The maligned bisphenol A

Summary – Bisphenol A is an industrial chemical that has been present in many hard plastic bottles and metal-based food and beverage cans since the 1960s. Recent studies using novel approaches to test for subtle effects raised some concern about its potential influence on the brain, behaviour and prostate gland development in foetuses, infants and young children. It is currently under extensive review.

Bisphenol A (BPA) is an industrial chemical used since the 1960’s as an ingredient in making a clear plastic known as polycarbonate. Polycarbonate is used to make a variety of common products including baby and water bottles, sports equipment, medical and dental devices, dental fillings and sealants, CDs and DVDs, household electronics, and eyeglass lenses. BPA is also found in epoxy resins, which act as a protective lining on the inside of metal-based food and beverage cans. It can leach into food, and a study of over 2,000 people found that more than 90 percent of them had BPA in their urine. Traces have also been found in breast milk, the blood of pregnant women and umbilical cord blood.

BPA is permitted for use in food contact materials in the European Union (EU) and in most other countries.  In the past, the European’s Scientific Committee on Food, the European Chemicals Bureau, the European Food Safety Authority, and the US Food and Drug Administration all concluded that current levels of BPA present no risk to the general population. However, recently it was found to exert detectable hormone-like properties, raising concerns about its presence in consumer products and foods contained in such products. Starting in 2008, several governments questioned its safety, prompting some retailers to voluntarily withdraw polycarbonate products. Canada was the first country to ban the use of BPA in baby bottles from 2010 followed by the European Commission in January 2011. In 2012, also the United States banned the use of BPA in baby bottles including in infant feeding cups.

Bisphenol A toxicity

There is a great diversity of opinion about the health effects of BPA. Overall, empirical evidence in support of negative health effects of BPA varies significantly across studies.  Standardised toxicity tests used globally for regulatory decision-making long supported the safety of current low levels of human exposure to BPA. However, results of recent studies using novel approaches and different endpoints found detrimental effects in laboratory animals at very low doses similar to estimated human exposure.

Several new studies evaluated developmental or behavioural effects that are not typically assessed in standardised tests. For example, perinatal exposure to BPA in rodents modified sex differences in the brain. In mice, prenatal exposure to BPA was associated with increased anxiety, aggression and cognitive impairment. In the offspring of BPA-exposed monkeys, males displayed less social behaviours and were more exploratory. In humans, BPA exposure during gestation has been associated with hyperactivity and aggression in young children and with anxiety and depression in older children. Together, these reports and many others demonstrate that BPA exposure during gestation affects several types of behaviours in a number of species.

It is clear that bisphenol A is a weak endocrine disruptor, which can mimic oestrogen and may lead to negative health effects. Early developmental stages seem to be the period of greatest sensitivity to its effects. Regulatory bodies have determined safety levels for humans, but those safety levels are being questioned or are under review as a result of the new findings. Experts in the field of endocrine disruptors have stated that the entire population may suffer adverse health effects from current BPA levels. In 2009, the Endocrine Society released a statement citing the adverse effects of endocrine-disrupting chemicals, and the controversy surrounding BPA.

In 2010, the WHO organised an expert meeting to review toxicological and health aspects of BPA supported by Health Canada, the European Food Safety Authority, the U.S. National Institute of Environmental Health Sciences and the US Food and Drug Administration. Although the meeting concluded that doses much higher than estimated human exposure were necessary for most toxicological effects, it did agree that for some emerging effects, like sex-specific neurodevelopment, anxiety, preneoplastic changes in mammary glands and prostate in rats, and impaired sperm parameters, a few studies showed associations at levels close to estimated human exposure. Because of the considerable uncertainty of the validity and relevance of these observations it was recommended that further research should be undertaken to reduce the uncertainty.

Re-evaluation of human risks

EFSA completed a full risk assessment of BPA in 2006 and set a limit of 0.05 mg/kg body weight per day that could be ingested daily over a lifetime without appreciable risk (Tolerable Daily Intake – TDI). It evaluated intakes of BPA through food and drink, for adults, infants and children and found that they were all well below the TDI.

