Pest Management Regulatory Agency
30 July 2013
ISSN: 1925-0967 (PDF version)
Catalogue number: H113-27/2013-1E-PDF (PDF version)
This page is a summary of the consultation document. If you would like to comment, please request the full consultation document.
To obtain a full copy of Proposed Re-evaluation Decision PRVD2013-01, Mancozeb, please contact our publications office.
Should you require further information please contact the Pest Management Information Service.
Summary
After a re-evaluation of the fungicide mancozeb, Health Canada's Pest Management Regulatory Agency (PMRA), under the authority of the
Pest Control Products Act, is proposing continued registration of most mancozeb uses in Canada and phase-out of certain uses with risk concerns.
An evaluation of available scientific information found that, under the current conditions of use:
The PMRA is soliciting from the public and all interested parties, information that may be used to refine the occupational, dietary, and environmental assessments and/or mitigate risks. During the consultation period, the registrant has the opportunity to provide additional data and propose changes to the use pattern that could be used to address the risk concerns. If additional scientific data and/or changes to the use pattern are not adequate to address the risk concerns, uses of mancozeb will be phased out.
Health Canada's pesticide re-evaluation program considers potential risks as well as the value of pesticide products to ensure they meet modern standards established to protect human health and the environment. Regulatory Directive DIR2001-03, PMRA Re-evaluation Program, presents the details of the re-evaluation activities and program structure. Re-evaluation draws on data from registrants, published scientific reports, information from other regulatory agencies and any other relevant information available.
This proposal affects all end-use products containing mancozeb registered in Canada. The PMRA will consider the information received during the comment period to address risk concerns and will make a final decision on mancozeb after that assessment is complete.
Proposed Re-evaluation Decision PRVD2013-01, Mancozeb is a consultation document that summarizes the science evaluation for mancozeb and presents the reasons for the proposed re-evaluation decision.
The information in Proposed Re-evaluation Decision PRVD2013-01, Mancozeb is presented in two parts. The Overview describes the regulatory process and key points of the evaluation, while the Science Evaluation provides detailed technical information on the human health, environmental and value assessment of mancozeb.
The PMRA will accept written comments on Proposed Re-evaluation Decision PRVD2013-01, Mancozeb up to 60 days from the date of publication of Proposed Re-evaluation Decision PRVD2013-01, Mancozeb. Please forward all comments to Publications.The key objective of the Pest Control Products Act is to prevent unacceptable risks to people and the environment from the use of pest control products. Health or environmental risk is considered acceptable if there is reasonable certainty that no harm to human health, future generations or the environment will result from use of or exposure to the product under its conditions or proposed conditions of registration. The Act also requires that products have value when used according to the label directions. Conditions of registration may include special precautionary measures on the product label to further reduce risk.
To reach its decisions, the PMRA applies hazard and risk assessment methods as well as policies that are rigorous and modern. These methods consider the unique characteristics of sensitive subpopulations in both humans (for example, children) and organisms in the environment (for example, those most sensitive to environmental contaminants). These methods and policies also consider the nature of the effects observed and the uncertainties present when predicting the impact of pesticides. For more information, please refer to the following:
Before making a re-evaluation decision on mancozeb, the PMRA will consider all comments received from the public in response to this consultation document. The PMRA will then publish a Re-evaluation Decision on mancozeb, which will include the decision, the reasons for it, a summary of comments received on the proposed registration decision and the PMRA's response to these comments.
For more details on the information presented in this summary, please refer to the Science Evaluation of Proposed Re-evaluation Decision PRVD2013-01, Mancozeb.
Mancozeb is a protectant contact fungicide with multi-site mode of action belonging to resistance management group M3 (British Crop Protection Council, 2004). It is used to control a broad spectrum of plant diseases on a wide variety of crops. Mancozeb belongs to the group of fungicides commonly known as ethylene bis (dithiocarbamates) (EBDCs), along with the active ingredients maneb, metiram and nabam. It should be noted that in Canada, nabam has no registered food uses and maneb has been voluntarily discontinued, which leaves use on food crops to mancozeb and metiram only. The EBDCs decompose to ethylene thiourea (ETU), whose cumulative risk profile is also being taken into account.
