UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 2046 

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

March 27,2011 

MEMORANDUM 

SUBJECT: Pine Oil: Human Health Risk Assessment Scoping Document in 

Support of Registration Review 

PC Code(s): 067002 DP Barcode(s)/No(s): 395374 

Decision No.: 456733 Registration Numbers: Multiple 

Petition No(s).: NA Regulatory Action: Human Health Registration Review 

Risk Assess Type: Single Chemical Case No(s).: 3113 

TXRNo.:NA CAS No(s): 8002-09-3 

MRID No(s).: NA 40 CFR: None 

FROM: Nathan Mottl, Biologist V~ ~ Talia Lindheimer, Chemist 

Michelle Centra, Pharmacologist 

Risk Assessment and Science Support Branch (RASSB) 

Antimicrobials Division (751 OP) 

TO: Rebecca von dem Hagen, Chemical Review Manager 

Regulatory Management Branch II 

Antimicrobials Division (751 OP) 

THRU: Timothy Leighton, Senior Scientist « ~ I 

Nader Elkassabany, Branch Chief ---7 I~ Risk Assessment and Science Support Branch (RASSB) 

Antimicrobials Division (751 OP) 

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EXECUTIVE SUMMARY 

 The Antimicrobials Division (AD) Registration Review Team has evaluated the status 

of the human health assessments for pine oil (Reregistration Review case 3113 and PC 

code 067002) (D395481 and D395482). The first pine oil registration was issued in 

December, 1947. A Reregistration Eligibility Decision (RED) document was issued for 

pine oil in 2006 (USEPA, 2006a). Toxicological end-points were identified, and a human 

health assessment (dietary, residential and occupational) was conducted for the RED. New 

toxicity and exposure study data have not been received since issuance of the RED. The 

Agency anticipates reviewing any data received in response to the RED as well as data 

requested in this registration review prior to conducting the registration review 

assessments for pine oil. 

The purpose of this document is to determine whether sufficient data are available to 

support registration review, report on whether past risk assessments are still applicable and 

adequate and to report whether new human health assessments are needed to support the 

registration review process. Toxicological end-points were identified, and a human health 

assessment (dietary, residential and occupational) was conducted during the reregistration 

process. 

 Currently there are 57 active pine oil registrations (6 technical products) registered 

under Section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Pine 

Oil (1-Methyl-4-isopropyl-1-cyclo-hexen-8-ol) is approved for use as an antimicrobial 

sanitizer, fungicide, mildewstat, deodorizer, disinfectant, virucide, and 

microbicide/microbistat to control animal pathogenic bacteria, ammonia producing 

bacteria, fungi, viruses and mold. 

 Pine oil-containing products include many use sites, such as eating establishments, 

food processing plants, commercial/institutional/industrial premises and equipment, 

household or domestic dwellings and contents, and medical sites. The active ingredient 

pine oil (PC Code 067002) is a mixture of terpenes produced by high temperature 

distillation of oil of turpentine or by catalytic hydration of terpenes that forms a sole active 

ingredient containing no impurities. End use products are formulated as soluble 

concentrates, ready to use liquid solutions, and pressurized sprays. 

Examples of some use sites where products containing pine oil may be used 

includes; but is not limited to: agricultural premises, food processing facilities, restaurants, 

schools, daycare centers, office buildings medical institutions, nursing homes, hospitals, 

and in the home. Surfaces treated with these products include; but are not limited to: 

floors, walls, sinks, countertops, textiles (laundering and soaking of diapers, baby 

clothing, adult clothing, etc), and other non porous surfaces (e.g. children’s toys). One 

label includes the use of this pine oil-containing product in dog baths. This use will not be 

assessed as a part of registration review because it is expected to be removed from the 

label. In the event it is not removed from the label, then it will need to be assessed as a 

conventional use pesticide. 

 The Agency anticipates that new toxicological end-points will need to be selected and 

new human health assessments will need to be conducted. The specific exposure 
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scenarios the Agency anticipates assessing is presented in Tables 4 through 6 and the 

anticipated data need are outlined in Section 10. New risk assessments for registration 

review will address the following exposures: 

 Dietary (indirect food), 

 Residential applicator, 

 Residential post application, 

 Aggregate, 

 Occupational handler, and 

 Occupational post application. 

Section 1. Chemical Identity 

 Pine Oil is a blend of chemicals that together, range in appearance from a colorless 

liquid to a pale yellow liquid. Pine Oil is a liquid at 25oC that is insoluble in water, but 

soluble in organic solvents such as toluene and isopropyl alcohol. The density is 7.94 

lb/gal (0.952 g/cm3

) at 20oC and has a molecular weight of 154.0 g/mole. The vapor 

pressure is 1.27 torr at 25o

C and the boiling point is 208oC (D248587). 

Table 1. Chemical Identity and Properties 

Common 

Name 

Pine Oil 

CAS name Pine Oil 

PC Code 067002 

CAS registry 

number 

8002-09-3 

Registration 

Review Case 

No. 

3113 

Structure 

Section 2. Toxicology 

Acute Toxicity 

 In acute toxicity studies, pine oil has been shown to have low toxicity by the oral route 

(Toxicity Category III), dermal route (Toxicity Category III) and inhalation route 

(Toxicity Category IV). Pine oil is a moderate skin irritant (Toxicity Category III), but 

shows a stronger response as an eye irritant (Toxicity Category II). The available dermal 

sensitization assay conducted with pine oil is considered unacceptable because an 

inadequate number of animals were used to make a determination of sensitization and 

positive controls were not tested in this study. The pine oil RED, published in 2006, 

identified the dermal (skin) sensitization study (OPPTS 870.2600) as a data gap. Acute 

toxicity for pine oil is presented below in Table 2. 

 
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Table 2. Acute Toxicity Data for Pine Oil Technical Grade Active Ingredient (97.9-100%)

Guideline Number

Study Type

MRID 

Number Results Toxicity 

Category

870.1100 Acute oral toxicity 40253502 LD50(males) = 3100 mg/kg 

LD50(females) = 2100 mg/kg 

LD50(combined) = 2700 mg/kg (M+F) 

III 

870.1200 Acute dermal toxicity 40253503 LD50 > 2000 mg/kg (M and F) III 

870.1300 Acute inhalation toxicity 43375208 LC50 > 3.67 mg/L IV 

870.2400 Acute eye irritation 43375209 Moderate irritation (corneal opacity,iritis, 

conjuctival irritation up to 16 days postapplication) 

II 

870.2500 Acute dermal irritation 43375210 Slight irritation (erythema up to 7 days, 

edema up to 4 days post-application) III 

870.2600 Skin sensitization 43375211 Unacceptable Study NA 

M = males; F = females; NA = not applicable 

Subchronic Toxicity 

 The database for subchronic toxicity of pine oil consists of a 90-day dermal toxicity 

study in rats. Included in this study is a 14-day dose range-finding study that was used to 

establish doses for the main study. 

