EPA Registration Division contact: Andrew Ertman; 703

- 308

- 9367

PP# 2E8068 EPA has received a pesticide petition PP# 2E8068 from BASF Corporation

, Research Triangle Park, NC 27709 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of Boscalid (BAS 510F); [3

- pyridinecarboxamide, 2

- chloro

- N

- (4'

- chloro(1,1'

- biphenyl)

- 2

- yl)

- ] in or on the raw agricultural commodity for A rtichoke , globe at 6.0 parts per million (ppm)

, Berry , low growing, s ubgroup 13

- 07G at 4.5 ppm , Bushberry,

s ubgroup 13

- 07B at 13 ppm, Caneberry, subgroup 13

- 07A at 6.0 ppm, E ndive , Belgium at 5 .0 ppm , Fruit, citrus, g roup 10

- 10 at 1.6 ppm, Fruit , p ome , g roup 11

- 10 at 3.0 ppm , Fruit, small, vine c limbing , except fuzzy kiwifruit, s ubgroup 13

- 07F , at 3.5 ppm , Oilseed , g roup 20

at 3.5 ppm, Persimmon at 7.0 ppm , Turnip, greens at 18.0 ppm, Vegetable , bulb g roup 3

- 07

at 3.0 ppm , Vegetable , fruiting, g roup 8

- 10 at 1.2 ppm, Vegetab le, root subgroup 1B, except sugarbeet, at 1.0 ppm and to amend 40 CFR part 180 by removing a tolerance for residues of Boscalid (BAS 510F); [3

- pyridinecarboxamide, 2

- chloro

- N

- (4'

- chloro(1,1'

- biphenyl)

- 2

- yl)

- ] in or on the raw agricultural commodity for Bu shberry

, s ubgroup 13B at 13 ppm, Caneberry , s ubgroup 13A at 6.0 ppm, Canola, seed at 3

. 5 ppm, Cotton, undelinted seed at 1 .0 ppm, Fruit, citrus, g roup 10 at 1.6 ppm, Fruit , p ome , g roup 11 at 3.0 ppm, Grape at 3

. 5 ppm, Strawberry

at 4

. 5 ppm, Sunflower, seed at 0

. 6 ppm, Vegetable , bulb, g roup 3 at 3.0 ppm , Vegetable , fruiting, g roup 8 at 1.2 ppm, and Vegetable, root , subgroup 1 A except sugarbeet, garden beet, radish , and turnip at 1.0 ppm

. EPA has determined that the petition contains data or information reg arding the elements set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry 1. Plant metabolism

. Nature of the residue studies (OPPTS Harmonized g uideline 860.1300) were conducted in grapes, lettuce and beans as representative crops in order to characterize the fate of boscalid ( B AS 510F) in all crop matrices. In all three crops the boscalid ( B AS 510F ) Residues of Concern (ROC) were characterized as parent boscalid ( B AS 510F) . A confined rotational crop study also determined that parent was the residue of concern in the representative crops of radish, lettuce and wheat. 2. Analytical method

. In plants , the parent residue is extracted using an aqueous organic solvent mixture followed by liquid/liquid partitioning and a column clean up. Quantitation is by gas chromatography using mass spectr ometry (GC/MS). In livestock the residues are extracted with methanol. The extract is treated with enzymes in order to release the conjugated glucu ronic acid metabolite. The residues are then isolated by liquid/liquid partition foll owed by column chroma tography. The hydroxylated metabolite is acetylated followed by a column clean

- up. The parent and acetylated metabolite are quantitated by gas chromatography with electron capture detection. 3. Magnitude of residues

. Field trials were carried out in orde r to determine the magnitude of the residue of boscalid ( B AS 510F ) in G lobe artichoke, Belgium endive, andpersimmon. Field trials were submitted previously on sunflower, rapeseed and cottonseed for individual tolerances; however these crops can now be co nsidered as representative crops for Crop Group 20, Oilseeds. Field trials in the representative commodities for the following crop groups were previously submitted for crop group tolerances: Bulb Vegetable 3

- 07, Fruiting Vegetable 8

- 10, Citrus Fruit 10

- 1 0, Pome Fruit 11

- 10, Caneberry subgroup 13

- 07A, Bushberry subgroup 13

- 07B, Small Fruit Vine Climbing subgroup 13

- 07F and Low Growing Berry subgroup 13

- 07G. These crop groups should be updated with the recent crop group changes. The number and locations o f field trials are in accordance with OPPTS Guideline 860.1500. Field trials were carried out using the maximum label rate, the maximum number of applications, and the minimum pre

- harvest interval for each

crop or crop group.