EFSA has updated its scientific advice on BPA several times since 2006, most recently updating its risk assessment in 2011, reaching similar conclusions.

In February 2012, following further consideration of new scientific studies, EFSA decided to undertake a full re-evaluation of the human risks associated with exposure to BPA through the diet, also taking into consideration the contribution of non-dietary sources to the overall exposure to BPA. The new opinion will review all the available data and scientific studies on dietary exposure published since EFSA’s 2006 Opinion. The Panel will further evaluate uncertainties about the possible relevance to human health of some BPA-related effects observed in rodents at low dose levels.

FDA is also continuing to consider the low dose toxicity studies of BPA as well as other recent peer-reviewed studies related to BPA. At this stage, FDA has stated its current perspective on BPA, its support for further studies, its establishment of a public docket for its assessment of BPA use in food contact applications. FDA has issued interim public health recommendations, including its view of the appropriate regulatory framework for BPA use in food contact applications. It is expressing the wish to pursue the issue in collaboration with international partners.

The bane of lead

SummaryFood commonly contaminated with lead poses a serious health problem. Lead accumulates in bone tissue and can be mobilised during pregnancy and breast feeding, disturbing normal brain development of the foetus and young child. The action taken by developed nations to cut lead pollution is slowly having a desired effect, but developing countries are lagging behind.

Lead is a heavy metal that has been mined and used for thousands of years, and poisoning humans in the process. Although lead poisoning is one of the oldest known work and environmental hazards, that only small amounts of lead is necessary to cause harm is a much later finding. There is actually no known amount of lead that is too small to not cause harm in some way.

Chronic lead poisoning is the biggest danger because of its long half-life when bound to bone tissue and a particular concern is children. Lead mobilised from bone stores in pregnant and breastfeeding women can disturb brain development of the foetus already in the womb and cause permanent impairment in early life of a child. The classic signs and symptoms in children are loss of appetite, abdominal pain, vomiting, weight loss, constipation, anemia, kidney failure, irritability, lethargy, learning disabilities, and behavioural problems. Slow development of normal childhood behaviours, such as talking and use of words, and permanent mental retardation can both be seen depending on the extent of lead exposure.

In adults, there is an association between blood lead concentration, elevated systolic blood pressure and chronic kidney disease at relatively low blood lead levels. Inorganic lead is also classified as a probable carcinogen in humans.

Environmental exposure

Abnormally high rates of death and illness among children were seen at the beginning of 2010 in Bukkuyum and Anka areas of Zamfara state in northern Nigeria. Investigations by the joint Environment Unit of the UN Office for the Coordination of Humanitarian Affairs and the UN Environment Programme revealed that the cause of the health problems was acute lead poisoning from the processing of lead-rich ore used in the gold extraction process in homes and compounds in the affected areas. More than 18,000 people were affected and 200 children reportedly died as a result of the poisoning.

In 2010, lead poisoning was detected in Central China’s Hunan province that left 19 villagers hospitalised. The patients came mainly from two villages in Guiyang county. The city’s environment protection department implicated and shut down a scrap lead recycling plant in Guiyang. This followed a case in 2009 where as many as 254 children younger than 14 were found to have excessive blood-lead levels in Jiahe county, which borders Guiyang county. Four of them, from three villages, were diagnosed with lead poisoning. A local lead smelter blamed for the massive lead-pollution incident in Jiahe was shut down.

Dietary exposure

Several women taking Ayurvedic medicines during pregnancy were detected with dangerous lead poisoning, US researches reported in August 2012, after investigating cases associated with the use of such traditional drugs. During a year-long survey, the New York City investigated six cases of lead poisoning associated with the use of 10 oral Ayurvedic medications made in India. Ayurvedic medicine is a Hindu system of traditional medicine native to India and a form of alternative medicine sometimes containing high levels of lead.

