Evaluation Report ERC2012-02, Tembotrione

Pest Management Regulatory Agency
2 October 2012
ISSN: 1911-8082 (PDF version)
Catalogue number: H113-26/2012-2E-PDF (PDF version)

Summary

Table of Contents

• Registration Decision for Tembotrione
• What Does Health Canada Consider When Making a Registration Decision?
• What Is Tembotrione?
• Health Considerations
• Environmental Considerations
• Value Considerations
• Measures to Minimize Risk
• What Additional Scientific Information Is Being Requested?
• Other Information

Registration Decision for Tembotrione

Health Canada's Pest Management Regulatory Agency (PMRA), under the authority of the  Pest Control Products Act and  Regulations, has granted conditional registration for the sale and use of Tembotrione Technical Herbicide containg the technical active ingredient tembotrione and Vios G3, containing the technical grade active ingredients tembotrione and thiencarbazone-methyl to control broadleaf weeds and grasses in field corn.

An evaluation of available scientific information found that, under the approved conditions of use, the product has value and does not present an unacceptable risk to human health or the environment.

Although the risks and value have been found acceptable when all risk reduction measures are followed, the applicant must submit additional scientific information as a condition of registration.

This summary describes the key points of the evaluation, while the Science Evaluation of Evaluation Report ERC2012-02, Tembotrione provides detailed technical information on the human health, environmental and value assessments of Tembotrione Technical Herbicide and Vios G3.

What Does Health Canada Consider When Making a Registration Decision?

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 or exposure to the product under its 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 modern, rigorous risk-assessment methods and policies. These methods consider the unique characteristics of sensitive subpopulations in humans (for example, children) as well as 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 when predicting the impact of pesticides. For more information on how the PMRA regulates pesticides, the assessment process and risk-reduction programs, please refer to the following:

• Protecting Your Health and the Environment
• Pesticide Registration Process
• Pesticide Risk Reduction Program

What Is Tembotrione?

Tembotrine is an active ingredient in Vios G3. Vios G3 contains 350 g/L of tembotrione, as well as 70 g/L of the registered active ingredient thiencarbazone-methyl. 

Vios G3 is a post-emergence herbicide that is applied to field corn using ground application equipment to control broadleaf and grassy weeds. Tembotrione inhibits the plant growth enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) in target weeds, affecting their growth and killing them in about 2 weeks.

Health Considerations

Can Approved Uses of Tembotrione Affect Human Health?

Tembotrione is unlikely to affect your health when used according to label directions. 

Potential exposure to tembotrione may occur through the diet (food and water) or when handling and applying the product. When assessing health risks, two key factors are considered:

• the levels where no health effects occur and
• the levels to which people may be exposed.

The dose levels used to assess risks are established to protect the most sensitive human population (for example, children and nursing mothers). Only uses for which the exposure is well below levels that cause no effects in animal testing are considered acceptable for registration. 

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. The health effects noted in animals occur at doses more than 100 times higher (and often much higher) than levels to which humans are normally exposed when tembotrione products are used according to label directions. 

The technical grade active ingredient Tembotrione was found to be a potential dermal sensitizer and requires the statement "Potential Skin Sensitizer" on the label.  

The end-use product Vios G3 was mildly irritating to the eye. For this reason, the statement "Caution - eye irritant" is required on the label. 

Tembotrione was not genotoxic. There was no evidence of carcinogenicity in the mouse. However, in long-term studies, there was evidence that tembotrione caused squamous cell carcinomas in the eye in rats due to long-term effects on that organ. There were indications that tembotrione potentially caused damage to the nervous system in rats and dogs at doses that caused other effects in test animals. The main signs of toxicity in animals given daily doses of tembotrione over longer periods of time were white areas on the eyes and keratitis-related changes to the cornea, mild haemorrhagic changes and liver, kidney and pancreatic changes. The risk assessment protects against these effects by ensuring that the level of human exposure is well below the lowest dose at which these effects occurred in animal tests. 

When tembotrione was given to pregnant animals, effects on the developing fetus were observed at doses that were toxic to the mother. However, since effects in the fetus were of a more severe nature than those seen in the mother, the fetus is considered more sensitive to tembotrione than the adult animal. Because of this observation, extra protective measures were applied during the risk assessment to further reduce the allowable level of human exposure to tembotrione.

Residues in Water and Food

Dietary risks from food and water are not of concern. 

