UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WA S HINGTON

, D .C. 20460

O F F IC E OF CH E MI C AL SAFETY AND

P O L L UTI O N PREVENTI O N

M E MORANDUM

Dat e : S e pt e mb e r I, 2 01 5

SU BJE CT : Z iram S co pin g D o cum e nt

PC C o de: 03480 5

Deci s i o n No.: 497363

P et iti on No.: NA DP Ba rco d c : 0423 9 5 1

Re gi s trati o n No.: 10 0 -8 8 9

, 100- 963

, 45728 -1 4

R eg ulat ory Action: R eg i s tration R e vi ew

Ri s k Assess m e nt T y p e: S in g l e C h emica l A g grega t e

TXR No.: N A Ca s e No.: 2 1 80

CAS N o .: 137-30-4

MR ID No. : NA 4 0 CF R: 1 80.1 1 6

FROM:

THROUGH:

T O : M a rqu ea D. Kin g

, Ph.D.

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, Ri s k Mana ge r Re v iewer

T h o m as Mo ri a rt y

, RM S I

Ri s k Ma n age m e nt and I mpl e mentation Br a nch I

P es ti c id e R eeva l ua ti o n Di v i s i o n ( 7508P )

At t ac h e d i s th e H E D I A D sc opin g d oc um e nt fo r th e fungicid e, Z iram ( al s o known a s z inc

d im e th y l d ithi oc ar ba m a t e) fo r purp os e s o f R eg i s trati o n Revi ew

. This document update s th e 2 00 3

R e r eg i s tr a ti o n E li g ibilit y D oc um e nt (RE D ) Ri sk Asses sment.Exec u t i ve S umm ary

HED and A D ha ve c on s ider e d th e available ri s k assessments for z ir a m a nd it s t ox i c it y, ex p os ure

and u s a ge d a taba ses

, a s well as th e most curr e nt Agency sc i e n ce a nd assessment policies. HED

a nd AD performed thi s evaluation in order to det e rmin e the sco p e of wo rk n e ce ssa r y to s upp ort

the established tol era nce s and ex istin g regi s tr a ti o ns durin g r eg i s tr a ti o n review. Th e prim a r y

sou rc e of inform at i o n for thi s evaluation was the most r ecen t co mpr c h ens i ve Z i ra m Hwnan

H ea lth Ri s k Assessment 1 c onduct e d to s upport the Sep temb e r 2003 US EPA Re g i stra tion

E li g ibilit y Decision ( R E D ) fo r Z iram 2

.

Zira m (Zinc dim e th y ldithioc a rbamat e) i s a dimeth y ldithi o carb a m ate fungicide used t o control

fungal di seases o n s tone fruit s pome fruits

, nut crops, vegetab l es and o rn ame nt a l s. It i s used to

prevent crop d a ma ge in the field and is also applied prior to har vest in g in order to preven t fruits

from deterioration in storage or transport. E PA has established tol e r ances of z iram on various

fruits a nd vegetab le s und e r Federal Food

, Drug and Cosmetic Act ( F FDCA) Sect i o n 408 (40

CF R § 18 0. 116 ). The antimicrobial us es of z iram are a s m a t e rial preservati ves in ad h es iv es,

cau lk s, sea l a nt s, wa llb oa rd

, and in exterior latex paint ( in-can-pr ese r va ti ve). R es id ent ial u se as a

rabbit repellant on outdoor ornamenta l s ha s b e en canceled s inc e the tim e of the RED

.

The toxicity d atabase fo r z ir a m is complete with th e exception of an immunotoxicity s tud y for

w hich the r eq uir e m e nt h as b ee n wa i ved ( HA S POC

, TXR No. 0057 1 06 3 ). T h e primar y target

o r gans of zira m appea r t o be th e nervou s system, Ii ve r

, and th yro id. A s in g l e oral do se causes

neurological imp a irm e nt s (a taxia a nd impair e d gait) while r e p eated s h o rt t erm exposu re re s ult s in

inhibition o f brain c h o line s t e ra se and brain neurotoxi c esterase in rat s. Liver hi s top at h o l ogy,

so m e tim es accompanied by increa ses in h e patic se rum e n zy m e l eve l s, was see n at var i ous do ses

in th e rat s ub c hroni c and chronic s tudi es and th e mou se carcinogenicity s tud y

. When

adm ini s t e r ed ora ll y

, z iram i s rapidly absorbed, distr i buted , a nd excreted within 72 hour s w ith a

negligible a m ou nt being distributed throu g hout the body. The tis s ue di s tribution an d excretion

data s u gges t s min i mal d e rm a l a b so rption.

In D ecember 2002

, the Cancer Assessment Revi ew Committe e (CA RC ) re

- eva lu a t ed the

carcin oge nic potential o f z iram to incorporate n ew ly r e cei ve d information

. Acco rdin g to the

E P A 's Drafl Guidel in es/o r Ca r c ino ge n Ri sk Assess m en t ( Jul y, 1 999), th e CARC reclassified

z ir a m as " Sugge s tive Evidence of Carcinogenicity

, but Not Sufficient t o Assess Hum a n

Ca rcin oge ni c Pot e ntial " based o n the occu1Tence of beni g n tumor s ( hemangioma s) in m a l e

CD(S D ) BR mal e rat s, s upp o rt e d b y an increa s in g trend in pr e putial g land adenomas in mal e

F344 rat s

. The Co mmitte e r e commended that no quantification of hum a n c arcin ogenic ri sk be

determined for z iram.

1 Ziram: I !ED Ri sk Assessmen t for the Rer eg i s tration Eligibility D ec i s ion ( R E D ) Do c um e nt. PC Code: 034805

Reregi st r a t ion Case # 2180, DP B arcode

, 0 2 88031 Submission Barcode S62 I 04 1

2 hllp: i/ www.re!!.ulation.gov / I D: E PA-H Q

- O PP-2 004-0 1 94

- 0002

3 Ziram a nd Fe r ba m : S umm ary of Hazard and Sc i e n ce Polic y Co uncil ( H AS P OC)

. Recomm e nd a ti o n s o n th e Requir e m e nt of an lmmun otoxic it y S tud y.TXR No. 0057106 D42395 I

. J. Lesh in

.

P age 2 of2 0Page 3 of 20

The 10x Food Quality Protection Act (FQPA) Safety Factor (SF) for the protection of infants and

children has been reduced to 3 X for the following reasons: (1) The toxicology and exposure

databases are complete and 2) There is no increased qualitative or quantitative susceptibility in

the rat or rabbit developmental toxicity studies (3) There are clearly defined NOAELs and

LOAELs in all submitted guideline studies (4) The dietary (food and drinking water) and

residential expo sure assessments will not underestimate the potential exposure for infants,

children, and/or women of childbearing age. The FQPA Safety Factor Committee concluded that

the safety factor is required for all population subgroups when assessing dietary and re sidential

exposures of all durations since there is quantitative evidence of increased susceptibility in the

developmental neurotoxicity study in rats.

