Item 19 Paper - Final

Item 19 Paper - Final




•The Australia New Zealand Food Authority (ANZFA) received an application from Monsanto Australia Ltd on 14 April 1997 to amend the Food Standards Code to include oil and linters derived from insect-protected cotton in the Table to clause 2 of Standard A18 – Food Produced Using Gene Technology;

•The Authority considered the Full Assessment report on Application A341 at ANZFA 55 in February 1999. The draft variation to the Food Standards Code was gazetted on 17 February 1999 and the period for public comment closed on 31 March 1999, although submissions were accepted beyond the closing date;

•The conclusion at full assessment of this application was that oil and linters derived from insect-protected cotton lines 531, 757 and 1076 can be regarded as substantially equivalent to oil and linters from unmodified cottonseed in respect of composition, safety, wholesomeness and end use;

  • At Inquiry, issues raised in public submissions included:

(i)Allergenic or toxic potential of food derived from Bt cottonseed;

(ii)Increased levels of insecticide in the human diet;

(iii)The presence of animal or insect genes in the food;

(iv)The acceptance and credibility of the applicant’s data;

(v)Development of insect resistance to Bt proteins;

(vi)Potential transfer of antibiotic resistance to intestinal microbes; and

(vii)Labelling of oil and linters from Bt cottonseed.

  • The conclusions of the Inquiry Report are:

-cottonseed oil and linters derived from insect-protected cotton lines 531, 757 and 1076 are considered to be substantially equivalent to the oil and linters from conventional cottonseed in respect of their composition, safety, wholesomeness and end use. There are no additional public health and safety concerns associated with the use of oil and linters derived from insect-protected cottonseed;

-while considerable general concern has been raised in public submissions regarding the use of gene technology in food production, there is no evidence that the consumption of oil and linters from the insect-protected cotton lines will lead to adverse health effects in humans;

-oil and linters derived from insect-protected cotton lines 531, 757 and 1076 would not require labelling under the current provisions of Standard A18 as they can be regarded as substantially equivalent to oil and linters derived from conventional cottonseed. It is noted however that the labelling provisions of Standard A18 are still under consideration by ANZFSC. On resolution, these foods will be required to comply with the amended labelling provisions;

- the proposed amendment to list oil and linters derived from insect-protected cotton lines 531, 757 and 1076 in the Table to Standard A18 is consistent with ANZFA’s section 10 objectives; and

- the regulatory impact analysis identified no disadvantages to either industry, government or consumers in the proposed amendment. The direct benefits of the proposed amendment primarily accrue to the cotton producers, with potentially a small benefit to the consumer. These benefits outweigh the costs associated with recommending against the amendment.


Standard A18 was adopted as a joint Australia New Zealand standard in July 1998

and came into effect on 13 May 1999. The standard prohibits the sale of food produced using gene technology unless it has first undergone a safety assessment by ANZFA and has been approved by the Australia New Zealand Food Standards Council (ANZFSC).

On 30 March 1999, ANZFSC approved a recommendation by ANZFA, under section 37 of the ANZFA Act, to allow foods produced using gene technology which were already in the marketplace, to remain on the market during the period of assessment by ANZFA providing they met specified criteria. The standard was amended to this effect by inserting clause 2A. These foods will, however, still undergo a rigorous safety assessment process.


The applicant initially submitted information pertaining to four lines of cotton – lines 531, 757 and 1076 containing the cry1Ac gene and line 1849 containing the cry2Aa gene. The Full Assessment report to this application therefore included a safety assessment of both genes and their protein product and referred to all four cotton lines.

On 30 April 1999, the Authority subsequently received a request from the applicant to separate the two different genetic constructs into two separate applications for technical reasons associated with characterisation of Line 1849 containing the cry2Aa gene. This request was formally accepted by the Authority and the applicant was advised of a separate application number (A389) pertaining to cottonseed oil and linters derived from cotton line 1849, known as INGARD cottonseed (Cry2Aa construct).

However, on 23 July 1999 the Authority again received advice from the applicant that a decision had been made not to proceed with commercialisation of cotton line 1849. Consequently, application A389 was withdrawn by the applicant, effective from that date. As a result of these changes to the original submission, this application now pertains only to lines 531, 757 and 1076 containing the cry1Ac gene construct.


The Authority considered 86 submissions pertaining to this application at Inquiry, with almost two thirds of these from New Zealand. Almost all of the submissions were opposed to the application due to ongoing concerns relating to the safety of the food both in the short and longer term, but also for a variety of environmental, ethical or philosophical reasons.

Although a significant proportion of these were detailed submissions, the technical information did not always relate specifically to food derived from Bt cotton, but often to unrelated genetic modifications in other plant crops or to broader issues relating to the use of biotechnology in food production.

