Lead poisoning in China

By Russell Ng and Hannah Beedham, Interns from Macquarie University

Part I - Background

Part II - Lead in China

Part III - Treatment and prevention of lead poisoning

References

Part III - Treatment of lead poisoning: Chelation therapy, anti-oxidants, ways to reduce and prevent lead exposure

Chelation therapy

This process involves the use of a drug called a chelating agent, which comes in many forms. The drug interacts with lead to form a chelate that can be eliminated in urine, faeces, or both. The intention of the use of such a drug is to reduce the lead content of target tissues, such as the brain, and to restore normal cellular and tissue function (Mortensen and Walson 1993). The three primary agents used for chelation are dimercaprol, edetate calcium disodium, and succimer (Gracia and Snodgrass 2007).

The focus of chelating therapy has been on the treatment of childhood lead poisoning and the therapy's effect on neuropsychological and behavioural development. In particular, the focus has been on at what the blood lead concentrations of the child needs to be before administering chelating agents, in particularly the FDA licensed drug, succimer (dimercaptosuccinic acid), which is taken orally (Dietrich et al 2004). It is accepted that the lower threshold for chelation be at 40µg/dL, due to some promising clinical observations of children undergoing the chelation therapy, even though the FDA-approved indication for use of the oral chelator succimer is for blood lead levels of 45 µg/dL. However, it is also well accepted that blood lead levels below 25 µg/dL should not treated by chelation therapy. Therefore there is uncertainty as to whether chelation should be used for blood lead levels of 25 to 39 (or 44) µg/dL (Mortensen and Walson 1993).

Along with the uncertainty of when to administer chelation therapy, its effectiveness in the reduction of target-tissue lead content and reversal of toxic effects has not been demonstrated in humans. While some chelating agents have been shown to increase urine or faecal lead elimination, chelation is still seen as relatively inefficient, as a course therapy may remove only 1% to 2% of body lead content. Furthermore, there is no evidence that available chelating agents have significant access to lead stored in the brain (Mortensen and Walson 1993). Adverse effects of chelators have been reported, and the uncertainty in their efficacy in reversing or preventing the neurotoxic effects of lead in children with 25 µg/dL blood lead concentrations have caused clinicians to avoid pharmalogical intervention in children with low blood levels (Gurer and Ercal 2000). In fact, Mortensen and Walson (1993) point to a study in rats that found brain lead content having increased following a single dose of ethylenediaminetetraacetate (CaNa­2EDTA). Such a finding raises concerns that CaNa­2EDTA, along with potentially other chelating agents, redistributes lead from less- to more-vulnerable body tissues, such as from bone to brain. Another known risk involved with chelation therapy is the rebound effect of chelators, where the blood lead levels may rebound to higher than pre-chelation levels if the person returns to the source of lead exposure (Mortenson and Walson 1993).

As a result, chelation is generally not indicated for adults with blood lead concentrations of <45 µg/dL because of the potential risk of adverse drug events and concerns about remobilized lead. Chelation for children with blood lead concentrations of <45 µg/dL still remains controversial (Gracia and Snodgrass 2007).

Antioxidants

Studies so far have suggested that antioxidants, either individually or in a combined therapy with chelating agents, can play an important role in reducing some toxic effects of lead. Some antioxidants, such as NAC (N-acetylcysteine), have been shown to have a potential for chelating lead and removing it from the bloodstream. This opens up the possibility of new therapeutic intervention options, as antioxidants are recognised as safe molecules, hence can be given to subjects with low lead concentrations in their blood even when it is not possible to remove them from exposure to lead (Gurer and Ercal 2000).

Ways to reduce and prevent lead exposure

It is thought that dairy products, and regular supplements of calcium, zinc or iron are effective in lowering the risk of lead poisoning in children (Dai and Fan 2007). Though the mechanism behind this is yet to be fully understood, it is thought that micronutrients, especially the presence of calcium in the intestinal lumen (the cavity where digested food passes through and from where nutrients are absorbed) may play a role by competing with lead for absorption (Liu et al. 2011).

A recent six-month study has suggested that breakfast may help protect children from lead poisoning. Scientists from China showed that children who regularly ate breakfast lowered their blood levels of lead by 15% compared with those who skipped the first meal of the day. The study then looked at the education level of the parents of the children that partook in the study, and found that parents with more education or who had technical or professional jobs were more likely to get their children to eat breakfast (Park 2011). Previous, yet related studies, have also shown that an empty stomach increases the absorption of lead, thus increasing blood lead levels, and that food in the gastrointestinal tract in fact reduces the absorption of ingested lead in adults (Liu et al. 2011).

At a more political level, laws and regulations concerning environmental control of lead and prevention of lead poisoning should be formulated by the government in cooperation with relevant departments. This includes the different institutions of health, education, science and technology, environmental protection agencies; and, importantly, society (Dai and Fan 2007). This is important, as China has more often than not failed to live up to its promises of ensuring heavy metal pollution is reined in. Chinese officials often put economic development ahead of environmental protection and community safety, which often result in cases of mass lead-poisonings which arouse public anger. In fact, the Minister of Environmental Protection Zhou Shengxian outlined a fresh plan in which the Chinese government will aim to cut pollution in key regions and industries, including lead-acid battery manufacturing and lead smelting by 15% of 2007 levels by 2015 (Martina 2011). Furthermore, standards and criteria should also be firmly established or altered, as implementation of these recommendations can help to achieve the goal of eliminating lead poisoning (Dai and Fan 2007). Measures need to be implemented to eliminate lead poisoning before they occur and affect nearby residents. Local governments always choose to shut down factories after a serious pollution incident occurs, but such action is too late to help those already affected. Surveillance before construction and during the operation of factories therefore has to be stricter (Ji et al 2011).

A clear example of this can be seen by the very recent action by the Chinese government, which closed down almost all lead-acid battery makers in China’s major producing regions. As quoted by Xu Hong, the head of the lead-acid battery branch at the China Electrical Equipment Industry Association, “regardless of the plants’ condition, they’ve all been shut down, and there is no timetable now to resume operations” (Sun 2011). “Closing these plants is good news for nearby residents, but unless Chinese provincial governments develop planning guidelines which can stop highly-polluting battery manufacturers from setting up somewhere else tomorrow, then it’s not good news for the Chinese population in general. Currently, provincial governments don’t seem to demand any assessment of a plant’s ability to comply with occupational health and environmental regulations. The risk is that the polluting equipment from the recently-closed down plant will simply be set up in another location.” (E.O’Brien, pers com 2011)