Acute and chronic dietary risk assessments 4 were last performed to support a crop group

tolerance for z iram on p ome f ruit based on current tolerances on representative commodities of

the crop group. Estimated acute dietary exposure is below HED’s level of concern for the U.S.

p opulation and all population subgroups at the 99.9 th percentile. The resulting ri sk estimates are

8.6% of the acute population adjusted dose (aPAD) for the U.S. p opulation and 72% of the

aPAD for Children 1

- 2 years old (the most highly exposed population subgroup). Estimated

chronic dietary risks are below HED’s level of concern for th e U.S. p opulation and all population

subgroups. The resulting risk estimates are <1% of the chronic PAD (% cPAD) for the U.S.

p opulation and 7.2% of the cPAD for a ll i nfants (the most highly exposed population subgroup).

Anticipated residues based on fiel d trials

, processing studies, washing studies, and monitoring

data and percent of crop treated (%CT) were used for both the acute and chronic dietary

exposure analyses (highly refined)

. The estimated drinking water concentrations ( EDWC s ) used

in the dietary risk assessment was provided by EFED 5

. The entire distribution of water residues

were incorporated into the acute dietary exposure analysis.

T here are no residential conventional uses currently registered for ziram; therefore, a quantitative

residential exposure risk assessment is not necessary for the conventional uses during registration

review. The need for spray drift and volatilization risk assessment for the conventional uses will

be examined during registration review

. Ther e are residential antimicrobial uses of ziram (paints,

yarns and fabrics) and these will need to be assessed during registration review. The paint use

will need to be re

- assessed using the 28

- day inhalation toxicity study that was submitted after the

RED a nd the yarns and fabric use will need to be assessed if it is determined that these yarns and

fabrics are used to manufacture household goods and apparel.

The previous occupational exposure assessment 6 completed for the RED, covered all exposure

scenarios relevant to ziram and no occupational handler or post

- application risks of concern were

identified with use of appropriate personal protective equipment (PPE). Updated occupational

exposure and risk assessments may be necessary as part of registration rev iew to reflect current

HED and AD policy regarding toxicological endpoint selection and exposure assessment

methodology.

4 Ziram (034805) Reregistration Case No. 2180. Acute and Chronic Dietary Exposure and Risk Analyses for the

Adding of the Remaining Pome Fruit Group Members. T. Morton. 2/25/2010. D 323410 & D323412

5 D323411, M. Barrett, 2/18/2010

.

6 Agricultural a nd O ccupational Exposure Assessment a nd Recommendations For The Reregistration Eligibility

Decision Document For Ziram

. T. Leighton. 9/12/2001. D276788

.Page 4 of 20

The toxicity, residue chemistry and occupational exposure databases for ziram are adequate for

registration review. As part of registration review, however, the endpoints, doses, and safety

factors (SFs) used in the most recent human health risk assessment may need to be re

- evaluated

according to current HED p olicy. Updated exposure and risk assessments may be conducted if

there are any significant changes to the EDWCs

, and/or to the current scenario

- specific surrogate

handler

- exposure data

.

Chemical Use P rofile

Ziram [zinc dimethyldithiocarbamate] is a dimethyldithiocarbamate fungicide used to control

fungal diseases on stone fruits, pome fruits, nut crops, vegetables and ornamentals. It is a white

powder with a melting point of 225.5

- 251 C, density of 1 .7 g/mL, vapor pressure of 1.8 x 10

- 5 Pa

at 25 C (1.4 x 10

- 7 mmHg), and octanol/water partition coefficient (log P

ow ) of 1.65 at 20 C.

Ziram is soluble in water at 65 ppm, slightly soluble in diethyl ether and ethanol, moderately

soluble in acetone, and s oluble in dilute alkali, carbon disulfide, and chloroform. Ziram is

incompatible with copper and mercury compounds, but is the most stable of the metallic

dimethyldithiocarbamates.

Conventional u ses supported by the Ziram Task Force include use as a fungi cide on almonds,

apples, apricots, blueberries, cherries, grapes, nectarines, peaches, pears, pecans, strawberries,

tomatoes, conifers, and ornamentals

. Applications are made by air, ground boom, air blast

sprayer, and high

- pressure hand wand at applicatio n rates ranging from 2.28 pounds active

ingredient per acre (lb ai/A) to 6.08 lb ai/A. Use of ziram on blackberries remains on product

labels, but the tolerance for this use has been revoked

. Applications of ziram include dormant

and foliar treatments.

Antimicrobial uses include paints, paper and paperboard, paper coatings , adhesives, fabrics,

films, and wallboard . The application rates range from 0.1% ai for paper coatings to 3.0% ai for

non

- exterior paints. Applications are made by pouring the ziram po wder into the process vessels,

tanks or hoppers that feed into the manufacturing processes

.

There is one ziram technical product (70506

- 179) registered to United Phosphorus, Inc. There

are two end use products and three 24(c) registrations for conventional uses and there is one end

use product (45728

- 14) for antimicrobial uses

. Both registered conventional end use products are

w ater d ispersible g ranule formulations and the registered antimicrobial product is a powder

formulation

.

The no menclature and physiochemical properties of ziram are presented in Tables 2.1 and 2. 2 of

A ppendix 2

.

Hazard Identification/Toxicology

The toxicity database for ziram is complete and it is sufficient for characterization of potential

developmental, reproductive, carcinogenetic, mutagenic, and neurotoxic, effects. Z iram is a

severe eye irritant, exhibits moderate acute toxicity via the oral and inhalation routes and low

toxicity via the dermal route. It is not irritating to the skin and is a moderate dermal sensitizer.Page 5 of 20

The mechanism of action is un known. The primary target organs of ziram appear to be the

nervous system, liver, and thyroid. A single oral dose causes neurological impairments (ataxia

and impaired gait) while repeated short term exposure results in inhibition of brain cholinesterase

and brain neurotoxic esterase in rats. Liver histopathology, sometimes accompanied by increases

in hepatic serum enzyme levels, was seen throughout the database at various doses in the rat

subchronic and chroni c studies and the mouse carcinogenicity study. When administered orally,

ziram is rapidly absorbed, distributed, and excreted within 72 hours with a negligible amount

being distributed throughout the body. The tissue distribution and excretion data suggest s

minimal dermal absorption. A 28

- day inhalation study revealed changes in the larynx,

metaplasia, hyperplasia, and necrosis with inflammatory infiltration of the epithelium and ventral

cartilage. The HASPOC, based on a weight of evidence approach has dete rmined that an

immunotoxicity study is not required for ziram at this time ( TXR# 0057106 ).

