1

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

E PA Registration Division contact: Reuben Baris (703)305-7356

Do w AgroSciences LLC

4F 8249

EPA ha s r eceived a pesticide petition (4F8249) from Dow A groSciences LLC, 9330 Zionsville R oad –Indianapolis

, Indiana 462 68 proposing, pursuant t o section 408(d) of t he F ederal F ood, Drug, and Cosmetic A ct (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR pa rt 180.417( a)(1) b y establishing a tolerance f or r esidues o f triclopyr

, [( 3,5,6- trichloro- 2- pyridinyl)oxy ] acetic acid, i ncluding its me tabolites a nd de gradates , in or on the r aw a gricultural c ommodity milk, fat at 0.7 ppm, a nd i ncreasing t he tolerance in milk f rom 0.01 ppm t o 0.6 ppm; and to amend 40 CFR pa rt 180.417( a)(2) by e stablishing tolerance s for t he c ombine d residues of triclopyr , [(3,5,6- trichloro- 2-pyridinyl)oxy] acetic acid a nd its me tabolite 3,5,6- trichloro- 2- pyridinol (TCP), calculated a s the s toichiometric equivalent of triclopyr in oro n th e r aw agricultural commo dities cattle, goat, hog, horse, and sheep meat byproducts at 0.7 ppm; by i ncreasing tolerances i n cattle, goat, hog, horse, and s h eep fat from 0.05 ppm to 0.09 ppm ; an d by i ncreasing tolerances in cattle, goat, hog, horse, and s h eep meat from 0.05 ppm to 0.08 ppm. E PA h as determined th at th e p etition c ontains d ata o rin formation r egar d ing th e elements set fo rth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the s u bmitted d ata a t this time o rw hether th e d ata supports g ranting o f th e petition. Additional data
may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism . The nature of residues is adequately understood and analytical methods are available for the determination o f triclopyr in milk and milk fat (cream). EPA has established that the qualitative nature of the residue is adequately understood based on two studies with [14C] triclopyr on grass. Nature of residue studies had shown that majority of the total radioactive residue was triclopyr. No significant amounts of the metabolites 3,5,6- tr icihloro-2-pyridinol and 2-methoxy-3,5,6-
tr ichloropyridine were detected. The Agency’s HED Metabolism Committee has concluded that the residue to be regulated in grass is triclopyr.

2. Analytical method. Adequate methodology is available for the enforcement of tolerances for tri clopyr residues of concern. Gas chromatography methods are available for the determination of triclopyr residues of concern. Residues of triclopyr, 3,5,6- trichloro -2-pyridinol, and 2-methoxy-3,5,6- trichloropyridine can be separately determined

.

3. Magnitude of residues. Magnitudes of residue studies (MOR) on grass were conducted in 1987, 1976, and 1974 and had been previously submitted (MRIDs2

00070045 and 41961001 )

. All samples were analyzed for triclopyr using method ACR 77.4. Brief summaries of t he MOR studies are as follows:

The 1987 MOR study was conducted at 11 sites located in 10 different states across the United States (3). XRM

- 4714 formulation (4 lb ae/gal), containing triclopyr as butoxyethyl ester, was applied on actively growing grass a s an aqueous diluted ground broadcast spray at a single nominal application rat e of 2.0, 4.0, or 6.0 lb ae/A. Grass forage and hay were collected at different sampling intervals o f 0

- 28 days after application. Grass forage samples were frozen after collect ion while hay samples were dried before freezing. The 1976 MOR study was conducted at 3 sites using XRM

- 4021 formulation (4 lb ae/gal) containing tricl opyr as butoxyethyl ester (2). XRM

- 4021 was applied as an aqueous diluted spray at a single nominal rate of 1.5 lb ae/A, either as ground (NY and OR sites)

or aerial (MO site) application. Grass forage samples were collected at different sampling intervals of 0

- 365 days after application and were frozen after collection.

