U.S. Environmental Protection Agency Office of Pesticide Programs Details of the Consultation for Department of State Use of Pesticide for Coca Eradication Program in Colombia, August 2002

Table of Contents

Executive Summary

1. Section 1. Description of Glyphosate Use in the U.S. For Comparison To Use in Colombia For Coca Eradication

   1. Use of Glyphosate in the United States Agricultural Use Sites
   2. Non-Agricultural Uses Including Forestry
   3. Properties of Glyphosate
   4. Formulation of Glyphosate
   5. Glyphosate Used With Surfactant For Foliar Absorption

2. Section 2. Human Health Risk Assessment For the Use of Glyphosate Herbicide As Part of the Aerial Eradication Program of Coca in Colombia, S.A.

   1. Hazard Identification
   2. Dose Response Assessment
   3. Exposure Assessment

3. Section 3. Review of Glyphosate Incident Reports With Special Reference To the Aerial Spraying Program in Colombia

   1. California Data–1982 Through 2000
   2. Literature Review
   3. A Study of Health Complaints Related To Aerial Eradication in Colombia
   4. Conclusions

4. Section 4. Ecological Risk Assessment For the Use of Glyphosate Herbicide As Part of the U.S. Supported Aerial Eradication Program of Coca in Colombia

   1. Background
   2. Ecological Risk Assessment
   3. Potential Spray Drift of Glyphosate
   4. Environmental Fate And Transport Assessment of Glyphosate
   5. Risk Characterization

EXECUTIVE SUMMARY

CONSULTATION REVIEW OF THE USE OF PESTICIDE FOR COCA ERADICATION IN COLOMBIA

The Department of State currently assists the Government of Colombia with training, contractor support, financial assistance, and technical and scientific advice for an aerial pesticide spraying program designed to eradicate illicit crops (coca and poppy). In accordance with a provision in its 2002 Appropriations Bill, Department of State has consulted with the U.S. Environmental Protection Agency (EPA) on two specific questions: that fumigation is "...being carried out in accordance with regulatory controls required by the Environmental Protection Agency as labeled for use in the United States" and, that the chemicals being used "...in the manner they are being applied, do not pose unreasonable risks or adverse effects to humans or the environment."

FINDINGS

EPA has reviewed information provided by Department of State concerning the pesticide formulation applied (combination of the pesticide active ingredient, glyphosate, and inert ingredients), and application rates and methods. According to the most recent figures (1999 sales and usage) glyphosate is the most widely used conventional pesticide in the United States. The Agency evaluates all pesticides used in the U.S. to determine whether they meet the U.S. safety standard of no unreasonable adverse effects. Consequently, EPA has a significant amount of information about glyphosate from a health and environmental standpoint because of our reviews of use conditions in the U.S. In the U.S., the Agency can assure significant controls on use and potential health and environmental impacts through the pesticide label, and through a state infrastructure which governs label compliance to address issues such as drift and worker and bystander exposure.

Based on a comparison of the glyphosate use pattern in Colombia, as described by the Department of State, and use in the U.S., EPA determined that the most equivalent U.S. uses of glyphosate would be forestry or rights-of-way. The glyphosate product which has been identified to us as used in Colombia is registered in both the U.S. and Colombia, although it has never been marketed in the U.S. The Agency found application rates described as used in Colombia to be within the parameters listed on U.S. labels. The addition of a spray adjuvant (to facilitate the formulation adhering to and penetrating the coca plant) is also in keeping with U.S. practice. While the specific spray adjuvant product identified as that used in Colombia is not sold in the U.S., similar substances and products are commonly used. Most U.S. labels for forestry and right-of-way use of glyphosate suggest application by helicopter. Since application in Colombia is done by fixed-wing aircraft, it is likely conducted at a higher speed and from a greater altitude, than would be typical in the U.S. Department of State has assured the Agency that mixers/loaders and applicators of the glyphosate formulation receive training comparable to U.S. label requirements for glyphosate products including the use of personal protective equipment such as gloves and goggles.

As for potential human health effects of the coca eradication program, there are no risks of concern for glyphosate, per se, from dermal or inhalation routes of exposure, since toxicity is very low. There is concern for acute eye toxicity due to an inert ingredient in the glyphosate formulated product used to treat coca. The potential eye effects are related to an inert ingredient, not the glyphosate itself, and greatest potential for exposure is expected for workers mixing and loading the concentrated glyphosate product. The components of the spray adjuvant, Cosmoflux 411F, are substances with low oral and dermal toxicity that have been approved for use in/on food by EPA and the Food and Drug Administration. There are no expected toxicological effects of concern for acute (short-term) or chronic (long-term) dietary exposure through food and water from the coca eradication program. Incident data from Colombia involving humans, livestock, mammals and birds, are based on potential exposure to glyphosate from fumigation of poppy fields, which may differ from use of and exposure to glyphosate from coca eradication, so conclusions should be made cautiously.

Relative to the potential environmental effects of the spraying program based on U.S. data, phytotoxicity to non-target plants outside of the application zone would be expected, since glyphosate is a broad spectrum herbicide. Given the application method described by Department of State, offsite exposure from spray drift is probable, as it would be under similar uses in the U.S. This proposed use of glyphosate itself does not appear to pose a significant direct risk to terrestrial or aquatic animals, although secondary adverse effects from the temporary loss of habitat in the spray area could occur. EPA would not expect any risk to birds and mammals, including livestock, based on dietary exposure to the active ingredient glyphosate. Anticipated effects to animals are based on an extrapolation of data related to North American species. Glyphosate does not have a high potential to leach to ground water or reach surface water as dissolved runoff but does have potential to contaminate surface water as a result of residues suspended in runoff water. A more refined assessment is difficult due to uncertainty regarding the exact formulation of the spray solution.

As part of its consultation, EPA reviewed available scientific studies and information on the human health and environmental effects of glyphosate and the inert ingredients and on exposure pathways; conducted a literature search for human health incidents related to glyphosate use in the U.S.; and summarized use patterns for glyphosate in the U.S., including use sites, methods and rates of application, and differing formulations. In addition, the Agency considered information, provided by non-governmental sources, concerning adverse effects reportedly connected to the eradication program.

Details of the Agency’s findings are provided in the attached document.

SECTION 1. Description of Glyphosate Use in the U.S. for Comparison to Use in Colombia for Coca Eradication

INTRODUCTION: The Biological and Economic Analysis Division (BEAD) within the Office of Pesticide Programs, Environmental Protection Agency, has been asked to describe the use of glyphosate within the United States with a more detailed description of its use in forestry sites so that methods of use in the United States may be used as a basis for comparison for coca eradication in Colombia (1).

SUMMARY: Glyphosate is the herbicide most widely used in the United States¹ (2). In agriculture this popularity is due, in large part, to the development of crops that are highly tolerant to broadcast applications of glyphosate which allows growers to use this non-selective herbicide as their principal method of weed control in certain crops. Growers have rapidly adopted glyphosate-based weed control programs with glyphosate tolerant crops because they are simple and economical (3). In addition, due to it’s unique properties, glyphosate is also widely used for non-agricultural weed control situations including home lawns and gardens, forestry and other non-crop sites where total vegetation control is desired.

Glyphosate must be applied to the target plant’s foliage to be effective. Glyphosate is non-selective in action, controlling a wide variety of plants. Once absorbed, it circulates to untreated portions of the plant; and it has no residual activity after contact with soil. Glyphosate may be applied using hand-held, ground-driven or aerial equipment; the choice of equipment is determined by the site to be treated. Although higher rates of application are allowed, actual rates per application in agricultural sites average less than 0.75 pounds of the active ingredient glyphosate per acre (Table One). For the non-agricultural site, forestry, use is allowed at rates per application ranging from 2 to 10 pounds per acre (2.2 to 11.2 kilograms of active ingredient/ hectare) of glyphosate in the form of the isopropylamine salt (6). This rate of use may also be expressed as 1.5 to 7.5 pounds per acre of acid equivalent (pure glyphosate; not a salt). A more detailed discussion of the use of glyphosate in the U.S. follows.

USE OF GLYPHOSATE IN THE UNITED STATES: Products containing glyphosate are registered with the U.S. Environmental Protection Agency, which means they may legally be used within the United States if used in accordance with label instructions.

Glyphosate may be used on over 400 crop and non-crop sites. The largest agricultural use sites include soybeans, cotton and field corn. The following table summarizes estimates the use of glyphosate in three primary agricultural use sites.

