Chlorothalonil Response to Comments DP# 402499

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Syngenta Comment: As previously noted, all Tuffcide products (antimicrobial uses) have been 

requested to be cancelled: Tuffcide 404 (EPA Reg No. 50534-115), Tuffcide 404 MUP (EPA 

Reg No. 50534-228), Tuffcide 500 (EPA Reg No. 50534-197), Tuffcide 960 (EPA Reg No. 

50534-114), and Tuffcide 960 MUP (EPA Reg No. 50534-227).

HED’s Response: As noted above, during Registration Review, all registered uses of 

chlorothalonil will be reviewed. The Agency is aware that GB Biosciences is in the process of 

removing antimicrobial uses from their technical formulations. A final review of currently 

registered labels/end-use products will be performed during Registration Review. These use 

patterns may still be included in the final assessment since there are other technical and end-use 

registrants with antimicrobial uses of chlorothalonil.

Comments Related to Hazard Assessment

Comment #4 from CA Rural Legal Assistance Foundation Concerning the Inhalation Toxicity 

Endpoint, Uncertainty Factors, and Required Studies:

We concur with the conclusion of RAB1 and the HED Science Advisory Board that using an oral 

endpoint may underestimate health risk by the inhalation route and that instead the lowest 

observed adverse effect level from the acute inhalation toxicology study should be used with 

appropriate uncertainty factors to assess acute, short-term and intermediate term inhalation risks 

until valid short and intermediate toxicity studies are obtained. Because of this uncertainty 

regarding inhalation toxicity, there is an urgent need for the Agency to set the FQPA safety 

factors at 3X for acute and 30X for repeat exposures for both residential and occupational 

exposures. Acute neurotoxicity, immunotoxicity, endocrine disruption, and reproductive health 

studies should also be required and additional uncertainty factors should be utilized in the 

interim.

HED’s Response: The Agency did use interim FQPA safety factors of 3X and 30X for acute and 

repeated inhalation exposure scenarios, respectively, in addressing the uncertainty associated 

with extrapolating toxicity findings from an acute toxicity study to longer exposure durations. 

Similar database uncertainty factors were applied to anticipated occupational scenarios. The 

toxicity database for chlorothalonil via the oral route of exposure is considered adequate and thus 

additional uncertainty factors are not warranted. The database includes multiple developmental 

and multi-generation reproductive toxicity studies. Further, the pending data requirements 

consisting of acute neurotoxicity and immunotoxicity studies are not expected to impact the 

current risk assessment based on what is known about the toxicology and mode of action of 

chlorothalonil via the oral route of administration. Moreover, the uncertainty regarding 

inhalation toxicity does not necessarily translate to uncertainty via other routes of exposure such 

as oral or dermal, particularly because the toxicity via the inhalation route is based on portal of 

entry effects. It should also be noted that the primary registrant for chlorothalonil has recently 

submitted to the Agency an immunotoxicity study and is actively working on addressing the 

current data gaps in the toxicity database, including the repeated inhalation exposure toxicity 

study. In regards to endocrine disruption, chlorothalonil was among the group of pesticide active 

ingredients on the initial list to be screened under the Endocrine Disruptor Screening Program 

(EDSP). The Agency will review all the available scientifically relevant information for 

chlorothalonil during the registration review process.

Comment #5 from PANNA Concerning the Inhalation Route of Exposure, Uncertainty 

Factors, and Required Studies:

The Agency is currently considering updates in risk assessment that will improve the ability to 
Chlorothalonil Response to Comments DP# 402499

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accurately assess the potential for harm, which is a promising direction. We urge the Agency to 

consider the “on the ground” evidence collected by citizen scientists and submitted in the 

PANNA report Pesticide Drift Monitoring in Minnesota. In our report, the air monitoring data 

indicates that residents living adjacent to areas of chlorothalonil application were exposed to low 

doses of chlorothalonil vapor in the air over extended periods of time throughout the summer. 

Using evidence from oral ingestion studies for risk assessment of chlorothalonil is likely to result 

in underestimating health risk by inhalation, as absorption occurs differently through these two 

routes of exposure. The current studies used for risk assessment take into account oral ingestion 

endpoints or acute inhalation exposure, but do not account for the low-dose exposure that 

residents in our report seem likely to encounter. Further, the studies utilized for inhalation risk 

assessment are based on inhalation of chlorothalonil as a dust or aerosol, which is inhaled less 

deeply than vapor. As the effects of long-term, low-dose exposure to chlorothalonil in vapor 

form are not known, our report provides on the ground evidence of an exposure route that is not 

currently considered in risk assessment.

The lowest observed adverse effect level should be used with uncertainty factors that take into 

account acute, short-term, and intermediate inhalation risks until further studies are obtained. 

We encourage the Agency to also consider using uncertainty factors for long-term, low-dose 

exposures to chlorothalonil vapor, as that is the type of exposure Minnesota residents 

encountered in our report. As the toxicity of inhaled chlorothalonil has not been accurately 

assessed, we urge the Agency to set the FQPA safety factors at 3X for acute and 30X for repeat 

exposures for residential and occupational exposures. Workers may also be exposed to longterm low doses via inhalation during their workday. Additional uncertainty factors should be 

used until further studies are obtained for acute neurotoxicity, immunotoxicity, endocrine 

disruption, and reproductive health studies.

HED’s Response: In characterizing inhalation risk associated with chlorothalonil, the Agency 

used measurements of air concentrations available from several air monitoring studies that are 

considered a good representation of actual human exposures to chlorothalonil. These air 

concentrations were used to assess acute (1 day), short-term (1-30 days), and intermediate-term 

(1-6 months) exposures. Average air concentrations were used for the intermediate-term 

assessment; making a health-protective assumption that a person could be exposed to the same 

air concentration every day for up to 6 months. Furthermore, different human equivalent 

inhalation concentrations were estimated from the same animal acute inhalation point of 

departure that account for different conservative daily and weekly exposure duration adjustments

(e.g., 24 hours/day, 7 days/week exposures was assumed for bystanders). Because of the 

conservative nature of the assumptions made in the hazard and exposure databases regarding 

inhalation exposures to chlorothalonil, no additional uncertainty factors are warranted at this 

time. The toxicity database for chlorothalonil via the oral route of exposure is considered 

adequate and the pending database requirements are not expected to impact the current risk 

assessment based on what is known about the toxicology and mode of action of chlorothalonil 

via the oral route of exposure.

Comment #6 from Syngenta Concerning the Inhalation Acute Toxicity Category:

On Page 1 and 2, EPA states: “Based on acute toxicity studies, chlorothalonil is highly toxic via 

the inhalation route of exposure (Category I). There was a high level of lethality reported in the 

critical acute inhalation toxicity study (LC50 = 0.032 [M] and 0.013 [F] mg/L).”

Syngenta Comment: Syngenta would like to point out that prior to the 23-Dec 2010 Draft HED 

Human Health Risk Assessment (Memo, G. Kramer et al., 12/23/10, D370486), chlorothalonil 
Chlorothalonil Response to Comments DP# 402499

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was categorized by EPA as an acute inhalation toxicity Category II. The reference to 

chlorothalonil as an acute inhalation toxicity Category I is based on a single study conducted in 

1993 (Holbert, 1993) with a reported LC50 of <0.05 mg/L. The material used in this study was a 

chlorothalonil technical material that was milled into very fine particles (>30% were <1.1 

micron) at the lowest exposure level, maximizing particle respiration well beyond what could 

occur in actual use scenarios. An extremely wide range of LC50 values have been reported in 

acute inhalation toxicity studies on chlorothalonil technical materials including 2.32 mg/L (Doig, 

2011), >0.09 mg/L (Shults, 1981 and Shults, 1993), which would result in acute inhalation 

toxicity Categories of III and II, respectively. The primary purpose of the acute inhalation 

toxicity test is to estimate a lethal concentration (LC50) value of a substance. The Holbert 

(1993) study included four concentration levels in male and female rats as part of the method of 

calculating an LC50 value. It was part of the study design to intentionally produce test 

atmospheres with 25% of the particle mass consisting of particles less than 1 micron diameter. 

