(PP#0E06068), Stone Fruit (PP#2E06303), and Tomatoes (PP#1E06303) (Deschamp P, 

D323441, 09/23/05). Additional documents used in this scoping document are cited below. 

Pyridaben [2-tert-butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one] is a selective 

contact miticide/insecticide that controls various types of phytophagous mites and insects in 

orchards and vineyards. Pyridaben is registered for use on tree nuts, pistachio, apple, pear, citrus 

fruits, grape, apricot, cherry, nectarine, peach, plum, prune, cranberry, ornamentals, and 

greenhouse-grown tomatoes. There are no registered residential uses of pyridaben. 

Under the new rules for toxicity data requirements (40 CFR §158.500, 10/26/2007), an 

immunotoxicity study is required for pyridaben. Once the data have been received and reviewed, 

the pyridaben HED Registration Review Team will re-evaluate the sensitivity determination, as 

well as the points of departure and safety factors used for risk assessment purposes. 

The existing residue chemistry database for pyridaben is adequate for risk assessment purposes. 

There are no registered residential uses of pyridaben. There is a potential for short- and 

intermediate-term occupational handler exposure to pyridaben during mixing, loading, and 

applying activities. Occupational risk assessments have been conducted for wettable powder 

formulations (in water soluble bags) and should also be conducted for aqueous solution 

formulations. Assessments using current standard operating procedures are needed for currently 

registered formulations of pyridaben. New pyridaben occupational exposure/risk assessments 

will be needed for Registration Review. 

Occupational postapplication exposure to pyridaben can occur via the dermal and/or inhalation 

routes. Postapplication exposure should be reassessed for certain pyridaben use sites using 

current HED policies. All other occupational exposure scenarios were assessed adequately and 

do not present risks of concern. 

Introduction 

HED has evaluated the status of the human health assessments for pyridaben to determine 

whether sufficient data are available and if any updates are needed to support Registration 

Review. HED has considered the most recent risk assessment for pyridaben (Deschamp P, 

D323441, 09/23/2005), HED and OPPIN databases for registration review. Pyridaben may be 

applied via handgun, airblast, groundboom, or chemigation (for certain use sites only) at 

maximum application rates of 0.5 lb ai/Acre and 0.19 lb ai per 100 gallons for greenhouse 

tomatoes, with a maximum of 2 applications per year for certain crops. 

Hazard Identification/Toxicology 

Pyridaben is a selective contact miticide/insecticide that controls various types of phytophagous 

mites and insects in orchards and vineyards. Pyridaben belongs to a class of pesticides known as 

pyridazinones. Pyridaben affects mite and insect metabolism by inhibiting the mitochondrial 

electron transport chain in target organisms (Dekeyser M, 20041

), but its mechanism of action in 

mammals has not been definitively identified. Other pyridazinones affect ATP usage or 

generation, but their specific mechanisms of action differ amongst the compounds.

 

1

 Dekeyser M, Acaricide mode of action, in Pest Management Science, pp 103-110 (2004)

Page 2 of 28 
Pyridaben’s toxicity database is complete, with the exception of a now required immunotoxicity 

study. The toxicity database for pyridaben does not indicate a distinct organ system being 

adversely affected. However, it has been shown in rats, mice, rabbits, and dogs that 

administration of pyridaben results in reduced body weight gain. Additionally, in both shortterm and long-term exposure, dogs administered pyridaben orally showed clinical signs of 

toxicity such as dehydration, diarrhea, food-like emesis, frothy emesis, soft stool, uninhibited 

salivation, and relaxed nictitans (membrane that functions as a third eyelid) in addition to 

reduced body weight gain. In an inhalation study, rats treated with pyridaben showed signs of 

toxicity such as red dried nasal discharge, increased ano-genital staining, in addition to decreased 

body weight gain. 

Pyridaben produced mild acute toxicity through oral, dermal, and inhalation exposure routes. It 

produced slight ocular irritation but has not been shown to be a dermal irritant or sensitizer. 

There are guideline acute and subchronic neurotoxicity studies as well as developmental toxicity 

studies in rats and rabbits (by the oral or dermal routes), and a multi-generation reproduction 

study in rats. The developmental and reproduction studies show no effects on reproduction and 

no increased susceptibility of rats or rabbits to in utero and/or postnatal exposure to pyridaben as 

demonstrated by higher lowest-observable-adverse-effect-levels (LOAELs) than those for 

maternal toxicity. In the acute and subchronic neurotoxicity studies, moderate clinical 

signs were seen only at relatively high doses; the effects were suggestive of neurotoxicity, but 

there were no supportive neuropathological (gross pathology including brain weights or 

histopathology) effects. 

Pyridaben’s mutagenicity battery indicated no evidence of genotoxic potential. Additionally, 

cancer studies utilizing both male and female rats do not demonstrate any evidence of 

carcinogenicity. Thus, pyridaben is classified as “Not Likely to Be Carcinogenic to Humans.”2

The pyridaben risk assessment team has re-evaluated all the available toxicology data along with 

the most recent human health risk assessment (Deschamp P, D323441, 09/23/2005). The team 

has determined that the toxicity endpoints and points of departure developed in the 2005 risk 

assessment continue to be valid for any risk assessment purposes. A detailed listing of the 

endpoints, doses and uncertainty factors selected for all exposures may be found in Attachment 

4. 

HED has selected an acute dietary endpoint for the general U.S. population, including infants 

and children based on the rat neurotoxicity study where increased incidence of piloerection, 

hypoactivity, tremors, partially closed eyes and decreased body weight gain and food 

consumption were observed in both sexes. For chronic dietary exposures, HED has selected an 

endpoint based the 1-year dog study where increased incidence of ptyalism, emesis and soft stool 

and decreased body weight gain was observed in females. The Food Quality Protection Act 

(FQPA) requires the Agency to consider sensitivities of the young to chemical exposure. The 

pyridaben risk assessment team has reviewed the entire database for pyridaben and determined 

there is no residual uncertainty regarding exposure to children at any developmental stage and 

 

2

 Memo: Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs 09/03/2009 

Page 3 of 28 
recommends that the FQPA safety factor be reduced to 1x for all exposure scenarios. This 

position continues to be valid. 

An immunotoxicity study is required as part of new data requirements in the 40 CFR § 158 for 

pesticide registration. However, in the absence of a specific immunotoxicity study, EPA has 

evaluated the available pyridaben toxicity database to determine whether an additional database 

uncertainty factor is needed to account for potential immunotoxicity. No evidence of 

immunotoxicity such as altered hematology, changes in lymphoid organ weights, and aberrant 

histopathology, was observed in any of the available toxicity studies. Because of the lack of 

evidence of immunotoxicity for pyridaben, EPA does not believe that conducting 

immunotoxicity testing will result in a NOAEL less than that used to derive the current cRfD. 

Consequently, the EPA believes the existing data are sufficient for endpoint selection for 

exposure/risk assessment scenarios and for evaluation of the requirements under the FQPA; 

therefore an additional database uncertainty factor does not need to be applied. 

However, it must be made clear that the immune system is highly complex and, thus, studies not 

specifically conducted to assess immunotoxic endpoints are inadequate to fully characterize a 

pesticide’s potential immunotoxicity. While data from hematology, lymphoid organ weights, 

and histopathology in routine chronic or subchronic toxicity studies might offer useful 

information on potential immunotoxic effects, these endpoints alone are insufficient to predict 

immunotoxicity. Therefore, an immunotoxicity study must be submitted for the risk assessment 

team to develop an enhanced understanding of the risks associated with pyridaben. 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (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. 

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. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors. Pyridaben is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingly, 

EPA anticipates issuing future EDSP test orders/data call-ins for all pesticide active ingredients. 

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

Page 4 of 28 
chemicals, the test guidelines, and the Tier 1 screening battery, please visit our website: 

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

Conclusion

A newly required immunotoxicity study is needed to support registration review of pyridaben. 

