Dazomet Registration Review Human-Health Assessment Scoping Document 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

Date: September 4, 2013 

SUBJECT: Dazomet. Human-Health Assessment Scoping Document in Support of 

Registration Review. 

PC Code: Dazomet PC Code: 035602, MITC 

PC Code: 0681 03 

DP Barcode: 0410391 

Decision No.: 476790 Registration No.: N/A 

Petition No.: N/A Regulatory Action: Registration Review Scoping Document 

Risk Assessment Type: N/ A Case No.: N/A 

TXR No.: N/A CAS No.: Dazomet: 533-74-4, MITC: 556-61-6 

MRID No.: N/A 40CFR: N/A 

FROM: Shalu Shelat, Industrial Hygienist ~~ 0\?----5{ ~.t( ) 

Nancy McCarroll, Toxicologist fll, tft...J~.~J-1 JUJU~r~((~ .:---o r,___t~l hr.!} Christopher Schlosser, Toxicologist z. r 

Risk Assessment Branch 1 (RAB 

and , c----J2C) 

Charles Smith, Senior Branch Chiee::=. c...J ~ b"' 

Risk Assessment Branch 1 (RAB 1) 

Nathan Mottl, Biologist 

Health Effects Division (7509P) 

;1/~t~r /1IPtt( cr 1~ /r3 

Risk Assessment and Science Support Branch 

Antimicrobials Division (751 OP) 

THROUGH: Felecia Fort, Branch Chief ~Ct ( 

Risk Assessment Branch 1 (RABV1) ()..J"0:)_ ?/(;'/J3 

p~~ s .iJ~- '11~1'5 p ~l. \ U-f\;-=trV'-- 11 ~Irs 

Health Effects Division (7509P) 

Steve Weiss, Branch ChiP.T--.LJ.I..NIY' 

Tim Leighton, Senior Scie 

Risk Assessment and Scienc upport Branch ........ j 

Antimicrobials Division (751 OP) 

TO: Dana Friedman, Chemical Review Manager 

Pesticide Re-Evaluation Division (7508P) 

Page 1 of29 
Dazomet Registration Review Human-Health Assessment Scoping Document 

Attached is the combined Health Effects Division (HED) and Antimicrobial Division (AD) 

human-health risk assessment scoping document for dazomet and MITC to support registration 

review. 

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Dazomet Registration Review Human-Health Assessment Scoping Document

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Executive Summary

Dazomet (tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione) is a non-selective soil 

fumigant with fungicidal, herbicidal, and nematicidal properties. The primary degradate for 

dazomet is methyl isothiocyanate (MITC). Dazomet and MITC also are active ingredients in a 

variety of antimicrobial products. The MITC antimicrobial products are addressed in a separate 

HED scoping document. The Health Effects Division (HED) and the Antimicrobial Division

(AD) have evaluated the status of the human-health assessments for dazomet to determine 

whether sufficient data are available to support Registration Review. HED and AD have also 

considered the most recent human-health risk assessments for dazomet with respect to toxicity, 

exposure, and usage databases, and the most updated Agency science policy and risk assessment 

methodologies to determine the scope of work necessary to support Registration Review. It is 

noted that metam sodium and metam potassium are other pesticides that produces MITC upon 

application, however this document does not quantify exposure to metam sodium, metam 

potassium, or MITC resulting from those applications, which are addressed in a separate 

document. 

The Amended Reregistration Eligibility Decision (RED) for Dazomet was issued in May 2009. 

The RED addressed the major conventional and antimicrobial uses of dazomet. The

conventional uses include applications to strawberries, tomatoes, golf greens/tees, nonbearing

crops, turf sites (establishing or renovating), ornamental sites (establishing or renovating), field 

nurseries (establishing or renovating), compost piles and potting soils. The antimicrobial uses 

include treatment during the production of pulp and paper; use as a material preservative 

treatment for paper coatings, non-food adhesives, epoxy flooring compounds, slurries, and high 

viscous suspensions; use as a biocide treatment during petroleum operations and in recirculating 

cooling water systems; and use as a remedial wood treatment to utility poles. No new 

conventional uses of dazomet have been registered since the RED was issued. However,

additional antimicrobial uses of dazomet in paint and finger paint were identified and will need

to be assessed during Registration Review.

The toxicity database for dazomet is adequate for Registration Review with the exception of an 

MITC reproduction and fertility effects study and the chronic/carcinogenicity studies. These 

studies were required as part of the 2009 Amended RED and are currently being performed. The 

registrants have completed and submitted a number of other MITC toxicity studies required as 

part of the 2009 Amended RED including an acute study via the inhalation route, a 

developmental toxicity screening test via the inhalation route, an unscheduled DNA synthesis in 

mammalian cells in culture study, and an immunotoxicity study via the inhalation route. The 

Agency will review and incorporate all of these studies during Registration Review. The focal 

points for the assessment of dazomet and MITC are occupational dermal exposure to dazomet

and occupational and residential inhalation exposure to MITC. There is a route specific dermal 

study available for dazomet (NOAEL from a rabbit 21-day dermal toxicity study was greater 

than 1000 mg/kg/day). There are a number of route specific MITC inhalation studies available 

including an acute inhalation neurotoxicity study in rats, a 28-day inhalation study in rats, and a 

13-week inhalation study in rats. There is also an eye irritation and odor threshold study 

performed with human subjects that indicates the irritation properties of MITC. During 
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Registration Review, the Agency will reevaluate the points of departure (PODs) and uncertainty 

factors (UFs) for the residential and occupational exposure assessments.

The residue chemistry and dietary-exposure databases are adequate to support current 

registration requirements. The current uses of dazomet have previously been determined to be 

non-food uses. In addition, based on environmental fate data, the residual contents in soils, and 

monitoring data, MITC is not expected to adversely impact the drinking water sources such as 

surface water and ground water. Dietary and drinking water assessments are not required during 

Registration Review.

The occupational and residential exposure databases for the conventional uses of dazomet are

adequate for Registration Review. The registrants have completed and submitted a field 

volatility study measuring the breakdown products of dazomet, including MITC and 

formaldehyde. HED will review and incorporate this study during Registration Review.

The occupational and residential exposure databases for the antimicrobial uses of dazomet are

not adequate for Registration Review. As part of the 2009 Amended RED, AD required 

occupational dermal and inhalation dazomet handler mixing/loading exposure data for open pour 

(liquids) and solid pour (solids) to assess the antimicrobial uses of dazomet. At this time, these 

data have not been submitted to the Agency. Additional product use information, handler 

exposure, and post-application exposure studies are required for the antimicrobial use of dazomet 

in paints and finger paints during Registration Review. Additionally, AD notes that the 2009 

Amended RED required that the application rate for the antimicrobial use of dazomet in epoxy 

floor compounds be lowered however current labels have not been revised to comply with this

requirement. AD will review and incorporate all of submitted antimicrobial exposure data

during Registration Review. 

No data deficiencies outside those previously discussed in the 2009 Amended RED were 

identified for the conventional uses of dazomet. However, the following data deficiencies were 

identified for the antimicrobial uses of dazomet in paints and finger paints:

Occupational/Residential Exposure:

o 875.1700: Product use information 1

o 875.1200/875.1400: Occupational dazomet handler dermal and inhalation 

exposure for open pour mixing/loading paint 2

o 875.1200/875.1400: Occupational dazomet handler dermal and inhalation 

exposure applying paint (airless sprayer and brush/roller) 2

o 875.1200/875.1400: Residential dazomet handler dermal and inhalation exposure 

applying paint (airless sprayer and brush/roller) 2

o 875.2400: Post-application dazomet dermal exposure for finger painting

o 875.2500: Post-application MITC inhalation exposure for painted rooms

 

1 This data will be used to identify and characterize dazomet/MITC concentrations in paint and finger paint.

2 AD notes that these data requirements may be fulfilled by completed or planned Antimicrobial Exposure 

Assessment Task Force studies.
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EPA anticipates conducting the following risk assessment updates during Registration Review:

Toxicology: 

o Reevaluation of the toxicity endpoint/dose selection may be necessary based on 

the recently submitted toxicological data.

Residue Chemistry: None

Dietary Exposure: None

Occupational/Residential Exposure:

o Revised HED and AD occupational dazomet handler risk assessments may be 

necessary based on the most recent exposure data, Agency policies, or if the 

toxicological reevaluation results in changes to the endpoints.

o AD anticipates the need for occupational/residential dazomet handler dermal and 

inhalation risk assessments for applying paint using an airless sprayer and 

brush/roller during Registration Review.

o AD anticipates the need for residential post-application dazomet dermal risk 

assessments for using finger paint during Registration Review.

o AD anticipates the need for residential post-application MITC inhalation risk 

assessments for painted rooms during Registration Review.

o Additional or revised HED residential bystander risk assessments may be 

necessary based on the most recent exposure data, Agency policies, or if the 

toxicological reevaluation of results in changes to the endpoints.

