Maximum Residue Limits (MRLs) for Specified Agricultural Compounds in Food

Maximum Residue Limits (MRLs) for Specified Agricultural Compounds in Food Proposed Amendment to the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 A Discussion Document March 2001

Maximum Residue Limits (MRLs) for Specified Agricultural Compounds in Food Proposed Amendment to the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 A Discussion Document

Published in March 2001 by the Ministry of Health PO Box 5013, Wellington, New Zealand ISBN 0-478-24320-0 ISBN 0-478-24323-5 HP3423 This document is available on the Ministry of Health s Web site: http://www.moh.govt.nz

Preface This discussion document invites public comment on proposed amendments to the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999. The amendments are to establish new, and amend existing, maximum residue limits (MRLs) for specified agricultural compounds. Notice of the discussion document is being widely circulated. Submissions are sought from interested people and organisations. When sent on behalf of an organisation, the submission should include the position within the organisation of the person making or signing the submission, and an indication of the extent of consultation, discussion and support within the organisation for the opinions and advice expressed. All submissions received will be considered and analysed before the development of policy advice for the Minister of Health. Any requests to change the MRLs, which this document proposes to amend or add to the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999, should be supported by adequate justification and technical data. Any new information provided to the Ministry of Health about the compounds discussed in this document will be considered, where it is relevant. Submissions should be sent to: Maximum Residue Limit Amendments Food Group Public Health Directorate Ministry of Health PO Box 5013 WELLINGTON facsimile:(04) 496 2340 The closing date for submissions is 9 May 2001. All submissions will be available under the Official Information Act 1982. Therefore, if you consider that all or part of your submission should be treated as confidential, please make this clear when making your submission. The Official Information Act 1982 requires all information held by the Ministry to be available for public scrutiny, and such information may only be withheld from release in exceptional circumstances.

Contents Introduction and Background 1 Managing the Potential Risk from Exposure to Agricultural Compound Residues 2 Risk assessment 2 Risk management 3 Risk communication 4 Proposal 5 Pirlimycin 5 Spectinomycin 6 Tolylfluanid 6 Eprinomectin 7 Indoxacarb 8 Ivermectin 9 Meloxicam 10 Nicarbazin 11 Prochloraz 12 Gibberellic acid 13 Assessment of Proposal 14 Protection of public health 14 Risk assessment and management 15 Hazard identification and characterisation 15 Exposure assessment 16 Risk characterisation 17 Implications for trade 18 Domestic food production 18 Imported foods 18 Exported foods 19 Consistency with international food standards 19 Implications for international obligations 19 Glossary of Terms 20 Relevant agencies 20 Technical terms 20 Appendices Appendix 1: Establishing an ADI 21 Appendix 2: Calculation of TMDI 23 References 24 viii Maximum Residue Limits (MRLs) for

Maximum Residue Limits (MRLs) for ix

Introduction and Background In New Zealand, maximum residue limits (MRLs) for agricultural compounds in food are contained in the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 ( the MRL Standard 1999 ). Amendments to the MRL Standard 1999 generally reflect new agricultural compounds on the market, or changes in the permitted uses of compounds already on the market. Although the governments of New Zealand and Australia have embarked on a joint food standards-setting system, the specification of MRLs for agricultural compounds in food is outside the scope of this joint system. This discussion document proposes changes to MRLs for agricultural compounds in foods grown for the New Zealand domestic market. The proposed MRLs are for foods sold domestically. However, under the Trans- Tasman Mutual Recognition Arrangement between Australia and New Zealand, New Zealand manufacturers can export to Australia foods that meet the New Zealand domestic requirements. Equally, foods that meet the Australian domestic requirements may be imported into New Zealand from Australian manufacturers. The ultimate purpose of the Arrangement is to facilitate trade between Australia and New Zealand. The Ministry of Agriculture and Forestry s Agricultural Compounds and Veterinary Medicines Group (ACVMG) has requested that MRLs for nine agricultural compounds be established in the MRL Standard 1999 and the exemption of one compound having a MRL set. MRLs represent the maximum permitted levels of agricultural compound residues in food, which may result from the recommended use of those compounds. In summary, the changes proposed are:?? the addition of new maximum residue limits for: Pirlimycin Spectinomycin Tolylfluanid?? the amendment of existing maximum residue limits for: Eprinomectin Indoxacarb Ivermectin Meloxicam Nicarbazin Prochloraz?? the exemption of the following compound from having a MRL specified: Gibberellic acid. Maximum Residue Limits (MRLs) for 1

