14 December 2004

FSANZ answers regarding food testing

Frequently Asked Questions on Genetically Modified Foods

During the public consultation periods for the genetically modified (GM) food applications, the Authority received written submissions from a range of non-government community groups and associations representing consumers and industry, and from the general public. The issues that were frequently raised in these submissions were often of a general nature relating to the processes used by the Authority in its assessment of a GM food, or more broadly to the safety and environmental concerns associated with the use of gene technology in food production.

The Authority has prepared responses to these frequently raised issues. The responses are grouped into three broad categories based on the subject matter: General Issues, Food Safety Issues and Environmental Issues.

Part 1. General Issues

Question.  How is the public kept aware of the approval process for GM foods?  

Answer

FSANZ has a transparent and consultative regulatory framework for developing food standards in Australia and New Zealand. For all matters relating to a change in the Food Standards Code, comments are sought from all stakeholders on two separate occasions during the assessment process. These public consultation periods are mandatory for all food standards matters including applications for GM foods. This system allows stakeholders to raise relevant issues that are then specifically addressed in assessment reports.

As part of the open and transparent system operating at FSANZ, all information and data relating to a GM food is accessible via a public register file. An exception to this occurs only when certain information is given confidential business information status by FSANZ.

Question.  Is company data used during the assessment of a GM food? If so, does this compromise the validity of the safety evaluation and the independence of FSANZ?

Answer

The responsibility for demonstrating the safety of any new food product on the market, lies with the developer of that product. This is similar to the situation with new chemicals and drugs. Therefore, when an applicant seeks approval for a new GM food, they must provide FSANZ with the evidence that supports the safety of the product. It is also a requirement that this data be generated within quality assurance guidelines that are based on internationally accepted protocols (i.e. approved methodology and Good laboratory Practice (GLP)) and stand up to external scrutiny (i.e. independent audits and documentation trails). To achieve this, the applicant submits to FSANZ, a comprehensive dossier of quality-assured raw experimental data for each GM commodity, on a case-by-case basis.

FSANZ scientists with expertise in molecular biology, toxicology and human nutrition assess the company data. FSANZ complements the experimental data with information from the scientific literature, other applications, other government agencies and the public. FSANZ scientists stay at the ' cutting edge' of the science through professional activities including participation on national and international expert Committees and workgroups. The summary report generated by FSANZ is also evaluated by independent experts. This provides additional assurance in FSANZ' s scientific capacity and integrity.  

Furthermore, during the public consultation phase of the assessment of a GM food, anyone can view and comment on the scientific report generated by FSANZ. Such an assessment process ensures that FSANZ receives valid data of high quality and from a range of sources during the course of the assessment.

Part 2.  The Safety of GM foods

Question.  How is the safety of GM foods assessed?  

Particular safety concerns are raised in association with GM foods. Some issues of major concern are that the testing of GM foods is inadequate and that there may be potential long-term risks associated with the consumption of the foods.

Answer

The community has a reasonable expectation that foods in the marketplace are safe and wholesome. However, even foods with a long history of safe use carry a level of risk that must be balanced against the benefits of a varied and nutritious diet. Absolute safety of the food supply can never be guaranteed. The risks are generally managed through the level of knowledge that already exists in the community about traditional foods. In this context,safetherefore means that there is a reasonable certainty of no harm.

Because GM foods are new, and a history of safe use is yet to be established, it is appropriate that a cautious approach is taken to their introduction into the food supply. This applies equally to any novel food where there is no established pattern of use. The purpose of the scientific and evidence-based pre-market assessment of a GM food is to establish on a case-by-case basis that the new food is at least as safe as the existing counterpart food.

The safety assessment for a GM commodity compares the molecular, toxicological and nutritional and compositional properties of the food to the non-GM form. The assessment focuses on the new gene product(s), including the intentional and unintentional effects of the genetic modification, and examines any compositional changes, including whether the genetic modification has altered the potential allergenicity and toxicity of the food. The assessment is therefore a comparative analysis using the commonly consumed conventional food as a benchmark for safety.  

