UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 9/3/ 15 

SUBJECT: Ferbam Scoping Document 

OFFICE OF CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

PC Code: 03480 I 

Decision No.: 506261 

Petition No.: NA 

DP Barcode: 427923 

Registration No.: 45728-7 

Risk Assessment Type: Single Chemical Aggregate 

TXR No.: NA 

Regula tory Action: Registration Review 

Case No.: 2180 

CAS No.: 14484-64-1 

MRID No.: NA 40 CFR: §180.114 

FROM: Jessica Kidwell, Risk Assessor ~~ 

Hannah 

Kelly O'

Pope-Varsalona

Rourke, Occupational/R 

, PhD, Toxicolog 

idential Expo ure Assessor ~""7 <[)~ ~ 

Thurston Morton, Chemist/Dietary Assessor , 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

THROUGH: Charles Smith, Acting Branch Chief 

Risk Assessment Branch IV 

Health Effects Division (7509P) 

TO: KJme Nguyen, Risk Manager Reviewer 

Thomas Moriarty, RMS I 

Risk Management and Implementation Branch 1 

Pesticide Reevaluation Division (7508P) 

Attached is the Health Effects Division's (HED's) scoping document for the fungicide ferbam 

(also known as ferric dimethyldithiocarbamate) for purposes ofregistration review. 

Executive Summary 

HED has considered the available risk assessments for ferbam and its toxicity, exposure and 

usage databases, as well as the most current EPA science and assessment policies. HED 

performed this evaluation in order to determine the scope of work necessary to support the 

established tolerances and existing registrations during registration review. The primary sources 

of information for thjs evaluation were the most recent comprehensive HED human health risk 

assessments (D304864, D304868, and D304867) conducted to support the 2005 USEPA 

Registration Eligibility Decision (RED) for ferbam (EPA-HQ-OPP-738-R-05-009). 
Ferbam/034801 Scoping Document Final

Page 2 of 39

Ferbam [ferric dimethyldithiocarbamate] is a broad spectrum fungicide registered for treatment

of disease in fruit trees, small fruits, and berries. Registered food uses include apple, citrus fruit,

cranberry, mango, nectarine, peach, and pear. It is used to prevent crop damage in the field and is

also applied prior to harvesting in order to prevent fruits from deterioration in storage or

transport. Dietary, drinking water, and occupational exposures are the relevant scenarios for

exposure to ferbam. There are no residential uses of ferbam.

No guideline studies are available for subchronic dermal toxicity, inhalation toxicity,

reproductive toxicity, neurotoxicity, immunotoxicity, mutagenic and carcinogenic effects.

Available toxicity/metabolism studies from the open literature on ferbam were compared with

data for other dimethyldithiocarbamates, primarily ziram and thiram. A comparison of available

rat metabolism data among these dimethyldithiocarbamates suggests that all these compounds

either dissociate or reduce into dimethyldithiocarbamate anions and are metabolized to carbon

disulfide and dimethylamine. The Hazard and Science Policy Council (HASPOC) met on

January 8, 2015 to discuss the need for a ferbam immunotoxicity study and on April 30, 2015 to

discuss the need for several other ferbam toxicity studies (subchronic dermal toxicity, inhalation

toxicity, reproductive toxicity, neurotoxicity, mutagenic and carcinogenic effects). Based on a

Weight of Evidence approach, which includes the consideration that ziram and thiram both have

complete enough toxicity databases from which missing toxicological information from ferbam’s

toxicity profile can be bridged, waivers were granted for all the aforementioned study

requirements. Based on this bridging decision, the ferbam toxicity database, combined with that

of thiram and ziram, is considered to be complete for risk assessment.

In the non-guideline studies submitted for ferbam, the primary target organs appear to be the

nervous system, thyroid, and reproductive system. Strong evidence of peripheral neurotoxic

effects was also reported for ziram and thiram. Two open literature non-guideline rat two year

chronic toxicity/carcinogenicity studies with ferbam showed no evidence of carcinogenicity.

Ziram was classified as “suggestive of carcinogenicity, but not sufficient to assess human

carcinogenic potential” with no quantification of human carcinogenic risk (i.e., a non-linear RfD

approach is adequate to account for all chronic toxicity, including carcinogenicity). Thiram is

classified as “not likely to be carcinogenic to humans.” Based on the bridging data, the cancer

classifications of thiram and ziram are protective of any potential carcinogenic effects of ferbam.

No quantification of cancer risk is required for ferbam. Due to the bridging of toxicity studies

from thiram, in addition to the available ferbam data, there is little concern for quantitative or

qualitative susceptibility effects for ferbam in rats following in utero pre- and post natal

exposures. The FQPA safety factor (SF) for ferbam was reduced to 1X.

The current common moiety plant method would likely include all the residues of toxicological

concern. The qualitative nature of the residue in plants and livestock is considered to be

adequately understood. Ferbam residues convertible to CS2 are the residue of concern for

tolerance expression and/or risk assessment in plants, livestock, rotational crops and drinking

water. Field trial data for apple and grape remain outstanding (GDCI-034801-26275). However,

optional bridging studies for ferbam, ziram and thiram on apple and grape could be submitted. 

Tolerances for cherry and grape are established, however, these uses are not on the label. The
Ferbam/034801 Scoping Document Final

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registrant has indicated they are not supporting cherry and grape uses. If these uses are not

supported the grape residue field trials will not be required. 

The acute and chronic dietary risk estimates for food and drinking water combined are below

HED’s level of concern (i.e., <100% of the acute and chronic population adjusted doses (PADs))

for the general U.S. population and all population subgroups. A new dietary exposure and risk

assessment will be conducted since the endpoints/PODs may be updated to reflect current

policies and significant changes have occurred with the drinking water models since the last

dietary exposure analysis in 2005. New drinking water models are currently being utilized which

were not in use for the 2005 dietary exposure assessment. In addition, the assessment will use the

newest version of DEEM and reflect updated consumption information.

U.S. tolerances are not numerically compatible with Codex or Canadian MRLs. The tolerance

residue levels will be examined during registration review to determine if further harmonization

can be achieved. Tolerances for the dimethyl dithiocarbamates (thiram, ziram, and ferbam) and

the ethylenebis-dithiocarbamates (EBDCs) are being converted to being expressed as carbon

disulfide equivalents, since it is difficult to distinguish among the various pesticides by analytical

methods alone. HED has recommended that all tolerances for dithiocarbamates, including

ferbam be converted to be expressed as carbon disulfide, so that the tolerance expression will be

compatible with Codex. Ferbam tolerances are in CS2 equivalents currently, however, the

expression needs updated.

While there are no residential uses of ferbam, residential bystander exposures resulting from offsite transport (i.e., spray drift or volatilization) may occur as a result of occupational applications

of ferbam. The need for spray drift and volatilization risk assessments for ferbam will be

examined during registration review.

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

scenarios relevant to ferbam (Daiss, R, 12/30/2004, D291030). Although no occupational

handler or post-application risks of concern were identified with use of appropriate personal

protective equipment (PPE), a revised assessment of occupational exposure was conducted as a

result of a later submission of a developmental neurotoxicity study (DNT) on thiram, which

identified post-application risks of concern (Daiss, R. 10/11/2005, D304867). Updated

occupational exposure and risk assessments will be necessary as part of registration review to

reflect revised toxicological endpoint selection and current HED policy regarding exposure

assessment methodology.

Chemical Use Profile

Ferbam [ferric dimethyldithiocarbamate] is a broad spectrum fungicide registered for treatment 

of disease in fruit trees, small fruits and berries. Registered food uses include apple, citrus fruit, 

cranberry, mango, nectarine, peach, and pear. Ferbam is a fine, black, free-flowing powder 

which decomposes at 180°C and has a density of 1.36 g/mL at 20°C and vapor pressure of <8.6 x 

10-7 Torr. Ferbam has low solubility in water (120 ppm) and is soluble in acetone, acetonitrile, 
Ferbam/034801 Scoping Document Final

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chloroform, and pyridine. Ferbam tends to decompose upon exposure to heat and moisture with 

prolonged storage.

The nomenclature and physiochemical properties of ferbam are presented in Table 2.1 of

Appendix 2. 

Hazard Identification/Toxicology

No guideline studies are available for subchronic dermal toxicity, subchronic inhalation toxicity,

reproductive toxicity, acute and subchronic neurotoxicity, immunotoxicity, or mutagenic or

carcinogenic effects. Available toxicity/metabolism studies from the open literature on ferbam

were compared with data for other dimethyldithiocarbamates, primarily ziram and thiram. A

comparison of available rat metabolism data among these dimethyldithiocarbamates suggests

that all these compounds either dissociate or reduce into dimethyldithiocarbamate anions and are

metabolized to carbon disulfide and dimethylamine. The Hazard and Science Policy Council

(HASPOC) met on January 8, 2015 to discuss the need for an immunotoxicity study (TXR No.

0057106) and on April 30, 2015 to discuss the need for several studies (subchronic dermal

toxicity, inhalation toxicity, reproductive toxicity, neurotoxicity, or mutagenic and carcinogenic

effects) (TXR No. 0055029) of ferbam. Based on a Weight of Evidence approach which includes

the consideration that ziram and thiram both have complete enough toxicity databases from

which missing toxicological information from ferbam’s toxicity profile can be bridged, waivers

were granted for all the aforementioned study requirements. Due to this toxicology bridging

decision, the ferbam toxicity database, combined with that of thiram and ziram, is considered to

be complete for risk assessment. The data requirements for ferbam are listed in Appendix 1,

Table 4.