Lead can leach out of ceramic cups and plates when the glaze is improperly fired or when the glaze has broken down because of wear from daily usage, particularly after repeated use in a microwave or dishwasher. Chips and cracks in ceramic ware also allow leaching of lead. When lead is released into food and drink from ceramics, hazardous levels can contaminate food substances and expose children and adults to toxic levels. Acidic juices pose a particular problem in promoting leaching of lead. In 2003, US authorities investigated a case of lead poisoning in a boy aged 20 months. The child was home full-time and consumed all meals and beverages using ceramic dinnerware. The ceramic dinnerware was manufactured in France and released levels of lead that were ten times higher than allowed.

There is still some debate about the real impact of low dose lead exposure from the general food supply or the immediate environment. It has been proposed that lead exposure in children is correlated with neuropsychiatric disorders such as attention deficit hyperactivity disorder and antisocial behaviour. Elevated lead levels in children have been shown to be correlated with higher scores on aggression and delinquency measures. A correlation has also been found between prenatal and early childhood lead exposure and violent crime in adulthood. Countries with the highest air lead levels have been found to have the highest murder rates, after adjusting for confounding factors.

Although the facts are there, the above correlations might be a little simplistic. However, it is likely that lead is one of several contributors in a multifactorial model for deviant behaviour and such findings cannot be easily dismissed. What is clear is that even low levels of lead exposure can affect brain development as evidenced by a lower IQ score.

Common lead sources

So what are the most common lead sources? The general public can be exposed to lead via food, water, air, soil and dust. Food is the major source in adults not affected by occupational exposure, although for children ingestion of soil and dust can also be important contributors. Lead used for soldering of food cans and the making of ceramic household goods and water pipes or lead added to paint and petrol can easily contaminate food directly or indirectly by leaking into the environment and finding its way into crops. Surprisingly, some herbal remedies still have lead added deliberately. A particular risk group is hunters and their families with high consumption of game meat because of the common use of lead ammunition.

Particularly high lead levels have been identified in game meat and offal, seaweed and dietary supplements like the herbal remedies mentioned above. However, because the presence of lead is so widespread in food, foods consumed in higher amounts like bread and rolls, tap water and potatoes contribute the most to lead exposure for the general public. It is thus very difficult for individuals to reduce their lead exposure from food. Collective remedial actions as outlined below can gradually reduce lead exposure.

Mode of action

The primary cause of lead’s toxicity is its interference with a variety of enzymes. Lead mimics other metals that take part in biological processes and interact with many of the same enzymes, thus interfering with the enzyme’s ability to catalyze its normal reactions. Among the essential metals with which lead interacts are calcium, iron, and zinc.

Lead also interferes with the release of neurotransmitters, chemicals used by neurons in the brain to send signals to other cells. Glutamate is one such neurotransmitter important in many functions including learning, with lead blocking its activation of NMDA receptors. The targeting of NMDA receptors is thought to be one of the main causes for lead’s toxicity to neurons

Remedial measures

International and European health-based guidance values for lead exposure have been amended several times as new information has come to light. In 2010, EFSA  concluded that existing recommendations were no longer appropriate and that, as there was no evidence for a threshold for a number of critical endpoints including developmental neurotoxicity and adult nephrotoxicity, it would not be proper to issue a guidance value. This conclusion was confirmed by JECFA in 2010, while also expressing a concern that there was potential at current levels of exposure for lead to affect neurodevelopment in infants, children and the foetus of pregnant women.

Internationally, control measures are now in place to regulate lead in a number of products. A range of preventative measures also exist at national and local levels. Recommendations by health professionals for lowering childhood exposures include banning the use of lead where it is not essential and strengthening regulations that limit the amount of lead in soil, water, air, household dust, and products. A 1978 law in the US restricts the use of lead in paint for residences, furniture, and toys to 0.06% or less. Legislative control measures have been taken to remove lead from paint, petrol, food cans and water pipes in Europe since the 1970s. Leaded petrol was banned in the European Union from 2000 with exemptions possible until 2005.

