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RI S KASS E S S MEIJT DATA In historical studies from 1977-78, as well as more recent data submitted by Uniroyal, daminozide produced vascular and lung tumors in mice. However, this oncogenic response may be linked to the presence of UDMH in the test material (possibly by metabolic conversion). UDMH also produced vascular and lung tumors. On the other'.lzand, the data from rat studies for both daminozide and UDMH is less significant. More specific information on these studies is shown in Table 1. The estimates of daminozide and UDMH residues in raw and produced foods are shown in Tables 2 and 3. The estimates of dietary exposure for the U.S. population as well as for specific age subsets are shown in Tables 4-9. T;lae lifetime risk of cancer for the general population due to dieta:ry exposure to UDMH was estimated to be 4 - 5 x 10-5. However, because children have a high ratio of food intake for their bodyweight and because such a high proportion of their diet comes from;foods that may have high levels of daminozide and/or UDMH residues, a cancer risk of 5-6 x 10-6 was estimated. THB NRI)C RElaORT The NRDC study, "Intolerable Risk: Pesticides in our Children's Food" examined the levels of pesticide residues found 11

in fruits 'and vegetables to determine whether they presented health hazard to preschoolers. The NRDC report quantified the preschooler's dietary exposure to 23 pesticide residues in 27 food items as well as the resultant potential health risks in terms of two endpoints--cancer and disruption in central nervous system functioning. Tlze principal findings of the study were that "Preschoolers are being exposed to hazardous levels of pesticides in fruits and vegetables. Between 5,500 and 6,000 (a risk range of 2.5 x 10 to 2.8 x 10, ) of the c»rrent population of American preschoolers may eventually get cancer solely as a result of their exposure before six years of age to eight pesticides or metabolites commonly found in fruits and vegetables." (]qRDC report, p.2) The report singled out UDNgi as "the greatest source of the cancer risk identified by NRDC." This risk was estimated as "240 times greater than the cancer risk considered acceptable by EPA following a full lifetime of exposure;" one out of 4000 children will get cancer as a result of ingesting Alar-treated apples. The report also recommended that Congress amend the current pesticide regulations to "close loopholes in EPA's and FDA's regulatory programs." Furthermore, NRDC raised concerns about how long it takes to lower tolerances or remove hazardous pesticides from t:he market, and recommended that EPA be granted the authority to takEe action more quickly. (The Executive Summary of the NRDC report: is attached.) 12

REGIIIJsTORY ACTION With his staff's data analyses and recommendations in hand, the current tolerance on Alar in apples due to expire January 31, 1989, and the findings of the NRDC report soon to be released, Jack Moore had to make a decision on Alar in addition to deciding whether or not to be interviewed for 60 Minutes. STUDY QUESTIONl3 1. Should Jack Moore appear on 60 Minutes? Discuss the pros and (cions of this decision, taking into account the fact that he is Acting Administrator of EPA. 2. :L,E he;agrees to the interview, how should Jack Moore prepare himself? 3. What regulatory decision should the Agency make on Alar? Should Jack Moore reveal this decision during his 60 Minutes interview? 4. :Cn addition to "Why hasn't EPA banned Alar?" and "Is the cairrent law adequate to protect the public from the risks of pesticides?", what additional questions should Jack Moore anticipate, and how should he'respond? 5. Vniat f,actors in addition to the "scientific facts" must Jack rkaore consider in his decision-making concerning Alar? 6. Is the current law adequate to protect the public from the risks of pesticides?

IML E .1 NEOPLASTIC RESPONSE REPORTED FOR DAMINOZIDE AND UDMH IN RODENT CARCINOGENICITY STUDIES Study Nune Species & Route DAMINOZII)E Toth, 19'77 Swiss mouse (drinking water) NCI, 19'7l3a B6C3F1 mouse (dietary) Tumor Site and Potency (if Calculated) Blood vessel sarcomas in males and females; alveolar/bronchiolar adenomas and carcinomas in males and females; kidney tumors in males Liver carcinomas in males; alveolar/ bronchiolar carcinomas and adenomas in males and females NCI, 19'713b F344 rat (dietary) Uniroya:L, CD-i mouse 1988a (dietary) UDMH Toth, 1!3'73 Swiss mouse , (drinking water) Toth, 19'77 Hamster (drinking water) Haun, 1984 F344 rat (inhalation) Haun, 1984 C57BL/6 mouse (inhalation) Uniroya7L,, CD-1 mouse 1988e (drinking water) Uterine endometrial adenocarcinomas and leiomyosarcomas in females Dose-related trend with regard to blood vessel tumors of liver in males and females; dose-related increase in alveolar/bronchiolar adenomas in males and females; no increases in vascular lung tumors by pairwise comparison Hemangiomas and hemangiosarcomas of liver in males and females; alveolar/bronchiolar adenomas and carcinomas in males and females; kidney and liver tumors in males.and females; Q1 estimated to be 8.9 (mg/kg/day) " Hemangiomas and hemangiosarsarcomas in I males; colon tumors in males and females Pancreatic islet cell adenomas and * carcinomas in males; Q , estimated to be 2.45 (mg/kg/day)'1; pulmonary adenomas ; and carcinomas in males ~ Hemangiomas and hemangiosarcomas in females; liver adenomas in females Blood vessel tumors of the liver in males and females; Q, estimated to be 0.88 (mg/kg/day)-'; alveolar/bronchiola adenomas in males and females; Q~ estimated to be 2.9 (mg/kg/day)- 6 ZOZ5546;-M