In the non-guideline studies submitted for ferbam, the primary target organs appear to be the

nervous system, thyroid, and reproductive system. Neurotoxic affects were seen in four separate

subchronic and chronic studies in rats and mice where effects included abnormal motor activity,

spinal paralysis, cystic lesions in cerebral cortex and cerebellum, collapsed cranium, decreased

life span and mortality starting at 23 mg/kg/day. Strong evidence of peripheral neurotoxic effects

was also reported for ziram and thiram. In three separate ziram studies, ataxia, salivation,

lacrimation, impaired gait, abnormal posture, inhibition of brain cholinesterase, brain neurotoxic

esterase, and increased motor activity were identified. Toxicity studies for thiram identified

unusual gait, hind leg abnormalities that developed into paralysis and atrophy of hind legs in

female rats, lethargy, reduced startle response, and no tail pinch response among other altered

activities reported. Thyroid anomalies following ferbam exposure included squamous metaplasia

at 32 mg/kg/day. Reproductive affects were demonstrated in two rat studies and were manifested

as decreased implantations and fetuses, increased reabsorptions, and increased relative testes

weight for males. 

Two open literature rat two year chronic toxicity/carcinogenicity studies with ferbam showed no

evidence of carcinogenicity. Ziram was classified as “suggestive of carcinogenicity, but not

sufficient to assess human carcinogenic potential” based on the occurrence of benign tumors

(hemangiomas) and preputial gland adenomas in male rats by the Cancer Assessment Review
Ferbam/034801 Scoping Document Final

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Committee (CARC) in 2002 (TXR No. 0051541). No quantification of human carcinogenic risk

was determined for ziram because the Agency discerned that using a non-linear approach (i.e.

RfD) is adequate to account for all chronic toxicity, including carcinogenicity. Thiram, is

classified as “not likely to be carcinogenic to humans.” Based on bridging, the cancer

classifications of thiram and ziram are protective of any potential carcinogenic effects of ferbam.

No quantification of cancer risk is required for ferbam.

No quantitative or qualitative susceptibility is evident in fetuses of rats exposed to ferbam in

utero. The decrease in fetal body weight and developmental anomalies were reported at the same

dose which produced decreased body weight changes, number of implants, and increased

percentage of resorptions and mortality effects in dams. Also, in a three-generation reproductive

toxicity study in rat, no fetal susceptibility effects were reported, i.e., no fetal as well as maternal

toxic effects at 12.5 mg/kg/day. However, a quantitative susceptibility was evident in a mouse

developmental toxicity study. The developmental anomalies (increased incidences for thick atrial

wall, thin ventricular wall, hydroureter, hydronephrosis, slight- or marked- collapsed cranium,

extraossification of supraoccipitals and malaligned sternebrae) were noticed in mice dosed at 228

mg/kg/day that produced no maternal toxic effects. Further, in another rat reproduction study a

qualitative susceptibility is evident in pups exposed to ferbam during lactation. Decreased pup

viability, survival and the reduced pup body weights were reported at a dose which produced

decreases in maternal body weight and food consumption during both gestation and lactation

periods. For thiram, there is no evidence for increased susceptibility following in utero exposures

to rats or rabbits and following pre- and post-natal exposures to rats for two generations. There is

low concern for the increased susceptibility seen in the developmental neurotoxicity toxicity

study for thiram since the dose response is well defined and this endpoint is used for assessing

the acute dietary risk for ferbam for the most sensitive population. This endpoint is also

protective of the developmental effects seen in the nonguideline ferbam mouse study and the

offspring effects seen in the ferbam reproduction study. Due to the bridging of studies from

thiram, there is little concern, as stated above, for quantitative or qualitative susceptibility effects

for ferbam in rats following in utero pre- and post natal exposures. Therefore, the FQPA safety

factor (SF) for ferbam was reduced to 1X. 

In a submitted non-guideline metabolism study, rats were administered [

35S]ferbam via oral

gavage. At the only dose tested (10 ml/kg), absorption was quantifiable but incomplete in the

gastrointestinal tract. At the latest time point analyzed, 24 h, the highest absorption levels were

recorded. Sixty-one percent of radioactivity had been absorbed via the gastrointestinal tract, of

which 17% was excreted in the feces, 23% in the urine, 18% in expired air, 2% in the brain, and

1% in bile (Hodgson et al., 1975). The same study showed that [

14C]ferbam administered via

oral gavage crossed the placenta of pregnant rats, was secreted into the milk of lactating rats,

absorbed by the pups, and excreted in the urine of the pups (Hodgson et al., 1975). None of the

dithiocarbamates appear to accumulate in tissue (Liesivuori and Savolainen, 1994).

In the scientific literature, dithiocarbamates block the conversion of dopamine to epinephrine and

norepinephrine causing the inhibition of catecholamine neurotransmitter synthesis in humans.

Transmission of nerve impulses involving norepinephrine are involved in the regulation of

gonadotropin releasing hormone (GnRH), responsible for release of follicle-stimulating hormone
Ferbam/034801 Scoping Document Final

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and luteinizing hormone (LH) (reviewed in Cecconi et al., 2007). Dimethyldithiocarbamates

have been shown to dissociate from their metal particles and possess chelating properties. As

chelators, these compounds have the potential to interact and interfere with sulfhydryls and

macromolecules (Fishbein, 1976 and Miller, 1982). A disruptive role for dithiocarbamates has

also been identified in the nitric oxide synthase (reviewed in Cecconi et al., 2007).

The acute, subchronic, and chronic toxicity profile tables for ferbam, thiram and ziram are

included in Appendix 1, Tables 1 and 2. Toxicity endpoints, points of departure (PODs), and

uncertainty/safety factors (UF/SFs) were selected for oral, dermal, and inhalation exposure

pathways for the Human Health Risk Assessment conducted in 2005 (D304864), and these are

shown in Appendix 1, Table 3. It should be noted that thiram toxicity studies were selected for

all of the ferbam endpoints. The toxicological doses/endpoints selected for ferbam risk

assessment have not been changed since the Reregistration Eligibility Documents (RED) in 2005

(D304864) with the exception of two endpoints, the acute dietary (females 13-49 years old) and

short and intermediate-term dermal. There was a revised assessment of dietary and occupational

exposure as a result of submission of a developmental neurotoxicity study (DNT) on thiram

(D304867). The DNT NOAEL of 1.4 mg/kg/day was selected for the acute reference dose for

women of reproductive age and for short and intermediate term dermal as it protective against

neurotoxic effect seen in offspring at 3.7 mg/kg/day. The point of departure selected for these

populations is conservative and is expected to be protective against the susceptibility seen in the

thiram DNT study and the ferbam mouse developmental and 2-generation reproduction rat

studies.

Conclusions: The toxicity database for ferbam is considered complete for risk assessment when

bridged with ziram and thiram. The HASPOC determined that a subchronic dermal study, 28-day

inhalation study, chronic toxicity/carcinogenicity study, mutagenicity battery, acute and

subchronic neurotoxicity studies, and immunotoxicity study are not required at this time based

on the consideration that the ferbam toxicity database will be bridged with that of thiram and

ziram. During registration review, the endpoints and safety factors for risk assessment will be

updated to reflect current policies.

Residue Chemistry

HED has used available ferbam-specific metabolism studies as well as ziram and thiram 

metabolism studies to satisfy the ferbam plant metabolism requirements for two crops and to 

characterize ferbam for risk assessment purposes. The metabolism and toxicity data support 

translation of ziram and thiram field trial data for dietary exposure assessment. A number of lines 

of evidence suggest that the dithiocarbamate fungicides are largely interconvertible and 

toxicologically equivalent to each other. Strong support for the equivalence of ferbam and thiram

comes from a series of environmental fate studies that indicate that ferbam in dilute aqueous 

solutions (≤50 ppm) is rapidly converted (half-lives of minutes) to thiram and the anion of 

dimethyldithiocarbamic acid (DCC). Other fate studies also show that ziram is also converted to 

thiram and DCC anion, and thiram itself forms DCC anion over time. Furthermore, based on the 

ziram grape and thiram apple metabolism studies, the current common moiety plant method (i.e., 

everything converted to CS2) would likely include the residues of the metabolites of 
Ferbam/034801 Scoping Document Final

Page 7 of 39

toxicological concern. The qualitative nature of the residue in plants is considered to be 

adequately understood. Ferbam residues convertible to CS2 are the residue of concern for 

tolerance expression and/or risk assessment in plants, livestock, and rotational crops. These 

same residues of concern are the residues of concern in drinking water for risk assessment.

Given the similar use patterns and environmental fate profile for ferbam, ziram and thiram, HED

will translate field trial data for all fruit crop groups from ziram and/or thiram to ferbam provided

that three acceptable bridging studies in diverse geographical locations for each commodity (with

two side-by-side field trials each using ferbam, ziram and thiram at identical application rates

and methods, PHI’s, etc.) are submitted for apple, peach and grape; and those studies indicate

residues are comparable for the different fungicides. Acceptable bridging studies have been

submitted for peach. Field trial data for apple and grape remain outstanding (GDCI-034801-

26275). However, optional bridging studies for ferbam, ziram and thiram on apple and grape

could be submitted. Tolerances for cherry and grape are established however, these uses are not

on the label. The registrant has indicated they are not supporting cherry and grape uses. If these

uses are not supported the grape residue field trials will not be required. 