The study also reported observational information (clinical signs and gross necropsy findings) 

which are not typically collected in a consistent or well-standardized way in this type of study. 

The Holbert 1993 study cannot be considered as representative of the acute inhalation toxicity 

database for chlorothalonil. Syngenta believes that it is inaccurate to refer to chlorothalonil as a 

Category I based on the results of a single study with results that have not been reproduced and 

that there is no reason why this study (Holbert, 1993) should be considered as “the critical acute 

inhalation toxicity study” for chlorothalonil.

HED’s Response: The Agency compiled all the available acute inhalation toxicity studies for 

chlorothalonil and used a weight-of-evidence approach before re-evaluating the acute inhalation 

toxicity category. The compiled acute inhalation toxicity studies were performed with either the 

milled/unmilled technical product or diluted/undiluted end-use product formulations. The 

Holbert 1993 study was selected on the basis that it meets all of the guideline requirements for an 

acute inhalation toxicity study, produced a well-defined dose response relationship, tested the 

lowest inhalation concentrations of chlorothalonil from the available inhalation studies, and was 

in line with the findings noted in the other acute inhalation toxicity studies.

Comment #7 from Syngenta Concerning the Inhalation Acute Toxicity Studies:

On Page 1, paragraph 2, EPA states: “The lack of a no-observed adverse-effect level (NOAEL) 

in several acute inhalation toxicity studies carried out with technical-grade chlorothalonil or enduse product formulations is also a concern.” 

Syngenta Comment: Syngenta would like to point out that a large degree of variation exists 

among acute inhalation toxicity studies, which are typically used for calculating lethal 

concentrations of chemical substances and have widely ranging reporting styles and content for 

nonlethal acute toxicity data. Chlorothalonil has irritant properties, indicating the ability to react 

on contact with sulfhydryl groups in mucosal tissues. For substances with contact irritant 

properties, it would be expected that it may be difficult to find a concentration that would not 

produce any irritation whatsoever. It is not appropriate to use acute inhalation toxicity studies to 

identify a NOAEL based on non-lethal toxicity endpoints, which are not evaluated consistently 

or using specific guidelines in these tests. It is even less appropriate to use an acute inhalation 

toxicity study, to determine a NOAEL for a substance with severe irritation properties because 

exposure levels typically selected in these studies are expected to be above the maximum 

tolerated dose (MTD) or perilethal. The variable collection of data and qualitative nature of the 

reported observations (clinical signs) do not make this study suitable for reproducible evaluation 

of non-lethality toxicity endpoints, especially at low exposure concentrations.
Chlorothalonil Response to Comments DP# 402499

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HED’s Response: The Agency evaluated the totality of the toxicity information available for 

chlorothalonil and noted that only a route-specific inhalation study would be adequate for risk 

characterization via the inhalation route of exposure. The Agency is fully aware that an acute 

toxicity study is not ideal for extrapolating findings to longer durations or establishing a 

NOAEL. However, in the absence of an appropriate study, the Agency used the best available 

information with appropriate uncertainty factors to account for deficiencies including 

extrapolation to longer exposure durations. The clinical signs reported in the Holbert 1993 study 

are consistent with other acute inhalation toxicity studies available for chlorothalonil. The 

qualitative nature of the reported clinical signs is not a basis for discounting the study since there 

is a robust dose-related dependency in severity and incidence rate, ultimately resulting in 

lethality.

Comment #8 from Syngenta Concerning the Effects Noted in the Inhalation Acute Toxicity 

Studies:

On Page 1, paragraph 2, EPA states: “Clinical signs consistent with respiratory-tract irritation 

(i.e., portal-of- entry effects) including nasal discharge, gasping, decreased activity, ptosis, and 

lethargy, were reported at all exposure concentrations tested across several acute inhalation

toxicity studies.” 

Syngenta Comment: Syngenta would like to point out the error in this statement. In the cited 

study (Holbert, 1993), the reported clinical signs varied at each exposure concentration. At the 

lowest concentration tested, 0.00208 mg/L, the reported clinical signs in males and females were 

piloerection (slight), activity decrease (slight), ptosis (slight), and respiratory gurgle (very slight).

Nasal discharge and gasping were only reported beginning at the 0.0226-mg/L exposure 

concentration.

HED’s Response: Because of the absence and/or “slight” nature of the clinical signs, the 

LOAEL from the Holbert 1993 study was classified as “minimal,” and only a 3X uncertainty 

factor was applied for extrapolating a NOAEL from a LOAEL. During registration review, the

Agency will attempt to be clearer regarding the clinical signs observed at each inhalation 

exposure concentration tested.

Comment #9 from Syngenta Concerning the Inhalation Endpoint Selection:

On Page 1, paragraph 2, EPA states: “The effects of short- and intermediate-term inhalation 

exposures (portal-of-entry or systemic) have not been studied. In the absence of such 

information, HED recommends that the lowest-observed adverse-effect level (LOAEL) from the 

critical acute inhalation toxicity study with appropriate uncertainty factors (UFs) be used as the 

point of departure (POD) to assess inhalation risks (acute, short-, and intermediate-term).”

Syngenta Comment: Syngenta does not agree that the Holbert, 1993 study is the critical acute 

inhalation study, as discussed above. Syngenta does not believe that this study should be used as 

the POD to assess inhalation exposure risk in humans. However, if this study is to be used 

temporarily for a POD, in the absence of an appropriate toxicological endpoint for an inhalation 

exposure risk assessment, Syngenta believes that the clinical effects (piloerection, activity 

decrease, ptosis, very slight respiratory gurgle) observed at the lowest concentration (containing 

>30 % particles of <1.1 micron diameter) were of such slight degree of severity that the addition 

of an UF for lack of NOAEL is not warranted.

HED’s Response: The Agency selected the Holbert 1993 study to derive a temporary POD for 

inhalation exposures because there was no repeated inhalation exposure toxicity study available 
Chlorothalonil Response to Comments DP# 402499

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for chlorothalonil. When an appropriate inhalation study is submitted and reviewed by the 

Agency, the POD may change according to the findings of the study. For the Agency, the 

addition of a 3X uncertainty for lack of a NOAEL factor is warranted due to the high incidence 

rate of the clinical signs reported at the lowest concentration tested in both genders and the 

relative narrow gap between the lowest tested inhalation concentration (i.e., LOAEL) and the 

LC50. The lowest concentration tested of 0.00208 mg/L is only 6.25-fold less than the fitted 

LC50 of 0.013 mg/L for female rats, indicative of a potentially steep dose response curve from 

mild clinical signs to lethality. This steepness of the dose response curve is also evident by gross 

pathology findings in the lungs suggesting pulmonary edema (increased weights and purple 

appearance) at the mid and high-exposure levels tested. Some of the clinical signs seen at the 

lowest concentration lasted for 1 day post-exposure suggesting that repeated exposures may lead 

to cumulative effects.

Comment #10 from Syngenta Concerning the Inhalation Endpoint Selection:

On Page 1, paragraph 2, EPA states: “At this LOAEL, there were no deaths (male or female) 

and the very slight to slight (severity) clinical signs of respiratory distress resolved after two days 

post-exposure. The use of this LOAEL that is based on mild portal-of-entry effects is likely to 

be protective against any systemic toxicity through the inhalation route of exposure.”