The Full Assessment report to this application discussed both general issues concerning the use of biotechnology in food production as well as issues specifically relating to Bt cotton. In addition, previous reports such as the Full Assessment and Inquiry reports to Proposal P97 which established Standard A18, also contain detailed responses to issues which are being expressed as ongoing matters of concern in the current submissions. Some issues previously discussed include the use of antibiotic resistance marker genes and the potential for allergenicity of the new food.

A subset of the submissions contained comments on public health and environmental matters unrelated to food issues, but nevertheless served to illustrate a growing wariness in consumers to food regulation, which is being reflected globally. As a result of this broad public concern, the issues raised frequently had no direct relevance to the food products encompassed by this application, namely refined oil and processed fibre produced from insect-protected cottonseed. However, in response to the broad concerns expressed in a majority of the submissions, this report will revisit some of the more general issues concerning the safety of genetically modified foods but relate these more specifically to food derived from insect-protected (Bt) cottonseed.

Five of the submissions received were generally in favour of the application. These were received from the Western Australian Food Advisory Committee, Victorian Food Safety Council, Nestle Australia Ltd, the Food Technology Association of Victoria and the Australian Food and Grocery Council (AFGC). In addition, InforMed Systems Ltd together with the New Zealand Nutrition Foundation were not opposed to the application provided that particular scientific concerns in relation to the characteristics of the introduced genetic material were considered during the assessment. They noted also that the first genetically modified food applications to be assessed by ANZFA pertain to gene modifications which do not confer an immediate benefit to consumers, such as improved nutritional characteristics, or better sensory or storage characteristics.


Allergenic or toxic potential of food derived from Bt cottonseed

The Australian Natural Therapies Association was particularly concerned with the possibility that new proteins in the food supply may pose allergy risks to consumers.

However, the submission also recognised that new proteins expressed in non-edible parts of the plant are not of concern in relation to food allergy. Similarly, the Environmental Health Branch of the South Australian Public and Environmental Health Service noted that the absence of protein or new genetic material in the oil and linters circumvents the concerns in relation to the potential for toxicity or allergenicity of the foods derived from Bt cotton. However, this submission also expressed the view that the data presented in the Full Assessment report did not demonstrate unequivocally that protein was absent in both the refined oil or processed fibre. Several other submitters noted that the Full Assessment report stated the detection limits of protein in the oil and linters from cotton line 531, but not specifically from the other cotton lines under assessment.

On a related issue, Go Mark Food Systems and Mr A. Ward were concerned with the possibility that the genetic modification could result in unintentional changes to existing components or inadvertently introduce a new allergenic protein to the food.


As detailed in the Full Assessment report, any potential for toxicity and allergenicity of this protein has been comprehensively discussed as part of the Authority’s safety assessment process.

The potential for allergenicity arises from the presence of certain protein components in food and any evaluation of the allergic potential of this particular food must address the following matters. Firstly, a review of the history of use of the Cry1Ac protein and the Bt organism, including toxicology studies; secondly, whether consumption of the food derived from the cotton plant provides a significant level of exposure to seed protein; thirdly, whether the genetic modification has resulted in compositional changes in the food components of the cottonseed such that they may contain additional or altered compounds with a potential for allergenicity. This evaluation also includes a comparison of the physicochemical properties and sequence homology of the new protein with those of known allergens to test for similarities at the molecular level. The combined data from these tests provided a broad base of knowledge about the food under consideration and, in the case of this application, revealed no likely potential for allergenicity. It should be noted that the evaluation of all of these matters is a standard procedure during the course of the safety assessment of foods produced using gene technology.

(i)History of use

With respect to the potential toxicity of the food derived from Bt cottonseed, as recently as July 1997 the Environmental Health and Safety Unit (EHSU) of the Department of Health and Family Services reviewed toxicology data provided in support of the registration of the INGARD gene in cotton. Part of this review was an assessment of a range of products in which the biological insecticide Bt is the active ingredient. Data were analysed from established toxicological studies carried out in different animal species including guinea pigs, rats, mice and rabbits. In addition, data from acute, short-term, sub-chronic and chronic experiments (up to 2 years) in several different species and via several different modes of administration were presented. Results from human studies, including workers and personnel involved in production, and monitored for 1-20 years were also available. Other human data consisted of completed extensive epidemiological studies on a large population of people (1.4 million) in the mid 1980s. Consistent with its use as an organic pesticide for over 30 years, commercial preparations of Bt are thus considered to be of very low or no toxicity to humans, other animal species, most beneficial insects and other non-target organisms.

Further, it should be noted that the Cry1Ac protein has been exempted by the National Registration Authority for Agricultural and Veterinary chemicals (NRA) from the requirement to establish a maximum residue limit (MRL) when present in INGARD cotton or when used as a topical application on food crops because of its demonstrated low toxicity and history of safe use. The public has thus been potentially exposed to Bt proteins in the diet through the consumption of commercially available fresh vegetables, either organically or conventionally grown, over a long period.