Uses of mancozeb belong to the following use-site categories: Forest and Woodlots; Ornamentals Outdoors; Greenhouse Food Crops; Industrial Oilseed Crops and Fibre crops (crops grown only for seed, non-food and non-feed); Seed Treatments Food and Feed; Terrestrial Feed Crops; and Terrestrial Food Crops. Mancozeb is applied using conventional ground or aerial application equipment, and drill box or slurry seed treatment equipment by farmers, farm and greenhouse workers and professional applicators. There is no residential use of mancozeb registered in Canada.
Risks of concern have been identified from dietary exposure to the ETU metabolite of mancozeb and for specific worker exposures to mancozeb.
Mancozeb is a broad spectrum fungicide of the ethylene bis(dithocarbamate) (EBDC) group of fungicides (metiram, maneb, zineb and nabam) that also metabolizes in the body and the environment to the common metabolite of the EBDC fungicides, ETU.
Potential exposure to mancozeb may occur through the diet, when handling the product or by entering treated sites. Similarly potential exposure to ETU may also occur through the diet, when handling the product or by entering treated sites, where application of the EBDC group of fungicides has occurred. When assessing health risks, two key factors are considered:
The dose levels used to assess risks are established to protect the most sensitive human population (for example children and nursing mothers).
Toxicology studies in laboratory animals describe potential health effects from varying levels of exposure to a chemical and identify the dose where no effects are observed.
Mancozeb is of low acute oral and inhalation toxicity to the rat and low dermal toxicity to the rabbit. It is a severe eye irritant and slight skin irritant to rabbits and is a dermal sensitizer in guinea pigs.
ETU is of low-moderate acute oral toxicity to pregnant/ non-pregnant mice, hamsters and rats. It is of low acute dermal and inhalation toxicity to rabbits and rats, respectively, non-irritating to rabbit skin and eyes, and is a dermal sensitizer in guinea pigs.
The primary endpoints for animals exposed to mancozeb are effects on the eye (bilateral retinopathy and loss of photoreceptor cells), thyroid and embryo-fetal loss. In a two-generation rat reproductive toxicity study, there was no effect on reproduction. At the highest dose tested, pups had delayed eye opening, in the presence of maternal toxicity. In a published mouse reproductive toxicity study, there was an increase in adverse effects on the reproductive system. When mancozeb was given to pregnant animals, effects on the developing fetus were observed at doses that were toxic to the mother. Due to the nature of these endpoints and their potential implications on the health of the fetus, additional factors were applied in the risk assessment to further reduce the allowable level of exposure to mancozeb.
For ETU, the most sensitive endpoints in laboratory animals were developmental, liver and thyroid effects. Based on supplemental reproduction toxicity studies, the thyroid was the primary target in adult rats and mice and the primary effect in pups was decreased survival. Developmental toxicity occurred via the oral and dermal routes of exposure, with rats being the most sensitive species. After dermal exposure on gestation days 12-13, all fetal rats had marked skeletal malformations, at non-maternally toxic doses. Although maternal thyroid toxicity is often associated with developmental effects, this potential thyroid-mediated mode of action was not applicable to developmental effects resulting from acute exposure as ETU was a direct developmental toxin in the rat. In published studies, no developmental effects were noted in hamsters or guinea pigs. In mice, the only developmental effect observed was an increase in incidence of supernumerary ribs. Cats had malformations in their offspring at doses that were also toxic to mothers. Rats may have a differential sensitivity because of the way ETU is metabolized, compared to the mouse, rabbit, hamster, guinea pig and cat.
Cancer concerns exist for mancozeb based on ETU, a metabolite of mancozeb. ETU has been shown to cause thyroid cancer in both mice and rats and liver cancer in female mice. The mutagenic test data on ETU yielded both positive and negative results.
The risk assessment compares the level of human exposure to the dose at which adverse effects occurred in animal tests.Dietary risks from food and water are of concern.
Dietary risks from food are not of concern for mancozeb. However, the cancer dietary risk from food and by extension from food and water is of concern for ETU.