1.0 Introduction

Dazomet (tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione) is a non-selective soil 

fumigant with fungicidal, herbicidal, and nematicidal properties. When dazomet is applied and 

mixed with moist soil or water, it quickly breaks down into several strong irritant products. One 

of these products is methyl isothiocyanate (MITC), which accounts for most of the fumigant 

activity. Dazomet and MITC also are active ingredients in a variety of antimicrobial products. 

The Health Effects Division (HED) and the Antimicrobial Division (AD) have evaluated the 

status of the human-health assessments for dazomet and MITC to determine whether sufficient 

data are available to support Registration Review. HED and AD have also considered the most 

recent human-health risk assessments for dazomet and MITC with respect to toxicity, exposure, 

and usage databases, and the most updated Agency science policy and risk assessment 

methodologies to determine the scope of work necessary to support Registration Review. Metam 

sodium and metam potassium are other pesticides that produces MITC upon application 

however, this document does not quantify exposure to metam sodium and metam potassium or 

MITC resulting from dazomet applications, which are addressed in a separate document.

The Amended Reregistration Eligibility Decision (RED) for Dazomet was issued in May 2009. 

The RED addressed the major conventional and antimicrobial uses of dazomet. The 

conventional uses include applications to strawberries, tomatoes, golf greens/tees, nonbearing 

crops, turf sites (establishing or renovating), ornamental sites (establishing or renovating), field 

nurseries (establishing or renovating), compost piles and potting soils. The antimicrobial uses 

include treatment during the production of pulp and paper; use as a material preservative 

treatment for paper coatings, non-food adhesives, epoxy flooring compounds, slurries, and high 

viscous suspensions; use as a biocide treatment during petroleum operations and in re-circulating 
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cooling water systems; and use as a remedial wood treatment to utility poles. No new uses of 

dazomet have been registered since the RED was issued. However, additional antimicrobial uses 

of dazomet in paint and finger paint were identified and will need to be assessed during 

Registration Review.

2.0 Hazard Identification/Toxicology

The 2009 Amended RED required a number of MITC toxicity studies, including the following: 

a neurotoxicity battery via the inhalation route (870.6200), 

a developmental toxicity screening test via the inhalation route (870.3550),

a reproduction and fertility effects study via the inhalation route (870.3800),

an unscheduled DNA synthesis in mammalian cells in culture study (870.5550),

an Immunotoxicity study via the inhalation route (870.7800),

a chronic/carcinogenicity rat study via the inhalation route (870.4200), and 

a chronic/carcinogenicity mouse study via the inhalation route (870.4200).

The registrants have completed and submitted the neurotoxicity study, the developmental study, 

the unscheduled DNA synthesis, and the immunotoxicity study and the Agency will review and 

incorporate these studies during Registration Review. The Agency has not received the 

reproduction and fertility effects study or the chronic/carcinogenicity studies at this time. Once 

these studies are completed and submitted they will be reviewed and incorporated during 

Registration Review.

Attachment 2 provides a summary of the acute, subchronic, and chronic toxicity profile for 

dazomet and MITC. The relevant data from the recently submitted studies have been 

incorporated into the toxicity profile. Attachment 2 provides a summary of the relevant 

toxicological endpoints used in dazomet and MITC 2009 risk assessment. During Registration 

Review, the Agency will reevaluate the MITC endpoints, points of departure (PODs), and 

uncertainty factors (UFs) for the residential and occupational exposure assessments based on 

current HED policy, recently submitted studies, and any other outstanding data.

No inhalation pharmacokinetic or metabolism studies are available at this time for dazomet or 

MITC. Dazomet is efficiently converted to MITC in vivo. Oral pharmacokinetic and 

metabolism studies in rats are available for dazomet and MITC. In those studies, dazomet and 

MITC were excreted mainly in urine with small amounts excreted in feces. Three different 

compounds (MITC, carbon dioxide [CO2], carbon oxide sulfide [COS]/carbon disulfide [CS2]) 

were found to be excreted in the lungs over a 73 hour collection period. Although the tissue with 

the highest uptake for all three compounds was the thyroid gland, it is notable that tissue 

retention of radioactive material was low in both sexes and at all doses. In the studies high 

uptake was also seen by the liver, kidneys, and lung, with the lowest level in testes, brain and 

eyes. Metabolic profiles detected in urine, liver, and the kidneys were similar for dazomet and 

MITC but there were some differences, mainly quantitative in nature. The consistent results seen 

in the dazomet and MITC oral pharmacokinetic and metabolism studies are further supported by 

the similarity in the oral doses causing similar toxic effects for dazomet and MITC in the 

available oral toxicity studies. Specifically, reduced body weight gain and food consumption in 
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addition to changes in hematological parameters were observed at low doses in oral toxicity 

studies with rats, mice, rabbits, and dogs.

In oral developmental toxicity studies with dazomet and MITC, effects such as fetal weight 

decrements, reduced ossification of various skeletal structures, and increased incidence of 

resorptions have been noted at similar molar dose levels. There is no quantitative susceptibility 

observed in the oral developmental and reproductive toxicity studies with dazomet and MITC. 

All of the developmental NOAELs are equal to or larger than the NOAELs for maternal toxicity. 

There is, however, qualitative susceptibility in two rabbit developmental toxicity studies with 

dazomet where increased incidence of resorptions were noted at a dose that resulted in maternal 

body weight gain decreases. 

The focal points for the assessment of dazomet and MITC are occupational dermal exposure to 

dazomet and occupational and residential inhalation exposure to MITC. The dazomet short- and 

intermediate-term dermal endpoints have previously been selected from an acute neurotoxicity 

study and a subchronic rat study, respectively. The dermal absorption of dazomet has been

estimated to be 4.5%. There are a number of route specific MITC inhalation studies available 

including an acute inhalation neurotoxicity study in rats, a 28-day inhalation study in rats, and a 

13-week inhalation study in rats. There is also an eye irritation and odor threshold study 

performed with human subjects that indicates the irritation properties of MITC.

Dazomet is currently classified as Group D-not classifiable as to human carcinogenicity. The 

evidence of in vitro mutagenicity for dazomet is, however, not manifested in whole animal 

studies. Thus, the issue of mutagenicity is not a concern for dazomet. For MITC, there are

currently insufficient data to characterize the cancer risk of MITC. As mentioned above, 

chronic/carcinogenicity studies for MITC were required as part of the 2009 RED. HED will 

reevaluate the carcinogenic potential of MITC during Registration Review after these studies are 

submitted and reviewed.

Conclusions: The toxicity databases for dazomet and MITC are adequate for Registration 

Review except for the outstanding toxicity studies (i.e., the reproduction and fertility effects 

study and the chronic/carcinogenicity studies) required in the 2009 Amended RED. During 

Registration Review, the Agency will reevaluate the points of departure (PODs) and uncertainty 

factors (UFs) for the residential and occupational exposure assessments based on current HED 

policy, recently submitted studies, and any other outstanding data.

3.0 Residue Chemistry

The residue chemistry databases for dazomet and MITC are adequate for Registration Review. 

Dazomet plant metabolism studies on strawberries and tomatoes indicate that the MITC 

generated from dazomet is degraded in the soil and the MITC degradates are taken up by the 

plant and incorporated into the natural plant constituents such as lipids, proteins, nucleic acids, 

hemicellulose, pectin, lignin, and polysaccharides. Residues of MITC were below the limit of 

quantitation in crop field trials conducted on strawberries and tomatoes. Therefore, the use of 

dazomet on strawberries and tomatoes are considered to be non-food uses and tolerances are not 

needed (C. Olinger; D287290; 08/16/04 and C. Olinger; D344375, 01/03/08).
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Conclusions: The residue chemistry database for dazomet is adequate for Registration Review.

4.0 Dietary Exposure

The dietary exposure databases for dazomet and MITC are adequate for Registration Review. 

As described in Section 3.0, the Agency previously decided that the uses of dazomet on 

strawberries and tomatoes are non-food uses.