Syngenta Comment: As stated above, if this study is to be used temporarily for a POD, in the 

absence of an appropriate toxicological endpoint for an inhalation exposure risk assessment, 

Syngenta believes that the clinical effects (piloerection, activity decrease, ptosis, very slight 

respiratory gurgle) observed at the lowest concentration (containing >30 % particles of <1.1 

micron diameter) were of such slight degree (severity) that the addition of an UF for lack of 

NOAEL is not warranted. Furthermore, by taking this approach in order to protect against portal 

of entry effects, a new standard is set for acceptable risk that would be analogous to using an 

acute eye or skin irritation test as a POD for an exposure risk assessment, with additional 

uncertainty factors for not having a NOAEL. By taking this approach, the method of protecting 

against systemic toxicity is to lower exposure concentrations to levels that would not be expected 

to produce local irritation. This is not an approach to risk assessment that has been tested or 

validated.

HED’s Response: In contrast to eye and skin irritation, which may not be related to systemic 

toxicity, the respiratory tract effects noted after inhalation exposure to chlorothalonil in the 

Holbert 1993 study (and other acute inhalation studies) seem to be directly related to lethality. 

This is evident by the increase in incidence and severity of the clinical signs with increasing 

levels of exposure and the relative short distance on the dose response curve between the lowest 

concentration tested and the estimated LC50, particularly in females (see above). Therefore, it is 

reasonable to assume that a POD based on the respiratory tract clinical signs would be protective 

of any potential systemic toxicity.

Comment #11 from Syngenta Concerning Submission of an Inhalation Study:

On Page 1, paragraph 2, EPA states: “If the registrant submits a subchronic inhalation study, 

with a subset of animals designed to identify the NOAEL for acute inhalation toxicity (i.e., after 

one day of exposure), then the current UFs may be reduced accordingly. Therefore, HED 

believes that the submission of a 90-day inhalation study (with acute toxicity measurements) is 

needed to refine the current residential risk assessments. Based on the lack of incident data 

related to inhalation effects and the fact that an acute inhalation toxicity study is being used to 

assess short and intermediate-term risk, the risk assessment can be characterized as 

conservative.”
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Syngenta Comment: Syngenta agrees with Agency regarding the lack of incident data and 

highly conservative risk assessment. Syngenta, on behalf of the chlorothalonil EDSP 

consortium, has expanded its role and presented a multi-staged investigation of the acute 

inhalation toxicity potential of chlorothalonil that will be used to reduce the uncertainties in the 

hazard database. EPA has agreed to this proposal and will receive a presentation of the 

preliminary data along with a protocol for a definitive inhalation study, anticipated to be 

available in 3Q 2012. Given that the chlorothalonil consortium (EDSP) is currently developing 

data with a scientifically-driven step-wise proposal that will require iterative design and technical 

approaches, it should be reflected in the scoping document that the studies are under way to 

develop the toxicology data needed for the inhalation exposure risk assessment.

HED’s Response: The Agency acknowledges that Syngenta, the primary Registrant of 

chlorothalonil, is currently working to address the data needs for a more refined inhalation risk 

assessment associated with the uses of chlorothalonil as pesticide. All available data submitted 

to the Agency will be considered during Registration Review.

Comment #12 from Syngenta Concerning Dermal Sensitization:

On Page 3, paragraph 3, EPA states: “In the previous risk assessment, chlorothalonil was 

classified as not being a dermal sensitizer. However, a published literature study in mice and 

guinea pig ranks chlorothalonil as an extremely potent contact allergen, inducing sensitization 

using only topical exposures on intact skin.”

Syngenta Comment: Syngenta would like to point out that chlorothalonil technical material is 

not a dermal sensitizer according to standard tests; however, several Syngenta formulation 

products have tested positively as dermal sensitizers and are appropriately labeled in accordance 

with the safety testing.

HED’s Response: During the registration review process, the Agency will consider all of the 

available information including studies published in the peer review literature. A weight-ofevidence approach will be used in any re-evaluation of the current dermal sensitizing 

classification.

Comment #13 from Syngenta Concerning Acute Inhalation Studies and Uncertainty Factors:

On Page 4, paragraph 1, EPA states: “There are only acute inhalation studies available for 

chlorothalonil. Its classification for acute inhalation toxicity is Category I (combined LC50 = 

0.020 mg/L). The non-lethal effects reported in acute studies even at the lowest concentration 

tested (i.e., no NOAEL attained) consist of clinical signs indicative of respiratory-tract effects 

including nasal discharge, gasping/difficulty breathing, decreased activity/lethargy, respiratory 

rates/gurgle, ptosis, and piloerection. The effects of short- and intermediate-term inhalation 

exposures (portal-of-entry or systemic) have not been studied and justify retaining the FQPA SF 

at 10X for repeated exposure scenarios. Since there is no NOAEL available for any of the 

available acute inhalation studies, but the reported portal-of-entry effects were relatively mild at 

the LOAEL for the critical study, an additional 3X factor should be added to all exposure 

scenarios, resulting in an overall FQPA SF of 3X and 30X for acute and repeated inhalation 

exposures, respectively.”

Syngenta Comment: As stated above, Syngenta does not feel that it is appropriate to classify 

chlorothalonil technical as Category I acute inhalation toxicity based on there being a wide range 

of reported LC50 values among chlorothalonil technical material acute inhalation toxicity studies 

that have been accepted by EPA. The Category I is based on a single study conducted in 1993 
Chlorothalonil Response to Comments DP# 402499

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(Holbert, 1993) with a reported LC50 of <0.05 mg/L. The material used in this study was a 

chlorothalonil technical material that was milled into very fine particles (>30% were <1.1 

micron) at the lowest exposure level, maximizing particle respiration well beyond what could 

occur in actual use scenarios. Also, Syngenta would like to point out the error in this statement.

In the study that is referred to (Holbert, 1993), the reported clinical signs varied at each exposure 

concentration. At the lowest concentration tested, 0.00208 mg/L, the reported clinical signs in 

males and females were piloerection (slight), activity decrease (slight), ptosis (slight), and 

respiratory gurgle (very slight). Nasal discharge and gasping were only reported beginning at the 

0.0226 mg/L exposure concentration. Syngenta does not agree that the Holbert, 1993 study is 

the critical acute inhalation study, as discussed above, and Syngenta does not believe that this 

study should be used to assess inhalation exposure risk in humans. However, if this study is to 

be used temporarily, in the absence of an appropriate toxicological endpoint for an inhalation 

exposure risk assessment, Syngenta believes that the clinical effects (piloerection, activity 

decrease, ptosis, very slight respiratory gurgle) observed at the lowest concentration (containing 

>30 % particles of <1.1 micron diameter) were of such slight degree (severity) that the addition 

of an UF for lack of NOAEL is not warranted. Furthermore, by setting the bar this low to protect 

against portal of entry effects with compounds that are known to produce acute irritation on 

contact, a new standard is set on an acceptable hazard profile that would be analogous to using 

an acute eye or skin irritation test to set a LOAEL with additional UFs for an exposure risk 

assessment. By taking this approach, the method of protecting against systemic toxicity is to 

lower exposure concentrations to levels that would not be expected to product local irritation.

This is not an approach to risk assessment that has been tested or validated.

HED’s Response: As noted in comment #10 above, in contrast to eye and skin irritation, which 

may not be related to systemic toxicity, the respiratory tract effects noted after inhalation 

exposure to chlorothalonil in the Holbert 1993 study (and other acute inhalation studies) seem to 

be directly related to lethality. This is evident by the increase in incidence and severity of the 

clinical signs with increasing levels of exposure and the relative short distance on the dose 

response curve between the lowest concentration tested and the estimated LC50, particularly in 

females (see above). Therefore, it is reasonable to assume that a POD based on the respiratory 

tract clinical signs would be protective of any potential systemic toxicity.

Comment #14 from Syngenta Concerning Immunotoxicity Study Requirement:

On Page 10, EPA states: “An immunotoxicity study is required as a part of new data 

requirements in the 40 CFR Part 158 for conventional pesticide registration.”

Syngenta Comment: Syngenta, on behalf of the chlorothalonil EDSP consortium, submitted the 

chlorothalonil immunotoxicity study April 3, 2012. In this study, groups of CD-1 mice were 

exposed to chlorothalonil for 28-days at dietary concentrations of 50, 750, and 2000 ppm. At the 

highest dose tested (equivalent to 345 mg/kg/day), there was no evidence of an 

immunosuppressive effect of chlorothalonil. The results of this study do not impact current risk 

assessments.

