EPA Registration Division contact: Barbara Madden; 703 - 305 - 6463 Interregional Research Project #4 Petition Number 3E8183 EPA has received a pesticide petition ( 3E8183 ) from Interregional Research Project #4 (IR - 4), Rutgers, The State University of New Jersey, 500 College Road East, Suite 201 W, Princeton, NJ 08540 request ing, 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 under [ §180.63 6 , for cis - and trans - 1,3 - dichloropropene, including its metabolites and degradates in or on the raw agricultural commodity p ineapple at 0.0 2 parts per million (ppm). I t is proposed that c ompliance with the tolerance levels specified in §180.636 is to be determined by measuring cis - and trans - 1,3 - dichloropropene and its metabolites cis - and trans - 3 - chloroacrylic acid, and cis

- and - trans - 3 - chloroallylalcohol, in or on the commodity. The p roposed tolerances are to support post plant use in pineapple, similar to the established drip irrigation use of 1,3 - dichloropropene in grapes . EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully eval uated 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. In the 2008 EPA review for post plant use in grapes, EPA HQ - OPP - 2007 - 0637 - 0005, t he plant metabolism of 1,3 - dichloropropene was assessed as adequately understood based on soybean, tomato and sugar beet metabolism studies . Although existing studies involve pre - plant appli cations, they were conducted at application rates more than 20 times the rate for grape (and still well in excess of the proposed pineapple) use. In studies with tomatoes and soybean, no parent, 3 - chloroacrylic alcohol, 3 - chloroallyl alcohol, or 3 - chloroac yrilic acid metabolites were detected, and incorporation into natural plant constituents was demonstrated. In sugar beet, parent and metabolites were not detected and parent was shown to have been metabolized and incorporated into sucrose. 2. Analytical method. Per the 20 08 final rule (Federal Register, Volume 7 3 , Number 30 , 8212 , Feb . 13 , 20 08 , EPA - HQ - OPP - 200 7 - 0 637 ; FRL - 8345 - 1 ), adequate enforcement methodology (GC/MS) is available to enforce the tolerance expression. Analytical methods determin e resi dues of 1,3 - dichlorpropene, 3 - chloroallyl alcohol, and 3 - chloroacrylic acid at trace concentrations in samples of pineapple using capillary gas chromatography with mass selective detection (GC/MS). 3. Magnitude of residues. M agnitude of Residue s tudies are available from Hawaiian field trials conducted with 3 applications at a maximum of 25.5 lb ai/ A (seasonal total of 76.5 lb ai/A) at a drip concent ration of approximately 150 ppm; these studies support the proposed label rates. At two of the trial locations, an additional plot2 was treated three times at 76.5 lb ai/A (seasonal total of 229.5 lb ai/A), at a drip concentration of 450 ppm. The application intervals were approximately 60 days and mature pineappl e were collected at a PHI approximately 120 days after the final application . Two decline trials treated at the seasonal total rate of 229.5 lb ai/A generated samples of pineapple approximately 7, 14, 21 and 35 days after the final application. For the c ombined data set, in the w hole fruit no 1,3 - dichloropropene , 3 - chloroallyl alcohol and 3 - chloroacrylic acid residues were observed above the validated limit of quantification of 0.0 03 ppm. B. Toxicological Profile The toxicity database for 1,3 - dichloropropene was recently summarized by the EPA in 2008 final rule (Federal Register, Volume 73, Number 30, 8212, Feb. 13, 2008, EPA - HQ - OPP - 2007 - 0637; FRL - 8345 - 1) . Findings in multiple studies demonstrate the olfactory region of the nasal cavity a ppeared to be the target organ in rats , while lung adenomas were induced in mice (EPA - HQ - OPP - 2007 - 0637 - 00 4, D340059, PC Code: 029001) . A summary of the EPA endpoints for 1,3 - dichloropropene and metabolites (3 - chloroallyl alcohol and 3 - chloroacrylic acid) are found in Federal Register, Volume 73, Number 30, 8212, Feb. 13, 2008, EPA - HQ - OPP - 2007 - 0637; FRL 8345 - 1 ). Relevant 1,3 - dichloropropene endpoints for tolerance petition are 1 ) Chronic RfD = cPAD = 0.0 25 mg/kg/day and 2) a Q 1 * value of 1.22 E10 - 1 (mg/kg/day) - 1 . Both chronic endpoints use the typical separate intra and inter - species 10X uncertainty factors (UF ) . 