Unfortunately lead remediation will take time to filter through the environment and many developing countries are lagging behind in making the efforts necessary. The lead problem will remain for decades to come and continued vigilance will be necessary. However, in an encouraging sign FDA, in an ongoing survey of 285 of the most important food products in the U.S. food supply, found that dietary intake of lead by a 2-year-old child had dropped more than 90 percent since 1979. Similarly, EFSA in a recent survey covering a shorter time period found that dietary exposure had been reduced by close to 25% between 2003 and 2010 in the overall population.

Deadly bug in sprouts

SummarySeed sprouting provides an ideal environment with optimal temperature and humidity for bacterial growth. Once the bugs are there they are very difficult to remove from fresh sprouts. A German case study shows the serious impact of sprout contamination with a particularly nasty bug that can cause diarrhoea, kidney disease and death.

On 21 May 2011, Germany reported an outbreak of Shiga-toxin producing Escherichia coli (STEC), serotype O104:H4. At the conclusion of the outbreak at least 4,300 cases of diarrhoeal disease, 773 cases of haemolytic uraemic syndrome (HUS) and 50 deaths across Europe linked to the outbreak in Germany had been reported to the European Centre for Disease Prevention and Control (ECDC). In addition, outside the EU eight cases of STEC and five cases of HUS, including one death had been reported in the USA, Canada and Switzerland through the international health regulations (IHR), all with recent travel history to Germany.

The clinical onset of the last outbreak-related case in Germany was 4 July 2011. The Robert Koch Institute (RKI) in Germany announced the end of the E. coli outbreak on 26 July 2011 after more than two months of intensive investigative activities.

Sprouted seeds

Early case-control studies conducted by the RKI demonstrated that clinical disease was associated with the consumption of fresh salad vegetables. The high proportion of adult women among cases, was consistent with fresh salad vegetables as the source of infection. This led to a false warning about some Spanish grown vegetables causing havoc for some Spanish growers. Later, a detailed cohort study demonstrated an association with sprouted seeds. Epidemiological studies on an associated French outbreak also implicated sprouted seeds as the outbreak vehicle.

A tracing back and tracing forward study showed that most of the clusters could be attributed to consumption of sprouted seeds from one producer in Germany. Investigation of the production site showed no evidence of environmental contamination. This left the seeds used for the sprout production as the prime suspect vehicle of infection. Fenugreek seeds were found to be common to both outbreaks and that a specific consignment of fenugreek seeds imported from Egypt was the most likely link between the outbreaks.

Import ban

A ban on imports into the EU of Egyptian fenugreek seeds and certain other sprouting seeds was imposed in July 2011 after the European Food Safety Authority said this was the most likely cause of the E. coli outbreaks.

The European Commission’s Food and Veterinary Office (FVO) visited Egypt in August 2011 and found that Egypt did not differentiate between seeds for sprouting and seeds for planting. The trace-back exercise found that three implicated lots were produced in upper Egypt by the same farmer in separate farms grown under organic conditions.

The Egyptian investigation found no evidence of STEC O104:H4 presence, although there was plenty of potential for contamination from human populations and animals, and problems with analytical methods. The FVO said Egypt must ensure that seeds produced specifically for sprouting must comply with hygiene rules and microbiological criteria.

Given an exchange of information with the Egyptian authorities and new measures to prevent contamination, the ban on fenugreek imports from Egypt was lifted on 31 March 2012.

Rare strain

The published data for STEC O104:H4 are scarce as this is a very rare serogroup infecting humans in Europe and globally. According to the information reported to ECDC, there were 10 reported cases of STEC O104:H4 infection in the EU Member States and Norway during 2004-2010. Five of the 10 cases between 2004 and 2010 were related to travel to Afghanistan (2008), Egypt (2010), Tunisia (2009, 2010) and Turkey (2009).

