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Guide to Commenters - Chlorpyrifos Revised Human Health Risk Assessment 

Docket # EPA-HQ-OPP-2008-0850 

Publication Date: January 14, 2015

Purpose of This Guide to Commenters: 

This guide is intended to assist commenters in providing input into the evaluation of human 

health effects from exposure to chlorpyrifos and any potential mitigation needed to address risk 

concerns. 

Summary and Questions 

The Environmental Protection Agency (EPA) is opening the public comment period for the 

Chlorpyrifos Revised Human Health Risk Assessment (RHHRA). The public is invited to 

comment on EPA’s RHHRA. Such comments and input could address, among other things, the 

Agency’s risk assessment methodologies and assumptions, as applied to this RHHRA, as well as 

possible mitigation for any risk as identified in the RHHRA. The Agency will carefully 

consider all comments, as well as any additional information or data provided in a timely 

manner, received during the public comment period and the responses to the questions presented 

below and any other information that is provided will help in developing the proposed 

registration review decision on chlorpyrifos. The chlorpyrifos RHHRA, as well as all 

chlorpyrifos documents, can be found at www.regulations.gov, in docket EPA-HQ-OPP-2008-

0850. The public comment period will be for 60 days from the January 14, 2015 Federal Register 

Notice announcing the availability of the assessment. 

This RHHRA shows some risks to workers who mix, load and apply chlorpyrifos pesticide 

products. A screening level drinking water analysis conducted as part of the RHHRA also shows 

that some chlorpyrifos use scenarios can lead to chlorpyrifos oxon concentrations in drinking 

water that pose exposure concerns from vulnerable watersheds in certain parts of the country. 

Factors including chlorpyrifos use, soil types, weather, and water treatment practices will 

influence drinking water exposure. Additional analyses are needed in order to pinpoint the 

community water systems where concentrations may be of concern. This RHHRA shows no 

additional risks from chlorpyrifos exposures in food or exposures to bystanders and workers 

from airborne chlorpyrifos. 

During this public comment period, stakeholders are specifically asked to provide information 

and data on the following questions that will assist EPA in developing the proposed registration 

review decision for human health for chlorpyrifos uses. 

Areas of Focus for Questions Regarding the Revised Human Health Assessment 

1. Occupational post-application exposures and risks were assessed for any crops where 

hand labor is anticipated following applications of chlorpyrifos. Chlorpyrifos parent 

compound is the residue of concern for occupational post-application exposures that 

occur outdoors; however, it may be possible that the formation of chlorpyrifos oxon is 

greater and its degradation slower in greenhouses when compared to the outdoor 

environment. Available exposure data indicate chlorpyrifos oxon may form in indoor 
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environments [J.L. Martinez Vidal, et al. (1998)]. In order to account for the potential 

formation of chlorpyrifos oxon in greenhouses, risks were estimated for worker reentry 

into treated greenhouses for the parent chlorpyrifos plus chlorpyrifos oxon using a 

conservative, total toxic residue approach. 

In the 2011 preliminary HHRA, additional studies to address the uncertainties regarding 

the formation and degradation of chlorpyrifos oxon in greenhouses were recommended. 

To date, no data have been submitted. 

We are seeking comment/input regarding the potential formation assessment of 

chlorpyrifos oxon in greenhouses including: a) whether commenters possess additional 

exposure data relating to the formation of chlorpyrifos oxon in greenhouses, b) the 

agency’s decision to assess chlorpyrifos oxon in greenhouses, or c) the methods used to 

assess worker reentry exposure to chlorpyrifos oxon in greenhouses (i.e., the total toxic 

residue approach). 

2. In January 2013, a preliminary assessment of the potential risks from chlorpyrifos 

volatilization was conducted. However, this assessment was revised in June 2014 

following submission of two vapor phase, inhalation toxicity studies by Dow 

AgroSciences which indicated no adverse effects occurred even at the saturation 

concentration for chlorpyrifos and chlorpyrifos oxon. Because these new studies 

demonstrated that no toxicity occurred even at the saturation concentration, which is the 

highest physically achievable concentration, there are no anticipated risks of concern 

from exposure to the volatilization of either chlorpyrifos or chlorpyrifos oxon. 

We are seeking comment regarding the determination of no risks of concern anticipated 

from volatilization exposures of either chlorpyrifos or chlorpyrifos oxon. 

3. The Agency has used a physiologically-based pharmacokinetic-pharmacodynamic model 

(PBPK-PD) to estimate points of departure (PoDs) for 10% red blood cell 

acetylcholinesterase/cholinesterase (AChE/ChE) inhibition following acute (single day, 

24 hours) and steady state (21-day) exposures for a variety of exposure scenarios for 

chlorpyrifos and/or chlorpyrifos oxon. The use of the PBPK-PD model alleviates the 

need for the application of the inter-species extrapolation factor (i.e., animal to human 

extrapolation). Moreover, the agency has used the PBPK-PD model to determine DataDerived Extrapolation Factors relevant for assessing potential variability in sensitivity 

across the human population for infants, children, and non-pregnant adults. For women 

of childbearing age, the agency is applying the standard 10X intra-species extrapolation 

factor since the PBPK-PD model cannot account for variability in physiology during 

pregnancy. 