 In the 90-day dermal toxicity study (MRID 40515401) conducted in the rat, pine oil 

(blend 1687) applied to the skin at doses of 0, 50, 113 or 226 mg/kg/day produced no 

systemic, treatment-related effects on mortality, clinical signs, body weight, food 

consumption, hematology, clinical chemistry, organ weights or gross pathology. 

Although dermal irritation was observed in this study, the incidence and severity of 

erythemia, desquamation and scabbing was not observed consistently within groups of 

treated rats and did not appear to be dose-related. For microscopic dermal changes, 

acanthosis and hyperkeratosis observed in rats treated with 226 mg/kg/day pine oil had 

similar incidences when compared with control animals. An accurate determination of a 

NOAEL in this 90-day dermal study was further complicated by use of a non-guideline 

dosing methodology and omission of some essential data, specific organ weights, clinical 

chemistries and hematology parameters. However, when tested over a broader dose range 

(47, 235, 470, 940, 3,760 or 7,520 mg/kg/day) using similar (non-guideline) testing 

methodologies for 14 days, dermal application of pine oil resulted in dose-related 

increases in incidence and severity of dermal irritation from 47 to 7,520 mg/kg/day as well 

as systemic decreases in mean body weight, mean body weight gain and food 

consumption at 3,760 mg/kg/day. These dose-range finding data suggest that the systemic 

toxicity NOAEL is less than or equal to 940 mg/kg/day, a dose close to the test limit dose 

(1,000 mg/kg/day). Considering the systemic toxicity and dermal irritation results of the 

90-day and 14-day dermal studies, a conservative systemic toxicity NOAEL of 226 

mg/kg/day was approximated for the 90-day dermal toxicity study (acceptable/nonguideline) and subsequently used in assessing risks from potential dermal exposures to 

pine oil. 
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 Subchronic toxicity testing of pine oil via other routes of exposure remains inadequate. 

No studies are available which address potential subchronic toxicity via the oral or 

inhalation routes from the indirect food and non-food uses of pine oil-containing pesticide 

products. 

 In the RED, the Agency held the requirement for a subchronic oral toxicity study (with 

additional neurotoxicity evaluations) in reserve pending submission of food residue data. 

In the absence of additional data that addresses the potential presence of pine oil in foods 

from the cleaning of countertops and other hard, non porous surfaces using currently 

registered products and the observation of neurotoxicity (ataxia, decreased motor control, 

impaired righting reflex prior to death) in the existing pine oil toxicity data base, the 

Agency is anticipating that a 90-day subchronic (oral) toxicity study (OPPTS 870.3100) as 

well as a 90-day (oral) neurotoxicity study (OPPTS 870.6200) will be needed to 

adequately characterize the hazard from potential oral exposures to pine oil (see 

Neurotoxicity). 

 

 For assessing potential inhalation exposures, a repeat-dose inhalation toxicity study is 

unavailable in the pine oil toxicity data base. Based on the use of pine oil 

disinfectant/cleaning products in occupational and residential settings via wiping, 

mopping, brushing, spraying, fogging, foaming and open pouring of these products or 

immersion into these products, the Agency is requiring a subchronic inhalation toxicity 

study (OPPTS 870.3465). The data/information from a subchronic inhalation toxicity 

study is critical for the proper characterization and quantification of hazard and risk to 

human health from potential inhalation exposures to pine oil. 

 

Prenatal Developmental Toxicity 

 In a prenatal developmental toxicity study in rats (MRID 40515201), dams were 

administered pine oil via gavage at dose levels of 0, 50, 600, or 1200 mg/kg/day from days 

6-15 of gestation. Maternal toxicity in the form of excess salivation, alopecia, and 

ungroomed coat as well as decreases in food consumption, body weight and body weight 

gain were observed at doses of 600 and 1,200 mg/kg/day. Mortality occurring in animals 

administered 1,200 mg/kg/day pine oil exhibited ataxia, decreased motor activity, and 

impaired righting reflex prior to death, raising the possibility of a neurotoxic effect. 

Further, increased adrenal gland weight was noted in dams administered 1,200 mg/kg/day. 

The maternal toxicity NOAEL established in this study is 50 mg/kg/day based on clinical 

observations, decreased body weight, body weight gain and food consumption observed at 

the LOAEL of 600 mg/kg/day. Dams treated with 600 and 1,200 mg/kg/day pine oil 

produced fetuses with decreased body weights in males only and both sexes, respectively. 

Fetal malformations, which included small eye orbit, microphthalmia, and depressed eye 

bulge, were reported in the 1,200 mg/kg/day dosage group. Additionally, skeletal 

examination showed increased fetal and litter incidence of non-ossified or incompletely 

ossified skull, vertebrae, manubrium, sternebrae, and pelvis while visceral examination 

showed dilation of the lateral ventricles (possible delayed brain growth) at 1,200 

mg/kg/day. The developmental toxicity NOAEL established for this study is 50 mg/kg/day 

based on decreased fetal weight, increased incidences of fetal malformations and delayed 

ossifications observed at the LOAEL of 600 mg/kg/day. This study is classified 
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acceptable-guideline for a prenatal developmental toxicity study in rats [OPPTS 870.3700; 

OECD 414] and is adequate for risk assessment purposes. 

Reproduction and Fertility Effects Toxicity 

 Although the Agency’s earlier decision (reregistration eligibility decision; RED, 2006) 

held the requirement of a two-generation reproduction and fertility effects study for pine 

oil in reserve, reproductive toxicity data is not part of the required Tier 1 toxicity testing to 

support registration of pine oil pesticide products. Consequently, a reproduction and 

fertility effects study conducted with pine oil is not required at this time. 

Chronic Toxicity 

 Chronic toxicity data are not required at this time since there are no chronic exposures 

based on the current labeled use patterns for pine oil. 

Carcinogenicity 

 Pine oil has not been classified as to its carcinogenicity. However, carcinogenicity data 

are not part of the required Tier 1 testing to support registration of pine oil pesticide 

products and therefore, are not required at this time. 

Mutagenicity 

 Acceptable mutagenicity studies including a reverse gene mutation (Ames) assay, a 

mouse micronucleus assay and an unscheduled DNA synthesis assay were conducted with 

either pine oil blend 012494 or 1687. No mutagenic or genotoxic responses were 

observed in these studies. In an in vitro mammalian cell gene mutation test, a negative 

mutagenic response was also observed for this chemical; however, this study was deemed 

unacceptable due to problems with the integrity (contamination) of the cell cultures. 

According to the pine oil RED published in 2006, an in vitro mammalian chromosome 

aberration test was identified as a data gap. The existing mutagenicity battery and description 

of test results for pine oil is presented below in Table 3. 

