. More attention should focus on the synergistic effect of multiple chemicals and multiple exposures.

Pesticide Reduction and Alternatives

Many localities have adopted pesticide policies or programs that require schools to use integrated pest management (IPM), prohibit use of toxic pesticides, and/or provide prior notification of pesticide application. IPM is a process that reduces dependence on toxic chemicals by seeking alternative approaches to dealing with pests by sealing off routes of entry, removing water and food attractants, using natural fertilizer for proper field maintenance, and substituting more natural cleansers and disinfectants.

Because of a growing awareness about pesticide exposure some communities are introducing legislation that will give neighbors advance notice of when a commercial pesticide application will occur. This allows neighbors to take necessary precautions to close their windows, keep children and pets indoors, or leave for a few hours if they choose.

Such a bill had been tossed around the New York State Legislature for three years. In response to the Long Island breast cancer activists the NY Assembly supported a bill which would include notification to parents of daycare centers and school children. The NY Senate not only left these important aspects out of their version, but bowing to industry demands, they decided the bill should be optional for each county within the state.

Rather than suffer another defeat, environmental advocates pushed for passage of the weakened Senate bill (June, 2000) and immediately embarked on amending it to include daycare centers and schools. I mention this to illustrate how “government” often favors the interests of industry over the interests of public health, in this case the health of children.

Location, Location and Location

With an eye to the bottom line, school districts often purchase inexpensive land upon which to erect school buildings. Such parcels are often located on covered landfills, some highly toxic like Love Canal in Niagara, NY, or on top of an oil field like the abandoned $125 million high school project in Los Angeles. Other sites are situated on old farm land where persistent chemicals may linger in soil, or next to a working farm with seasonal pesticide spraying, or downwind from a toxin-spewing industrial facility.

Invisible Danger from Power Lines

Another poor choice for locating a school is near high power lines. Electromagnetic fields (EMFs) may be invisible, but that does not mean they are safe Scientific studies are controversial and inconclusive, depending on the source of information.

Most of the studies indicating a health risk have been done outside the United States. Swedish researchers observed a clear dose-response relationship between increasing magnetic-field exposure and the occurrence of childhood leukemia. Children in homes exposed to average power-line fields of more than one milligauss had twice the risk of developing leukemia as children living in homes exposed to fields of less than one milligauss. Children exposed to more than two milligauss had almost three times the risk; and children exposed to more than three milligauss had nearly four times the risk.13

Admittedly, this test was conducted on exposure to children’s domiciles. However, since children spend a substantial part of a day at school, any EMF exposure at the school site might have significant impact on children’s health.

In spite of the lack of conclusive evidence in our own country, there have been many instances when parents, or workers, suspected a problem and initiated investigation on their own. This is precisely what occurred in 1991 at an elementary school in Bolingbrook Illinois, located within seventy to 100 feet of a utility right-of-way containing a 345,000-volt transmission line and a 138,000-volt line.

Engineers from the utility company took magnetic field readings throughout the building. The rooms closest to the power lines had the highest levels, between two and a half to eight milligauss. A week later, engineers from the University of Illinois Institute of Electronics and Electrical Engineering recorded a magnetic field as high as 20(!) milligauss in one fourth grade classroom, which had to be evacuated. Measurements taken at another elementary school located several miles away from the power lines recorded ambient fields of as little as .1 and .4 milligauss.14

An informal 1993 survey of the affected school revealed some interesting findings. Out of forty faculty members in the building, seven, whose classrooms were closest to the power lines, developed a variety of cancers, had one baby with birth defects, and one young student died of brain cancer.15

The most frustrating thing is that parent and faculty concerns were ignored by the school administrators, health officials, the EPA, and the utility company. The reason? A threatened drop in property values. This scenario plays out in communities all across America.

A similar problem in Houston, Texas in 1985, had a more positive outcome when a jury found “clear and convincing evidence” of potential power-line health risks and awarded damages to the school district, forcing the utility to relocate their power lines.16

In 1994 an elementary school in Clifton, New Jersey, adjacent to two very high voltage transmission lines recorded magnetic fields between 23.7 and 41.6 milligauss. At about the same time measurements taken by a parent at an early childhood center on Long Island, New York recorded a magnetic field in excess of 90 milligauss! This was later confirmed by engineers from the utility company. It was believed to be caused by a high current cable running through the floor of the classroom.17

Whenever a small independent study shows a possible link between EMFs and health risks, the industrial/scientific community responds by saying more studies are needed. However, little or no grant money is made available to do independent research. On many occasions researchers working with generous grants have had the grants canceled and their positions curtailed if their findings were contrary to corporate interests.