HED’s Response: The Agency has received, but not reviewed the immunotoxicity study with 

chlorothalonil. During registration review, the Agency will include the findings of this and other 

pending studies submitted to the Agency.

Comment #15 from Syngenta Concerning Endocrine Disruption Study Requirement:

On Page 11, EPA states: “However, as required by FFDCA section 408(p), chlorothalonil is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).”
Chlorothalonil Response to Comments DP# 402499

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Syngenta Comment: Syngenta, on behalf of the chlorothalonil EDSP consortium, has already 

submitted all of the mammalian EDSP studies, all of which have shown no endocrine effects.

The remaining two EDSP tier 1 assays (AMA and FSTRA) are scheduled to be completed by 

October 3, 2012 (as per an approved time-extension request).

HED’s Response: The Agency has received the EDSP Tier 1 mammalian assays. Once all the 

data (mammalian and ecological) have been received and reviewed, the PODs and SFs used for 

risk assessment purposes will be examined and a new risk assessment performed if necessary. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

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

Comments Related to Incident Reporting

Comment #16 from CA Rural Legal Assistance Foundation Concerning Analysis of Incident 

Reporting:

We recommend further analysis of frequency and severity of human health incidents during 

registration review and note that the California pesticide illness database (Cal-PIQ) includes 55 

cases of possible to definite pesticide illness involving exposure to only chlorothalonil between 

1992 and 2009. Several cases in this database add further support to the need to reconsider 

chlorothalonil's dermal sensitization classification as illustrated in the attached table of California 

Chlorothalonil Pesticide Illnesses Involving Rashes. However, the many obstacles to reporting 

of pesticide illnesses, particularly among farmworkers, must be considered in interpreting a "lack 

of incident data related to inhalation effects" alluded to in this proposal. In their 2008 study of 

pesticide illness incidence, Dr. Geoffrey Calveli and other researchers delineated the many 

factors contributing to underreporting, including failure of affected workers to get medical care, 

seeking medical care in Mexico outside the U.S. surveillance system, misdiagnosis, and health 

provider lack of knowledge of symptoms of occupational exposure and their neglect of the duty 

to report, in the 30 states where reporting is required (AJIM 2008: 51:883-898). They also note 

that 76% of farmworker illnesses in Washington and 34% in California, the states with the most 

established surveillance systems, were identified through the workers' compensation system, and 

that Oregon (7%) and Texas (4%) were the only other states identifying pesticide illnesses 

through workers' compensation. These researchers observed that in the NAWS 1999 survey, 

1.4% of farmworkers interviewed attributed health effects to pesticide exposure from drift, spills, 

or cleaning and repair of pesticide equipment and containers, suggesting a rate of illness 20-fold 

higher than found through surveillance.

HED’s Response: EPA agrees with CA Rural Legal Assistance Foundation that there should be 

further analysis of the frequency and severity of human-health incidents during registration 

review. As stated in the incident memo for chlorothalonil (S. Recore, 1/12/12, 2012,D397570), 

based on the frequency and severity of incident cases and AHS results, for chlorothalonil, these 

incident data may warrant further analysis in the preliminary risk assessment phase of 

Registration Review. As part of the further analysis for registration review other databases will 

be analyzed, including California’s Pesticide Illness Surveillance Program and NIOSH 

SENSOR.

EPA understands that under-reporting does occur and the incidents reviewed likely do not 

represent all exposures. However, incident information can be an important source of feedback 

to the Agency – incidents of severe outcome, or a suggested pattern or trend among less severe 

incidents, can signal the Agency to further investigate a particular chemical or product.
Chlorothalonil Response to Comments DP# 402499

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Comments Related to Residue Chemistry and Dietary Exposure Assessment

Comment #17 from Syngenta Concerning Dietary Exposure:

On Page 4, EPA states: “The most recent dietary exposure assessment was performed in 

conjunction with the December 2010 human-health risk assessment conducted by HED in 

conjunction with a registration request for use on low-growing berry subgroup 13-07G; 

bushberry subgroup 13-07B; onion, bulb subgroup 3-07A; and onion, green subgroup 3-07B 

(D370486, G. Kramer, et al.; 23-Dec-2010). HED was unable to make a safety finding due to 

inhalation risks and the proposed uses were subsequently withdrawn.”

Syngenta Comment: Please note that because the IR-4 petition was withdrawn, the December 

2010 assessment was neither finalized nor posted for public comment and therefore we believe it 

should be referred to as a draft assessment. The most recent finalized dietary exposure 

assessment was completed in September 2008 (D353241, G. Kramer, et al.; 4-Sept-2008).

HED’s Response: The 2010 risk assessment was finalized (D370486, G. Kramer, et al.; 23-

DEC-2010). 

Comment #18 from Syngenta Concerning Residue Chemistry and Tolerances:

On Page 5, EPA states: “The residue chemistry database is sufficient to support the current 

registrations. The following data requirement remains outstanding: multiresidue method 

recovery data for the 4-hydroxy metabolite.

Syngenta Comment: In 1993, analytical and independent lab validation (ILV) methods for 

parent and the 4-hydroxy metabolite were submitted to EPA (before the 1999 RED was issued). 

The MRID Number for the analytical method is 42875908 and for the ILV is 42875909.

HED’s Response: The studies cited by Syngenta address GLN 860.1340. The data gap cited by 

HED concerns multiresidue method testing as specified in GLN 860.1360. 

Comment #19 from Syngenta Concerning Residue Chemistry Data Requirements:

On Page 12, EPA states: “The database does not contain any information for the 4-hydroxy 

metabolite. In the Chlorothalonil Residue Chemistry RED Chapter, the multiresidue method 

recovery data for chlorothalonil trichloro impurity were incorrectly attributed to the 4-hydroxy 

metabolite; see DP# 228522, W. Smith. Multiresidue method recovery data for the 4-hydroxy 

metabolite thus remain outstanding.”

Syngenta Comment: In 1993, analytical and independent lab validation methods for parent and 

the 4-hydroxy metabolite were submitted to EPA (before the 1999 RED was issued). The MRID 

Number for the analytical method is 42875908 and for the ILV is 42875909.

HED’s Response: The studies cited by Syngenta address GLN 860.1340. The data gap cited by 

HED concerns multiresidue method testing as specified in GLN 860.1360. 

Comment #20 from Syngenta Concerning Dietary Exposure Assessment:

On Page 13, EPA states: “The most recent dietary exposure and risk assessment was performed 

in conjunction with the December 2010 human-health risk assessment conducted by HED 

(D370486, G. Kramer, et al.; 23-DEC-2010).”

Syngenta Comment: As previously noted, due to the IR-4 petition-withdrawal, the HED 
Chlorothalonil Response to Comments DP# 402499

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December 2010 assessment was neither finalized nor posted for public comment and should 

therefore be referred to as a draft assessment. The most recent finalized dietary exposure 

assessment was completed in September 2008 (D353241, G. Kramer, et al.; 4-Sept-2008).

HED’s Response: The 2010 risk assessment was finalized (D370486, G. Kramer, et al.; 23-

DEC-2010). 

Comments Related to Residential Exposure Assessment

Comment #21 from Syngenta Concerning Residential Exposure and Current Use Pattern:

On Page 5, EPA states: “....In the most recent risk assessment, inhalation risk concerns for the 

short-/intermediate-term exposure durations were identified for residential handlers using treated 

paint, post-application exposure from inhaling vapors from treated paint, and for bystander 

volatilization inhalation exposure. ...With regard to the antimicrobial uses, there is potential for 

dermal and incidental oral exposure to pressure-treated wood that is used in residential structures 

such as porches and steps.... It will also be necessary to reassess the paint uses and determine if 

the precautionary labeling strategy required by the RED is still valid or if paints containing 

chlorothalonil should have labeling that can only be accomplished by having separate 

registrations for each paint product.”