This comparative analysis is regarded by organisations such as the World Health Organisation (WHO)/Food and Agriculture Organisation (FAO), the Organisation for Economic Cooperation and Development (OECD) and the Codex Alimentarius Commission as the most practical approach for assessing the safety of a GM food. FSANZ regularly reviews procedures for assessment to ensure that recent scientific and regulatory developments are reflected in the process. At the international level, FSANZ is actively involved in the development of a framework for the assessment of GM foods within the Codex Alimentarius Commission.

Detailed information about the risk assessment process for GM foods can be obtained in a recent publication entitled GM Foods and the Consumer - ANZFA Occasional Paper Series No.1, published in June 2000.

Question.  Are there potential long-term risks associated with the consumption of the foods?

Answer

Long-term animal toxicity studies are not generally applicable to the testing of whole foods. Such studies are commonly used in the safety assessment of many compounds including pesticides, pharmaceuticals, industrial chemicals and food additives. In these cases, the test substance is well characterised, of known purity, of no nutritional value, and human exposure is generally low. It is therefore possible to feed such compounds to laboratory animals at a range of doses (using amounts greatly above expected human exposure levels) in order to identify any potential adverse effects. Establishing a dose-response relationship is a pivotal step in toxicological testing. By determining the level of exposure at which no adverse effects occur, a safe level of exposure for humans can be established which includes appropriate safety factors.

By contrast, traditional toxicological testing is not applicable to the assessment of whole foods. Foods are complex mixtures of constituents and have wide variations in composition and nutritional value. Due to its bulk, a food can only be fed to laboratory animals at low multiples of the amounts that might be present in the human diet and it is therefore not possible to conduct normal dose-response experiments in the same way that these experiments are conducted for medicines and chemicals. In addition, a key factor in these experiments is the need to maintain the nutritional value and balance of the diet. A diet that consists entirely of a single food can cause adverse effects on nutritional status, potentially masking any other smaller effect of a component or components of the food being tested in the animals. The observations from single food studies can therefore be confounded by a range of adverse effects not directly related to the food being tested.

The safety assessment of a GM food relies more appropriately on information from animal toxicity studies using only the new protein rather than the whole food. In addition, these experiments can be done for each new protein in the food (if the modification involves more than one newly introduced gene) and at a range of doses. The animal toxicity testing using a single protein can demonstrate that the protein itself will have no adverse effects in humans when consumed as part of a food. While animal experiments using a single new protein can provide more meaningful information than experiments on the whole food, additional reassurance regarding the safety of newly-expressed protein can be obtained by examining the digestibility of the new protein in laboratory conducted in vitro assays using conditions which simulate the human gastric system. Such experiments indicate whether the new protein behaves like normal dietary protein

Question.  Is the composition of GM foods different to the composition of non-GM foods? Do GM foods have a different nutritional value?

Answer

Sometimes, compositional data of GM food differs slightly from the non-GM control line. Statistically significant differences observed in the comparative evaluation are assessed by FSANZ in terms of their relevance in a biological system. In order to determine if the differences have biological significance, ANZFA compares these values to those of other commercial varieties and in literature ranges. The use of published ranges and historical control data as comparators in safety assessment studies is normal for interpreting biological and analytical variation.  

To date, the significant differences between test and control lines tend to be small and they are usually within the range that would be expected for other commercial varieties. In these cases, FSANZ concludes that the difference has no biological relevance and certainly does not pose a risk to consumers. Sometimes, differences can be explained by differences in locations or seasons. Generally, the differences do not occur consistently in all locations and are therefore not considered to indicate a trend.  

Question. Does genetically modifying a food decrease its nutritional value?

Answer

There is no evidence to suggest that genetic modification per sereduces the nutritional value of food. To assess this, FSANZ evaluates the major constituents of the food (fat, protein, carbohydrate, fibre, ash and moisture) as well as the key nutrients (amino acids, vitamins, minerals, fatty acids). This approach enables both the intentional effects and any unintentional compositional changes in the food to be assessed.