Table 3. Mutagenicity Battery Studies for Pine Oil 

Guideline, Study Type

MRID/Classification

Description of Results

870.5100 (84-2) Reverse Bacterial Gene 

Mutation (Ames) Assay 

MRID 43375212 

Classification: Acceptable

Pine Oil Blend 012494 showed no evidence of a mutagenic effect 

(no increase in induced mutant colonies over background) at 

concentrations of 0.1, 1.0, 100, 1000, or 10000 μg/plate using S. 

typhimurium strains TA 98, 100, 1535 and 1537 with or without 

metabolic activation. 
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870.5300 (84-2) In vitro Mammalian Cell 

Gene Mutation Test 

MRID 40341402 

Classification: Unacceptable

Pine Oil Blend 1687 showed no evidence of genotoxicity (increase 

of induction of mutant colonies over background) in Chinese 

Hamster Ovary (CHO) cells exposed at concentration of 100, 130, 

170, 200 or 250 nl/ml (-S9 activation) and 50, 100, 200, 300 or 400 

nl/ml (+S9 activation). This study is classified unacceptable 

because mycoplasm contamination was not monitored and several 

cultures were lost due to contamination during conduct of the 

assay. 

870.5395 (84-2) Mammalian Erythrocyte 

Micronucleus Test 

MRID 403414403 

Classification: Acceptable

Pine Oil Blend 1687 is not mutagenic since it did not cause a 

significant increase in micronucleated polychromatic erythrocytes 

when administered via single i.p. injection to mice at doses of 116, 

578 or 1155 mg/kg, in the presence or absence of metabolic 

activation. 

870. 5550 (84-2) Unscheduled DNA 

Synthesis in Rat Primary Hepatocytes with 

a Confirmatory Assay 

MRID 40341404 

Classification: Acceptable

Pine Oil Blend CSMA 1687 did not indicate a positive mutagenic 

response (no significant increase in net nuclear grain counts of rat 

primary hepatocytes) at dose levels up to and including 0.03 μg/ml. 

Dose levels tested above 0.03 μg/ml were found to be cytotoxic. 

Neurotoxicity 

Based on the absence of oral subchronic toxicity data and the observation of potential 

neurotoxic effects (ataxia, decreased motor control, impaired righting reflex prior to death) 

in the rat prenatal toxicity study, the Agency held a subchronic oral toxicity study (with 

additional neurotoxicity evaluations) in reserve pending submission of food residue data 

(Pine Oil RED, 2005). However, no data have been submitted which address the potential 

presence of pine oil in foods that may occur following use (indirect-food) of registered 

pesticide products containing pine oil. Consequently, the data base for neurotoxicity 

remains incomplete. A 90-day oral neurotoxicity study is anticipated as needed to 

properly characterize potential neurotoxic risks from repeat oral exposures to pine oilcontaining products (see Subchronic Toxicity). 

Dermal Penetration 

 Dermal penetration data are not required at this time. 

Metabolism and Pharmacokinetics 

 Metabolism and pharmacokinetic data are not required at this time. 

Toxicity Endpoint Selection for Human Health Assessments 

 On February 24, 2004, the Antimicrobials Division’s Toxicity Endpoint Selection 

Committee (ADTC) reviewed the available toxicology data for pine oil and considered 

toxicological doses and endpoints for use as appropriate in acute dietary (general 

population and females 13+ RfDs) and chronic dietary (RfD) exposure scenarios as well 

as toxicological doses, endpoints, data base uncertainty factors, FQPA safety factors and a 

target margin of exposure (MOE) for non-dietary, short-term/intermediate-term incidental 

oral (residential), short-term/intermediate-term dermal (occupational/residential) and 

short-term/intermediate-term inhalation (occupational/residential) exposure scenarios. For 
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a detailed summary, see Antimicrobials Division’s Toxicity Endpoint Selection 

Committee (ADTC) report for pine oil. 

 However, the existing doses, endpoints, data base uncertainty factors, FQPA safety 

factor and target MOEs are subject to reevaluation during registration review including 

any new toxicity data via future submissions/literature publications which may become 

available for pine oil. 

Section 3. Dietary Assessment 

Dietary Exposure 

 As provided in the RED (USEPA, 2006a), the Antimicrobials Division (AD) 

considered potential dietary exposures to pine oil residues in food (see Table 4). Several 

registered product labels exist in which pine oil is used as a disinfectant in restaurants, 

kitchens, cafeteria, food storage areas, counter tops, stove tops, drain boards, microwaves, 

food processing plants, and picnic tables. The Agency has relied on conservative 

assumptions and methodologies developed by the Food and Drug Administration (FDA) 

to estimate dietary exposures resulting from the indirect food contact uses of pine oil, 

however, to include the additional data required as a part of registration review, a dietary 

assessment will need to be completed. 

 Pine oil is exempt from the requirement of a tolerance under 40 CFR 180.1035 for use in 

honey and beeswax. Currently there are no registered products for this use; therefore, as 

recommended in the RED, the Agency is upholding the recommendation that this tolerance is 

revoked as a part of registration review. 

Drinking Water Exposure 

All registered uses of pine oil are indoors and are not likely to contaminate surface 

or ground water. In the event that pine oil is released into a waste stream (chemically, 

pine oil consists mainly of cyclic trepan alcohols but also contains terpene hydrocarbons, 

ethers, and esters), its constituents are expected to volatilize rapidly from surface water, 

are highly biodegradable, have short half-lives in water, and have low mobility in soils. 

Hence, as concluded in the RED, there is low probability of surface or ground water 

contamination and a drinking water assessment is not needed (USEPA, 2006a). 

Table 4: Dietary Use Patterns for Pine Oil

Scenario Use Patterns Route of Exposure

Dietary Exposure

Cleaning of countertops and other hard non 

porous surfaces in eating areas*

Food Processing Facilities 

Beverage Processing Facilities

Ingestion of residues

*Utensils and glassware are restricted from being cleaned with pine oil products. 
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Section 4. Residential Handler and Post Application Exposure and Risk 

Pine oil, found in many residential-use products, is used as a cleaner, disinfectant, 

sanitizer, fungicide, mildewstat, and deodorizer. The handler scenarios used in the past 

residential exposure assessment were selected to encompass multiple uses, and at the same 

time, represent high end exposures. The two uses assessed included the handling of liquid 

general purpose cleaners (via the methods of mopping and wiping) and dog wash use for 

the dermal (intermediate-term only) and inhalation routes. The dog wash use will not be 

assessed as a part of registration review because it is expected to be removed from the 

label. In the event it is not removed from the label, then it will need to be assessed as a 

conventional use pesticide. 

Short-term handler exposures via the dermal and inhalation (to both aerosol and vapor) 

routes will need to be assessed for the scenarios that were considered in the RED along 

with additional use patterns that were not included (identified in Table 5). As provided in 

the RED, there are also uncertainties associated with the surrogate databases that were 

utilized in completing the assessment. For all of the aforementioned reasons, an updated 

residential handler exposure assessment will be required for registration review. 