Environmental fate data suggest that there is a low potential for the parent compound dazomet to 

be present in drinking water due to the rapid degradation of dazomet to MITC in the 

environment. MITC from dazomet applications could potentially move to surface water through 

runoff under an intense rainfall and/or if continuous irrigation occurs right after dazomet

application. However, the Henry’s Law Constant of 1.79 x 10-4 atm-m

3

/mol for MITC suggests 

that it would volatilize quickly from surface water. In addition, under most field conditions, the 

potential for significant ground water contamination of MITC is unlikely due to its volatilization 

and fast degradation in soil. MITC was not detected in any available non-targeted ground water 

monitoring samples within the USA. Based on environmental fate data, the residual contents in 

soils, and monitoring data, the Agency does not expect MITC to adversely impact the drinking 

water sources such as surface water and ground water.

Based on the discussion above, no dietary or drinking water assessments have been previously 

performed for dazomet or MITC.

Conclusions: The dietary exposure database for dazomet is adequate for Registration Review. 

Dietary and drinking water assessments are not anticipated during Registration Review.

5.0 Residential Exposure

The residential exposure database for the conventional uses of dazomet is adequate for 

Registration Review. The 2009 Amended RED required a field volatility study measuring the 

breakdown products of dazomet, including MITC and formaldehyde (835.8100). The registrants 

have completed and submitted this study and the Agency will review and incorporate it during 

Registration Review.

The residential exposure database for the antimicrobial uses of dazomet is not adequate for 

Registration Review. Product use information, residential handler dazomet dermal and 

inhalation exposure data for applying paint (airless sprayer and brush/roller), post-application 

MITC inhalation exposure data resulting from painted rooms, and post-application dazomet 

dermal exposure data to finger paints is required for the antimicrobial use of dazomet in paints

and finger paints during Registration Review. 

There are currently no registered conventional residential uses of dazomet. However, there is the 

potential for residential bystander inhalation exposure to MITC after a soil fumigation 

application of dazomet. The Agency has specifically focused on assessing acute MITC 

inhalation exposures resulting from dazomet applications because peak MITC air concentrations 
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typically occur in the first 24 or 48 hours after application. There is also the potential for 

inhalation exposure to MITC via ambient air however, dazomet use is minor when compared to 

metam sodium and metam potassium use thus it is likely that almost all MITC in ambient air 

would result from metam sodium/potassium applications. Ambient air exposure to MITC is

addressed in the Metam Sodium, Metam Potassium, and MITC HED scoping document. There 

are registered antimicrobial residential uses of dazomet in paint and finger paint. There is also 

the potential for residential post-application inhalation exposure to MITC after a room is painted 

with using paint that contains dazomet.

Conventional Uses

There is one recent document that analyzed acute residential bystander inhalation exposure to 

MITC based on numerous field volatility studies and PERFUM (Probabilistic Exposure and Risk

model for Fumigants) air modeling for a variety of dazomet applications (Shelat and Smith; 

D360773; 4/30/2009). The results of this assessment shows that bystander inhalation exposure 

to MITC after a soil fumigation application of dazomet can vary depending on a variety of 

factors such as application method, agricultural tarps, water seals, and a number of soil 

parameters (i.e., soil moisture, organic content, etc.). For many application scenarios, the 

PERFUM air modeling results showed that acceptable MITC air concentrations were attainable 

at some distance from a treated field and thus buffer zones were required to protect residential 

bystanders. The 2009 Amended Reregistration Eligibility Decision (RED) for Dazomet provides 

more information on buffer zone development.

Antimicrobial Uses

In the most recent dazomet AD risk assessment (C. Walls; D335651; 06/04/08) no residential 

uses were assessed. Since that time, the Agency has identified a polymer preservative dazomet 

use as an in-can preservative in paints and finger paints that has potential for residential 

exposure. These uses could potentially result in residential handler and post-application 

exposures. The Agency will need to assess these uses during Registration Review. The Agency 

anticipates that the following residential handler and post-application exposure scenarios are of 

potential concern for the dazomet paint and finger paint uses:

Painting with an airless sprayer (dermal and inhalation exposure);

Painting with a brush/roller (dermal and inhalation exposure);

Finger painting (dermal and hand-to-mouth incidental ingestion exposure); and

MITC bystander inhalation exposure from painted rooms.

During registration review, additional data are needed to support the labeled dazomet uses in 

paint and finger paint. For the paint uses, product use information (Series 875.1700) that 

characterizes dazomet/MITC concentrations in paint, dazomet dermal and inhalation handler 

exposure data (Series 875.1200/875.1400) for applicators painting (brush/roller and airless 

sprayer), and MITC post-application inhalation exposure data (Series 875.2500) resulting from 

painted rooms is required. For the finger paint uses, product use information (Series 875.1700) 

that characterizes dazomet/MITC concentrations in finger paint as well as dermal (dazomet) 

post-application exposure data (Series 875.2400) for finger painting is required. The post-
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application dermal exposure data will be used to verify the actual dislodgeable dermal 

dazomet/MITC residues on an adult hand and this data can be subsequently used to extrapolate 

children exposure while finger painting. Once these data are submitted to the Agency, it will be 

reviewed and incorporated into the dazomet antimicrobial residential risk assessment during 

Registration Review. 

Conclusions: 

The residential exposure database for the conventional uses of dazomet is adequate for 

Registration Review. HED will review and incorporate the submitted field volatility study

during Registration Review. Additional or updated PERFUM modeling and ambient air analyses 

may be required during Registration Review if the points of departure (PODs) or uncertainty 

factors (UFs) for the residential exposure assessment change based on the toxicological data 

required as part of the 2009 Amended RED.

During Registration Review, HED also plans to update the fumigant factors document (Dawson, 

Smith, and Shelat; D385314; 1/11/2011). The fumigant factors document provides a discussion 

of values and parameters used as the basis for buffer reduction credits (i.e., tarps) as well as for 

establishing GAPs (i.e., soil moisture) for the fumigants. This document impacts all of the soil 

fumigants including dazomet.

The residential exposure database for the antimicrobial uses of dazomet is not adequate for 

Registration Review. Product use information and residential handler and post-application 

dermal and inhalation exposure data are required for the antimicrobial use of dazomet in paints 

and finger-paints during Registration Review. AD will review and incorporate these data during 

Registration Review. 

6.0 Aggregate-Risk Assessment

Acute and chronic aggregate-risk assessments were not previously performed for dazomet or 

MITC because no dietary and drinking water assessments were performed (see Section 3.0 and 

4.0 above).

Conclusions: 

Acute and chronic aggregate risk assessments are not anticipated during Registration Review.

7.0 Occupational Exposure

The occupational exposure database for the conventional uses of dazomet is adequate for 

Registration Review. The occupational exposure database for the antimicrobial uses of dazomet 

is not adequate for Registration Review. In the 2009 Amended RED, dermal and inhalation

dazomet handler exposure data for the open pour (liquids) and solid pour (solids) mixing/loading 

scenarios was required for occupational antimicrobial uses of dazomet. At this time, these data 

have not been submitted to the Agency. Post-application inhalation MITC exposure data were 

also required as part of the 2009 Amended RED. Since that time, the registrants have submitted 

an observational MITC post-application inhalation exposure study for the pulp/paper industry 

use. AD is currently evaluating this study and as well as a Data Call-In (DCI) waiver request 
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that states that this study should be considered worst case and fulfill all the MITC postapplication inhalation exposure study requirements. Product use information, open pour 

mixing/loading occupational handler dazomet dermal and inhalation exposure data, and

occupational handler dazomet dermal and inhalation exposure data for applying paint (airless 

sprayer and brush/roller) are required for the antimicrobial use of dazomet in paints during 

Registration Review. 

There is a variety of conventional and antimicrobial uses of dazomet. The conventional uses 

include applications to strawberries, tomatoes, golf greens/tees, nonbearing crops, turf sites 

(establishing or renovating), ornamental sites (establishing or renovating), field nurseries 

(establishing or renovating), compost piles and potting soils. The antimicrobial uses include 

treatment during the production of pulp and paper; use as a material preservative treatment for 

paper coatings, non-food adhesives, epoxy flooring compounds, slurries, and high viscous 

suspensions; use as a biocide treatment during petroleum operations and in re-circulating cooling 

water systems; use as a remedial wood treatment to utility poles; and use in paints.

Occupational Handlers

Conventional Uses

There is potential for occupational handler dermal exposure to dazomet and inhalation exposure 

to MITC to occur based on the registered conventional uses of dazomet. The most recent HED 

document that analyzed potential occupational handler risks to dazomet and MITC is the 2009 

risk assessment (Shelat and Smith; D360773; 4/30/2009). HED utilized surrogate data from the 

Pesticide Handlers Exposure Database (PHED) and the Outdoor Residential Exposure Task 

Force (ORETF) to assess occupational handler dermal exposures to the soil fumigant uses of 

dazomet in the 2009 assessment. These assessments were considered conservative because 

PHED and ORETF data are based on non-volatile chemicals while dazomet can quickly break 

down to MITC. In many cases, short- and intermediate-term dermal risks exceed HED’s level of 

concern for the soil fumigant uses of dazomet.