Managing the Potential Risk from Exposure to Agricultural Compound Residues The potential risk to public health from agricultural compounds is managed through three separate processes: risk assessment, risk management, and risk communication. Risk assessment Risk assessment for agricultural compound residues consists of assessing the toxicological risk of exposure to these residues and identifying the maximum residue limits, which the compounds should not exceed. This process is discussed in more detail later in this document. The primary purpose of setting specific MRLs for agricultural compounds 1 in food is to protect the health of the consumer. Other issues taken into account include avoiding unnecessary restrictions to trade, and consistency with international standards and obligations. Risk assessment for the 10 agricultural compounds was carried out by ACVMG. ACVMG prepared reports on new agricultural compounds and also recommended maximum residue limits for specific food commodities. The Ministry of Health has reviewed the ACVMG assessment to ensure that public health is not at risk. Both the ACVMG and the Ministry of Health follow international assessment principles for agricultural compounds. The principles are derived from the World Health Organization (WHO), the Food and Agriculture Organization (FAO) and the relevant committees of the Codex Alimentarius Commission (Codex). 2 1 2 The New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 uses the definition of agricultural compound as it is defined in section 2 of the Agricultural Compounds and Veterinary Medicines Act 1997. The Codex Alimentarius Commission (CAC) is an international food agency established by FAO and WHO, which produces an international food standard code. 2 Maximum Residue Limits (MRLs) for

Risk management Risk management aims to ensure that no consumer experiences adverse health effects as a result of exposure to permitted levels of agricultural compound residues in their diet (over the consumer s lifetime). This risk management process uses information obtained during the risk assessment to set standards (the MRLs) and to ensure policies are in place to reduce the possibility of such adverse health effects. Following its risk assessment, ACVMG prepares an application to the Ministry of Health, which includes a request for new MRLs to be established, or amendments to existing MRLs to be undertaken. The Ministry of Health reviews ACVMG s assessment to ensure that the protection of public health is maintained. The Ministry s review considers the acceptability and accuracy of the assessment, as well as justifications and methodology. The MRL Standard 1999 contains a default residue level of 0.1 mg/kg 3 (clause 6(b)). This means that if no MRL for a particular agricultural compound is listed in the MRL Standard 1999, then food containing residues of that compound can only be sold if the residue does not exceed 0.1 mg/kg. During the registration process for listed agricultural compounds in New Zealand, ACVMG identifies residues of compounds in the specified foods that are likely to exceed the 0.1 mg/kg default limit as a result of the recommended use. These use patterns are based on Good Agricultural Practices (GAP) or Good Practice in the Use of Veterinary Drugs (GPVD). In some agricultural compounds, lower limits than the default are identified as necessary for trade purposes. The concepts of GAP and GPVD reinforce the responsible use of agricultural compounds (FAO 1993). An MRL based on GAP reflects nationally authorised (that is, the registered or recommended) safe uses of agricultural compounds under actual conditions for effective and reliable pest control. It is intended that the agricultural compound be applied in a manner that leaves a residue in the smallest amount practicable. Therefore, an MRL based on GAP is relevant to a specific agricultural environment where similar crops and pest pressures exist. This means that it may not be feasible to adopt another country s MRLs for specific agricultural compounds. MRLs and GAP are the mechanisms used to manage the risks from consumption of foods that may contain residues of agricultural compounds. MRLs and GAP are determined nationally and their assessment and risk evaluation are based on international (FAO/WHO) guidelines. 3 X mg/kg is equivalent to X parts per million. Maximum Residue Limits (MRLs) for 3

Risk communication If the Ministry of Health s review demonstrates that the proposed MRLs are adequate to protect public health, the Ministry will undertake public consultation on the proposal. The purpose of this document is both to inform the public and to seek the consumers view of the proposed amendments to the MRL Standard 1999. After consideration of all submissions, the Ministry will make a recommendation to the Minister of Health to accept, advise revision of, or decline the proposed amendments. 4 Maximum Residue Limits (MRLs) for

Proposal This section provides background on the 10 agricultural compounds and outlines three categories of proposed changes to the MRL Standard 1999. 1 It is proposed to amend the MRL Standard 1999, to regulate the use of the following agricultural compounds to good agricultural or veterinary practices (GAP or GVP) in New Zealand growing conditions by adding new maximum residue limits for the following compounds: Pirlimycin Pirlimycin is used for the treatment of clinical and subclinical mastitis in lactating dairy cattle. It is currently registered in Europe and in the US. It is not licensed for human consumption but is similar to the antibiotic clindamycin, which is used in human medicine. Clindamycin is used occasionally for respiratory tract infections and topical use for acne. Pirlimycin can only be used by or on the order of a licensed veterinarian. It can therefore only be used for the specific treatment of mastitis in cattle and cannot be used broadly (such as being added to feed). The estimated daily intake of Pirlimycin is well below the acceptable daily intake (ADI) for toxicological effects. At these proposed levels, it is considered unlikely for Pirlimycin would pose any risk to human health or that antibiotic resistance through food consumption would develop. The US MRLs range from 0.4 mg/l in milk to 0.5 mg/l in liver. European MRLs range from 0.1 mg/kg in milk, muscle and fat to 1.0 mg/kg in liver. It is proposed that the following MRL entry be added in appropriate alphabetical order to the First Table of the MRL Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Pirlimycin Cattle milk 0.1 mg/kg Cattle liver 0.5 mg/kg Cattle kidney 0.1 mg/kg Cattle fat 0.05 mg/kg Cattle muscle 0.05 mg/kg Maximum Residue Limits (MRLs) for 5