Syngenta Comment: As noted previously, Syngenta (representative of GB Biosciences) has 

requested cancellation of all of their antimicrobial uses of chlorothalonil including uses in paint 

formulations or in pressure-treated wood.

HED’s Response: As noted above, during Registration Review, all registered uses of 

chlorothalonil will be reviewed. The Agency is aware that GB Biosciences is in the process of 

removing antimicrobial uses from their technical formulations. A final review of currently 

registered labels/end-use products will be performed during Registration Review. These use 

patterns may still be included in the final assessment since there are other technical and end-use 

registrants with antimicrobial uses of chlorothalonil.

Comment #22 from Syngenta Concerning Residential Post-application Inhalation Exposure 

for Golfers:

On Page 14, paragraph 2, EPA states: “Post-application inhalation exposure was also identified 

as a potential exposure pathway for golfers on treated courses, but the residential bystander 

assessment was expected to cover those potential exposures.”

Syngenta Comment: The residential bystander assessment assumes that an individual is exposed 

to the same air concentration for 24 hours per day. This is inconsistent with the exposure 

durations for residential golfers in the 2012 Residential SOPs which lists an exposure time of 4 

hours per day for greens, tees and fairways for adults (2 hours per day for 5-year old children) 

and 1 hour per day for greens and tees for adults. Although these duration assumptions are 

specifically listed for dermal exposure, the duration of inhalation exposure should be identical. 

Syngenta would also like to point out that there is published air monitoring data available that 

specifically addresses chlorothalonil use on golf course turf; i.e., “Environmental fate of 

metalaxyl and chlorothalonil applied to a bentgrass putting green under southern California 

climatic conditions,” L. Wu, et al., Pest. Manag. Sci., Vol 58, 2002, pg 335-342, and “Inhalation 

health risk to golfers from turfgrass pesticides at three north-eastern U.S. States,” R. R. Murphy 

and D. A. Haith, Environ. Sci. Technol., Vol. 41, 2007, pg 1038-1043. Additional air monitoring 

data for turf re-entry workers is also available from the Agricultural Re-entry Task Force 
Chlorothalonil Response to Comments DP# 402499

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(ARTF) study ARF057 for workers involved in high contact activities with chlorothalonil-treated 

golf course turf. The potential exposure of residential golfers to air concentrations of 

chlorothalonil would be expected to be significantly less than that of golf course maintenance 

workers. Please see Appendix 3 for references to Syngenta’s comments on residential bystander 

post-application exposure.

HED’s Response: The Agency acknowledges that the post-application inhalation exposure 

duration for golfers to chlorothalonil may be less than that assumed for residential bystanders. 

The Agency notes the references provided, and will review these as necessary during 

Registration Review. The Agency is also aware of the ARTF data related to maintenance worker 

exposure on golf courses and will incorporate this data, as appropriate, during Registration 

Review for chlorothalonil.

Comment #23 from Syngenta Concerning Residential Exposure to Paints:

On Page 14, EPA states: “The residential exposure assessment included inhalation risk estimates 

for residential handlers using treated paint (Table A5.I), post-application inhalation risk 

estimates for residents from exposure to treated paint (Table A5.2), post-application incidental 

oral risk estimates for incidental ingestion of paint chips by children (Table A5.3), and a 

residential bystander assessment to address potential volatilization of chlorothalonil from treated 

fields (Table A5.4). In that assessment, dermal risk was not quantified since no hazard was 

identified via the dermal route for chlorothalonil.”

Syngenta Comment: Because Syngenta (representative of GB Biosciences) has requested 

cancellation of the antimicrobial uses, there are no Syngenta products that would provide a 

potential for residential handler and post-application dermal or inhalation exposure from 

antimicrobial uses of chlorothalonil including the use in treated paints.

HED’s Response: As noted above, during Registration Review, all registered uses of 

chlorothalonil will be reviewed. The Agency is aware that GB Biosciences is in the process of 

removing antimicrobial uses from their technical formulations. A final review of currently 

registered labels/end-use products will be performed during Registration Review. These use 

patterns may still be included in the final assessment since there are other technical and end-use 

registrants with antimicrobial uses of chlorothalonil.

Comment #24 from Syngenta Concerning Residential Post-application Exposure to PressureTreated Wood:

On Page 15, EPA states: “There are three products (1022-584, 50534-115, 71581-2) that allow 

pressure treatment of wood.”

Syngenta Comment: As previously noted, Syngenta (representative of GB Biosciences) has 

requested the cancellation of antimicrobial uses of chlorothalonil including Tuffcide 404 (EPA 

Reg No. 50534-115). There are therefore no Syngenta products that would provide a potential 

for dermal or incidental oral exposure to pressure-treated wood that is used in residential 

structures such as porches and steps.

HED’s Response: As noted above, during Registration Review, all registered uses of 

chlorothalonil will be reviewed. The Agency is aware that GB Biosciences is in the process of 

removing antimicrobial uses from their technical formulations. A final review of currently 

registered labels/end-use products will be performed during Registration Review. These use 

patterns may still be included in the final assessment since there are other technical and end-use 
Chlorothalonil Response to Comments DP# 402499

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registrants with antimicrobial uses of chlorothalonil.

Comment #25 from Syngenta Concerning Residential Bystander Post-application Inhalation 

Exposure:

On Page 15, EPA states: “The Agency developed a preliminary bystander volatilization 

inhalation exposure assessment for chlorothalonil utilizing currently available inhalation toxicity 

and air monitoring data. The chlorothalonil bystander volatilization inhalation exposure 

assessment compared the maximum air concentration detected in each of the monitoring studies 

to the acute HEC for residential bystanders. This comparison was done to represent a potential 

resident who lives next to a treated field and may be exposed to the peak concentration of 

chlorothalonil volatilizing off the field over a 24-hour period. In addition, the arithmetic mean 

chlorothalonil air concentration from each study was compared to the short-/intermediate-term 

HEC for residential bystanders. This comparison was done to represent a potential seasonal 

exposure. None of the air concentrations results in acute risks of concern; however, there were a 

couple of average air concentrations from some sites that resulted in short-/intermediate-term 

risks of concern.”

Syngenta Comment: Chlorothalonil is classified, based on its vapor pressure, as a low to 

moderately low volatile pesticide. Residues of chlorothalonil that remain in the air post 

application are much more likely to be due to contaminated particulates than true volatiles. Air 

monitoring data that is used to calculate potential residential bystander exposure should be based 

on samples collected with filtered sampling tubes to ensure that the calculations are based on 

potentially respirable residues. If filtered sampling tubes are not utilized, then the sampling zone 

should be sufficiently above the ground surface so as to not capture coarse heavy particulates 

that are non-respirable. There is a significant body of published air monitoring data much of 

which was not considered in the residential bystander inhalation exposure assessment including 

peer reviewed publications and studies done under Good Laboratory Practice (GLP) such as CADPR and CA-ARS studies and USGS surveys. A summary of the study results are listed below.