HED currently has no exposure data to assess handler MITC exposures during or following

dazomet applications in agricultural scenarios, however a number of MITC inhalation exposure 

studies are available for metam sodium. These studies examined a variety of tasks associated 

with metam sodium applications such as loading and applying. In some cases, acute as well as 

short- and intermediate-term risks exceed HED’s level of concern for MITC at baseline (MOEs < 

10 for acute and MOEs < 30 for short- and intermediate-term). Even with the addition of an 

organic vapor respirator, some acute as well as short- and intermediate-term risks exceed HED’s 

level of concern for MITC. Based on this data, HED had concluded there were some concerns 

for MITC inhalation exposure for occupational handlers performing application tasks in the field 

as well as workers performing tasks near dazomet treated areas.

Antimicrobial Uses

There is potential for occupational handler dermal and inhalation exposure to dazomet to occur 

based on the registered antimicrobial uses of dazomet. The most recent AD document that 

analyzed potential occupational handler risks to dazomet is the 2008 risk assessment (C. Walls; 
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D335651; 06/04/08). AD utilized standard assumptions, expert knowledge, and surrogate unit 

exposure data from the Chemical Manufacturers Association (CMA) antimicrobial exposure 

study and the Pesticide Handlers Exposure Database (PHED) to assess occupational handler 

exposures to the antimicrobial uses of dazomet in the 2008 assessment. In some cases, 

intermediate-term dermal and inhalation risks exceeded AD’s level of concern (e.g., calculated 

MOEs were less than the target MOE of 100) for the antimicrobial uses of dazomet. The 2009 

Amended RED required a number of mitigation measures to address these risk concerns. AD 

notes that current dazomet antimicrobial labels do not reflect the 2009 Amended RED 

requirement that the application rate for the use of dazomet in epoxy floor compounds be 

lowered (maximum application rate of 0.35%).

In the 2009 Amended RED, dermal and inhalation dazomet handler exposure data for the open 

pour (liquids) and solid pour (solids) mixing/loading scenarios (875.1200/875.1400), application 

exposure monitoring data reporting (875.1600), product use information (875.1700 and 

875.2700), description of human activity (875.2800), and data reporting and calculations 

(875.2900) were required for occupational antimicrobial uses of dazomet. At this time, these 

data have not been submitted to the Agency. During registration review, additional data are

needed to support the labeled dazomet uses in paint. For the paint uses, product use information 

(Series 875.1700) that characterizes dazomet/MITC concentrations in paint, occupational handler 

dazomet dermal and inhalation exposure data (Series 875.1200/875.1400) for open pour 

mixing/loading, and dazomet dermal and inhalation handler exposure data (Series 

875.1200/875.1400) for applicators painting (brush/roller and airless sprayer) is required. Once 

all of these data are submitted to the Agency, it will be reviewed and incorporated into the 

dazomet antimicrobial occupational risk assessment during Registration Review. 

Occupational Post-Application

Conventional Uses

There is potential for occupational post-application inhalation exposure to MITC resulting from 

the registered conventional uses of dazomet. HED previously determined there were inhalation 

risk concerns for workers reentering fumigated fields 48 hours after application. As part of the 

2009 Amended RED, the Agency placed various restrictions on reentry of workers into 

fumigated fields. With these restrictions, HED believes that risks to reentry workers will not 

exceed the HED’s level of concern.

Antimicrobial Uses

There is potential for occupational post-application inhalation exposure to MITC resulting from 

the registered antimicrobial uses of dazomet. The most recent AD document that analyzed 

potential occupational post-application risks to MITC is the 2008 risk assessment (C. Walls; 

D335651; 06/04/08). In that assessment, AD detailed the potential concerns for post-application 

inhalation exposures to MITC for workers in the vicinity of dazomet applications in pulp/paper 

industries, as well as in coatings manufacturing, oil-field operations, and cooling water tower 

facilities because MITC is a highly volatile chemical. As a result, the 2009 Amended RED 

required post-application MITC inhalation exposure data for all enclosed facilities that utilize 

dazomet. Since that time, the registrants have submitted an observational MITC post-application 

inhalation exposure study for the pulp/paper industry use. The study measured the inhalation 
Dazomet Registration Review Human-Health Assessment Scoping Document

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potential exposures to workers in indoor and outdoor settings. The registrants have also recently 

submitted a DCI waiver request that states that the pulp/paper industry MITC study should be 

considered worst case and fulfill all the MITC post-application inhalation exposure study 

requirements. The Agency will review and incorporate the pulp and paper study during 

Registration Review as well as determining if it addresses all of the other indoor and outdoor 

antimicrobial uses of dazomet (e.g. coatings manufacturing, oil-field operations and recirculating cooling towers). 

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

Review process for the conventional uses of dazomet and MITC. HED may be required to 

update the occupational handler assessments during Registration Review if the points of 

departure (PODs) or uncertainty factors (UFs) for the occupational exposure assessment change 

based on the toxicological data required as part of the 2009 Amended RED.

The occupational exposure database for the antimicrobial uses of dazomet is not adequate for 

Registration Review. As part of the 2009 Amended RED, AD required occupational dermal and 

inhalation dazomet handler mixing/loading exposure data for open pour (liquids) and solid pour 

(solids) to assess the antimicrobial uses of dazomet. At this time, these data have not been 

submitted to the Agency. Additional product use information, handler exposure, and postapplication exposure studies are required for the antimicrobial use of dazomet in paints and 

during Registration Review. Additionally, AD notes that the 2009 Amended RED required that 

the application rate for the antimicrobial use of dazomet in epoxy floor compounds be lowered 

however current labels have not been revised to comply with this requirement. AD will review 

and incorporate all of submitted antimicrobial exposure data during Registration Review. 

Updated occupational handler assessments may also be required during Registration Review if 

the points of departure (PODs) or uncertainty factors (UFs) for the residential exposure 

assessment change based on the toxicological data required as part of the 2009 Amended RED.

8.0 Public Health and Pesticide Epidemiology Data

An updated review of dazomet (and MITC from dazomet applications) incident reports was 

recently prepared by HED (Recore and Evans, D414491, 08/29/2013). For this evaluation, both 

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 was consulted for pesticide incident data 

on the active ingredient dazomet. Dazomet is not included in the Agricultural Health Study 

(AHS) and therefore no information from AHS was included in this report.

The IDS includes reports of alleged human health incidents from various sources, including 

mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Section 6 (a) (2) reports 

from registrants, other federal and state health and environmental agencies and individual 

consumers. IDS contain reports from across the U.S. and most incidents have all relevant 

product information recorded. Reports submitted to the IDS represent anecdotal reports or 

allegations only, unless otherwise stated in the report. IDS records incidents resulting in higher

severity outcomes in more detail, in a module called the Main IDS module. This system stores 
Dazomet Registration Review Human-Health Assessment Scoping Document

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incident data for death, major and moderate incidents, and it includes more details about the 

location, date and nature of the incident.

In Aggregate IDS, from January 1, 2008 to February 19, 2013, there were 7 reported incidents 

involving dazomet. These incidents were classified as minor severity. For the Main IDS, from 

January 1, 2008 to February 19, 2013, there was one incident reported in the database. This 

incident was classified as moderate severity.

The SENSOR-Pesticides database covers 11 states from 1998-2009, although reporting varies 

from state to state. Cases of pesticide-related illnesses are ascertained from a variety of sources, 

including: reports from local Poison Control Centers, state Department of Labor workers’ 

compensation claims when reported by physicians, reports from State Departments of 

Agriculture, and physician reports to state Departments of Health. Although both occupational 

and non-occupational incidents are included in the database, SENSOR-Pesticides focuses on 

occupational pesticide incidents, and is of particular value in providing that information. The 

state coordinator at the 11 respective state Departments of Health conducts case follow-up 

activities such as obtaining medical records to verify symptoms and severity. Using standardized 

protocol and case definitions derived from poison center reporting, the state SENSOR-Pesticide 

coordinator enters the incident information into the state-based system which is sent to NIOSH 

annually to be aggregated. 