Spectinomycin Spectinomycin is a broad-spectrum antibiotic used for the treatment of piglets, lambs and goat kids. It has been used in human medicine, but is not currently marketed in New Zealand for human use. It is currently registered in Europe and has been considered by Codex. European MRLs are 0.3 mg/kg muscle, 0.5 mg/kg for fat, 2 mg/kg liver and 5 mg/kg kidney. The proposed MRLs are the same as those set by Codex. An ADI has been set by the European Agency for the Evaluation of Medicinal Products (EMEA). When the daily intake of Spectinomycin is below this value it should have no adverse effect on human health. Details of this calculation can be found in Appendix 1. It is proposed that the following MRL entry be added in appropriate alphabetical order to the First Table of the MRL Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Spectinomycin Sheep kidney 5 Sheep liver 2 Sheep fat 2 Sheep muscle 0.5 Tolylfluanid This compound is a broad spectrum fungicide, used generally for preventive application against noxious fungi. It is mainly used on:?? pome fruit, to control apple and pear scab?? berries, to control grey mold, powdery mildews and various leaf spot?? vegetables and ornamentals. Tolylfluanid residue is made up two components: the parent compound Tolylfluanid, and the DMST 4 metabolite. Only the parent compound is considered for MRLs. This is because there are only low levels of the DMST metabolite present (less than 6%), to be in line with Codex, and the availability of suitable analytical methods. The Codex MRL for Tolylfluanid for pome fruit is 5 mg/kg. The proposed MRL of 1.0 mg/kg for Tolylfluanid, with a 14-day withholding period, is unlikely to pose any risk to human health. 4 N, N-dimethyl-N?-p-tolysulphamide. 6 Maximum Residue Limits (MRLs) for

In apple processing studies summarised by JMPR 5 levels of less than 0.1 mg/kg Tolylfluanid and DMST metabolite were found in apple sauce, juice and preserves made from apples containing 0.4 3.6 mg/kg Tolylfluanid. It is proposed that the following MRL entry be added in appropriate alphabetical order to the First Table of the MRL Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Tolylfluanid Apples 1.0 mg/kg 2 It is proposed to amend the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999, to regulate the use of the following agricultural compounds to good agricultural or veterinary practices (GAP or GVP) in New Zealand growing conditions by amending existing maximum residue limits for the following compounds: Eprinomectin Eprinomectin is a semi-synthetic compound used for the treatment of internal and external parasites in cattle and in lactating cows, developed exclusively for veterinary medicine. Eprinomectin comprises eprinomectin B1a (90%) and eprinomectin B1b (10%); with eprinomectin B1a being the marker residue. It is proposed that all MRLs stated for the compound Eprinomectin refer to bovine foods rather than mammalian. By making the Eprinomectin MRLs specific to bovine foods, the maximum residue limits for other mammalian meat fall to the default level. By making the MRLs specific to bovine foods, the MRLs can be increased (as proposed) and therefore the withholding period can be decreased. European MRLs for Eprinomectin are muscle 0.05 mg/kg, fat 0.25 mg/kg, liver 1.5 mg/kg, kidney 0.3 mg/kg and milk 0.02 mg/kg; JECFA 6 MRLs are muscle 0.1 mg/kg, fat 0.25 mg/kg, liver 2 mg/kg, kidney 0.3 mg/kg and milk 0.02 mg/kg. It is proposed that the New Zealand Eprinomectin MRL for milk be reduced from 0.03 mg/kg to 0.02 mg/kg to be consistent with European MRLs. 5 6 Joint Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. Joint Expert Committee in Food Additives. Maximum Residue Limits (MRLs) for 7

The existing entry in the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 reads: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Eprinomectin (as eprinomectin B1a) Mammalian fats, milks 0.03 Mammalian meat other than fat or liver 0.03 Mammalian liver 0.6 Mammalian kidney 0.1 It is proposed that the following MRL entry replace the existing entry for Eprinomectin in the First Table of the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Eprinomectin (as eprinomectin B1a) Bovine muscle 0.05 Bovine fat 0.25 Bovine liver 1.5 Bovine kidney 0.3 Bovine milk 0.02 Indoxacarb Two changes are proposed for the compound Indoxacarb; firstly it is proposed that under Indoxacarb the term apples be amended to pome fruit. Fruit such as pears will then also be covered by this new term. Indoxacarb residues are considered in the same manner for all pome fruit. The second change is to add a new MRL. It is proposed to add an MRL value of 0.5 mg/kg for vegetable brassicas. Indoxacarb is an oxadiazine insecticide effective against lepidotern insects such as caterpillars. The compound has a low volatility because it is made up of a 75:25 ratio of active (S) isomer to inactive (R) isomer. Both the active and inactive isomer are considered in residue analysis. Codex does not currently have an MRL for Indoxacarb. In the US, MRLs for apples are 1.0 ppm and 5.0 ppm for vegetable brassicas; in Australia MRLs are 2.0 ppm for pome fruit and 2.0 ppm for vegetable brassicas. If growers follow the suggested method of treatment, expected residues for vegetable brassicas will range from 0.2 mg/kg for broccoli to 0.5 mg/kg for cabbage. 8 Maximum Residue Limits (MRLs) for