HED will consider the existing toxicity database as well as all additional toxicity studies received 

during registration review and will reevaluate the sensitivity determination, as well as the points 

of departure and safety factors, used for risk assessment purposes 

Residue Chemistry

The existing residue chemistry database for pyridaben is adequate for risk assessment purposes. 

All submitted residue chemistry data have been reviewed and found sufficient to estimate and 

characterize dietary exposure and to support current registrations. The qualitative nature of 

pyridaben residues in plants and livestock is adequately understood. In the submitted plant 

metabolism studies (orange, apple, eggplant) pyridaben is highly metabolized yielding minor 

metabolites. The submitted livestock metabolism studies also indicate that pyridaben is highly 

metabolized yielding minor metabolites including PB-7 [2-tert-butyl-5-(4-(1-carboxy-1-

methylethyl)benzylthio)-4-chloropyridazin-3(2H)-one] and PB-9 [2-tert-butyl-5-[4(-1,1-

dimethyl-2-hydroxyethyl)benzylthio-4-chloropyridazin-3(2H)-one]. Although these metabolism 

studies are adequate to support existing uses, if uses are proposed for grain crops and/or leafy 

vegetables, additional metabolism data using either a grain crop or leafy vegetable will be 

required. Adequate analytical methods exist for data collection and tolerance enforcement. 

Adequate storage stability, processed food, and plant/animal magnitude of the residue data exist. 

Tolerances are established under 40 CFR §180.494 for residues of the insecticide pyridaben that 

result from agricultural uses. The permanent tolerance expression for all commodities is in terms 

of the parent only for plant commodities and parent only plus metabolites PB-7 and PB-9 for 

livestock commodities. Pyridaben dietary risk assessments should include the parent pyridaben 

and all metabolites containing the pyridazinone ring for plants, and parent pyridaben and its 

metabolites, PB-7 and PB-9, for ruminant meat byproducts. The tolerance expression for 

pyridaben needs to be updated to reflect current Agency policy, as follows: “Tolerances are 

established for residues of pyridaben, including its metabolites and degradates, in or on the 

commodities in the table below. Compliance with the tolerance levels specified below is to be 

determined by measuring the insecticide pyridaben [2-tert-butyl-5-(4-tert-butylbenzylthio)-4-

chloropyridazin-3(2H)-one] on the following plants, and of the insecticide pyridaben and its 

metabolites, [2-tert-butyl-5-(4-(1-carboxy-1-methylethyl)benzylthio)-4-chloropyridazin-3(2H)-

one] and [2-tert-butyl-5-[4(-1,1-dimethyl-2-hydroxyethyl)benzylthio-4-chloropyridazin-3(2H)-

one] on animals.” 

Due to updated methods for calculating livestock dietary burden (June 2008), the livestock 

dietary burdens should be reassessed to evaluate potential secondary residues of pyridaben and 

its metabolites in/on livestock commodities due to consumption of feed items with pyridaben 

residues resulting from the established food/feed commodities (e.g., almond hulls and wet apple 

pomace). The repository currently has analytical standards of parent pyridaben from both BASF 

and Nissan which do not expire until 2016. However, reference standards for all pyridaben 

Page 5 of 28 
metabolites are not currently in stock. HED requests that all metabolites listed in the 40 CFR 

§180.494 tolerance be submitted. 

There are no Codex or Mexican tolerances for pyridaben and, thus, no compatibility questions 

exist. However, there are Canadian tolerances for pyridaben in/on apples; cattle, meat; 

peaches/nectarines; sweet cherries; tart cherries; goat, meat; grapes; horse, meat; milk; almonds; 

pears; sheep, meat; strawberries; tomatoes; cucumbers; and peppers. There are compatibility 

issues with Canada for some of these crops due to differences in crop grouping and livestock 

residue definitions (Attachment 2). 

Dietary Exposure and Risks 

The most recent acute and chronic dietary exposure assessments were below HED’s level of 

concern for the general U.S. population and all population subgroups examined (Wassell W, 

D316834, 05/12/2005). The dietary risk assessment incorporated all available information 

including usage data (percent crop treated). Percent crop treated estimates of agricultural uses 

were last provided in 2004. For registration review, these values will need to be updated in a 

new dietary exposure assessment. A comparison of previously used percent crop treated values 

(2004) and more recently reported values (2009) is presented in Attachment 3. 

Acute

A refined acute dietary exposure assessment (probabilistic) was conducted for pyridaben. The 

assumptions of this dietary exposure assessment are as follows: (1) probabilistic assessment 

based upon residue distribution files or anticipated-residue estimates derived from crop field trial 

data were utilized for most commodities; (2) processing factors from processing studies were 

utilized for most processed commodities; and (3) percent crop treated estimates and projected 

market-share estimates were utilized for most crops. 

For the acute analysis, the most highly exposed population subgroup is children 1 to 2 years old. 

The acute exposure at the 99.9th percentile for children 1 to 2 years old is 0.0275 mg/kg/day, 

which utilizes 63% of the acute population adjusted dose (aPAD) for pyridaben. The acute 

dietary exposure at the 99.9th percentile for the U.S. population is 0.0110 mg/kg/day, which 

utilizes 25% of the aPAD for pyridaben. This assessment is considered to be highly refined. 

Chronic

A partially refined chronic dietary exposure assessment was conducted for pyridaben. The 

assumptions of this dietary exposure assessment are as follows: (1) anticipated residue estimates 

were derived from proposed and established tolerance levels; and (2) percent crop treated 

estimates and projected market-share estimates were utilized for most crops. 

For the chronic analysis, the most highly exposed population subgroup is children 1 to 2 years 

old. The chronic exposure for children 1 to 2 years old is 0.00233 mg/kg/day, which utilizes 

47% of the chronic population adjusted dose (cPAD) for pyridaben. The chronic dietary 

exposure for the U.S. population is 0.000672 mg/kg/day, which utilizes 13% of the cPAD for 

pyridaben. This assessment is considered to be partially refined. 

Drinking Water

Page 6 of 28 
Residues of concern in water consist of the parent compound only. The Environmental Fate and 

Effects Division (EFED) performed a screening level surface and ground water modeling to 

estimate drinking water concentrations (Costello K, 02/10/2004). FIRST Version 1.1.0 modeling 

was used to estimate surface water concentrations and SCI-GROW Version 2.3 was used to 

estimate ground water concentrations. Modeling methodology has been modified since the last 

assessment and an updated drinking water assessment will be needed during the registration 

review process to determine if pyridaben uses impact the estimated drinking water 

concentrations (EDWCs). 

Conclusion

As part of registration review, a new dietary risk assessment should be conducted which utilizes 

the most current version of the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCIDTM, Version 2.03). The new dietary exposure 

assessment should also evaluate potential secondary residues of pyridaben and its metabolites 

in/on livestock commodities due to consumption of feed items with pyridaben residues resulting 

from the established food/feed commodities (e.g., almond hulls and wet apple pomace). The 

new dietary exposure assessment should also directly incorporate updated drinking water 

estimates into the dietary risk assessment. Additionally, should a review of the Pesticide Data 

Program (PDP) and percent crop treated information show that food residues have significantly 

changed, the anticipated residues may need to be revised and incorporated into the acute and 

chronic dietary risk assessments. 

Residential Exposure

Residential Handlers

Pyridaben is not currently registered for use by homeowners or in residential settings; therefore, 

no residential handler exposure is expected. 

Residential Post Application 

Pyridaben is not currently registered for use by homeowners or in residential settings. 

Postapplication exposure resulting from volatilization or spray drift is expected to be unlikely to 

occur as pyridaben is not applied aerially, which increases the likelihood of exposure resulting 

from spray drift. 