Reference doses define levels to which an individual can be exposed over a single day (acute) or lifetime (chronic) and expect no adverse health effects. Generally, dietary exposure from food and water is acceptable if it is less than 100% of the acute reference dose or chronic reference dose (acceptable daily intake). An acceptable daily intake (ADI) is an estimate of the level of daily exposure to a pesticide residue that, over a lifetime, is believed to have no significant harmful effects.
Dietary exposure was estimated for mancozeb as well for the ETU metabolite. As mancozeb is not expected to occur in drinking water, the mancozeb assessment includes chronic and acute risk estimates from food consumption only whereas the ETU assessment includes acute, and chronic risk estimates from consumption of both food and water. In addition, a cancer risk assessment was conducted for ETU from exposure through food and drinking water.
The acute exposure from food only for mancozeb is 37% of the acute reference dose for females 13 to 49 years of age, and is less than 2% for all other subpopulations. The chronic exposure is 2.5% of the ADI for the general population and ranges from 1.7% to 10% for all subpopulations, the most exposed subpopulation being the children aged 1 to 2 years old. Thus, acute and chronic dietary risks are not of concern.
During the re-evaluation it was determined that ETU is a residue of toxicological concern. As a result, toxicological endpoints were determined for this metabolite and separate acute, chronic and cancer dietary risk assessments were conducted.
The acute exposure from food only for ETU is 25% of the acute reference dose for females 13 to 49 years of age. The chronic exposure is 12% of the ADI for the general population and ranges from 8% to 43% for all subpopulations, the most exposed subpopulation being children 1 to 2 years of age. Thus, acute and chronic dietary risks are not of concern. However, the cancer risk from dietary exposure of the general population to ETU was 4 × 10-6 for food alone and is of concern. A lifetime cancer risk that is less than 1 × 10-6 (one in a million) is usually considered acceptable risk for the general population when exposure occurs from pesticide residues in or on food, and to persons otherwise unintentionally exposed. Further information on how the potential cancer risks from pesticides are assessed can be found in the Science Policy Notice SPN2000-01, A Decision Framework for Risk Assessment and Risk Management in the Pest Management Regulatory Agency.
The aggregate acute exposure of ETU (from food and drinking water) is 49% of the acute reference dose for females aged 13 to 49 years. The aggregate chronic exposure is 22% of the ADI for the general population and ranges from 17% to 58% of the ADI for all subpopulations, the most exposed subpopulation being all infants less than 1 year old. Thus, acute and chronic aggregate (food + water) risks are not of concern. However, the aggregate cancer risk for the general population was 8 × 10-6 and is of concern.
Non-occupational risks from spray drift exposure or from being a patron of a "Pick Your Own" facility are not of concern.
Mancozeb is not registered for residential uses; however, bystander exposure may occur when a pesticide drifts from target spray areas and travels to nearby fields or residential areas during or shortly after application. Risk estimates associated with bystander inhalation exposure, are not of concern, for adults, youths and children.
Exposure of the general population could also occur by participating in "pick your own" (or U pick) activities. "Pick Your Own (PYO)" facilities are considered commercial farming operations that allow public access for harvesting in large-scale fields or orchards treated with commercially labelled mancozeb products. Risk estimates associated with exposure incurred during harvesting activities, are not of concern, for adults, youths and children.
Aggregate risk from spray drift or from being a patron of a "Pick Your Own" facility was not assessed.
An aggregate risk assessment combining exposure from food and drinking water and non occupational exposure was not conducted, as exposure to the ETU metabolite from either food alone or food plus water is of concern.
Most occupational risks to handlers are not of concern when used according to revised label directions.
Most occupational risks are not of concern for agricultural scenarios. Based on the precautions and directions for use on the original product labels reviewed for this re-evaluation, risk estimates associated with certain mixing, loading and applying activities reach target Margins of Exposure (MOEs) and are not of concern. For those uses that failed to reach the target endpoints, mitigation measures such as additional personal protective equipment, engineering controls and restrictions on the amount handled per day are required to reduce potential exposure and protect workers' health. Cancer risks are not of concern with the additional personal protective equipment and engineering controls required to reach non-cancer targets.
There are a few seed treatment scenarios (commercial treatment and on-farm treatment with dry application) where exposure estimates do not reach target MOEs even when mitigation measures are considered. Cancer risks are also of concern for on-farm seed treatment (dry application) of oat seed.