Table 5: Summary of Use Patterns for Pine Oil

Scenario Use Patterns Route of Exposure

Residential Handler

Residential homeowner cleaning with a 

product containing pine oil via:

Wiping

Mopping

Trigger Pump Spray

Liquid Open Pour

Low Pressure Spray

Brush 

Immersion

Dermal

Inhalation (aerosol and vapor) b

Residential Post 

Application

Children crawling on cleaned floors 

Children mouthing cleaned toys

Adult and Children Laundered Clothing

Adult and Children Pre-soaked Clothinga

Dermal

Inhalation (vapor) b

Incidental Oral

a The use of pre-soaking baby clothes and diapers does not indicate laundering. If the label, Reg. # 82771-1 

is revised to indicate laundering post-soaking, then an assessment of laundering with pine oil containing 

products will only be necessary. 

b

 The vapor pressure is 0.2 mm Hg at 20°C (USEPA, 2006a), which is greater than the EPA cutoff of E-4 

mmHg, therefore warranting an assessment of exposures to vapors. 
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The residential post-application scenario considered for the RED includes exposure to 

residue from hard surfaces (i.e., floors) that have been mopped with a product containing 

pine oil along with the laundering of clothing. The laundering of textiles and discussions 

of this use pattern are presented in an addendum to the RED (USEPA, 2006b). Pine oil 

has a relatively high vapor pressure (0.2 mmHg @ 20 C), such that there is concern for 

potential vapor inhalation exposure. 

Additional routes of post-application exposures have been identified upon review of 

the registered labels. There are also uncertainties associated with the assumptions used in 

the post-application assessment in support of the RED (i.e. percent transfer of residues 

from cleaned floor, leaching of pine oil from the laundered textiles, etc) that will need to 

be addressed. Upon a submission of the necessary information, a post application 

exposure assessment will be completed for registration review, as appropriate, additional 

scenarios will be incorporated into the revised aggregate assessment. 

Section 5. Aggregate Exposure and Risk 

A short-term aggregate assessment was not conducted in the pine oils RED since a 

short-term toxicological endpoint was not selected. For the RED, the adult exposures from 

dietary exposures and inhalation exposures resulting from mopping were aggregated, but 

omitted exposures resulting from wiping with hard surface cleaners. For exposures to 

toddlers, only the short-term incidental oral exposure resulting from cleaning floors with 

pine oil containing products (post application) were aggregated with dietary exposures. An 

intermediate term aggregate assessment will need to be considered as a part of registration 

review, as one was not completed for the RED. 

Upon a reevaluation and selection of toxicological endpoints, combined with the 

revised dietary and residential exposure assessment expected as a part of this registration 

review case, the aggregate assessment will need to be revised to include additional 

scenarios for the routes of dietary and residential exposures along with both the short- and 

intermediate-term durations. The values representing aggregate exposure and risks will 

need to be recalculated as a part of this registration review case. 

Section 6. Occupational Handler and Post Application Exposure and Risk 

 Short-term inhalation exposures and intermediate-term dermal and inhalation 

exposures from contact with pine oil were assessed for handling pine oil-containing 

cleaning products via low pressure spray, wiping, and mopping applications (USEPA, 

2006a). Post application exposures via the dermal and inhalation routes were deemed 

likely to be minimal when compared to handler exposure because of product dilution with 

water. Therefore, for the RED, a separate screening-level assessment was not conducted 

for occupational post application scenarios. 

 The occupational exposure assessment utilized surrogate databases, for which 

uncertainties have been identified. Also, upon a review of the registered labels, additional 

occupational scenarios were identified and will need to be assessed. Based on these 

conclusions, an occupational risk assessment will be required to support registration 

review. It also needs to be considered that based on a review of data that are submitted in 
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response to the RED and registration review of pine oil, assessment of post-application 

occupational exposures may become necessary. 

Table 6: Occupational Summary of Use Patterns for Pine Oil

Scenario Use Patterns Route of Exposure

Occupational Handler

Occupational (i.e. janitorial) worker cleaning 

with a product containing pine oil via:

Wiping

Mopping

Trigger Pump Spray

Liquid Open Pour

Low Pressure Spray

High Pressure Spray a

Coarse Mechanical Spray 

Brush

Immersion

Foaming Apparatus 

Fogging (wet misting) Systems

Dermal

Inhalation (aerosol and vapor) b

Bystander Exposure

Bystanders in the vicinity of an area that is 

being cleaned Inhalation (vapor) b

a

 EPA Reg. #4313-14 includes this use pattern for occupational handlers, and is not carried out by residential 

handlers; hence this is why the use pattern is not necessary to assessed for residential handlers.

b

 The vapor pressure is 0.2 mm Hg at 20°C (USEPA, 2006a), which is greater than the EPA cutoff of E-4 

mmHg, therefore warranting an assessment of exposures to vapors 

Section 7. Incidents 

There are 283 pine oil related human incidents that have been reported to the EPA’s 

Office of Pesticide Program’s Incident Database (IDS). Oral, dermal, inhalation, and 

ocular exposures have all been reported. 

 Ingestion of pine oil products is frequently reported. In IDS, there have been 13 

reported death incident cases as a result of ingestion of pine oil containing products (some 

ingestions may be due to pine oil’s pleasant aroma). The most common symptoms 

reported for oral exposure include: coughing, choking, vomiting, nausea, abdominal pain, 

shortness of breath, drowsiness, lethargy, and loss of consciousness. 

 The most common symptoms reported for cases involving dermal exposure were skin 

irritation/burning, rash, itching, skin discoloration/redness. Symptoms associated with 

allergic skin reactions include blisters, and hives. 

 The most common symptoms reported for cases involving inhalation exposure were 

coughing, choking, sneezing, respiratory irritation/burning, asthma/difficult breathing, 
Page 12 of 29 

shortness of breath, and respiratory depression. Reported incidents for inhalation also 

include headaches, shaking, numbness, drowsiness, lethargy and unconsciousness. 

 

 Ocular effects including eye irritation (burning and redness), corneal abrasion, eye 

swelling, eye discharge/infection and visual defect/blurred vision are common symptoms 

that have been reported with use of pine oil-containing products. 

Section 8. Cumulative 

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

on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity 

finding as to Pine Oil and any other substances and Pine Oil does not appear to produce a 

toxic metabolite produced by other substances. For the purposes of this action, therefore, 

EPA has not assumed that Pine Oil has a common mechanism of toxicity with other 

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

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

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

common mechanism determinations and procedures for cumulating effects from 

substances found to have a common mechanism on EPA’s website at 

http://www.epa.gov/pesticides/cumulative/.