A query of SENSOR-Pesticides 1998-2009 identifies 2 cases, stemming from 2 events, involving 

dazomet. Both cases involve a single active ingredient. One case occurred in California in 1999, 

and was moderate in severity. No case narrative was entered. The second case occurred in 

California in 2005 and was low in severity. This case applied product to a telephone pole to 

control for termites and developed a rash. Both cases were work-related.

Based on the low frequency and severity of incident cases reported for dazomet in both IDS and 

NIOSH 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 Registration Review risk 

assessment.

9.0 Tolerance Assessment and International Harmonization

There are currently no tolerances for dazomet and MITC (see Section 3.0 above).

 

10.0 Environmental Justice

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

most recent dazomet human-health risk assessment, in accordance with U.S. Executive Order 

12898, “Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations,” 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The 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 
Dazomet Registration Review Human-Health Assessment Scoping Document

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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 highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information.

11.0 Cumulative

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to dazomet or MITC and any other substances. For the purposes of this assessment, therefore, 

EPA has not assumed that dazomet or MITC has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

12.0 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for potassium and sodium 

nitrate, EPA reviewed these data and selected the most sensitive endpoints for relevant risk 

assessment scenarios from the existing hazard database. However, as required by FFDCA 

section 408(p), potassium and sodium nitrate are subject to the endocrine screening part of the 

Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 
Dazomet Registration Review Human-Health Assessment Scoping Document

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Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 

chemicals identified for EDSP screening was published on June 14, 20131and includes some 

pesticides scheduled for Registration Review and chemicals found in water. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines and the Tier 1 screening battery, please visit our website.2

In the interim, EPA is making no human health or environmental safety findings 

associated with the EDSP screening of dazomet. Before completing this Registration Review, 

the Agency will make an EDSP FFDCA section 408(p) determination.

13.0 Human Studies

Past dazomet and MITC risk assessments rely on an intentional doing eye irritation and odor 

threshold study in human subjects (MRID no. 44400401) as the basis for the acute MITC 

endpoint. The Human Studies Review Board (HSRB) reviewed this study at a May 2-3, 2006 

meeting. The HSRB concluded that all applicable requirements of EPA’s Rule for the Protection 

of Human Subjects of Research (40 CFR Part 26) were satisfied in the study and that there was 

no regulatory barrier to continued reliance on these studies.

Past dazomet and MITC risk assessments also rely in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as PHED and the Outdoor Residential 

Exposure Task Force (ORETF) Database. EPA has reviewed all the studies supporting these 

multi-pesticide generic exposure databases, and has found no clear and convincing evidence that 

the conduct of any of them was either fundamentally unethical or significantly deficient relative 

to the ethical standards prevailing at the time the research was conducted. All applicable 

requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) 

have been satisfied, and there is no regulatory barrier to continued reliance on these studies.

14.0 Risk Assessment Updates, Data Deficiencies, and Label Revisions

No data deficiencies outside those previously discussed in the 2009 Amended RED were 

identified for the conventional uses of dazomet. However, the following data deficiencies have 

been identified for the antimicrobial uses of dazomet in paints and finger paints:

Occupational/Residential Exposure:

o 875.1700: Product use information 3

o 875.1200/875.1400: Occupational dazomet handler dermal and inhalation 

exposure for open pour mixing/loading paint 1

 

1

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

2

http://www.epa.gov/endo/

3 These data will be used to identify and characterize dazomet/MITC concentrations in paint and finger paint.
Dazomet Registration Review Human-Health Assessment Scoping Document

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o 875.1200/875.1400: Occupational dazomet handler dermal and inhalation 

exposure applying paint (airless sprayer and brush/roller) 2

o 875.1200/875.1400: Residential dazomet handler dermal and inhalation exposure 

applying paint (airless sprayer and brush/roller) 2

o 875.2400: Post-application dazomet dermal exposure for finger painting

o 875.2500: Post-application MITC inhalation exposure for painted rooms

EPA anticipates conducting the following risk assessment updates during Registration Review:

Toxicology: 

o Reevaluation of the toxicity endpoint/dose selection may be necessary based on 

the recently submitted toxicological data.

Residue Chemistry: None

Dietary Exposure: None

Occupational/Residential Exposure:

o Revised HED and AD occupational dazomet handler risk assessments may be 

necessary based on the most recent exposure data, Agency policies, or if the 

toxicological reevaluation results in changes to the endpoints.

o AD anticipates the need for occupational/residential dazomet handler dermal and 

inhalation risk assessments for applying paint using an airless sprayer and 

brush/roller during Registration Review.

o AD anticipates the need for residential post-application dazomet dermal risk 

assessments for using finger paint during Registration Review.

o AD anticipates the need for residential post-application MITC inhalation risk 

assessments for painted rooms during Registration Review.

o Additional or revised HED residential bystander risk assessments may be 

necessary based on the most recent exposure data, Agency policies, or if the 

toxicological reevaluation of results in changes to the endpoints.

 

1 AD notes that these data requirements may be fulfilled by completed or planned Antimicrobial Exposure 

Assessment Task Force studies.
Dazomet Registration Review Human-Health Assessment Scoping Document

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15.0 References

Memoranda Relevant to Registration Review.

Author Barcode Date Title

C. Olinger D287290 08/16/04 Dazomet Non-Food Use Status

C. Olinger D344375 01/03/08 Dazomet. Non-Food Use Status.

C. Walls D335651 06/04/08

Dazomet: Revised Occupational and Residential Exposure 

Assessment of Antimicrobial Uses for the Reregistration 

Eligibility Decision (RED) Document. 

S. Shelat D360773 4/30/2009 Dazomet: Updated Final Revised HED Chapter of the 

Reregistration Eligibility Decision Document (RED).

J. Dawson, C. 

Smith, and S. 

Shelat

D385314 1/11/2011

Methyl Bromide (PC Code 053201), Chloropicrin (PC 

Code 081501), Dazomet (PC Code 035602), Metam 

Sodium and Potassium (PC Codes 039003 & 039002), 

MITC (PC Code 068103), DP Barcode 385314, Second 

Update To Health Effects Division Recommendations for 

Good Agricultural Practices and Associated Buffer Credits

S. Recore and E. 

Evans D414491 8/29/13 Dazomet: Review of Human Incidents

Attachments: 

Attachment 1: Chemical Identity Table.

Attachment 2: Dazomet and MITC Acute, Subchronic, and Chronic Toxicity Profile

Attachment 3: Dazomet and MITC Endpoint Selection Tables.
Dazomet Registration Review Human-Health Assessment Scoping Document

Page 19 of 29

Attachment 1: Chemical Identity Table.

Physical and Chemical Properties of Dazomet and MITC

Parameter Dazomet MITC

Mode of Pesticidal Action generates MITC

The registrants have hypothesized that 

MITC interacts with a group of cation 

channels known as the transient receptor 

potential (TRP) family (see also Bandell,

Story, Hwang, et al., 2004). In particular 

the report suggests that TRPA1 may be the 

target.

Appearance white crystalline solid colorless crystalline solid

Melting Point 104 - 105 C 35-36 C

Vapor Pressure N/A 20 mm of Hg at 25 C

Partition Coefficient N/A 1.05 at 20 C

Solubility in Water < 0.1 g/100 mL at 18 C 8.94 g/L at 20 C

Toxic Impurities None1 None1

1 There are no major toxic impurities; however, there are several toxic degradate compounds.
Dazomet Registration Review Human-Health Assessment Scoping Document

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Attachment 2: Dazomet and MITC Acute, Subchronic, and Chronic Toxicity Profile

Acute Toxicity of Methyl Isothiocyanate (PC Code 068103 )

Guideline

No.

Study Type MRID #(S). Results Toxicity Category

81-1 Acute Oral-Rat 00162331 LD50 = 82 mg/kg ~

 55 mg/kg ~

II

81-2 Acute Dermal-Rat 00162330

42443501

LD50 = 136-436 mg/kg ~

 181 mg/kg ~ 

I

81-3 Acute Inhalation-Rat 45919410 LC50 = 0.54 mg/L II

81-4 Primary Eye Irritation 00162328 corrosion of the cornea and 

conjuctivae

I

81-5 Primary Skin Irritation 00162329 all animals died within one 

hour

I

Acute Toxicity of Dazomet (PC Code 035602)

Guideline

No.