Postapplication risks are not of concern for most uses provided additional mitigation measures are followed. Some of these mitigation measures may not be agronomically feasible.
Postapplication occupational risk assessments consider exposures to workers entering treated sites in agriculture. Based on the current use pattern for agricultural scenarios reviewed for this re-evaluation, postapplication risks to workers performing activities, such as thinning, pruning and scouting of some crops, did not meet current standards and are of concern. However, when the proposed mitigation measures such as lengthened restricted entry intervals (REIs) are considered, the risks to postapplication workers are not of concern for most crops. Some of the proposed REIs are not agronomically feasible such that the lengthened REIs are not a viable risk mitigation measure option.
For greenhouse tomatoes, the risks to workers performing any postapplication activity are of concern.
There are incidents reported for human health involving mancozeb in Canada. Incident reports for mancozeb have involved skin rashes or contact dermatitis, nausea, dizziness, eye irritation and minor gastrointestinal upset in humans, and moderate nervous system effects in one report involving animals.
Mancozeb poses a potential risk to terrestrial and aquatic organisms, therefore additional risk reduction measures need to be observed. ETU is a transformation product of mancozeb and other ethylene bis(dithiocarbamate) (EBDC) pesticides, that poses a potential risk to terrestrial mammals, therefore, risk-reduction measures are required with the use of the parent mancozeb.
When mancozeb is released into the environment it decomposes rapidly via hydrolysis into mancozeb complex, which consists of variable/low molecular weight polymeric chains (polymer fragments), monomeric species, intermediate species, transformation products and other un-identified materials. In the terrestrial environment, mancozeb complex is non-persistent and binds strongly to soils, therefore, mancozeb parent and mancozeb complex are not expected to leach into groundwater.
ETU is a transformation product formed from mancozeb and other EBDC pesticides (for example, metiram, maneb, nabam). It is not used for pest control like true pesticides. ETU forms via chemical reactions in water, through action of light and by microbial action after the application of mancozeb to the environment. ETU undergoes rapid breakdown in soil, through microbial action but the rate depends on the soil moisture levels and could be slightly to moderately persistent in soil. ETU generally does not bind strongly to soils and has high to very high mobility in soil, indicating it could reach surface water and groundwater. Canadian water monitoring data have confirmed ETU detections in surface water but not in groundwater.
In the aquatic environment, mancozeb complex formed after the rapid hydrolysis of mancozeb parent is slightly persistent under aerobic conditions. Anaerobic aquatic conditions appear to be conducive for slowing down mancozeb parent transformation. Therefore, mancozeb complex is expected to persist longer under anaerobic conditions. ETU is slightly persistent in the aquatic environment under aerobic conditions and moderately persistent to persistent under anaerobic conditions. Mancozeb residues are not expected in the air because of its low volatility and it has a low potential for bioaccumulation in biota. ETU may partition into air as indicated by its high vapour pressure, however, if it reaches air it is unlikely to be persistent (T1/2 ranges from <2 hours to 9 days). ETU has a low potential for bioaccumulation in biota.
Mancozeb may pose a risk to beneficial arthropods used in Integrated Pest Management programs, birds, small wild mammals, and to aquatic organisms. ETU may also pose a risk to small wild mammals. The risk to beneficial predatory arthropods from mancozeb triggers a requirement for precautionary label statements. Birds and small wild mammals are at risk from feeding on treated seed and in and around areas of foliar application due to the consumption of contaminated food items. To reduce exposure to birds and small wild mammals associated with feeding on treated seed, an environmental hazard statement will be added to all seed treatment product labels stating that any spilled or exposed seeds must be incorporated into the soil or otherwise cleaned-up from the soil surface. Options to reduce the risk to birds and mammals posed by foliar spray applications are limited. In order to minimize the potential exposure of aquatic organisms to mancozeb, an unsprayed area (spray buffer zone) is needed between the sprayer and downwind sensitive habitats. The width of these spray buffer zones will be specified on the product label. Aquatic organisms will be at negligible risk due to the formation of ETU from the use of mancozeb.
There are currently no environmental incident reports involving mancozeb in Canada.
Mancozeb is registered for use on a broad range of food and non-food sites for the control of a wide range of economically important fungal diseases.