Environmental Setting Reported Range of Air Concentrations

(ng/m3) Reference

Outdoor agricultural area, CA 92 samples; <7.0 CA-ARB, Fresno County 1989

Outdoor agricultural area, CA 120 samples; <4 – 4.6 CA-ARB, Ventura County 1990

Outdoor agricultural area, ND 13 samples, <0.006 – 7.8* (mean 1.4) Hawthorne, et al., JEQ, 1993

Sierra Nevada mountains, CA 12 samples; <0.0015 – 1.9 (mean 0.6) LeNoir, et al., ETC, 1999

Outdoor agricultural area, CA 160 samples; <4.3 (mean 1.3) CA-DPR, Lompoc 2000

Outdoor agricultural area, Franklin Field

Airport, CA 117 samples; <0.1 – 76.4 (mean 1.2) Majewski, USGS survey 2002

Outdoor agricultural area, Sacramento

Int. Airport, CA 117; <0.1 – 52.8 (mean 1.0) Majewski, USGS survey 2002

Outdoor urban area, Sacramento Metro

Airport, CA 115 samples; <0.1 – 10.2 (mean 0.3) Majewski, USGS survey 2002

Outdoor agricultural and urban areas, 

CA 121 samples; <0.45 – 14 (mean 1.3) CA-EPA, Fresno County 2002

Cambridge, MD 27 samples; 0.036 – 2.5 (mean 0.23) McConnell, et al., JEQ 2003

Cheeka Peak, WA 16 samples; <0.00167 – 0.052 (mean 

0.012) Killin, et al., JGR, 2004

Outdoor agricultural area, CA 153 samples; <13.7 – 53.2 (mean 13.2) CA-DPR, (Ben) Parlier 2006

Outdoor agricultural area, CA 153 samples; <13.7 – 53.2 (mean 13.8) CA-DPR, (Cha) Parlier 2006

Outdoor agricultural area, CA 153 samples; <13.7 – 53.2 (mean 15.0) CA-DPR, (Mar) Parlier 2006

Outdoor agricultural area, PEI, Canada 

(2003)

18 samples: filter: 6 – 414 (mean 54) 

PUF: 8 – 95 (mean 26) Garron, PMS 2011

Outdoor agricultural area, PEI, Canada 

(2004)

17 samples; filter: 6 – 78 (mean 31) 

PUF: <1 – 36 (mean 15) Garron, PMS 2011

Outdoor agricultural area, PEI, Canada 

(2005)

9 samples; filter: 4 – 40 (mean 16) PUF: 

4 – 179 (mean 41) Garron, PMS 2011
Chlorothalonil Response to Comments DP# 402499

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*All chlorothalonil detects were found on the 50 micron quartz fiber filter only.

**Glass fiber filter with 1.6 micron cut-off; PUF residues <1.6 micron.

In the draft 2010 human-health risk assessment, the EPA utilized ambient air monitoring data 

from the Pesticide Action Network of North America (PANNA) that was neither published in a 

peer-reviewed journal nor performed under GLP. One of the PANNA reports, “Pesticide drift 

monitoring in Minnesota June 13, 2006 – August 13, 2009,” was not publically available until 

May 2012, yet preliminary summary data from this study was utilized by EPA/HED in the draft 

December 2010 human-health risk assessment. The air monitoring data from the other PANNA 

report “Air monitoring in Hastings, Florida October 1 – December 6, 2007” and the majority of 

the data from the Minnesota PANNA study were collected at a height of 1-2 meters off the 

ground, using PANNA drift catchers with unfiltered sampling tubes. Therefore, an evaluation of 

the PANNA residue data cannot be made in terms of respirable particles that contain 

chlorothalonil. Syngenta would like to point out that only one sampling point (Site A, Pine 

Point, MN) from either of the PANNA reports appears to meet the U.S. EPA ambient air siting 

criteria.

Syngenta would also like to point out that there are multiple layers of conservatism built into this 

preliminary bystander exposure assessment, including the following:

There is an inherent assumption that chlorothalonil residues are volatilized off the site of 

application.

o Chlorothalonil has a vapor pressure of 5.7 x 10-7 mmHg at 25 C. This places 

chlorothalonil into the category of “low volatility pesticide” (VP ≤ 1 x 10-6 mmHg 

at temperatures ranging from 20-30°C).

o Therefore, airborne residues of chlorothalonil would be due either to drift or to 

particulates.

The acute and short-/intermediate-term HEC calculations assume a daily duration of 

exposure of 24 hours for the residential bystander times either one day (acute) or seven 

days (short-/intermediate-term).

o Syngenta believes that it is highly unlikely that any individual would be outside 

and exposed to the same air concentration for 24 hours.

o Populations move from site to site on a daily basis such as going to work or 

school and back to home.

o There is a lack of incident data related to inhalation effects from chlorothalonil.

o As stated earlier, there are data available for air monitoring of workers re-entering 

areas following treatment with chlorothalonil and this data shows that there were 

no reports of incidents or illnesses from any of these workers related to inhalation 

effects.

HED’s Response: The Agency acknowledges the issue regarding the phase of chlorothalonil 

during bystander exposure (i.e., particulate versus vapor phase). This issue impacts the 

toxicological/hazard characterization side of the risk assessment, as well as the exposure side, as 

noted in the above comment. During Registration Review, the Agency will review the available 

monitoring studies to ensure transparency regarding the methods utilized in collecting the data

and characterize as best as possible the applicability and limitations of the available data. In the 

2010 risk assessment, the Agency used the available air-monitoring data in an attempt to provide 

a preliminary approach to estimating potential bystander exposure. This approach was based on 

advice and input from the FIFRA Scientific Advisory Panel (SAP) in December 2009. The risk 

assessment included characterization of the bystander risk estimates, including identification of 

several limitations and assumptions (some of which are mentioned in the above comment). The 
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Agency notes the information provided in the above comment regarding the additional air 

monitoring data, and encourages the Registrant to submit any additional information it may have,

which the Agency will consider and review during Registration Review. 

Comments Related to Occupational Exposure Assessment

Comment #26 from CA Rural Legal Assistance Foundation Concerning Environmental 

Justice:

As a result of the 1999 registration review of chlorothalonil, registrants agreed to prohibition of

residential turf uses to protect residential handlers and their children, while heavy use in 

agriculture that exposes applicators and fieldworkers has been allowed to continue. Children and 

other family members of workers and rural residents in turn suffer take-home exposure through 

residues brought home on clothes and drift exposure if the family lives near agricultural fields. 

This disproportionately impacts low-income, minority farmworkers and rural agricultural 

families, placing those with the least access to any or adequate health care services at increased 

risk of impacts to their health.

HED’s Response: The Agency has a firm commitment to promoting environmental justice in 

this country.1 In fact, environmental justice is one of the seven priorities that the EPA 

Administrator established for the Agency’s future.2 EPA's risk assessments and risk 

management decisions for chlorothalonil have been developed in a manner that is consistent with 

this goal. Previous chlorothalonil risk assessments are, and the future Registration Review risk 

assessment will be, universally protective of all people regardless of race, color, national origin, 

culture, education, or income. With respect to take-home exposures, the Agency has undertaken 

numerous steps to ensure that it is adequately protecting farm children, including initiating data 

gathering on exposure of children in agricultural areas to pesticides. During Registration 

Review, EPA will review ongoing research, as it pertains to chlorothalonil, and take appropriate 

steps, as necessary, to address any exposure concerns regarding children. In addition, as noted in 

the response to Comment #1 above, the Agency acknowledges that spray drift is a potential 

source of exposure to residents and has been actively engaged in a number of initiatives to help 

prevent such exposure. These initiatives include: (1) broadening our understanding of the 

science and predictability of pesticide drift based on many new studies, (2) improving the clarity 

and enforceability of product label use directions and drift restrictions, (3) facilitating the use of 

drift reducing application technologies and best management practices to minimize drift, and (4) 

promoting applicator education and training programs. The Agency developed and issued for 

public comment a draft PR Notice on Pesticide Drift Labeling in 2009. The purpose of the draft 

PR Notice is to provide guidance to registrants and applicants for registration on labeling 

statements concerning pesticide drift, and to inform the public of EPA’s policies with regard to 

pesticide drift. Along with the development of the draft PR Notice, the Agency is taking a 

number of other actions to address pesticide drift, including facilitating adoption of driftreducing technologies by applicators, providing access to information on best management 

practices to reduce drift, and supporting education and training programs.