In addition to those cases reported to ECDC, a review of the scientific literature revealed that STEC O104:H4 has been isolated twice in Germany in 2001 and once in Korea in 2005. The German isolates differed from the 2011 outbreak strain.

Inherent problems in sprout production

The preparation of fresh sprouted seeds rarely includes a step where bacterial contamination is eliminated. Hence, food preparation of fresh sprouted seeds is based on the understanding that they are sold as ready-to-eat, i.e. safe to eat as is, or following only minimal preparation. For fresh produce, this assumes and relies on a production process which prevents contamination and an ability to detect contamination when it occurs. These conditions have proven not to be satisfied in this case.

Aspartame controversy

SummaryNormal use of the synthetic sweetener aspartame in diet products is considered safe by several national and international authorities, but has been questioned by public groups raising a range of concerns. The European Food Safety Authority, in a re-evaluation of the safety of aspartame to be completed by May 2013, recently requested more information on potential degradation products.

Aspartame is a low-calorie, intense sweetener which is approximately 200 times sweeter than sucrose (table sugar). It is used to sweeten a variety of foods and beverages such as drinks, desserts, sweets, chewing gum, yoghurt, energy-reduced and weight control products and as a table-top sweetener. Aspartame was first approved for use in dry goods in 1981 and for carbonated beverages in 1983 by the U.S. Food and Drug Administration. During the 1980s, aspartame was authorised for use in foods and as a table-top sweetener by several EU Member States. European legislation harmonising its use in food wa introduced in 1994.

Early controversy

Aspartame was discovered by accident in 1965, when James Schlatter, a chemist of the G.D. Searle Company was testing for an anti-ulcer drug and licked his contaminated finger to pick up a piece of paper. He noticed an intense sweet taste. The company set out to benefit from his findings and patented the substance. Early controversy over aspartame safety was due to perceived irregularities in the aspartame approval process during the 1970s and early 1980s, including allegations of conflicts of interest and claims that aspartame producer G.D. Searle had withheld and falsified safety data. Aspartame consumption has since been claimed to cause 92 different health side effects including brain tumors, preterm delivery, birth defects, diabetes, emotional disorders and chronic neurological disruptions including epilepsy/seizures. Most claims are populistic in nature without credible scientific backing, but there are also some published scientific studies providing initial support for the theories. The published reports have been reviewed several times by government authorities in different countries without any clear confirmation of their validity.

It has been shown that even at very high doses of aspartame (over 200 mg/kg), no aspartame as such is found circulating in the body due to its rapid breakdown. Hypotheses of adverse health effects have thus focused on the three metabolites aspartic acid, methanol and phenylalanine, which are formed through hydrolysis of aspartame in the small intestine. However, aspartame is far from a unique source of the three metabolites. Aspartic acid (aspartate) is one of the most common amino acids in the typical diet and in a fairly high consumer of aspartame, it still provides only between 1-2 % of the daily intake of aspartic acid. Equally, the amount of methanol formed from aspartame is less than that found in fruit juices and citrus fruits, and there are other dietary sources for methanol such as fermented beverages. Phenylalanine is one of the essential amino acids and is required for normal growth and maintenance of life. Common foods such as milk, meat, and fruit provide far greater amounts of this metabolite than aspartame.

Adverse health effects

There has been some speculation that aspartic acid, in conjunction with other amino acids like glutamate, may lead to excitotoxicity, inflicting damage on brain and nerve cells. However, clinical studies have shown no signs of neurotoxic effects, and studies of metabolism suggests it is not possible to ingest enough aspartic acid and glutamate through food and drink to levels that would be expected to be toxic.