Conclusion

Because pyridaben is not registered for use in residential settings, there is currently no risk 

concern for residential exposure. If exposure data and methodologies for estimating exposure 

have changed for issues such as volatilization, spray drift and track-in from field applications to 

residential settings, then a new exposure assessment may be requested. 

Aggregate Risk Assessment 

Since there are no residential uses of pyridaben, there is no concern for short- and intermediateterm aggregate risk from the residential pathway. Aggregated exposure/risk from the food and 

drinking water pathways are presented above. 

Page 7 of 28 
Occupational Exposure 

Pyridaben is registered for use on various raw agricultural commodities (RACs) and 

ornamentals. There is a potential for short- and intermediate-term exposure to pyridaben during 

mixing, loading, and applying activities. Occupational risk assessments have been conducted for 

wettable powder formulations (in water soluble bags); however pyridaben is also available as an 

aqueous solution. Modifications to the occupational handler exposure assessment are needed. A 

new occupational handler risk assessment will be needed for registration review. 

Occupational Handlers

Attachment 5 summarizes the occupational scenarios that exist for pyridaben and whether or not 

each scenario has been previously assessed. Attachment 5 summarizes the occupational risks for 

pyridaben that have been previously assessed. All pyridaben labels require long pants, longsleeved shirts, shoes plus socks, gloves (chemical resistant), and goggles or a face shield. Some 

labels also require a respirator for handling activities (EPA Registration Numbers: 81880-5, 

33906-23, 81880-4, 33906-19, 33960-21, and 81880-3). 

Data sources that have been used in previous occupational assessments include PHED for unit 

exposure values. For registered uses of pyridaben for mixer loader scenarios no risks of concern 

were identified (Arthur J, D261499, 11/30/1999; Arthur J, D261499, 09/11/2003). For uses on 

stone fruits and greenhouse tomatoes the total short- and intermediate-term combined dermal and 

inhalation margins of exposure (MOEs; assessed with gloves and open cab) ranged from 110 to 

36,000, resulting in no risks of concern to HED (Arthur J, D261499, 09/11/2003). For pyridaben 

use on citrus, apples, apricots, cherries, pears, peaches, plums, almonds, pistachios, grapes, and 

cranberries, the total short- and intermediate-term combined dermal and inhalation MOEs 

(assessed with gloves and open cab) ranged from 170 to 14,000, resulting in no risks of concern 

to HED (Arthur J, D261499, 11/30/1999). For the use sites allowing airblast application, the 

mixer/loader and applicator scenarios should be assessed with wettable powder and aqueous 

solutions. Use sites registered with aqueous solution, include tree nuts, stone fruits, and 

pistachios. 

Occupational Postapplication

Occupational postapplication exposure to pyridaben can occur via the dermal and/or inhalation 

routes. Postapplication exposure is expected to occur for short- and intermediate-term durations. 

Long-term exposure is not expected even for greenhouse tomato use sites because a maximum of 

two applications per growing season are permitted and are separated by a 30-day treatment 

interval. 

The pyridaben technical material is classified as Toxicity Category III for acute dermal, acute 

inhalation, and primary eye irritation. Per the Worker Protection Standard (WPS), a 12-hour 

restricted entry interval (REI) is required for chemicals classified under Toxicity Category III. 

However, using the short- and intermediate-term dermal toxicity endpoints and data from two 

dislodgeable foliar residue (DFR) studies (MRID No. 436804-25, MRID No. 440292-03) with 

pyridaben, MOEs for post-application exposure exceed HED’s level of concern at the 12 hour 

REI for certain crops and activities. Longer REIs are needed to reach the level of concern (LOC) 

of 100 for certain crops in California where dissipation was the slowest of the sites studied 

(Attachment 5). In conjunction with Registration Reviews, pyridaben labels should be revised to 

Page 8 of 28 
incorporate the additional REIs in California for tree crops (REI of 5 days in CA, almonds and 

pistachios REI of 12 hours for mechanical operations and 10 days for hand/manual activities), 

grapes (13 days in CA), and cranberries (12 hours). Using the short- and intermediate-term 

dermal toxicity endpoints and data from the DFR study with pyridaben use on California citrus, 

the MOEs for all major postapplication activities for stone fruits reach the LOC of 100 on the 

day of treatment, Day 0, for all crops and, therefore, do not exceed HED’s level of concern. 

Inhalation exposure is expected to be negligible for most postapplication scenarios. However, 

due to the enclosed nature of greenhouses, the airborne concentration of volatile or semi-volatile 

pesticides may result in concerns for greenhouse workers following application of such 

pesticides. The WPS for Agricultural Pesticides contains requirements for protecting workers 

and bystanders from inhalation exposures during and after greenhouse applications through the 

use of ventilation requirements. 

Based on the Agency's current practices, a quantitative postapplication inhalation exposure 

assessment was not performed for pyridaben at this time. However, volatilization of pesticides 

may be a potential source of postapplication inhalation exposure to individuals nearby to 

pesticide applications. The Agency sought expert advice and input on issues related to 

volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report 

on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The 

Agency is currently evaluating the SAP report and may, as appropriate, develop policies and 

procedures to identify whether to incorporate postapplication inhalation exposure into the 

Agency’s risk assessments, and methods to assess postapplication inhalation exposure. If new 

policies or procedures are implemented, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for pyridaben. 

Conclusion

The following occupational exposure scenarios listed below will need to be assessed or 

reassessed for Registration Review using current ORE policies and currently established toxicity 

endpoints. All other occupational exposure scenarios do not need to be revised and do not 

present risks of concern. At the time of the registration review risk assessment, if exposure data 

and methodologies for estimating exposure have changed for issues such as spray drift, 

volatilization, and track-in from field applications to residential settings these inputs will be 

incorporated into the assessment. Additionally, if toxicity endpoints related to 

occupational/residential exposure change, the risk assessment may need to be revised. 

ORE Assessments Needed

• New occupational risk assessments will be needed to assess mixer/loader and applicator 

exposure from airblast application to citrus, tree nuts (Crop Group 14), apples, stone 

fruits (Crop Group 12), cranberry, grapes, pear, and pistachio. 

• A new occupational risk assessment, including postapplication exposure, will be needed 

for pyridaben application to ornamentals as the use site has not previously been assessed. 

• The new occupational risk assessment for almonds should reflect current HED acres 

treated values. 

Page 9 of 28 
• Aqueous solution products need to be assessed for tree nuts, stone fruits, pistachio, and 

pears. 

Public Health and Pesticide Epidemiology Data

The OPP Incident Data System (IDS) and the Centers for Disease Control and 

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

Notification System for Occupational Risk-Pesticides (SENSOR) database were consulted for 

pesticide incident data on the active ingredient pyridaben (S. Recore and K. Oo, DP374530, 20 

May 2010). 

For IDS, no incidents were reported occurring in the United States from 2002 to the present for 

the single chemical only (pyridaben). For NIOSH SENSOR from 1998 to 2006, there are 11 

cases reported for pyridaben in the database. Of these cases, 4 were reviewed because, in these 

cases, pyridaben was used as a single chemical only and had a certainty classification of definite, 

probable, or possible, as these cases provide more certain information about the potential effects 

of pyridaben exposure. All of the reviewed cases were classified as low or moderate severity. 

The health effects reported include: two cases of ocular symptoms (50%), two cases of 

gastrointestinal symptoms (50%), one case of neurological symptoms (25%), and one case of 

respiratory symptoms (25%). Proportions relate to the total number of symptoms, not the total 

number of cases, i.e., an individual may report multiple symptoms to the database. One of these 

cases was bystander exposure to pyridaben. A 33 year old pregnant female was exposed while 

performing a greenhouse inspection. She experienced ocular and respiratory symptoms. In three 

cases the details are unknown. Pyridaben is not included in the AHS, and therefore not 

considered in this report. 

Based on the low severity and low number of incident cases, there does not appear to be a 

concern at this time that would warrant further investigation. The Agency will continue to 

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

included in the risk assessment. 