-~AbL~ 2 ESTIMATES OF DAMINOZIDE LEVELS 'IN RAW AND PRODUCED FOODS COIyMODITY PERCENT OF CROP TREATED AVERAGE, ppm DAMINOZIDE * Apples 1.00 Apple sauce (-baby ) 0.50 " " (-adul t) 0.40 Ap;ple juice (-baby ) 0.50 " t1 (-adul t) 0.40 Dried raw apples 8.00 # Dried cooked apple s 4.00 # Cherries, sweet an d sour 30 23.7 Che:rry filling (an d juice) 1.5 Grapes 0.0 Grape j uice 0.02 Grape preserves 0.02 Nectarines 3 14.5 Peaches 3 11.3 Peaches, canned 11.3 Pearkuts 0.80 Peanut butter 0. 8 0- Pea r.iut oil 0.80 Pea.rs 3 8.8 Pears, canned 8.8 Beef meat 0.01 " kidney 0.2 11 fat 0.01 " milk 0..01 Poultry teat 0.001 " eggs 0.002 Tomatoes, whole 10 0.20 Tomato j tiice 10 0.30 # Tomato puree 10 0.66 # Tomato paste 10 1.10 # Cat;'iip 10 0.50 # * For commodity items beef, beef byproducts, milk, poultry and eggs, the residue values were extrapolated from feeding studies. # Residue levels for dried apples includes a concentration factor of 8. For processed tomato products, the average residue of 0.2 ppm was multiplied by the following concentration factors to derive the value used in calculating exposure: 1.5 for tomato juice, 3.3 for tomato puree, 5.4 for tomato paste, and 2.5 for catsup.

-fAdLE 3 . ESTIMATES OF UDMH LEVELS IN RAW AND PRODUCED FOODS COMMODITY PERCENT OF CROP TREATED AVERAGE, ppb UDMFi * Apples 2.6 Apple saLtdce (-baby) 33.3 n gu (-adult) 14 0 Apple juice (-baby) . 44.0 of m (-adult) 23.9 Dried raNr apples 20.8 # Dried cooked apples 352.0 # Cherries, sweet and sour 30 18.6 Cherry filling (and juice) 108.1 Grapes 0.0 Grape juice 1.5 Grape preserves 1.5 Nectarines 3 25.0 Peaches 3 21.3 Peaches, canned 21.3 Peanuts 24.9 Peanut butter 24.9 Peanut oil 24.9 Pears 3 11.9 Pears, canned 11.9 Beef ineat: 2.0 " kic[ney 2.0 " fat: 2.0 m mi].1+e 2.0 Poultry meat 0.5 ir egCfs> 0.5 Tomatoes, whole 10 1.6 Tomato juice 10 2.4 # Tomato puree 10 5.3 # Tomato paste 10 . 8.6 # Catsup 10 4.0 .# * For beef, beef byproducts, milk, poultry and eggs, the residue values were extrapolated from feeding studies. Residue levels for dried apples includes a concentration factor of 8. For processed tomato products, the average residue of 1.6 ppb was multiplied by the following conc:entration factors to derive the value used in estimating exposure: 1.5*for tomato juice, 3.3 for tomato puree, 5.4 for tomaio paste; and 2.5 for catsup.

TAbt-E.4 ESTIMATES OF DAMINOZIDE DIETARY EXPOSURE FOR THE U.S. POPULATION * OMMODI'C!t AVERAGE DAILY CONSUMPTION (a food/ka bwt/day) RESIDUE LEVELS (in ppm EXPOSURE or ma/ka)(ma dam./ka/day) Apples, fresh 0.3074 1.00 0.000307 Apples, cooked: fresh and jui ce 0.2004 0.50 0.001000 Dried raw apples 0.0001 8.00 0.000001 # Dried cooked apple s 0.0001 4.00 0.0000004 # Apple juice, raw 0.1709 0.50 0.000085 Cherries, raw fres and raw 3uice h 0.0105 7.11 0.000075 Cherries, cooked: fresh and ju ice 0.0251 1.50 0.000038 Eggs 0.5803 0.002 0.000001 Grapes 0.0438 0.02 0.000001 Grape juice 0.0901 0.02 0.000002 Wine andl sherry 0.0842 0.02 0.000002 Nectarines 0.0130 0.45 0.000006 Peaches. 0.2154 0.34 0.000073 Peanuts, raw, cooked, and oil 0.0748 0.80 .0.000060 Pears 0.1225 0.26 0.000032 Meat 2.2318 0.20 0.000446 Milk 1.3705 0.01 0.000014 Tomatoes, whole 0.4920 0.20 0.000098 Tomato juice 0.0551 0.30 0.000017 # Tomato puree 0.1702 0.66 0.000112 # Tomato paste 0.0395 1.10 0.000043 # Catsup 0.0420 0.50 0.000021 # TOTAL 0.000951 or 9.5 x 10'4 mg/kg/day + For commodity items meat, milk, and eggs, the residue values were extrapolated from feeding studies data. Residue levels for dried apples includes a concentration factor of 8. For processed tomato products, average residue of 0.2 ppm was multiplied by the following concentration factors: 1.5 for tomato juica, 3.3 for tomato puree, 5.4 for tomato paste, and 2.5 for catsup. 1 p~a~?-cent of exposure (0.95 x 10~5 mg/kg/day) used to estimate UDMH contribution from metabolic conversion of daminozide to UDMH when estimating risk in Table 16.