Table One. 2000 Glyphosate Use in U.S. Agriculture: In Total and for the Three Major Use Sites

Site	Acres Grown (million acres)	Base Acres Treated (million acres)1	Percent of Crop Treated2	Total Acres Treated (million acres)3	Pounds Applied (million lbs ai)	Avg. Number of Apps	Avg. Application Rate (lbs ai/acre/app)
All Ag. Sites	–	–	–	102.7	73.5	–	–
Corn	73.8	6.6	9%	7.3	4.4	1.1	0.59
Cotton	14.4	8.1	56%	13.8	9.5	1.7	0.67
Soybeans	71.0	44.0	62%	57.2	41.8	1.3	0.68

Source: USDA, National Agricultural Statistics Service (NASS) 2000 field crop chemical use (May, 2001), and EPA proprietary data.
¹Base acres treated = acres treated 1 or more times with glyphosate.
²Percent of crop treated = base acres treated with glyphosate divided by acres grown.
³Total acres treated = based acres treated with glyphosate multiplied by the average number of applications of glyphosate.

In addition to agricultural use, EPA estimates that 16-22 million pounds of the technical grade active ingredient were applied to non-agricultural sites in 1999 (this is the most recent year for which adequate data are available). The estimate includes both home owner and professional applications as well as use on forested lands (11). Based on EPA data for 1999, an estimated 1-2 million pounds of glyphosate was applied to forest acres, with more than 650,000 forest acres treated.

AGRICULTURAL SITES: In certain annual crops, glyphosate may be applied before planting (preplant) to control existing weeds; often replacing tillage as a weed control measure in "no-till" crop culture systems designed for reducing soil erosion. However, most of the glyphosate currently used in agricultural sites is used in a cropping system employing crop varieties that have been developed to be resistant to glyphosate so that glyphosate may be applied "over-the-top" of the resistant crop to kill susceptible weeds. The most prevalent of these systems is the Round-up Ready Soybean® system. These soybeans, which are highly tolerant to glyphosate, were marketed starting in 1996. Since then this system has been widely and rapidly adopted; in 1990-1991, glyphosate ranked 11^th among conventional pesticides used in the U.S. with annual use estimated to be 18.7 million pounds (4). In 2000, glyphosate was the most widely used herbicide in soybeans; nearly 42 million pounds of glyphosate were applied to soybeans alone (2) with over 60 percent of soybeans surveyed by USDA’s National Agricultural Statistical Service treated with glyphosate (5). Round-up®, a glyphosate product marketed for agricultural use is formulated with a surfactant during manufacture to facilitate foliar absorption. The following table (Table Two) summarizes the use rates specified in label instructions for Roundup Original^TM product herbicide concentrate (12) which contains the isopropylamine salt of glyphosate for use in glyphosate-tolerant soybeans.

Table Two. Allowed Rate of the Isopropylamine Salt of Glyphosate Per Application in Tolerant Soybeans

NON-AGRICULTURAL USES INCLUDING FORESTRY: BEAD has been asked to describe the use of glyphosate in U.S. forestry sites since that use most closely corresponds to the use of glyphosate in Colombia for coca control. For simplicity this document only refers to Accord® which is intended specifically for forestry use (6). This product contains the isopropylamine salt of glyphosate (41.5%), and is labeled for non-agricultural uses including Forestry Site Preparation and Utility Rights-of Way, Forestry Site Conifer and Hardwood Release, and Wetland Sites in the U.S. Table Three describes the rates at which it may be used. It is recommended for use in site preparation prior to planting any tree species, including Christmas tree and silvicultural nursery sites (7). Specific methods of application for forestry uses include: aerial spraying; spraying from a truck, backpack or hand-held sprayer; wipe application; frill treatment; cut stump treatment (7).

For forestry site preparation it may be applied using either ground or aerial equipment at rates from 2 to10 pounds glyphosate active ingredient per acre which is equivalent to 2.2-11.2 kilograms of active ingredient per hectare (Table Three). It may also be applied using hand-held equipment. Product instructions specify that a non-ionic surfactant be added to the spray mixture for all forestry uses at a rate of 0.5 to 1.5 percent by spray volume (2 to 6 quarts of surfactant per 100 gallons of spray solution). It may also be combined with certain residual herbicides to extend the period of weed control beyond that obtained with glyphosate alone.

The isopropylamine salt of glyphosate may also be used in forestry conifer and hardwood release as a directed spray or by using selective equipment. This product may also be used in or around wetland sites generally at no more than 5 quarts of product per acre (5 lbs isopropylamine salt of glyphosate per acre which is equal to 5.6 kg/ha) using over-water broadcast application (5).

Table Three. Rate of Isopropylamine Salt of Glyphosate Per Application For Certain Use Sites

PROPERTIES OF GLYPHOSATE: Glyphosate is a foliar-active herbicide; to exert herbicidal properties it must enter the plant through foliage (or in some cases, the stem). Glyphosate applied to foliage is absorbed by leaves and rapidly moves through the plant. It acts by preventing the plant from producing an essential amino acid. This reduces the production of protein in the plant, and inhibits plant growth.

Glyphosate has systemic activity, meaning that it circulates through the plant’s vascular system; affecting the entire plant, not just the treated foliage. Other foliar-active herbicides, like paraquat for example, are contact herbicides; affecting only the portion of the plant onto which they are applied. After treatment with a contact herbicide, a plant may then regrow from untreated portions, often necessitating re-treatment for complete control. The advantage to a systemic herbicide is that if applied at an appropriate dose, it can kill an entire plant, thus preventing regrowth from an untreated plant part such as a root.

Glyphosate has no residual activity, once adsorbed to soil it quickly becomes unavailable to plants and no longer has herbicidal activity. This means that a plant that would ordinarily be susceptible to glyphosate can be planted shortly after an application of glyphosate; this is common practice in U.S. agriculture. In contrast, some herbicides have month-long or even year-long residual activity which limits the plants that may be grown following their use.

Glyphosate is non-selective. Some herbicides are selective in their action, controlling only grassy weeds in a broadleaf crop like soybeans, for example. However, glyphosate exerts herbicidal action on a variety of plants; it is active on grasses, herbaceous plants including deep rooted perennial weeds, brush, some broadleaf trees and shrubs, and some conifers. However, glyphosate does not control all broadleaf woody plants. Plants vary in their susceptibility to glyphosate, so the treatment of dose in important. Plants of certain species and older plants are less susceptible to glyphosate Timing is critical for effectiveness on some broadleaf woody plants and conifers.

FORMULATIONS OF GLYPHOSATE: Glyphosate and four salts of the parent glyphosate molecule are currently used as active ingredients in registered pesticide products in the U.S.(9). These products are registered with the U.S. EPA for use in the U.S. in many different crop, non-crop, industrial and residential sites.

Table Four. Number of Products and Sites for Different Formulations of Glyphosate

GLYPHOSATE USED WITH SURFACTANT FOR FOLIAR ABSORPTION: Since glyphosate is only effective if absorbed by plant foliage, glyphosate is combined with a surfactant to facilitate its absorption. Many herbicide concentrates, including glyphosate, are mixed with water before application. Without a surfactant, the aqueous spray mixture is repelled by the plant’s waxy cuticle layer ("beads up"), and quickly runs off the plant’s surface, preventing absorption.

Surfactants are commonly used as wetting agents with herbicides and in other products such as laundry and dishwashing detergent. Non-ionic surfactants, which are comprised of alcohols or fatty acids and considered an all-purpose surfactant are commonly used with glyphosate-containing products. Surfactants are frequently added during manufacture of the herbicide concentrate. If not, a non-ionic surfactant is generally mixed with the herbicide and water before spraying to enable the liquid to make better contact with the waxy cuticle of the plant. These glyphosate products, which are formulated without a surfactant, are considered "non-loaded" (10).

A short description of international usage of glyphosate, including Colombia, appears after the following references to the above discussion.

(1) Description of Use of Glyphosate in Coca Eradication in Colombia in attachment to a letter from Secretary of State Colin Powell to Environmental Protection Agency Administrator Governor Christine Whitman.

(2) Donaldson, D., T. Kiely, and A. Grube. Pesticide Industry Sales and Usage, 1998 and 1999 Market Estimates. June 2002. Biological and Economic Analysis Division, Office of Pesticide Programs, U.S. Environmental Protection Agency.

(3) Gianessi, L.P., Silvers, C., Sankula, S., and Carpenter, J. Plant Biotechnology: Current and Potential Impact for Improving Pest Management in U.S. Agriculture - An Analysis of 40 Case Studies. June 2002. National Center for Food and Agricultural Policy.

(4) Glyphosate - Reregistration Eligibility Decision. United States Environmental Protection Agency. September 1993.

(5) Agricultural Chemical Usage - 2000 Field Crops Summary. May 2001. United States Department of Agriculture. National Agricultural Statistics Service.

(6) Accord® Herbicide Specimen Label. Available on-line from CDMS.

(7) Pesticide Fact Sheet. Prepared for the U.S. Department of Agriculture, Forest Service.