Study Type MRID #(S). Results Toxicity Category

81-1 Acute Oral 00132468 LD50 = 596 mg/kg ~

LD50= 415 mg/kg ~

LD50= 519 mg/kg 

(combined)

II

Based on female 

values

81-2 Acute Dermal-Rats 42328802 LD50 = >2000 mg/kg III

81-3 Acute Inhalation 41563003 LC50 =>8.40 mg/L ~

 7.29 mg/L ~

IV

81-4 Primary Eye Irritation 41563002 slight to well defined 

conjunctival redness and 

chemosis. Returned to 

normal within 72 hours

III

81-5 Primary Skin Irritation 42328801 non-irritating to the skin of 

male rabbits

IV

81-6 Dermal Sensitization 47014505 and 

44031801

Not a sensitizer N/A
Page 21 of 29

Subchronic, Chronic, and Other Toxicities on Dazomet and MITC

Guideline No./ Study 

Type

Dazomet MITC 

MRID No. (year)/ Classification 

/Doses

Results MRID No. (year)/ 

Classification /Doses

Results

870.3100

90-Day oral toxicity 

rodents (rat)

41865502 (1987)

Acceptable/guideline

0, 30, 90, 300, 600 ppm

M: 0, 1.5, 4.5, 13.7, 28.0 mg/kg/day

F: 0, 1.7, 5.3, 15.4, 32 mg/kg/day

NOAEL = 1.5 mg/kg/day

LOAEL = 4.5 mg/kg/day based on 

increased liver weight and liver to 

body weight ratio; increased incidence 

of pronounced foci in the liver

Not available 

870.3100

90-Day oral toxicity 

rodents (mouse)

Not available Not available 

870.3150

90-Day oral toxicity in 

nonrodents (dog)

41866501 (1987)

Acceptable/guideline

0, 25, 100, 400/200 ppm

M: 0, 0.87, 3.5, 7.25 mg/kg/day

F: 0, 0.92, 3.5, 8.09 mg/kg/day

NOAEL = 3.5 mg/kg/day

LOAEL = 7.25 mg/kg/day based on 

increase in relative liver to body 

weight ratio and increased 

hemosiderosis in the spleen of males 

and females

Not available 

870.3200

21/28/30-Day dermal 

toxicity

40299101(1987)

Acceptable/guideline

0, 10, 100, 1000 mg/kg/day 

Dermal and Systemic NOAEL= 1000 

mg/kg/day

00132815 (1983)

Unacceptable/guideline

0, 0, 120, 240, or 480 

mg/kg/day

NOAEL < 120 mg/kg/day

LOAEL = 120 mg/kg/day based on 

decreased body weight gain and food 

intake. Severe necrosis and corrosion of the 

skin. 

41221406 (1986)

Unacceptable/guideline

0, 1.0, 10.0, and 100 mg/kg/day

NOAEL = 1 mg/kg/day

LOAEL = 10 mg/kg/day based on 

decreased serum albumin and increased 

globulin values in addition to increased 

liver weights. Irritation at all doses 

870.3250

90-Day dermal toxicity

Not available Not available 
Page 22 of 29

Guideline No./ Study 

Type

Dazomet MITC 

MRID No. (year)/ Classification 

/Doses

Results MRID No. (year)/ 

Classification /Doses

Results

870.3465

28-Day inhalation 

toxicity

Not available 45314802 (1987)

Acceptable/guideline

0, 5.1, 19.9, 100 ug/L

Systemic

NOAEL = 5 mg/m3(1.7 ppm).

LOAEL = 19.9 mg/m3,(6.8 ppm), based on 

clinical signs consistent with irritation in 

both sexes and increased neutrophilic 

polymorphonuclear granulocytes in the 

blood of males. 

Extrathoracic (ET) region

ET NOAEL = 19.9 mg/m3(6.8 ppm)

ET LOAEL = 100 mg/m3,(34 ppm), based 

on observation of pathological changes of 

the nasal cavity (metaplasia of respiratory 

epithelium and atrophy of the olfactory 

epithelium). 

Tracheabronchial (TB) region

TB NOAEL is 19.9 mg/m3(6.8 ppm)

TB LOAEL = 100 mg/m3(34 ppm), based 

on observation of pathological changes 

(tracheal epithelial proliferation and single 

cell necrosis, bronchopneumonia and 

bronchial and bronchiolar epithelial 

proliferation). 

870.3465

90-Day inhalation 

toxicity

Not available 41221407 (1978)

Acceptable/guideline

0, 3.16, 30.67, and 137.13 ug/L 

for 4 hours/day

0, 2.1, 20.6, and 91.9 ug/L 

extrapolated to 6 hour exposure

NOAEL = 3.16 ug/L

LOAEL = 30.67 ug/L based on decreased 

body weight, food efficiency and blood 

protein values accompanied by increased 

water intake. 

870.3465

90-Day inhalation 

toxicity (rats)

Not available 48869801 (2012)

Acceptable/guideline

0,1, 5, or 15 ppm

0, 3, 15, or 50 ug/L for 6 

hours/day

Portal of Entry

NOAEL = 3 ug/L

LOAEL = 15 ug/L based on lesions in the 

larynx and the nasal cavity.

Systemic

NOAEL = 50 ug/L , highest dose tested 

(HDT)
Page 23 of 29

Guideline No./ Study 

Type

Dazomet MITC 

MRID No. (year)/ Classification 

/Doses

Results MRID No. (year)/ 

Classification /Doses

Results

870.3465

90-Day inhalation 

toxicity (mice)

48869601 (2012)

Acceptable/guideline

0,1, 5, or 20 ppm

0, 3, 15, or 60 ug/L for 6 

hours/day

Portal of Entry

NOAEL = 3 ug/L

LOAEL = 15 ug/L based on lesions in the 

larynx, the trachea and the nasal 

cavity. 

Systemic

NOAEL = 15 ug/L 

LOAEL = 60 ug/L based on reduced body 

weights (M & F).

870.3700a

Prenatal 

developmental in 

rodents

41483701 (1987)

Acceptable/guideline

0, 3, 10, or 30 mg/kg/day 

Maternal NOAEL = 10 mg/kg/day

LOAEL = 30 mg/kg/day based on 

reduced body weight gain and 

decreased food consumption. 

Developmental NOAEL = 30 

mg/kg/day

44733602 (1998)

Acceptable/guideline

0, 3, 10, or 30 mg/kg/day

Maternal NOAEL = 3 mg/kg/day

LOAEL = 10 mg/kg/day based on 

salivation and decreased body weight gain. 

Developmental NOAEL =10 mg/kg/day

LOAEL = 30 mg/kg/day based on reduced 

fetal weight and an increased incidence of 

the skeletal variation of unossified 

sternebra(e).

45919417 (1987)

Unacceptable/guideline 

0, 3, 10, or 30 mg/kg/day

Maternal NOAEL = 10 mg/kg/day

LOAEL = 30 mg/kg/day based on 

decreased body weight gain and food 

consumption. 

Developmental NOAEL =10 mg/kg/day

LOAEL = 30 mg/kg/day based on higher 

number of runts and reduced placental 

weights.

870.3700b

Prenatal 

developmental in 

nonrodents (rabbit)

92028011 (1980)

Unacceptable/guideline

0, 25, 50, 75 mg/kg/day

0, 6.25, 12.5, 25 mg/kg/day

Maternal NOAEL = 12.5 mg/kg/day 

LOAEL = 25mg/kg/day based on the 

reduced body weight gain.

Developmental NOAEL = 12.5 

mg/kg/day 

LOAEL = 25 mg/kg/day based on the 

increased incidence resorptions and 

resorptions/dam

45919418 (1986)

Unacceptable/guideline

0, 1, 3 or 10 mg/kg/day

Maternal tentative NOAEL = 3 mg/kg/day

Tentative LOAEL = 10 mg/kg/day based 

on reduced body weight gain and food 

consumption.

Developmental NOAEL =10 mg/kg/day

LOAEL > 10 mg/kg/day
Page 24 of 29

Guideline No./ Study 

Type

Dazomet MITC 

MRID No. (year)/ Classification 

/Doses

Results MRID No. (year)/ 

Classification /Doses

Results

870.3700a

Prenatal 

developmental in 

rodents (rats) 

inhalation

48779701 (2012)

Acceptable/guideline

0,1, 4, or 12 ppm

0, 3, 12, or 35 ug/L for 6 

hours/day

Maternal NOAEL = 12 ug/L 

LOAEL = 35 ug/L based on decreased 

body weight, body weight gain, corrected 

body weight gain, and food consumption.

Developmental NOAEL = ≥35 ug/L 

(HDT)

870.3700b

Prenatal 

developmental in 

nonrodents (rabbits) 

inhalation

48779501 (2012)

Acceptable/guideline

0,1, 5, or 15 ppm

0, 3, 15, or 50 ug/L for 6 

hours/day

Maternal NOAEL = 15 ug/L 

LOAEL = 50 ug/L based on mortality, 

clinical signs associated with the 

respiratory tract, unkempt appearance, blue 

areas on the face, gross findings in the 

respiratory tract and stomach, decreased 

body weight gain, and decreased food 

consumption.