Question. How is the concept of substantial equivalence used as part of the safety assessment process? Why is DNA not included in the assessment of substantial equivalence?

The use of the concept of substantial equivalence as part of the safety assessment process has been questioned on the premise that differences at the DNA level make foods substantially different.

Answer

The comparative approach, previously referred to as substantial equivalence, embodies the concept that GM foods can be assessed to a large extent by comparison to the benchmark of commonly consumed foods already regarded as safe (the traditional or non-modified counterpart) (WHO 2000). The comparison is usually made at the level of the composition of the food.

This allows the safety assessment to focus on any significant differences between the GM food and its conventionally produced counterpart. Phenotypic differences are not normally considered in the comparison, if that difference does not significantly change the characteristics for composition of the new food relative to the conventional food. This is partly because differences in phenotype can occur with every breeding event and often arise also as a result of certain environmental factors.

The comparative approach allows for an evaluation of the important constituents of a new food in a systematic manner while recognizing that there is general acceptance that normally consumed food produced by conventional methods is regarded by the community as safe. It is important to note that, although a GM food may be found to be different in composition to the traditional food, this in itself does not necessarily mean that the food is unsafe or nutritionally inadequate.   Each food needs to be evaluated on an individual basis with regard to

The comparative approach was first espoused by a 1991 Joint FAO/WHO Consultation where it was noted that the 'comparison of a final product with one having an acceptable standard of safety provides an important element of safety assessment '(WHO 1991). Since this time, the concept has been integrated into safety assessment procedures used by regulatory authorities worldwide. It has thus been in use for approximately ten years and has been an integral part of the safety assessment of some 40 products.

Although the approach has attracted criticism, it remains the most appropriate mechanism for assessing the nutritional and food safety implications of foods produced using gene technology (WHO 2000). It is generally agreed also that continual review of the concept, in response to the criticism, provides a useful stimulus to ensure that safety assessment procedures are kept at the forefront of scientific knowledge (Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology, Geneva, 2000; Expert Panel Report on the Future of Food Biotechnology, Royal Society of Canada 2000; Report of the New Zealand Royal Commission on Genetic Modification, 2001; Genetically Modified Plants for Food Use and Human Health - An Update. The Royal Society, London, 2002).

Substantial equivalence refers to only one aspect of the safety assessment of new foods including GM foods. The concept is not used to come to a final decision for approval of a food, but is used to identify similarities and differences between the GM food and a comparator which has a history of safe food use.

The comparison can include physical characteristics and compositional factors, as well as an examination of the levels of naturally occurring allergens, toxins and anti-nutrients

The reason that differences at the level of the DNA or gene are not considered to make a GM food different, is that these changes do not necessarily result in differences in the food. That is, the DNA itself is not considered to change the makeup of the food.  

Question. Are there risks associated with the possible introduction of new toxins and allergens in GM foods?

Answer

A major part of the safety assessment of any GM food commodity is an analysis of information about the genetic modification and the resultant changes in the plants, to determine whether new toxins or allergens have been introduced. Where the genetic change has introduced a new protein into the food, the protein is analysed in detail by a range of biochemical assays to test its potential to cause toxicity or allergenicity. We know a lot about what makes up the chemical   composition of particular commodities (e.g. potatoes, corn, cotton etc) and if we obtain a complete molecular characterisation, nutritional and compositional analysis, potential for toxicity and allergenicity, then we have no grounds to suspect that a new toxin or allergen will be produced?

Toxicity studies include animal toxicity experiments using the purified protein, and   analysis using published information on known protein toxins. Similarly, although there is no direct test for allergenicity, comparisons are made on the physical and chemical properties of a new protein with those of known food allergens. Any similarities between the new protein and a known allergen are investigated further to establish their significance in the prediction of allergenicity. This may involve using immunochemical studies using sera from allergic individuals.