The 1974 MOR study was conducted at 7 sites located in 6 different states across the United States (1). All 7 sites received ground application and one site received an ae rial application, in addition. XRM

- 3724 formulation (3 lb ae/gal), containing triclopyr as triethyamine salt, was applied on actively growing grass as an aqueous diluted spray at a single nominal ap plication rate of 1.5 lb ae/A. Grass forage samples were collected at different sampling intervals of 0

- 365 days after application and were frozen after collection.

An acceptable dairy cattle feeding study has been submitted to the Agency. Four lactating Friesian/ Holstein dairy cows were fed with diets containing tri clopyr in increasing doses for four

- week period per dose at rates equivalent to 0

- 1000 ppm feed. Daily whole milk fr om each cow was collected. For each cow a combined proportional sample was constructed from the PM and AM samples, on the basis of milk yields recorded at the corresponding milkings sampled

. Cream samples were collected from the combining evening morning milk by pooling 2 quarts of milk from each cow at each dose on Days 22 and 26. Tissue samples were collected from each cow immediately after slaughter. The revised tolerance of triclopyr in milk is 0.6 ppm and the new tolerance in milk fat is 0.70 ppm

. The revised tolerance of triclopyr and its metabolite TCP (calculated as the stoichiometric equivalent of triclopyr) in meat is 0.08 ppm, in fat is 0.09 ppm and deletion of kidney and liver tolerance and establishment of meat, byproducts ( including liver and kidney ) at 0.08 ppm

. These proposed tolerances were derived from the worst case animal dietary burden, which was estimated from grass commodities containing triclopyr at tolerance levels of 700 ppm for grass forage and 200 ppm for grass hay and are adequat e to allow grazing of lactating dairy cattle on pasture or rangeland treated with triclopyr formulations according to label.

B. Toxicological Profile

1. Acute toxicity. Acute toxicity studies were performed with triclopyr acid, triclopyr

- TEA and triclopyr

- BEE.3

i. For triclopyr acid, the acute oral LD50 was 729 mg/kg for males and 630 mg/kg for females; while acute dermal LD50 was >2000 mg/kg.

ii. For triclopyr

- TEA, the acute oral LD50 was 1847 mg/kg for males and females; the acute dermal LD50 was >2000 mg/kg; the acute inhalation LC50 was >2.6 mg/L; it was corrosive to eyes, not irritating to skin but was a skin sensitizer

.

iii. For triclopyr

- BEE, the acute oral LD50 was 803 mg/kg for males and females; the acute dermal LD50 was >2000 mg/kg; the acute inhalation LC50 was >4.8 mg/L; it was minimal irritation to eyes, not irritating to skin but was a skin sensitizer

.

The developmental NOAEL of 100 mg/kg/day from a rat developmental study with triclopyr BEE was recommended for the acute dietary risk asse ssment for general population. This NOAEL was selected based on the toxicity observed at the next highest dose (lowest eff ect level) of 300 mg/kg/day in which mortality, clinical signs, decreased body weight gains, decreased food consumption, increased water consumption, and increased relative kidney a nd liver weights were recorded. However, the reference dose for acute dieta ry risk assessment for females (13

- 50 years old) is based on a 2

- generation reproductive toxicity study with triclopyr acid in rats with a NOAEL of 5 mg/kg/day and uncertainty factor of 100. The NOAEL was selected based on the increased incidence of F2 pup with exencephaly and ablepharia at the next dose level of 25 mg/kg/day. Thus, the population sub

- group of particular interest that would be evaluated in the acute exposure assessment are females (13

- 50 years old).