How many childhood leukemias, or latent health problems might be related to EMF exposure in the school or home setting will remain a mystery.

Cell Towers

As though high voltage transmission lines were not enough of a menace, a new threat looms on the horizon (no pun intended). Cell towers are popping up all over the landscape. The rapidly expanding telecommunications industry finds schools to be very desirable sites.
Offers from telecommunications companies to rent space are very tempting to school districts struggling to balance budgets. Industry reps are quick to point out there are no definitive studies “proving” a connection to cancer. It is not even legal for citizens to raise health concerns regarding placement of cell towers in their communities. Critics point to studies done in Australia, New Zealand, Sweden, Poland and elsewhere, but are easily dismissed.

Washington Wakening

It may be a while before progress is made about EMF exposure, but to finish up on a positive note there is something afoot regarding pesticides in the school environment.

Thanks to the tireless efforts of the National Campaign Against the Misuse of Pesticides (NCAMP) and other environmental/health groups, there is now a bill before congress called the School Environment Protection Act (SEPA), S.1716 / H.R.3275. This bill gives national attention to the urgent need to better protect children from pesticides typically used in schools.

Parents, health providers, and others interested in children’s health are urged to contact their Senators and Congressional Representatives recommending they co-sponsor this bill, or at least support it. More information about the bill is available from NCAMP’s website, www.ncamp.org, or email, ncamp@ncamp.org.

References

  1. Landrigan, P, et al, Pesticides and Inner-City Children: Exposures, Risks, and Prevention, Environmental Health Perspectives, Vol. 107, Supplement 3, pp. 431-7, June, 1999
    2. Ibid.
    3. Ibid.
    4. Spitzer, Eliot, NYS Atty. Gen., The Secret Hazards of Pesticides: Inert Ingredients, Environmental Protection Bureau, Albany, NY
    5. Deuhring, C., Carpet Concerns, Part Two, Informed Consent, Jan/Feb 1994
    6. Ibid.
    7. “School Pesticide Fact Sheet: Why take a Chance When Alternatives Work,” New York Coalition for Alternatives to Pesticides (NYCAP), Albany, NY
    8. Danserau, C., Protecting Children from Toxic Exposures: A New Emphasis on Children, Alternatives, Vol.16, No.4 Winter 1997, Washington Toxics Coalition
    9. Healthy Schools Network NEWS, Winter ‘99, Albany, NY
    10. Ibid.
    11. Montague, P., Rachel’s Environmental Health Weekly, #648, April, 29, 2000 Annapolis, MD
    12. Ibid.
    13. Brodeur, P., The Great Power-Line Cover-Up, Little, Brown, & Co., NY, 1995
    14. Ibid.
    15. Ibid.
    16. Ibid.
    17. Ibid.

 

 

6. Article:

 

Environ Health Perspect. 2006 April; 114(4): 584–590.

Published online 2005 October 20. doi: 10.1289/ehp.8202.

Copyright This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article’s original DOI.

 

Research – Children’s Health

Renal and Neurologic Effects of Cadmium, Lead, Mercury, and Arsenic in Children: Evidence of Early Effects and Multiple Interactions at Environmental Exposure Levels

 

Claire de Burbure,1 Jean-Pierre Buchet,1 Ariane Leroyer,2 Catherine Nisse,2 Jean-Marie Haguenoer,2 Antonio Mutti,3 Zdenek Smerhovský,4 Miroslav Cikrt,4 Malgorzata Trzcinka-Ochocka,5 Grazyna Razniewska,5 Marek Jakubowski,5 and Alfred Bernard1

1Unit of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, Catholic University of Louvain, Belgium

2Centre de recherches en santé-travail-ergonomie-Laboratoire Universitaire de Médecine du Travail, Université Lille 2, Lille, France

3Laboratorio di Tossicologia Industriale, Universita degli Studi di Parma, Parma, Italy

4National Institute of Public Health, Prague, Czech Republic

5Nofer Institute of Occupational Medicine, Lodz, Poland

 

Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children’s health is little known. We studied their effects on two main targets, the renal and dopaminergic systems, in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. Children provided blood and urine samples for the determination of the metals and sensitive renal or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and β2-microglobulin were negatively correlated with blood lead levels (PbB), suggesting an early renal hyperfiltration that averaged 7% in the upper quartile of PbB levels (> 55 μg/L; mean, 78.4 μg/L). The urinary excretion of retinol-binding protein, Clara cell protein, and N-acetyl-β-d-glucosaminidase was associated mainly with cadmium levels in blood or urine and with urinary mercury. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid, with complex interactions brought to light. Heavy metals polluting the environment can cause subtle effects on children’s renal and dopaminergic systems without clear evidence of a threshold, which reinforces the need to control and regulate potential sources of contamination by heavy metals.