In addition, any GM food safety assessment requires detailed information about naturally occurring toxins and allergens in the particular food commodity. The purpose of this requirement is to focus on any changes in the amounts of any pre-existing natural toxins and/or allergens in the food that may have occurred due to the modification.

It is also possible to develop foods specifically where such compounds are significantly reduced or eliminated. For example, research is underway on certain proteins in peanuts that are known to be the cause of major allergies in susceptible individuals. One advantage of gene technology, in comparison with other methods, is that any transferred genes are well characterised and defined, thus the possibility of developing a food with a new toxic or allergenic compound is likely to be reduced.

Further details on the assessment for toxicity and allergenicity can be obtained from GM Foods and the Consumer- ANZFA Occasional Paper Series No 1 (2000).

Question.  Is there potential for an increase in antibiotic resistance in humans resulting from the use of  antibiotic resistance marker genes in GM foods? Can novel genes be transferred to bacteria in the human gut?

Answer

This issue arises because of the use of antibiotic resistance marker genes (ARMGs) in the development of GM plants.   Antibiotic resistance marker genes are linked to the gene of interest, to enable the initial selection of the transformed cells. Those cells that contain the antibiotic resistance marker gene, and hence the gene of interest, will be able to grow in the presence of the antibiotic. Those cells that do not contain the marker gene cannot grow and are therefore eliminated during the selection procedure.

The possibility has been raised that ingestion of food containing copies of antibiotic resistance genes could facilitate the transfer of the gene to bacteria inhabiting the gut of animals and humans. It is argued that these genes may then be transferred to disease causing bacteria and that this would compromise the therapeutic use of antibiotics.

This issue is considered in two parts:i) the likelihood that transfer would occur and ii)  the impact if such an event occurred. Firstly, the potential for the transfer of antibiotic resistance genes from plants to microorganisms residing in the human gastrointestinal tract is very low given the complexity of steps required for gene transfer and expression  [ 1 ]. Recent studies with humans showed that no GM material survived the passage through the whole digestive tract and that the likelihood of functioning DNA being taken up by bacteria in the human or animal gut is extremely low [ 2 ].

Antibiotic resistant bacteria are naturally occurring, ubiquitous and normally inhabit the gut of animals and humans. The transfer of antibiotic resistance genes is much more likely to arise from this source and from their medicinal use, rather than from ingested GM food. Furthermore, the majority of antibiotic resistance marker genes used in the development of GM commodities do not confer resistance to antibiotics that are in common therapeutic usage in humans. However, as the technology develops and alternative marker genes emerge, there is a general consensus that the continued use of antibiotic marker genes in GM food crops should eventually be phased out [ 3 ].

Part 3. Environmental and broad regulatory issues

Question. Who is considering the potential environmental risks associated with GM foods?

Answer

Environmental issues are considered as part of the comprehensive assessment processes of the Office of the Gene Technology Regulator (OGTR) in Australia, and the Environmental Risk Management Authority (ERMA) in New Zealand. Since June 2001, OGTR regulates activities with all GMOs and any ' gap ' products (that is, products for which no other regulator has responsibility).

FSANZ does not have the authority to assess matters relating to environmental risks resulting from the release of GM crops into the environment. However, information is shared between FSANZ and these other regulatory agencies in both Australia and New Zealand. The interface between FSANZ and OGTR specifically requires reciprocal notifications and advice relating to GM food matters.

In Australia, the current regulatory system includes a number of agencies with specific roles in the control and regulation of GM products (such as imports, food, agricultural and veterinary chemicals). These include:

• Food Standards Australia New Zealand (FSANZ)
  
  
• The Office of the Gene Technology Regulator (OGTR)
  
  
• The Therapeutic Goods Administration (TGA)
  
  
• The National Registration Authority for Agricultural and Veterinary Chemicals (NRA)
  
  
• The Australian Quarantine and Inspection Service (AQIS)

The safety of GM foods continues to be assessed and regulated by FSANZ under the direction of the Australia New Zealand Food Regulation Ministerial Council comprising Health and Agricultural Ministers from the Commonwealth, each Australian State and Territory, and New Zealand.