Section 9. Endocrine Disruption 

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

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

subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include 

endpoints which may be susceptible to endocrine influence, including effects on endocrine 

target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, 

pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard 

assessments, EPA evaluates acute tests and chronic studies that assess growth, 

developmental and reproductive effects in different taxonomic groups. As part of the 

reregistration hazard assessment for Pine Oil, EPA reviewed these data and selected the 

most sensitive endpoints for relevant risk assessment scenarios from the existing hazard 

database. However, as required by FFDCA section 408(p), Pine Oil is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

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

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

an effect produced by a “naturally occurring estrogen, or other such endocrine effects as 

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

the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays 

to identify the potential of a chemical substance to interact with the estrogen, androgen, or 

thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and 

are found to have the potential to interact with E, A, or T hormonal systems will proceed 

to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests 

are necessary based on the available data. Tier 2 testing is designed to identify any adverse 
Page 13 of 29 

endocrine-related effects caused by the substance, and establish a dose-response 

relationship between the dose and the E, A, or T effect. 

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

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the 

first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert 

ingredients. Pine Oil is not among the group of 58 pesticide active ingredients on the 

initial list to be screened under the EDSP. Accordingly, as part of registration EPA will 

issue future EDSP orders/data call-ins, requiring the submission of EDSP screening assays 

for Pine Oil. 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/.review, 

Section 10. Conclusions 

a. Data Needs 

 The Antimicrobial Division (AD) anticipates requiring further exposure and 

toxicity studies will be required for registration review, as submission of these studies will 

permit an assessment of several residential and occupational handler and post 

application/bystander scenarios. Table 7 lists the toxicity data needs and the rationales for 

these data requirements. Appendix A provides the toxicity data justifications. Appendix B 

provides the dietary data justifications. Table 8 provides a summary of exposure scenarios 

and data needs. The exposure data justifications are provided in Appendix C. 

Table 7. Toxicity Studies Needed for Pine Oil Registration Review

Study Needed Guideline Rationale

90-Day Oral Toxicity 870.3100*

Pine oil disinfectant and cleaning products 

applied to hard, non-porous surfaces in 

occupational and residential settings may 

result in dietary (indirect food) exposures in 

children and adults and/or incidental oral 

(hand-to-mouth) exposures in children. The 

Agency is requiring a 90-day subchronic (oral) 

toxicity study because: (1) this study is a 

guideline required test under 40 CFR Part 158, 

(2) it is one of the Tier I mammalian toxicity 

data requirements for registration of indirect 

food-use pesticides, (3) the lack of routespecific, repeat-dose (oral) toxicity data 

precludes estimation of the magnitude of 

potential dietary risks to humans from 

indirect-food uses of pine oil products for 

disinfection/sanitization purposes in 

occupational and residential settings, (4) 

ingestion of pine oil products is the most 

frequently reported route of poisoning in 

humans, and (5) data from a subchronic (oral) 

toxicity study conducted with pine oil would 

provide a more complete characterization of 
Page 14 of 29 

overall mammalian toxicity and a better 

understanding of the effects of pine oil on 

human health.

90-Day Inhalation Toxicity 870.3465

Pine oil disinfectants and cleaning products 

are used in occupational and residential 

settings via wiping, mopping, brushing, 

spraying, fogging, foaming and liquid open 

pouring of these products or immersion into 

these products. A route-specific, subchronic 

toxicity study is critical for proper 

characterization and quantification of hazard 

and risk to human health from potential 

inhalation exposures to pine oil. Before 

initiating the study, registrants should consult 

with EPA to determine if the inhalation 

toxicity study should be based on vapors or 

aerosols. Worker exposure is likely to occur to 

both vapors and aerosols.

90-Day Oral Neurotoxicity 

(Subchronic; Neurotoxicity 

Screening Battery)

870.6200*

A 90-day subchronic (oral) neurotoxicity 

study for pine oil is required because (1) the 

existing chemical toxicity data base shows 

evidence of neurotoxicity as was noted in the 

acute oral, acute inhalation and the prenatal 

developmental toxicity studies, (2) other 

chemicals within the same class as the active 

ingredient (i.e., terpenoids) are known 

neurotoxic agents, (3) there is the potential for 

dietary exposures to children and adults from 

the indirect-food uses (application of pine oil 

disinfectants and cleaning products to hard, 

non-porous surfaces) of pine oil-containing 

pesticide products in occupational and 

residential settings, and (4) data obtained from 

a 90-day (oral) neurotoxicity study may 

provide critical scientific information 

(neurotoxic effects) via the oral route of 

exposure as well as a dose and toxicological 

endpoint of concern for quantification of risks 

from the indirect-food uses of pine oilcontaining pesticide products.

*The Agency will accept a combined 90-day oral and 90-day neurotoxicity study. The combined study 

would follow the 90-day (oral) subchronic toxicity guideline and incorporate additional neurotoxicity 

evaluations in the testing paradigm. For a combined study, it is recommended that a protocol be submitted 

to the Agency for review prior to initiation of the study. 

 
Page 15 of 29 

Table 8. Exposure Studies Needed for Pine Oil Registration Review 

Study Needed Guideline Rationale

Indoor Exposure (several 

routes of exposures in the 

indoor setting)

875.1200

875.1400

875.1600

875.2500

875.2800

Exposures via the dermal and inhalation 

routes may occur during the handling and 

application of pine oil containing products 

via open pouring of concentrate, wiping, 

mopping, trigger pump spray, low pressure 

spray, brushing, and immersion. 

Also based on the vapor pressure of this chemical 

there is concern for bystanders in the vicinity of a 

room that is being cleaned.

Surface Residue Dissipation 

(toys, textiles)

875.2300

875.2800

875.2900

Incidental oral exposures from hand to mouth 

activities may occur as a result of product 

application to surfaces (floors, toys)

Incidental oral and dermal exposures may occur 

from children wearing laundered or soaked items 

of clothing.

Nature of the Residue on 

Surfaces

Migration Study

No Guideline

Child and adult dietary exposures as a result of 

pine oil containing products being used to clean 

hard non porous surfaces in food settings such as 

kitchen countertops.

Product Use information & 

Description of Human 

Activity

875.1700

875.2700

875.2800

Use information and human activity will be 

useful when evaluating exposures and assist in 

the planning of exposure studies.

a. Label issues 

To reduce residential exposure, the Agency recommended in the RED that label 

mitigation language be added to limit the “full strength” rates (i.e., treatment solutions above 

0.31%) to a maximum dilution rate of 0.31%. It has been noted that some of the recent labels 

have not been changed to reflect the mitigation stated in the RED. 

Section 11. Reliance on Human Studies 

Past pine oil risk assessments have not relied to any extent on human studies. 

There is therefore no current need to address the scientific soundness, ethical 
Page 16 of 29 

acceptability, need for review by the Human Studies Review Board, etc. that are often 

required to utilize certain research involving intentional exposure of human subjects in an 

EPA risk assessment. 

Section 12. References 

USEPA, 2011. PINE OIL (1-Methyl-4-isopropyl-1-cyclo-hexen-8-ol): Revised 

Toxicology Hazard Characterization for the Human Health Assessment Scoping 

Document in Support of Registration Review of Pine Oil. Memorandum from M. Centra. 