Developmental NOAEL = ≥50 ug/L 

(HDT)

870.3800

Reproduction and 

fertility effects 

41865301 (1989)

Acceptable/ guideline

0, 5, 30, 180 ppm

0, 0.5, 3, or 17- 19 mg/kg/day

Parental/Systemic NOAEL = 0.5 

mg/kg/day

LOAEL = 3 mg/kg/day based on 

increased incidence and severity of 

hepatic intracellular neutral lipids in 

male rats; decreased body weight in 

F1 males.

Reproductive NOAEL = 17- 19 

mg/kg/day

-19 mg/kg/day (HDT)

40974601 (1987)

Unacceptable/guideline

0, 2, 10, and 50 ppm

M P: 0, 0.16, 0.76 and 3.58 

mg/kg/day

F P: 0, 0.21, 1.01, and 4.76 

mg/kg/day

M F1 0, 0.15, 0.71, 3.4 

mg/kg/day

F F1: 0, 0.19, 0.87, 4.22 

mg/kg/day

Parental/Systemic NOAEL = 10 ppm, 

0.71 mg/kg/day 

LOAEL = 50 ppm, 3.4 mg/kg/day based 

on decreased body weight gain in F1 males.

Reproductive NOAEL = 50 ppm, 3.4M/ 

4.22F mg/kg/day

LOAEL > 50 ppm, 3.4M/ 4.22F mg/kg/day

Offspring NOAEL = 50 ppm, 3.4M/ 4.22F 

mg/kg/day 

LOAEL > 50 ppm, 3.4M/ 4.22F mg/kg/day

870.4100a

Chronic toxicity 

rodents

41865001 (1989)

Acceptable/guideline 

0, 5, 20 or 80 ppm

M: 0, 0.2, 0.9 or 3.71 mg/kg/day

F: 0, 0.3, 0.84 or 4.83 mg/kg/day

NOAEL = 0.84 mg/kg/day 

LOAEL= 4.83 mg/kg/day based on 

significant trend but not pair wise 

increased incidence of neoplastic and 

non-neoplastic pathology

See combined chronic/carcinogenicity 
Page 25 of 29

Guideline No./ Study 

Type

Dazomet MITC 

MRID No. (year)/ Classification 

/Doses

Results MRID No. (year)/ 

Classification /Doses

Results

870.4100b

Chronic toxicity dogs

41967701 (1989)

Acceptable/guideline

0, 15, 50, 150 ppm

M: 0, 0.028, 1.05, 3.15 mg/kg/day

F: 0, 0.35, 1.12, 3.50 mg/kg/day 

NOAEL 0.35 mg/kg/day

LOAEL = 1.15 mg/kg/day based on 

increased liver to body weight ratio 

and increased pigmentation in the 

liver

41240701 (1988)

Unacceptable/guideline

0, 0.04, 0.4, 2.0 mg/kg/day

NOAEL = 0.4 mg/kg/day

LOAEL = 2.0 mg/kg/day based on 

excessive salivation, RBC measures, and 

increased liver weights.

870.4300

Combined Chronic/

Carcinogenicity rats

41865401 (1989)

Acceptable/guideline 

0, 5, 20, 80, 320 ppm

M: 0, 0.23, 0.94, 3.81, 16.36 

mg/kg/day

F: 0, 0.29, 1.19, 5.09, 21.5 

mg/kg/day

NOAEL = 0.94 mg/kg/day 

LOAEL= 3.81 mg/kg/day based on 

increased serum albumin, globulins, 

total protein, hemoglobulin, 

hematocrit, and RBC in female rats

and serum cholesterol in male rats

00150078 (1984)

Unacceptable/guideline 

0, 2, 10, and 50 ppm 

0, 0.2, 1.0 and 5 mg/kg/day

NOAEL = 50 ppm

LOAEL = > 50 ppm 

870.4300

Chronic/

Carcinogenicity mice

41865101 (1989)

Acceptable/guideline 

0, 20, 80 or 320 ppm

M: 0, 3.9, 15.6 or 69.9 mg/kg/day

F: 0, 5.7, 21.4 or 95.0 mg/kg/day

NOAEL = 3.9 mg/kg/day

LOAEL = 15.6 based on increased 

liver masses in male mice at 78 

weeks; increased liver weight in 

female mice at 78 weeks

00150075 (1980)

Unacceptable/guideline

0, 5, 20, 80, and 200 ppm

M: 0, 0.82, 3.30, 11.83, and 

25.71 mg/kg/day 

F: 0, 0.91, 3.66, 13.03, 29.03 

mg/kg/day

NOAEL = 20 ppm; 0.82 M/0.91 F 

mg/kg/day

LOAEL = 80 ppm, 3.30 M/ 3.66 F 

mg/kg/day based on decreased body weight 

gain throughout the majority of the study 

and reduced water consumption. 

870.5100 

Reverse Gene 

Mutation – Salmonella 

typhimurium

00131909 (1979)

Unacceptable/Guideline

0, 12.3- 1000 μg/plate -S9

0, 3.7 - 1000 μg/plate +S9

Negative

.

41221410 (1978)

Acceptable/Guideline

0, 0.5, 1, 5, 10, 50, 100, 500 and 

1000 μg/disc +/-S9

Negative in S. typhimurium and 

Escherichia coli WP2 uvrA up to severely 

cytotoxic concentrations (500 and 1000 

μg/disc +/-S9)

00131910 (1980)

Acceptable/Guideline

0, 3.7 - 300 μg/plate -S9

0, 12.3 - 1000 μg/plate +S9 (both 

Aroclor 1254-induced and 

phenobarbital induced) 

Negative up to cytotoxic doses

(≥ 300 μg/plate +/-S9.

870.5250

Sex-linked recessive 

lethal test in

Drosophilia 

melanogastre 

00131916 (1970)

Acceptable/Guideline

0, 0.025 and 0.05 mg/mL

Negative Not available
Page 26 of 29

Guideline No./ Study 

Type

Dazomet MITC 

MRID No. (year)/ Classification 

/Doses

Results MRID No. (year)/ 

Classification /Doses

Results

870.5300

In vitro mammalian 

cells gene mutation 

test (mouse lymphoma 

cells) 

00131912(1980)

Acceptable/Guideline

0, 0.6, 0.8, 1.0, 2.0, 4.0, and 5.0. 

μg/mL +/-S9

Positive –S9 only at concentrations 

≥0.6 μg/mL -S9

Not available

870.5300

In vitro mammalian 

cells gene mutation 

test-- Chinese hamster 

ovary (CHO) cells at 

the HGPRT locus 

41497901 (1985)

Acceptable/Guideline

0, 0.1, 0.0215, 0.0464, 0.1, 0.215, 

and 0.464 μg/mL +/-S9

Positive concentration-related 

increases in the mutation frequency 

(MF) at 0.215 and 0.464 μg/mL -S9 & 

0.1, 0.215 and 0.464 μg/mL +S9 

Not available

870.5375

In vitro chromosome 

aberration –

mammalian cells 

(human lymphocytes)

41482302 (1989)

Unacceptable

0, 0.0001, 0.0004, 0.002, 0.01, and 

0.05 μg/mL -S9; 0.004, 0.02, 0.1, 

0.5, 2.5, and 12 μg/mL +S9

Negative; inappropriate 

concentrations tested 

41221411 (1988)

Acceptable/guideline

0, 3.0 & 5.0 μg -/+S9

Negative in human lymphocytes up to a 

cytotoxic concentration (5.0 μg -/+S9)

870.5375

In vitro chromosome 

aberration –

mammalian cells 

(mouse lymphoma 

cells)

00131912(1980)

Acceptable/Guideline

0, 0.6, 0.8, 1.0, 2.0, 4.0, and 5.0. 