Aggregate dietary intake estimates (food plus water) revealed that the general population and infants, the subpopulation which would ingest the most tembotrione relative to body weight, are expected to be exposed to less than 96% of the acceptable daily intake. Based on these estimates, the chronic dietary risk from tembotrione is not of concern for all population sub-groups. Tembotrione is not carcinogenic, therefore a chronic cancer dietary risk assessment is not required. 

An aggregate (food and water) dietary intake estimate for the highest exposed population (infants) was 136% of the acute reference dose. However, this is considered acceptable, since the estimation is highly conservative and the use of tembotrione in Vios G3 has been granted a 3 year conditional registration pending the submission of additional environmental studies to refine the dietary exposure to water.  

The  Food and Drugs Act prohibits the sale of adulterated food, that is, food containing a pesticide residue that exceeds the established maximum residue limit (MRL). Pesticide MRLs are established for Food and Drugs Act purposes through the evaluation of scientific data under the Pest Control Products Act. Food containing a pesticide residue that does not exceed the established MRL does not pose an unacceptable health risk. 

Residue trials conducted throughout Canada and the United States using tembotrione on corn were acceptable to support the domestic uses. No new MRLs in/on corn are recommended at this time as MRLs for corn (field, sweet and pop) were previously recommended to cover residues in imported commodities. The MRLs for this active ingredient in animal commodities as a result of domestic use on field corn can be found in the Science Evaluation of Evaluation Report ERC2012-01, Tembotrione.

Occupational Risks From Handling Vios G3

Occupational risks are not of concern when Vios G3 is used according to the label directions, which include protective measures.

Farmers and custom applicators who mix, load or apply Vios G3, as well as field workers re-entering freshly treated fields, can come in direct contact with tembotrione residues on the skin or through inhalation of spray mists.

Therefore, the label will specify appropriate personal protective equipment such as long-sleeved shirt, long pants, chemical-resistant gloves, socks and shoes, chemical-resistant coveralls, goggles or faceshield, or engineering controls for anyone conducting specific tasks with the end-use product. In addition, restrictions on the amount of product handled per day, and restricted-entry intervals for certain post-application activities are required. Taking into consideration these label requirements, risks to agriculture workers are not of concern.

For bystanders, exposure is expected to be much less than that of field workers and is considered negligible. Therefore, health risks to bystanders are not of concern.

Environmental Considerations

What Happens When Tembotrione Is Introduced Into the Environment? 

Tembotrione is highly mobile and exhibits variable persistence in soil. It is considered to have the potential to leach. Specific information is required to understand the extent of its persistence in different kinds of soils and the potential risk of leaching to groundwater. Tembotrione is toxic to small mammals, terrestrial plants, freshwater vascular plants, and estuarine/marine invertebrates. Tembotrione poses a negligible risk to earthworms, honey bees, birds, freshwater invertebrates, freshwater and marine fish, and freshwater and marine algae.

Tembotrione exhibits variable persistence in both soil and water. The abiotic processes of hydrolysis, phototransformation and volatilization are not significant transformation/dissipation pathways. Tembotrione residues are not expected to be present in the atmosphere, nor is long-range aerial transport expected as a result of volatilization. The octanol-water partition coefficient (log K_ow -1.07 at pH 7) indicates that there is limited potential for bioaccumulation in organisms.
 
Tembotrione is stable to anaerobic biotransformation in the terrestrial environment. Aerobic biotransformation in soil is an important transformation route, though tembotrione transforms at significantly different rates in different soils. Based on submitted information, it was determined that the 80^th percentile of the aerobic soil biotransformation half-life values was 127 days. Laboratory studies indicate that tembotrione is expected to have high to very high mobility in soils. Since the pKa is 3.2, tembotrione is expected to be dissociated into its anionic form at environmentally relevant pH, and is therefore more likely to leach in neutral to alkaline soils.

Tembotrione is very highly soluble in water (28.3 g/L at pH 7). In aquatic systems, it is stable to hydrolysis and anaerobic biotransformation. In aerobic aquatic biotransformation studies, tembotrione partitioned from water into the sand or sediment. The biotransformation half-lives ranged from 64-222 days in the water/sediment systems. The environmental risk assessment for tembotrione was conducted with a tembotrione alone product at a seasonal rate of 184.8 g/ha per year. At the 184.8 g/L rate, tembotrione is expected to reach ground water. However, the rate of tembotrione applied with Vios G3 is 38.5 g/ ha year.

In the terrestrial field dissipation study in an eco-region relevant to Canada, the dissipation half-life was 11.4 days, and tembotrione was not detected below the top 15 cm of the soil profile. Although this suggests a lack of persistence under field conditions, it is possible that leaching below the depth of interest occurred.