Environmental Justice

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

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

to Address Environmental Justice in Minority Populations and Low-Income Populations,” 

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

Chemical Safety and Pollution Prevention (OCSPP) typically considers the highest potential 

exposures from the legal use of a pesticide when conducting human health risk assessments, 

including, but not limited to, people who obtain drinking water from sources near agricultural 

areas, the variability of diets within the U.S., and people who may be exposed when harvesting 

crops. Should these high exposures indicate potential risks of concern, OCSPP will further 

refine the risk assessments to ensure that the risk estimates are based on the best available 

information. 

Cumulative

The Agency has not determined whether pyridaben shares a common mechanism of toxicity with 

other chemical substances. Prior to a final Registration Review decision for pyridaben, the 

Page 10 of 28 
Agency will determine if there is any new information, such as new hazard or exposure data or 

information on changes to the use pattern, which would affect the cumulative risk assessment. 

Should the Agency determine that new information on pyridaben is available that could 

potentially impact the cumulative risk assessment and result in a risk of concern, the Agency will 

revisit the cumulative risk assessment.

Human Studies 

Past pyridaben risk assessments 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 the Pesticide Handlers Exposure Database (PHED) and the 

Agricultural Reentry Task Force (ARTF) 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. 

Data Requirements 

HED does not anticipate that additional residue chemistry, toxicology or occupational/residential 

exposure data will be required for the pyridaben registration review process, with the exception 

of the following study listed below: 

• Immunotoxicity Study (OPPTS 870.7800) (See Attachment 6) 

Page 11 of 28 
References 

1. Deschamp P, Amendment to HED Human Health Risk Assessment: Pyridaben in/on Hops 

(PP#1E06226), Tropical Fruit (PP#3E06460), Strawberries (PP#0E06068), Stone Fruit 

(PP#2E06303), and Tomatoes (PP#1E06303); DP Barcode: D323441 (2005) 

2. Wassell W, Pyridaben in/on Hops (PP#1E06226), Tropical Fruit (PP#3E06460), 

Strawberries (PP#0E06068), Stone Fruit (PP#2E06303), and Tomatoes (PP#1E06303). 

HED Human Health Risk Assessment; DP Barcode: D316833 (2005) 

3. Wassell W, PP#6F4651/FAP#6H5745, PP#9E6002, PP#7F4881 and PP#5F4543; 

Pyridaben (OracleTM Miticide/Insecticide, EPA Reg. No. 7969-125) in/on Apples, Cranberry, 

Peach, Nectarine, Plum, Prune, Cherry, Apricot, Grape, Pistachio, Citrus and Tree Nuts 

Crop Groups and Livestock Commodities; DP Barcode: D264767 (2000) 

4. Cutchin W, ID#98MA0006 SECTION 18 EXEMPTION FOR THE USE OF PYRIDABEN ON 

CRANBERRIES IN MASSACHUSETTS; DP Barcode: D245233 (1998)

5. Kramer G, Risk Assessment for Use of the New Chemical Insecticide Pyridaben in/on Citrus, 

Apples, Pears, Almonds, Peaches, Plums and Grapes; DP Barcode: D233114, D233166, 

D233164, D234191, D233248, D233250, D233244, D233247, D233252, D233522, and 

D227535

6. Cimino P, ID# 96DE0007 SECTION 18 EXEMPTION FOR USE OF PYRIDABEN ON 

APPLES IN THE STATE OF DELAWARE; DP Barcode: D227688 

7. Madden B, Pyridaben (129105): Risk Assessment for an Experimental Use Permit (7969-

EUP-GA) for Use of Pyridaben on Apples (5G4589/5H5731); DP Barcode: D220682 and 

D220683 

8. Arthur J, Petition# 6F4721: Occupational and Residential Risk Assessment to Support New 

Uses of Pyridaben on Stone Fruits (Crop Group 12), Hops, Strawberries, Tropical Fruit and 

Greenhouse Tomatoes; DP Barcode: D261499 

9. Arthur J, Occupational and Residential Risk Assessment to Support Request for a Section 3 

Registration of the Pyridaben on Citrus, Apples, Apricots, Cherries, Pears, Peaches, Plums, 

Almonds, Pistachios, Grapes and Cranberries; DP Barcode: D261499 

Page 12 of 28 
Attachments

1. Chemical Identity and Physiochemical Properties 

2. International Residue Limit Summary (IRLS) 

3. Percent Crop Treated Data Comparison 

4. Endpoint Selection Table and Toxicity Profile 

5. Occupational Exposure Tables 

6. Data Call-In Table

Page 13 of 28 
Attachment 1: Chemical Identity and Physiochemical Properties

Pyridaben Structure and Nomenclature. 

Chemical Structure 

Empirical Formula C19H25ClN2OS 

Common Name Pyridaben (ANSI approved) 

Company Experimental Name BAS 300 

IUPAC Name 2-tert-butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one 

CAS Name 4-chloro-2-(1,1-dimethylethyl)-5-[[[4-(1,1-dimethylethyl)phenyl]methyl]thio]-3(2H}-

Pyridazinone

CAS Registry Number 96489-71-3 

End-Use Product/EP Pyramite Miticide/Insecticide (EPA Reg. No. 7969-124) 

Nexter Miticide/Insecticide (EPA Reg. No. 7969-106) 

Chemical Class pyridazinone class of pesticides 

Known Impurities of Concern None 

Physiochemical Properties of Pyridaben. 

Parameter Value 

Molecular Weight 364.9 

Melting point/range 111-112°C 

pH 6.81 in a solution containing 90.1 mg/L 

Density 1.03 kg/L at 20°C 

Water solubility (20°C) 0.012 μg/mL 

Solvent solubility (20°C to 25°C) 

57 g/L in ethanol 

10 g/L in hexane 

390 g/L in xylene 

320 g/L in cyclohexane 

110 g/L in benzene 

63 g/L in n-octanol 

460 g/L in acetone 

Vapor pressure 

1.9 x 10-6 mmHg at 20°C 

(0.25 mPa at 20°C) 

8.21 x 10-5 mm Hg at 25̊ C 

Dissociation constant, pKa N/A 

Octanol/water partition coefficient, log(KOW) Log KOW = 6.37 (at 23°C) 

Page 14 of 28 
Pyridaben Residues of Concern for Tolerance Setting Purposes.

Residue CAS Name Structure

Pyridaben 4-chloro-2-(1,1-dimethylethyl)-5-[[[4-(1,1-

dimethylethyl)phenyl]methyl]thio]-3(2H)-

pyridazinone 

PB-7 2-tert-butyl-5-[4-(1-carboxy-1-methylethyl) 

benzylthio]-4-chloropyridazin-3(2H)-one 

PB-9 2-tert-butyl-5-[4-(1,1-dimethyl-2-hydroxyethyl) 

benzylthio]-4-chloropyridazin-3(2H)-one 

Page 15 of 28 
Attachment 2: International Residue Limit Summary (IRLS) 

Summary of US and International Tolerances and Maximum Residue Limits. 