B. Toxicological Profile 1. Acute toxicity

. B ased on available acute toxicity data , boscalid and its formulated products do not pose acute toxicity risks. The acute toxicity studies place technical Boscalid ( BAS 510 F ) in toxicity category IV for acute oral; category III for acute dermal and category IV for acute inhalation. Boscalid is category IV for both eye and skin irritation and it is not a dermal sensitizer. For Globe artichoke, Belgium endive, and persimmon, the product proposed is Pristine® fungicide (BAS 516 02/04F) , a w ater dispersible granule (WG) formulation containing a 2:1 mixture of boscalid (BAS 510F ) and pyraclostrobin (BAS 500F). Pristine® fungicide (BAS 516 02/04F) has an acute oral toxicity category of III, acute dermal of category III, acute inhalation of cat egory IV, eye irritation of category III, skin irritation of category IV, and is not a dermal sensitizer. For the expanded crop groups, t he product s proposed are Endura® fungicide ( BAS 51 0 02/04 F ) containing boscalid (BAS 510F) as the active ingredient and Pristine® fungicide (BAS 516 02/04F)

. Endura® fungicide (BAS 510 02/04F) has an acute oral toxicity category of III, acute dermal of category III, acute inhalation of category IV, eye irritation of category III, skin irritation of category IV, and is not a dermal sensitizer. 2. Genotoxicty

. Ames Test (1 Study; gene point mutation): Negative; In Vitro CHO/HGPRT Locus Mammalian Cell Mutation Assay (1 Study; point gene mutation): Negative; In Vitro V79 Cell Cytogenetic Assay (1 Study; Chromosome Damage): N egative; In Vivo Mouse Micronucleus (1 Study; Chromosome Damage): Negative; In Vitro Rat Hepatocyte (1 Study; DNA damage and repair): Negative. B oscalid has been tested in a total of 5 genetic toxicology assays consisting of in vitro and in vivo studies. It can be stated that Boscalid did not show any mutagenic, clastogenic or other genotoxic activity when tested under the conditions of the studies mentioned above. Therefore, boscalid does not pose a genotoxic hazard to humans. 3. Reproductive and develo pmental toxicity

. The potential reproductive and developmental toxicity of boscalid was investigated in a two

- generation rat reproduction study as well as in rat and rabbit teratology studies. There were no adverse effects on reproduction in the two

- gene ration study at any dose tested. The reproductive NOAEL is 10,000 ppm (1165 a nd 1181 for males and females, r espectively), the highest dose tested.

. Toxicity to the offspring was seen at 1,000 ppm in the form of decreased pup weights in the F2 males, an d at 10,000 ppm in the form of decreased pup weights for both males andfemales of both the F1 and F2 generations. The offspri ng NOAEL is 100 and 1000 ppm (11 and 116 mg/kg b.w./day) for males and females, respectively. In males of the F1 generation, redu ced body weight and reduced body weight gain were observed at 10,000 ppm. Additionally, hepatocyte degene ration was observed in male animals of both the F0 and F1 generations at 10,000 ppm. The parental systemic NOAEL is 1000 and 10,000 (113 and 1181 mg/k g b.w./day) for males and females, respectively No teratogenic effects were noted in either the rat or rabbit developmental studies. In the rat study, evidence of maternal or developmental toxicity was not observed at any dose (highest dose tested of 1,00 0 mg/kg b.w./day). In the rabbit teratology study, at the high dose of 1,000 mg/kg b.w./day a maternal body weight gain decrease compared to controls of 81% was observed during the treatment period. Reduced food consumption, reduced body weight and abort ions in three dams, were also seen at 1,000 mg/kg b.w./day. The NOAEL for both maternal and developmental toxicity was det ermined to be 300 mg/kg b.w/day