In December 2002, the Cancer Assessment Review Committee (CARC) re

- evaluated the

carcinogenic potential of ziram to incorporate newly received information. According to the

EPA ’s Draft Guidelines for Carcinogen Risk Assessment (July, 1999), the CARC reclassified

ziram as “Suggestive Evidence of Carcinogenicity, but Not Sufficient to Assess Human

Carcinogenic Potential” based on the occurrence of benign tumors (hemangi omas) in m ale

CD(SD)BR male rats, supported by an increasing trend in preputial gland adenomas in male

F344 rats. The Committee recommended that no quantification of human carcinogenic risk be

determined for z iram. Therefore, the Agency has determined that quantification of risk using a

non

- linear approach ( i.e. , RfD) will adequately account for all chronic toxicity, including

carcinogenicity, that could result from exposure to ziram. In addition, the Committee determined

that no conclusion can be reached r egarding the potential of ziram to induce chromosome

aberrations in the whole animal. Based on the acceptable in vitro data with purified ziram, an in

vivo concern is not apparent. However, when the in vivo data were revisited, it was found that

there wa s no information in the published studies regarding the purity of the ziram samples and

that the studies were compromised by other serious deficiencies. Consequently, the dominant

let hal assay is no longer required and the available acceptable studies sati sfy the guidelines for

mutagenicity.

The acute, subchronic, and chronic toxicity profile tables for ziram are included in Appendix 1,

Table 1 and 2. Toxicity endpoints, points of departure (PODs), and uncertainty/safety factors

( UF/SFs) were selected fo r oral, dermal, and inhalation exposure pathways for the Human Health

Risk Assessment conducted in 2001, and these are shown in Appendix 1

, Table 3

.

Upon review of the toxicology data and consideration of all available data including the open

literature, the endpoints for risk assessment and all uncertainty factors may be re

- evaluated

during registration review to reflect current HED policies.

Conclusions: The toxicity data base for ziram is considered complete and is adequate for

assessing potential carcinogenetic, mutagenic, developmental, neurotoxic, reproductive

, and

immunotoxic effects. During registration review, the endpoints and safety factors for risk

assessment may be updated to reflect current policies.Page 6 of 20

Residue Chemistry

Conventional Uses

The qualitative nature of the residue of ziram in plants and livestock is adequately understood.

The additional metabolism data required in the RED have been submitted and reviewed. The

HED Metabolism Assessment Review Committee (MARC ) had determin ed that the current

carbon disulfide ( CS 2 ) common moiety method would likely include the residues of toxicological

concern. This conclusion was confirmed by new apple and livestock metabolism studies. Ziram

residues convertible to CS 2 are the residue of co ncern for tolerance expression and/or risk

assessment in plants, livestock, rotational crops and drinking water. The enforcement method for

ziram is the same as for other dithiocarbamates and involves decomposing the dithiocarbamate

moiety to CS 2 using HCl and a reducing agent. A ziram

- specific residue analytical method

(LC/MS/MS method KP

- 028

- 03) is available.

Additional blueberry and grape field trial data, storage stability data, and apple washing studies

have been submitted and reviewed since the RED. 7 The ziram tolerance expression has been

updated to reflect current guidance (Knizner, 5/27/09) and to harmonize with CODEX by

expressing residues as carbon disulfide. The tolerance for residues of ziram on blackberries has

expired, therefore, t he use should be removed from the labels

.

Acute and chronic dietary risk assessments were last performed to support a crop group tolerance

for z iram on p ome f

ruit, based on current tolerances on representative commodities of the crop

group. Residue input s were highly refined, based on field trial data for almonds and pecans,

FDA monitoring data for apples, apricots, berries, grapes, cherries, nectarines, peaches, pears,

and tomatoes, empirical processing and washing factors from processing and washing stu dies,

and percent of crop treated (%CT). The EDWC s used in the dietary risk assessment was

provided by EFED. The entire distribution of water residues were incorporated into the acute

dietary exposure analysis. Estimated acute dietary exposure is below HE D’s level of concern for

the U.S. p opulation and all population subgroups at the 99.9 th percentile. The resulting risk

estimates are 8.6% of the acute population adjusted dose (aPAD) for the U.S. p opulation and

72% of the aPAD for Children 1

- 2 years old (t he most highly exposed population subgroup).

Estimated chronic dietary risks are below HED’s level of concern for the U.S. p opulation and all

population subgroups. The resulting risk estimates are <1% of the chronic PAD (% cPAD) for

the U.S. p opulation an d 7.2% of the cPAD for a ll i nfants (the most highly exposed population

subgroup). Anticipated residues based on field trials, processing studies, washing studies, and

monitoring data and percent of crop treated (%CT) were used for both the acute and chroni c

dietary exposure analyses (highly refined).

7 Ziram Summary Document

. G. Otakie. 1 2/15/2011. D361913, D347188, D347191, D323420

, D323421,

D279059

. Submission of Storage Stability Data for Ferbam, Thiram, and Ziram in Peach in Response to HED Memorandum

DP# 384363, 03/24/11 and Submission of Storage Stability Data for Ferbam in Mango in Response to HED

Memorandum DP# 304865, 05/12/11. G. Otakie, 3/22/2012

.

And Ziram

- OPPTS 860.1500/Washing Study

– Apples

. G. Otakie

, 1/04/2006

And Ziram (034805) Reregistration Case No. 2180. Magnitude of the Residue of Ziram in/on Blueberries. DP

Barcode D279177. MRID Nos. 45512001 and 45534501. T Morton, 1/17/2002Page 7 of 20

Conclusions for Conventional Uses: Residue field trial data are adequate to support the

currently registered uses, except blackberries and tomatoes. Residue data are required to ensure

the adequacy of the t olerance if these uses are to continue. A new dietary exposure and risk

assessment may need to be conducted if there are changes to the ziram toxicological PODs or

UFs or significant changes to the EDWCs. Additionally, 5 years have passed and anticipated

residues and %CT were used for the dietary exposure analysis. The assessment, if conducted,

will use the newest version of DEEM and reflect updated consumption information.

Antimicrobial Uses

Ziram is used as a material preservative to control bacterial degradation in products such as latex

paint (in

- can

- preservative), paper and paperboard, paper coatings, adhesives, dried films and

industrial yarns and fabrics, and short term spoilage protection for water reduced industrial

materials. There are no tolera nce exemptions for z iram under FFDCA Section 408. Ziram has

been cleared as an indirect food additive by the US Food and Drug Administration (US FDA)

under FFDCA s ection 409 for use in the manufacture of adhesive and components of adhesive

(21CFR§175.105), polymers (21CFR§177.2600), and for animal glue (21CFR§178.3120).