2. Genotoxicty.

i. Triclopyr acid was negative (non

- mutagenic) in an Ames assay with and wit hout hepatic enzyme activation. It was also negative in a rec

- assay in B. subtilis , in host

mediated assay at doses up to 70 mg/kg in mice, in cytogenetic assay for chromosomal aberration at doses up to 70 mg/kg administrated singly or for 5 days to rats. Triclopyr acid did not produce any evidence of unscheduled DNA synthesis, as determined by radioactive tracer procedures (nuclear silver grain counts), in rat primary hepatocyte cultures exposed up to cytotoxic levels. It was negative for the dominant lethal mutagenic effect in treated male rats which were fed for 9 consecutive weeks at doses up to 70 mg/kg/day and mated to virgin females. Triclopyr acid was negative for the dominant lethal m utagenic effect in treated male rats at doses up to 70 mg/kg/day given by oral intubation followed by mating to 2 untreated females per week for 7 weeks

. ii. Triclopyr

- BEE was non

- mutagenic, in an Ames assay with and without hepatic enzyme activation , was not clastogenic in mouse micronucleus test up to 600 mg/kg (HDT) and did not cause DNA damage or inducib le repair in the rat hepatocyte unscheduled DNA synthesis. On the basis of the results from this battery of tests, it is concluded that, triclopyr is not mutagenic or genotoxic.

3. Reproductive and developmental toxicit y

.4

i . Developmental toxicity in the rat with triclopyr acid, the maternal NOAEL was < 50 mg/kg/day and maternal LOAEL was 50 mg/kg/day based on increased clinical signs. The developmental NOAEL was 100 mg/kg/day and developmental LOAEL was 200 mg/kg/day based on increase incidence of fetuses and litters with retarded ossification of skull b ones, and two litters (one fetus per litter) with cleft palate and brachycephaly.

ii . Developmental toxicity in the rat with triclopyr

- BEE, the maternal NOAEL was 100 mg/kg/day and maternal LOAEL was 300 mg/kg/day based on mortality, clinical signs,

necro psy findings, decreased body weight gains, decreased food consumption, increased water consumption, and increased relative kidney and liver weight. The developmental NOAEL was 100 mg/kg/day and developmental LOAEL was 300 mg/kg/day based on increased incid ence of hydrocephalus, cleft palate, microphthalmia/anophthalmia, retinal folds, thin diaphragm/protrusion of the liver, decreased fetal weight and visceral and skeletal anomalies and variants.

ii i . Developmental toxicity in the rabbit with triclopyr

- BEE, the maternal NOAEL was 30 mg/kg/day and maternal LOAEL was 100 mg/kg/day based on mortality. The developmental NOAEL was 30 mg/kg/day and developmental LOAEL was 100 mg/kg/day based on decreased total live fetuses and increased total fetal deaths, as well as increased fetal and/or litter incidence of skeletal anomalies and variants.

iv . Developmental toxicity in the rat with triclopyr

- TEA, the maternal NOAEL was 100 mg/kg/day and maternal LOAEL was 300 mg/kg/day based on mortality. The developmental NOAEL was 100 mg/kg/day and developmental LOAEL was 300 mg/kg/day based on decreased fetal weight, increased fetal and litter incidence of skeletal anomalies, increased fetal incidence of unossified sternebrae.

v . Developmental toxicity in the rabbit with triclopyr

- TEA, the maternal NOAEL was 30 mg/kg/day and maternal LOAEL was 100 mg/kg/day based on mortality, abortions, decreased body weight gain, decreased food efficiency, increased liver and kidney weight. The developmental NOAEL was 30 mg/kg/day and developmental LOAEL was 100 mg/kg/day based on decreased live fetuses and increased embryonic deaths due to abortions.

v i. Two

- generation reproduction toxicity study in rats, the parental/systemic NOAEL was 5 mg/k g/day in males and in females and parental/systemic LOAEL was 25 mg/kg/day in males and females based on increased incidence of proximal tubular degeneration in male and female P1 and P2 rats. The r eproductive/ o ffspring NOAEL was 5 mg/kg/day in males and females and r eproductive/ o ffspring LOAEL was 25 based on increased incidence of F2 pups with exencephaly and ablepharia.