(8) D. Lantagne., M. Koelling, and D. Dickman. Effective Herbicide Use in Christmas Tree Plantations. Michigan State University Extension.

(9) U.S. Environmental Protection Agency, Office of Pesticide Programs. Search of the Reference Files System dated June 11, 2002.

(10)Miller, P., and P. Westra. Crop Series: Production. Colorado State University.

(11) EPA Proprietary Information

(12) Roundup Original Herbicide^TM Supplemental Labeling for Postemergence Applications to Soybeans with Roundup Ready® Gene. Available online from CDMS.

BEAD was asked to report on the use of glyphosate in forestry sites since it seemed similar to the use pattern for coca eradication. However, it is not clear how closely this use approximates that for coca eradication. Glyphosate is typically applied to forestry sites using helicopters at air speeds of 50-70 knots (about 60-80 miles per hour). Application to forestry sites by fixed wing aircraft, if practiced at all, is extremely rare (1). The recommended rate of application for pine release (conifer release) is 1.5 to 2 pounds active ingredient per acre.

Aerial application to other sites comprises less than one percent of the total amount of glyphosate applied in the United States (3).

In addition to surfactants, drift control agents may be added to the spray mixture for forestry uses in an effort to prevent drift to off target sites. BEAD has not investigated the prevalence of use or the effectiveness of these products.

BEAD estimates total global use of glyphosate to be between 350 and 360 million pounds of glyphosate per year. Annual use in the United States is approaches 100 million pounds of active ingredient and an estimated 250 to 260 million pounds of glyphosate is used outside of the United States. Use of glyphosate in Colombia accounts for between four and five million pounds of this use. Primary sites in Colombia include coffee, bananas, pasture-land and rice (3).

(1) Personal communication between Virginia Werling, United States Environmental Protection Agency and John Taylor, United States Forest Service on August 9, 2002.

(2) Hamilton, R.A. "2002 North Carolina Agricultural Chemicals Manual - Chemical Weed Control In Forest Stands" Extension Forest Resources Department, North Carolina State University. Available on-line at http://ipm.ncsu.edu/agchem/chptr8/821.pdf

(3) United States Environmental Protection Agency Proprietary Data.

The Department of State has requested that the US Environmental Protection Agency (EPA), Office of Pesticide Programs (OPP) provide a human health risk assessment for the aerial coca eradication in Colombia. The Department of State (DoS) has requested that the risk assessment address whether or not the aerial eradication program in Colombia is being carried out in accordance with regulatory controls required by the EPA as labeled for use in the United States, and the chemicals used, in the manner in which they are being applied, do not pose unreasonable risks or adverse effects to humans and or the environment. According to information provided by DoS, the eradication program, includes the use of a spray mixture of a glyphosate containing pesticide product, an adjuvant (Cosmo-Flux 411F) and water. The glyphosate tank mixture is applied in an over the top aerial foliar application in certain provinces within Colombia. To facilitate the request, the DoS met with members of OPP on April 18 and sent a written request, dated May 8, 2002, with documentation on the coca eradication program, including a description of the pesticide spray mixture components, application methods, target site identification, and potential exposures. DoS also supplied EPA with incident reports for aerial eradication of illicit poppy in Colombia.

The Field and External Affairs Division (FEAD) of OPP, which has the responsibility of managing the EPA’s role of providing technical information and assistance to DoS for this program, forwarded the DoS request to Health Effects Division (HED), the Environmental Fate and Effects Division (EFED), and the Biological and Economics Assessment Division (BEAD) for scientific assessments. The HED of OPP is charged with estimating the risk to human health from exposure to pesticides. Registration Action Branch 1 (RAB1), Reregistration Branch 1 (RRB1) and the Chemistry and Exposure Branch (CEB) of HED as a team have performed the assessment requested by the Department of State and have evaluated the potential hazard, exposure, and risk to human health from the U.S. supported coca eradication program Colombia.

A summary of the findings and an assessment of human risk resulting from the use of glyphosate in Colombia to eradicate coca is provided in this document.

Unless otherwise specified, all information pertaining to the U.S. supported coca eradication program in Colombia was provided to the Agency from two sources: (1) Department of State (DoS) Presentation, DoS Coca Eradication Program, 4/18/02, (2) DoS document entitled Chemicals Used for the Aerial Eradication of Illicit Coca in Colombia and Conditions of Application.

According to the State Department, the glyphosate tank mixture is applied as an over the top aerial foliar application to coca in certain provinces within Colombia. The tank mixture sprayed for eradication of coca in Colombia contains 55% water, 44% of glyphosate herbicide product, and 1% adjuvant (Cosmo-Flux 411F). Up to two applications of the glyphosate tank mixture are sprayed over coca crops at a maximum of 1.25 gallons of product/Acre. In order to assess the hazard of what was sprayed in Colombia, components of the mixture were evaluated separately.

The Cosmo-Flux 411F adjuvant used in the glyphosate tank mix is produced by a Colombian company and is not sold in the U.S. All ingredients identified as contained in this product are substances that are not highly toxic by oral or dermal routes. They may cause mild eye and skin irritation. Cosmo-Flux 411F consists mainly of (information not included as it may be entitled to confidential treatment) with a nonionic surfactant blend primarily composed of (information not included as it may be entitled to confidential treatment).

The available hazard data base on experimental animals indicates that the Glyphosate technical grade active ingredient (TGAI) has low acute toxicity via the oral and dermal routes. It is a mild eye irritant and a slight dermal irritant. It is not a dermal sensitizer. The requirement for an acute inhalation study was waived since no respiratory or systemic toxicity was seen following subchronic inhalation exposure in rats. In the subchronic and chronic oral toxicity studies (1-year dog, 24-month mouse, 2-year chronic/carcinogenicity rat, and 2-generation rat reproduction), systemic toxicity manifested most commonly as clinical signs, decreases in body weight and/or body weight gain, decreased food consumption, and/or liver and kidney toxicity at doses equal to or above the limit dose (1000 mg/kg/day). No dermal or systemic toxicity was seen following repeated dermal exposures. There was no quantitative or qualitative evidence for increased susceptibility in fetuses following in utero exposure to rats and rabbits in developmental toxicity studies or following pre/post-natal exposure to rats in the 2 generation reproductive toxicity study in rats. Effects in the offspring were observed only at or above treatment levels which resulted in evidence of appreciable parental toxicity.

The Food Quality Protection Act (FQPA) Safety Factor Committee (SFC) concluded that the safety factor, to protect infants and children, of 10x be removed (reduced to 1x). The Hazard Identification Assessment Review Committee (HIARC) met on March 26, 1998 and, again, on November 20, 2001. The most recent report of the HIARC for glyphosate has the complete assessment of the endpoints selected for dietary exposure and residential/occupational exposure. No endpoints were selected for the acute Reference Dose (RfD) since no hazard attributed to a single dose was identified from the oral toxicity studies, and there are no concerns for developmental or reproductive toxicity. In addition, the HIARC did not identify endpoints of concern for dermal and inhalation exposures for any exposure period (short term 1-30 days, intermediate term- 1 to 6 months, or long term- 6 months to lifetime) since no hazard was identified due to the low toxicity of glyphosate. HIARC did identify an incidental oral endpoint for short- and intermediate-term exposure. The chronic dietary RfD of 1.75 mg/kg/day was based on diarrhea, nasal discharge, and mortality in a rabbit developmental toxicity study. Glyphosate was not mutagenic in a full battery of assays. Based on the lack of evidence for carcinogenicity in two acceptable studies in mice and rats, glyphosate is classified as a "Group E" chemical (no evidence of carcinogenicity to humans).

An exposure and risk assessment is required for an active ingredient if: (1) certain toxicological criteria are triggered and (2) there is potential for exposure. Upon review and analysis of the hazard database in total, the Agency’s HIARC did not identify a hazard of concern for acute dietary, dermal, or inhalation exposures. Therefore, quantitative estimates of risk for these exposure durations have not been conducted (TXR No. 0050428, W. Dykstra, 22-JAN-2002).

Acute dietary exposure is possible for persons consuming livestock or food crops which have been inadvertently sprayed as a result of the aerial eradication program in Colombia. However, since glyphosate is a contact herbicide that systemically kills plants after absorption through leaves, dietary exposure due to consumption of treated crops is expected to be limited. In addition, since an acute dietary endpoint was not identified in the hazard database, no significant risk due to acute dietary food exposure to glyphosate residues is expected. Based on the fact that a coca field is sprayed no more than twice to eradicate the crop, no chronic food exposure is expected.

Handler (e.g., individuals mixing the concentrated formulated product to prepare the tank mix and loading the tank mix in the aircraft) exposure is anticipated for short-term (1-30 days) and, possibly intermediate-term (1-6 months) durations based on the frequency of application and duration of the spray program.