D ietary exposures from the antimicrobial uses of z iram with the food contact notifications is

negligible compare to the conventional uses as a fungicide.

Additionally, the re are non

- food uses of ziram as a material preservative in manufacturing latex

paint, paper and paper board, paper coatings, dried films, industrial yarns and fabrics and short

term spoilage protection for water reduced industrial materials

. Since these are non

- food use s, no

dietary exposure is expected.

Conclusions for Antimicrobial Uses: For the antimicrobial uses of ziram a quantitative dietary

exposure assessment and residue chemistry data are not require d at this time.

Residential Exposure

Conventional Uses

The registered conventional uses for ziram are not expected to result in residential exposure;

therefore, a quantitative residential exposure assessment has not been conducted and would not

be required for registration review.

Residential bystander exposu res resulting from off

- site transport (e.g., spray drift or

volatilization) may occur as a result of applications of ziram. The potential for spray drift will be

quantitatively evaluated for each pesticide during the Registration Review process which ensu res

that all uses for that pesticide will be considered concurrently. The approach is outlined in the

revised (2012) Standard Operating Procedures for Residential Risk Assessment (SOPs)

–

Residential Exposure Assessment Standard Operating Procedures Addend a 1: Consideration of

Spray Drift. This document outlines the quantification of indirect non

- occupational exposure to

drift. In terms of volatilization, the Agency has developed a Volatilization Screening Tool and a

subsequent Volatilization Screening An alysis

( http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219 ). During RegistrationPage 8 of 20

Review, the Agency will utilize this analysis to determine if data ( i.e.

, flux studies, route

- specific

inhalation toxicological studies) or further analysis is required for ziram.

Conclusions for Conventional Uses: There are no residential conventional uses currently

registered for ziram; therefore, a quantitative residenti al exposure risk assessment is not

necessary for the conventional uses during registration review. The need for spray drift and

volatilization risk assessment for the conventional uses will be examined during registration

review

.

Antimicrobial Uses

Residential h andler exposures (dermal and inhalation) are anticipated during the airless sprayer

and brush/roller application of ziram preserved paint. These exposures were evaluated in the

RED assuming an application rate of 0.29 lbs a i per gallon of pain t and the MOEs were 74 for

airless spray painting and 350 for brush roller painting. Because the MOE of 74 for airless spray

painting was below the target MOE of 300 the risk was of concern. To mitigate this risk, the

RED specified that the rate for exteri or paint be lowered to 1 percent ( i.e. 0.1 lb ai/gallon). The

rate for interior paints was not lowered because it was assumed that residential handlers only use

airless sp r ayers for exterior painting. This mitigation is present on the current labels.

The industrial yarn and fabrics use results in post application exposure s if these yarns and fabrics

are used in the manufacturer of apparel that can be worn by children (dermal exposure) or

household items such as towel and blankets that can be mouthed by chi ldren (incidental oral

exposure)

. These exposures were not assessed in the RED and thus will need to be assessed

during registration review.

Conclusions for Antimicrobial Uses : There are residential antimicrobial uses of ziram (paints,

yarns and fabrics) a nd these will need to be assessed during registration review

. The paint use

will need to be re

- assessed using the 28

- day inhalation toxicity study that was submitted after the

RED and the yarns and fabric use will need to be assessed if it is determined t hat these yarns and

fabrics are used to manufacture household goods and apparel

.

Aggregate Risk Assessment

I n accordance with the Food Quality Protection Act ( FQPA )

, EPA must consider and aggregate

pesticide exposures and risks from three major sources: food, drinking water, and residential

exposures. The aggregate risk assessment evaluates the combined risk from dietary exposure

(food and water) and any non

- occupational (residential) uses. T here are currently no

conventional residential uses for ziram; however, there are antimicrobial uses for ziram and the se

may need to be included in the aggregate risk assessment along with dietary exposure (food and

water). See dietary exposure and antimicrobial r esidential exposure assessment s discussed above.Page 9 of 20

Occupational Exposure

Conventional Uses

Occupational handler and post

- application exposures are expected based on the registered

agricultural uses of ziram on agricultural sites and ornamentals

. Ziram is currently formulated as

a water dispersible granule. The application rates range from 2.28 lb ai/A to 6.08 lb ai/A

, and

may be applied via air, ground boom, air blast sprayer, and high

- pressure hand wand.

Occupational exposure scenarios applicable to z iram range from short

- term (1 to 30 days) to

intermediate

- term (30 days to six months) duration for agricultural crops

, and may extend to

long

- term duration (six months to one year ) for ornamentals

.

The occupational handler assessments of agricultur al use indicate that

, for the water

- dispersible

granule (also referred to as dry flowable ) formulation

, all of the potential exposure scenarios

provide dermal and inhalation margins of exposure ( MOEs) greater than or equal to 100 at the

baseline clothing a ttire of long pants, long sleeved shirts, no gloves, and no respirator while

using open systems. However, based on the acute inhalation toxicity category II classification

and the revie w of the ziram incident reports, a dust/mist respirator wa s recommended in the RED

to protect against inhalation exposure. Although the incident data do not indicate direct

respiratory illness, the respiratory effects are reported as part of the “systemic” and

“combination” categories. Because most current labels require a du st/mist respirator, incidents

may increase if the requirement for a respirator were to be removed. Based on the CARC’s

revised cancer classification of ziram

, a quantitative assessment of human carcinogenic risk is

not required.

Several levels of post

- application exposure activities have been identified ranging from “low”

activities such as weeding and scouting in immature plants to very high activities such as

harvesting or thinning fruit from trees. Adequate d islodgeable foliar residue (DFR) data are

available for apples, and were used to assess all use sites; additional DFR data are not needed at

this time. The short

- and intermediate

- term post

- application assessments indicate that the

potential restricted entry interval (REI) ( i.e.

, the day after tre atment that the MOEs reaches 100),

based on the toxicity of the active ingredient, is 0 days for all crops and all activit i es. Although

MOEs of 100 are achieved for all crops and all activities on day 0, ziram is in acute Tox I

category for eye irritation, and therefore, in accordance with the Worker Protection Standard, the

REI is 48 hours.