4. Sub c hronic toxicity.

i. In a 90

- day oral study in rats with triclopyr acid, the NOAEL was 5 mg/kg/day in males and females , and LOAEL was 20 mg/kg/day in males and females based on degeneration5

of the proximal tubules of the kidneys

.

i i . In a 90

- day oral study in rats with triclopyr

- BEE
, the NOAEL was 7 mg/kg/day in males and < 7 mg/kg/day in females , and LOAEL was 28 mg/kg/day in males, 7 mg/kg/day based on increased relative kidney weight (M) and decreased red blood cell content, hemoglobin content, and packed cell volume (F). Degeneration of the proximal tubules of the kidneys was seen in males at 70 and 350 mg/kg/day and females at 350 mg/kg/day highest dose tested (HDT).

i ii. I n a 183

- day oral study in dogs with triclopyr acid, the NOAEL was ≤2.5 mg/kg/day (HDT) in males and females, and LOAEL was >2.5 mg/kg/day in males and females based on toxicologically non

- significa nt decreased rate of phenolsulfothalein (PSP) due to competition between triclopyr and PSP for renal excretion.

i v

. In a 3

- week dermal study on rabbits with triclopyr

- BEE, the NOAEL was 1000 mg/kg/day (males and females), and LOAEL was > 1000 mg/kg/day based on decreased alkaline phosphatase in both sexes and increased absolute and relative liver weight in males were considered marginal and not of toxicological significance.

5. Chronic toxicity

.

i. In a 228

- day feeding study in dogs with triclopyr acid, the NOAEL was 10 mg/kg/day in males and females, and LOAEL was 20 mg/kg/day in males and females based on decreased body weight gain (in males), decreased hematological parameters (in males), changes in clinical chemistry (in both sexe s), and liver histopathology (in both sexes).

ii. In a 1

- year feeding study in dogs with triclopyr acid, the NOAEL was ≤5 mg/kg/day in males and females, and LOAEL was >5 mg/kg/day in males and females based on changes in clinical chemistry which are due not to toxicity, but a physiologic response of the dog based on limited ability of the dog to excrete organic acids at higher plasma concentrations.

iii. In a 2

- year rat chronic / carcinogenicity study with triclopyr acid the NOAEL was 12 mg/kg/day in males, ≤ 36 mg/kg/day in females , and LOAEL was 36 in males, > 36 mg/kg/day in females based on marginal increases in proximal tubular degeneration at 6 months. Increase in adrenal gland pheochromocytoma in males and significant trend (<0.05) for mammary gl and adenocarcinoma in females.

iv. In 22

- months mouse chronic / carcinogenicity study with triclopyr acid the NOAEL

was 84 mg/kg/day in males, 109.5 mg/kg/day in females , and LOAEL was 143 mg/kg/day in males, 135 mg/kg/day in females based on decreased weight gain

. No evidence of carcinogenicity in males , but females had a significant trend (< 0.05) for mammary gland adenocarcinoma

. EPA has established the reference dose (RfD) for triclopyr at 0.05 mg/kg/day for chronic risk assessment. The RfD is based on a 2

- generation reproductive toxicity study with6

triclopyr acid in rats with a NOAEL of 5 mg/kg/day and uncertainty factor of 100. The NOAEL was selected based on the increased incidence of proximal tubular degeneration in some P1 and P2 parents of both sexes at the next dose level of 25 mg/kg/day.

Carcinogenicity

. A cancer risk assessment is not required. The Agency’s Carcinogenicity Peer Review Committee, according to 1986 Guideline for carcinogenic risk assessment, has established that triclopyr is classified as “Group D chemical”

– not classifiable as to human carcinogenicity (16). The guidelines on Agency’s cancer classification hav e been changed. According to the current Guidelines (2005) triclopyr w ould be classified as ‘Not likely to be carcinog enic to humans’ which would be equivalent to ‘Group D chemical’ classification per 1986 Guidelines

.