ESTIMATES OF UDMH DIETARY EXPOSURE FOR THE U.S. POPULATION * AVERAGE RESIDUE DAILY LEVELS CONSUMPTION (in ppb EXPOSURE oDITY (cx food/kcr bwt/day) or ua/kq) (ua UDMH/kg/day) les, fre:all 0.3074 les, coo)ced : fresh and juice 0.2004 ed raw apples 0.0001 ed cooked apples 0.0001 le juice, raw 0.1709 rries, raw fre'sh and raw juice 0.0105 rerries, cooked: fresh aind juice 0.0251 s 0.5803 pes 0.0438 pe juice 0.0901 e and sherry 0.0842 ctarines 0.0130 ches , 0.2154 anuts, raw, cooked and oil 0.0748 ars 0.1225 at 2.2318 k 1.3705 matoes, whole 0.4920 mato juice 0.0551 mato puree 0.1702 ~mato paste 0.0395 F ! sup 0.0420 2.6 0.000799 44.0 0.008818 20.8 0.000002 # 352.0 0.000035 # 33.3 0.005691 5.6 0.000059 108.1 0.002713 0.5 0.000290 0.0 0.000000 1.5 0.000135 1.5 0.000126 0.8 0.000010 0.6 0.000129 24.9 0.001863 0.4 0.000049 2.0 0.004464 2.0 0.021068 1.6 0.000787 2.4 0.000132 # 5.3 0.000902 # 8.6 0.000340 # '4.0 0.000168 # 0.000047 or 4.7 x 10.5 + mg/kg/day For commodity items meat, milk, and eggs, the residue values were extrapo].zated from feeding studies data. All beef, beef byproducts and poultry were combined under "meat" in this table. Residue levels for dried apples includes a concentration factor of 8. For processed tomato products, average residue of 1.6 was multiplied by the following concentration factors: 1.5 for tomato juice, 3.3 for , tomato puree, 5.4 for tomato paste, and 2.5 for catsup. 1 percent. of daminozide exposure (0.95 x 10-4 mg/kg/day) added to total UDMIi dietary-exposure in Table 16 used to estimate 1 percent conversiein of daminozide in the gut.

6. -T ~ &-E TAS ESTIMATES OF AVERAGE DAILY E%FOSDRE TO DAMINOZIDE FOR SELECTED AGE SUBSETS Subset (Age and Other) Exposure (mg/kg/day) AVERRWE (U.S. POPULATION) 0.000951 Nursing infants (<1 year old) 0.003396 Non-nursing infants (<1 year old) 0.005427 Child»en (1 - 6 years old) 0.002786 Children (7 - 12 years old) 0.001514 Males (13 ® 19 years old) 0.000730 Females (13 - 19 years, not pregnant or nursing) 0.000662 Females (13 + years, pregnan t) 0.000692 Females (13 + years, nursing) 0.000824 Females. (20 + years, not pre gnant . or nursing) 0.000575 Males (20 + years old) 0.000523

-TA~LF- 7 ESTIMATES OF UDMFi DIETARY RISR FOR THE U.S. POPULATYON . . (interim Q¢j = 0.88 mg/kg/day) Commod:Hy Dietary Exposure Lua/kajday) Dietary Risk * Milk Apples Red meatv Cherries Peanuts Eggs Grapes Poultry TomatoE.: Peaches Pears Nectarines 0.021068 0.015331 0.004464 0.002772 0.001863 0.000290 0.000261 0.000252 0.000234-0.00234 0.000129 0.000049 0.000010 1.8 x 10'5 1.4 x 10-5 3.9 x 10-6 2.4 x 10'6 1.6 x 10.6 2.5 x 10'T 2.3 x 10~7 2.2 x 10'7 2.1X10,T-2.1X10-6 1.1 x 10,7 4.3 X 10-8 8.8 x 10,9 TOTALS 0.046715 4.1 X 10-' +[0.009500 estimated metabolic UDMH from daminozide) 0.84 X 10'5 4.9 X 10' * Refer, to II.C.3.b. "Uncertainties that Could Overestimate the Risk (2-3) "*.. iV