Enforcement Method

A colorimetric analytical method is available to enforce the proposed tolerances. The Pesticide 

Analytical Manual (PAM) Vol. II lists Method I, II, III, IV, and A for the determination of 

dithiocarbamate residues in/on plant commodities. These methods are based on the 

decomposition of dithiocarbamates with release of CS2. Using these methods, the CS2 is swept 

through a trap to remove any H2S and into a reaction tube containing a solution of copper acetate 

and an amine. A colored copper dithiocarbamate complex is formed and its absorbance read as a 

measure of the original dithiocarbamate. The stated limit of detection (LOD) for Method I is 0.5-

4.0 ppm. Ferbam is only partially recovered using FDA multiresidue methods. 

Dietary Exposure and Risk

The most recent dietary (food and water) exposure assessment was conducted in 2005 (R. Daiss, 

3/3/2005, D291049,) and the revised dietary and drinking water assessment (R, Daiss, 

10/11/2005, D304867,) using the Dietary Exposure Evaluation Model (DEEM-FCID, Version 

2.03), and the Lifeline Model Version 2.0 which use food consumption data from the USDA’s 

Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. Tier II 

estimated drinking water concentrations used in the analyses were calculated by EFED using the 

PRZM/EXAMS surface water model (J. Melendez, 8/19/04, D293028). 

A refined probabilistic acute dietary-exposure assessment was performed using maximum 

percent crop treated, average field-trial residue values for blended commodities, distribution of 

field trial residues, and empirical processing factors. For the chronic dietary exposure analysis, 

average field trial residues and average percent crop treated (CT) were used. Empirical 

processing factors were also used. Dietary risk estimates were determined considering exposures 

from food plus drinking water using EDWCs for surface water sources provided by EFED. 
Ferbam/034801 Scoping Document Final

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The acute dietary risk estimates for food and drinking water combined are below HED’s level of 

concern (i.e., <100% of the aPAD) for the general U.S. population and all population subgroups. 

Using DEEM-FCID, acute dietary exposure at the 99.9th exposure percentile is estimated at 

0.0075 mg/kg bw/day for the general U.S. population (15% of the aPAD) and 0.2090 mg/kg 

bw/day (42% of the aPAD) for children 1-2 years old, the population subgroup with the highest 

% aPAD dietary exposure to ferbam. The revised DEEM model acute dietary exposure estimate 

for the population subgroup females 13-49 years old is 44% of the aPAD.

The refined chronic dietary risk estimates for food and water combined are below HED’s level of 

concern (i.e., <100% of the cPAD of 0.015 mg/kg bw/day) for the general U.S. population and 

all population subgroups. Using the DEEM-FCID software, dietary exposure is estimated at 

0.0001 mg/kg bw/day for the general U.S. population (<1% of the cPAD) and 0.0002 mg/kg 

bw/day (<1% of the cPAD) for children 1-2 years old, the population subgroup with the highest 

estimated chronic dietary exposure to ferbam.

Conclusions for Residue Chemistry, Enforcement Method, and Dietary Exposure and Risk: Field 

trial data for apple and grape remain outstanding (GDCI-034801-26275). However, optional 

bridging studies for ferbam, ziram and thiram on apple and grape could be submitted. Tolerances 

for cherry and grape are established however, these uses are not on the label. The registrant has 

indicated they are not supporting cherry and grape uses. If these uses are not supported, the grape 

residue field trials will not be required. A new dietary exposure and risk assessment will need to 

be conducted if there are changes to the ferbam toxicological endpoints/PODs or UFs or 

significant changes to the EDWCs. The assessment, if conducted, will use the newest version of 

DEEM and reflect updated consumption information.

Residential Exposure

There are no registered residential uses for ferbam; therefore, a residential exposure assessment

is not needed for registration review.

Residential bystander exposures resulting from off-site transport (e.g., spray drift or

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

be quantitatively evaluated for each pesticide during the Registration Review process which

ensures 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 Addenda 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 Analysis

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration

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 ferbam. 
Ferbam/034801 Scoping Document Final

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Conclusions: There are no residential uses registered for ferbam; therefore, a residential

exposure assessment is not necessary during registration review. The need for spray drift and

volatilization risk assessment for ferbam will be examined during registration review.

Aggregate Risk Assessment

In accordance with the Food Quality Protection Act (FQPA), HED 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. However, since there are no

residential uses for ferbam, the ferbam aggregate risk assessment includes only dietary exposure

(food and water). See dietary exposure assessment discussed above.

Occupational Exposure

Occupational handler and post-application exposures are expected based on the registered

agricultural uses of ferbam. Ferbam is currently formulated as a water dispersible granule. The

application rates range from 2.7 lb ai/A to 4.6 lb ai/A, and may be applied via chemigation, 

groundboom, air blast sprayer, and mechanically-pressurized hand wand; aerial application is 

prohibited. Occupational exposure scenarios applicable to ferbam range from short-term (1 to 30

days) to intermediate-term (30 days to six months) duration. 

The occupational handler assessments indicate that, for the currently registered uses, all of the

potential exposure scenarios result in dermal and inhalation margins of exposure (MOEs) greater

than or equal to the LOC of 100 with baseline clothing attire consisting of long pants, long

sleeved shirt and shoes plus socks. The current label requires the addition of gloves and a

respirator for airblast application.

Several levels of post-application exposure activities have been evaluated, ranging from “low

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

activities such as harvesting or thinning fruit from trees. Adequate dislodgeable foliar residue 

(DFR) data for ziram, which has a similar chemical structure and properties, are available for

apples and grapes. These data were used to assess all scenarios; additional DFR data are not 

needed at this time. Although the short- and intermediate-term post-application assessment

conducted for the RED indicated that MOEs reach the LOC of 100 on the day of application, a 

revised assessment was conducted as a result of a later submission of a DNT study on thiram, 

which identified post-application risks of concern (Daiss, R. 10/11/2005, D304867). The

restricted entry interval (REI) on the current label is 24 hours.

Conclusions: The occupational exposure database is adequate to support the registration review 

of ferbam. A new occupational exposure and risk assessment will need to be conducted if there 

are changes to the ferbam toxicological PODs or UFs or significant changes to current policies 

and exposure assessment methodology. 
Ferbam/034801 Scoping Document Final

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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 ferbam (Recore, S. and Evans, E. 

7/9/2015, D427982). The purpose of the database search is to identify potential patterns in the 

frequency and severity of the health effects attributed to ferbam exposure. There were no 

incidents reported in the IDS involving ferbam. A review of SENSOR-Pesticides 1998-2011 

identifies 19 cases, stemming from 15 events, involving ferbam. Of these, nine cases are single 

a.i., one case was a self-harm attempt by ingestion and was removed from the analysis. Of the 

eight remaining single a.i. cases, four cases were moderate in severity and four cases were low in 

severity. Ferbam is not included in the Agricultural Health Study (AHS).

Conclusions: Based on the low (or no) frequency and severity of incident cases reported for

ferbam to both IDS and SENSOR-Pesticides, 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.

Tolerance Assessment and International Harmonization

U.S. permanent tolerances are established under 40 CFR §180.114 for the registered uses of

ferbam in/on a number of commodities. Codex, Mexican, and Canadian maximum residue limits

(MRLs) for residues of ferbam have been established for some of the same commodities which

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

export purposes. While residue definitions are compatible with Codex, and expressed as carbon

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

The current tolerance residue levels will need to be reevaluated once the additional field trial

data are submitted. International harmonization will also be considered at the same time. See

Appendix 2, Table 2.2.

The tolerance expression for ferbam has been reviewed and should be updated as follows based 

on HED’s Interim Guidance on Tolerance Expressions (S. Knizner, 5/27/09). The tolerance 

expression should read: Tolerances are established for residues of the fungicide ferbam (ferric 

dimethyldithiocarbamate), including its metabolites and degradates, in or on the commodities in 

the table below. Compliance with the tolerance levels specified below is to be determined by 

measuring only those ferbam residues convertible to carbon disulfide, expressed as carbon 

disulfide, in or on the commodity.

A copy of the International Residue Limit Status (IRLS) sheet is attached to this memorandum.
Ferbam/034801 Scoping Document Final

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Table 1. Tolerance Summary for Ferbam.

Commodity Current Tolerance (ppm CS2)

Apple 4.0

Cherry 4.0

Cranberry 4.0

Fruit, citrus, group 10 4.0

Grape 4.0

Nectarine 4.0

Peach 4.0

Pear 4.0

Mango 4.0

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 Address Environmental Justice in Minority Populations and Low-Income 

Populations," http://www.epa.gov/compliance/environmentaljustice/resources/policy/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 

areas, 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 toxicity. At a September 2001 meeting of the

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

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

mechanism of toxicity with other chemical substances (dithiocarbamates). The basis for 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.
Ferbam/034801 Scoping Document Final

Page 12 of 39

Human Studies

The 2005 RED and supporting risk assessments relied in part on data from studies in which adult

human subjects were intentionally 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; and the Agricultural Reentry Exposure Task Force

(ARTF) database, are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that

review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics

review may have included review by the Human Studies Review Board. Descriptions of data

sources, as well as guidance on their use, can be found at the Agency website1

. 