6. Animal metabolism. Disposition and metabolism of 14 C

- triclopyr in rats demonstrated that triclopyr was well absorbed after oral administration. Excretion was relatively rapid with a majority of radioactivity eliminated in the urine by 24 hours. At the high dose of 60 mg/kg, urinary elimination of 14 C

- tricl opyr was decreased due to apparent saturation of renal elimination mechanisms. Fecal elimination of 14 C

- triclopyr was a minor route of excretion, as was elimination via exhaled air. Un

- metabolized parent chemical represented >90% of urinary radioactivity, with the remainder accounted for by the metabolite 3,5,6

- trichloro

- 2

- pyridinol (3,5,6

- TCP), and possible glucuranide and/or sulfate conjugates of 3,5,6

- TCP. Plasma elimination following intravenous administration of 14 C

- triclopyr was consistent with a one

- compartment model with an elimination half

- life of 3.6 hour and zero

- order kinetics from 0

- 12 hours at the 60 mg/kg dose

.

7. Metabolite toxicology

. In animal metabolism studies, <10% 3,5,6

- trichloro

- 2

- pyridinol (TCP) was found as a significant metabolite. Toxicity of TCP was studies in a toxicity package of studies viz. acute, sub

- chronic, genotoxicity, developmental toxicity studies revealed that the TCP has similar toxicity as of parent molecule, triclopyr. EPA in 1998 has also made the same conclusion i n EPA R.E.D facts on triclopyr.

8

. Bioequivalency

. T oxicology studies conducted with triclopyr have been performed using both the free acid and the triethylamine salt from of triclopyr. Bioequivalency of the two chemical forms of triclopyr ha s been addressed through the conduct of special studies with the triethylamine from of triclopyr

. These studies, which included data on comparative disposition, plasma half

- life, tissue distribution, hydrolytic cleavage under physiological and environmental conditions for triclopyr triethylamine salt were found to adequately address the issue of bioequivalence

. In addition, subchronic toxicity studies supported the pharmacokinetics data in demonstrating bioequivalence

.

9

. Endocrine disruption

. The examination of the existing triclopyr data

- set including reproductive toxicity studies did not reveal any potential for specific modulation of endocri ne systems in the test species. There is no evidence to suggest that triclopyr has an effect on the endocrine system.

10

. Immunotoxicity

. The existing data

- set on the triclopyr does not suggest any7

indication of immunotoxic potential of triclopyr. However, recently, a 28

- day immunotoxicity study was conducted on the male F344/DuCrl (most sensitive species and sex for triclopyr toxicity). Triclopyr up to 250 mg/kg/day did not caused the immunotoxicity in rats confirms the non

- immunotoxic potential of triclopyr.

1 1

. Neurotoxic ity. There is no indication that triclopyr is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional UFs to account for neurotoxicity, as also specified in the Triclopyr Pesticide Tolerance document (2002)

.

C. Aggregate Exposure

1. Dietary exposure

. The exposure and risk resulting from agricultural uses of triclopyr was considered for the U.S. population and special sub

- populations. There are
two direct sources of exposure to humans considering triclopyr ’s uses across all labels: from food intake and from consuming drinking water

. The exposure and risk are estimated in this report for different durations of both routes of exposure and their aggregated contribution. In an aggregate assessment, exposures from food residues were combined with conservative estimates of potential water residues , as well as potential residential exposure

. The current approach of the EPA Office of Pesticide Programs (OPP) is to use a tiered approach for acute dietary risk assessmen t that proceeds from very conservative assumptions about food residues, to inclusion of more realistic residue values measured closer to the point of consumption

.

i. Food. The process of dietary risk assessment of pesticides considers chronic and acute exposures to the U.S. population and sensitive population sub

- groups. A dditional exposures from potential residues in drinking water were also combined with acute and chronic food exposure estimat ions

. The Dietary Exposure Evaluation Model (DEEM

- FCID, ver sion 4.02 ), a commercially available software package, was used to estimate exposure to triclopyr via food consumption by the general U.S. population and certain subgroups. The model combined the consumption data and residue data for a given pesticide to a nalyze dietary risk.

