Document ID: EPA-HQ-OPP-2005-0157-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-06-27T04:00Z

COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION 

EPA Registration Division contact: Tony Kish, 703-308-9943	

ABERCO A

PetitionPP

Ppppp

	EPA has received a pesticide petition # 5F6904 from ABERCO Inc., 9430
Lanham-Severn Road, Seabrook, MD 20706 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. 

1. by establishing a tolerance for residues of 

propylene oxide in or on the raw agricultural commodity grape, raisin
at 1.0 ppm; fig at 3.0 ppm; and plum, prune, dried at 2.0 ppm. 

2. Further the petitioner proposes to delete 40 CFR 180.491 sections
(a)(2) and (a)(4).  These directions are described on the label and are
no longer required in the tolerance expression.

EPA has determined that the petition contains data or information
regarding 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                                       

. 

Propylene Oxide is reported to potentially metabolize in plants to
propylene chlorohydrin and propylene bromohydrin, and propylene glycol. 
Currently only propylene oxide is contained in the tolerance expression.

. 

	

	

3. Magnitude of the Residue

  

Fig, Prune and Raisin

Samples of fig, prune and raisin were treated with a mixture of 8% PPO:
92% CO2 for 48 hours at a rate of 35 lb/1000 ft3 at 27oC (0.05 oz active
ingredient per ft3).  In raisins residues fell to not detectable after 7
days.  For figs residues of PPO were less than 0.5 PPM after 2 days and
for prunes residues dropped to below 0.1 PPM after 2 days.  

 

B. Toxicological Profile

.  

The acute oral rat LD50 for propylene oxide has been reported by various
investigators in various species. The average value was 689 mg/kg.  
This value would place propylene oxide into EPA’s acute oral toxicity
labeling Category III.

The acute dermal toxicity of propylene oxide has been studied in the
standard rabbit model and been found to exceed 1200 mg/kg.  The reported
LD50 values would place propylene oxide into EPA’s acute dermal
toxicity labeling Category II.

The acute 4-hour inhalation LC50 for propylene oxide has been reported
by various investigators in various species. The reported values all
exceed 4 mg/L.   These values place propylene oxide into EPA’s acute
inhalation toxicity Category III.

Propylene oxide is severely irritant to the eye and is in EPA’s eye
irritation Category I.

Propylene oxide is severely irritant to the skin and is in EPA’s skin
irritation Category I.

Propylene oxide is a dermal sensitizer.

.  

The genotoxicity and mutagenicity of propylene oxide has been studied in
a variety of test systems. Generally, positive results are reported in
in vitro test systems and, with a few exceptions, negative results are
reported in in vivo tests.  

In vivo exposure in well controlled studies propylene oxide generally
does not produce mutations or other gene damage. 

.  

There is no clear evidence that propylene oxide is a developmental or
reproductive toxicant.  A summary of two major studies is presented
below.

NIOSH sponsored an investigation of the developmental toxicity of
inhaled propylene oxide in Sprague-Dawley rats and rabbits.

The only evidence of fetal malformations seen in rats was an increase in
wavy ribs and reduced ossification in rats exposed from gestation days
1-16. The incidence of rib dysmorphology and reduced ossification of
fetal ribs and vertebrae were more frequent in exposed animals. In this
study, propylene oxide was considered not teratogenic but fetotoxicity
and reproductive effects were observed. These were related to maternal
toxicity of the exposure level in rats. In rabbits, clear evidence of
maternal toxicity was not observed but the exposure level used was from
12.5% to 25% of the probable 4 hour acute LC50 in the rabbit. 

Hayes et al. (1988) conducted a 2-generation reproductive toxicity study
in F344 rats exposed to propylene oxide by inhalation. No
treatment-related effect was observed in any of the following
reproductive parameters: fertility, litter size and neonatal growth, and
survival. Furthermore, no effects attributable to propylene oxide
exposure were observed at gross pathological examination in either the
adults or weanlings or histopathological examination of the pups. In
this study PPO did not produce reproductive toxicity.  A  NOAEL for
reproductive effects of 300 ppm [713 mg/cu.m (which was the highest dose
tested)] and a NOAEL for changes in body weight of 100 ppm [238 mg/cu.m]
were identified.

A number of studies are available for evaluation of the toxicity of
propylene oxide under sub-chronic and chronic administration conditions.
These are inhalation studies but are useful for the evaluation of
potential toxicity following dietary ingestion since: (a) the PPO
systemic dose can be calculated for these studies; and, (b) in each of
these studies careful examination of toxicity endpoints and of non-tumor
lesions was made.

Based on these and other toxicology studies (acute toxicity,
carcinogenicity, sub-chronic / chronic toxicity, and developmental and
reproductive effects, the following toxicity endpoints can be selected
for propylene oxide:

Toxicology Endpoints for Propylene Oxide

Exposure Scenario	Dose (mg/kg/day)	Endpoint	Study

Acute Dietary	NOAEL = 305 mg/kg

UF = 500

FQPA SF = 1	LOAEL = 305 mg/kg/day in rats based on weight loss, ataxia,
and axonopathy effects.

 

Acute RfD = 0.61 mg/kg/day

Acute PAD = 0.61 mg/kg/day

	Rat 7-week inhalation study (Onishi et al., 1988)

Chronic (non-cancer) dietary	NOAEL = 20.3 mg/kg/day

UF = 300

FQPA SF = 1

Rat -> Human Stability Factor (RHSF) = 50-x

	LOAEL = 60.9 mg/kg/day in rats (weight gain depression, slight increase
in mortality).