In Canada, mancozeb is registered to control a broad range of pests including control of some of the most destructive plant diseases: early and late blights (Alternaria solani and Phytophthora infestans, respectively) of tomatoes and potatoes; downy mildew (Plasmopara viticola) of grapes; downy mildew (Pseudoperonospora cubensis) of cucurbits, apple scab (Venturia inequalis) and cercospora blight of sugarbeets (Cercospora beticola) to name a few. End-use products containing mancozeb encompass one of the broadest ranges of label uses of any fungicide in Canada including over 40 crop and non-agricultural sites and more than 70 diseases.
Mancozeb remains a key fungicide for sustainable pest management on several important crops and diseases. To date there are no recorded incidences of resistance, despite a long history of use against high risk diseases, due to its multi-site mode of action that helps manage fungicide resistance development to other active ingredients.
In Canada mancozeb has been used extensively in agriculture and horticulture for over 45 years and is an integral component of many pest management programs to slow down or prevent the development of fungal isolates that are resistant or at high risk to develop resistance to other fungicides. It is an essential tool for maintaining the continued availability of many other fungicides having a single site mode of action and that are at high risk for the development of resistance. Mancozeb provides an efficient and economical method of controlling a broad spectrum of fungal diseases. Mancozeb is the co formulation, tank-mixing or rotational partner of choice for many older, as well as newer lower risk fungicides. Mancozeb is the product of choice for the following uses:
Some uses of mancozeb have few or no registered or viable alternative active ingredients.
Mancozeb has several uses, with few or no registered or viable alternatives, that were registered through the User Requested Minor Use Label Expansion (URMULE) program including:
Labels of registered pesticide product include specific instructions for use. Directions include risk-reduction measures to protect human and environmental health. These directions must be followed by law. As a result of the re-evaluation of mancozeb, the PMRA is proposing further risk-reduction measures in addition to those already identified on mancozeb product labels. Additional risk-reduction measures are discussed below.
Based on available data and current assessments showing potential health and environment risks, Health Canada is proposing phase-out of some uses of mancozeb. These uses include commercial (slurry and dry application) and on-farm (dry application) seed treatment for barley, corn, flax, oat and wheat, and potato seed piece and application on orchard crops including apples, pear, grapes and greenhouse tomato. During the transition to phase-out, additional measures are proposed to reduce potential risk. The additional measures are discussed in Section 9.1 of Proposed Re-evaluation Decision PRVD2013-01, Mancozeb.
To protect mixer/loader/applicators:
To protect workers entering treated sites:
To mitigate potential aggregate risk from use of multiple EBDC:
Additional toxicology, exposure and environment data are required as a condition of continued registration under Section 12 of the Pest Control Products Act. The registrants of this active ingredient must provide these data or an acceptable scientific rationale to the PMRA within the timeline specified in the decision letter. No additional scientific data are being requested for those uses which are proposed for phase-out. However, during the consultation period, the registrants may consider submission of further data or propose changes to the use pattern that could be used to address risk concerns. These data are identified Section 9.2 of Proposed Re-evaluation Decision PRVD2013-01, Mancozeb.
In light of the proposed phase-out of the following uses of mancozeb:
The PMRA requests the following value information for the identified key or important uses, of mancozeb, especially those that are proposed for phase-out:
Health Canada is proposing continued registration of most uses of mancozeb in Canada and phase-out of certain other uses. Further risk mitigation measures are proposed and additional data is required to address potential risk identified in this assessment. As part of the consultation process, the registrant has the opportunity to propose changes to the use pattern and provide additional data to address risk concerns. If additional scientific data and/or changes to the use pattern are not provided or fail to address the risk concerns, uses of mancozeb with risk concerns will be phased out. Following consultation, and consideration of comments received, a final decision document will be published outlining the mitigation measures and confirmatory data requirements.
Before making a re-evaluation decision on mancozeb, PMRA will consider all comments received from the public in response to Proposed Re-evaluation Decision PRVD2013-01, Mancozeb. The PMRA will then publish a Re-evaluation Decision Document, which will include the decision, the reasons for it, a summary of comments received on the proposed decision and the PMRA's response to these comments.