US Canada Mexico1 Codex

Residue Definition: 

40 CFR 180.494 

pyridaben [2-tert-butyl-5-(4-tertbutylbenzylthio)-4-chloropyridazin-3(2H)-one] 

on plant commodities, and 

pyridaben [2-tert-butyl-5-(4-tertbutylbenzylthio)-4-chloropyridazin-3(2H)-one] 

and its metabolites (2-tert-butyl-5-(4-(1-

carboxy-1-methylethyl)benzylthio)-4-

chloropyridazin-3(2H)-one] and (2-tert-butyl-5-

[4(-1,1-dimethyl-2-hypdroxyethyl)benzylthio-4-

chloropyridazin-3(2H)-one) on animal

commodities

4-chloro-2-(1,1-

dimethylethyl)-5-[[[4-

(1,1-

dimethylethyl)phenyl] 

methyl]thio]-3(2H)-

pyridazinone 

None 

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

Commodity US Canada Mexico1 Codex 

Almond, hulls 4.0 None 

Apple 0.5 0.5 

Apple, wet pomace 0.75 

Canistel 0.10 

Cattle, fat 0.05 

Cattle, meat 0.05 0.05 

Cattle, meat byproducts 0.05 

Citrus 0.5 

Citrus, dried pulp 1.5 

Citrus, oil 10.0 

Fruit, stone, group 12 2.5 

1.5 

 peaches/ nectarines 

1.3 

 sweet cherries 

1.3 

 tart cherries 

Goat, fat 0.0 

Goat, meat 0.05 0.05 

Goat, meat byproducts 0.05 

Grape 1.5 0.3 

Hog, fat 0.05 

Hog, meat 0.05 

Hog, meat byproducts 0.05 

Hop, dried cones 10.0 

Horse, fat 0.05 

Horse, meat 0.05 0.05 

Horse, meat byproducts 0.05 

Mango 0.10 

Milk 0.01 0.01 

Nut, tree, group 14 0.05 0.05 

almonds 

Papaya 0.10 

Page 16 of 28 
Summary of US and International Tolerances and Maximum Residue Limits. 

US Canada Mexico1 Codex

Pear 0.75 0.75 

Pistachio 0.05 

Sapodilla 0.10 

Sapote, black 0.10 

Sapote, mamey 0.10 

Sheep, fat 0.05 

Sheep, meat 0.05 0.05 

Sheep, meat byproduct 0.05 

Star apple 0.10 

Strawberry 2.5 2.0 

Tomato 0.15 0.15 

Cranberry (regional) 0.5 

Cucumbers - 0.1 

Peppers - 1.0 1

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

Page 17 of 28 
ATTACHMENT 3: Percent Crop Treated Data Comparison 

Percent Crop Treated Data Comparison for Pyridaben 

Percent Crop Treated Percent Crop Treated 

Crop 2004 Avg. 2009 Avg. 2004 Max. 2009 Max. 

1 Almonds <2.5 <2.5 4 5

2 Apples 10 10 20 20

3 Cherries <2.5 <2.5 4 7

4 Grapefruit 15 25 35 40

5 Grapes 5 5 10 10

6 Lemons <2.5 <1 4 <2.5

7 Nectarines (CA only) 9 4 (CA only) 15 10

8 Olives (CA only) <1 NA (CA only) 1 NA

9 Oranges 5 5 8 10

10 Peaches 5 <2.5 8 5

11 Pears 15 15 22 30

12 Pistachios (CA only) <1 NA (CA only) 1 NA

13 Prunes & Plums 5 <2.5 8 5

14 Sugar Beets (CA only) <1 NA (CA only) 1 NA

15 Tangelos (CA only) 13 20 (CA only) 20 25

16 Tangerines 15 35 25 60

17 Walnuts <2.5 <2.5 4 5

Page 18 of 28 
Attachment 4: Endpoint Selection Table and Toxicity Profile 

Summary of Toxicological Doses and Endpoints for Pyridaben for Use in Human Risk Assessments. 

Exposure Scenario Point of 

Departure 

Uncertainty / 

FQPA Safety 

Factors 

RfD, PAD, Level of 

Concern for Risk 

Assessment 

Study and Toxicological Effects 

Acute Dietary 

(Females 13-50 years 

of age) 

N/A N/A N/A No study applicable to a single oral exposure has been identified 

Acute Dietary 

(General population 

including infants and 

children) 

NOAEL = 44 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

Acute RfD = 

0.44 mg/kg/day 

aPAD = 

0.44 mg/kg/day 

Acute Neurotoxicity – Rat 

LOAEL = 80 mg/kg/day 

Based on: Increased incidence of piloerection, hypoactivity, tremors 

and partially closed eyes. Decreased body weight gain and food 

consumption 

Chronic Dietary (All 

populations) 

LOAEL = 0.5 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

Chronic RfD = 

0.005 mg/kg/day 

cPAD = 

0.005 mg/kg/day 

Chronic Feeding – Dog 

LOAEL = 0.5 mg/kg/day 

Based on: Increased incidence of ptyalism, emesis and soft stool 

Decreased body weight gain in females 

Short-Term 

Incidental Oral (1-30 

days) 

NOAEL = 5 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

LOC for MOE 

Residential = 100 

Occupational = N/A 

Developmental – Rabbit 

Maternal 

LOAEL = 15 mg/kg/day 

Based on: Increase in abortions. Decrease in maternal body weight, 

body weight gain, food consumption 

Intermediate-Term 

Incidental Oral 

(1-6 months) 

NOAEL = 1.0 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

LOC for MOE 

Residential = 100 

Occupational = N/A 

90-Day Feeding – Dog 

LOAEL = 4.0 mg/kg/day 

Based on: Increased incidence of ptyalism. Decreased body weight 

gain 

Short-Term Dermal 

(1-6 months) 

NOAEL = 100 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

LOC for MOE 

Residential = 100 

Occupational = 100 

21-Day Dermal – Rat 

LOAEL = 300 mg/kg/day 

Based on: Decreased body weight gain 

Intermediate-Term 

Dermal 

(1-6 months) 

NOAEL = 100 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

LOC for MOE 

Residential = 100 

Occupation = 100 

21-Day Dermal – Rat 

LOAEL = 300 mg/kg/day 

Based on: Decreased body weight gain 

Long-Term Dermal 

(>6 months) 

LOAEL = 0.5 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

LOC for MOE 

Residential = 100 

Occupation = 100 

Chronic Feeding – Dog 

LOAEL = 0.5 mg/kg/day 

Based on: Increase incidence of ptyalism, emesis and soft stools and 

in F: Decreased body weight gain 

Short-Term 

Inhalation 

(1-30 days) 

NOAEL = 

0.261 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

LOC for MOE 

Residential = 100 

Occupation = 100 

30-Day Inhalation – Rat 

LOAEL = 0.783 mg/kg/day 

Based on: Increased incidence of dried red nasal discharge. 

Decreased body weight gain and albumin levels 

Page 19 of 28 
Summary of Toxicological Doses and Endpoints for Pyridaben for Use in Human Risk Assessments. 

Exposure Scenario Point of 

Departure 

Uncertainty / 

FQPA Safety 

Factors 

RfD, PAD, Level of Study and Toxicological Effects 

Concern for Risk 

Assessment 

Intermediate-Term 

Inhalation (1-6 

months) 

NOAEL = 

0.261 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

LOC for MOE 

Residential = 100 

Occupation = 100

30-Day Inhalation – Rat 

LOAEL = 0.783 mg/kg/day 

Based on: Increased incidence of dried red nasal discharge. 

Decreased body weight gain and albumin levels 

Long-Term 

Inhalation 

(>6 months) 

NOAEL = 

0.261 

mg/kg/day 

UFA = 10x 

UFH = 10x 

FQPA SF = 1X 

LOC for MOE 

Residential = 100 

Occupation = 100

30-Day Inhalation – Rat 

LOAEL = 0.783 mg/kg/day 

Based on: Increased incidence of dried red nasal discharge. 

Decreased body weight gain and albumin levels 

Cancer 

(Oral, Dermal, and 

Inhalation) 

Chemical classified as “Group E” 

Based on lack of evidence of carcinogenicity in male and female rats and male and female mice. 

For additional information see HIARC memorandum dated 22 June 1998. 

UF = Uncertainty Factor, UFDB = Uncertainty Factor in the database, FQPA SF = Special FQPA Safety Factor, 

NOAEL = No Observed Adverse Effect Level, LOAEL = Lowest Observed Adverse Effect Level, PAD = Population Adjusted Dose (a = acute, c = chronic), 

RfD = Reference Dose, MOE = Margin of Exposure, LOC = Level of Concern, N/A = Not Applicable 

Subchronic, Chronic, and Other Toxicity Profile of Pyridaben Technical. 