Antimicrobial Uses

Occupational handler dermal and inhalation exposures are expected based on the registered

antimicrobial uses of ziram as a materials preservative. The antimicrobial product (45728

- 14) is

formulated as a powder containing 98% ai and the application rates range from 0.1 % ai for

paper coatings to 3% ai for paints. E xposures are anticipated when this powder is open poured

into process vessels or hoppers during the manufacturing of materials such as paints, adhesives,

paperboard, paper coatings, industrial yarns and fabrics. The label requires that rubber gloves

and a “ mask or pesticide respirator jointly approved by the M ining Safety and Health

Administr ation and the National Institute for Occupational Safety and Health ” be worn duringPage 10 of 20

the handling of the powder. Exposures are also anticipated during the airless sprayer or

brush/roller application of ziram preserved paints. The exposure durations for bo th exposure

scenarios range from short

- term (1 to 30 days) to intermediate

- term (30 days to six months).

The occupational handler exposures for open pouring of powder for material preservation were

assessed in the RED assuming the use of chemical resista nt gloves and a PF5 dust/mist

respirator. T he total MOEs ranged from 250 for large batch (1000 gallons per day) paint

preservation at the maximum application rate to 670,000 for small batch (100 gallons per day)

general preservation at the minimum applicat ion rate. The handler exposures during paint

application were assessed assuming that long sleeve shirts and long pants were worn and the

MOEs were 30 for airless spray application and 170 for brush/roller application

. The MOE of 30

w as of concern because i t did not exceed the target MOE of 100

. This risk was mitigated in the

RED by reducing the rate to 1.0 percent for exterior paints.

Conclusions. The occupational exposure database is adequate to support the Registration

Review process for ziram. Occupati onal handler and post

- application exposure assessments

conducted for the conventional uses in the 2003 RED did not identify risks of concern for any of

the remaining uses. Exposure assessments conducted for the antimicrobial uses in the 2003 RED

also did not identify risks of concern if certain mitigation measures included on the labels.

Registration Review may include updated occupational exposure and risk assessments based on

current policies and exposure assessment methodology

. In particular, the inhalation exposures

for the antimicrobial uses will need to be re

- evaluated for registration review using the 28

- day

inhalation toxicity study that was submitted after the RED.

Public Health and Pesticide Epidemiology Data

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease

Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH)

Sentinel Event Notification System for Occupational Risk

- Pesticides (SENSOR) databases were

consulted for pesticide incident data on the active ingredient ziram (pc code: 034805) 8 . The

purpose of the database search is to identify potential patterns in the frequency and severity of

the health effects attributed to ziram exposure. Ziram is in the Agricultural Health Study ( AHS )

. EPA notes a potential link between ziram and retinal degeneration reported in the AHS

population of pesticide applicators but recognizes the preliminary natu re of these data. The

Agency will update its summary and review of the epidemiological literature concerning ziram

during regulatory review.

Conclusions: Based on the low frequency and low severity of cases involving ziram reported in

both IDS ( 200 9

- 2014 ) and SENSOR

- Pesticides ( 1998

- 2010 ) , there does not appear to be a

concern at this time that would warrant further investigation

. The Agency will continue to

monitor the incident information and if a concern is triggered, additional analysis will be

included in the risk assessment.

8 E. Evans and S. Recore. D424449 12/16/2014. Ziram: Tier I Review of Human Incidents.Page 11 of 20

Tolerance Assessment and International Harmonization

U.S. permanent tolerances are established under 40 CFR § 180.116 for the registered uses of

ziram in/on a number of commodities. Codex and Canadian maximum residue lim its (MRLs) for

residues of ziram have been established for some of the same commodities which have

tolerances in the United States (U.S.). Mexico adopts U.S. tolerances and/or Codex MRLs for its

export purposes. While residue definitions are compatible wit h CODEX, and expressed as

carbon disulfide

, some U.S. tolerances are not numerically compatible with Codex or Canadian

MRLs. The tolerance residue levels may need to be examined during registration review to

determine if further harmonization can be achiev ed. See Appendix 2, Table 2.3

.

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions

to Addre ss Environmental Justice in Minority Populations and Low

- Income Populations,"

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf

. The Office of

Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use

of a pesticide when conducting human health risk assessments, including, but not limited to,

people who obtain drinking water from sources near agricultural are as, the variability of diets

within the U.S., and people who may be exposed when harvesting crops. Should these high

exposures indicate potential risks of concern, OPP will further refine the risk assessments to

ensure that the risk estimates are based on the best available information.

Cumulative Risk Assessment

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of

chemicals sharing a common mechanism of toxici ty. At a September 2001 meeting of the

Federal Insecti cide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) it

was determined that there was insufficient evidence to suggest that Ziram shares a common

mechanism of toxicity with other chemical substances (dithiocarbamates). The basis fo r this

conclusion is described in detail in the HED document, “The Determination of Whether

Dithiocarbamate Pesticides Share a Common Mechanism of Toxicity” (12/1/2001). The

document can be found on EPA’s website at

http://www.epa.gov/oppsrrd1/cumulative/dithiocarb.pdf

.

Human Studies

The 2001 RED and 2001 risk assessment relied in part on data from studies in which adult

human subjects were intenti onally exposed to a pesticide or other chemical. These data, which

include studies from Pesticide Handler Exposure Database (PHED) 1.1; the Agricultural Handler

Exposure Task Force (AHETF) database; the Agricultural Reentry Exposure Task Force (ARTF)

datab ase; and Exposure Science Advisory Committee (ExpoSAC) Policy 14 (Standard Operating

Procedures for Seed Treatment), are (1) subject to ethics review pursuant to 40 CFR 26, (2) have

received that review, and (3) are compliant with applicable ethics require ments. For certain

studies, the ethics review may have included review by the Human Studies Review Board.Page 12 of 20

Descriptions of data sources, as well as guidance on their use, can be found at the Agency

website 9

.

Risk Assessment Updates and Data Deficiencies

 Residue field trial data are required to suppo rt the currently registered use on tomatoes to

ensure the adequacy of the tolerance.

 Residue field trial data are required to support the currently registered use on

b lackberries

, h owever, s ince the tolerance for use of ziram on blackberry has expired,

HED recommends that the use should be removed from the label

. If blackberries are

removed from the label, then the field trial data would no longer be required

.

 Updated exposure and risk assess ments may be conducted if there are any significant

changes to ziram toxicological endpoints, points of departure, Food Quality Protection

Act safety factor or other uncertainty factors, standard operating procedures, or exposure

data or assumptions.

 Der mal (Guideline 875.1200) and inhalation (Guideline 875.1400) indoor exposure

studies are needed to evaluate handler exposures for: (1) Mixing/loading of ziram powder

for material preservation and (2) Brush/Roller and airless sprayer application of

preserve d paints. These studies are needed to support the antimicrobial uses for the

preservation of materials such as paint, paper/paperboard, paper coatings and adhesives.

 An indoor surface residue study (Guideline 875.2300) is needed to evaluate dermal and

inc idental oral exposures to ziram treated textiles that are used to manufacture apparel or

household items such as towels and blankets. This study is needed to support the

antimicrobial use for the preservation of industrial yarns and fabrics.

