Document ID: EPA-HQ-OPP-2007-0020-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-06-27T04:00Z

Study Title

	Notice of Filing to Establish 

An Import Tolerance for Thiram in Bananas

	Guideline Requirement

	August 3, 1996 Food Quality Protection Act

	Author

	Vincent J. Piccirillo, Ph.D., DABT

	Consultant Toxicologist

	Sponsor

	Taminco Inc.

	Report Date

	November 15, 2006

	Study Identification Number

	Taminco Inc.

	Thiram1006b

	Page 1 of 6

	STATEMENT OF NO DATA CONFIDENTIALITY CLAIMS

STATEMENT OF NO DATA CONFIDENTIALITY CLAIMS

No claim of confidentiality is made for any information contained in
this study on the basis of its falling within the scope of FIFRA
0(d)(1)(A), (B) or (C).

Company:  Taminco Inc.

Company Agent:  Vincent J. Piccirillo                                
Date:  November 22, 2006                                                
     

   

                                                   



	STATEMENT OF GOOD LABORATORY PRACTICES COMPLIANCE

Good Laboratory Practices and Quality Assurance statements are not
relevant for this document. 

Company Agent:   Vincent J. Piccirillo                                  
Date: November 22, 2006                

                                                                 

Title: Authorized Agent for Taminco

I.	Statutory Findings and Information Summary

Taminco is requesting the establishment of an import tolerance for the
fungicide Thiram on bananas.  Thiram is currently registered for foliar
treatments on strawberries and peaches, for seed treatment prior to
planting for numerous vegetable and field crops and as a turf fungicide
on golf course tees and greens and, with restrictions, as an animal
repellent on residential ornamental plants. An import tolerance is being
maintained for thiram on apples. 

A. Residue Chemistry

1.  Plant metabolism.  The metabolism and chemical nature of residues of
thiram in plants has been extensively evaluated and is adequately
understood. 

            2.  Analytical method.  Banana samples were analyzed
according to Analytical   Method# Meth-100, Revision #4, "Determination
of Thiram in Raw Agricultural Commodities, Processed Commodities and
Other Plant Material."   Detection and quantitation for thiram (as CS2)
were conducted using gas chromatography (GC) employing sulfur-specific
flame photometric detection (FPD).  The limit of quantitation (LOQ) was
0.05 ppm.

3.  Magnitude of residues.  Banana residue trials were conducted in 5
countries that represent the major banana growing countries that export
bananas to the United States.  Formulations containing either 42% thiram
or 60% thiram were applied at a rate of 1.12 pounds thiram per acre.  
Application began when the fruit had completely emerged from the flower,
were trimmed and bagged.  The applications continued on a five to seven
day basis until immediately prior to harvest maturity for a total of 10
applications.   Analytical results support the establishment of import
tolerance of 0.5 ppm for whole bananas and 0.3 ppm for banana pulp. The
LOQ for the analytical method was 0.05 ppm.

B.  Toxicology Profile

A Reregistration Eligibility Decision has been rendered for thiram.  The
studies used for acute and chronic dietary risk assessments are
summarized in the sections below.   

ation LC50 for was ≥ 3.46 mg/L (Toxicity Category III).  Thiram is a
moderate eye irritant, a very slight dermal irritant and may be a skin
sensitizer.   

2. Acute dietary toxicity endpoints.	

An acute neurotoxicity study provided the endpoint for the acute dietary
risk assessment for all populations.  In the acute neurotoxicity study,
Sprague-Dawley rats/sex/dose were orally gavaged at 0, 5, 150, and 600
mg/kg, and were subsequently evaluated in functional observational
batteries (FOB) and motor function observations.  Neuropathological
evaluations were performed.  The Lowest Observed Adverse Effect Level
(LOAEL) was 150 mg/kg based on FOB effects (lethargy, lower temperature,
reduced startle response, no tail pinch response), reduced motor
activity, and reduced brain weights. The No Observable Adverse Effect
Level (NOAEL) for neurotoxicity was 5 mg/kg.  The acute reference dose
(ARfD) for the general population was 0.05 mg/kg.