March 16, 2012 

USEPA, 2011. PINE OIL (1-Methyl-4-isopropyl-1-cyclo-hexen-8-ol): Revised 

Toxicology Hazard Characterization for the Human Health Assessment Scoping 

Document in Support of Registration Review of Pine Oil. TXR 1003232. Memorandum 

from M. Centra. D395481. January 25, 2012 

USEPA, 2006a. Reregistration Eligibility Document for Pine Oil. Case 3113. September 

2006.

USEPA, 2006b. Addendum to Residential Occupational and Residential Exposure 

Assessment of Pine Oil for the Reregistration Eligibility Decision Document (RED). 

Memorandum from C. Walls. June 26, 2006. 

D395482. Memorandum from T. Lindheimer, Chemist to N. Mottl, Biologist. Subject: 

Summary of Dietary, Residential and Occupational Exposures for the Pine Oil 

Registration Review Scoping Document. January 20, 2012. 

D248587. Memorandum from C. Jiang, Chemist to Julie Fairfax, Product Manager, Team 

36. Subject: Review of Product Chemistry Package for the Pure Active Ingredients 

(PAI’s) for Pine Oil. October 1, 2007. 
Page 17 of 29 

Appendix A. Toxicity Data Justifications 

 
Page 18 of 29 

Guideline Number: 870.3100* 

Study Title: 90-Day Oral Toxicity 

Rationale for Requiring the Data 

The Agency is requiring a 90-day subchronic (oral) toxicity study because: (1) this study is a required test guideline 

under 40 CFR Part 158, (2) it is one of the Tier I mammalian toxicity data requirements for registration of indirect 

food-use pesticides, (3) the lack of route-specific, repeat-dose (oral) toxicity data precludes estimation of the 

magnitude of potential dietary risks to humans from indirect-food uses of pine oil products for 

disinfection/sanitization purposes in occupational and residential settings, (4) ingestion of pine oil products is the 

most frequently reported route of poisoning in humans, and (5) data from a subchronic (oral) toxicity study 

conducted with pine oil would provide a more complete characterization of overall mammalian toxicity and a better 

understanding of the effects of pine oil on human health. 

Practical Utility of the Data 

1. How will the data be used? 

The 90-day (oral) subchronic toxicity study is intended to provide critical scientific information (potential systemic 

toxicities) associated with repeated, route-specific (oral) exposures to pesticide products containing pine oil for a 

period of 90 days. Data obtained from a subchronic toxicity study conducted via the oral route of exposure may also 

provide a dose and a toxicological endpoint of concern for quantification of risks from the indirect food-uses of pine 

oil in occupational and residential settings. 

2. How could the data impact the Agency’s future decision-making?

The Agency could establish a dose and toxicological endpoint from this study that is more conservative than the 

doses/endpoints currently used to conduct quantitative risk assessments for pine oil. If used as the source of a dose 

and toxicological endpoint for route-specific (oral) risk calculations, these new data would provide an estimate of the 

magnitude of this potential risk as well as providing a more complete characterization of overall mammalian toxicity 

and a better understanding of the effects of pine oil on human health. 

*The Agency will accept a combined 90-day oral and 90-day neurotoxicity study. The combined study 

would follow the 90-day (oral) subchronic toxicity guideline and incorporate additional neurotoxicity 

evaluations in the testing paradigm. For a combined study, it is recommended that a protocol be submitted 

to the Agency for review prior to initiation of the study.

 
Page 19 of 29 

Guideline Number/Study Title: 

870.3465 90-Day Inhalation Toxicity

Rationale for Requiring the Data 

Although the inhalation route is one of the major routes of potential human exposure to pine oil for several 

occupational and residential handler scenarios, a repeat-dose inhalation toxicity study is not available in the pine oil 

toxicology data base. Based on the use of pine oil disinfectants and cleaning products in occupational and residential 

settings via wiping, mopping, brushing, spraying, fogging, foaming and liquid open pouring of these products or 

immersion into these products, a route-specific subchronic toxicity study is critical for proper characterization and 

quantification of hazard and risk to human health from inhalation exposures to pine oil. Therefore, the Agency is 

requiring a repeat-dose (subchronic) inhalation toxicity study conducted with the active ingredient, pine oil. 

Practical Utility of the Data 

1. How will the data be used? 

These data will allow the Agency to conclude more definitively whether or not there are any concerns for potential 

inhalation toxicity from the indirect food-uses and non-food uses of pine oil-containing pesticide products. This 

study may also provide a dose and toxicological endpoint applicable to a quantitative inhalation risk assessment. A 

repeat-dose inhalation toxicity study can be designed to simulate both a real world route of human exposure as well 

as a specific duration of exposures to varying (vapor and aerosol) concentrations of the test material. A detailed 

toxicological examination including the histopathology of the respiratory system would also be conducted in an 

inhalation toxicity study and thereby, provide a better understanding of potential adverse effects resulting from 

exposure to pine oil via the inhalation route. 

2. How could the data impact the Agency’s future decision-making? 

In the absence of repeat inhalation toxicity data, the Agency is currently unable to estimate inhalation risks to persons 

using products which contain pine oil for disinfection/sanitization purposes in occupational and residential settings. 

If used as the source of dose and effect for route-specific and duration appropriate inhalation risk calculations, 

information from a repeat-dose inhalation toxicity study would provide an estimate of the magnitude of this potential 

risk as well as providing a more complete characterization of overall mammalian toxicity and a better understanding 

of the effects of pine oil on human health. 
Page 20 of 29 

Guideline Number: 870.6200* 

Study Title: 90-Day Oral Neurotoxicity (Subchronic; Neurotoxicity Screening Battery) 

Rationale for Requiring the Data 

The Neurotoxicity Screening Battery (OPPTS 870.6200) is designed to evaluate the potential adverse effects on the 

nervous system from exposure to pesticide chemicals. The Agency believes that existing pine oil studies are 

inadequate in their assessment of behavioral effects and do not use optimal methods to evaluate the potential toxicity 

to the nervous tissue structure and function. To detect and characterize these potential effects more fully, more 

sensitive testing is required. The objective of this neurotoxicity testing is to evaluate the incidence and severity of the 

functional and/or behavioral effects, the level of motor activity, and the histopathology of the nervous system. The 

subchronic neurotoxicity study is intended to detect possible effects resulting from repeated or long-term exposures. 

Therefore, the Agency is requiring a 90-day subchronic (oral) neurotoxicity study for pine oil. A neurotoxicity 

evaluation for pine oil must be conducted because (1) the existing chemical toxicity data base shows evidence of 

neurotoxicity as was noted in the acute oral, acute inhalation and the prenatal developmental toxicity studies and, (2) 

other chemicals within the same class as the active ingredient (i.e., terpenoids) are known neurotoxic agents and (3) 

there is the potential for dietary exposures from the indirect-food uses of pine oil-containing pesticide products in 

occupational and residential settings. 