Based on the use pattern described by the DoS, short-term dermal post-application exposures are expected for persons pruning, or leaf pulling treated coca plants immediately after spray events. In cases such as glyphosate, where the vapor pressure is negligible, OPP experience with post-application data suggests that inhalation exposure is minimal and OPP does not quantitatively assess post-application inhalation exposure. Intermediate- and long-term post-application exposures are not expected due in part to the fact that a coca field is sprayed twice to eradicate the crop. Additionally, glyphosate is a translocated herbicide which is rainfast within 48 hours after spraying. Therefore, potential exposure to dislodgeable residues of glyphosate after 48 hours is expected to be minimal.

DoS states that pilots are instructed not to spray fields where people are present. Therefore, incidental oral exposure (hand-to-mouth) resulting from individuals being directly sprayed by glyphosate was not assessed. Non-dietary incidental oral exposure was not quantitatively assessed for the use of glyphosate in Colombia.

There is potential for exposure to bystanders in areas near those targeted for spraying. However, the technology and other safeguards described by DoS as being used in this program are consistent with common approaches in the United States for reducing spray drift. Therefore, it is likely that drift is minimized in this program if all procedures are adhered to and operational equipment is in working order.

From the review of Colombian glyphosate product human incident reports for poppy eradication, it should be emphasized that the overwhelming majority (95%) of the illnesses reported are likely background incidents unrelated to the spraying of herbicide to poppy. The remaining 5% increase could be due to a variety of causes and do not support a conclusion that the spraying of the glyphosate tank mixture was responsible for these complaints. Furthermore, the individual with the highest potential for exposure would be the mixer loader. They are handling the concentrated glyphosate product and the tank mix. The incidence data that has been submitted to the Agency by DoS, does not include any incident reports for those individuals. There are data to suggest that the poppy spray eradication program could have resulted in minor skin, eye, or respiratory irritation, and perhaps headache or other minor symptoms. However, the detailed information on timing of application, history of exposure, and medical documentation of symptoms related to exposure to glyphosate tank mix were not available. Given the limited amount of documentation, none of the data in the report from Colombia provide a compelling case that the spraying of the glyphosate mixture has been a significant cause of illness in the region studied. Prospective tracking of reports of health complaints, documenting times of exposure and onset of symptoms, are recommended during future spray operations to evaluate any potential health effects and ameliorate or prevent their occurrence.

A direct comparison of the epidemiological data in Colombia (which is from aerial application to poppy) to the conditions of use, (as presented at the April 18, 2002 briefing for aerial application to coca by DoS to OPP risk assessors), would be limited. The briefing and the materials provided did not address the conditions of use for poppy. Nor was the Agency provided any human incident data for the coca eradication program. Subsequent to the April 18 briefing HED received an e-mail communication from OPP/Field and External Affairs Division, stating that DoS informed EPA that the application rate for poppy was lower than that for coca. According to the DoS, the use pattern of the glyphosate mixture on poppy differs from the use on coca. Other details of the differences between the two spray programs have not been supplied to the Agency. Specifically, the Agency has no information as to the exact makeup of the tank mixture sprayed on poppy, or whether the same glyphosate product and adjuvants used in the coca eradication program were used in the poppy eradication program. The Agency also has questions as to the geographical area differences, the frequency of repeated applications, and the size of the area treated on each spray mission. Therefore, generalized conclusions drawn from human incident data as a result of application to opium poppy, in comparison to conditions of use for the coca eradication program should be made with caution.

The glyphosate formulated product used in the coca eradication program in Colombia contains the active ingredient glyphosate, a surfactant blend, and water. The acute toxicity test of the glyphosate technical is classified as toxicity category III for primary eye irritation and toxicity category IV for acute dermal and oral toxicity, and skin irritation. It is not a dermal sensitizer. However, the surfactant used in the formulated product reportedly can cause severe skin irritation and be corrosive to the eyes, as would be expected for many surfactants. The label for the formulated product used in the coca eradication program in Colombia includes the "Danger" signal word. These findings suggest that any of the reports of toxicity to the eye may be due to the surfactant, not glyphosate per se. The product has been determined to be toxicity category I for eye irritation, causing irreversible eye damage.

There may be a correlation between the ocular toxicity caused by the surfactant and reported incidents of ocular effects. This is supported by data obtained from the California Pesticide Illness Surveillance Program (1982-2000). In 1992 the glyphosate product was reformulated in the US to reduce the amount of surfactant which posed a hazard to the eye. From 1982 through 1991, there were 221 illnesses involving the eye or 22.1 cases per year. From 1994 (allowing 2 years for the product to be introduced into trade and widespread use) through 2000, there were 65 illnesses involving the eye or 9.3 cases per year, a decline of 58%. Therefore, these data support the finding that use of the reformulated glyphosate product since 1992, has resulted in a significant drop in illnesses. Overall, the total illnesses due to glyphosate declined by 39% from the 1982-1991 time period to the 1994-2000 time period, largely due to reduction in eye injuries.

The greatest potential for eye exposure is expected for workers mixing and loading the concentrated glyphosate product. There is also the potential for eye exposure as a result of entering treated fields after treatment to perform pruning or harvesting activities.

During an April 18 briefing, the Department of State agreed to supply the Agency with a full battery of the six acute toxicity tests on the tank mix. To date this information has not been received. Until such information is supplied to the Agency, EPA cannot evaluate the potential ocular or dermal toxicity resulting from direct contact with the tank mixture. Therefore, due to the acute eye irritation caused by the concentrated glyphosate formulated product and the lack of acute toxicity data on the tank mixture, the Agency recommends that DoS consider using an alternative glyphosate product (with lower potential for acute toxicity) in future coca and/or poppy aerial eradication programs.

EPA regulates pesticides under two statutes, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA). FIFRA provides the authority to register and review pesticides as well as the authority to suspend and cancel if use poses unreasonable risks. FFDCA provides authority to set maximum residue levels (tolerances) for pesticides used in or on foods or animal feeds.

Section 3 of FIFRA provides authority to register (license for sale and distribution) pesticide products. The label of the pesticide product specifies the use (pest and crop/site), amount of product to be applied, frequency, timing of use, restrictions, storage and disposal practices and precautionary statements. The active ingredient in a pesticide product is the "ingredient which will prevent, destroy, repel, or mitigate any pest." The inert or other ingredient(s) in a pesticide product is "an ingredient which is not active." The registrant must provide data for the Agency to assess potential environmental and human health risks. The data required to make a safety finding are dependent on the intended use, e.g., food use vs non-food use. The data requirements for pesticides may be found in 40 CFR Part 158. For human health risk assessment, data is required to permit characterization of hazard and exposure.

Data requirements on the chemical identity and composition of the formulated pesticide product, may be found in 40 CFR 158.150. The list of ingredients for a pesticide product and the percent of each ingredient in the formulation are contained in the confidential statement of formula (CSF). The CSF is FIFRA confidential business information (CBI) and is entitled to treatment as trade secret or proprietary information. Agency risk assessments do not typically contain this information. In finalizing the current document, FEAD and HED consulted with OPP’s Information Resources and Services Division/Public Information and Records Integrity Branch regarding CBI. It was determined that the document did contain some CBI and therefore, some sections have been adapted.

Residue chemistry data required as per 40 CFR 158.240 support the ability of the Agency to estimate the amount of pesticide that will result in food as a result of application of the pesticide according to the product labels directions for use. The magnitude of the residue studies for crop field trials use the typical end use product as the test material. The livestock feeding studies are required whenever a pesticide residue will be present in livestock feed. The livestock feeding studies evaluate the magnitude of the resulting pesticide residue in meat, milk, poultry, and eggs. The studies are conducted with the technical grade of the active ingredient or the plant metabolites Residue chemistry data are also required to identify any potential metabolites of concern. These data are used to determine the tolerances for the parent and or metabolites. Additional data is required on environmental fate, degradation, metabolism, and dissipation.

Hazard data required for human health risk assessment are provided in 40 CFR 158.340. The use of the active ingredient (i.e., food use or non-food use) will determine what studies are required. The acute toxicity data on the technical grade of the active ingredient are used for classification and precautionary labeling for protective clothing requirements, and worker reentry intervals. The only studies that are required to be conducted on the manufacturing use product or end use product are the acute toxicity studies. The remaining toxicology studies (e.g., developmental toxicity, reproduction, subchronic, chronic feeding, or carcinogenicity studies) require that the test substance is the technical grade of the active ingredient. Subchronic toxicity studies provide data on potential target organ toxicity and are also used to select dose levels for long term or chronic toxicity studies. Chronic toxicity or carcinogenicity studies are conducted for food use chemicals to determine potential effects following prolonged or repeated exposure that may have a latency period for expression. The test animals are exposed orally for a significant portion of their life span. Developmental toxicity studies are required in two species (usually the rat and rabbit) for food use chemicals. They are conducted to detect alterations in the normal development of fetuses following in utero exposure. The 2-generation rat reproductive toxicity study is required to assess potential alterations in gonadal function, estrus cycles, mating, conception, birth, lactation, weaning, as well as growth and development of offspring. The Agency also requires a battery of mutagenicity studies to assess the potential induction of changes in the genetic material of cells. The above studies are required for food use active ingredients. In general, less data is required for non-food use active ingredients and inerts unless a concern has triggered additional testing.