. Neurotoxicity was not observed at any dose in the developmental neurotoxicity study. Reduced pup body weights were observed at the high and mid dose levels of 1000 and 10,000 ppm (118 and 1,183 mg/kg b.w./day, respectively). No developmental toxicit y was seen at the low dose of 14 mg/kg b.w./day (100 ppm). Although no maternal toxicity was seen in t his study, other studies which evaluated more parameters at simil ar doses of boscalid demonstrated maternal toxicity. The Agency concluded that there are no residual uncertainties for pre

- and postnatal toxicity as the degree of concern is low for the susc eptibility seen in the above studies, and the dose and endpoints selected for the overall risk assessments will address the concerns for the body weight effects seen in the offspring. Although the dose selected for overall risk assessments (21.8 mg/kg b.w ./day) is higher than the NOAEL's in the 2

- ge neration reproduction study (1 1 mg/kg b.w./day) and the developmental neurotoxicity study (14 mg/kg b.w./day), these differences are considered to be an artifact of the dose selection process in these studies. For example, there is a 10

- fold dif ference between the LOAEL (113 mg /kg b.w./day) and the NOAEL (1 1 mg/kg b.w./day) in the two generation reproduction study. A similar pattern was seen with regard to the developmental neurotoxicity study, where there is al so a 10

- fold difference between the LOAEL (147 mg/kg b.w./day) and the NOAEL (14 mg/kg b.w./day). There is only a 2

- 3

- fold difference between the LOAEL (57 mg/kg b.w./day) and the NOAEL (21.8 mg/kg b.w./day) in the critical chronic dog study which was use d for risk assessment. Because the gap between the NOAEL and LOAEL in the 2

- generation reproduction and developmental neurotoxicity studies was large and the effects at the LOAEL's were minimal, the true no

- observed

adverse

- effect

- level was probably consi derably higher. Therefore, the selection of the NOAEL of 21.8 mg/kg b.w./day from the 1

- year dog study is conservative and appropriate for the overall risk assessments. In addition, the endpoints for risk assessment are based on thyroid effects seen in mu ltiple species (mice, rats and dogs) and after various exposure durations (subchronic and chronic exposures) which were not observed at the LOAEL's in either the 2

- generation reproduction or the developmental neurotoxicity studies. Based on these data, th e Agency concluded that there are no residual uncertainties for pre

- and post

natal toxicity.4. Subchronic toxicity

. The subchronic toxicity of boscalid was investigated in 90

– day feeding studies with rats, mice and dogs, and in a 28

– day dermal administ ration study in
rats. Additionally a 90

– day neurotoxicity study in rats was performed. Generally, mild toxicity was observed including alterations in various clinical chemistry parameters and effects on the liver and thyroid

. In the rat, effects observe d were increased thyroid weight and increased incidence of thyroid hyperplasia as well as follicular epithelial hypertrophy. Increased liver weights and an increased incidence of marked fatty changes in the liver were observed in mice Changes observed in dogs were increased serum alkaline phosphatase and liver weights. The lowest subchronic toxicity NOAEL was from the dog study (7.6/8.1 mg/kg b.w./day in males and females, respectively). In the 28

– day repeat dose dermal study, no systemic effects were no ted up to the highest dose tested of 1,000 mg/kg b.w./day. In a 90

– day rat neurotoxicity study , n o signs of neurotoxicity were observed in the pups or adults. The NOAEL is the highest tested of 15,000 ppm (1,050 /1,272 mg/kg b.w./day in males and females , respectively ). 5. Chronic toxicity

. The chronic toxicity/oncogenicity studies with boscalid include a
12

– month feeding study with Beagle dogs, an 18

– month B63CF1 mouse feeding study, a 24

– month Wistar rat chronic feeding study and a 24

– month Wistar rat on cogenicity study. At the highest dose tested in dogs, effects observed consisted primarily of increased liver and thyroid weights and some serum clinical chemistry changes. The NOAEL was 800 ppm (21.8 mg/kg b.w./day males; 22.1 mg/kg b.w./day females).
In the mouse oncogenicity study, d ecreased body weights were seen in both m ales and females at 8000 ppm ( 1345 and 1804 mg/kg b.w./day for males and females, respectively ) and in males at 2000 ppm (331 mg/kg b.w./day)