9 http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and

http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.htmlPage 13 of 20 Table 1 . Ziram Toxicology Profile

Guideline No./ Study Type MRID No. (year)/ Classification

/Doses Results

870.3100

90

- Day oral toxicity

- rat 42450301 (1992)

Acceptable/guideline

0, 100, 300, 1000 ppm

M: 0, 7.4, 21.4, 67.8 mg/kg/day

F: 0, 8.8, 24.2, 76.9 mg/kg/day NOAEL = M: 7.4, F: 8.8 mg/kg/day

LOAEL = M: 21.4, F: 24.2 mg/kg/day based on

decreases in body weight, body weight gain, food

consumption, and minimal histopathological changes

in the fem ale liver

870.3150

90

- Day oral toxicity

- dog N/A (requirement fulfilled by chronic

dog study) N/A

870.3200

21/28

- Day dermal toxicity

rabbit 41297001 (1989)

Acceptable/guideline

M&F: 0, 100, 300, 1000 mg/kg NOAEL = M: >1000, F: 300 mg/kg

LOAEL = F: 1000 mg/kg based on decreased body

weight and food consumption and clinical chemistry

suggestive of minimal hepatotoxicity. A LOAEL

was not observed in males.

870.3250

90

- Day dermal toxicity NA NA

870.3465

90

- Day inhalation toxicity 47628201 (2001) [28

- day inhalation

nose only study]

Acceptable/guideline

0.095, 0.318, 1.153, 2.898 μg/L NOAEL = 0.095 μg/L

LOAEL = 0.318 μg/L based on changes in the

larynx characterized by squamous metaplasia of the

ventrolateral epithelium, hyperplasia of the ventral

epithelium, necrosis of the ventral cartilage and

subepithelial inflammatory infiltration

870.3700a

Prenatal developmental

- rat 41908701 (1990)

Acceptable/guideline

F: 0, 1, 4, 16, 64 mg/kg/day Maternal NOAEL = 4 mg/kg/day

LOAEL = 16 mg/kg/day based on decreased body

weights, reduced food consumption, salivation, and

increased water intake.

Developmental NOAEL = 4 mg/kg/day

LOAEL = 16 mg/kg/day based diaphragmatic

thinning

870.3700b

Prenatal developmental

rabbit 00161316 (1986)

Acceptable/guideline

F: 0, 3, 7.5, 15 mg/kg/day Maternal NOAEL = 3 mg/kg/day

LOAEL = 7.5 mg/kg/day based on decreased body

weight gain.

Developmenta l NOAEL = 7.5 mg/kg/day

LOAEL = 15 mg/kg/day based on increased

incidence of resorptions and post

- implantation loss.

870.3800

Reproduction and fertility

effects

- rat 43935801 (1996)

Acceptable/guideline

0,72, 207, 540 ppm

F 0 males: 0, 5.3, 14.8, 37.5 mg/kg/day

F 0 females: 0, 6.1, 16.8, 42.8 mg/kg/day

F 1 males: 0, 5.6, 16.7, 42.7 mg/kg/day

F 1 females: 0, 6.3, 18.4, 47.5 mg/kg/day Parental/Systemic NOAEL = 14.8 mg/kg/day

LOAEL = 37.5 mg/kg/day based on reduced body

weights, body weights gains, and food consumption

in the F 0 and F 1 males and females.

Offspring NOAEL = 16.8 mg/kg/day

LOAEL = 42.8 mg/kg/day based on decreased body

weights at birth in F 2 pups and during lactation in F 1

and F 2 pups.Page 14 of 20

870.4100a

Chronic toxicity

- CD rat

870.4100a

Chronic toxicity

- F344 rat

870.4100a

Chronic toxicity

- F344 rat 43404201 (1994)

Acceptable/guideline

0, 60, 180, 540 ppm

M: 0, 2.5, 7.7, 23.7 mg/kg/day

F: 0, 3.4, 10.2, 34.6 mg/kg/day

NTP (1983)

Acceptable/guideline

0, 300, or 600 ppm

M: 0, 11, or 22 mg/kg/day

F: 0, 13,or 26 mg/kg/day

45770201 (1983)

Acceptable/guideline

0, 20, 200, or 2,000 ppm

M: 0, 0.70, 6.9, or 74 mg/kg/day

F: 0, 0.83, 8.5, or 91 mg/kg/day NOAEL = not established

LOAEL = M: 2.5, F: 3.4 mg/kg/day based on

histopathological findings in various organs.

NOAEL = M: 22, F: 26 mg/kg/day based on lack of

effect.

LOAEL = M: >22, F: >26 mg/kg/day

NOAEL = M: 0.70, F:0.83 mg/kg/day

LOAEL = M: 6.9, F: 8.5 mg/kg/day based on slight

anemia in females, decreases in the absolute and

relative weight of the crural muscle in both sexes,

atrophy of the crural muscle in both sexes, increased

mucosal cornification of the stomach in both sexes,

follicular cell hypertrophy of the thyroid in females,

and rhinitis of the nasal cavity in females.

870.4100b

Chron ic toxicity

- dog 42823901 (1993)

Acceptable/guideline

0, 50, 185, 700 ppm

M: 0, 1.6, 6.6, 17.4 mg/kg/day

F: 0, 1.9, 6.7, 20.6 mg/kg/day NOAEL = M: 1.6, F: 1.9 mg/kg/day

LOAEL = M: 6.6, F: 6.7 mg/kg/day

based on decrease in body weight gain in the females

and liver histopathology in males.

870.4200a

Carcinogenicity

CD rat

870.4200a

Carcinogenicity

- F344 rat

870.4200a

Carcinogenicity

- F344 rat Same as chronic toxicity

- CD rat above

(870.4100a).

Same as chronic toxicity

- F344 rat above

(870.4100a).

Same as chronic toxicity

- F344 rat above

(870.4100a). Evidence of carcinogenicity based on

increased incidence of benign hemangiomas in CD

male rats at 23.7 mg/kg/day

Evidence of carcinogenicity based on

increased incidence of thyroid C

- ce ll carcinoma in

male rats at 22 mg/kg/day

Evidence of carcinogenicity based on increased

incidence of preputial gland adenomas in male rats at

74 mg/kg/day.