Guideline 

No. 

Study Type MRID No. (year) / Doses / Classification Results 

90-Day Oral 

Toxicity in 

Rodents 

(Rat) 

42680126 (1988) 

0, 30, 65, 155, 350 ppm 

M: 0, 2.3, 4.94, 11.55, 25.71 mg/kg/day 

F: 0, 2.64, 5.53, 12.84, 27.68 mg/kg/day 

Acceptable / Guideline 

NOAEL = M: 4.94, F: 2.64 mg/kg/day 

LOAEL = M: 11.55, F: 5.53 mg/kg/day 

Based on in M and F: Decreased body weight gain, food consumption, 

and food efficiency 

870.3100 

90-Day Oral 

Toxicity in 

Rodents 

(Mouse) 

43064101 (1988) 

0, 30, 90, 270, 810 ppm 

M: 0, 4.07, 13.02, 40.09, 119.2 mg/kg/day 

F: 0, 4.92, 14.65, 43.14, 124.6 mg/kg/day 

Acceptable / Guideline 

NOAEL = M: 4.07, F: 4.92 mg/kg/day 

LOAEL = M: 13.02, F: 14.65 mg/kg/day 

Based on in M and F: Decreased body weight gain 

42680127 (1989) 

0, 0.5, 1.0, 4.0, 16.0 mg/kg/day 

Acceptable / Guideline 

NOAEL = 1.0 mg/kg/day 

LOAEL = 4.0 mg/kg/day 

Based on in M and F: Decreased body weight gain and clinical signs 

such as ptyalism, emesis, soft stool/diarrhea and trembling 

870.3150 90-Day Oral 

Toxicity in 

Nonrodents 

(Dog) 

42680128 (1989) 

0, 2.4, 12, 60, 300 mg/kg/day 

Supplementary 

NOAEL = <2.4 mg/kg/day 

LOAEL = ≤2.4 mg/kg/day 

Based on decreased body weight gain 

Page 20 of 28 
Subchronic, Chronic, and Other Toxicity Profile of Pyridaben Technical. 

Guideline 

No. 

Study Type MRID No. (year) / Doses / Classification Results 

870.3200 21/28-Day 

Dermal Toxicity 

(Rat) 

42680130 (1992) 

0, 30, 100, 300, 1000 mg/kg/day 

Acceptable / Guideline 

Dermal 

NOAEL = >1000 mg/kg/day 

LOAEL = Not Established 

Systemic 

NOAEL = 100 mg/kg/day 

LOAEL = 300 mg/kg/day 

Based on F: Decrease in body weight 

870.3250 90-Day Dermal 

Toxicity 

N/A Study not available 

870.3465 30-Day Inhalation 

Toxicity 

(Rat) 

In place of: 

90-Day Inhalation 

Toxicity 

42680131 (1989) 

0, 0.00087, 0.003, 0.010 g/L 

Acceptable / Non-Guideline 

NOAEL = 0.00087 mg/L (0.227 mg/kg) 

LOAEL = 0.003 mg/L (0.783 mg/kg) 

Based on in M and F: Clinical signs of toxicity observed were dried red 

nasal discharge and increased yellow ano-genital staining and in F only: 

Decreased body weight and body weight gain 

870.3700a Prenatal 

Developmental in 

Rodents 

(Rat) 

42680139 (1988) 

0, 2.5, 5.7, 13.0, 30.0 mg/kg/day 

Acceptable / Guideline 

Maternal 

NOAEL = 4.7 mg/kg/day 

LOAEL = 13 mg/kg/day 

Based on decrease in body weight, body weight gain and food 

consumption 

Developmental 

NOAEL = 13 mg/kg/day 

LOAEL = 30 mg/kg/day 

Based on decrease in fetal weights and incomplete ossification in 

selected bones 

870.3700b Prenatal 

Developmental in 

Nonrodents 

(Rabbit) 

42680142 (1988) 

0, 1.5, 5, 15 mg/kg/day 

Acceptable / Guideline 

Maternal 

NOAEL = 5 mg/kg/day 

LOAEL = 15 mg/kg/day 

Based on decreases in body weight, body weight gain and food 

consumption, and abortions 

Developmental 

NOAEL = 5 mg/kg/day 

LOAEL = 15 mg/kg/day 

Based on an increase in abortions and an increase in the “12/13" and 

“13/13" ribs 

Page 21 of 28 
Subchronic, Chronic, and Other Toxicity Profile of Pyridaben Technical. 

Guideline 

No. 

Study Type MRID No. (year) / Doses / Classification Results 

Prenatal 

Development in 

Nonrodents 

[Dermal] 

(Rabbit); 

43680416 

0, 70, 170, 450 mg/kg/day 

Acceptable / Guideline 

Maternal 

Dermal 

NOAEL for dermal toxicity = not established 

LOAEL for dermal toxicity = 70 mg/kg/day 

Based on skin reactions. 

Systemic 

NOAEL = 70 mg/kg/day 

LOAEL = 170 mg/kg/day 

Based on body weight loss and decreased food consumption. 

Developmental 

NOAEL = 170 mg/kg/day 

LOAEL = 450 mg/kg/day 

Based on retarded fetal growth and increased incidence of incompletely 

ossified skulls 

870.3800 Reproduction and 

Fertility Effects 

(Rat) 

42680144 (1990) 

0, 10, 28, 80 ppm 

M: 0, 0.78, 2.20, 6.31 mg/kg/day 

F: 0, 0.94, 2.41, 7.82 mg/kg/day 

Acceptable / Guideline 

Parental 

NOAEL = M: 2.20, F: 2.41 mg/kg/day 

LOAEL = M: 6.31, F: 7.82 mg/kg/day 

Based on in M and F: Decreased body weight gain and food efficiency 

Reproductive 

NOAEL = M: 6.31, F: 7.82 mg/kg/day 

LOAEL = M: >6.31, F: >7.82 mg/kg/day 

Based on in M and F: No effect on reproductive parameters at the dose 

levels tested in this study 

Offspring 

NOAEL = M: 2.2, F: 2.41 mg/kg/day 

LOAEL = M: 6.31, F: 7.82 mg/kg/day 

Based on decreased pup body weights from PND 7-25 and decreased 

pup body weight gains throughout lactation 

42680134 (1990) 

0, 1.0, 4.0, 16.0, 32.0 mg/kg/day 

Acceptable / Guideline 

NOAEL = Not Established 

LOAEL = 1.0 mg/kg/day 

Based on in M and F: Clinical signs such as thinness, dehydration, 

diarrhea, food-like emesis, frothy emesis, soft stool, ptyalism and 

relaxed nictitans and in F only: Decreased body weight gain 

870.4100b Chronic toxicity 

(Dog) 

42680135 (1991) 

0, 0.5 mg/kg/day 

Acceptable / Guideline 

(with MRID# 42680134) 

NOAEL = Not Established 

LOAEL = 0.5 mg/kg/day 

Based on in M and F: Clinical signs of toxicity such as Ptyalism, 

emesis, soft stools and in F only: Decreased body weight gain 

870.4200b Carcinogenicity 

(Mouse) 

42680137 (1990) 

0, 2.5, 8, 25, 80 ppm 

M: 0, 0.27, 0.81, 2.78, 8.88 mg/kg/day 

F: 0, 0.29, 0.91, 2.78, 9.74 mg/kg/day 

Acceptable / Guideline 

NOAEL = M: 2.78, F: 2.78 mg/kg/day. 

LOAEL = M: 8.88, F: 9.74 mg/kg/day 

Based on in M and F: Decreased body weight gain and food efficiency 

and in M only: Changes in organ weights, and changes in 

histopathology 

No evidence of carcinogenicity 

Page 22 of 28 
Subchronic, Chronic, and Other Toxicity Profile of Pyridaben Technical. 