. Also in males at 8000 ppm, increased li ver weights and an increased incidence of peripherial hypertrophy of the liver were observed. The NOAEL was 400 ppm and 2000 ppm ( 65 and 443 mg/kg b.w./day) for male and female mice, respectively. In both the rat chronic and oncogenicity studies, the h ighest dose tested of 15,000 ppm exceeded a maximum tolerated dose (MTD) and was discontinued after 17 months. Effects observed at the next highest dose of 2,500 ppm (110/ 150 mg/kg b.w./day for males and females, respectively) were increased thyroid weig hts and histopatholigical changes in the thyroid which included follicular cell hypertrophy, hyperplasia and adenomas . The NOAEL was 500 ppm (22 and 30 mg/kg b.w./day for male and female rats, respectively )

. No evidence of treatment

- induced oncogenicity w as observed in the mouse s tudy

. In the rat, a slight increase in thyroid follicular cell adenomas was seen in both sexes at the high dose when the data from both chronic and oncogenicity bioassays are combined. A non - genotoxic (threshold) mode of action (MOA) for the thyroid follicular cell adenomas was demonstrated from results of several studies. Based on review of the available data, the Reference Dose (RfD) for boscalid was based on a 1

- yea r feeding study in dogs with a NOAEL of 21.8 mg/kg b.w./day. Using an uncertainty factor of 100, the RfD is calculated to be 0.218 mg/kg b.w./day . Based on the acute toxicity data, an acute dietary risk assessment is not needed. Threshold effects

.Boscalid was shown to be non - carcinogenic in mice . There was a slight increase in thyroid follicular cell adenom as at the high dose in both sexes in the rat. A non - genotoxic ( threshold ) MOA was demonstrated for the thyroid tumors. The Agency concluded a carcinogenicity classification of “suggestive evidence of carci nogenicity” and that a dose response assessment for cancer was not needed.
6. Animal metabolism

. In the rat, the predominant route of excretion of boscalid (BAS 510F) is fecal with urinary excretion being minor. The half

- life of boscalid is less than 24 hours. Saturation of absorption appears to be occurring at the high dose level. Boscalid is rapidly and intensively metabolized to a large number of biotransformation products. The hydroxylation of the diphenyl moiety was the quantitatively most importan t pathway. Second most important was the substitution of the Cl of the 2

- chloropyridine part against SH by conjugation with glutathione. No major differences were observed. In hens and goats the residues of concern were determined to be parent, the hydr oxylated metabolite M510 F01 (2

- chloro

- N

- (4'chloro

- 5

- hydroxy

- biphenyl

- 2

- yl)nicotinamide), and the glucuronic acid of the metabolite M510 F02.
7. Metabolite toxicology

. No additional studies were required for metabolite toxicology. 8. Endocrine disruption

. No specific tests have been conducted with boscalid to determine whether the chemical may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or other endocrine effects. However, there were no significant find ings in other relevant toxicity studies (i.e., subchronic and chronic toxicity, teratology and multi

- generation reproductive studies) which would suggest that boscalid produces endocrine related effects.

C. Aggregate Exposure 1. Dietary exposure

. An asse ssment was conducted to evaluate the potential risk due to chronic dietary exposure of the U.S. population and sub

- populations to residues of boscalid . Tolerance values for boscalid ( BOSCALID ) have previously been established and are listed in U.S. 40 CFR § 180.589. This analysis included all crops with established boscalid tolerance values, new tolerances for artichoke, Belgium endive and persimmon and tolerances for the updated crop groups 3

- 07, 8

- 10, 10

- 10, 11

- 10, 13

- 07A, 13

- 07B, 13

- 07F, 13

- 07G and 20. i. Food

. Acute Dietary Exposure Assessment An acute assessment was not needed since the U.S. EPA Toxicological Endpoint Selection (TES) Committees had previously evaluated the boscalid toxicity data and determined there were no toxic effects attributabl e to a single dose. Therefore, a quantitative acute dietary exposure and ris k assessment were not required.