Comment #27 from CA Rural Legal Assistance Foundation Concerning Restricted Entry 

Intervals:

Current chlorothalonil product labels, which allow workers to reenter a field only 12 hours after 

application if an eye wash is provided for workers, defy logic and are a glaring environmental 

 

1

 http://www.epa.gov/environmentaljustice/ and http://www.epa.gov/osp/ej.htm

2

 http://blog.epa.gov/administrator/2010/01/12/seven-priorities-for-epas-future/ 
Chlorothalonil Response to Comments DP# 402499

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injustice, because incident data show that eye irritation can occur more than 48 hours after 

application. During re-registration, restricted entry intervals must be reevaluated and increased 

to adequately prevent adverse eye effects, cancer, and any other acute and chronic health effects.

HED’s Response: Chlorothalonil is classified as Toxicity Category I for eye irritation, which,

under the Worker Protection Standard, necessitates a 48-hour REI. During the previous reregistration process for chlorothalonil, the Agency acknowledged that residue data for 

chlorothalonil did not indicate that residues dissipated to a level where eye irritation is no longer 

a concern at the end of the 48-hour interval. Depending on plant growth, rainfall, and the timing 

and type of irrigation, residues of eye irritation concern might exist for seven days or more 

following application. Due to the uncertainties in determining a set time interval when eye 

irritation from residues are no longer a concern, the Agency required that, for at least seven days 

following the application of chlorothalonil, (1) eye wash containers be made available to workers 

and (2) workers were orally informed of the fact that the residues could be highly irritating to 

their eyes, the precautions to avoid getting residues in their eyes, and the actions they should take 

if they got residues in their eyes. During Registration Review, exposures to residues of 

chlorothalonil from all routes will be re-examined and the restricted entry interval will be revisited.

Comment #28 from CA Rural Legal Assistance Foundation Concerning Dermal Exposure 

Contribution to Cancer Risk:

According to Agency review, chlorothalonil has been classified as a likely human carcinogen 

based on all routes of exposure due to elevated incidence of kidney tumors. Dermal exposure to 

chlorothalonil by handlers, irrigators and workers performing hand labor in treated fields, thus, 

needs to be assessed, because the amount of chlorothalonil absorbed dermally contributes to 

cancer risk. Agricultural workers have among the highest reported rates of occupational skin 

disorders, so the rate of absorption needs to be adjusted to take into account enhanced absorption 

through skin irritated by exposure to chlorothalonil, other pesticides, irritating crop plants such 

as tomato, sunlight and other factors. California Department of Pesticide Regulation has 

previously used an absorption rate of 13% for intact skin.

HED’s Response: The Agency has reviewed an in vitro dermal penetration study based on 

human skin that shows that a majority (89.1-97.5%) of radiolabeled chlorothalonil remains in the 

skin, and does not appear to become systemically available with time. Further, the Agency has 

reviewed two 21-day dermal toxicity studies in rats where there were no systemic effects 

identified; the effects reported consisted of dermal irritation/effects. Therefore, the likelihood 

that dermal exposures would contribute significantly to systemic effects such as kidney tumors is 

low. During Registration Review, the Agency will review all available data as it relates to 

exposure and potential for adverse effects.

Comment #29 from CA Rural Legal Assistance Foundation Concerning Surrogate Data and 

Assumptions used in Occupational Exposure Assessment:

We do not agree with the statement that the ORETF, AHETF, and ARTF data are more reliable 

than the PHED databases. The PHED contains 1700 replicates of worker exposure, several times 

more than the other databases, and the PHED data are not proprietary. The proprietary industry 

databases (ORETF, AHETF, and ARTF) incorporate a number of problematic assumptions and 

procedures:

1. Fewer than 15 events per scenario provide insufficient statistical power and cannot 

adequately represent the full range of the distribution. This greatly limits the database's 
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ability to adequately describe inter-worker variation, as well as its applicability to the 

larger worker populations (consisting of hundreds of thousands of workers nationwide).

2. Hand rinses and face and neck wipes underestimate exposure because they fail to capture 

pesticide residues absorbed through the skin during the time between exposure and data 

collection. Researchers have found that some pesticide residues are quickly absorbed 

through the skin (Fenske R and Lu C (1994). Determination of Handwash Removal 

Efficiency: Incomplete Removal of the Pesticide Chlorpyrifos from Skin by Standard 

Handwash Techniques. American Industrial Hygiene Association Journal 55:425-32). 

Any delay in collecting the rinses or wipes, therefore, increases the exposure 

underestimate. In a different study, hand wipes produced a 10-fold underestimate of 

exposure (Fenske R, et al. (1999). Comparison of Three Methods for Assessment of 

Hand Exposure to Azinphos-methyl (Guthion) During Apple Thinning. Applied 

Occupational & Environmental Hygiene 14:618-33).

3. Those who know they are being studied will obviously be particularly careful as they 

engage in mixing and loading tasks. The spills and splashes of real life will occur less 

frequently during studies. Moreover, protective clothing and equipment provided in 

AHETF studies will undoubtedly be well-maintained and they will fit properly. This is 

quite regularly not the case in the real world.

4. The ARTF methodology used to develop their generic agricultural re-entry exposure 

database assumes that occupational exposure to a pesticide is based on the degree of 

contact that a worker has with the foliage of a particular crop. Rather than testing each 

type of crop, the ARTF establishes transfer coefficients to reflect the worker pesticide 

exposure from categories of activities. The ARTF "transfer coefficients" measure the 

amount of pesticide residue readily transferred from the foliage of a crop to the worker's 

skin during the course of certain activities, such as thinning or pruning. The ARTF data 

are not based on actual data pertaining to particular pesticide uses.

Dermal and inhalation exposure studies should not have been waived in 2006 and should be 

required at this time. We also strongly object to moving away from risk calculations designed to 

protect the maximally exposed workers by assuming maximum application rates and maximum 

treated acres per day. In fact, the Agency's assumption that agricultural workers are only 

exposed to pesticides eight hours a day, five days a week does not reflect real life situations 

where agricultural workers often labor for 10 or 12 hours per day, six days a week, travel long 

distances to reach their residences, and lack resources to wear a clean set of clothing to work 

each day.

HED’s Response: Current Agency guidance recommends the use of unit exposure values 

derived from a number of sources. For some scenarios, this still does include PHED. PHED 

houses the majority of occupational pesticide handler exposure data the Agency uses in 

occupational handler exposure assessments, however, the Agency has recognized and 

acknowledged the limitations with the existing data. In recent years, the Agency and 

stakeholders have expressed a desire to augment or replace this database with one that has as its 

foundation a more contemporary dataset and one whose exposure monitoring followed a more 

robust, consistent, and statistically-driven sampling design. In January 2007, the Agency 

presented to a FIFRA SAP both the limitations to existing data and the proposed development of 

new data by an industry consortium, the AHETF. With joint input by Health Canada’s PMRA 

and California’s DPR throughout the data development processes, the Agency believes that the 

AHETF and ORETF data are superior, and that use of these data will result in more reliable and 

scientifically defensible exposure assessments. Additionally, the Agency considers exposure 

data submitted by registrants outside of the AHETF or ORETF, to be the most appropriate data 
Chlorothalonil Response to Comments DP# 402499

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for some scenarios and are used in a similar fashion. In response to the specific issues identified 

in the above comment regarding the task force data:

1. The task force monitoring data does contain at least 15 events per scenario; in most 

studies, 25 monitoring units were included. Overall, small samples is not specific to the 

task force studies and pertains to other exposure databases, including some of the sample 

sets in PHED.

2. The Agency has acknowledged the potential inefficiency of the hand rinses and face/neck 

wipes monitoring methods. This particular issue was addressed at the HSRB and a 

method was agreed upon by which to account for the uncertainty associated with these 

sampling methods in an attempt to avoid potentially underestimating exposure.

3. The Agency agrees that studies should not reflect workers acting in ways they otherwise 

wouldn't (i.e., being particularly careful). The task force studies monitor real workers in 

real situations. No attempt is made to provide additional protective clothing or 

equipment. Workers are monitored in the clothing they would normally wear, and with 

protective equipment normally worn depending on the use/activity. In addition, the 

AHETF studies are actually designed to ensure exposure measurements, and may include 

having workers engage in additional activities (e.g., mix/load more than once). In this 

respect, exposure may be inflated compared to typical behaviors. 