Risk Assessment Updates and Data Deficiencies

• Additional field trial data for apple and grape were required in the DCI (GDCI-034801-

26275), unless acceptable bridging studies for ferbam, ziram and thiram on apple and

grape are submitted and ferbam labels are amended to match the use patterns in the field

studies. HED will translate field trial data for all fruit crop groups from ziram and/or

thiram to ferbam, provided three acceptable bridging studies in diverse locations (with

two side-by-side field trials each using ferbam, ziram, and thiram at identical application

rates and methods, PHIs, etc) are submitted for apple and grape; and indicate that

residues are comparable for the different fungicides and furthermore that the use

directions for ferbam are revised to be the same as the use on the proposed translated

data. The bridging study would not be required to use all three fungicides for all three

crop groups if the registrant does not propose to translate from both ziram and thiram to

ferbam for any individual crop group. Tolerances for cherry and grape are established

however, these uses are not on the label. The registrant has indicated they are not

supporting cherry and grape uses. If these uses are not supported the grape residue field

trials will not be required.

• Updated exposure and risk assessments will be conducted if there are any significant

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

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

data models or assumptions. 

 1 http://www.epa.gov/pesticides/science/handler-exposure-data.html and

http://www.epa.gov/pesticides/science/post-app-exposure-data.html
Ferbam/034801 Scoping Document Final

Page 13 of 39

References

Banijamali, A.; Gay, M.; Kehoe, D. et al. (1990) Elimination and Distribution of Thiram 

Following Nine Week Sub-Chronic Administration in Rats (Multiple Dose Treatment): Lab 

Project Number: 87114: 8850: 8850-1. Unpublished study prepared by Hazleton Labs, Inc.; 

Uniroyal Chem., Inc. and Analytical Dev. Corp. 151 p. (also MRID 42235702).

Cecconi S., Paro R., Rossi G., Macchiarelli G. (2007) The effects of the endocrine disruptors 

dithiocarbamates on the mammalian ovary with particular regard to mancozeb. Current 

Pharmaceutical Design, 13, 2989-3004.

Daiss, R. 12/30/2004. D291030.Occupational Exposure Assessment and Recommendations for 

the Reregistration Eligibility Decision (RED) for Ferbam. 

Daiss, B. 3/3/2005. D291049. Revised Ferbam Acute and Chronic Dietary Exposure 

Assessments for the Reregistration Eligibility Decision.

Daiss, R. 4/19/2005. D304864. Revised Ferbam HED Risk Assessment for Reregistration 

Eligibility Document (RED). B. Daiss. 

Daiss, R. 10/11/2005. D304867. Revised Addendum to the Risk Assessment Recommendations 

for the Reregistration Eligibility Decision (RED) for Ferbam. 

Fishbein L. (1976) Environmental health aspects of fungicides. Dithiocarbamates. J. Toxicol. 

Environ. Health, 1, 713-735.

Haworth, S., Lawlor, T, Mortelmans, K, Speck, W & Zeiger, E. (1983) Salmonella mutagenicity 

test results for 250 chemicals. Environ. Mutagenesis, Suppl. 1,3-142

Hodge, H.C.; Maynard, E.A.; Downs, W.; et al. (1952) Acute and short-term oral toxicity tests of 

ferric dimethyldithiocarbamate (ferbam) and zinc dimethyldithiocarbamate (ziram). J. Amer.

Pharm. Ass., Scientific Ed. XLI(12): 662-665. Also in unpublished submission received Dec 25, 

1962 under PP0393; submitted by E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.; 

CDL:090425-B) (also MRID 00083232).

Hodge, H.C.; Maynard, E.A.; Downs, W.L.; et al. (1956) Chronic oral toxicity of ferric 

dimethyldithiocarbamate (ferbam) and zinc dimethyldithiocarbamate (ziram). J. Pharm.

Experim. Thera. 118(2):174-181. (Also in unpublished submission received Dec 25, 1962 under 

PP0393; submitted by E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.; CDL: 090425-A)

(also MRID 00083231).

Hodgson, J.R., Hoch, J.C., Cassles, T.R., Helion, D.O., and Lee, C.C. (1975) Metabolism and 

disposition of ferbam in the rat. Toxicol. Appl. Pharmacol., 33, 505-513.
Ferbam/034801 Scoping Document Final

Page 14 of 39

Kidwell, J. 2/6/2003. TXR No. 0051541. Ziram: Second Report of the Cancer Assessment 

Review Committee.

Knizner, S. 05/27/2009. “Interim Guidance on Tolerance Expressions,” EPA Memorandum.

Lee C., Russel J., Minor J. (1978) Oral toxicity of ferric di- methyl dithiocarbamate (ferbam) and 

tetramethylthiuram disulfide (thiram) in rodents. J. Toxicol. Environ. Health, 4, 93-106 (also 

MRID 00143817).

Leshin, J. 4/30/2015. TXR No. 0057106. Ziram and Ferbam: 4 Summary of Hazard and Science 

Policy Council (HASPOC). Recommendations on the Requirement of an Immunotoxicity Study.

Leshin, J. 8/14/2015, TXR No. 0055029 Ferbam: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting of April 30, 2015: Recommendations on the Need for a 

Subchronic Dermal, 28-day Inhalation, Chronic Toxicity/Carcinogenicity, Mutagenicity, and 

Acute and Subchronic Neurotoxicity Studies. 

Liesivuori, J. and Savolainen, K. (1994) Dithiocarbamates. Toxicology, 91, 37-42

McGregor, D.B., Brown, A, Cattanach, P., Edwards, L, McBride, Do, Riach, C. & Caspaiy, WJ. 

(1988) Responses of the L5178Y tk+ /tk- mouse Iymphoma cell forward mutation assay: III. 72 

coded chemicals. Environ. Mol. Mutagenesis, 12, 85-154

Miller D.B., (1982) Neurotoxicity of the pesticidal carbamates. Neurobehavioral Toxicology and

Teratology, 4, 779-787.

Otakie, G. December 16, 1999; HED Metabolism Assessment Review Committee ad hoc Meeting 

of 12/09/ 99. Ziram/Ferbam Metabolism. Chemical Nos. 034805 and 034801. Barcodes D261844 

and D261846.

Otakie, G. 3/3/2005. D291050. Revised Ferbam Residue Chemistry Considerations for

Reregistration Eligibility Decision. 

Otakie, G. 3/24/2011. D384363. Thiram Spotrete F Fungicide (EPA Reg. No. 45728-26)

Amendment to Add Use on Peaches; and Reregistration Data - Magnitude of the Residue of

Ferbam, Thiram, and Ziram in Peaches-Dithiocarbamate Fungicide Formulation Bridging Study.

Occupational Exposure Assessment and Recommendations for the Reregistration Eligibility

Decision (RED) for Ferbam. R. Diass. 12/30/2004. D291030.

Recore, S. and Evans, E. 7/9/2015. D427982. Ferbam: Tier I (Scoping) Review of Human

Incidents and Epidemiology.
Ferbam/034801 Scoping Document Final

Page 15 of 39

Short, R.; Russel, J.; Minor, J.; et al. (1976) Developmental toxicity of ferric

dimethyldithiocarbamate and bis(dimethylthiocarbamoyl)disulfide in rats and mice. Toxicol.

Appl. Pharmacol., 35:83-94 (also MRID 00143816).

U. S. EPA. September 2005. Reregistration Eligibility Decision for

Ferbam. http://www.regulation.gov/ ID: EPA-HQ-OPP-738-R-05-009
Ferbam/034801 Scoping Document Final

Page 16 of 39

Appendix 1
Ferbam/034801 Scoping Document Final

Page 17 of 39

Table 1. Acute Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID Results MRID Results MRID Results

870.1100 Acute 

Oral

40561501 LD50 > 5000mg/kg 

(m/f)

Category IV

41340401a

42429301b

43701301a

LD50 =320 mg/kg (M&F)

LD50 = 381 mg/kg (M)

LD50 = 267 mg/kg (F)

Category II

LD50 >2000 mg/kg (M&F)

Category III

LD50 =2068 mg/kg (M&F)

LD50 = 2719 mg/kg (M)

LD50 = 2060 mg/kg (F) 

Category III

00153548 LD50 =2.6 g/kg

Category III

870.1200 Acute 

Dermal

40561502 LD50 >4000 mg/kg 

(m/f)

Category III

41340402a LD50 > 2000 mg/kg (M & 

F)

Category III

00147099 LD50 ≥ 2.0 g/kg

Category III

870.1300 Acute 

Inhalation

41508101 LC50 = 0.4 mg/L, 

Category II

41442001a LC50 =0.07 mg/L (M&F)

LC50 =0.08 mg/L (M)

LC50 = 0.06 mg/L (F) 

Category II

00152556 LC50 ≥ 0.1 mg/L

Category II

870.2400 

Primary Eye 

Irritation

40561503 Slight eye irritant

Category III

41643001a

41454401b

Severe irritation

Category I

Severe irritation

Category I

00147100 Moderate eye irritant

Category II

870.2500 

Primary Skin 

Irritation

40561505 Very slight to slight 

dermal irritant

Category IV

41643002a

41454602b

Not a dermal irritant

Category IV

Not a dermal irritant

Category IV

00147101 Very slight dermal irritant

Category IV

870.2600 Dermal 

Sensitization

40561504 Weak dermal 

sensitizer

41643003a Moderate dermal sensitizer; 

30% sensitization rate

00153068 Moderate dermal sensitize

a Technical b 76% formulation
Ferbam/034801 Scoping Document Final

Page 18 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

870.3100 90-day 

Oral Toxicity

(rodent)

MRID 00143817 

(Lee et al., 1978)

Acceptable/Nonguideline

0, 23, 66, 109, 331 

mg/kg/day (m)

13 weeks/CD Rats

NOAEL = 23 mg/kg/day

LOAEL = 66 mg/kg/day 

based on decreased body 

weight gain and food 

consumption

At 109 and 331 mg/kg/day, 

increased mortality (30% 

between 3rd and 5th week 

for109 mg/kg/day and 

100% in less than 1 week 

for 331 mg/kg/day), 

histopathological changes 

(golden pigmentation of 

reticulo endothelial cells) 

in spleen and mesentric 

lymph nodes were seen.