Chronic Dietary Exposure Assessment A partially refined Tier 1 chronic dietary exposure assessment was conducted assu ming tolerance level residues , experimentally determined processing factors , 100% crop treated factors for all crops and NHANES Consumption data from 2003

- 1008 using version 3.14 of the Dietary Exposure Evaluation Module (DEEM

- FCID) software. Residues in animalcommodities (i.e. meat , meat byproducts, fat, milk, eggs) were included at the tolerance levels currently established and listed in U.S. 40 CFR § 180.589.

Dietary exposure estimates were compared against the established boscalid chronic Population Adjusted Dose (cPAD) of 0.2 18 mg/kg b.w./day for all populations. Results of the chronic dietary assessments are listed in the Table 1. The estimated chronic dietary exposure from crops and animal commodities was less than 28 % of the cPAD for all subpopulations. Additional refine ments such as the use of anticipated residues and adjusted crop treated factors would further reduce the estimated chronic dietary exposure. The results in Table 1 demonstrate there are no safety concerns for any subpopulation based on established and new uses, and the results clearly meet the FQPA standard of reasonable certainty of no harm.

Table 1. Summary of Chronic Dietary Exposure Assessment Considering Crops with Established and Proposed Tolerances for Boscalid Population Subgroups Exposure Esti mate (mg/kg b.w./day) %cPAD

U.S. Population 0.020542 9.4
All Infants 0.035194 16.1
Children 1

- 2 years 0.059105 27.1
Children 3

- 5 years 0.043517 20.0
Children 6

- 12 years 0.02428 11.1
Youth 13

- 19 years 0.013975 6.4
Adults 20

- 49 years 0.017067 7.8
Adu lts 50+ years 0.018957 8.7
Females 13

- 49 0.01734 8.0 %cPAD = percent of chronic population adjusted dose Exposure estimates based on tolerance values, default processing factors, and 100% CT for all crops/commodities

.

ii. Drinking water

. Based on PRZM/EXAMS and SCI

- GROW models, the estimated drinking water exposure concentrations of boscalid for chronic exposure were 26 ppb for surface water and 0.63 ppb for ground water. Drinking water contributions were assessed based on the maximum estimated b oscalid water concentrations (26 ug/L), and water consumption and body weights reported in NHANES 2003

- 1008 Consumption surveys , using version 3.14 of the
DEEM

- FCID software. The chronic estimated water exposure values are summarized in Table 2. Minimal exposure of boscalid occurs through drinking water with < 1.0% cPAD for all subpopulations.Table 2. Results for Boscalid Chronic Water Exposure Analysis Considering the Maximum Estimated Chronic Drinking Water Concentration using
DEEM

- FCID Population Water Exposure Estimate %aPAD Subgroups (mg/kg b.w./day)
U.S. Population 0.000544 0.2 All Infants (< 1 year old) 0.001404 0.6 Children (1

- 2 years old) 0.000785 0.4 Children (3

- 5 years old) 0.000662 0.3 Children (6

- 12 years old) 0.000477 0.2
Youth (13

- 19 years old) 0.000397 0.2 Females (13

- 49 years old) 0.000543 0.2 Adults (20

- 49 years old) 0.000537 0.2

Adults (50+ years old) 0.000541 0.2 cPAD = chronic population adjusted dose Based on estimated acute surface water value of 26 ug/L

Acute Aggr egate Exposure and Risk (Food and water) Since the U.S. EPA Toxicological Endpoint Selection (TES) Committees has evaluated the Boscalid toxicity data and determined there was no toxicological endpoints for acute dietary exposure, the determination of an a cute aggregate exposure and risk evaluation was not required.

Short

- and Intermediate Term Aggregate Exposure and Risk (food,water, and residential) Short

- and intermediate

- term aggregate exposure takes into account residential exposure plus chronic exp osure from food and water. Residential exposure is used to refer to non

occupational and non

- dietary exposure. No new residential uses are currently being registered for boscalid that would increase non

- dietary exposure. The residential exposure
value u sed in this risk assessment was previously determined by the EPA (Federal Register, Volume 68, No 146, July 30, 2003) and considers dermal exposure to adults from the golf course use. The MOE presented in the Table 3 is considered to be representative fo r youth playing golf because youth and adults possess similar body surface area to weight rations and because the dietary exposure for youth (13

- 19 years old) is less than that of the general US population.