The Agency conducts separate risk assessments for all pesticide active ingredients and has conducted risk assessments for some inerts. The remaining inerts are cleared by the Agency. It should be understood that whenever the inert ingredient was cleared, whenever the tolerance exemption was established, the inert met the standards of the time. Inert ingredients, also known as "other ingredients," are the carrier for the active ingredients which allow the product to deliver the active ingredient at a specific rate and ensure proper distribution during application. Currently there are over 3200 inert ingredients cleared by EPA for use in various domestic pesticides products. There are two major classifications: non-food use (such as lawn care products and bathroom cleaners), and food-use, which require an exemption from the requirement of a tolerance and can also be used in non-food products.

The Agency has a newly developed methodology for evaluating low or low/moderate toxicity chemical substances by way of a screening process that incorporates elements of a tiered approach (US EPA, May 2002). Use of this process will permit the Agency to clear more chemicals of low to moderate toxicity for use in pesticide products. The Agency is aware that some chemicals may be used as inert ingredients in some formulations and as active ingredients in other formulations. EPA believes this methodology is appropriate for evaluating some low toxicity chemicals regardless of whether they are categorized as active or inert ingredients. The new process will permit the Agency to be able to conduct more in-depth evaluations of other ingredients that are of potentially higher toxicity. Chemicals of higher toxicity that can not be appropriately addressed in the lower tiers would be evaluated in a manner substantially similar to that of an active ingredient. Later as the Agency begins to review chemical-specific or surrogate information in the open literature, the preliminary tier determination may be revised (US EPA, May 2002).

Inert ingredients that are exempt from tolerance are listed in 40 CFR 180.1001 (c). The inert ingredients in the glyphosate formulation have been approved by the Agency. The components of the adjuvant (Cosmo-Flux 411F), that DoS indicates have been sprayed on coca plants in Colombia have also been determined to be approved for use on food by the Agency.

The two federal statutes for regulating pesticides in the US give EPA limited authority to regulate the sale, or use of adjuvants in the US. EPA only has authority to regulate the pesticide product itself. For example, if a chemical in an adjuvant was intentionally included in the formulation of a pesticide product, the chemical would be regarded as an inert ingredient. In the US as with all countries, adjuvants are commonly used and added to pesticides as wetting agents, spreaders. emulsifiers, antifoamers, penetrants, or for other purposes. These may contain surfactants, solvents, or other types of chemicals to achieve the desired purpose.

An adjuvant is a subsidiary ingredient or additive product added to a pesticide in a mixture that aids the effectiveness of the primary or active ingredient. Adjuvants are most commonly added to tank mixes of pesticide products prior to application to the site to be treated. Adjuvants are not directly subject to FIFRA registration if no pesticidal claims are made. Pesticide manufacturers choose whether or not to address on their product labels the use of adjuvants with their product(s). However, when added to a tank mix for application to a food or feed crop/site, the individual components must be cleared under FFDCA. While adjuvant products are not registered on the federal level, they are subject to registration under some state laws. The states of Washington and California are two states that register adjuvants. The adjuvant (Cosmo-Flux 411F) used in the glyphosate tank mix is produced by a Colombian company and is not sold in the U.S. The Department of State has agreed to provide the Agency with acute toxicity data performed on the actual tank mix that has been sprayed in Colombia.

The glyphosate product used in Colombia according to the Department of State was registered in the US in April 1974. From 1974-1992 the product was registered for use on a number of agricultural and nonagricultural sites. The product had a "Warning" signal word for eye irritation. In 1992, the registrant submitted an eye irritation study that was categorized as Toxicity Category I and required a "Danger" signal word. The registrant decided that they did not want to market a glyphosate product with a "Danger" signal word. Around July 1992, the registrant registered a reformulated glyphosate product for use in the United States that had the percentage of surfactant reduced to a level that produced Toxicity Category II eye irritation. The original product was re-labeled - "Not for use in the United States". Because the Agency never rescinded the registrations for the use sites that were on the initial label before it was changed, the product technically remains registered for use on numerous agricultural and nonagricultural sites although it is not currently labeled for these uses. In November 2001, the Company submitted a label for the original product for ground and aerial application to control undesirable vegetation in nonagricultural sites. This registration was intended to register a glyphosate product that corresponds to the product being used in Colombia. In February 2002 the product name was changed and the maximum application rate was reduced as per the request of the registrant.

Hazard identification is the first step in the risk assessment process. The objective is to qualitatively characterize the inherent toxicity of a chemical. Scientific data are evaluated to establish a causal relationship between the occurrence of adverse health effects and exposure to a chemical. Because high quality controlled toxicology studies on humans are frequently unavailable, regulatory scientists rely on animal data to estimate hazard to support regulatory decision making. Prior to and subsequent to initial registration, the Agency has required the registrants of glyphosate products to submit appropriate studies according to contemporary study requirements and testing protocol requirements.

The available hazard data base on experimental animals indicates that glyphosate has low acute toxicity via the oral and dermal routes with LD₅₀s > 5000 mg/kg. It is a mild eye irritant and a slight dermal irritant. It is not a dermal sensitizer. The requirement for an acute inhalation study was waived since no respiratory or systemic toxicity was seen following subchronic inhalation exposure in rats. In the subchronic and chronic oral toxicity studies (1-year dog, 24-month mouse, 2-year chronic/carcinogenicity rat, and 2-generation rat reproduction), systemic toxicity manifested most commonly as clinical signs, decreases in body weight and/or body weight gain, decreased food consumption, and/or liver and kidney toxicity at doses equal to or above the limit dose (1000 mg/kg/day). No dermal or systemic toxicity was seen following repeated dermal exposures. There was no quantitative or qualitative evidence for increased susceptibility in fetuses following in utero exposure to rats and rabbits in developmental toxicity studies or following pre/post-natal exposure to rats in the 2-generation reproductive toxicity study in rats. Effects in the offspring were observed only at or above treatment levels which resulted in evidence of appreciable parental toxicity. Glyphosate was not mutagenic in a full battery of assays. Based on the lack of evidence for carcinogenicity in two acceptable studies in mice and rats, glyphosate is classified as a "Group E" chemical (no evidence of carcinogenicity to humans).

1. Polyoxyethylene alkylamine (POEA). POEA is a compound that is used as a surfactant with many glyphosate formulations. In a safety evaluation and risk assessment of glyphosate, the Roundup formulation and the surfactant POEA, Williams et al. (2000) reported that POEA can cause severe skin irritation and be corrosive to the eyes. In subchronic oral studies, POEA was mainly a gastrointestinal irritant in rats at high doses (~ 100 mg/kg/day) and in dogs at lower doses (30 mg/kg/day). In a developmental toxicity study in rats, POEA did not cause any developmental effects up to 300 mg/kg/day, but did induce maternal toxicity at 100 and 300 mg/kg/day (Farmer et al., 2000). The concentrated formulated Roundup product can also be strongly irritating to the eyes and slightly irritating to the skin (Williams et al., 2000).

2. (information not included as it may be entitled to confidential treatment) are substances that are not highly toxic by oral or dermal routes and are not irritating to the skin. They may cause mild, transient eye irritation. Many (information not included as it may be entitled to confidential treatment) are known not to be sensitizers (study citation not included as it may be entitled to confidential treatment). The molecular weight of a (information not included as it may be entitled to confidential treatment) determines its biological properties, and, thus, its toxicity. The lower molecular weight (information not included as it may be entitled to confidential treatment) tend to be more toxic than the higher-weighted (information not included as it may be entitled to confidential treatment) and are absorbed by the digestive tract and excreted in the urine and feces, while the higher molecular weight (information not included as it may be entitled to confidential treatment) are absorbed more slowly or not at all (study citation not included as it may be entitled to confidential treatment). (information not included as it may be entitled to confidential treatment) have low acute and chronic toxicity in animal studies. No significant adverse effects have been noted in inhalation toxicology studies, carcinogen testing, or mutagen assays. High oral doses have resulted in toxic effects to the kidneys and loose feces (study citation not included as it may be entitled to confidential treatment). Topical dermal application of (information not included as it may be entitled to confidential treatment) to burn patients with injured skin has resulted in toxicity (study citation not included as it may be entitled to confidential treatment).