Guideline 

No. 

Study Type MRID No. (year) / Doses / Classification Results 

870.4300 Combined 

Chronic Toxicity/ 

Carcinogenicity 

(Rat) 

42680132 (1990) 

0, 4, 10, 28 120 ppm 

M: 0, 0.16, 0.4, 1.13, 5 mg/kg/day; 

F: 0, 0.2, 0.54, 1.6, 6.52 mg/kg/day 

Acceptable / Guideline 

NOAEL = M: 1.13, F: 1.6 mg/kg/day 

LOAEL = M: 5, F: 6.52 mg/kg/day 

Based on in M and F : Decreased body weight gain and in M only: 

Decreased ALT 

No evidence of carcinogenicity 

870.5100 Bacterial Reverse 

Mutation Test 

(Salmonella 

typhimurium, 

Escherichia coli) 

42680145 (1986) 

Series of doses ≤5000 μg/plate in presence 

or absence of S9 metabolic activation 

Acceptable / Guideline 

Negative in two independent bacterial/mammalian microsome reverse 

mutation assays 

870.5300 In vitro

Mammalian Cell 

Gene Mutation 

Test 

(Chinese Hamster 

V79 Cells) 

42680149 (1989) 

Series of test concentrations ≤50 μg/mL 

(limit solubility) in the presence or absence 

of S9 metabolic activation 

Unacceptable / Guideline 

Negative for inducing forward gene mutations at the HGPRT locus 

870.5375 In vitro

Mammalian 

Chromosome 

Aberration Test 

(Chinese Hamster 

Lung Cells) 

42680148 (1989) 

Series of doses ≤50 ug/mL in presence or 

absence of S9 metabolic activation 

Acceptable / Guideline 

Negative for inducing structural chromosome aberrations 

870.5395 Mammalian 

Erythrocyte 

Micronucleus Test 

(Mouse) 

42680147 (1988) 

Series of doses ≤ 140 mg/kg 

Acceptable / Guideline 

Negative micronucleus induction in the bone marrow cells 

870.5500 Bacterial DNA 

Damage or Repair 

Tests 

(Escherichia coli) 

42680146 (1986) 

Series of doses ≤10000 ug/mL in presence 

or absence of S9 metabolic activation 

Acceptable / Guideline 

Negative for inducing primary DNA damage in Escherichia coli repair 

deficient strains WP 67 or CM871. 

Cytotoxicity was not demonstrated for the DNA competent strain 

(WP2) or the DNA deficient strains at any dose. 

870.6200a Acute 

Neurotoxicity 

Screening Battery 

(Rat) 

43680412 (1995) 

Nominal Doses 

0, 50, 100, 200 mg/kg 

Actual Doses 

M: 0, 44.3, 79.6, 190 mg/kg

F: 0, 44.5, 99.7, 190 mg/kg 

Acceptable / Guideline 

NOAEL = 50 mg/kg 

M: 44.3, F: 44.5 mg/kg 

LOAEL = 100 mg/kg 

M: 79.6, F: 99.7 mg/kg 

Based on in M and F: Clinical signs of toxicity (piloerection, 

hypoactivity, tremors, and partially closed eyes), and decreased food 

consumption and body weight gain 

870.6200b Subchronic 

Neurotoxicity 

Screening Battery 

(Rat) 

43680413 (1995) 

0, 30, 100, 350 ppm 

M: 0, 2.5, 8.5, 28.8 mg/kg 

F: 0, 2.8, 9.3, 31.1 mg/kg 

Acceptable / Guideline 

NOAEL = M: 8.5, F: 9.3 mg/kg/day 

LOAEL = M: 28.8, F: 31.1 mg/kg/day 

Based on in M and F: Decreases in body weight, body weight gain, 

food consumption and food efficiency 

Page 23 of 28 
Subchronic, Chronic, and Other Toxicity Profile of Pyridaben Technical. 

Guideline 

No. 

Study Type MRID No. (year) / Doses / Classification Results 

870.6300 Developmental 

Neurotoxicity 

N/A Study Is Not Required. 

Amendment to HED Human Health Risk Assessment: Pyridaben in/on 

Hops (PP#1E06226), Tropical Fruit (PP#3E06460), Strawberries 

(PP#0E06068), Stone Fruit (PP#2E06303), and Tomatoes 

(PP#1E06303) 

“Further evaluation of the toxicity database and the entire weight of 

evidence has lead to the conclusion that the FQPA Safety Factor be 

reduced to 1X and a developmental neurotoxicity study not be 

required.” 

870.7485 Metabolism and 

Pharmacokinetics 

(Rat) 

43258901 (1994) 

Single Dose: 3, 30 mg/kg 

14 Doses (1 Dose per Day): 3 mg/kg/day 

Acceptable / Guideline 

Absorption of an oral dose of NC-129 was fairly rapid but incomplete 

at all dose levels. The presence of a significant percentage of excreted 

radioactivityin bile at the high dose (20-30%) indicates that some of the 

absorbed test material was excreted by this route and/or reabsorbed 

from the intestinal tract for subsequent biliary elimination. 

The gastrointestinal tract was a major site for distribution. 

Metabolism 

Urinary, fecal and liver metabolites of 14-C-NC-129 were isolated and 

identified. At the low dose, the main urinary component from 

administration of Pz-labeled test material was the P-9 metabolite or 

mercapturic acid conjugate of pyridazinone moiety. The B-11 and B15 metabolites were the main components in urine after administration 

of Bz-labeled test material. In feces, the main component observed 

after administration of both the Pz- and Bz-labeled test material and 

representing approximately 20% of the dose, was unmetabolized parent 

compound. Some evidence of gluduronide conjugates of NC-19 was 

observed for bilary metabolites, but no definitive characterization could 

be performed. The liver contained several metabolites from 

adinistration of either Pz- or Bz-labeled test material, but these 

comprised 1.6% or less of the dose. 

Elimination 

Feces were the major route for elimination, 80-97% AD, across all dose 

groups for both labels. At the high dose, it seems that some of the dose 

(20-30% AD) was excreted through the biliary elimination. 

870.7800 Immunotoxicity N/A Study Is Required But Not Available 

Page 24 of 28 
Attachment 5: Occupational Exposure Tables 

Occupational Mixer/Loader and Applicator Exposure Scenarios for Registered Uses of Pyridaben 

Crop/Use Site Application 

Equipment 

Assessed 

Possible 

Application 

Types 

Formulation 

Types 

Risk 

Assessment 

Needed 

Notes 

Citrus Hand-gun, 

airblast, 

groundboom 

Hand-gun, 

airblast, 

groundboom 

WP in Water 

Soluble Bags 

No N/A 

Ornamentals N/A Ground 

Equipment 

WP in Water 

Soluble Bags 

Yes No prior risk assessment completed 

Almond* Hand-gun, 

airblast, 

groundboom 

Hand-gun, 

airblast, 

groundboom 

WP in Water 

Soluble Bags 

and Aqueous 

Solution 

Yes Assessed 30 acres treated in 1999, however 

using crop specific estimates of farm size. 