Similarly, in New Zealand as well as FSANZ for food, other government departments and agencies, play a particular role in the regulatory process. These include:

• The Ministry of Agriculture and Forestry (MAF)
  
  
• The Ministry of Health (MoH)
  
  
• The Ministry of Research, Science and Technology (MoRST)

Question. Are the residues of particular herbicides higher in foods derived from herbicide-tolerant crops?

Answer

Agricultural chemicals such as herbicides can only legally be used if the chemical has been registered for use in Australia by the NRA and/or New Zealand by ERMA, and it has been demonstrated that any residue, at specified levels, does not lead to adverse health impacts. The concentration of a chemical residue that may be present in a food is regulated through setting maximum residue limits (MRLs) in the Food Standards Code. The MRL is the highest residue concentration that is legally permitted in the food commodity type and applies equally to GM or conventional food crops. The MRL is based on safety data and the registered conditions of use of that chemical in conjunction with a specific commodity. In practice, residual levels of a chemical present in a food may be well below the MRL.

It is important to note that MRLs are not direct public health and safety limits but rather, are primarily indicators of appropriate agricultural usage. MRLs are always set at levels lower than, and normally very much lower than, the health and safety limits. The MRL is determined following a comprehensive evaluation of scientific studies on chemistry, metabolism, analytical methods and residue levels.

In Australia, the National Registration Authority (NRA) applies to FSANZ to amend the appropriate standard in the Food Standards Code. In New Zealand, MRLs are set by the Ministry of Health, generally following a request from, and in collaboration with, the Ministry of Agriculture and Forestry. Only following demonstration that the use of agricultural and veterinary chemicals will not result in unsafe residues will the MRL enter into food law, through its inclusion in either the Australia New Zealand Food Standards Code, or the New Zealand Mandatory Food Standard 1999 (Maximum Residue Limits of Agricultural Compounds).

Where a GM crop has been modified for herbicide resistance, there is a concomitant reliance on the use of the corresponding herbicide during cultivation of the crop. Generally weed management strategies rely on the use of multiple herbicides used at particular stages of development of the crop. In contrast to this pattern of usage, the cultivation of a herbicide resistant crop, whether generated through gene technology or by conventional plant breeding methods, generally results in a reduction in the total amount of herbicides used on the crop. However, whatever the means of production, residues of any chemicals in the food must comply with the relevant MRL for that commodity.

Question. Is post market surveillance of GM foods undertaken?

Answer

The need for post-market monitoring and surveillance systems to be established for assessing the long-term health impacts of GM foods has been often raised by a number of stakeholders. There are currently no official mechanisms within Australia and New Zealand for monitoring the long-term impacts of GM foods. In Australia and New Zealand, as in most other countries, the responsibility for post-market surveillance is covered by an ongoing duty of care on the part of the developer. The developer is expected to monitor for existing and emerging risks that may be associated with its product and notify regulatory authorities whenever new information is uncovered.

In any discussion of post-market surveillance in relation to the evaluation of GM foods and products, it should be noted that one important consideration is that GM food products should not be placed on the market if any question associated with negative health effects is left unanswered during the pre-market safety assessment. A robust, science-based assessment, such as used by FSANZ and others, should minimise the need for post market surveillance. Furthermore, in the future, the new labelling requirements in Australia and New Zealand will help to ensure a much better knowledge of whether particular foods contain GM ingredients and, if so, which ingredients. From that time, it might be possible to link data on the health of individuals with information on their consumption of GM foods of differing types. The United Kingdom' s Food Standards Agency (FSA) began an 18 month feasibility study to determine whether long-term monitoring of novel foods is possible (Baynton, 1999). The idea is that if variation at district level regarding food purchasing and consumption can be detected, it may be possible to link this variation to health outcomes at district level. The results of the study might lead to recommendations with respect to the future surveillance of novel foods, and FSANZ has expressed an interest in collaborating with the FSA in the substantive study, should it proceed.

August 2002

Source: (here)