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

(Rat)

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 

female liver

40773601 (1988)

Unacceptable/guideli

ne

0, 50, 500, or 1000 

ppm

(0, 2.5, 25, or 50 

mg/kg bw/day)

Rat

NOAEL = could not be 

determined due to lack 

of information on 

stability. 

LOAEL = 25 

mg/kg/day, based on 

decreases in bodyweight gain, 

hematology and clinical 

chemistry parameters.

870.3150 90-day 

Oral Toxicity

(nonrodent)

N/A (requirement fulfilled by subchronic dog 

study; see Special Studies)

N/A (requirement fulfilled by chronic dog 

study)

41503608 (1990) 

Acceptable/guideline

0, 75, 250, or 500 

ppm 

(0, 1.94-2.58, 6.17-

7.85, or 10.55-14.69 

mg/kg bw/day)

(dog)

NOAEL = 1.9 

mg/kg/day. 

LOAEL = 6.3

mg/kg/day, based on 

adverse changes in 

clinical chemistry, and 

decreases in mean body 

weight and food 

consumption.

870.3200 21-day 

Dermal Toxicity Waived

41297001 (1989)

Acceptable/guideline

M&F: 0, 100, 300, 

1000 mg/kg

(Rabbit)

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 

42642501 (1992)

Acceptable/guideline

0, 250, 500, or 1000 

mg/kg bw/day

(rabbit)

NOAEL = 300 

mg/kg/day.

LOAEL = 1000 

mg/kg/day, based on 

decreases in bodyweight gain and food 

consumption as well as 

alterations in clinical 

chemistry.
Ferbam/034801 Scoping Document Final

Page 19 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

LOAEL was not 

observed in males.

870.3250 90-day 

dermal Waived

N/A N/A

870.3465 90/28-day 

Inhalation Waived

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

Study required and has been called in.

870.3700a 

Developmental Toxicity 

(rodent)

MRID 00143816 

(Short et al., 1976)

Acceptable/Nonguideline

0, 11, 114 

mg/kg/day

GD 6-15

(rat)

Maternal NOAEL = 11 

mg/kg/day

LOAEL =114 mg/kg/day 

based on 25% mortality, 

decreased body weight 

gain of dams, decreased 

number. of implants/dam, 

fetuses/dam, and 

increased. number of 

resorptions

Developmental NOAEL = 

11 mg/kg/day

LOAEL = 114 mg/kg/day 

based on decreased fetal 

body weight,

41908701 (1990)

Acceptable/guideline

F: 0, 1, 4, 16, 64 

mg/kg/day

(Rat)

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 

00151610 (1978)

Unacceptable/guideli

ne

0, 12.5, 25, 50, or 

100 mg/kg bw

(Rat)

40534101; 41498301 

(1988)

Acceptable/guideline

Maternal NOAEL = 

12.5 mg/kg.

LOAEL = 25 mg/kg, 

based on reduced bodyweight gains and food 

consumption.

Developmental NOAEL 

could not be 

determined.

LOAEL = 12.5 mg/kg, 

based on reduced 

ossification.

Maternal NOAEL 

could not be 

determined. 
Ferbam/034801 Scoping Document Final

Page 20 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

MRID 00143816 

(Short et al., 1976)

Acceptable/Nonguideline

0, 23, 228 

mg/kg/day

GD 6-14

(Mouse)

increased incidences of 

developmental anomalies 

(HDT vs Controls: 

unossified sternebrae20/31 vs 9/76, slightly 

collapsed cranium-7/31 vs 

0/76, malformed cranium2/35 vs 0/90 , 

hydrocephalus 2/35 vs 

0/90, hematoma-2/73 vs 

0/180 and cleft palate-1/35 

vs 0/90) were observed

Maternal NOAEL = 228 

mg/kg/day

LOAEL =None

Developmental NOAEL 

=23 mg/kg/day

LOAEL = 228 mg/kg/day 

based on increased no. of 

developmental anomalies 

(HDT vs Controls): thick 

atrial wall (5/88 vs 0/100), 

thin ventricular wall (8/88 

vs 0/100), hydroureter 

(13/88 vs 1/100), 

hydronephrosis (26/88 vs 

21/100), slight- (6/96 vs 

0/107) or marked-(1/96 vs 

0/107) collapsed cranium , 

extraossification of 

supraoccipitals (37/96 vs 

16/107) and malaligned

sternebrae (13/96 vs 

6/107).

diaphragmatic 

thinning

0, 7.5, 15, or 30 

mg/kg bw

(Rat)

LOAEL = 7.5 mg/kg, 

based on decreases in 

body-weight gain, 

alopecia, scars, 

damaged digits, redstained paws and 

excessive salivation.

Developmental

NOAEL = 7.5 mg/kg. 

LOAEL = 15 mg/kg 

based on retarded 

growth and rudimentary 

13th rib, and reduced 

ossification.
Ferbam/034801 Scoping Document Final

Page 21 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

870.3700b 

Developmental 

Toxicity (nonrodent)

N/A

00161316 (1986)

Acceptable/guideline

F: 0, 3, 7.5, 15 

mg/kg/day

(Rabbit)

Maternal NOAEL 

= 3 mg/kg/day

LOAEL = 7.5 

mg/kg/day based on 

decreased body 

weight gain.

Developmental 

NOAEL = 7.5 

mg/kg/day

LOAEL = 15 

mg/kg/day based on 

increased incidence 

of resorptions and 

post-implantation 

loss.

40444702(1987)

Acceptable

0, 1, 3, 5, 7.5, 10, 20, 

40, or 80 mg/kg bw

(range-finding)

(Rabbit)

40577301 (1987)

Acceptable

0, 1, 2.5, or 5mg/kg 

bw

(range-finding)

(Rabbit)

42223601 (1992)

Acceptable

0, 1, 5, or 10 mg/kg 

bw

(Rabbit)

Maternal NOAEL = 3

mg/kg bw/day.

LOAEL = 5 mg/kg/day, 

based on decreased 

maternal body-weight 

gains. 

Developmental

NOAEL was not 

determined.

LOAEL was not 

determined.

Maternal NOAEL = 5

mg/kg bw/day.

LOAEL was not 

determined. 

Developmental

NOAEL = 5 mg/kg.

LOAEL was not 

determined.

Maternal NOAEL = 10

mg/kg bw/day

LOAEL was not 

determined 

Developmental

NOAEL = 10 mg/kg

LOAEL was not 

determined.

870.3800 

Reproduction

MRID 00143816 

(Short et al., 1976)

Acceptable/Nonguideline

0, 23, 66,109 

mg/kg/day 

13 weeks 

treatment to males 

during premating

(Rat)

Systemic NOAEL (Males) 

= 23 mg/kg/day

LOAEL = 66 mg/kg/day 

based on decreased body 

weight and food 

consumption. At HDT, 

30% mortality between 2nd

and 6th week of treatment, 

decreased body weight and 

43935801 (1996)

Acceptable/guideline

0,72, 207, 540 ppm

F0 males: 0, 5.3, 

14.8, 37.5 

mg/kg/day

F0 females: 0, 6.1, 

16.8, 42.8 

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 

42095901 (1991)

Acceptable/guideline

0, 30, 60, or 180 ppm

(F0: 0/0, 1.2/1.9, 

2.4/3.9, or 8.5/11.8 

mg/ kg bw/day 

[M/F])

(F1: 0/0, 1.5/2.0, 

3.24.3, or 9.2/13.4 

mg/kg bw/day [M/F]

Parental/Systemic 

NOAEL = 30 ppm (1.9 

mg/kg/day [M/F]).

LOAEL = 60 ppm 

(2.6/3.1.7 mg/kg/day 

[M/F]) based on 

decreases in bodyweight gain and food 

consumption.
Ferbam/034801 Scoping Document Final

Page 22 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

MRID 00143816 

(Short et al., 1976)

Acceptable/Nonguideline

0, 15, 51 

mg/kg/day

14 days treatment 

to females prior to 

mating

(Rat)

MRID 00143816 

(Short et al., 1976)

Acceptable/Nonguideline

0, 7.6, 41 

mg/kg/day (before 

birth)

0, 23, 152 

mg/kg/day (after 

birth)

GD 16 through 

PND 21

food consumption were 

observed.