1,3 - Dichloropropene is classified as likely to be carcinogen to human ; thus the Q* value is conservatively used for 1,3 - D and its metabolites for cancer assessment . 1. Acute toxicity. For non - occupational scenarios, EPA established an inhalation point of departure of 454 ppm and a Human Equivalent Concentration (HEC) of 75.67 ppm based on clinical signs and decreased body weight in rat acute inhalation toxicity studies (EPA - HQ - OPP - 2007 - 0637 - 00 4, D340059 and EPA - HQ - OPP - 2007 - 0637 - 005, D347789 ). 2. Genotoxicty. . As noted in the 2007 assessment (EPA - HQ - OPP - 2007 - 0637 - 00 4, D340059), some in vitro genotoxicity studies conducted on 1,3 - D were negative while in others there was positive evidence for genotoxicity; however, the positive studies suffered from confounding factors such as presence of a genotoxic stabilizing agent, use of test reagents tha t introduced artifacts and/or deficiency in glutathione - based detoxification. In multiple relevant and reliable in vivo systems with normal physiologica l levels of glutathione, 1,3 - D was consistently non - genotoxic. 3. Reproductive and developmental toxi city. Rabbit and rat inhalation developmental toxicity studies were submitted to the Agency for the 2007 assessment. Per the 2007 assessment, (and subsequent 2008 assessment) developmental toxicity was not observed in either study at any dose, but maternal toxicity was observed at all doses in the rat study and at the mid - and high - doses in the rabbit study (EPA - HQ - OPP - 2007 - 0637 - 0034, D340059 and EPA - HQ - OPP - 2007 - 0637 - 005, D347789). It was noted that although oral developmental toxicity studies were not subm itted, the Agency considered the inhalation developmental studies to be sufficient (EPA - HQ - OPP - 2007 - 0637 - 0034, D340059 and EPA - HQ - OPP - 2007 - 0637 - 005 , D347789).3 An inhalation rat reproduction study was submitted for the 2007 assessment. The 2007 assessment noted that although local and systemic effects were observed in the parent, no effects were observed in the off - spring, and no effects on reproduction were observed (EPA - HQ - OPP - 2007 - 0637 - 0034, D340059). 4. Subchronic toxicity. Non - occupational short - , intermediate - and long - term inhalation points of departure (POD) and HECs have been established for 1,3 - D. The short - term inhalation POD and HEC are 20 and 5 ppm respectively and are based on decreased maternal body weight gain in the inhalation rabbit de velopmental toxicity study. For intermediate inhalation exposure, the POD and HEC are respectively 10 ppm and 0.205 ppm based on nasal effects in the 13 - week rat inhalation toxicity study ( EPA HQ - OPP - 2007 - 0637 - 005, D347789) . Examination of the existing 1, 3 - D data set did not reveal any evidence of toxic effects on the immune system. In addition, there was no evidence of immunotoxicity in a recent 28 - day Sheep Red Blood Cell (SRBC) T - cell Dependent Antibody Response Assay (TDAR) in F344 rats (OPPTS 870.7800 ). The NOEL was 25 mg/kg/day. There is no need for further examination of potential effects of 1,3 - D on the immune system . 5. Chronic toxicity. A chronic reference dose of 0.025 mg/kg bw/day was established based on the NOAEL of 2.5 mg/kg bw/day from the combined chronic toxicity/carcinogenicity study in B6C3F1 mice. An uncertainty factor of 100 (10 interspecies; 10X intraspecies) was used (EPA - HQ - OPP - 2007 - 0637 - 005, D347789). The FQPA safety factor has been reduced to 1X (EPA - HQ - OPP - 2007 - 0637 - 005, D34778 9). 1,3 - D is currently classified by EPA as likely to be carci nogenic in humans . Based on a multi - stage model with a 3⁄4 scaling factor, a Q* of 1.22x 10 - 1 (mg/kg/day) - 1 has been established for dietary risk assessment (EPA - HQ - OPP - 200 7 - 0637 - 005, D347789 ). For the long - term inhalation exposure scenario, the POD and HEC were 5 ppm and 0.182 ppm, respectively, based on nasal histopathology in the B6C3F1 inhalation mouse oncogenicity study (EPA - HQ - OPP - 2007 - 0637 - 005, D347789). For inhalation risk, the Q1 * = 4x1 0 - 6 (μg/m3 ) - 1 or 1.8 x10 - 2 ppm - 1(EPA - HQ - OPP - 2007 - 0637 - 005, D347789) . 