Practical Utility of the Data 

1. How will the data be used? 

A subchronic neurotoxicity study would provide critical scientific information needed to characterize potential 

hazard to mammalian nervous systems from exposure to pesticides. For pine oil, this study can provide data on a 

wide range of functional tests for evaluating neurotoxicity including sensory effects, neuromuscular effects, learning 

and memory and histopathology of the nervous system. In addition, a neurotoxicity study can be used to select 

endpoints and doses for use in risk assessment of many exposure scenarios and are considered a primary data source 

for reliable reference dose calculation. Furthermore, the Agency has established an oral reference dose (RfD) for 

assessing dietary risks for a number of chemicals where neurotoxicity was the most sensitive endpoint of concern 

(i.e., cholinesterase inhibition). 

2. How could the data impact the Agency’s future decision-making?

The Agency could establish a dose and toxicological endpoint from the new study that is more conservative than the 

doses/endpoints used previously (Pine Oil RED, 2006) to conduct quantitative risk assessments for pine oil. If used 

as the source of a dose and toxicological endpoint for route-specific (oral) risk calculations, these new data would 

provide an estimate of the magnitude of this potential risk, a more complete characterization of overall mammalian 

toxicity and a better understanding of the effects of pine oil on human health. In the absence of this data, additional 

database uncertainty factor may also be applied when conducting a risk assessment using the currently available 

studies, thereby increasing the Agency’s level of concern. 

*The Agency will accept a combined 90-day oral and 90-day neurotoxicity study. The combined study 

would follow the 90-day (oral) subchronic toxicity guideline and incorporate additional neurotoxicity 

evaluations in the testing paradigm. For a combined study, it is recommended that a protocol be submitted 

to the Agency for review prior to initiation of the study. 
Page 21 of 29 

Appendix B: Dietary Data Justifications 

 
Page 22 of 29 

Guideline Number: No Guideline Study Title: Nature of Residue on Surfaces 

Guideline Number: No Guideline Study Title: Migration Study 

Rationale for Requiring the Data 

These residue chemistry studies will allow the Agency to conduct chemical-specific, quantitative dietary risk 

assessments that utilize the measured quantities of pine oil that will be available for dietary consumption when food 

contact surfaces that have been freshly treated with pine oil-containing products. The Nature of the Residue on 

Surfaces study will determine whether residues persist on treated food-contact surfaces, the identity of those residues, 

and a measured upper limit on total surface residue level. The Migration Studies are automatically required but may 

be waived depending on the outcome of the Nature of the Residue on Surfaces study. Migration Studies determine 

the concentrations of specific residues of toxicological concern transferred from treated food-contact surfaces to 

various types of food coming in contact with these surfaces. Data from these studies will replace any default leaching 

and migration rates used in earlier risk assessments. 

The Agency initially assessed exposures to residues on counter tops by assuming that 10% of the available pesticide 

migrates to the food commodity and is available for ingestion; this value is completely arbitrary and may 

underestimate or overestimate exposure and human risk. Furthermore, no consideration was given to dissipation/loss 

of surface residues via volatilization, identity of degradates, or preferential migration of residues to certain types of 

food depending on porosity, water or fat content, etc. 

Practical Utility of the Data 

1. How will the data be used? 

The Nature of the Residue on Surfaces study will be used to determine whether the active ingredient remains on the 

treated food-contact surface, whether it degrades, to what it degrades, and the upper limit on total food-contact 

surface residues. This study may negate the need for a dietary risk assessment, may be used as an upper (yet more 

refined) exposure limit, and may be used to either waive or provide direction for the Migration Studies. Migration 

Studies determine the concentrations of specific residues of toxicological concern transferred from treated foodcontact surfaces to various types of food coming in contact with these surfaces. 

2. How could the data impact the Agency’s future decision-making? 

If pine oil residues transfer from treated surfaces to food, human exposure will occur. These studies will permit the 

conduct of chemical-specific, quantitative dietary risk assessments that are much more refined than earlier 

assessments and in which the Agency has higher confidence. This information will permit a determination of which 

use patterns are expected to result in exposures less than the Agency’s level of concern, which ones must be 

supported by additional data, and which ones are likely to have risks of concern and, therefore, must be mitigated. In 

addition, these data will permit a more realistic estimate of human aggregate risk. 

 
Page 23 of 29 

Appendix C: Exposure Data Justifications 

 
Page 24 of 29 

Guideline Number: 875.1200 Study Title: Indoor Dermal Exposure 

Rationale for Requiring the Data 

Very limited worker exposure monitoring data are available for antimicrobial pesticides when considering the dermal 

route of exposure that results from handling pine oil containing products. Additionally there is limited data regarding 

the dermal exposures that may occur when individuals contact surfaces that are cleaned with such products. EPA 

used these limited data to perform screening level risk assessments for the pine oil RED. 

The existing data in the Chemical Manufacturers Association (CMA) database and Pesticide Handlers Exposure 

Database (PHED) for worker exposure scenarios are limited in scope and quality. The CMA data also has QA/QC 

problems, including the lack of field fortification, laboratory recoveries, and/or storage stability information. In 

addition the CMA data have an insufficient number of replicates. 

EPA presented the need for additional handler exposure data to the January 2007 Science Advisory Panel (SAP) as 

well as to the April 2007 Human Studies Review Board (HSRB) and both groups agreed that additional data are 

warranted. 

To protect handlers from dermal exposures to pesticides, EPA requires dermal exposure monitoring data. The RED 

identified the lack of chemical-specific dermal exposure data, which this study will provide. The data are needed to 

support handler exposures for the residential and occupational users. 

Practical Utility of the Data 

1. How will the data be used? 

The dermal exposure data will be used to assess the residential and occupational exposure to individuals cleaning and 

disinfecting a variety of hard non porous surfaces. The cleaning processes are performed via a range of methods, and 

the generation of the dermal exposure data will allow method specific assessments to be completed.

2. How could the data impact the Agency’s future decision-making?

The dermal exposure data will provide more accurate estimations of the dermal risks to individuals using pine oil 

containing products. These data will be used to generate a sound risk assessment to more accurately reflect the 

actual exposure. If future risk assessments are performed in the absence of these data, the Agency will have a 

significant degree of uncertainty in its regulatory decision-making process and current mitigation measures (i.e., 

personal protective equipment) may not provide adequate protection for workers that may contact pine oil in 

industrial settings. The lack of these data will limit the flexibility of the Agency and registrants with respect to 

decisions made from high-end screening level assessments that may overestimate exposures. 

 
Page 25 of 29 

Guideline Number: 875.1400 Study Title: Indoor Inhalation Exposure 

Guideline Number: 875.2500 Study Title: Inhalation Exposure (Post Application) 

Rationale for Requiring the Data 

Note: Inhalation exposure data are needed for both residential and occupational uses. 