Keywords: arsenic, biomarkers, cadmium, dopaminergic, heavy metals, interactions, lead, mercury, renal

 

Environmental pollution of industrialized countries by heavy metals such as lead, cadmium, mercury, and the metalloid arsenic is largely the consequence of past emissions by nonferrous industries. Although stringent measures and controls have been put into place during the last decades, high levels of these pollutants still persist in the soils and sediments—and therefore also in the food chain—with possible consequences of chronic environmental exposure of the populations living in those areas. Moreover, natural contamination such as geologic arsenic or lifestyle-related factors such as the inorganic mercury in dental amalgam can further contribute to increase the burden of human exposure to these toxicants.

Most of our knowledge concerning the health effects of toxic metals largely stems from studies conducted on populations with relatively high exposure usually to individual metals in industry or in heavily polluted environments. Very few studies have addressed the possible effects of chronic low environmental exposure to mixtures of these metals, particularly with regard to their possible interactions, although this is precisely the situation most commonly encountered by the general population of industrialized countries. Furthermore, there is a definite paucity of data concerning children, a specific cause for concern because children are known to absorb metals more readily than adults and are particularly sensitive for biologic and developmental reasons (Fels et al. 1998).

Among possible target organs of heavy metals, the kidney and central nervous system appear to be the most sensitive ones. Inorganic heavy metals have been known for a long time to be nephrotoxic at relatively high levels of exposure, with numerous reports of tubulointerstitial nephritis possibly leading to renal failure, in most cases linked to high occupational or environmental exposure (Fowler 1996). Early signs of renal dysfunction can, however, be found with exposure to low environmental levels of these heavy metals, consisting in decreased glomerular filtration rate (GFR) (lead) or increased urinary loss of tubular enzymes (cadmium). These effects have been described mainly in adults, but certain reports have also shown them to occur in children (Bernard et al. 1995; Verberk et al. 1996). Neurotoxic effects of heavy metals are also well documented, especially for mercury and lead, with numerous reports of neurobehavioral changes after occupational exposure and of developmental effects in children with pre- or early postnatal exposure (Davidson et al. 2004; Lidsky and Schneider 2003). However, experimental studies suggest that other metals such as cadmium and arsenic could also interfere with the nervous system and that all four metals may influence the dopaminergic system in different ways (Lafuente et al. 2003b; Pohl et al. 2003). There is, however, a need to elucidate which exposure levels are likely to cause these biologic effects, particularly in children, and to what extent the four metals could interfere and interact in mixed exposures.

To address some of these issues, in the present study we focused on populations of children living in three separate European regions known for their historical levels of pollution in France, Poland, and the Czech Republic. The levels of exposure to cadmium, lead, mercury, and arsenic were determined in about 800 children together with a set of sensitive biomarkers of kidney function and of the dopaminergic system.

Studied European areas.

France. The environmentally exposed area studied concerned 10 municipalities in the Nord-Pas-de-Calais located in an 8-km radius around both a zinc smelter (near the city of Auby) and a lead and zinc smelter (near the city of Noyelles-Godault) 3.5 km apart. The foundries had both been operational since the second half of the 19th century and had liberated vast quantities of heavy metals in the atmosphere until 1975, and then gradually reduced their emissions by more than 90% to slightly more than 24 tons of lead and 950 kg of cadmium in 1996; the Noyelles-Godault smelter closed down in 2003. Soil contamination varied between 100 and 1,700 ppm for lead (values > 1,000 ppm in a 500-m radius around the foundries), between 0.7 and 233 ppm cadmium, and between 101 and 22,257 ppm zinc, the highest values being found within 500 m of the smelters. Lead and cadmium level determinants were mainly linked to habitat distance from the factories, drinking tap water, and, for cadmium, consumption of local produce, fish, and crustaceans (Leroyer et al. 2000, 2001). The French control area concerned 20 municipalities of the same region that were unpolluted by heavy metals.