6. Animal metabolism. A guideline oral metabolism study in rats and a pharmacokinetic study were reviewed by the Agency during the 2007 assessment (EPA HQ - OPP - 2007 - 0637 - 004, D340059 ) . Per the 2007 assessment, the studies indicate that 1,3 - D is rapidly absorbed and distributed. There was rapid elimination in the urine and as CO 2 in expired air and small amounts in the feces. Nine metabolites were isolated from urine with two being ident ified as 1,3 - DCP - mercapturic acid and the sulfoxide derivative. 7. Degradate toxicology . The toxicity of the key degradates, 3 - chloroacrylic acid and 3 - chloroallyl alcohol (both mixtures of cis and trans isomers) was assessed in acute and subchronic toxicity studies, genotoxicity studies and rat developmental toxicity studies. Based on the results of these studies, the 2007 and 2008 EPA assessments note that the toxicity of these degradates is within the same order of magnitude as the parent compound and high dose effects are generally similar (EPA - HQ - OPP - 2007 - 0637 - 0034, D340059 and EPA - HQ - OPP - 2007 - 0637 - 005, D347789). Thus, in addition to parent 1,3 - D, these degradates are included in the chronic and canc er dietary exposure and risk4 assessments . 8. Endocrine disruption . The Agency is required under the FFDCA, as amended by FQPA, to develop an Endocrine Disruptor Screening Program (EDSP). When additional appropriate screening and/or testing protocols being considered under the Agency’s EDSP have been developed, 1,3 - D may be subjected to further screening and/or testing to better characterize effects related to endocrine disruptio n. C. Aggregate Exposure Risk assessments for 1,3 - dichloropropene food uses include 3 - chloroacrylic acid and 3 - chloroallyl alcohol (both mixtures of cis and trans isomers) metabolite . T o cover the required risk assessment s , t he 20 08 rule relied on several documents: 2008 risk assessment (D 347789 and D340059), drinking water and residential assessment (D346778) and c haracterization of drinking water . Together these are the starting point for the updated risk assessments required to support a new pineapple tolerance for 1,3 - dichloropropene : chronic and cancer assessments for 1,3 - dichloropropene, 3 - chloroacrylic acid and 3 - chloroallyl alcohol (both mixtures of cis and trans isomers) . 1. Dietary exposure. Dietary Exposure assessments for 1,3 - dichloropropene, 3 - chloroacrylic acid and 3 - chloroallyl alcohol (both mixtures of cis and trans isomers) were conducted using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM - FCIDTM, Version 3.10) was used which incorporates NHANES 2003

– 2008 2 - day consumption data . i. Food. A conservative analysis (Tier 1) was conducted with the assumption that 100% of crops with registered and proposed uses of 1,3 - D would be treated and the residues would be present at the 0.018 ppm. This is a conservative exposure estimate based on the summation of the L OQ (0.003 ppm) for each of the six available analyte . This is a conservative approach because no residues were observed in the MOR study and thus this dietary assessment is unlikely to underestimate risk . ii. Drinking water . Per Federal Register, Volume 7 3 , Number 30 , 8215 , Feb 13 , 20 08 , EPA - HQ - OPP - 2007 - 0637 ; FRL - 8345 - 1 , food and water exposure is considered within the dietary assessment for 1,3 - dichloropropene ; EPA assumptions for water exposures are reported as based on a combination of modeling and m onitoring information . For 1,3 - dichloropropene , a surface drinking water exposure value of 16.2 ppb and a ground drinking water exposure value of 0.14 ppb are used for chronic assessments. iii. Resulting Dietary Assessments. a) Acute Dietary for 1,3 - Dichloropropene (Food and Surface Water ) [Acute dietary risk assessments are performed for food use pesticides , if a toxicological study has indentified a possible effect of concern occurring as a result of a one day or single exposure. No such effects were identified in the toxicological studies for 1,3 - D (EPA - HQ - OPP - 2007 - 0637 - 005, D347789). Therefore, acute dieta ry exposure5 assessments are not required . b) Chronic Diet ary for 1,3 - dichloropropene, 3 - chloroacrylic acid and 3 - chloroallyl alcohol (both mixtures of cis and trans isomers) ( Food and Surface Water or Ground Water ) The EPA assessment in 2008 concluded that t he most highly exposed sub - group is infants , if the surface water value is used but children 1 - 2, if the ground water value is used . In 2008, t he estimated exposure to 1,3 - dichlropropene and metabolites for food and water based on surface water sources ut ilizes < 5% of the cPAD for the most highly exposed population group, infants < 1 year old. When instead groundwater is considered from food and water (ground water sources) would utilize < 1% of the cPAD for the most highly exposed population group (chil dren 1 to 2 years). Th is 200 8 1,3 - dichloropene dietary assessment (D 347789 ) was used as a starting point to update and reflect exposure from pineapple, the proposed tolerance for the 1,3 - dichloropene residues from the field studies was not corrected for p ercent crop treated ( calculated at 100% PCT ) . The updated chronic 1,3 - dichloropene dietary assessment results in 1,3 - dichloropene exposures from food and surface water of 4. 6 % of the cPAD for infants (non - nursing) , which is the population group receiving the highest exposure. This is a 0.02% change relative to the previous findings. Exposure of 1,3 - dichloropropene from food and ground water is estimated as 2 .2 % of the cPAD for children 1 to 2 year s of age . For the general population, the updated exposur e is estimated as 1.4 % of the cRfD . c) Cancer Assessment for 1,3 - Dichloropene For the cancer assessment, the same exposure data from the chronic dietary assessment based on D347789 were used along with a Q 1 * potency value of 0. 122 (mg/kg/day) - 1

. Without pineapple , the resulting predicted exposure to the US general population (food and surface water) is 0.000 344 mg/kg/day with an associated lifetime risk of 4 E - 5 and (food and ground water) is 0.000 006 mg/kg/day with an associated lifetime risk of 7 E - 6 . When exposure for pineapple is added, t he resulting output of life time risk for food and surface water is 4. 28 E - 5 and for food and ground water is 1.79 E - 6 . T he resulting increase for pineapple ( food and surface water ) is 0. 28 E - 06 or a 7 % increase in the calculated risk. The aggregated chronic dietary cancer risk assessment estimates the exposure of the US general population to 1,3 - D and its metabolites from food and water. Calculated exposure to food and water from ground water sources was 7 x10 - 7 and th e exposure from food and water from surface water sources was 4 x 10 - 5 (EPA - HQ - OPP - 2007 - 0637; FRL - 8345 - 1). In the 2007 and 2008 assessments the Agency stated that although risk from drinking water from surface water exceeded the general standard of 10 - 6, it should be noted that concentrations of 1,3 - D in tap water from ground water wells were 100 times lower than those found in the field ground water study (D340059 and D347789) and several orders of magnitude lower than modeled estimated of 1,3 - D in groun dwater . Therefore, it is highly likely that actual drinking water concentrations from surface water sources would also be lower. The Agency concluded that it did not have a concern for the aggregate cancer risk from oral exposures to 1,3 - D and its metabol ites (EPA - HQ OPP - 2007 - 0637; FRL - 8345 - 1) .6 2. Non - dietary exposure . The proposed use of 1,3 - dichloropropene for pineapple production will cause no numerical change to the non - food assessments. Therefore, the last aggregate risk assessments conducted by the Agency and relied on in the 20 08 Final Rule ( Per Federal Register, Volume 73, Number 30, 8215, Feb 13, 2008, EPA - HQ - OPP 2007 - 0637; FRL - 8345 - 1 ) are considered applicable starting points for the additional but minimal increased potential exposure from u se on pineapples . iii. Resulting Aggregate Assessments . ( Importantly, the Agency has already determined that for the acute, short - , intermediate - , and long - term assessments, the toxicity endpoints selected for inhalation and dietary exposures should not be aggregated since no common endpoints were identified at the LOAEL in studies conducted via the oral or inhalati on routes. And also that because the types of tumors observed in the inhalation and oral studies were different, the oral and inhalation cancer estimates are not aggregated . ) a) Acute Aggregate No acute dietary exposure assessment is required . The acute inhalation MOEs remain unchanged and do not exceed the Agency’s