Cosmo - Flux 411F (Adjuvant)

The Cosmo-Flux 411F adjuvant product used in the glyphosate tank mix is produced by a Colombian company and is not sold in the U.S. The Agency is not in possession of toxicity data from direct dosing of test animals with Cosmo-Flux 411F. However, the Agency has made a hazard assessment based on the toxicity of the individual components. As stated above, sale or use of spray adjuvant products in the U.S. are generally not regulated by EPA. However, the DoS has provided the EPA with a copy of this product’s label and a description of the product ingredients. To be able to provide an opinion on hazard characterization of the Cosmo-flux ingredients, the EPA relied on available technical information from various sources. Cosmo-Flux 411F consists mainly of (information not included as it may be entitled to confidential treatment) with a nonionic surfactant blend primarily composed of (information not included as it may be entitled to confidential treatment). All ingredients of this product are substances that are not highly toxic by oral or dermal routes. They may cause mild eye and skin irritation. All components of the adjuvant have been approved for use in/on food by EPA (40 CFR 180.1001, Letter from R.Forrest/EPA, to R.Woolfolk/DoS, 7/30/2001).

1. (information not included as it may be entitled to confidential treatment). The (information not included as it may be entitled to confidential treatment) can cause dermal and ocular irritation and, in high doses orally, can cause significant toxicity. However, small amounts are not a concern and these substances have been approved as food additives by the FDA and are exempt from tolerances by EPA on certain commodities.

2. (information not included as it may be entitled to confidential treatment). The other major component of Cosmo-Flux 411F, (information not included as it may be entitled to confidential treatment), is not considered highly toxic. It may cause mild eye and skin irritation. The corresponding (information not included as it may be entitled to confidential treatment), has low subacute, subchronic and chronic oral toxicity and is used as a direct food additive and a component in cosmetics. The higher molecular weight (information not included as it may be entitled to confidential treatment) is less likely to be absorbed orally or dermally and most likely of less toxicological concern. The other minor components, are not known to be highly toxic compounds and would not be of toxicological concern at the concentrations and conditions in which they are used.

Dose response analysis is the second step in the risk assessment process i.e.; characterization of the quantitative relationship between exposure (dose) and response based on studies in which adverse health effects have been observed. The objective is to identify endpoints of concern which correspond to the route and duration of exposure based on the exposure patterns.

HED selects doses and endpoints (effects of concern) for risk assessment via an internal peer review process. HED uses a standing Committee - the Hazard Identification Assessment Review Committee (HIARC), to consider the available hazard data (studies required to be submitted by registrants in 40 CFR part 158 and open peer reviewed literature) to identify endpoints for use in risk assessment.

Ideally, each safety study identifies a dose level that does not produce a biologically or statistically significant increased incidence of an adverse effect or no observable adverse effect level (NOAEL). The threshold dose is the smallest dose required to produce a detectable effect. Below this dose, there is no detectable response. Glyphosate

On March 26, 1998 and, again, on November 20, 2001 the HED HIARC met to examine the hazard data base and identify dietary endpoints for Females 13-50 years old, as well as the General Population, the chronic reference dose. The HIARC also considered toxicological endpoints for incidental oral exposure (on 20-NOV-01) appropriate in residential exposure risk assessments.

The most recent report of the HIARC for glyphosate has the complete assessment of the endpoints selected for dietary and residential/occupational exposures (W. Dykstra, 01/22/02; TXR# 0050428). OPP calculates acute (24 hour or single day) and chronic (continuous lifetime exposure) RfDs for the purposes of calculating dietary risk for food and drinking water. The RfD is calculated by dividing the appropriate no observed adverse effect level by a ten fold factor for interspecies variability ("average" human sensitivities might be up to 10 times that of lab animals) and a ten fold factor for intraspecies variability (i.e., some individuals within a population might be 10 times more sensitive than the "average" person).

For glyphosate, no endpoints were selected for the acute RfD since no hazard attributed to a single dose was identified from the oral toxicity studies, and there are no specific concerns for toxic effects on the developing fetus or infants and children. In addition, the HIARC did not identify endpoints of concern for dermal and inhalation exposures for any exposure period (short term- 1 to30 days, intermediate term- 1 to 6 months, or long term- 6 months to lifetime) since no hazard was identified due to the low toxicity of glyphosate (TXR No. 0050428, W. Dykstra, 22-JAN-2002). The chronic dietary RfD of 1.75 mg/kg/day was based on diarrhea, nasal discharge, and mortality in a rabbit developmental toxicity study. A summary of doses and toxicological endpoints selected for various relevant exposure scenarios are summarized in Table 1.

Table 1. Glyphosate Endpoint Selection Table

EXPOSURE SCENARIO	DOSE (mg/kg/day)	ENDPOINT	STUDY
Acute Dietary (24 hour or single exposure)	An effect of concern attributable to a single dose was not identified from the oral toxicity studies; there are no concerns for developmental or reproductive toxicity.
Chronic Dietary (continuous lifetime exposure)	NOAEL = 175 uncertainty factor (UF) = 100	Maternal toxicity based on clinical signs (diarrhea and nasal discharge)resulting in mortality of some dams at 350 mg/kg/day	Developmental toxicity -Rabbit
		Chronic RfD = 2.0 mg/kg/day
Incidental Oral, Short- (1-30 days), and Intermediate-(1-6 months) Term	NOAEL= 175	Maternal toxicity based on clinical signs (diarrhea and nasal discharge)resulting in mortality of some dams at 350 mg/kg/day	Developmental toxicity -Rabbit
Dermal, Short-, Intermediate-and Long-Term	No hazard was identified, therefore quantification of dermal risk is not required. No systemic toxicity was seen at the Limit Dose (1000 mg/kg/day) following repeated dermal applications to New Zealand White rabbits.
Inhalation, Short-, Intermediate-, and Long-Term	Quantification of inhalation risk is not required because 1) no hazard was identified in the 28 day inhalation toxicity study in rats - NOAEL = 0.36 mg/L (highest dose tested (HDT)); lowest observable adverse effect level (LOAEL) not established based on 6 hours/day, 5 days/week for 4 weeks and 2) due to the physical characteristics of the technical (wetcake), exposure to high levels of the active ingredient is unlikely via the inhalation route, so there was no purpose to test at higher doses.

On August 3, 1996 the FQPA amended FIFRA and FFDCA. Section 408(b)(2)(C) of the Federal Food, Drug, and Cosmetic Act addresses exposure of infants and children. Under this provision EPA must apply the default 10X safety factor when establishing, modifying, leaving in effect or revoking a tolerance or exemption for a pesticide chemical residue, unless the EPA concludes, based on reliable data, that a different safety factor would protect the safety of infants and children. Risk assessors, therefore presume that the default 10X safety factor applies and should only recommend a different factor, based on an individualized assessment, when reliable data shows that such different factor is safe for infants and children that it does not rely on a default value or presumption in making decisions under Section 408 where reliable data are available that support an individualized determination. The OPP FQPA Safety Factor Committee (SFC) makes specific case-by-case determinations as to the need and size of the additional factor if reliable data permit. Determination of the magnitude of the overall safety factor or margin of safety involves evaluating the completeness of the toxicology and exposure databases and the potential for pre- or post-natal toxicity. Individualized assessments may result in the use of additional factors greater or less than, or equal to 10X, or no additional factor at all. (OPP Guidance Document on Determination of the Appropriate FQPA Safety Factor(s) in Tolerance Assessment, 2002)

The HIARC addressed the potential enhanced sensitivity of infants and children from exposure to glyphosate as required by the FQPA of 1996 at the March 26, 1998 meeting and reaffirmed the decision at the November 20, 2001 meeting. The HIARC concluded the following:

• Based on the available data, there was no evidence of quantitative and qualitative increased susceptibility to in utero and/or postnatal exposure to glyphosate in rats or rabbits.
•  Based on a weight of evidence consideration, the HIARC decided not to require the conduct of a developmental neurotoxicity study with glyphosate to evaluate the potential for developmental neurotoxic effects because there was no evidence of neurotoxicity and neuropathology in adult animals.

The FQPA SFC met on April 6, 1998 to evaluate the hazard and exposure data for glyphosate. The FQPA SFC concluded that the safety factor of 10x be removed (reduced to 1x) since there is no evidence of quantitative or qualitative increased susceptibility of the young demonstrated in the prenatal developmental studies in rats and rabbits and pre/post natal reproduction study in rats. In addition the toxicology data base is complete, a developmental neurotoxicity study is not required, and the dietary (food and drinking water) exposure assessments will not underestimate the potential exposures for infants and children.