Czech Republic. The environmentally polluted area studied was centered around the historic site of Pribram, known for its mining since the 10th century. Indeed, silver, lead, and other precious metals extracted in that area represented, at the end of the 19th century, 97.7% of the total Austro-Hungarian production. Uranium mining also appeared in the 20th century but ceased in 1991; the metal mines of Pribram ceased ore mining in 1979. The lead smelter examined in our study emitted > 250 metric tons of lead per year into the atmosphere until 1982, when filters were installed, reducing emissions to < 20 metric tons per year (Bernard et al. 1995). Soil lead levels in 1994 varied between 100 and > 5,000 ppm (values > 1,000 ppm within 1,000 m of the smelter). The control area was in a nonpolluted rural area, Sedlcany, located east of Pribram.

Poland. The environmentally polluted area studied consisted of small villages located within a 10-km radius around the copper mills of Legnica, where a previous study concerning children had indicated that 22% of children had blood lead levels (PbB) > 100 μg/L (Jakubowski et al. 1996). The control area was in a nonpolluted rural region free of heavy industry, Gorzow, in northwest Poland.

Studied population. After protocol approval of the study by the local ethical committees, a total of 804 children 8.5–12.3 years of age from France, Poland, and the Czech Republic took part in the study: 400 French children (200 boys: 101 exposed, 99 controls; 200 girls: 99 exposed, 101 controls), 215 Polish children (99 boys: 50 exposed, 49 controls; 116 girls: 59 exposed, 57 controls), and 189 Czech children (97 boys: 49 exposed, 48 controls; 92 girls: 45 exposed, 47 controls). Exposed children had lived at least 8 years near non-ferrous smelters, whereas their controls were recruited from areas unpolluted by heavy metals in the same region of each country. Children were recruited on a volunteer basis with letters sent via schools to their parents, explaining the objectives and protocol of the study as well as the selection criteria (no diabetes or renal disease and, for girls, absence of menses). We considered as volunteers only children meeting these criteria and whose parents had given their written permission for examination of their child and sampling of blood and urine. Lead concentrations in polluted soils were, on average, > 200 ppm, with values > 1,000 ppm in the immediate vicinity of the factories. The study protocol was approved by local ethical committees and complied with all applicable requirements of U.S. and/or international regulations.

Biologic samples. Biologic samples were collected with the written permission of either the children’s parents or the person responsible for them. Blood samples were collected and centrifuged, and 2 mL of serum were stored at –80°C until analysis. The usual precautions were taken to avoid external contamination during collection, storage, and processing of samples by checking that all containers were metal-free. Untimed urine samples were collected during daytime and stored at –20°C. Because of the small volumes of some samples, all biologic parameters could not be determined in all subjects; the exact numbers that could be analyzed are indicated in the tables.

Analyses. All analyses of renal and dopaminergic biomarkers were performed under similar experimental conditions in the same laboratory (Brussels) within 6 months of collection. In contrast, metals were analyzed in each country using methods that were standardized and controlled at the beginning of the project. Standardization involved the combined analysis of the initial 10% of all samples, performed by all partners, and the results were judged satisfactory according to the criteria of Bland and Altman (1986). We conducted the common analyses for all three cohorts as follows: Serum creatinine (CreatS) and urinary creatinine (CreatU) were measured by the methods of Heinegard and Tiderstrom, and Jaffé, respectively (Price et al. 1996); serum cystatin C (CystCS), serum β2-microglobulin (B2MS), and urinary retinol-binding protein (RBPU) were quantified by automated latex immunoassays (Bernard et al. 1981). The total activity of N-acetyl-β-d-glucosaminidase in urine (NAGTU) was determined colorimetrically using a NAG kit (PPR Diagnostics Ltd., London, UK), as described elsewhere (Price et al. 1996). These renal markers were selected because they are known to be among the most sensitive and reliable indicators for screening renal damage in populations that are occupationally or environmentally exposed to heavy metals (Bernard and Hermans 1997). Urinary homovanillic acid (HVAU), one of the end-products of dopamine metabolism, was assayed in urine using isocratic HPLC, whereas serum prolactin (PRLS), whose secretion is under control of the dopaminergic system, was measured in serum by chemiluminescent enzyme immunoassay, as previously described (Alvarez Leite et al. 2002). We asssessed heavy metal exposure by measuring by atomic absorption spectrometry for PbB, whole-blood cadmium (CdB), urinary cadmium (CdU), and urinary mercury (HgU) as described previously (de Burbure et al. 2003; Leroyer et al. 2000, 2001). Urinary arsenic levels (AsU) were studied only in Polish and Czech children and were measured after arsine generation as the sum of inorganic arsenic and its methylated metabolites (monomethylarsonic acid, dimethylarsinic acid) without notable interference by seafood trimethylated arsenicals (Buchet et al. 2003). All urinary parameter assays were adjusted for CreatU. Urine samples with a creatinine concentration < 0.3 or > 3.0 g/L (81 children; range, 0.17–3.07 g/L) were excluded from the data analyses.