The existing entry in the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 reads: Column 1 Compound Indoxacarb (both isomers) Column 2 Food Apples Column 3 Permissible Proportions (mg/kg) 0.5 mg/kg It is proposed that the following MRL entry replace the existing entry for Indoxacarb in the First Table of the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Indoxacarb (both isomers) Pome fruit 0.5 Vegetable brassicas 0.5 Ivermectin It is proposed to set an MRL for the compound Ivermectin in milk. Ivermectin is a broad spectrum antiparasitic drug 7 for the treatment and control of Ivermectinsensitive internal and external parasites of cattle. The farmer administers it as an oral drench. It is made of a mixture of 22,23-dihydro-avermectin B 1a (80%) and 22,23-dihydro-avermectin B 1b,(20%); 22,23-dihydro-avermectin B 1a is used as the marker residue. An Ivermectin MRL of 0.01mg/kg is proposed for cattle milk, which is the same as the provisional Codex MRL. The existing entry in the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 reads: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Ivermectin Cattle liver 0.10 Cattle fat 0.04 Other liver (except cattle) 0.015 Other fat (except milk fat) 0.02 Other meat 0.01 7 A broad spectrum antiparasitic drug is one that can be used to treat a wide range of parasites. Maximum Residue Limits (MRLs) for 9

It is proposed that the following MRL entry be added to the existing entry for Ivermectin in the First Table of the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Ivermectin Milk 0.01 Meloxicam It is proposed to set an MRL for the compound Meloxicam, a non-steroidal antiinflammatory drug (NSAID). It is used in the treatment of respiratory infection (in combination with appropriate antibiotics) in young cattle. Currently neither Codex nor US FDA MRLs for Meloxicam exist. European MRLs range from 0.015 mg/kg for milk to 0.065 mg/kg for cattle liver and kidney. The existing entry in the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 reads: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Meloxicam Cattle liver 0.05 Cattle kidney 0.035 Cattle meat 0.025 It is proposed that the following MRL entry be added to the existing entry for Meloxicam in the First Table of the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Meloxicam Milk 0.015 10 Maximum Residue Limits (MRLs) for

Nicarbazin Nicarbazin is an effective drug for preventing intestinal and caecal coccidiosis in poultry. It is used for the prevention rather than the treatment of disease. Amendment 4 of the New Zealand (Maximum Residue Limits of agricultural Compounds) Mandatory Food Standard 1999 set Nicarbazin MRLs at 0.2 mg/kg for poultry muscle, poultry offal and poultry fat. This limit has been identified as problematic for poultry producers. This low level creates longer than desired holding periods and restricts poultry producers feeding regimes. Hence this MRL has been reassessed and it has been proposed to amend Nicarbazin MRLs to 0.5 mg/kg for poultry muscle, poultry offal and poultry fat. An MRL of 0.5 mg/kg would allow Nicarbazin to be used in line with good use practices. Australian Nicarbizan MRLs range from 5 mg/kg to 20 mg/kg, and the US Nicarbazin MRL is set at 4 mg/kg. The Codex MRL is set 0.2 mg/kg. The recalculated Nicarbazin National Estimated Daily Intake is a small percentage of the ADI. As a result the proposed MRL of 0.5 mg/kg would be unlikely to pose any risk to public health and, while above the Codex MRL the proposed MRL is significantly below that of other countries. The existing entry in the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 reads: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Nicarbazin Muscle of poultry 0.2 Offal of poultry 0.2 Fat of poultry 0.2 It is proposed that the following MRL entry replace the existing entry for Nicarbazin in the First Table of the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Nicarbazin Muscle of poultry 0.5 Offal of poultry 0.5 Fat of poultry 0.5 Maximum Residue Limits (MRLs) for 11

Prochloraz Prochloraz is a protective fungicide registered and used in New Zealand. It is used on crops such as stonefruit, wheat, barley, avocados and mushrooms to protect crops against brown rot, foliar diseases, anthracnose and brown spot. It is proposed that the residue definition of Prochloraz in the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 be amended to include metabolites that contain the 2,4,6-trichlorophenol moiety as well as the parent compound. This caters for the presence of metabolites. This proposal will bring the Prochloraz MRL in line with Codex. The change in definition will not affect the MRLs. The proposed residue definition of Prochloraz for the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 is: Prochloraz (sum of Prochloraz and its metabolites containing the 2,4,6- trichlorophenol moiety, expressed as Prochloraz. The existing entry in the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999 reads: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Prochloraz Cereals 0.3 Avocados 5 Mushrooms 0.5 Papaya 2 It is proposed that the following MRL entry replace the existing entry for Prochloraz in the First Table of the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999: Column 1 Compound Column 2 Food Column 3 Permissible Proportions (mg/kg) Prochloraz Cereals 0.3 (sum of Prochloraz and its metabolites Avocados 5 containing the 2,4,6-trichlorophenol moiety) Mushrooms Papaya 0.5 2 12 Maximum Residue Limits (MRLs) for

