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 requesting, 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 [§180.636, for cis- and trans-1,3-

dichloropropene, including its metabolites and degradates in or on the raw agricultural 

commodity pineapple at 0.02 parts per million (ppm). It is proposed that compliance 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 proposed 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 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. In the 2008 EPA review for post plant use in grapes, EPAHQ-OPP-2007-0637-0005, the 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 applications, 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-chloroacyrilic 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 2008 final rule (Federal Register, Volume 73, 

Number 30, 8212, Feb. 13, 2008, EPA-HQ-OPP-2007-0637; FRL-8345-1), adequate 

enforcement methodology (GC/MS) is available to enforce the tolerance expression. 

Analytical methods determine residues 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. Magnitude of Residue studies 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 concentration of approximately 150 ppm; these 

studies support the proposed label rates. At two of the trial locations, an additional plot 
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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 pineapple 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 combined data set, in the whole fruit no 1,3-dichloropropene, 3-chloroallyl alcohol 

and 3-chloroacrylic acid residues were observed above the validated limit of 

quantification of 0.003 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 appeared to be the target 

organ in rats, while lung adenomas were induced in mice (EPA-HQ-OPP-2007-0637-004, 

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; FRL8345-1).

Relevant 1,3-dichloropropene endpoints for tolerance petition are 1) Chronic RfD 

= cPAD = 0.025 mg/kg/day and 2) a Q1 * 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-2007-0637-004, D340059 and EPA-HQ-OPP-2007-0637-005, 

D347789).

2. Genotoxicty. . As noted in the 2007 assessment (EPA-HQ-OPP-2007-0637-

004, 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 that introduced artifacts and/or deficiency in glutathione-based 

detoxification. In multiple relevant and reliable in vivo systems with normal 

physiological levels of glutathione, 1,3-D was consistently non-genotoxic.

3. Reproductive and developmental toxicity. 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 submitted, 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). 
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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 developmental 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 (EPAHQ-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, D347789).

1,3-D is currently classified by EPA as likely to be carcinogenic 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-2007-0637-005, 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 * = 4x10-6 (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 (EPAHQ-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 

CO2 in expired air and small amounts in the feces. Nine metabolites were isolated from 

urine with two being identified 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 cancer dietary exposure and risk 
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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 disruption.

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. To cover the required risk assessments, the 2008 rule relied on several 

documents: 2008 risk assessment (D347789 and D340059), drinking water and 

residential assessment (D346778) and characterization 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 LOQ (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 73, Number 30, 8215, Feb 13, 

2008, 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 monitoring 

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 dietary exposure 
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assessments are not required.

b) Chronic Dietary 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 the 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, the estimated exposure to 1,3-dichlropropene and metabolites for food and 

water based on surface water sources utilizes < 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 (children 1 to 2 years). This 2008 1,3-dichloropene

dietary assessment (D347789) 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 percent 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 years of age. For the general 

population, the updated exposure 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 Q1 * 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 0.000344 mg/kg/day with an associated lifetime risk of 4E-5 and 

(food and ground water) is 0.000006 mg/kg/day with an associated lifetime risk of 7E-6. 

When exposure for pineapple is added, the resulting output of life time risk for food and 

surface water is 4.28E-5 and for food and ground water is 1.79E-6. The resulting 

increase for pineapple (food and surface water) is 0.28E-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 the 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 groundwater. 

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 metabolites (EPA-HQOPP-2007-0637; FRL-8345-1).
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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 2008 Final 

Rule (Per Federal Register, Volume 73, Number 30, 8215, Feb 13, 2008, EPA-HQ-OPP2007-0637; FRL-8345-1) are considered applicable starting points for the additional but 

minimal increased potential exposure from use 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 inhalation 

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 Term, Intermediate Term and Chronic Term. All non-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 not 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 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 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 concentrations 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 (D347789 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-
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dichloropropene. In the 2008 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 appear 

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 and 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 

metabolites and thus can be considered negligible.

2. Infants and children. Section 408(9b) (2) (C) of FFDCA provides that the EPA 

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 2008 (Federal 

Register, Volume 73, Number 30, 8215, Feb 13, 2008, EPA-HQ-OPP-2007-0637; FRL8345-1), Final Rule; 1,3-dichloropropene), EPA published endpoints for both 1,3-

dichloropropene which reduced the FQPA safety factor to a 1X uncertainty factors 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 grapes.