Statistical analysis. We used categorical variables for sex and area of residence, and all continuous variables except age were normalized by log-transformation before statistical analysis. Parameter distribution normality was assessed with the Shapiro-Wilk test. The logarithmic transformation was satisfactory for body mass index (BMI), PbB, CdU, CreatS, CreatU, serum Clara cell protein (CC16S), urinary Clara cell protein (CC16U), CystCS, B2MS, PRLS, NAGTU, and RBPU. We calculated normal rank values according to the Blom procedure for CdB, HgU, and HVAU. We compared group means by the unpaired Student’s t-test or, in cases of more than two groups, by Duncan test after analysis of variance (ANOVA). In addition, we analyzed the influence of sex, exposure, and their possible interaction by two-way ANOVA for each country. Determinants of renal and dopaminergic parameters studied were traced by stepwise multiple regression analysis using as independent variables log PbB, rank CdB, rank HgU, log AsU where applicable (Czech and Polish), log CreatU, log BMI, age, sex, and area of residence, as well as all first-order metal interaction terms. Polish and Czech children were assessed both separately (French children were studied previously: de Burbure et al. 2003; Leroyer et al. 2000, 2001) and together to study the impact of arsenic. All multiple regression analyses were conducted each time twice, considering either CdB or CdU as the cadmium exposure indicator. Although all urinary parameters were adjusted for CreatU, we performed multiple regression analyses by again testing CreatU levels to eliminate any residual effect of the diuresis. Stepwise multiple regression analyses used a p-level equal to 0.25 for entry and a level of 0.05 for staying in the model. The level of statistical significance was set at p < 0.05. To illustrate the relationships between some parameters and a specific element, we used equations describing the multiple regression models to adjust the dependent variable for the mean value covariates included in the model (when necessary, female sex and a CreatU of 1 g/L were selected). The means of these corrected values in groups according to four ranges of increasing values of the specific element (quartiles) were then compared. Where parameter values were corrected for determinants other than a single metal exposure parameter, the latter was considered in quartiles to allow ANOVA and testing of the significance of differences between mean values. The consideration of quartiles of a second element in each quartile of a first one helped to illustrate the presence of interactions between elements. When an element influenced a studied parameter both alone and in an interaction with another one, the total population of children was divided into quartiles according to the first element, and each of these was divided into quartiles according to the element playing in interaction only. We used the statistical package SAS (version 6; Cary, NC, USA) (particularly the univariate, GLM, and REG procedures) for all statistical analyses.

Table 1 shows the mean values of all biologic parameters between control and exposed children separated by sex and country. As expected, both boys and girls of all three countries had significantly higher levels of PbB and CdB in exposed areas compared with their respective controls. There was no significant difference in HgU levels between exposed and control children in France or Poland. Czech children in the polluted area actually had lower HgU and AsU levels than did their controls, whose AsU levels were unexpectedly almost double those of other cohorts. Comparison of metal levels in the different countries revealed that French children in both the exposed and control areas had significantly higher levels of HgU, CdB, and CdU than did Czech and Polish children, whereas Polish children from the exposed area had significantly higher PbB levels than did all the others. In each country, the influence of sex and its interaction with exposure was studied by a two-way ANOVA. Boys had significantly higher PbB levels than girls, but no sex-related difference was observed for the three other metals. As expected, girls had higher PRLS and lower CreatS compared with boys, both significantly so in France and Poland. No interaction between sex and exposure was found in most biomarkers except in some groups for CC16U and CystCS.

Table 1

Parameters studied according to country, sex , and level of exposure of children.