3 It is proposed to amend the MRL Standard 1999, to regulate the use of the following agricultural compounds to good agricultural or veterinary practices (GAP or GVP) in New Zealand growing conditions by exempting the following compound from having an MRL specified... Gibberellic acid It is proposed that gibberellic acid be exempt from an MRL but a limitation on its use be imposed. Gibberellic acid and the gibberellins are naturally occurring plant growth regulators that stimulate cell division and elongation, and thus modify the rate at which plants grow. Growth regulators are defined as pesticides under the Pesticides Act 1979. They are approved for use on a wide range of crops in many countries. The compound used consists of gibberellic acid (GA3) and small amounts of the gibberellins GA4, GA7 and potassium gibberellate. It is proposed that gibberellic acid be used on a wide range of fruit and vegetable crops in New Zealand. Residue studies in a number of countries indicate that residues arising from gibberellic acid cannot be distinguished from those occurring naturally. This leads to difficulty in obtaining accurate residue data that reflect the levels of gibberellic acid arising from its use as a plant growth regulator. Therefore, the control of the maximum amount that can be on the plant can only be established by setting a maximum use rate (exemption from MRL). The US EPA has exempted gibberellic acid from the requirement for a tolerance when used at rates not exceeding 250 g/acre (equivalent to 617 g/ha). Growth regulators fall under the definition of a pesticide under the Pesticides Act 1979, therefore a regulation of its use must be established. It is proposed that gibberellic acid be exempted from the need for an MRL in New Zealand because of its very low mammalian toxicity, therefore very low risk to public health; low use rates proposed for New Zealand; and the very conservative estimate that this proposed use will lead to residues that will contribute less than 4% of the ADI. It is also noted that gibberellins are naturally present in many food crops. It is proposed that the following entry be added to the Second Table of the New Zealand (Maximum Residue Limits of Agricultural Compounds) Mandatory Food Standard 1999: Substance Gibberellic acid (gibberillins GA3, GA4 and GA7 and Potassium gibberellate) Conditions or Limitation As a plant growth regulator applied at <200 g ai/ha/year. Maximum Residue Limits (MRLs) for 13

Assessment of Proposal The proposed amendment to the MRL Standard 1999 assesses the agricultural compounds against the following criteria:?? the need to protect public health?? avoiding unnecessary restrictions to trade?? maintaining consistency between New Zealand food standards and those applying internationally?? the need to meet New Zealand s international obligations. Protection of public health ACVMG has assessed both the residue and toxicological data supplied as part of the registration process for the agricultural compounds. The proposed MRLs reflect the highest level of residue permissible in the specified food commodity that may result from the recommended uses of the agricultural compounds under New Zealand conditions. ACVMG advises that the proposed uses are compatible with the principles of GPVD or GAP. The MRLs are set so that exposures to residues at or below the levels stated in the standard are consistent with international standards for acceptable daily intakes of residues in food. The Ministry of Health, after receiving the proposal from ACVMG, accepts that ACVMG has used internationally accepted procedures and criteria to assess the implications to public health and safety of these levels of residues (potentially) entering the food supply. No adverse health effects in the public are expected from residues of the specified agricultural compounds as a consequence of existing and new uses. The health risk assessment, based on the above criteria, concludes that there is no appreciable risk to people through consumption of a diet containing these agricultural compound residues up to the proposed MRLs. 14 Maximum Residue Limits (MRLs) for

Risk assessment and management Risk assessment for agricultural compound residues consists of assessing the toxicological risk of exposure to these residues and identifying the maximum residue levels which the compounds should not exceed. The risk assessment is carried out by the Ministry of Agriculture and Forestry s ACVMG. ACVMG provides technical support to the Animal Remedies Board and Pesticides Residue Board. ACVMG reviews the toxicological data of the agricultural compounds and advises the Boards as to the toxicological acceptability of any proposed product. All companies wishing to market agricultural compounds for use in New Zealand must register with the Animal Remedies and Pesticides Residues Boards. Companies must submit significant scientific data to show that the compound can be used in a manner that does not have an adverse effect on public health. The data must contain a minimum assortment of scientific studies, showing accuracy and integrity. It should also comply with international guidelines, such as the Organization for Economic Cooperation and Development Guidelines for Testing of Chemicals (OECD 1981), and Good Laboratory Practice (GLP). The studies must include data on acute toxicity, reproduction toxicity, (effect of the compound on reproduction), carcinogenicity and mutagenesis (carcinogenic effect of the compound) to name but a few. Risk assessment in the development of MRLs is based on:?? hazard identification? identification of known or potential adverse health effects in humans produced by agricultural compounds which may be present in a particular food and cause an adverse effect?? hazard characterisation? evaluation of the nature of the adverse effects associated with agents (biological and others) present in food. Also referred to as the dose-response assessment for chemical hazards?? exposure assessment? evaluation of the likely intake of agents (biological and others) via food, as well as exposures from other sources where relevant?? risk characterisation? estimation of the severity and occurrence of known potential adverse health effects in a given population, based on hazard identification, hazard characterisation, and exposure assessment. Hazard identification and characterisation ACVMG evaluates the residue and toxicological data supplied by applicants to identify any adverse health effect that may occur if consumers were exposed to excessive levels of an agricultural compound residue. Hazard characterisation is carried out to estimate the level of exposure to a compound below which no adverse effects are expected. In risk assessment, potential health hazards need to be identified first. In the hazard identification phase of the risk assessment, the results from each toxicity study are examined, with a focus on the relationship between chemical dose and Maximum Residue Limits (MRLs) for 15