μg/mL +/-S9

Positive –S9 only at concentrations of 

4 or 5 μg/mL -S9

870.5380

Mammalian 

spermatogonia 

cytogenetic assay in 

Chinese hamsters

41497902 (1985)

Acceptable

0, 10, 33, and 100 mg/kg

Negative Not available

870.5395

Micronucleus Assay –

Mice

41497903 (1985)

Acceptable/Guideline

0, 45, 90 and 180 mg/kg

Negative up to a toxic dose (180 

mg/kg) 

48631101 (2011)

Acceptable/guideline

0, 20, 40, and 100 ppm 

(inhalation)

Negative up to a toxic concentration (100 

ppm)

870.5500

Bacterial DNA damage 

or repair tests—

Bacillus subtilis rec 

assay

41482301 (1987)

Acceptable/Guideline

0, 1, 10, 100, 500, 1000, 2500, 5000 

and 10,000 μg/plate +/-S9

Negative for preferential inhibition up 

to a cytotoxic concentration (≥10 

μg/plate +/-S9) 

41221410 (1978)

Unacceptable

0, 20, 100, 200, 500, 1000, and 

2000 μg/disc –S9

Negative
Page 27 of 29

Guideline No./ Study 

Type

Dazomet MITC 

MRID No. (year)/ Classification 

/Doses

Results MRID No. (year)/ 

Classification /Doses

Results

Unscheduled DNA 

Synthesis -Rat 

Hepatocytes (in vivo)

41482303 (1986)

Acceptable

0, 37.5, 75, 150, and 300 mg/kg

Negative Not available

870.5900

In vitro sister 

chromatid exchange –

mammalian cells 

(mouse lymphoma 

cells)

00131912(1980)

Acceptable/Guideline

0, 0.6, 0.8, 1.0, 2.0, 4.0, and 5.0. 

μg/mL +/-S9

Negative Not available

In vitro cell 

transformation in 

BALB 3T3 cells

00131914 (1978)

Unacceptable

0, 0.025, 0.05, 0.1, 0.2, and 0.4 

μg/mL -S9

Negative Not available

870.6200a

Acute neurotoxicity 

screening battery

43465302 (1994)

Acceptable/guideline 

0, 50, 130, and 450 mg/kg (M)

0, 15, 50, and 150 mg/kg (F)

NOAEL = 15 mg/kg (F)* 

LOAEL = 50 mg/kg (M & F) for 

neurobehavioral effects, based on 

FOB findings and reduced number of 

rearings. 

Not available 

870.6200a

Acute neurotoxicity 

screening battery 

inhalation (rats)

48675701 (2011)

Acceptable/guideline 

0, 20, 40, or 80 ppm (0, 0.06, 

0.12, or 0.24 mg/L

Portal of Entry

LOAEL = 20 ppm (0.06 mg/L) based on 

mild to severe necrosis of the olfactory 

epithelium (1/6 M; 5/6 F), which was not 

resolved in the 2-week exposure time.

Systemic/Neurotoxic

NOAEL = 20 ppm (0.06 mg/L) LOAEL = 

40 ppm (0.12 mg/L, based on rales and 

gasping on study days 1 & 2 and decreased 

locomotor activity on study day 0 in both 

sexes. 

870.6200b

Subchronic 

neurotoxicity 

screening battery

43465301 (1994)

Acceptable/guideline 

0, 50, 200, 400 ppm 

M: 0, 4, 16, 36 mg/kg/day

F: 0, 4, 15, 34 mg/kg/day

NOAEL = Not established

LOAEL = 4 mg/kg/day based on fatty 

degeneration of the liver

Not available 
Page 28 of 29

Guideline No./ Study 

Type

Dazomet MITC 

MRID No. (year)/ Classification 

/Doses

Results MRID No. (year)/ 

Classification /Doses

Results

870.6300

Developmental 

neurotoxicity

Not available Not available 

870.7600

Dermal penetration

Not available Not available 

870.7800

Immunotoxicity

(Inhalation)

Not available 148694901 (2011)

Acceptable/guideline 

0, 1, 3 or 10 ppm

(0,3, 9 or 30 μg/L) 6 hours/day 

for 28 days 

Systemic:

LOAEL = 10 ppm (30 μg/L), HCT

NOAEL = Not established

Immunotoxicity:

LOAEL = 10 ppm (30 μg/L), HCT

NOAEL = Not established

Special Study: Human 

Eye Irritation and Odor 

Threshold

Not available 44400401 (1996)

Acceptable/non-guideline

0, 0.22, 0.6, 0.8, 1.9, 3.3 ppm

One-minute exposure, the NOAEL for eye 

irritation is 3.3 ppm due to a lack of 

response in any parameter tested. 

4-14 minutes, the NOAEL for eye irritation 

is 0.6 ppm based on responses on the Likert 

subjective scale at 1.9 ppm. 

1-8 hours, based on the statistically 

significant subjective (Likert scale) 

responses at 0.8 ppm MITC at 1-4 hours 

and the statistically significant eyeblink 

responses at 2 and 3 hours, 0.22 ppm was 

designated as the NOAEL for this study

*= Data were submitted by Certis USA during the Phase 5 comment period, which outlined pre-dosing motor activity measurements in both 

controlsand test groups of females. Based on this information, the LOAEL of 15 mg/kg was revised to be a NOAEL (DP Barcode: 352796, 

2008).

1 HED’s Hazard and Science Policy Council (HASPOC) has determined that an Immunotoxicity study is not required for dazomet (A. Dunbar; 

5/22/13; TXR 0056663).
Dazomet Registration Review Human-Health Assessment Scoping Document

_______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Page 29 of 29

Attachment 3: Dazomet and MITC Endpoint Selection

Summary of Toxicological Dose and Endpoints for Use in Dazomet 

Oral and Dermal Human Health Risk Assessments

Exposure

Scenario

Dose Used in Risk 

Assessment

Uncertainty Factors 

and Level of Concern 

for Risk Assessment

Study and Toxicologial Effects

Dermal 

Short-Term 

(1 - 30 days)

Occupational

Oral LOAELa,d = 15 

mg/kg/day

Occupational = LOC

for MOE = 1000 b,c

Acute neurotoxicity study (MRID 43465302) 

LOAELf = 15 mg/kg in females (6.75 mg/kg MITC 

equivalents; decreased motor activity) based on 

neurobehavioral effects FOB findings and reduced 

number of rearings. 

Dermal 

Intermediate-Term 

(1 - 6 months)

Occupational

Oral NOAELa,d = 1.5 Occupational = LOC

for MOE = 100 b,c

Subchronic toxicity- feeding rats (MRID 41865502) 

LOAELf= 4.5 mg/kg/day based on increased liver 

weight, liver:body weight ratio and pronounced foci of 

fatty degeneration in the liver

Dermal 

Long-Term 

(> 6 Months)

Occupational

Long-Term exposure via the dermal route is not expected considering the use pattern and its stability in the 

environment. 

Cancer Classification: Not classifiable as human carcinogen.

a Use 4.5% dermal absorption to convert oral dose to dermal equivalent; b Level of Concern = LOC; c Margin of 

Exposure (MOE); d NOAEL = no observed adverse effect level; f LOAEL = lowest observed adverse effect level.

Summary of Toxicological Dose and Endpoints for Use in MITC Occupational and Residential 

Human Health Inhalation Risk Assessment

Risk Assessment Study NOAEL/LOAEL Endpoints HECsc

/HCs d

Acute

Non-occupational

and

Occupational

Eye irritation study 

(MRID 44400401)

One minute NOAELa

= 3.3 ppm

4-14 minutes 

NOAELa= 0.6 ppm

1-8 hours NOAELa= 

0.22 ppm 

Subjective responses to the 

Likert scale and eyeblink 

responses

One minute HC = 3.3 ppm

UF = 10

4-14 minutes HC = 0.6 ppm

UF = 10

1-8 hours HC = 0.22 ppm 

UF = 10

Short- and 

IntermediateTerm Inhalation

(1 day to 6 

months)

Non-occupational

28-day inhalation 

study in rat

(MRID 43514802)

NOAELa= 6.8 ppm 

LOAELb= 34 ppm

Metaplasia of respiratory 

epithelium and atrophy of 

the olfactory epithelium

HEC = 0.16 ppm 

UF = 30

Occupational Same as non-occupational HEC = 0.68 ppm

UF = 30e

Long-Term 

Inhalation

(>6 months)

Non-occupational

28-day inhalation 

study in rat

(MRID 43514802)

NOAELa= 6.8 ppm 

LOAELb= 34 ppm

Metaplasia of respiratory 

epithelium and atrophy of 

the olfactory epithelium

HEC = 0.16 ppm 

UF = 300

Occupational Same as non-occupational HEC = 0.68 ppm

UF = 300 e

Cancer Classification: Insufficient data to characterize cancer risk

a NOAEL = no observed adverse effect level; b LOAEL = low observed adverse effect level; c HEC = Human equivalent 

concentration; d HC = Human concentration.; e HECs differ between non-occupational and occupational scenarios because the 

residential HEC is based on 24-hour exposures occurring 7 days per week, whereas the occupational HEC is based on 8-hour 

exposures occurring 5 days per week.