Reproductive NOAEL 

(Males ) = 109 mg/kg/day

LOAEL = None

Offspring NOAEL = 109

mg/kg/day

LOAEL = None

Systemic NOAEL 

(Females) =None 

LOAEL = 15 mg/kg/day 

based on decreased food 

consumption.

At HDT, decreased body 

weight and food 

consumption were noticed.

Reproductive NOAEL 

(Females ) = 51

mg/kg/day

LOAEL= None

Offspring NOAEL = 51

mg/kg/day

LOAEL = None

Systemic NOAEL 

(Females)= 7.6 mg/kg/day

LOAEL = 41 mg/kg/day 

based on decreased body 

weight and food 

consumption in dams

Reproductive

NOAEL(Females) = N/A

LOAEL = N/A

Offspring NOAEL = 23

mg/kg/day

F1 males: 0, 5.6, 

16.7, 42.7 

mg/kg/day

F1 females: 0, 6.3, 

18.4, 47.5 

mg/kg/day

(rat)

in the F0 and F1

males and females.

Offspring NOAEL 

= 16.8 mg/kg/day

LOAEL = 42.8 

mg/kg/day based on 

decreased body 

weights at birth in 

F2 pups and during 

lactation in F1 and 

F2 pups.

(rat)

45441203 (1997)

Acceptable/guideline

0, 20, 60, or 180 ppm

(0, 1.4, 4.2, or 12.2 

mg/kg bw/day)

(rat)

Reproductive NOAEL 

was not determined.

LOAEL >180 ppm (8.9 

mg/kg/day).

Offspring NOAEL = 

180 ppm (11.8 

mg/kg/day).

LOAEL = 60 ppm (3.9 

mg/kg/day), based on 

decreased mean body 

weight.

Parental/Systemic 

NOAEL = 20 ppm (1.4 

mg/kg/day).

LOAEL = 60 ppm (4.7 

mg/kg/day) based on 

reduced body-weight 

gains during gestation.

Reproductive NOAEL 

≥ 180 ppm (12.2 

mg/kg/day).

LOAEL was not 

determined.

Offspring NOAEL = 

20 ppm (1.4 

mg/kg/day).

LOAEL = 60 ppm (4.2 

mg/kg/day), based on 

decreases in pup body 

weight and body-weight 

gain.
Ferbam/034801 Scoping Document Final

Page 23 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

(Rat)

MRID 00085454 

(Sherman, 1966)

Acceptable/Nonguideline

0, 12.5 mg/kg/day 

(m/f)

3 months 

treatment during 

each generation 

(F0, F1, F2)

(Rat)

LOAEL = 152 mg/kg/day 

based on reduced viability, 

lactation indices, and 

reduced body weight of the 

pups.

Note: Cross feeding 

studies indicate reversal 

effects. Control pups 

nursed by dams in HDT 

had poor viability and 

growth. Pups from HDT 

nursed by control dams 

had good viability and 

normal body weight.

Systemic NOAEL= None

LOAEL = None

Reproductive NOAEL = 

12.5 mg/kg/day

LOAEL = None

Offspring NOAEL = 12.5

mg/kg/day

LOAEL = None

870.4100a Chronic 

Toxicity (rodent)

MRID 00083231 

(1956)

Acceptable/Non 

Guideline

0, 1.25, 12.5, 125 

mg/kg/day

2 years

ai not specified

(Ex-Wistar Rats)

NOAEL = 12.5 mg/kg/day

LOAEL = 125 mg/kg/day 

based on decreased body 

weight gain, 100% 

mortality, decreased life 

span (430 days vs 600-700 

days) abnormal hindleg 

grasping action at 2 or 

more months postdosing 

and cystic lesions in the 

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

(CD-rat)

NTP (1983)

Acceptable/guideline

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 

N/A
Ferbam/034801 Scoping Document Final

Page 24 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

MRID 00143817 

(Lee et al., 1978)

Acceptable/Nonguideline

0, 8, 32, 80 

mg/kg/day (m)

0, 9, 37, 96 

mg/kg/day (f)

(CD Rats)

cerebral cortex and 

cerebellum.

Note: testicular atrophy 

was present in mid and 

high dose groups, however 

not dose dependent.

NOAEL = 8 mg/kg/day

LOAEL = 32 mg/kg/day 

based on decreased body 

weight, food consumption, 

increased relative spleen 

weight in both males and 

females and increased 

relative testes weight and 

histological changes such 

as increased incidence of 

squamous metaplasia in 

thyroid, and/or severity of 

fatty infiltration in the 

pancreas in males.

At 96 mg/kg/day, ataxia 

which included an unusual 

gait, spreading of the hind 

limbs and dragging of the 

hind feet was noticed in 

1/24 females and partial 

paralysis of caudal to the 

lumbar region of the spine 

during 52-53 weeks was 

noticed in 2/24 females. 

HDT group had increased 

relative thyroid weight in 

both males and females.

0, 300, or 600 ppm

M: 0, 11, or 22 

mg/kg/day

F: 0, 13,or 26 

mg/kg/day

(F344 rat)

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

(F344 rat)

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 Chronic 

Toxicity (nonrodent)

MRID 00083231 

(Hodge et al., 

1956)

NOAEL = 5 mg/kg/day

LOAEL = 25 mg/kg/day 

based on 100% mortality 

42823901 (1993)

Acceptable/guideline

0, 50, 185, 700 ppm

NOAEL = M: 1.6, 

F: 1.9 mg/kg/day

41967901 (1991)

Acceptable/guideline

0, 30, 90, or 250 ppm

NOAEL (M) = 30 ppm 

(0.84 mg/kg/day).
Ferbam/034801 Scoping Document Final

Page 25 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

Acceptable/Non 

Guideline 0, 0.5, 

5, 25 mg/kg/day 

ai not specified

(1 yr Dog)

after 5-9 months, and 

convulsive seizures.

Note: n=1 per sex/group

M: 0, 1.6, 6.6, 17.4 

mg/kg/day

F: 0, 1.9, 6.7, 20.6 

mg/kg/day

(Dog)

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.

M; 0, 0.84, 2.61, or 

7.35 mg/kg bw/day

F: 0, 0.90, 2.54, or 

7.23 mg/kg bw/day

(dog)

NOAEL (F) = 90 ppm 

(2.54 mg/kg/day).

LOAEL (M) = 90 ppm 

(2.61 mg/kg/day, based 

on increased mean 

cholesterol levels.

LOAEL (F) = 250 ppm 

(7.23 mg/kg/day), based 

on increased mean 

cholesterol levels and 

increased liver-to-body 

weight ratios.

870.4200a 

Oncogenicity (rat)

MRID 00083231 

(Hodge et al., 

1956)

Acceptable/Non 

Guideline

0, 1.25, 12.5, 125 

mg/kg/day

2 years

ai not specified

(Ex-Wistar Rat)

MRID 00143817 

(1978)

Acceptable/Nonguideline

0, 8, 32, 80 

mg/kg/day (m)

0, 9, 37, 96 

mg/kg/day (f)

(CD Rat)

No evidence of 

carcinogenicity

No evidence of 

carcinogenicity

Same as chronic 

toxicity-CD rat 

above (870.4100a).

(CD rat)

Same as chronic 

toxicity-F344 rat 

above (870.4100a).

(F344 rat)

Same as chronic 

toxicity-F344 rat 

above (870.4100a).

(F344 rat)

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-cell 

carcinoma in male 

rats at 22 

mg/kg/day 

Evidence of 

carcinogenicity

based on increased 

incidence of 

preputial gland 

adenomas in male 

N/A
Ferbam/034801 Scoping Document Final

Page 26 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

rats at 74 

mg/kg/day.

870.4200b 

Oncogenicity 

(mouse)

N/A

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

(CD-1 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

(B6C3F1 mouse)

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 

hyperplasia and 

decreased body 

weight gain in CD1 males. No 

evidence of 

carcinogenicity

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/bronchiola

r adenomas and of 

combined 

42313401 (1992)

Acceptable/guideline

M: 0, 15, 150, or 300 

ppm F: 0, 15, 300, 

or 600 ppm

M: 0, 2.5, 24, and 57 

mg/kg bw/day

F: 0, 3.1, 57, and 112 

mg/kg bw/day

NOAEL = 15 ppm 

(M/F: 2.5/3.1 mg/kg 

bw/day).

LOAEL (M) = 150 ppm 

(24 mg/kg bw/day.

LOAEL (F) = 300 ppm 

(57 mg/kg/day), based 

on decreases in mean 

body weight and mean 

body-weight gain, 

anemia, and nonneoplastic lesions in the 

eyes, non-glandular 

stomach and urinary 

bladder.

No evidence of 

carcinogenicity.
Ferbam/034801 Scoping Document Final

Page 27 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

alveolar/bronchiola

r adenomas or 

carcinomas in 

female B6C3F1 

mice at ≥131 

mg/kg./day

870.4300 

Chronic/Oncogenicity Waived

42157601 (1991)

Acceptable/guideline

0, 30, 150, or 300 

ppm (0, M: 0, 1.5, 

7.3, and 14.7 mg/kg 

bw/day

F: 0, 1.8, 8.9, and 

18.6 mg/kg bw day

(Rat)

NOAEL = 30 ppm 

(M/F: 1.5/1.8 

mg/kg/day).

LOAEL = 150 ppm 

(M/F: 7.3/8.9 

mg/kg/day), based on 

changes in hematology, 

clinical chemistry, 

incidences of bile duct 

hyperplasia and 

reduction in mean 

body-weight gain. 