The exposure assessment is the third step in the risk assessment process. The objective is to determine the source, type, frequency, magnitude, and duration of actual or hypothetical contact by humans with the agent of interest. To conduct this assessment EPA relied upon the information provided by DoS from two sources: (1) Department of State (DoS) Presentation, DoS Coca Eradication Program, 4/18/02, (2) DoS document entitled Chemicals Used for the Aerial Eradication of Illicit Coca in Colombia and Conditions of Application. These data were used in accordance with standard policies and procedures used by the Agency in conducting pesticide exposure assessments.

Acute dietary exposure is possible for persons consuming livestock or food crops which have been inadvertently sprayed as a result of the aerial eradication program in Colombia. However, since glyphosate is a contact herbicide that systemically kills plants after absorption through leaves, dietary exposure due to consumption of treated crops is expected to be limited. Since a coca field is sprayed no more than twice to eradicate the crop, no chronic food exposure is expected. Based on an evaluation of the hazard database, the Agency did not identify a toxic effect attributed to a single oral dose. Therefore, an acute dietary risk assessment was not performed (TXR No. 0050428, W. Dykstra, 22-JAN-2002). No significant risk due to dietary exposure to glyphosate residues is expected.

The tank mixture sprayed for eradication of coca in Colombia contains 55% water, 44% of glyphosate herbicide product, and 1% adjuvant (Cosmo-Flux 411F). No more than two applications of the glyphosate tank mixture are sprayed over coca crops at a maximum of 1.25 gallons/Acre (equivalent to 1.1 gallons/Acre of glyphosate product, 0.03 gal/Acre of Cosmo-Flux 411F, and 0.12 gal/Acre of water). DoS also stated that the average field size for coca in Colombia is 3-5 hectares (approximately 7-12 acres). The program for aerial eradication of coca treats a maximum of 1000 Acres/day, during 3-5 missions/day.

Exposure is expected for workers mixing and loading the glyphosate formulated product and tank mix, and applicators applying the pesticidal mixture via fixed-wing aircraft. Mixers, loaders, and applicators (handlers) have the potential for dermal exposure to the concentrate glyphosate formulated product or tank mix from droplets contacting the skin. There is also the potential for inhalation exposure to the concentrated glyphosate formulated product or mixed formulation from breathing in aerosolized spray droplets.

According to the DoS, the mixer/loaders are trained on the label requirements for handling the chemicals in the spray mixture, first aid, and use of personal protective equipment (PPE). The required PPE according to the label includes long-sleeved shirts and long pants, waterproof gloves, shoes and socks, and protective eyewear. PPE is expected to mitigate potential exposure to handlers. Exposure to handlers is anticipated for short-term (1-30 days) durations. There also may be the possibility for intermediate-term(1-6 months) handler exposure for individuals mixing, loading, and applying the glyphosate mixture to multiple fields for more than 30 days. However, the Agency does not have information pertaining to the duration of coca spray programs or number of days spent mixing, loading, and applying the glyphosate mixture.

An occupational handler exposure and risk assessment is required for an active ingredient if: (1) certain toxicological criteria are triggered and (2) there is potential exposure to handlers (i.e., mixers, loaders, applicators, etc.) during use. Upon review and analysis of the hazard database in total, the Agency’s HIARC did not identify a hazard of concern for dermal or inhalation short- and intermediate-term exposures. Therefore, quantitative estimates of risk for short-term dermal and inhalation have not been conducted (TXR No. 0050428, W. Dykstra, 22-JAN-2002). No significant handler risk is expected.

Post-application Exposure

According to the DoS, Colombian coca plants (Erythroxylum species) are woody perennial shrubs native to the Andean region. Coca plants have leaves with waxy cuticles which retard herbicide uptake in the plant. The coca bushes grow to approximately chest level and are harvested mainly by leaf pulling, 4 to 5 times per year. Coca plants grow from seedlings to a harvestable plant in 12 to 18 months. Representatives from DoS indicated that, growers will prune the coca plants, immediately after spraying, in order to salvage the coca crop. Specifically, since glyphosate is a contact herbicide that works systemically to kill the plant after absorption through the leaves, workers may enter fields immediately after spraying in order to prune or pull off the coca leaves in order to prevent the coca plant from dying. In the US, most uses of glyphosate are applied to kill weeds - which are the target. In general, glyphosate is not applied in the US to destroy or kill the raw agricultural commodity. The intended US uses are for undesired vegetation in and around crop fields, forests, industrial areas and residential areas (for more detailed information, please refer to the June 28, 2002 memorandum entitled Description of Glyphosate Use in the U.S. for Comparison to Use in Colombia for Coca Eradication from Virginia Werling and Timothy Kiely to Jay Ellenberger).

DoS states that pilots are instructed not to spray fields where people are present. Therefore, based on the use pattern described by the DoS, potential short-term dermal exposures are expected for persons pruning, or leaf pulling treated coca plants immediately after spray events. These activities are expected to result in dermal exposure from treated foliage contacting the skin. In cases such as glyphosate, where the vapor pressure is negligible, HED experience with post-application data suggests that inhalation exposure is minimal and therefore, HED does not quantitatively assess post-application inhalation exposure. Intermediate- and long-term post-application exposures are not expected due in part to the fact that a coca field is sprayed no more than twice.

Additionally, glyphosate is a translocated herbicide which is rainfast (unable to be rinsed off by water) within 48 hours after spraying. Therefore, potential exposure to dislodgeable residues of glyphosate after 48 hours is expected to be minimal. Glyphosate has no residual soil activity. Results from the first 12 months of bareground field dissipation trials from eight sites show that the median half-life (DT50) for glyphosate (Roundup) applied at maximum annual use rates (7.95 lb a.i./acre, 10.7 lb a.i./acre) was 13.9 days with a range of 2.6 (Texas) to 140.6 (Iowa) days. Acceptable aerobic soil, aerobic aquatic and anaerobic aquatic metabolism studies demonstrate that under those conditions at 25^oC in the laboratory glyphosate degrades rapidly with half-lives of approximately 2, 7 and 8 days respectively. The reported half-lives (DT50) from the field studies conducted in the coldest climates, i.e. Minnesota, New York. and Iowa, were the longest at 28.7, 127.8, and 140.6 days respectively indicating that glyphosate residues in the field are somewhat more persistent in cooler climates as opposed to milder ones (Georgia, California, Arizona, Ohio, and Texas) (Memo, J.Carleton, 10/26/98, D238931). The climate in Colombia would favor a shorter half life than the colder regions of the US. Thereby, HED believes glyphosate would not be persistent or be available for intermediate-term or long-term post-application exposures in the Colombian climate.

A post-application exposure and risk assessment is required for an active ingredient if: (1) certain toxicological criteria are triggered and (2) there is potential exposure. Upon review and analysis of the hazard database in total, the Agency’s HIARC did not identify a hazard of concern for these durations or routes of exposure. Therefore, quantitative estimates of risk for short-term dermal and inhalation have not been conducted (TXR No. 0050428, W. Dykstra, 22-JAN-2002). No significant post-application risk due to glyphosate exposure is expected as a result of this use.

Since DoS states that pilots are instructed not to spray fields where people are present, incidental oral exposure (hand-to-mouth) resulting from being directly sprayed by glyphosate was not assessed. Non-dietary incidental oral exposure was not quantitatively assessed for the use of glyphosate in Colombia.

As a point of comparison, screening level risk estimates for toddler incidental oral exposures (hand-to-mouth) to the U.S. for registered residential turf uses of glyphosate have been calculated (D280831, Memo, W.Donovan, 20-FEB-2002). All resulting risks for toddler incidental oral exposure do not exceed HED’s level of concern. The assumptions for toddler incidental oral exposures, (based on the maximum application rate of 1.62 lbs acid equivalent (ae)/Acre), are expected to be conservative. For example, it is assumed that there is no dissipation of transferable residues, so that toddlers are exposed to day of treatment residues for each day of exposure. Even though the application rate for the coca eradication program is higher (3.3 lbs ae/Acre), using the same standard screening level assumptions as used in the residential assessment for the U.S. registered turf use and taking the higher application rate into account, the potential risk would not exceed HED’s level of concern.

As indicated in the turf assessment, glyphosate was directly applied to residential lawns and did not result in exposures of concern to HED. Although spray drift is always a potential source of exposure to residents nearby aerial spraying operations, AgDrift® (a spray drift model) consistently predicts drift from applications is only a fraction of the applied rate (lb ai/acre). Based on this assessment, HED believes that it is unlikely that there is a higher potential for risk of exposure to spray drift from agricultural operations.

The greatest potential for eye exposure is expected for workers mixing and loading the concentrated glyphosate product. Potential exposure is expected through 2 main pathways: (1) exposed hands transferring the glyphosate product to the eye(s), (2) splashing of the liquid concentrated glyphosate product into the workers’eye(s). However, the label requires mixer/loaders to wear protective eyewear and this level of PPE is expected to mitigate the potential for eye exposure.