On the other hand, there is clear proof that people with the rare genetic disorder called phenylketonuria (that is tested for in many countries at birth) should keep phenylalanine levels in the diet low. In affected persons, usual levels of phenylalanine in the diet can cause problems with brain development, leading to progressive mental retardation, brain damage, and seizures.  Other concerns about the safety of phenylalanine from aspartame largely centers around hypothetical changes in neurotransmitter levels as well as ratios of neurotransmitters to each other in the blood and brain that could lead to neurological symptoms. Reviews of the literature have found no consistent findings to support such concerns, and while high doses of aspartame consumption may have some biochemical effects, these effects are not seen in toxicity studies to suggest aspartame can adversely affect neuronal function.

The methanol produced by the metabolism of aspartame is absorbed and quickly converted into formaldehyde and then completely converted to formic acid, which, due to its long half life, is considered the primary mechanism of toxicity in methanol poisoning. With regards to formaldehyde, it is rapidly converted in the body, and the amounts of formaldehyde from the metabolism of aspartame is trivial when compared to the amounts produced routinely by the human body and from other foods and drugs. At the highest expected human doses of consumption of aspartame, there is no increased blood levels of methanol or formic acid, and ingesting aspartame at the 90th percentile of intake would produce 25 times less methanol than would be considered toxic.


Concern about possible carcinogenic properties of aspartame was originally raised and popularised in the mainstream media in the 1970s and again in 1996 by suggesting that aspartame may be related to brain tumours. Independent agencies reanalysing multiple studies based on such claims could not confirm any credible association between aspartame and brain cancer.

Later the European Ramazzini Foundation of Oncology and Environmental Sciences (ERF) released  study results in 2007 and 2010 which claimed that aspartame could increase some malignancies in rats, concluding that aspartame is a potential carcinogen at normal dietary doses. These conclusions were contradicted by other carcinogenicity studies which found no significant danger. After reviewing the foundation’s claims, independent experts have discounted the study results. Reported flaws were numerous and included comparing cancer rates of older aspartame-consuming rats to younger control rats; a diet leading to possible nutritional deficiencies; lack of animal randomisation; overcrowding and a high incidence of possibly carcinogenic infections; and misdiagnosing of hyperplasias as malignancies.

Reviews of numerous carcinogenicity studies in animals, epidemiologic studies in humans, as well as in vitro genotoxicity studies have found no significant evidence that aspartame causes cancer in animals, damages the genome, or causes cancer in humans at doses currently used.

Neurological and psychiatric symptoms

Numerous allegations have been made in popular media purporting neurotoxic effects of aspartame leading to neurological or psychiatric symptoms such as seizures, headaches, and mood changes. Reviews of the biochemistry of aspartame have found no evidence that the doses consumed would plausibly lead to neurotoxic effects. Comprehensive reviews have not found any evidence for aspartame as a cause for these symptoms, although one review did provide a theoretical biochemical background of neurotoxicity and suggested further testing.

A review of the pediatric literature did not show any significant findings for safety concerns with regards to neuropsychiatric conditions such as panic attacks, mood changes, hallucinations or with ADHD or seizures.

Headaches are the most common symptom reported by consumers as associated with aspartame consumption. While there are some indications that aspartame might be one of many dietary triggers of migraines, in a list that includes “cheese, chocolate, citrus fruits, hot dogs, monosodium glutamate, aspartame, fatty foods, ice cream, caffeine withdrawal, and alcoholic drinks, especially red wine and beer”, other studies have failed to prove such links.

The current state of play

Although aspartame and its metabolites have been studied in a wide range of populations including infants, children, adolescents, and healthy adults, even at very high doses, without identifying any safety concerns in healthy adults and children there are still some lingering doubts. However, equally to the proof of safety needed for authorisation of an additive for use in food, to withdraw such an approval requires some verified safety concerns. That is not yet the case for aspartame.

The good thing is that concerned consumers can identify food containing aspartame by looking at the ingredients lists on product labels. Like all food additives, aspartame has been assigned an “E-number” following authorisation. Its presence in foods can be indicated either by name (i.e. “aspartame”) or by its number E 951.