Also used larger unit exposures, and will 

therefore result in lower MOEs. Assessment 

needed for liquid formulation 

Apple Hand-gun, 

airblast, 

groundboom 

Hand-gun, 

airblast, 

groundboom 

WP in Water 

Soluble Bags 

No 

 

N/A 

Cherry** Hand-gun, 

airblast, 

groundboom 

Hand-gun, 

airblast, 

groundboom 

WP in Water 

Soluble Bags 

and Aqueous 

Solution 

Yes Assessment needed for liquid formulation 

Cranberry Hand-gun, 

airblast, 

groundboom 

Hand-gun, 

airblast, 

groundboom also 

chemigation 

WP in Water 

Soluble Bags 

Yes Assessment needed for chemigation 

application (M/L only) 

Grapes Hand-gun, 

airblast, 

groundboom 

Hand-gun, 

airblast, 

groundboom 

WP in Water 

Soluble Bags 

No 

 

N/A 

Pear Hand-gun, 

airblast, 

groundboom 

Hand-gun, 

airblast, 

groundboom 

WP in Water 

Soluble Bags 

No 

 

N/A 

Pistachio Hand-gun, 

airblast, 

groundboom 

Hand-gun, 

airblast, 

groundboom 

WP in Water 

Soluble Bags 

and Aqueous 

Solution 

Yes Assessment needed for liquid formulation 

Tomato (Greenhouse) M/L high pressure 

handwand, M/L 

airblast, M/L 

groundboom, A 

high pressure 

handwand, A 

airblast, A, 

groundboom 

M/L high pressure 

handwand, M/L 

airblast, M/L 

groundboom, A 

high pressure 

handwand, A 

airblast, A, 

groundboom 

WP in Water 

Soluble Bags 

Yes PHED unit exposure for "high pressure 

handwand" was used because it most closely 

matched the"handgun" scenario for 

pyridaben application to greenhouse 

tomatoes and was therefore used 

6 oz per 100 gal listed on the label. 21.3 oz 

= 1.0 lb ai from master label. 6.0oz max 

single application rate listed on this label = 

0.28 lb ai/acre, did not assess M/L/A 

*Representative of the tree-nut crop group, includes Almond, Beech Nut, Brazil Nut, Butternut, Cashew, Chestnut, Chinquapin, Filbert (hazelnut), 

Hickory Nut, Macadamia Nut, Pecan, Walnut 

**Representative of stone fruits group, including apricot, cherry (sweet and tart), nectarine, peach, plum, plumcot, and prune (fresh) 

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Summaries of Occupational Post Application Risk of Pyridaben by Use Site 

Crop/Use Site DP#, Date Maximum 

Transfer 

Coefficient 

DFR 

(μg/cm2) 

MOE Maximum REI required 

(italic is California-Specific)

Citrus 261499, 1999 10,000 0.865 100 5 days 

Ornamentals N/A N/A N/A N/A N/A 

Almond* 261499, 1999 10,000 0.867 100 10 days for hand/manual activities 

Apple 261499, 1999 10,000 0.865 100 5 days 

261499, 1999 10,000 0.865 100 5 days 

Cherry** 

261499, 1999 3,000 1.11 260 5 days 

Cranberry 261499, 1999 4,000 0.267 200 12 hours 

Grapes 261499, 1999 15,000 0.58 100 13 days 

Pear 261499, 1999 10,000 0.865 100 5 days 

Pistachio 261499, 1999 10,000 0.867 100 10 days for hand/manual activities 

Tomato 

(Greenhouse) 

261499, 2003 1,000 1.11 790 12 h 

*Representative of the tree-nut crop group, includes Almond, Beech Nut, Brazil Nut, Butternut, Cashew, Chestnut, Chinquapin, Filbert 

(hazelnut), Hickory Nut, Macadamia Nut, Pecan, Walnut 

**Representative of stone fruits group, including aprictot, cherry (sweet and tart), nectarine, peach, plum, plumcot, and prune (fresh) 
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Summary of Representative Occupational Handler Exposure Scenarios and Risks for Pyridaben (all using Water Soluble Bag

Unit Exposure (mg/lb ai)1 Dose (mg/kg/day)2 Short/Intermediate Te

Risk (MOE)3

Exposure 

Scenario 

Assessed 

DP# Maximum 

Application 

Rate Assessed 

Acres 

Treated 

(acres/day) Dermal Inhalation Dermal Inhalation Dermal Inhala

Mixer/Loader 

WP for 

handgun 

sprayer 

D261499, 

11/30/99 

0.5 10 0.0098 0.00024 0.0007 0.000017 140,000 15,0

WP for Airblast 

sprayer 

D261499, 

11/30/99 

0.5 40 0.0098 0.00024 0.0028 0.000069 36,000 3,8

WP for 

Groundboom 

D261499, 

11/30/99 

0.5 80 0.0098 0.00024 0.0056 0.00014 18,000 1,9

WP for High 

Pressure 

Handwand 

D261499, 

9/11/03 

0.19 1000 

gallons 

0.0098 0.00024 0.00027 0.0000065 370,000 40,0

Applicator 

Hand Gun 

Sprayer5

D261499, 

11/30/99 

0.5 10 1.3 0.0039 0.093 0.00028 1,100 93

Application 

AirBlast Open 

Cab 

D261499, 

11/30/99 

0.5 80 0.36 0.0045 0.103 0.0013 970 20

Groundboom 

Sprayer (open 

cab) 

D261499, 

11/30/99 

0.5 80 0.017 0.00074 0.008 0.00042 12,500 62

High Pressure 

Handwand6

D261499, 

19/11/2003 

0.19 1000 

gallons 

1.8 0.079 0.049 0.0021 2,000 12

Groundboom 

Sprayer (open 

cab) 

D261499, 

19/11/2003 

0.5 80 0.014 0.00074 0.008 0.00042 12,500 62

1 Unless otherwise specified, unit exposure values are for workers wearing baseline clothing, (i.e., long-sleeved shirt, long pants, shoes and socks) 2 Daily Dose =[Application Rate (lb ai/A) x Acres Treated (A/day) x Unit Exposure(mg/lb ai handled)]/Body Weight 3 MOE = NOAEL/Daily Dose. Short and Intermediate-term Dermal NOAEL=100 mg/kg/day. Short and Intermediate-term Inhalation NOAEL=0.261 mg/kg/day4 Total Risk MOE = 1/(1/MOEdermal + 1/MOEinhalation) 5 PHED unit exposure for "right-of-way sprayer" most closely matches the hand gun scenario for pyridaben application and is therefore used here. 6 PHED unit exposure for "high-pressure handwand" most closely matches the "hand-gun" scenario for pyridaben application on greenhouse tomatoes, and is therefore 
Attachment 6: Data Call-In Table 

Guideline Number: 870.7800 

Study Title: Immunotoxicity

Rationale for Requiring the Data 

This is a new data requirement under 40 CFR Part 158 as a part of the data requirements for registration of a 

pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional immunotoxicity testing and is 

designed to evaluate the potential of a repeated chemical exposure to produce adverse effects (i.e., suppression) on 

the immune system. Immunosuppression is a deficit in the ability of the immune system to respond to a challenge of 

bacterial or viral infections such as tuberculosis (TB), Severe Acquired Respiratory Syndrome (SARS), or 

neoplasia. Because the immune system is highly complex, studies assessing functional immunotoxic endpoints are 

helpful in fully characterizing a pesticide’s potential immunotoxicity. These data will be used in combination with 

data from hematology, lymphoid organ weights, and histopathology in routine chronic or subchronic toxicity studies 

to characterize potential immunotoxic effects. 

Practical Utility of the Data 

How will the data be used? 

These animal studies can be used to select endpoints and doses for use in risk assessment of all exposure scenarios 

and are considered a primary data source for reliable reference dose calculation. For example, animal studies have 

demonstrated that immunotoxicity in rodents is one of the more sensitive manifestations of TCDD (2,3,7,8-

tetrachlorodibenzo-p-dioxin) among developmental, reproductive, and endocrinologic toxicities. Additionally, the 

EPA has established an oral reference dose (RfD) for tributyltin oxide (TBTO) based on observed immunotoxicity 

in animal studies (IRIS, 1997). 

How could the data impact the Agency's future decision-making? 

If the immunotoxicity study shows that the test material poses either a greater or a diminished risk than that given in 

the interim decision’s conclusion, the risk assessments for the test material may need to be revised to reflect the 

magnitude of potential risk derived from the new data. 

 

If the Agency does not have this data, a 10X database uncertainty factor may be applied for conducting a risk 

assessment from the available studies. 

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