Food consumption data from NHANES/WWEIA food consumption survey data, i.e., the 2005

- 2010 data were used in this assessment. The food consumption data, i.e., foods as consumed, were translated into raw agricultural commodities and their food forms using recipe translation files contained within the DEEM software.

a. Acute dietary exposure

. EPA has established an acute reference dose (aRfD) for the purpose of the acut e dietary assessment set at 0. 05 mg/kg/day for f emales 13

- 50 years old , the population sub

- group of concern . This was based on the NOAEL of 5 mg/kg/day is based on a 2

- generation reproductive toxicity study with triclopyr acid in rats with a NOAEL of 5.0 mg/kg/day and uncertainty factor of 100. The 100

- fold safety factor includes intraspeci es and interspecies variations. Exposures fro m all existing and proposed residues result in very low acute exposures

. Using the above assumptions for the assessment, the food + refined water exposure to triclopyr for females 13

- 50 years old8

at the 95 th percentile was estimated to be 0.0 25328 mg/kg/day that utilized 51 % of the aRfD.

b. Chronic dietary exposure

. EPA has established a chronic reference dose (cRfD) for triclopyr at 0.0 5 mg/kg/day for all population subgroups. The cRfD is based on a 2

- generation reproductive toxicity study in rats with a NOAEL of 5.0 mg/kg/day and uncertainty factor of 100. The 100

- fold safety factor includes intraspecies and interspecies variations. No additional FQPA safety factor is required . The food + refined
water exposure for the overall U.S. population was estimated for the assessment to be 0.00 4447 mg/kg/day that utilize d 8 .9 % of the cRfD using the refined Tier 2 conservative exposure assumptions of 100% crop treated , tolerance values and USDA

- PDP refined water values

. The population subgroup with the highest potential for exposure was Children 1

- 2 years old with food + water exposure of 0.0 26612 mg/kg/day that represented 53 % of the cRfD.

c. Cancer dietary exposure

. A cancer risk assessment is not required

.

ii. Drinking Water

. Direct measurements of triclopyr in drinking water were available from USDA

- PDP sources which were more realistic than e stimates of potential water concentrations resulting from agricultural use of triclopyr were using two environmental models, SCI

- GROW and GENEEC which assum es certain environmental degradation properties for triclopyr and modeled dynamics of ground water and surface water bodies. Based on the USDA

- PDP monitoring data for the 2002

- 2003 timeframe, the averag e concentration from drinking water sources in multiple states across 8 99 water samples with triclopyr at or above the LOD, was 24.9 ppt (0.0000249 ppm). Based upon PDP data, water samples were measured from 2002

- 2010, inclusive of both maximum and average concentrations from drinking water sources in multiple states. A total of 3261 water sample s were analyzed for triclopyr. Of the 3261 samples, 565 had detects of triclopyr at or above the Level of Detection (LOD). The maximum concentration during this per iod of ti me was 566 ppt (0.000566 ppm). This refined number is appropriate for refined chronic dietary assessment. The appropriate maximum concentration in water for the acute dietary assessment is 400 ppm set from the Drinking Water Level of Concern (DWLOC) of 0.4 ppm (400 ppb) established as part of the registration of the aquatic uses of triclopyr dimethyl amine

. The potential, acute, aggregate exposures from food and drinking water for females 13

- 50 years old is approximately 0.0 25328 mg/kg

- bw/day or 51 % of the acute reference dose (aRfD) for the upper 9 5 th %tile of the population using a n assessment refined for water

. Potential chronic exposure to water residues was estimated using 0.566 ppb for the two commodities, i.e., “water, direct, all sources” and “water, indirect, all sources” for input to DEEM

- FCID for chronic water (Tier II) analysis. After considering all existing and proposed uses, the exposure to triclopyr residues is 53 % of the chronic reference dose for the most exposed population sub

- group, Children 1

- 2 year s old

.

2. Non

- dietary exposure

. Triclopyr is currently registered for use that could result9

in short

- term and intermediate

- term residential exposure and the Agency has determined that it is appropriate to aggregate chronic food and water and short

- term exposures for triclopyr, as well as aggregate chronic food and water and intermediate

- term exposures for triclopyr

.