870.4200b

Chronic/Carcinogenicity

CD

- 1 mouse 43373701 (1994)

Acceptable/guideline

0, 29, 75, 225, 675 ppm

M: 0, 3, 9, 27, 82 mg/kg/day

F: 0, 4, 11, 33, 95 mg/kg/day NOAEL = M: 9, F: 11 mg/kg/day

LOAEL = M: 27, F: 33 mg/kg/day based on

decreased absolute brain weight in both sexes and

increased incidence of urinary bladder epithelial

hyperplas ia and decreased body weight gain in CD

- 1

males. No evidence of carcinogenicity

870.4200b

Chronic/Carcinogenicity

B6C3F1 mouse NTP (1983)

Acceptable/guideline

0, 600, or 1200 ppm

M: 0, 122, or 196 mg/kg/day

F: 0, 131, 0r 248 mg/kg/day NOAEL = M:196 mg/kg/day; not established for

females;

LOAEL = M: >196, F: 131 mg/kg/day based on

increased incidence of alvelolar epithelial

hyperplasia in females

Evidence of carcinogenicity based on increased

incidence of alveolar/bronchiolar adenomas and of

combined alveolar/bronchiolar adenomas orPage 15 of 20 carcinomas in female B6C3F1 mice at  131

mg/kg./day

Gene Mutation

870.5265 Salmonella/

mammalian activation gene

mutation assay 00147462 (1984)

Acceptable/guideline

41642901 (1990)

Acceptable/guideline

Haworth, et al. (1983)

Acceptable/guideline The test article was positive for gene mutation

induction in strain TA100 (±S9).

The test article was mutagenic when tested above 50

μg/plate (+S9).

The test article was positive in strains TA100 (±S9)

and TA1535 (+S9)

Cytogenetics

870.5375

in vitro mammalian

cytogenetics assay 41287802 (1989)

Acceptable/guideline

Gulati (1989)

Acceptable/guideline There was no evidence of structural chromosomal

aberrations over background.

The test article was positive for chromosomal

aberrations (±S9).

870.5300 mammalian cell

gene mutation assay 45806501(1999)

Acceptable/guideline No reproducible increase in the mutation frequency

of mouse lymphoma cells was seen

870.5300 mammalian cell

gene mutation assay McGregor, et al. (1988)

Acceptable/guideline The test article was positive for gene mutation

induction (

- S9).

870.5395 mammalian

erythrocyte micronucleus

test Proudock, R.L. and Taylor, K. (1992

Unacceptable

- maximum tolerated dose

not tested, dosing regime not justified,

and non

- standard procedures used. The test article was negative in the peripheral blood

of CD

- 1 Swiss mice fed levels of 25, 75, 225, or 675

ppm for 89 days.

Other Genotoxicity

870.5550, Unscheduled

DNA synthesis 41287801 (1989)

Acceptable/guideline There was no evidence that unscheduled DNA

synthesis was induced.

870.6200a

Acute neurotoxicity

screening battery 43362801 (1994)

Acceptable/guideline

M&F: 0, 15, 300, 600 mg/kg NOAEL = not established

LOAEL = M&F: 15 mg/kg/day based on ataxia and

slight impairment of gait in males.

870.6200b

Subchronic neurotoxicity

screening battery 43413701 (1994)

Acceptable/guideline

0, 72, 207, 540 ppm

M: 0, 5, 14, 34 mg/kg/day

F: 0, 6, 16, 40 mg/kg/day Systemic NOAEL = M: 14, F: 16 mg/kg/day

LOAEL = M: 34, F: 40 mg/kg/day based on

decreased body weight and body weight gains.

Cholinesterase NOAEL = M: 14, F: 6 mg/kg/day

LOAEL = M: 34, F: 16 mg/kg/day based on brain

cholinesterase inhibition in both sexes and bra in

neurotoxic esterase activity in the males.

870.6300

Developmental

neurotoxicity 43935801 (1996)

Unacceptable/guideline

0, 72, 207, 540 ppm

Maternal gestation: 0, 5, 13, 32

mg/kg/day

Maternal lactation: 0, 11, 30, 79

mg/kg/day Maternal NOAEL = 13 mg/kg/day

LOAEL = 32 mg/kg/day based on reduced body

weights and/or body weights gains, and decreased

food consumption during gestation and lactation.

Offspring NOAEL = not established

LOAEL = 5 mg/kg/day based on increased motor

activity.Page 16 of 20

Appendix 1

Table 2. Acute toxicity of Ziram

Guideline No./Study Type MRIDs Results Tox Category

870.1100 Acute Oral 41340401 a

42429301 b

43701301 a LD 50 =320 mg/kg (M&F)

LD 50 = 381 mg/kg (M)

LD 50 = 267 mg/kg (F)

LD 50 >2000 mg/kg (M&F)

LD 50 =2068 mg/kg (M&F)

LD 50 = 2719 mg/kg (M)

LD 50 = 2060 mg/kg (F) II

III

III

870.1200 Acute Dermal 41340402 a LD 50 > 2000 mg/kg (M & F) III 87 0.6300

Developmental

Neurotoxicity Study 47900401 (2009)

Acceptable/Non

- guideline

0, 72, 207, 540/360 ppm

0, 8.6, 24, 46.6 mg/kg/day Maternal NOAEL = 8.6 mg/kg/day

LOAEL = 24 mg/kg/day based on decreases in body

weights, body weight gain, and food consumption

d uring gestation and/or lactation.

Offspring NOAEL = 8.6 mg/kg/day

LOAEL = 24 mg/kg/day based on increased

locomotor activity, decreased habituation, and

decreases in body weights and body weight gains.

870.7485

Metabolism and pharmaco

kinetics

- rat 42391001 (1992)

Unacceptable/guideline

M&F: 15, 352 mg/kg or 15 mg/kg/day The test material was rapidly absorbed and excreted

via the urine and expired air, and significant amounts

were excreted in the feces. Small amounts were

widely distributed in the body. Metabolites were not

identified.

870.7485

Metabolism

- rat 46731701 (2001) main

Acceptable/Guideline

Series of 8 pilot studies

15 or 150 mg/kg/day (main)

See DER for a listing of studies and

doses

46731702

(comparison study

– in Appendix to

DER) The test material was absorbed and excreted mainly

via the expired air , urine , and smaller amounts were

excreted in the feces. Small amounts were widely

distributed in the body , with the highest tissue

concentrations found in the liver, fat, kidney, spleen,

lung, thyroid, and adrenals . Metabolites were

identified.

870.7600

Dermal penetration Same as 21

- day dermal rabbit

(870.3200) and rabbit oral

developmental (870.7600). The test material was minimally absorbed.