No evidence of 

carcinogenicity.

870.5100 

Mutagenicity – Gene 

Mutation – bacterial

Waived

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)

870.5265 Gene 

Mutation Waived

00147462 (1984)

Acceptable/guideline

The test article was 

positive for gene N/A
Ferbam/034801 Scoping Document Final

Page 28 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

Salmonella/mammali

an activation gene 

mutation assay

41642901 (1990)

Acceptable/guideline

Haworth, et al. 

(1983)

Acceptable/guideline

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)

870.5300 

Mutagenicity – Gene

Mutation –

mammalian

Waived

45806501(1999)

Acceptable/guideline

McGregor, et al. 

(1988)

Acceptable/guideline

No reproducible 

increase in the 

mutation frequency 

of mouse 

lymphoma cells 

was seen

The test article was 

positive for gene 

mutation induction 

(-S9).

00160621 (1986)

Acceptable/guideline

0.001-56.0 μg/mL 

(±S9)

(V79 Chinese 

Hamster Cells at the 

HPRT Locus)

No evidence of 

mutagenicity with or 

without metabolic 

activation.

870.5375 

Mutagenicity –

Cytogenetics -

Structural 

Chromosomal 

Aberrations

Waived

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).

40510901 ( 1987)

Acceptable/guideline

0.56, 1.0, or 2.4 

μg/mL (-S9)

1.8, 5.6, or 18.0 

μg/mL (+S9)

(Chromosomal 

Aberration Assay in 

Chinese Hamster 

Ovary Cells)

Significant dose-related 

increases in 

chromosomal 

aberrations with and 

without metabolic 

activation. Classified

as a clastogen.
Ferbam/034801 Scoping Document Final

Page 29 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

870.5395 Mammalian 

Erythrocyte 

Micronucleus test

Waived

Proudock, R.L. and 

Taylor, K. (1992

Unacceptable -

maximum tolerated 

dose not tested, 

dosing regimen not 

justified, and nonstandard 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. 

40510902 (1987)

Acceptable/guideline

38, 189, or 377 

mg/kg

Administration of 38, 

189, or 377 mg/kg 

thiram did not cause a 

significant increase in 

the frequency of 

micronucleated 

polychromatic 

erythrocytes (MPEs) 

harvested from male 

and female mice.

870.5550 

Unscheduled DNA 

Synthesis in Primary 

Rat 

Hepatocytes/Mammal

ian Cell

Waived

41287801 (1989)

Acceptable/guideline

There was no 

evidence that 

unscheduled DNA 

synthesis was 

induced.

00156064 (1985)

0.03, 0.1, 0.3, 1.0, 

3.0, or 10.0 μg/mL

Did not induce DNA 

repair.

870.6100a Acute 

Delayed 

Neurotoxicity (hen)

N/A N/A N/A

870.6100b 90-day 

Neurotoxicity (hen) N/A

Waived (TXR 0056685)

870.6200a Acute 

Neurotoxicity 

Screening Battery 

(rat)

Waived

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.

45589101 ( 1993)

Unacceptable/nonguideline

0, 10, 25, 60, or 150 

mg/kg bw

42912401 ( 1993)

Acceptable/guideline

0, 5, 150, or 600 

mg/kg bw

NOAEL = 10 mg/kg.

LOAEL = 25 mg/kg, 

based on decreases in 

food consumption in 

males and females.

BMDL10 = 64.94 

mg/kg.

LOAEL = 150 mg/kg, 

based on FOB effects at 

21/2 hours post-dosing; 

reduced motor activity 

at 31/2 hours, and at 7 

and 14 days posttreatment. 
Ferbam/034801 Scoping Document Final

Page 30 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

870.6200b 

Subchronic 

Neurotoxicity 

Screening Battery 

(rat)

Waived

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 brain 

neurotoxic esterase 

activity in the 

males.

43012701 (1993)

Acceptable/guideline

0, 30, 125 or 500 

ppm (0/0, 1.74/2.04, 

7.26/8.07, and 

28.63/31.82 mg/kg 

bw/day [M/F])

NOAEL = 30 ppm 

(1.74/2.04 mg/kg/day 

[M/F]).

LOAEL = 125 ppm 

(7.26/8.07 mg/kg/day 

[M/F]), based on 

increased numbers of 

rearing events and 

elevated incidences of 

hyperactivity in females 

at weeks 8 and 13.

870.6300 

Developmental 

Neurotoxicity (DNT)

N/A

43935801 (1996)

Unacceptable/guideli

ne

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 

46455201 (2004)

Acceptable/guideline

0, 20, 45, or 90 ppm

0, 1.4, 3.7, or 7.2 

mg/kg bw/day

Maternal NOAEL = 45 

ppm (3.7 mg/kg/day).

LOAEL = 90 ppm (7.2 

mg/kg/day), based on 

decreased body weight, 

body-weight gain, and 

food consumption, 

clinical signs of 

toxicity, and FOB 

findings.

Offspring NOAEL = 

20 ppm (1.4 mg/kg/day.

LOAEL = 45 ppm (3.7 

mg/kg/day) based on 

increased locomotor 
Ferbam/034801 Scoping Document Final

Page 31 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

47900401 (2009)

Acceptable/Nonguideline

0, 72, 207, 540/360 

ppm 

0, 8.6, 24, 46.6 

mg/kg/day

increased motor 

activity.

Maternal NOAEL 

= 8.6 mg/kg/day

LOAEL = 24 

mg/kg/day based on 

decreases in body 

weights, body 

weight gain, and 

food consumption 

during 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.

activity in females on 

PND17.

870.7485 General 

Metabolism

Acceptable/NonGuideline

Hodgson et al., 

1975 and JMPR

(Rat)

40-70% of 35S label 

absorbed in 24 h, 23% in 

urine, 18% in air, 1% in 

bile, <1% small amount in 

tissues. CS2 was the only 

compound found in the 

expired air.

43% of 14C in urine, 1.4% 

in bile, 0.6% in air (Note: 

the label was in the methyl 

carbon and this would not 

detect CS2)

42391001 (1992)

Unacceptable/guideli

ne

M&F: 15, 352 

mg/kg or 15 

mg/kg/day

(Rat)

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. 

42235701 No DER 

(Gay et. al., 1991)

41503607 No DER 

(Norris, 1989)

42235702 No DER 

(Banijamali et al., 

1990)

(Rats)

Rats (6 male + 6 

female) were dosed 

orally for 14 days with 

unlabeled thiram at 2 

mg/kg bw then with 

[

14C]thiram at 2 mg/kg 

bw on day 15 (Nomeir 

and Markham, 1990). 

Expired air and excreta 

were collected for a 

further 96 hours and 

then the animals were 

slaughtered for tissue 
Ferbam/034801 Scoping Document Final

Page 32 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

Hunt and Gilbert, 

1976

Acceptable/Nonguideline

35S-Ferbam 

(0.45mg/kg) 

and 3H-Ferbam 

(0.74mg/kg) -

Total 1.19 mg/kg 

bw, Single oral 

dose, One animal 

tested

(Sheep)

Hunt and Gilbert, 

1976

Unacceptable/Non

-guideline

35S-Ferbam 

(0.45mg/kg)

Single oral dose, 

One animal tested

(Sheep)

14C-ferbam crossed the 

placenta into the fetus.

In lactating rats, 14Cradioactivity was secreted 

into milk, absorbed by 

pups and excreted in pups 

urine.

35S-12% in urine and 11% 

in feces;

3H-62% in urine and 20% 

in feces

(majority of label 

eliminated in urine at 31-

47 h and in feces in 18-23 

h) 

14% in urine, 10% in feces

Dimethylamine and thiram 

were not found; Air was 

not analyzed

(Note: Dimethylamine 

metabolite would not be 

expected detected with 35Slabel)

46731701 (2001) 

main

Acceptable/Guidelin

e 

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)

Metabolites were 

not identified.

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.

collection. 

Approximately 33-35% 

of the administered 14C 

was eliminated in the 

urine, 2.6-5.3% in the 

feces and 47-48% in the 

expired air. The nature 

of the volatile 14C was 

not investigated in 

detail, but 75-85% of it 

was collected in a KOH 

trap suggesting CO2, or 

COS, with the 

remainder collected in a 

reagent for CS2. Norris 

(1991) identified by 

HPLC the metabolites 

in the urine of the rats 

from the single dose 

study of Gay (1987) 

and the multiple dose 

study of Nomeir and 

Markham (1990). 

There were no sex 

differences in the 

metabolism but the 

proportions of some of 

the metabolites 

depended on the dosage 

level and the time after 

dosing. 

[www.fao.org/docrep/

W5897E/w5897e5a.htm

]

870.7600 Dermal 

Penetration N/A

Same as 21-day 

dermal rabbit 

(870.3200) and 

The test material 

was minimally 

absorbed

Dermal absorption was estimated to be 1% 

(D291237, 2003)
Ferbam/034801 Scoping Document Final

Page 33 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

rabbit oral 

developmental 

(870.7600).

870.7800 

Immunotoxicity Waived (TXR No. 0057106) Waived (TXR No. 0057106)

48646401 (2011)

Acceptable/guideline

0, 15/17.5, 150, or 

450 ppm

(0, 3, 25, 74 

mg/kg/day)

(Mouse)

Systemic NOAEL = 

450 ppm (74 

mg/kg/day, the highest 

dose tested).