toxic effect. Each study uses a range of chemical doses and measures the number and types of different toxicological responses in laboratory animals. From this, the highest dose which does not produce a toxic effect is identified. This is the no observed adverse effect level (NOAEL). The NOAEL is divided by a margin of safety, which usually includes a factor of 10 to account for potentially greater sensitivity of humans as compared with laboratory animals, and an additional factor of 10 to protect sensitive individuals. The result is an acceptable daily intake (ADI). More information on the ADI is provided in Appendix 1. Exposure assessment The exposure assessment estimates how much residue consumers could theoretically be exposed to from all the existing and proposed new uses of the agricultural compound. The Ministry of Health assesses dietary intake and verifies that MAF has assessed intake appropriately based on the best data and processes available, and that the calculations factor in high consumers and sensitive population groups using the Life in New Zealand 24-hour dietary recall survey (Hillary Commission 1991) or other data as appropriate. To assess the potential exposure of consumers, ACVMG calculates the theoretical maximum daily intake (TMDI) and compares this with the ADI. The TMDI calculation is further outlined in Appendix 2. The TMDI calculation includes consideration of the amount of foods eaten from national and overseas food consumption data and estimates the dietary intake of agricultural compounds to help predict any possible consequences of low-level, long-term exposure (that is, chronic exposure). The TMDI calculation deliberately overestimates the potential intake by using data from consumers potentially exposed to the highest level of residues (through their diet) to err on the side of public safety. ACVMG also factors in dietary considerations for different consumption patterns of children to ensure sensitive populations are protected. For most agricultural compounds it is the cumulative effects of long-term exposure that are of concern to the general population, where potential exposure only exists through the diet. Few agricultural compounds pose an acute (short-term) hazard to consumers. The assessment of TMDI is based on the FAO/WHO procedures, Guidelines for Predicting Dietary Intake of Pesticide Residues (WHO 1989). Where appropriate, the procedures were modified to accommodate the 12 recommendations from a 1995 joint FAO/WHO consultation in York, England, for improvement of existing procedures (WHO 1995). The predicted residue intakes from the proposed new uses, in addition to the intake from any existing uses, were in each case found to be below the established ADI for the respective agricultural compound. A residue is deemed acceptable provided that the TMDI is less than the ADI. 16 Maximum Residue Limits (MRLs) for

The following table lists the ADI, the TMDI and the percentage of the ADI that the TMDI represents for the consumers (those potentially exposed to the highest level of residues) for each of the listed agricultural compounds. Agricultural Compound ADI (mg /kg b.w.*/day) TMDI (? g /kg b.w./day) TMDI as % of ADI Eprinomectin 0.01 (EU) 3.97 39.70 Ivermectin 0.001 (NZ/AUS) 0.14 14.00 Meloxicam 0.00125 (EU) 0.16 12.80 Pirlimycin 0.1 (EU) 1.22 1.22 Spectinomycin 0.04 (EU) 2.01 5.03 Tolylfluanid 0.05 (NZ) 5.06 10.12 Nicarbazin 0.4 (Codex) 0.58 0.15 Prochloraz 0.01 (Codex) Indoxacarb 0.02 (NZ) 3.10 15.50 * b.w. = body weight. Risk characterisation A risk characterisation is the expression of health risk in quantitative or qualitative terms. In this case, the expression is the proportion of the ADI represented by the TMDI. The health risks from agricultural compounds, and most other chemicals that are not regarded as carcinogens, are assumed to have a threshold below which no adverse effects are expected in the general population. The risk characterisation therefore relies on the ADI as the benchmark for protection of public health. As already discussed under the hazard identification step, the ADI adds a large margin of safety, resulting in a level well below what is observed to cause the slightest effects in animal studies. To further ensure that a health protective MRL value is reached, the TMDI deliberately overestimates the true agricultural compound residue intake as it does not take into consideration a number of reduction factors, including:?? at harvest most treated crops contain residues well below the MRL?? residues are normally reduced through storage, preparation, commercial processing, and cooking?? it is unlikely that each and every food for which a MRL is proposed will have been treated with the agricultural compound during the lifetime of the consumer. Maximum Residue Limits (MRLs) for 17