Tembotrione has six transformation products relevant to the environment. They are labeled M1 through M4, and M6 and M7. Though they show moderate to very high mobility in soil, they are not persistent. None of the transformation products were shown to be of ecotoxicological concern.

Non-target organisms that may be vulnerable to adverse effects resulting from potential tembotrione exposure include terrestrial plants, freshwater aquatic plants, estuarine/marine invertebrates, and small mammals.

Value Considerations

What Is the Value of Vios G3

Vios G3, a post-emergence herbicide, controls broadleaf weeds and grasses in field corn. 

Vios G3 is a post-emergence herbicide for the control of certain broadleaf weeds and grasses in field corn. A single application of 46 g ai/ha Vios G3 provides control and suppression of certain weeds.  

Application of Vios G3 is compatible with integrated weed management practices and with conservation tillage and conventional crop production systems. Vios G3 is a post-emergence herbicide applied after weeds have emerged. Growers can therefore better assess whether the herbicide is necessary or suitable for particular weed species. Vios G3 can be used in tank mix with glyphosate.  

Although several herbicides for post-emergence control of grasses in field corn are available, they are limited to Herbicide Groups 2 and 15. Vios G3, containing tembotrione as a Group 27 Herbicide, provides Canadian corn growers with an alternative product to control grasses that are developing resistance to existing chemistries.

Measures to Minimize Risk

Labels of registered pesticide products include specific instructions for use. Directions include risk-reduction measures to protect human and environmental health. These directions must be followed by law. 

The key risk-reduction measures on the label of Vios G3 to address the potential risks identified in this assessment are as follows.

Key Risk-Reduction Measures

Human Health

Because there is a concern with farmers, custom applicators, or fieldworkers re-entering freshly treated fields coming into direct contact with Vios G3 on the skin or through inhalation of spray mists, anyone mixing, loading and applying Vios G3 must wear appropriate personal protective equipment.

The Vios G3 label specifies that anyone mixing/loading or applying the product must wear chemical-resistant coveralls and shoes plus socks. Workers mixing/loading Vios G3 must also wear chemical-resistant gloves and protective eyewear. Workers must not apply Vios G3 Herbicide to more than 150 hectares per day. The Vios G3 label requires that workers do not enter treated fields for 12 hours after application.

In addition, standard label statements to protect against drift during application were added to the product label.

Environment

Due to the risks identified for tembotrione, specific mitigation measures are necessary to protect the environment. In order to protect terrestrial and nearby freshwater and estuarine/marine habitats, both aquatic spray buffer zones (1 m) and terrestrial spray buffer zones (10 m) have been determined to be necessary for tembotrione-containing end-use products. If tembotrione is applied in combination with other pesticides, the most restrictive spray buffer zones must be observed. Toxicity label statements are required for sensitive organisms including non-target plants, aquatic invertebrates, and small mammals.

What Additional Scientific Information Is Being Requested?

Although the risks and value have been found acceptable when all risk-reduction measures are followed, the applicant must submit additional scientific information as a condition of registration. More details are presented in the Science Evaluation of Evaluation Report ERC2012-02, Tembotrione or in the section 12 Notice associated with these conditional registrations.

Human Health

To further refine the dietary exposure to tembotrione residues in water, additional environmental studies are required to estimate adequate Estimated Environmental Concentration values.

Environment

Assessments identified a high potential for tembotrione to leach to groundwater in certain use situations. The potential for reaching groundwater occurs under conditions reflective of major use areas. Additional data are required to aid in further characterizing the potential of tembotrione leaching to groundwater. The required data will be derived from four outdoor lysimeter studies which are to be conducted in Canada on soils with a pH range of 5.8-7 (pH measured in water).

Value 

Data are required from additional field trials in which the efficacy of the tank mix of glyphosate + Vios G3 at 46 g ai/ha is directly compared to that of glyphosate + a thiencarbazone-methyl alone formulation to confirm the tembotrione value at the current rate of 38.5 g ai/ha. Data are to be generated for WSSA Group 2 resistant weeds wherever possible, in addition to broadleaf weeds.

Other Information

As these conditional registrations relate to a decision on which the public must be consulted, the PMRA will publish a consultation document when there is a proposed decision on applications to convert the conditional registrations to full registrations or on applications to renew the conditional registrations, whichever occurs first. 

The test data cited in Evaluation Report ERC2012-02, Tembotrione (i.e. the test data relevant in supporting the registration decision) will be made available for public inspection when the decision is made to convert the conditional registrations to full registrations or to renew the conditional registrations (following public consultation). If more information is required, please contact the PMRA's Pest Management Information Service.