Table 3. Estimated Short/Intermediate Term Aggregate Exposure and Risk of BoscalidPopulation NOAEL (mg/kg/day) Target MOE 1 Food Exposure (mg/kg/day) Water Exposure (mg/kg/day) Residential Exposure 2 (mg/kg/day) Total Exposure (mg/kg/day) MOE 3

US 21.8 100 0.020542 0.000544 0.0008 0.0218 86 996

1 Target MOE is 100.

2 Residential Exposure = Exposure to adult while playing golf.

3 Aggregate MOE = (NOAEL / (Food + Water + Residential Exposure)

Chronic Aggregate Exposure and Risk (food and water) The aggregate chronic risk includes residues of bosc alid from food and water (Table 4). Exposures from residential uses are not included in the chronic aggregate assessment. The results demonstrate there are no safety concerns for any subpopulation based on established and new uses, and that the results cl early meet the FQPA standard of reasonable certainty of no harm.

Table 4. Estimated Chronic Aggregate Exposure and Risk of Boscalid

Population Subgroup cPAD (mg/kg/day) Food Exposure (mg/kg/day) Water Exposure (mg/kg/day) Total Exposure (mg/kg/day) % cPAD U.S. Population 0.218 0.020542 0.000544 0.021086 10 All Infants (< 1 yr old) 0.218 0.035194 0.001404 0.036598 17 Children 1

- 2 years 0.218 0.059105 0.000785 0.05989 27 Children 3

- 5 years 0.218 0.043517 0.000662 0.044179 20 Children 6

– 12 years 0 .218 0.02428 0.000477 0.024757 11

Youth 13

- 19 years 0.218 0.013975 0.000397 0.014372 7 Adults 20

- 49 years 0.218 0.017067 0.000543 0.01761 8 Adults + 50 0.218 0.018957 0.000537 0.019494 9 Females 13

- 49 0.218 0.01734 0.000541 0.017881 8

2. Non

- dieta ry exposure

. No new residential uses are currently being registered for
boscalid that would increase non

- dietary exposure. A non

- occupational dermal post

application exposure/risk assessment for individuals golfing and harvesting fruit at “U

Pick” farms a nd orchards was previously conducted by EPA (Federal Register, Volume 68, No 146, July 30, 2003). Because U

- Pick is a one

- time event (duration < 1 day) and the EPA found that the oral studies indicated there were no endpoints appropriate to quantitate

acu te risk. Therefore, only the golfing scenario was evaluated with respect to non

occupational, non

- dietary exposure. The dermal MOE’s for adults playing golf were 27,000

– 74,000. Although specific MOE’s were not calculated for youths playing golf, the

a dult MOEs are considered representative since the body surface area to weight ratios for adolescents do not vary significantly from those of adults.D. Cumulative Effects Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify , or revoke a tolerance, the Agency consider ‘‘available information’’ concerning the cumulative effects of a particular pesticide’s residues and ‘‘other substances that have a common mechanism of toxicity.’’ BAS 510 F is a foliar fungicide chemically belo nging to the carboxin class of fungicides. BAS 510 F acts in the fungal cell by inhibiting mitochondrial respiration through inhibition of the succinate

- ubiquinone oxidase reductase system in Complex II of the mitochondrial electron transport chain. BAS 51 0 F shares this mode of action with only one other currently registered U.S. pesticide

- carboxin. The EPA is currently developing methodology to perform cumulative risk assessments. At this time, there is no available data to determine whether BAS 510F h as a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, BAS 510F does n ot appear to produce a toxic metabolite produced by other substances

.

E. Safety Determination

1. U.S. population

. Based on this risk assessment, BASF concludes that there is a reasonable certainty that no harm will result to the general population from the aggregate exposure to boscalid residues.

2. Infants and children

. Based on this risk assessment, BASF concludes that there is a reasonable certainty that no harm will result to infants or children from the aggregate exposure to boscalid residues.

F

. International Tolerances Several maximum residue level s (MRL) ha ve been established for Boscalid (BAS 510F) in multiple plant and animal commodities by the Codex Alimentarius Commission

. National and Import MRLs have also been established for multiple c ommodities in several countries in all regions of the world.