As TMDI 8 is less than ADI (TMDI < ADI) then it is highly unlikely that the ADI would be exceeded in practice as long as the major crop uses are covered by permissible proportions (or MRLs). This is particularly true, given that the TMDI overestimates the true agricultural compound residue intake. Implications for trade The MRLs have been recommended on the basis of internationally approved protocols and criteria. The recommended MRLs are designed to protect public health and safety by reinforcing the concepts of GPVD and GAP under New Zealand environmental conditions for domestically produced food. Domestic food production Domestic food production should be facilitated by the proposed new uses. Any apparent restriction has been proposed to reinforce actual GPVD or GAP in New Zealand and should not impose any unnecessary additional costs on producers. Imported foods The proposed changes are the same as more enabling and should facilitate trade. Under the MRL Standard 1999, imported food commodities may comply with either the appropriate Codex food standard for agricultural compound residue limits or the residue limits stated in the MRL Standard 1999. Under the Codex system, if no specific agricultural compound residue commodity standard has been set, then no detectable residue should be found in foodstuffs in trade. The proposed changes to the MRL Standard 1999 could ease the importation of some foodstuffs. 8 If TMDI is greater than ADI (which is not the case for the named agricultural compounds MRLs), this does not necessarily mean that adverse health effects would be expected in consumers. However, the dietary intake estimate must be refined using the national estimated daily intake (NEDI) calculation. The NEDI calculation takes into account a number of factors to refine the estimates of long-term dietary intake of agricultural compound residues, for example, the median residue data from supervised trials, the proportion of crop or food commodity treated and the residue definition. When all the refinements to the calculation have been made, using the best available data, and the estimated intake still indicates the potential for consumers to be exposed to residue levels above the ADI for significant periods of time, then the proposed and existing uses are reviewed. If at this point the intake concerns still cannot be resolved, then the proposed new use may not be accepted. 18 Maximum Residue Limits (MRLs) for

Exported foods The proposed maximum residue limits do not apply to exports. Export food commodities must comply with any requirements of the country receiving the produce. Occasionally, MRLs are set to ensure international market access for the food commodities listed. Such MRLs are often below the 0.1 mg/kg default limit. Consistency with international food standards There is no absolute requirement that the MRLs for New Zealand domestic production to be the same as those set by the Codex or as those for Australia or any other country. This is because the residue limits are nationally specific and relevant to the agricultural environment where similar crops or stock and pest or disease pressures exist. Implications for international obligations The proposed new MRLs are consistent with the obligations of the Trans-Tasman Mutual Recognition Arrangement (the TTMRA) between Australia and New Zealand for setting joint food standards. MRLs for agricultural compounds presently fall outside the scope of the joint Australia New Zealand food standard setting system. This is because the residue limits are nationally specific and relevant to the agricultural environment where similar crops or stock and pest or disease pressures exist. Although the proposed MRLs are for foods sold domestically, under the TTMRA between Australia and New Zealand, New Zealand manufacturers can export foods that meet the New Zealand domestic requirements to Australia. Equally, foods which meet the Australian domestic food requirements may be imported into New Zealand by Australian manufacturers. The ultimate purpose of the TTMRA is to facilitate trade between Australia and New Zealand. The proposed new MRLs are consistent with the obligations of the World Trade Organization (WTO) Agreement on the Application of Sanitary and Phytosanitary (SPS) Measures. The limits have been recommended on the basis of internationally approved protocols and criteria that are accepted by the WTO. In addition, under the MRL Standard 1999, imported food commodities may comply with either the appropriate Codex food standard for agricultural compound residue limits or the New Zealand standard. Maximum Residue Limits (MRLs) for 19

Glossary of Terms Relevant agencies ACVMG ANZFA Codex EMEA ESR FAO JECFA JMPR MAF OECD USEPA WHO Agricultural Compounds and Veterinary Medicines Group Food Assurance Authority of the Ministry of Agriculture and Forestry Australia New Zealand Food Authority Codex Alimentarius Commission The European Agency for the Evaluation of Medicinal Products Institute of Environmental and Scientific Research Food and Agriculture Organization Joint Expert Committee on Food Additives Joint Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues Ministry of Agriculture and Forestry Organization for Economic Cooperation and Development United States Environmental Protection Agency World Health Organization Technical terms ADI ARD GAP GEMS GLP GPVD MRLs NEDI NOAEL NOEL TMDI Isomers Acceptable Daily Intake Acute Reference Dose Good Agricultural Practice Global Environmental Monitoring System Good Laboratory Practice Good Practice in the Use of Veterinary Drugs Maximum Residue Limits National Estimated Daily Intake No Observed Adverse Effect Level No Observed Effect Level Theoretical Maximum Daily Intake Chemicals with different molecular structures but having the same chemical composition 20 Maximum Residue Limits (MRLs) for