Systemic LOAEL was 

not established.

Under conditions of this 

study, the 

Immunotoxicity 

NOAEL = 150 ppm (25 

ppm)

Immunotoxicity 

LOAEL= 450 ppm (74 

mg/kg/day) based on 

treatment related 

decreases in anti-SRBC 

antibody response.

Special studies

28-Day Oral toxicity

MRID 00083232 

(Hodge et al., 

1952)

Acceptable/Non 

guideline

0, 7.5, 37.5, 188, 

375 mg/kg/day 

(m/f)

(Ex-Wistar Rats)

MRID 00083232 

(Hodge et al., 

1952)

0, 5, 25 

mg/kg/day

Acceptable/Non 

guideline

NOAEL = None

LOAEL = 37.5 mg/kg/day 

based on slight anemia and 

decreased body weight.

HDT had 50% mortality 

during the third and fourth 

week along with anemic 

effects.

NOAEL =None

LOAEL = 5 mg/kg/day 

based on decreased RBCs 

and hemoglobin

Note: n=1/group
Ferbam/034801 Scoping Document Final

Page 34 of 39

Table 2. Subchronic and Chronic Toxicology Profiles of Dimethyl Dithiocarbamates

Studies

Ferbam Ziram Thiram

MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results MRID / 

Classification / 

Doses

Results

(Dog) Severe vomiting and 

malaise at 100 mg/kg/day; 

however, no data provided.
Ferbam/034801 Scoping Document Final

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Table 3. Summary of Toxicological Doses and Endpoints for ferbam for Use in Dietary and Occupational Human Health Risk Assessments

Exposure/ Scenario Point of 

Departure

Uncertainty/FQPA Safety 

Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General Population, 

including Infants and 

Children)

NOAEL= 5

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Acute RfD = 0.05

mg/kg/day

aPAD =0.05 

mg/kg/day

Acute Neurotoxicity Study – Rat (Thiram; MRID 

42912401)

LOAEL = 150 mg/kg/day based on FOB effects (lethargy, 

lower temperature, reduced startle response, no tail pinch 

response) and reduced motor activity

Acute Dietary

(Females 13-49 

years of age)

NOAEL= 1.4 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Acute RfD = 

0.014 mg/kg/day 

Dev. Neurotoxicity Study – Rat (Thiram; MRID 

46455201)

LOAEL = 3.7 mg/kg/day based on increases in motor 

activity seen in female offspring on PND 17 

Chronic Dietary (All 

Populations)

NOAEL= 1.5

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x 

Chronic RfD = 

0.015

mg/kg/day

cPAD = 0.015 

mg/kg/day

Combined Chronic Toxicity/Carcinogenicity Study – Rat 

(Thiram; MRID 42157601)

LOAEL = 7.3 mg/kg/day based on changes in 

hematology, clinical chemistry, incidences of bile duct 

hyperplasia, and reduction in mean body weight gain

Incidental Oral 

All Durations

Endpoints of concern were not selected for incidental oral exposure scenarios (short and intermediate terms), since there are no 

residential uses (e.g., turf) supported for ferbam.

Dermal Short-Term 

(1-30 days)

NOAEL= 1.4

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Occupational LOC

for MOE = 100

Dev. Neurotoxicity Study – Rat (Thiram; MRID 

46455201)

LOAEL = 3.7 mg/kg/day based on increases in motor 

activity seen in female offspring on PND 17 

Dermal 

Intermediate-Term 

(1-6 months)

NOAEL= 1.4

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Occupational LOC

for MOE = 100

Dev. Neurotoxicity Study – Rat (Thiram; MRID 

46455201)

LOAEL = 3.7 mg/kg/day based on increases in motor 

activity seen in female offspring on PND 17

Inhalation 

All Durations

NOAEL= 1.5

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x UFDB = 10x

Occupational LOC 

for MOE = 1000

Combined Chronic Toxicity/Carcinogenicity Study – Rat 

(Thiram; MRID 42157601)

LOAEL = 7.3 mg/kg/day based on changes in 

hematology, clinical chemistry , incidences of bile duct 

hyperplasia, and reduction in mean body weight gain
Ferbam/034801 Scoping Document Final

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Table 3. Summary of Toxicological Doses and Endpoints for ferbam for Use in Dietary and Occupational Human Health Risk Assessments

Exposure/ Scenario Point of 

Departure

Uncertainty/FQPA Safety 

Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Cancer (oral, dermal, 

inhalation)

Based on bridging, the cancer classifications of thiram and ziram are protective of any potential carcinogenic effects of ferbam. No 

quantification of cancer risk is required for ferbam. 
Ferbam/034801 Scoping Document Final

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Data requirements (40 CFR 158.340) for ferbam are provided in the following table. Use of the 1998 

guideline numbers does not imply that the 1998 guideline protocols were used.

Table 4. Toxicology Data Requirements for Ferbam

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (nonrodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 90-Day Inhalation (28-day)

yes

yes

waived*

waived*

waived*

yes

yes

-

-

-

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (nonrodent)

870.3800 Reproduction

yes

NA

yes

yes

-

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (nonrodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

NA

waived*

yes

yes

yes

-

-

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5xxx Mutagenicity—Structural Chromosomal Aberrations

870.5xxx Mutagenicity—Other Genotoxic Effects

waived*

waived*

waived*

waived*

-

-

-

-

870.6100a Acute Delayed Neurotoxicity (hen)

870.6100b 90-Day Neurotoxicity (hen)

870.6200a Acute Neurotoxicity Screening Battery (rat)

870.6200b 90-Day Neurotoxicity Screening Battery (rat)

870.6300 Develop. Neurotoxicity (DNT)

NA

NA

waived*

waived*

NA

-

-

-

-

-

870.7485 General Metabolism

870.7600 Dermal Penetration

870.7800 Immunotoxicity

yes

NA

waived**

yes

-

-

Special Studies for Ocular Effects

Acute Oral (rat)

Subchronic Oral (rat)

Six-month Oral (dog)

no

yes

no

no

yes

no

*TXR No.: XXXXXXX

**TXR No.: 0057106
Ferbam/034801 Scoping Document Final

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Appendix 2

Table 2.1 Nomenclature and Physical/Chemical Properties Ferbam, Ziram, Thiram

Common name Ferbam Ziram Thiram

Chemical structure

Molecular Formula C9H18N3S6Fe C6H12N2S4Zn C6H12N2S4

Molecular Weight 416.5 305.8 240.4

IUPAC name ferric dimethyldithiocarbamate zinc bis(dimethyldithiocarbamate) tetramethylthiuram disulfide

CAS name tris(dimethylcarbamoditioato)iron (T-4)-bis(dimethyldithiocarbamatoS,S’)zinctetramethylthioperoxydicarbonic 

diamide

CAS # 14484-64-1 137-30-4 137-26-8

PC Code 034801 034805 079801

Melting point/range 180 C 226-251 C 142-150 C

pH of 1% aqueous susp NA 6.9-7.5 5% solubility NA

Density or specific 

gravity

0.6 kg/l 1.71 g/mL 0.32-0.35 g/mL

Water solubility 

(20°C)

130 mg/L 1.58-18.3 mg/L 18 mg/L

Solvent solubility 

(20°C)

soluble in organic solvents with 

high dielectric constant, e.g., 

chloroform, pyridine, acetonitrile, 

acetone

acetone 2.88, methanol 0.22, 

toluene 2.33, n-hexane 0.07 (g/L)

ethanol <10, acetone 80, chloroform 

230, hexane, dichloromethane 170, 

toluene 18, isopropanol 0.7 (g/L)

Vapor pressure at 20°C < 8.6x10-7 torr < 1 x 10-3 mPa 2.3 mPa

Dissociation constant 

(pKa)

NA NA NA

Octanol/water partition 

coefficient (Kow)

Kow logP -1.6 Kow logP 1.23 Kow logP 1.73

UV/vis absorption 

spectrum

NA NA NA

thiram and petroleum ether (0.0005 g/100 mL), benzene (4.12 g/100 mL), acetone (6.97 g/100 mL), xylene (0.91 

g/100 mL), and methanol (0.184 g/100 mL) at 20-25 C.
Ferbam/034801 Scoping Document Final

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Table 2.2 International Residue Limits .

Ferbam (PC Code 034801; Date of Request xx/xx/xx)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.114

Plants: ferbam (ferric 

dimethyldithiocarbamate), calculated as 

carbon disulfide 

Ferbam: (OC-6-

11)-

tris(dimethylcarba

modithioatokS,kS')iron 

(calculated as 

zineb)

ferbam 

(ferric 

dimethyld

ithiocarba

mate), 

calculated 

as carbon 

disulfide

Plant: total 

dithiocarbamates, 

determined as CS2,

evolved during acid 

digestion and expressed as 

mg CS2/kg.

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

US Canada Mexico1 Codex2

Apple 4.0 7 4 5

Cherry 4.0 7 4 0.2

Cranberry 4.0 7 4 5

Fruit, citrus, group 10 4.0 --- 4 2 Orange, 10 Tangelo and 

mandarin

Grape 4.0 7 4 5

Nectarine 4.0 7 4

Peach 4.0 7 4 7

Pear 4.0 7 4 5

Mango 4.0 7 4 2 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.