	A developmental neurotoxicity study in rats provided the endpoint for
the acute dietary risk assessment. In that study, 4 groups of 24 female
Crl:CD(SD)BR IGS rats received diets containing 0, 20, 45 or 90 ppm
thiram from gestation day 3 through postnatal day 20.  The maternal
systemic and neurotoxicity LOAEL was 90 ppm based on decreased body
weight, body weight gain and food consumption, clinical signs of
toxicity and FOB findings.  The maternal NOAEL was 45 ppm.  The
offspring systemic and neurotoxicity LOAEL was 45 ppm based on increased
locomotor activity in females on PND 17.  The offspring NOAEL was 20
ppm.  The ARfD for females 13+ was 0.014 mg/kg/day.     

3. Chronic dietary toxicity endpoints.  

Two studies were selected to provide the endpoint for chronic dietary
risk assessment.   These studies were a combined chronic
toxicity/carcinogenicity study in rats and a chronic oral toxicity study
in dogs. 

In the combined chronic/oncogenicity study, Thiram technical was
administered to albino rats Crl:CD®(SD)BR (60/sex/dose) in the diet at
concentrations of 0, 16.3, 119, 262 ppm.for 104 weeks.  The LOAEL was
119 ppm (based on a reduction in body weight gain, changes in hematology
and clinical chemistry parameters, and an increased incidence of bile
duct hyperplasia.  The NOAEL was 16.3 ppm (1.8 mg/kg/day for females and
1.5 mg/kg/day males).

Thiram was administered to 6 beagle dogs/sex/dose in the diet at levels
of 0, 30, 90, and 250 ppm for 52 weeks.  The LOAEL was 90 ppm (2.6
mg/kg/day) based on elevated cholesterol levels and increases in
liver-to-body weight ratio. The NOAEL was 30 ppm (0.84 mg/kg/day).

These studies were considered co-critical in establishing the cRfD. 
Based on the overall results, the Agency determined that the NOAEL for
chronic toxicity was 1.5 mg/kg;day. The chronic reference dose (cRfd)
was  0.015 mg/kg/day. 

C.  Aggregate Exposure 

	An aggregate risk assessment was performed by USEPA during the RED
process to encompass the domestic uses of thiram.  There will not be any
domestic applications to bananas so an aggregate risk assessment
including this use is not appropriate. 



D.  Cumulative Effects

The USEPA is developing methodologies for assessing cumulative risks for
chemicals having common mechanisms of toxicity.   No available data
indicate that the toxic effects produced by thiram would be cumulative
with those of any other chemical compounds. 

E.  Safety Determination 

	Dietary safety determinations were performed by addition of the dietary
exposures derived from imported bananas to the dietary exposures
calculated by the USEPA in its dietary risk assessments during the RED
process. 

1.  Acute dietary safety determination.  The acute dietary exposure for
the General U.S. Population was 32.9% of the ARfD.  The most highly
exposed population was Children 1-2 years of age with dietary exposure
of 87.9% of the ARfD.  The dietary exposure of Females 13+ was 74.8% of
the appropriate ARfD.   

2. Chronic dietary safety determination.  Chronic dietary exposure for
the General U.S. Population and the multiple population subgroups was at
or below 3.7% of the CRfD, with the most highly exposed population group
being Children 1-2 years of age (3.7%).   

F. International Tolerances

,

_

`

b

c

d

g

j

#

$

%

&

g

h

i

j

ž

Ÿ

 

¡

¢

£

¤

¥

Ø

Ù

Ú

摧㺟@ᬀj

£

¥

¦

Ù

"

#

S

T

~

¸

Â

Ü

ü

#

$

R

S

hiocarbamate), ferbam, propineb, polycarbamate, mancozeb, maneb and
metiram which are calculated as carbon disulfide.  Applicable MRLs
(Codex, February 2006) for thiram are apples (5 ppm), bananas(2 ppm),
stone fruits ( 7 ppm) and strawberries (5 ppm).    

                                                  Thiram 1006b	

 PAGE  1