D. Cumulative Effects

Dow AgroSciences has submitted to EPA an assessment of common mechanism of toxicity of triclopyr and other related compounds. Data indicate that cumulative toxicological effects of triclopyr with other environmental compounds are unlikely. Triclopyr also shares a common metabolite, 2,5,6

- trichloro

- 2

- pyridinol (TCP) with the insecticide chlorpyrifos / chlorpyrifos

- methyl . The Agency found no risk of concern based on the assessment of likely combined exposures to TCP from both triclopyr and chlorpyrifos / chlorpyrifos

- methy l

. E. Safety Determination

1. U.S. population

. Using the above conservative exposure assumptions and taking into account the completeness and reliability of the toxicity data, acute and chronic dietary food exposure to triclopyr from milk, milk fat and fat using tolerance values and

re finement (Tier 2 ) of the water values using USDA

- PDP data, resulted in risk estimates of 8.9 % of cRfD for the general U. S. population when the amended fat tolerance, milk tolerance and additional milk fat tolerance w as included in the assessment with all existing uses of triclopyr . Generally, EPA has no concern for exposures below 100% of the chronic reference dose (cRfD) because the cRfD represents the level at or below which daily dietary exposures over a lifetime will not pose appreciable risks to human health.

Likewise, the acute dietary food exposure at 95 th percentile for f emales 13

- 50 years old

, the population sub

- group of concern is 51 % of acute reference dose (aRfD). Therefore, there is no concern for exp osure because the acute RfD represents the level at or below which a single daily exposure will not pose appreciable risks to human health.

Cancer dietary risk assessment was not required

.

Short

- term and intermediate

- term risks are considered appropriate to aggregate with chronic food and water exposures for triclopyr

. Adjusting for the above newly calculated exposure for food and water (mg/kg per day) resulting from amended and proposed tolerances, short

- and intermediate

- term aggregate MOEs d o not exceed the LOC

. Therefore, based on these risk assessments, Dow AgroSciences concludes that there is reasonable certainty that no harm will result to the U. S. population from aggregate exposure to triclopyr residues.

2. Infants and children

. EPA uses a weight evidence approach in determining what safety factor is appropriate for assessing risks to infants and children. This approach takes into account the nature and severity of the effects observed in pre

- and post

- natal10

studies and other info rmation such as epidemiological data. The completeness and adequacy of the toxicity database is also considered.

Toxicity database and exposure data for triclopyr are complete. EPA has considered in
utero and/or postnatal exposure in the acceptable prenatal developmental toxicity studies with rat and rabbits as well as in a 2

- generation reproductive toxicity study in rats . EPA has previously determined that no additional safety factor to protect infants and children is necessary for triclopyr for ass essing risk to infants and children

. Using the conservative assumptions described above, the chronic dietary exposure to triclopyr will utilize 14 % of the cRfD for All Infants (<1 yr old), 53 % of the cRfD for children 1

- 2 yrs old and 29 % of the cRfD for children 3

- 5 yrs old. In assessing the potential for additional sensitivity of infants and children to residues of triclopyr

, data from developmental toxicity studies in rats and rabbits and a 2

- generation reproduction study in the rat ar e considere d. The developmental toxicity studies are designed to evaluate adverse effects on the developing organism resulting from pesticide exposur e during prenatal development. Reproduction studies provide information relating to effects from exposure t o the pesticide on the reproductive capability and potential systemic toxicity of mating animals and on various parameters associated with the well

- being of offspring. T he completeness and adequacy of the toxicity data base is also considered. EPA has prev iously determined that no additional safety factor to protect infants and children is necessary for triclopyr and that the RfD of 0.0 5 mg/kg/day is appropriate for assessing risk to infants and children.

Therefore, based on the completeness and reliabilit y of the toxicity data and the conservative exposure assessment, Dow AgroSciences concludes with reasonable certainty that no harm will result to infants and children from the aggregate exposure to triclopyr from all current and proposed ending uses.

F. International Tolerances

MRLs for residues of triclopyr have been established by EPA, Australia , Canada, and Japan

. Based upon a review of the tolerance values it can be concluded that the tolerances in milk and related commodities are not harmonized. The disharmony may be attributed to differing definitions of the milk commodity and the corresponding fat content.