We are seeking comment regarding use of the PBPK-PD model to determine the 

appropriate extrapolation factors in the RHHRA. 

4. Separate PoDs have been calculated for dietary (food, drinking water), residential, and 

occupational exposures by varying inputs on types of exposures and populations exposed. 
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Examples of inputs include: duration; route (dermal, oral, inhalation); body weights 

which vary by lifestage; exposure duration (hours per day, days per week); and exposure 

frequency [events per day (eating, drinking)]. 

We are seeking comment regarding the exposure inputs used for the derivation of PoDs 

using the PBPK-PD model for each of the exposure scenarios considered in the RHHRA. 

5. The agency has conducted a weight of evidence analysis integrating data from 

mechanistic studies, animal behavior studies, epidemiology, and a dose reconstruction 

analysis. Given the totality of the evidence, the agency concludes that chlorpyrifos likely 

played a role in the neurodevelopmental outcomes reported by the Columbia University 

investigators but uncertainties such as the lack of an established mode of action/adverse 

outcome pathway (MOA/AOP) for neurodevelopmental effects and the exposure to 

multiple AChE-inhibiting pesticides precludes definitive causal inference. However, 

there is sufficient uncertainty in the human dose-response relationship for 

neurodevelopmental effects which prevents the agency from reducing or removing the 

statutory 10X Food Quality Protection Act (FQPA) Safety Factor. The FQPA 10X 

Safety Factor will be retained for infants, children, youths, and women of childbearing 

age for all exposure scenarios. 

We are seeking comment on the RHHRA’s conclusions regarding retaining the 10X 

FQPA Safety Factor to account for the uncertainties related to neurodevelopmental 

outcomes observed in the chlorpyrifos database. 

Questions regarding drinking water assessment 

6. The drinking water assessment presents an approach for identifying individual 

watersheds and community water systems with high (i.e., drinking water concentrations 

greater than the drinking water level of concern (DWLOC) exposure of chlorpyrifos and 

chlorpyrifos oxon. What uncertainties and assumptions should be considered or are 

introduced when a watershed scale assessment approach is utilized as opposed to a 

national or regional scale assessment? 

7. If you are aware of any regional, state, county, and/or local surface water/drinking water 

monitoring data for chlorpyrifos and the oxon, that were not considered in EPA’s 

assessment, please provide those data to us. 

8. Based on empirical data that examined the formation and decline of chlorpyrifos oxon 

under simulated drinking water conditions [i.e., chlorination (the primary disinfection 

process used by community drinking water treatment systems], the drinking water 

assessment considers that all the chlorpyrifos in source surface water is converted to the 

oxon during the drinking water treatment process and distributed to end users. 

We are seeking comment or any information on the decline of chlorpyrifos and 

formation/decline of chlorpyrifos oxon under other drinking water treatment conditions 

or combinations of drinking water treatment conditions. 
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Questions regarding additional information on chlorpyrifos use 

1. The agency conducted the occupational and residential exposure assessments and the 

drinking water assessment based on use of a master use summary document. The detailed 

information on application rates and use patterns is the basis for these assessments. In 

order to clarify of chlorpyrifos usage, the agency obtained input from the chlorpyrifos 

registrants to compile the master use summary document to be reflective of the use 

profile of all active product labels. The document, among other information, presents all 

registered uses of chlorpyrifos and corresponding maximum single application rates, 

equipment types, re-entry intervals (REIs), etc. 

We are seeking comment as to a) whether the master use summary document is 

accurately reflective of current chlorpyrifos labeling and b) whether the occupational and 

residential exposures and drinking water assessment are representative of current 

chlorpyrifos labeling. 

2. If you are a grower, what is the lowest application rate of chlorpyrifos (in either 

formulated lb/acre or active ingredient lb/acre) that is feasible for management of critical 

pests in your fields? Please provide as much detail as possible (specific pests involved, 

reasons why the rate is the minimum useful one, etc.). 

3. If you are a grower, what is the minimum number of applications per year that you would 

consider feasible for effective use of chlorpyrifos in your crop, and why? 

4. If you are a grower, please comment on what time of year you typically use chlorpyrifos, 

and what the time range of any such applications may be. 

5. If you are a grower, please provide information regarding acres treated per application 

per day (i.e., field size treated per day), specific to your growing region and pest 

spectrum 

6. If you are a grower, please comment on what application methods you most 

frequently/typically use? 

7. If you are a grower, please comment on what formulation types you most frequently use? 

8. If you are a grower, please comment on the application timing (date of first application 

and application intervals) by crop – national, state, and county? For example, when 

during the growing season do chlorpyrifos applications predominately occur in tree and 

vine crops?