870.7800

Immunotoxicity Waived by HASPOC (TXR No. 0057106)

.Page 17 of 20 Table 2. Acute toxicity of Ziram

Guideline No./Study Type MRIDs Results Tox Category

870.1300 Acute Inhalation 41442001 a LC 50 =0.07 mg/L (M&F)

LC 50 =0.08 mg/L (M)

LC 50 = 0.06 mg/L (F) II

870.2400 Primary Eye Irritation 41643001 a

41454401 b Severe irritation

Severe irritation I

I

870.2500 Primary Skin

Irritation 41643002 a

41454602 b Not a dermal irritant

Not a dermal irritant IV

IV

870.2600 Dermal Sensitization 41643003 a Moderate dermal sensitizer; 30% sensitization rate NA

a Technical b 76% formulation

Table 3. Summary of Ziram Toxicity endpoints

EXPOSURE

SCENARIO DOSE

(mg/kg/day) ENDPOINT STUDY

Acute Dietary

(Female 13+) 1,2 NOAEL = 7.5

UF=100

FQPA SF=3 Increased incidence of resorptions and post

implantation loss Prenatal Oral Developmental / Rabbit

Acute RfD (Female 13

- 50) = 0.075 mg/kg

Acute Population Adjusted Dose (aPAD) =0.025 mg/kg/day

Acute Dietary

(Gen. Population) 1,2 LOAEL = 15

UF = 300

FQPA SF = 3 Ataxia and slight impairment of gait Acute Oral Neurotoxicity / Rat

Acute RfD (Gen. Population) = 0.05 mg/kg

Acute Population Adjusted Dose (aPAD) =0.017 mg/kg/day

Chronic Dietary NOAEL = 1.6

UF = 100

FQPA SF = 3 Decreased body weight gain at a LOAEL of

6.6 mg/kg/day 52

- Week Oral Toxicity / Dog

Chronic RfD = 0.016 mg/kg/day

Chronic Population Adjusted Dose (cPAD) =0.005 mg/kg/day

Dermal, Short

- and

Intermediate

- Term 3,4 NOAEL = 7.5

MOE = 100 (Occupational) 5

and

300 (Residential ) Increased incidence of resorptions and post

implantation loss Prenatal Oral Developmental / Rabbit

Dermal, Long

- Term NOAEL = 1.6

MOE = 100 (Occupational)

and 300 (Residential) Decreased body weight gain. 52

- Week Oral Toxicity / Dog

Inhalation, Short

- and

Intermediate

- Term NOAEL = 7.5

MOE = 100 (Occupational) 5

and 300 (Residential ) Increased incidence of resorptions and post

implantation loss Prenatal Oral Developmental / Rabbit

Inhalation, Long

- Term NOAEL = 1.6

MOE = 100 (Occupational)

and 300 (Residential) Decreased body weight gain.

52

- Week Oral Toxicity / Dog

1. The dose and endpoint for population subgroup Females (13

- 50) was not selected for risk assessment because the aPAD for Acute Dietary exposure

(0.017 mg/kg) for general population is protective of developmental effects which are selected as an endpoint for Females (13

- 50) (aPAD (0.025 m g/kg).

2. FQPA SF of 3x for all dietary and residential exposure/risk assessments was applied.Page 18 of 20

3. The appropriate dermal (1%) or inhalation absorption factor (100%) was used since the NOAEL is from an oral study.

4. Residential MOE (Margin of Exposure) = 100xSF 3x=300; occupational MOE for all durations=100

5. The dermal and inhalation MOEs for the occupational exposure of short

- term duration are combined because the toxicological effects are the same

(increased incidence of resorptions and post implantation loss). The dermal and inhalation MOEs for the occupational exposure of intermediate

- term

duration are combined because the toxicological effects are the same (increased incidence of resorptions and post implantation loss).

Appendix 2

TABLE 2 .1. Test Compound Nomenclature.

Compound Chemical Structure

Common name Ziram

Company experimental name Not provided

IUPAC name zinc bis(dimethyldithiocarbamate)

CAS name Zinc dimethyldithiocarbamate

CAS # 137

- 30

- 4

End

- use product/(EP)

TABLE 2 .2. Physicochemical Properties of Ziram.

Parameter Value Reference

Melting point (°C) 225.5 to 251

DP# 280352

, G

. Otakie , 1/17/02 pH not available

Relative Density 1.7097 g/mL

Water solubility 65 ppm

Solvent solubility soluble in dilute alkali, carbon disulfide and chloroform ;

moderately soluble in acetone: and slightly soluble in

diethyl ether and ethanol

Vapor pressure (Pa) (25°C) 1.8x10

- 5

Dissociation constant (pK

a ) not available

Octanol/water partition coefficient Log(K OW ) at

20 o C 1.65

UV/visible absorption spectrum not availablePage 19 of 20

Table 2.3 International Residue Limits

Ziram (PC Code 034805; Date of Request 9/19/14)

Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition :

US Canada Mexico 1 Codex 2, 3, 4

40 CFR: 180.116

zinc ethylenebisdithiocarbamate*

*being changed to carbon disulfide zinc

dimethyldithiocarbamate

(calculated as zineb) Total dithiocarbamates,

determined as CS2,

evolved during acid digestion and

expressed as mg CS 2 /kg

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 1 Codex 2, 3, 4

Almond 0.1 0.1 (*) 2, 4

Apple 7.0 7 5 pome fruits 4

Apricot 7.0 7 7 stone fruits 4

Blueberry 7.0 7

Cherry, sweet 7.0 7 cherries 0.2 cherries 5

Cherry, tart 7.0

Grape 7.0 7 5 5

Huckleberry 7.0 7

Peach 7.0 7 7 stone fruits 4

Pear 7.0 7 5 pome fruits 4

Pecan 0.1 0.1 (*) 3

Quince 7.0 7 5 pome fruits 4

Strawberry 7.0 7 5 5

Tomato 7.0 7 2 5

MRLs with NO US Equivalent

Beans 7

Blackberries 7

Celery 7

Cranberries 7

Dry blackeyed peas 7

Garden beet roots 7

Gooseberries 7

Lettuce 7

Loganberries 7

Nectarines 7

Onions 7

Peanuts 7

Peas 7

Raspberries 7

Spinach 7

Succulent shelled blackeyed

peas 7

Root and tuber vegetable,

group 1 7 carrot roots, garden beet

roots, radish roots,

rutabaga roots, turnip

roots

Brassica vegetables, group 5 7 broccoli, Brussels

sprouts, cabbages,

cauliflowers, collards,

kales, kohlrabies

Vegetable, fruiting, group 8 7 eggplants, peppers,

tomatoesPage 20 of 20

Summary of US and International Tolerances and Maximum Residue Limits

Residue Definition :

US Canada Mexico 1 Codex 2, 3, 4

Vegetable, cucurbit, group 9 7 cucumbers, melon,

pumpkins, squash,

summer squash

Completed: M. Negussie; 09/24/14

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP =

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

3 Based on trials with ziram

4 Based on trials with dithiocarbamates including ziram

5 Based on trials with dithiocarbamates other than ziram

.