Level of Concern. b) Short T erm, Intermediate Term and Chronic Term . All n on - dietary inhalation MOEs are considered to be unchanged from the previous assessment; therefore all inhalation MOEs do not exceed the Agency’s level of concern, which is 30 for inhalation . For chronic dietary, the updated exposure estimates which include pineapple all remain less than <5% of the cPAD for all populations. c) Lifetime Aggregate Cancer Exposure for 1,3 - Dichloropropene . The Agency has previously stated that for inhalation the Agency does no t have a concern for the cancer risk from 1,3 - D. The use in pineapples does not impact that conclusion. The aggregated chronic dietary cancer risk assessment estimat es the exposure of the US general population to 1,3 - D and its metabolites from food and water. Calculated exposure to food and water from ground water sources was 7 x10 - 7 and the exposure from food and water from surface water sources was 4 x 10 - 5 ( Federal Register, Volume 73, Number 30, 8215, Feb 13, 2008, EPA - HQ - OPP - 2007 - 0637; FRL - 8345 - 1 ). In the 2007 and 2008 assessments the Agency stated that although risk from drinking water from surface water exceeded the negligible standard it should be noted that co ncentrations of 1,3 - D in tap water were considerably lower than those found in the field ground water study ( D347789 and D340059 ). Therefore, it is highly likely that actual drinking water concentrations from surface water sources would also be lower ( D347 789 and D340059 ). The Agency concluded that it did not have a concern for the aggregate cancer risk from oral exposures to 1,3 - D and its metabolites ( Federal Register, Volume 73, Number 30, 8215, Feb 13, 2008, EPA - HQ - OPP - 2007 - 0637; FRL - 8345 - 1 ) D. Cumulative Effects The risk estimates summarized in this report result only from the use of 1,3 -7 dichloro pro pene . In the 20 08 final rule for 1,3 - dichloropropene ( Federal Register, Volume 73, Number 30, 8215, Feb 13, 2008, EPA - HQ - OPP - 2007 - 0637; FRL - 8345 - 1 ), EPA reiterated that 1,3 - dichloropropene does not share a common mechanism of toxicity with other substances: EPA has not made a common mechanism of toxicity finding as to 1,3 - dichloropropene and any other substances and 1,3 - dichloropropene does not appe ar to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that 1,3 - dichloropropene has a common mechanism of toxicity with other substances . E. Safety Determination 1. U.S. population. The aggregate risk assessments support a finding that there is a reasonable certainty that no harm will result to the general population from aggregate exposure to 1,3 - dichloropropene when exposure from pineapples is included . For the acute an d chronic assessments, there were no MOEs below 70 for inhalation ; hence there were no risk concerns. The aggregate cancer risk including surface water exceeds the range of 10 - 6 , but the agency noted the conservative nature of the surface water exposure assessment and the much lower groundwater exposure assessment and concluded that it did not have a concern for the aggregate cancer risk from oral exposures to 1,3 - D and its metabo lites and thus can be considered negligible. 2. Infants and children . S e ction 408 ( 9b) (2) (C) of FFDCA provides that the E PA apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the data base on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. In 20 08 ( Federal Register, Volume 73, Number 30, 8215, Feb 13, 2008, EPA - HQ - OPP - 2007 - 0637; FRL 8345 - 1 ), Final Rule; 1,3 - dichloropropene ), EPA published endpoints for both 1,3 - dichloropropene which reduced the FQPA safety fac tor to a 1X uncertainty factor s for all applicable endpoints The risk assessments provided support a finding that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to 1,3 - dichloropropene when exposure from pineapple is included . For the acute and chronic assessments, there were no MOEs below established LOC values ; hence there were no risk concerns. F. International Tolerances Based on a search of the USDA FAS Pesticide MRL database ( http://www.mrldatabase.com/ ), to the best of our knowledge there are no international or Codex Maximum Residue Limits for residues of 1,3 - D for any pineapple commodities. The EU has established 0.05 ppm for 1,3 - D g rapes .