Another new protein expressed in the cottonseed is neomycin phosphotransferase II (NPT II) which is an enzyme which metabolises the antibiotic neomycin, as well as related antibiotics such as kanamycin, and thus confers resistance to these antibiotics. The health aspects of specific marker genes and the enzymes they produce are discussed in more detail below.

(ii)Exposure data

The data analysed at full assessment indicated that both of the introduced proteins were present at approximately 0.001% or less of fresh weight in the leaf and seed tissue of each of the insect-protected cotton lines. This represents a low level of expression and thus a very small fraction of the total protein in the seed. Furthermore, the oil and linters derived from the cottonseed undergo extensive processing and refinement which effectively eliminates all protein before they are used as food. Thus, humans are not considered to be exposed to any detectable cottonseed proteins, whether or not they are new proteins.

Plant protein was not able to be detected in refined oil to a sensitivity of 1.3 parts per million (ppm) total protein. The absence of protein in the oil is expected for all lines and all production batches since quality assurance measures ensure that all are subjected to identical processing treatments which eliminate the protein from the finished product. If any plant protein is present following these treatments, it is present at vanishing amounts which are below currently available analytical methods of detection. Consequently, from a food perspective, refined cottonseed oil can be regarded as a highly purified product.

As indicated in the full assessment, a low level of Cry1Ac protein was detected in raw cotton linters, most likely because of adventitious contamination with a small amount of hull material from the seed. However, the raw linters undergo extensive processing which removes any trace levels of seed protein and subsequent fractions were found to be analytically free of protein. In view of these results, the cleaned linters can also be regarded as a highly purified product.


Lastly, the compositional analyses of cottonseeds from the insect-protected lines in comparison with the control line do not indicate any change in constituents that represents a food safety concern. The theoretical possibility, however remote, that levels of a previously unknown toxin, allergen or antinutrient might be elevated as an unintended consequence of the modification is not supported by any of the technical data or information provided either by the applicant or in submissions. On the contrary, the nutritional study conducted over a period of four weeks in rats indicates that the insect-resistant line is equivalent to the normal line in its suitability to support growth and provide adequate nutrition.

Increased levels of ‘insecticide’ in the human diet

Several submitters, including Ms I. Bailey, expressed concerns in relation to human health from consuming foods containing what was referred to in the submissions as an ‘insecticide’, referring to the Bt protein. With similar concerns, Mr E. Dempsey asserts that genetic modification of crops to contain Bt protein will lead to higher levels of this pesticide in the human diet.


These concerns can be addressed in two ways. Firstly, the Bt protein has been extensively tested for toxicity in humans and other animals and there are no health and safety concerns associated with its use in agricultural situations. It has been used as an insecticidal agent by the organic farming industry for over 30 years. Secondly, the human food use of this plant is restricted to the oil extracted from the cottonseed and, to a lesser extent, to the linters (short fibres attached to the cottonseed). Following processing into food grade material, neither of these components of the plant contains sufficient Bt protein to be detected by sensitive analytical techniques, and therefore may be regarded as highly refined products. Consumers of the food obtained from Bt cotton are therefore not exposed to detectable amounts of proteins from the seed or other parts of the plant.

To summarise previous information, the Bt protein Cry1Ac, is a protein produced by the Bacillus thuringiensis (Bt) organism, a common soil microbe that has insecticidal properties (For reviews see Biocontrol Science and Technology, OECD Workshop, 1994 and Analytical Chemistry of Bacillus thuringiensis, Ed. L. Hickle and W. Fitch, 1990). It is termed a biopesticide because the bacteria which produce it occur naturally in the environment, in virtually all soils. Although it is effective at destroying certain insect pests, it is not chemically related to synthetic chemical pesticides. It is toxic only to certain Lepidopteran insects that express another protein (referred to as a receptor) in the insect intestinal wall which specifically binds to the Cry1Ac protein. As animals, including humans, lack the particular receptor protein in the intestine, the Bt protein does not elicit the same toxic effect as in Lepidopteran insects. The Cry1Ac protein ingested by animals is subjected to the same degradative processes as any other extraneous protein which may be consumed as or with food.

Presence of animal or insect genes in the food

As a vegetarian, Mr G. Clarke expressed a concern of consuming animal or insect genes present in some genetically modified plants.


Foods derived from Bt cotton lines 531, 747 and 1076 contain copies of new genetic sequences derived from bacteria, and regulatory sequences copied from a common plant virus, but not from animals or insects. In the consumption of fresh fruit and vegetables, consumers would be readily exposed to naturally occurring soil microbes and even common plant viruses that are widespread in the environment.

It is recognised and accepted that many in the community wish to make food choices for a variety of reasons based on philosophical, cultural, religious and ethical considerations. ANZFA’s legal powers only allow consideration of whether the food products derived from Bt cottonseeds are as safe as the products derived from unmodified cottonseeds. In this regard, the presence of foreign genes from animals or insects is not an issue for concern in this case.