There is also the potential for eye exposure as a result of entering treated fields immediately after treatment to perform pruning or harvesting activities. Specifically, persons dermally contacting treated foliage may transfer residues from the hand to the eye. However, the Agency currently does not have a defined method or model to assess quantitative eye exposures resulting from occupational or residential exposures to pesticides. For products registered for use in the United States which have high acute toxicity to the eye, mitigation of exposure to potential eye effects for post-application workers is done by lengthening restricted entry intervals (REI).

Due to spray drift, there is potential exposure for persons in areas near those targeted for spraying. Exposure through drift is not expected to exceed that which is identified in the exposure characterization provided above. The coca eradication program described by the Department of State has incorporated several features designed to minimize the potential for off-target drift, provide quality assurance on a mission-by-mission basis, and evaluate the performance of the program to the extent possible given current conditions. Three types of aircraft are used in the program including the Ayres Corporation T65 Thrush, modified OV10D Bronco aircraft converted from military observation use to spray aircraft, and the Air Tractor AT802. The T65 and AT802 are common to the agricultural sector in the United States. The nozzles are Accu-Flow as described at the April 18, 2002 briefing to the Agency. The droplet spectra characteristics, under use conditions for these nozzles, produce a very large droplet which has a volume median diameter (VMD) between 300 and 1500 microns. Use of droplets this size is consistent with minimizing spray drift in agriculture in the United States. A surfactant (Cosmo-Flux 411F) is also used in the spray solution along with water and the glyphosate formulated product. The use of spray adjuvants (in this case Cosmo-Flux 411F) in pesticide product formulations and/or the spray solution is also consistent with common agricultural practices in the United States.

The quality assurance standard operating procedures identified as incorporated into the program are also consistent with standard agricultural practices. These include reconnaissance of the spray sites, use of global positioning satellite technology (GPS), and criteria for aborting missions (e.g., based on climatological conditions or presence of persons or livestock in the treatment areas). Reconnaissance of spray sites is intended to define the treatment zones through the use of sophisticated GPS mapping which is then overlaid with GPS spray records from missions to evaluate performance. GPS technology is used for planning, assessments of mission performance, and for archival purposes to evaluate potential claims against the program.

Finally, to a limited extent where feasible, DoS reports that on-site ground inspections for spray efficacy and potential adverse effects are performed. Reports suggest approximately 90 percent efficacy in the spray swath and minimal collateral damage to surrounding vegetation (e.g., aerial photos of treated areas) based on information supplied by the DoS at the April 18, 2002 briefing.

The Agency did not complete a quantitative risk analysis of the drift potential of glyphosate in the water/surfactant solution used in this program. However, the technology and other safeguards used in this program are consistent with common approaches in the United States for reducing spray drift. Therefore, it is likely that drift is minimized in this program if all procedures are adhered to and operational equipment is in working order. At the April 2002 briefing, it was indicated to the Agency that quantitative spray drift studies had been completed by the DoS in conjunction with the University of Georgia. These were not supplied to the Agency nor were they considered in this evaluation. Additionally, it should be noted that the Agency did not review the primary source of information provided (e.g., the method by which the VMD was determined was not described, written application protocols describing target site conditions when applications would be aborted were not provided, and methods for scoring or measuring off-target damage were not provided).

Dr. Jerry Blondell is a health statistician and the point of contact for human incident data in the EPA Pesticide Program. He has reviewed the poppy incident data from Colombia and compared these data to the glyphosate incident data reported from California and the Poison Control Center. The entire review can be found beginning on page 38 of this document.

The report, prepared by the Department of Narino, Municipality of El Tablon De Gomez, makes a concerted effort to identify any health problems that might be related to use of the glyphosate tank mix in aerial eradication programs. The study was commissioned by the U.S. Embassy in Bogota and conducted independently by Dr. Camilo Uribe, Director of Clinica Uribe Cualla, the national poison control center. Sections of this report are summarized below with the sections numbered in bold corresponding to the original report.

An exact comparison of the epidemiological data in Colombia (which is from aerial application to poppy) relative to the conditions of use, presented at the April 18, 2002 briefing (for aerial application to coca) by DoS to OPP risk assessors, would have limitations and uncertainties. The briefing did not address the conditions of use for poppy. DoS also did not provide human incident data for the coca eradication program. Subsequent to the April 18 briefing HED received an e-mail communication from OPP/ Field and External Affairs Division, stating that the application rate for poppy was lower than that for coca. According to the DoS, the use pattern of the glyphosate mixture on poppy also differs from the use on coca. Other details of the differences between the two spray programs have not been supplied to the Agency. Specifically, the Agency has no information as to the exact makeup of the tank mixture sprayed on poppy, or whether the same glyphosate product and adjuvants used in the coca eradication program were used in the poppy eradication program. Therefore, generalized conclusions drawn from human incident data as a result of application to opium poppy, in comparison to conditions of use for the coca eradication program should be made with caution.

This report primarily concerns the area around the municipality of El Tablon in southern Colombia. The total population is given as 16,770, of which 89% is categorized as rural. The main crops in this area include coffee, corn, wheat, oats, potatoes, and illicit opium poppy. It is known that a variety of other pesticides, more toxic than glyphosate, are used on these crops. The municipality has three health centers, including Aponte, which is the focus of this report. The Aponte health center is staffed by a medical doctor, a nurse, and a nurse’s aide. Aerial eradication of the illicit opium poppy reportedly occurred in this region in June, July, and November of 2000.

The Narino Departmental Health Institute provided summary morbidity and mortality information for the El Tablon De Gomez area and the Aponte settlement for the year 1999. Data for the year 2000 had not yet been officially released, but estimates are provided. These data are reported here to provide an approximate description of glyphosate tank mix exposure upon use on coca fields in Colombia. However, no quantitative conclusions can be drawn from these data. Six illnesses likely to be related to pesticide exposure were identified and tabulated. They include, acute diarrhea, acute respiratory infection, dermatitis, intoxication, conjunctivitis and headache. The authors note that the first three illnesses listed (diarrhea, respiratory infection, and dermatitis) are likely to be related to problems with inadequate nutrition, housing, and lack of health services. The basis for this listing of symptoms is not specified, but it does agree with the list of symptoms likely to result from exposure to glyphosate products based on Poison Control Center data, California surveillance reports, and the world literature. Total morbidity for 1999 and estimated morbidity for 2000 are given in the Table below for El Tablon De Gomez and the Aponte Settlement below. Note, however, that the overwhelming majority of these illnesses did not occur at the time of spraying and, therefore, could not be related to spray exposure.

The Aponte settlement is contained within the El Tablon De Gomez area, where there has been a concern for herbicide spraying-related health effects. Figures in the report are listed by five separate age groups. This reveals that the majority of the cases of diarrhea and respiratory infection occurred in children less than five years old, as would be expected given known demographics of those health effects. Nationwide data show that 53% of intoxications are suicides or suicide attempts, but it is not clear how many of the four poisonings listed above might be suicidal or, more importantly, are due to other products such as medications. In both Tables 2 and 3 there is an increase of 5% from 1999 to the estimate for 2000 for the total of the six suspected illnesses. Given that spraying is reported to have occurred in 2000 and not 1999, this suggests that the overwhelming majority (95%) of illnesses reported would be background incidence unrelated to the spraying of herbicide. The remaining 5% increase could be due to a variety of causes and do not support a conclusion that the glyphosate tank mixture was responsible for these complaints.

In addition to the summary of general morbidity in the population, there is a mandatory health reporting system in Colombia for 34 illnesses including pesticide poisonings. The review of these records found no reports of pesticide poisoning for the municipality of El Tablon in the year 2000 or the first 9 weeks of 2001. Weekly reports were examined to determine how many pesticide poisonings were reported each month. It did not appear that the times of spraying correlated with reports of pesticide intoxication.

Out of a total of 125 reported pesticide poisonings in 61 weeks, 15 occurred during 5 weeks when spraying eradication occurred. Given the variation in the data, this could easily be due to chance and be unrelated to exposure from the spraying of the glyphosate tank mixture. More work is required to determine whether locations of the 15 suspect poisoning matched the location and timing of spraying.

In 2000, the Narino Department of Health requested all municipalities to report the human health effects of pesticide spraying. Ten municipalities supplied the reports. They are:

Three municipalities including Tablon de Gomez, Barbacoas, and Magui reported no cases. However, the reports were completed prior to the November spraying in Barbacoas and Magui and prior to (or perhaps during) the July and before the November spraying in Tablon de Gomez. Buesaco reported one patient with sore throat, numbness in limbs,