We conducted multiple regression analyses taking sex, CreatU, the levels of all four metals, and their first-order interactions as independent variables on the whole population, taking two models, with either CdB or CdU, into consideration (Table 2). Remarkably, the three markers of GFR—CreatS, CystCS, and B2MS—were negatively correlated with PbB levels in both models. CystCS was the only parameter not influenced by any other determinant. CreatS correlated also negatively with CdU, and both models evidenced an interaction between PbB and HgU increasing CreatS. B2MS and CC16S, on the other hand, were also negatively correlated with HgU. RBPU and CC16U showed a significant positive correlation with both CdB and CdU levels, whereas NAGTU increased significantly with both CdU and CdB and with HgU levels in both models. Dopaminergic markers indicated a decrease in PRLS and a corresponding increase in HVAU with rising CdB, CdU, and HgU. Removing CreatU from the independent variables (used to eliminate any residual influence of diuresis) did not alter the above results but revealed an added negative correlation of B2MS with CdB (data not shown). In the combined Czech and Polish populations, AsU was found to be a positive determinant of CC16U and as an interactive term, modulating several of the associations with PbB, CdB, CdU, and HgU indicated above (data not shown).

Table 2

Multiple regression analysis of the determinants of renal and neurologic biomarkers in the whole population of children.

We assessed dose–effect relationships by dividing the children in quartiles of increasing levels of the metals in urine or blood and comparing by ANOVA the values of renal or neurologic biomarkers adjusted for other covariates. As illustrated in Figure 1, levels of CreatU, CystCS, and B2MS decreased in a dose-dependent way with increasing PbB, with an apparent threshold around 50 μg/L PbB, where statistical significance was reached. The increased RBPU or CC16U was also closely related to the internal dose of cadmium, with no detectable threshold in the case CdB and a threshold around 1 μg/g creatinine for CdU (Figure 2). A similar pattern emerged for the increased NAGTU with cadmium exposure (Figure 3), indicating also a very low threshold for both CdB (0.31 μg/L) and CdU (0.58 μg/g creatinine). NAGTU increased with HgU from very low concentrations, as low as 0.06 μg/g creatinine, when adjusting for CdB or CdU (Figure 3). As shown in Figure 4, similar dose–effect relationships with no detectable or very low thresholds were also observed with dopaminergic markers, confirming the decrease in PRLS and increase in HVAU with rising CdB, CdU, and HgU.

Figure 1

Mean concentrations of CreatS, B2MS, and CystCS in the total population of children divided in quartiles of PbB, after standardization for other cofactors. Variables preceded by R are ranked variables. (A) CreatS after standardization for CreatU, sex, (more …)
Figure 2

Mean RBPU and CC16U in the total population of children divided in quartiles of CdB or CdU, after standardization for other cofactors. Variables preceded by R are ranked variables. (A) RBPU after standardization for CreatU, RCdB × RHgU, and PbB (more …)

 

Figure 3

Mean concentrations of NAGTU in the total population of children divided in quartiles of CdB, CdU, or HgU after standardization for other cofactors, considering either CdB or CdU as independent variable. Variables preceded by R are ranked variables. ( (more …)
Figure 4

Mean concentrations of ranked HVAU and PRLS in the total population of children divided in quartiles of CdB, CdU, or HgU after standardization for other cofactors, considering either CdB or CdU as independent variable. Variables preceded by R are ranked (more …)

The most interesting metal interactions with regard to renal biomarkers are illustrated in Figure 5. In particular, it can be seen that HgU inhibits the PbB-related renal hyper-filtration (i.e., the PbB-related decrease in CreatS), whereas it potentiates the increased NAGTU linked to CdB. By contrast, AsU appears to inhibit the increase in CreatS associated with CdB, and PbB tends to antagonize the CdB-related rise in NAGTU. With regard to dopaminergic markers (data not shown), PbB appears to antagonize the significant HgU-related decrease in HVAU, whereas HgU exacerbates the increase in HVAU linked to CdB.

Figure 5

Mean concentrations of CreatS or NAGTU in children divided in quartiles of PbB or CdB concentrations and further subdivided in quartiles of AsU or HgU. Variables preceded by R are ranked variables. (A) Whole population (n = 600) after standardization (more …)

Although children living around nonferrous smelters were significantly more exposed to lead and cadmium than were their controls, the mean levels of lead, cadmium, mercury, and arsenic in blood or urine of all studied groups were well within the range of values normally found in the European population, including children, as described in other European studies (Camerino et al. 2002; Hotz et al. 1999; Staessen et al. 2001). Even the higher mean PbB levels observed in Pribram (Czech Republic) were noticeably lower (by half) than those described in that same area about 10 years before the present study (Bernard et al. 1995). It was, however, clear that the children of the three countries, albeit selected by means of identical criteria, varied significantly with regard to the metal baseline levels as observed in control cohorts. These variations most probably reflect differences in the environmental levels of these metals as well as in the lifestyle of these children, in particular, their dietary habits, home environment, and dental care. The 2-fold increase in AsU levels observed in the Czech control children was nevertheless an unexpected finding, eventually linked to high arsenic levels in the local underground water, probably because of known gold deposits in the region.