Appendix 1: Establishing an ADI The lowest no observed adverse effect level (NOAEL) or no observed effect level (NOEL) is taken from the most sensitive animal species used in the appropriate study. For most compounds where the long-term (chronic) hazard is of concern, appropriate studies are of long-term or lifetime duration. For those compounds that pose a short-term (acute) hazard, then short-term studies are appropriate. The ADI is defined by WHO as being: the daily intake which, during an entire lifetime, appears to be without appreciable risk on the basis of all the known facts at the time (WHO 1987). Without appreciable risk is further defined to mean: the practical certainty that injury will not result even after a lifetime of exposure (WHO 1987). The acute reference dose (ARD) is a quantitative expression of the acceptable amounts of residue that persons may ingest in short-term situations, such as from a single portion or during a single day, without any expectation of harm. Two uncertainty factors (or safety factors) are applied to the NOAEL to establish the ADI or ARD. The first factor (the NOAEL divided by 1 to 10) is to accommodate the variation between species laboratory animals are biologically different to humans. This factor allows for the possibility that people may be even more sensitive to the toxic effects of the chemical than the test system. The second factor is to accommodate the variation in the human species the human population is far more diverse and lives longer in a far more complex environment than do laboratory animal populations. The second factor (NOAEL divided by 1 to 10 again) allows for the possibility that some individuals within the general population may be more sensitive to the toxic effects of the chemical than the majority of the population. Young children are often considered to be part of this group of particularly sensitive individuals. A further factor (NOAEL divided by 1 to 10 a third time) may be used if the toxicological data pack is deficient in some way (but further studies are in progress to rectify the deficiency), or some other circumstance indicates that an even greater margin is required. The ADI or ARD equals the NOAEL divided by the combined factor, usually 100 or 1000, depending on the specific details presented in the toxicological evaluation. Maximum Residue Limits (MRLs) for 21

The following table lists the NOAELs and ADIs established for the agricultural compounds listed in this proposal. Agricultural compound Eprinomectin Ivermectin Meloxicam Pirlimycin Spectinomycin Tolylfluanid Nicarbazin Prochloraz Indoxacarb Gibberellic acid b.w. = body weight NOAEL (mg /kg b.w. /day) 10 100 1.0 0.1 0.125 12.5 200 300 1.0 2.0 ADI (mg /kg b.w. /day) 0.01 (EU) 0.001 (NZ/AUS) 0.00125 (EU) 0.1 (EU) 0.04 (EU) 0.05 (NZ) 0.4 (Codex) 0.01 (Codex) 0.02 (NZ) 3 22 Maximum Residue Limits (MRLs) for

Appendix 2: Calculation of TMDI The TMDI is calculated by multiplying the established or proposed MRLs (or permissible proportions) by the average New Zealand daily per capita estimated consumption for each food commodity. The products are then added up. TMDI = sum of (Fi x MRLi) where Fi = New Zealand per capita food consumption for a given food commodity and MRLi = permissible proportion (MRL) corresponding to that food commodity. The consumption estimates are derived from food balance sheets, based on New Zealand s food production, imports and exports. Waste at the household or individual level is usually not considered. If food consumption data are not available for a commodity, then the consumption value for a similar food is used. MRLs (or permissible proportions) for fat-soluble agricultural compounds are specified for the fat portion of the animal product. Meat (mammalian), poultry meat and milk consumption figures are normally corrected by factors based on the assumption that the average fat contents are 20% for meat, 10% for poultry (with adhering skin) and 4% for whole milk. Where a food is imported in a significant amount it may be more appropriate to use the Codex MRL for that percentage of the crop and the New Zealand MRL for the domestically produced amount. The calculated TMDI, assuming a person s weight of 60 kg, is compared with the agricultural compound s ADI, that is: TMDI / 60 (kg) = ADI (mg/kg body weight). Maximum Residue Limits (MRLs) for 23

References FAO. 1993. Codex Alimentarius Commission Procedural Manual, 8th edition. Rome: Food and Agriculture Organization. FAO. 1988. Pesticide Residues in Food: 1988 evaluations. Part 1 Residues. Rome: Food and Agriculture Organization. Hillary Commission. 1991. Life in New Zealand: Commission report (Volume 1). Wellington: Hillary Commission for Recreation and Sport. OECD. 1981. Guidelines for Testing Chemicals. Paris: Organization for Economic Cooperation and Development. WHO. 1987. Environmental Health Criteria: 70 principles for the safety assessment of food additives and contaminants in food. Geneva: World Health Organization. WHO. 1989. Guidelines for Predicting Dietary Intake of Pesticide Residues. GEMS/Food. Geneva: World Health Organization. WHO. 1995. Recommendations for the Revision of the Guidelines for Predicting Dietary Intake of Pesticide Residues. Report of a FAO/WHO consultation, WHO/FNU/FOS/95.11. Geneva: World Health Organization. 24 Maximum Residue Limits (MRLs) for