4. Ideally, transfer coefficients studies would be submitted for each type of crop. As a wide 

range of crop-specific hand labor tasks occur in production agriculture, generating data 

and transfer coefficients for each crop-activity combination would be prohibitively 

expensive and unnecessary given the reasonable similarities between crops and activities. 

The “clustering” approach taken by ARTF, developed in consultation with regulatory 

agencies, is based on monitoring of selected activities used to represent similar types of 

activities as defined by the crop, the ergonomics of the post-application activity, and the 

potential for contact with pesticide residues. Development of ARTF data and its 

subsequent use in this “clustering” fashion was favorably reviewed at a 2008 FIFRA SAP 

(December 2 - 5, 2008: Scientific Issues Associated with Worker Reentry Exposure 

Assessment).

The Agency has not made changes to its use of maximum application rates and high-end acres 

treated in risk assessments, and will use those values, as appropriate, in the Registration Review 

process. 

Comment #30 from CA Rural Legal Assistance Foundation Concerning Respiratory 

Protection:

We are puzzled as to how the need for respiratory protection could be reduced if a more healthprotective inhalation reference dose is adopted.

HED’s Response: Because there is no inhalation study of appropriate length available to assess 

short- and intermediate-term exposures, HED relied upon an acute study (in which no NOAEL 

was achieved) to assess short- and intermediate-term exposure. Additional UFs were applied for 

both the lack of a NOAEL and the lack of a subchronic inhalation study. Therefore, HED has 

requested a 90-day inhalation study for chlorothalonil that will provide toxicological data more 

relevant to the potential exposure scenarios. If the registrant submits a subchronic inhalation 

study, with a subset of animals designed to identify the NOAEL for acute inhalation toxicity 

(i.e., after one day of exposure), then the current UFs may be reduced accordingly. Using a 

NOAEL from a relevant study, with potentially lower uncertainty factors, may result in 

estimated risks being not of concern with less personal protective equipment.
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Comment #31 from CA Rural Legal Assistance Foundation Concerning Occupational Postapplication Inhalation Exposure:

Occupational post application inhalation exposure may be higher than bystander inhalation 

exposure because workers within a field are closer to the source of volatilized drift and may have 

additional exposure to suspended dust containing chlorothalonil. In addition, such inhalation 

exposure is more extensive, since workers remain in the fields for long periods of time, unlike

bystanders. Occupational post-application inhalation exposure should therefore be evaluated 

separately.

HED’s Response: The Agency acknowledges that there are multiple potential sources of postapplication inhalation exposure to individuals performing post-application activities in 

previously treated fields. These potential sources include volatilization of pesticides and 

resuspension of dusts and/or particulates that contain pesticides, as noted in the above comment. 

The Agency sought expert advice and input on issues related to volatilization of pesticides from 

a FIFRA SAP in December 2009. As policies and procedures are developed to assess 

occupational post-application inhalation exposure, these will be incorporated, as appropriate, into 

the risk assessment for chlorothalonil during Registration Review. 

Comment #32 from Syngenta Concerning Occupational Exposure and the Current Use 

Pattern:

On Page 6, EPA states: “With respect to the antimicrobial uses, the occupational handler 

exposures that occur from the use of chlorothalonil for material preservation were assessed in the 

RED; however, these assessments may also have to be repeated during registration review to 

account for changes in the toxicological PODs. In particular, the handler exposures from the 

open pouring of wettable powder will have to be reassessed because the antimicrobial wettable 

powder products are not packaged in water-soluble packaging as required by the RED. In 

addition, exposures that occur from the use of chlorothalonil as a wood preservative may have to 

be assessed because they were not assessed previously.”

Syngenta Comment: As noted previously, Syngenta (representative of GB Biosciences) has 

requested cancellation of all of their antimicrobial uses of chlorothalonil including uses during 

sapstain treatment and pressure treatment of wood.

HED’s Response: As noted above, during Registration Review, all registered uses of 

chlorothalonil will be reviewed. The Agency is aware that GB Biosciences is in the process of 

removing antimicrobial uses from their technical formulations. A final review of currently 

registered labels/end-use products will be performed during Registration Review. These use 

patterns may still be included in the final assessment since there are other technical and end-use 

registrants with antimicrobial uses of chlorothalonil.

Comment #33 from Syngenta Concerning Occupational Exposure and the Current Use 

Pattern:

On Page 17, EPA states: “There is the potential for dermal and inhalation exposure to 

occupational handlers from the currently registered use pattern of chlorothalonil.”

Syngenta Comment: Because Syngenta (agent of GB Biosciences) has requested cancellation of

all of its antimicrobial use products, there are therefore no Syngenta or GB Biosciences products 

that would provide a potential for occupational handler and post-application dermal or inhalation 

exposure from antimicrobial uses of chlorothalonil, including the use in treated paints.
Chlorothalonil Response to Comments DP# 402499

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HED’s Response: As noted above, during Registration Review, all registered uses of 

chlorothalonil will be reviewed. The Agency is aware that GB Biosciences is in the process of 

removing antimicrobial uses from their technical formulations. A final review of currently 

registered labels/end-use products will be performed during Registration Review. These use 

patterns may still be included in the final assessment since there are other technical and end-use 

registrants with antimicrobial uses of chlorothalonil.

Comment #34 from Syngenta Concerning Occupational Handler Assessment:

On Page 17 and in Table A6.1 of Attachment 6, EPA states: “The most recent occupational 

handler exposure assessment was conducted in December of 2010 (Memo, K. Lowe, 23-DEC201O; D371456). Numerous occupational handler scenarios have been assessed in the past; 

however, the toxicological PODs were revised for the most recent risk assessment and; therefore, 

only the exposure scenarios and resulting risk estimates from that assessment have been included 

in Table A6.1 of the attachments. As mentioned in the residential exposure section, dermal risk 

was not quantified in the most recent assessment since no hazard was identified via the dermal

route for chlorothalonil and the inhalation assessment was conducted using a HEC calculated 

from a POD from an acute inhalation study. HED determined that inhalation risks were of 

concern for both acute exposures (i.e., MOEs were <100) and short-/intermediate-term exposure 

(i.e., MOEs were <1,000).”

Syngenta Comment: On page 17 and in Table A6.1 of Attachment 6, there appear to be some 

errors in the calculation of the acute MOE values. For example a worker doing mixing/loading 

of liquids for aerial application or for chemigation, assuming an application rate of 3 lb ai/A and 

350 acres/day, would have a baseline inhalation MOE of 53 and with a PF5 respirator the MOE 

would be 264. Similarly, a worker doing mixing/loading of liquids for groundboom applications, 

assuming an application rate of 3 lb ai/A and 80 acres/day, would have a baseline inhalation 

MOE of 232. Additionally, a worker applying sprays via groundboom, with the same rate and 

area/day assumption, would have a baseline inhalation MOE of 149. In the footnotes of Table 

A6.1 of Attachment 6, HED values are listed as 0.174 mg/kg/day for acute exposure and 0.052 

mg/kg/day for short-/and intermediate-term exposures. Syngenta respectfully requests that the 

algorithm and ventilation assumptions used to calculate these HED values be clarified in the 

document, as we were unable to reproduce these values based on the information in either the 

draft EPA/HED 2010 assessment or the EPA 2012 scoping assessment.

HED’s Response: The unit exposure values for occupational handler assessments have been 

updated recently. The MOEs presented in the 2010 risk assessment are reflective of the available

surrogate data at that time. During Registration Review, the most up-to-date surrogate values 

and assumptions will be used to assess all registered uses. In addition, the inhalation 

toxicological endpoint selection and subsequent HEC/HED values may be re-evaluated based on 

available information. The Registration Review assessment will include all algorithms and 

assumptions used in the exposure calculations to provide a transparent assessment.