The most interesting and consistent finding evidenced by our study in children was an overall inverse relationship between CreatS, B2MS, CystCS, and PbB, suggesting that environmental lead induces an early renal hyperfiltration, similar to that described in experimental animals with lead-induced renal cortex hypertrophy (Khalil-Manesh et al. 1992). The increase in GFR induced by lead can be estimated using equations relating the GFR to CreatS, CystCS, and B2MS (Donadio et al. 2001; Risch et al. 1999). Depending on the serum marker used, the increase in GFR ranged from 7 to 11% in children in the upper PbB quartile (> 55 μg/L; mean PbB, 78.4 μg/L). Renal hyperfiltration had already been described in lead smelter workers with much higher PbB levels (Roels et al. 1994; Weaver et al. 2003a) but not yet in a general population with low environmental exposure, and never to our knowledge in children. One explanation brought forward for these observations comes in part from the hyperfiltration theory, described as a paradoxical increase in GFR linked to altered glomerular hemodynamics (Weaver et al. 2003a). According to recent experimental studies, the initial mechanism may well depend on lead-induced production of reactive oxygen species up-regulating cyclooxygenase (COX-2) expression in the vascular smooth muscle wall (Courtois et al. 2003). These findings would also tie in with those in workers with lead-induced renal hyperfiltration who show a decreased production of prostaglandin (PGF2) and an increased production of thromboxane (Roels et al. 1994). Moreover, this explanation is supported by recent findings in lead-exposed workers showing in addition that the renal response to lead, including hyperfiltration, was modulated by genetic polymorphisms in δ-aminolevulinic acid dehydratase (ALAD 2 allele or ALAD 1-2 genotype) and nitric oxide synthase (eNOS variant allele) genes (Weaver et al. 2003b). Interestingly, although CystCS was affected only by PbB levels, both CreatS and B2MS were also found to correlate with cadmium or mercury independently or in interaction with PbB. These relationships could be explained by various competitive interactions between metals for intracellular binding sites, causing, for instance, a displacement of lead from its renal store, as has been shown with both cadmium and mercury (Fowler 1998).

With regard to tubular effects, the most interesting effects were consistent increases in the RBPU, CC16U, and NAGTU in correlation to cadmium levels. Of note, these increases were found with both CdB and CdU, thus excluding the possibility of secondary associations due to the dependence of the urinary excretion of proteins and cadmium on the integrity of renal function. These findings provide further evidence that environmental cadmium, even at currently observed levels, can affect the renal tubules of children. Interestingly, urinary mercury levels were found to correlate with some tubular markers, both in interactions (CC16U and RBPU) and independently of other metals (NAGTU). To our knowledge, there are no reports showing evidence of tubular dysfunction at such low levels of HgU. What is particularly disturbing with these tubular effects is the very low threshold of metal exposure from which they become statistically significant. For instance, RBPU and CC16U were observed to increase significantly from mean CdU (< 1 μg/g creatinine) and CdB (< 0.5 μg/L) that are in the range of mean values currently observed in most industrialized countries. These thresholds are five to ten times lower than those established in adult populations living in heavily polluted environments, such as in China or Japan, suggesting that children’s kidneys could be much more sensitive to heavy metals than those of adults.

An important issue to bear in mind in the interpretation of our data is that the renal effects observed in this study could reflect an early renal response to metals that could be purely adaptative and/or reversible depending on the type of metal and the studied end point (Roels et al. 1997). Renal hyperfiltration has commonly been observed in various renal diseases and clinical conditions such as early type I diabetes, sickle cell disease, obesity, and high-protein diet; but in most cases it is associated with clinical anomalies such as hypertension, and it is much more pronounced than that observed in the present study (Courtois et al. 2003; Friedman 2004). The small lead-related renal hyperfiltration observed in our study could merely reflect hemodynamic changes due to an interference of lead with prostaglandin metabolism, which quite conceivably could be transient and entirely reversible. Similarly, the preclinical tubular effects associated mainly with cadmium and mercury could also be the manifestation of proximal tubular alterations, which could also be reversible if one refers to observations made in adults with incipient cadmium nephropathy (Roels et al. 1997). However, given the very few studies performed in children, it is difficult to assess the actual biologic and clinical significance of these early renal changes in children. It cannot be excluded that these effects could be potentially adverse, rendering, for instance, the kidneys more sensitive to other stressors later in life.