Chronic RfD = 3.38 mg/kg/day

Chronic PAD = 3.38 mg/kg/day

	Reuzel and Kuper (1983) 2-year inhalation toxicity / carcinogenicity
study in SD rats

Chronic (cancer) dietary

Not likely to be carcinogenic to humans via relevant routes of exposure

	Developmental Effects

Was not teratogenic in the rat or rabbit. Fetotoxicity and effects on
maternal reproductive parameters observed but related to maternal
toxicity. 

	Reproductive Effects

Did not produce reproductive toxicity in a well conducted
multi-generation reproductive effects study. 

	

. 

On the basis of in vitro experiments, 2 metabolic pathways have been
suggested.  Propylene oxide was found to be a substrate for rat liver
glutathione epoxide transferase, while nonenzymic conjugation was
negligible.  

The nonenzymatic hydrolysis to 1,2-propanediol is rather slow.  At 37
°C, the half-life for the uncatalysed reaction in a neutral medium was
found to be 87 h.

Propanediol can be excreted unchanged via the kidneys and can be
oxidized to lactic and pyruvic acid.  

.

Propylene oxide has two metabolites, propylene chlorohydrin and
propylene bromohydrin.  Essentially propylene chlorohydrin is
unreactive.  The Agency has not required either hydrin to be part of the
tolerance expression.

.  

There is no evidence that propylene oxide functions as an endocrine
disruptor.

C. Aggregate Exposure



. 

This petition seeks modification and addition to the tolerances of
propylene oxide on processed spices, dried herbs, cocoa, nutmeats
(except peanuts), raisins, figs and prunes (only tolerances on raisins,
figs and prunes are new).  Of these only nutmeats represent a
significant dietary contributor.  Processed spices and dried herbs are
not used in a manner that would provide a significant dietary
contributor of pesticide residues.  Cocoa powder is also used in cooking
and foods to be further processed (i.e. baked goods).  Less than 1% of
the fig, raisin and prune crops would be treated and residues do not
exceed 1 PPM on any of these commodities.  

.  

The combined exposure to propylene oxide from all uses (except figs,
prunes and raisins) is summarized below.

Table: 90th %-ile PPO Diet Dose (residues assumed at tolerance level)

Group	90%-ile PPO- Consumption (nuts, spices, and cocoa)	Mid-point BW
(Kg)	90%-ile PPO Dietary  Dose

U.S. Population	Nut: 82.5 µg/day

Spice: 4.5 µg/day

Cocoa: 0.65 µg/day	70 kg	1.18 µg/kg/day

0.064 µg/kg/day

0.0093 µg/kg/day

Total: 1.25 µg/kg/day

Infants < 1 year	Nut: 0 µg/day

Spice: 4.5 µg/day

Cocoa: 0.65 µg/day	7.3 kg	0 µg/kg/day

0.616 µg/kg/day

0.089 µg/kg/day

Total: 0.705 µg/kg/day

Children, 1 – 6 years	Nut: 50.7 µg/day

Spice: 4.5 µg/day

Cocoa: 0.65 µg/day	17 kg	2.98 µg/kg/day

0.265 µg/kg/day

0.038 µg/kg/day

Total: 3.28 µg/kg/day

Children, 7 – 12 years	Nut: 84.0 µg/day

Spice: 4.5 µg/day

Cocoa: 0.65 µg/day	32 kg	2.63 µg/kg/day

0.141 µg/kg/day

0.020 µg/kg/day

Total: 2.79 µg/kg/day 

Males > 13 years	Nut: 86.7 µg/day

Spice: 4.5 µg/day

Cocoa: 0.65 µg/day	80 kg	1.08 µg/kg/day

0.056 µg/kg/day

0.0081 µg/kg/day

Total: 1.14 µg/kg/day

Females > 13 years	Nut: 83.4 µg/day

Spice: 4.5 µg/day

Cocoa: 0.65 µg/day	60 kg	1.39 µg/kg/day

0.075 µg/kg/day

0.011 µg/kg/day

Total: 1.48 µg/kg/day

. 

Since propylene oxide is currently utilized only in fumigation chambers
and is a volatile chemical, no drinking water contamination is expected.

2 Non-Dietary exposure.  

Other than those that handle propylene oxide and off-gassing of
fumigated quantities, no other forms of exposure to propylene oxide are
anticipated.

D. Cumulative Effects

Proplyene oxide is not known accumulate in animal tissue of any kind,
therefore no cumulative effects are expected.

E. Safety Determination

Based on estimates of total dietary exposure (excluding figs, prunes and
raisins), should this tolerance amendment go into effect, the percent
risk cup occupancy for various standard subpopulations of interest are
shown in the following tables. 

Percent Risk Cup Occupancy for Chronic Dietary Exposure to

PPO Residues at Tolerance Levels as Consumed

Population Group	PPO Dietary Dose	Percent Risk Cup 

cRfD = 3.38 mg/kg/day

U.S. Population	1.25 (g/kg/day	0.037%

Infants < 1 year	0.705 (g/kg/day	0.021%

Children, 1 - 6 years	3.28 (g/kg/day	0.097%

Children, 7 - 12 years	2.79 (g/kg/day	0.083%

Males, > 13 years	1.14 (g/kg/day	0.034%

Females, > 13 years	1.48 (g/kg/day	0.044%

Revised March 8, 2007

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