Contrary to findings in lead-exposed workers (Govoni et al. 1987; Lucchini et al. 2000), lead did not appear to increase PRLS in the various children populations. CdB and HgU, by contrast, were both negatively correlated with PRLS but correlated positively with HVAU. These correlations, which indicate an increased dopamine metabolism, agree with recent experimental data in rats, showing that cadmium interferes with biogenic amine release from the hypothalamus, thereby inhibiting prolactin secretion (Lafuente et al. 2003a), whereas inorganic mercury stimulates increased striatal dopamine levels (Faro et al. 2003). These observations are also consistent with recent results in adults occupationally exposed to inorganic mercury (Carta et al. 2003). Arsenic, except for its interactive effects, did not directly influence either PRLS or HVAU, contrary to experimental evidence, indicating that effects reported in animals do not occur at low environmental exposure levels (Delgado et al. 2000; Rodriguez et al. 1998).

In conclusion, our data show that heavy metals polluting the environment can cause subtle effects on the children’s renal and dopaminergic systems. In particular, renal hyperfiltration appears an early response to lead, whereas cadmium exposure is associated with subtle tubular effects modulated by coexposure to mercury and lead. These findings at current low environmental exposure levels, sometimes with no detectable threshold, reinforce the need to control and regulate potential sources of contamination by heavy metals.

 

Footnotes

This study was supported by the Fourth and Fifth Research, Technological Development and Demonstration programs of the European Commission and by the French Association for Metals and Health (AMSE). A.B. is Research Director of the National Fund for Scientific Research, Belgium.

 

 

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7. Other Articles of Interest:

 

Finley JW. Does environmental exposure to manganese pose a health risk to healthy adults? Nutr Rev. 2004 Apr;62(4):148-53 PMID: 15141430

 

Gottschalk LA, Rebello T, Buchsbaum MS, Tucker HG, Hodges EL. Abnormalities in hair trace elements as indicators of aberrant behavior.  Compr Psychiatry. 1991 May-Jun;32(3):229-37.
PMID: 1884602

 

Lemmen CA, Holden CE, Benedek EP.  Criminal responsibility and solvent exposure (Case Report). New Dir Ment Health Serv. 1996 Spring;(69):59-66.

 

Yura A, [Indoor air pollution in newly built or renovated elementary schools and its effects on health in children]  Nippon Koshu Eisei Zasshi. 2005 Aug;52(8):715-26. Japanese.  PMID: 16218412

 

Shendell DG, Winer AM, Stock TH, Zhang L, Zhang JJ, Maberti S, Colome SD. Air concentrations of VOCs in portable and traditional classrooms: results of a pilot study in Los Angeles County. J Expo Anal Environ Epidemiol. 2004 Jan;14(1):44-59. PMID: 14726944
Shendell DG, Winer AM, Weker R, Colome SD. Evidence of inadequate ventilation in portable classrooms: results of a pilot study in Los Angeles County.  Indoor Air. 2004 Jun;14(3):154-8.
PMID: 15104781

 

Shendell DG, Prill R, Fisk WJ, Apte MG, Blake D, Faulkner D. Associations between classroom CO2 concentrations and student attendance in Washington and Idaho.  Indoor Air. 2004 Oct;14(5):333-41.
PMID: 15330793

Shaughnessy RJ, Haverinen-Shaughnessy U, Nevalainen A, Moschandreas D. A preliminary study on the association between ventilation rates in classrooms and student performance.Indoor Air. 2006 Dec;16(6):465-8. PMID: 17100667

Mendell MJ, Heath GA. Do indoor pollutants and thermal conditions in schools influence student performance? A critical review of the literature. Indoor Air. 2005 Feb;15(1):27-52. Review. Erratum in: Indoor Air. 2005 Feb;15(1):67. PMID: 15660567

Daisey JM, Angell WJ, Apte MG. Indoor air quality, ventilation and health symptoms in schools: an analysis of existing information. Indoor Air. 2003 Mar;13(1):53-64. PMID: 12608926

Meininghaus R, Kouniali A, Mandin C, Cicolella A. Risk assessment of sensory irritants in indoor air–a case study in a French school.  Environ Int. 2003 Jan;28(7):553-7. PMID: 12504150