For human risk assessments, exposures via the inhalation route from the use of a variety cleaning methods such as 

low pressure spraying or fogging, where aerosols would be generated are important to consider. In addition, 

inhalation exposures from liquid pouring are evident in exposure studies in the Pesticide Handlers Exposure Database 

(PHED). The existing Chemical Manufacturer Association (CMA) data base and PHED for these scenarios are 

limited in scope for QA/QC and number of monitoring units. EPA presented the need for additional handler 

exposure data to the January 2007 Science Advisory Panel (SAP) as well as to the April 2007 Human Studies Review 

Board (HSRB) and both groups agreed that additional data are warranted. 

Specifically for pine oils, the Agency conducted a handler risk assessment using limited, preliminary exposure data 

as well as EFAST to calculate bystander inhalation exposures to the post cleaning vapors that are expected to be 

generated (e.g. to children crawling on floors after cleaning. These use patterns triggers the need for chemical- and 

use pattern-specific residential and occupational exposure data upon which to base a robust quantitative risk 

assessment. 

This data requirement may be satisfied either by conducting an inhalation exposure monitoring study or by 

cooperating with the Agency to develop and conduct small chamber studies to determine air emission rates, which 

then may be used to estimate inhalation exposure in occupational and residential settings. 

Practical Utility of the Data 

1. How will the data be used? 

The inhalation exposure data would be used to assess the residential short-term duration of cleaning with pine oil 

products. For occupational uses, the inhalation exposure data would be used to assess the short- and intermediateterm exposures from cleaning. These data will also be used to assess bystander exposures to the vapors that may 

result from the relatively high vapor pressure of pine oil. 

2. How could the data impact the Agency’s future decision-making?

The inhalation exposure data would be used to determine the accuracy of the inhalation risks to both residential and 

occupational workers using the formulated products in residential and industrial settings. If future risk assessments 

are performed without these data, the Agency will have to assume a significant degree of uncertainty in its regulatory 

decision-making process and current mitigation measures (i.e., personal protective equipment) may not provide 

adequate protection for workers that may contact pine oil in industrial settings. The lack of these data will limit the 

flexibility of the Agency and registrants with respect to decisions made from high-end screening level assessments 

that may overestimate exposures. 

 
Page 26 of 29 

Guideline Number: 875.1600 and 875.2900 

Study Title: Data Reporting and Calculations (Handler and Post Application) 

Rationale for Requiring the Data 

This data requirement is linked to the dermal and inhalation exposure data also being required. The submission of 

these monitoring data serves as quality assurance and control (QA/QC) for the dermal and inhalation data. These 

data are intended to ensure that the product manufacturer and registrant conducting the study adhere to a defined set 

of quality criteria and meet the study requirements of the Agency. These data allow the Agency to determine if the 

quality of data provided will serve the risk assessment needs and support the registrant’s goal for product registration 

review. Submission of exposure monitoring data reporting increases the Agency’s confidence in the data submitted. 

Rationale for Requiring the Data/Practical Utility 

1. How will the data be used? 

These studies will be used to validate the data provided from the indoor dermal and inhalation applicator exposure 

studies. These data are important because it allows EPA to assess the adequacy and quality of the exposure study. 

Information that must be submitted includes a description of the purpose of the study and what requirement(s) it is 

intended to satisfy, a summary of the study, a comprehensive section on materials, methods, and calculations, a 

section interpreting the scientific results of the study, a discussion of quality assurance, identification of the location 

of the raw data, and any references, communications, and protocols relevant to the conduct of the study. 

2. How could the data impact the Agency’s future decision-making?

The data will be needed to interpret the exposure data that are reported in support of this registration review process. 

If the exposure monitoring data reporting is not submitted in conjunction with the indoor dermal and inhalation 

applicator exposure studies, the Agency may not be able to utilize the studies to the fullest extent to conduct its 

human health exposure and risk assessments. 

 
Page 27 of 29 

Guideline Number: 875.1700 and 875.2700 

Study Title: Product Use Information (Outdoor and Indoor) 

Rationale for Requiring the Data 

Product use information is a narrative description of which, when, and how materials are preserved when the product 

is actually applied; it is not a field study. A description of how products containing pine oils are used will provide a 

comprehensive, realistic assessment of its potential applications and resulting handler and postharvest exposure. 

Descriptions are needed of: (i) what specific types of materials are treated; (ii) the conditions to which pine oils will 

be exposed (temperatures, pH’s, etc); etc. These will provide a comprehensive, realistic assessment of potential 

residential and occupational exposures. Therefore, these data are required. 

Product use information permits EPA to more accurately assess pesticide exposure to applicators by describing how 

the pesticide is actually used and applied. EPA requires this information because differences in use can translate to 

significant differences in exposure, and thus in risk. The Agency historically has used its best professional judgment 

based on its years of experience and general use information from the registered product labels, and product 

chemistry data. 

The guideline for postapplication product use information was presented to the FIFRA Science Advisory Panel 

(SAP) in March 1998. (The draft guideline is available at 

http://www.epa.gov/scipoly/sap/meetings/1998/march/contents.htm.). The guideline for applicator product use 

information should be substantially similar to the one for postapplication. 

Practical Utility of the Data 

1. How will the data be used? 

The description of the materials preserved, application techniques, and degradation conditions will be used to 

determine the exposure scenarios for which exposure studies will be required for use in risk assessment. 

The description of the materials preserved, application techniques, and physicochemical disposition will be used to 

determine the exposure scenarios for which exposure studies will be required for use in risk assessment and for the 

Agency to determine how representative the exposure data are of the “real-world” use scenarios. 

2. How could the data impact the Agency’s future decision-making? 

These data will enable the Agency to understand how the registered products are applied and to ensure that the risk 

assessment is inclusive of the types of exposures occurring during pesticide use and from any potential post 

application contact. This information will permit a determination of which use patterns are expected to result in 

exposures less than the Agency’s level of concern, which ones must be supported by additional data, and which ones 

are likely to have risks of concern and, therefore, must be mitigated. 

 
Page 28 of 29 

Guideline Number: 875.2300 Study Title: Indoor Residue Dissipation 

Rationale for Requiring the Data 

These leaching/migration data will allow the Agency to conduct chemical specific quantitative assessments that 

utilize the measured quantities of pine oil leaching/migrating from: 

a) floors that have been freshly cleaned with a pine oil containing product 

b) clothing that has been laundered or pre soaked with pine oil containing products 

c) toys that have been cleaned with pine oil containing products 

d) food contact surfaces that have been freshly cleaned with pine oil containing products 

Data from these studies will replace any default leaching and migration rates used in the risk assessment. The 

Agency specifically utilized the following generic non chemical-specific assumptions: 

a) Regarding the quantity of solution residue left on the floor after cleaning, as a conservative measure, it has been 

assumed that 25% of the product remains after the final mopping. 

b) To quantify the percent transfer of pine oil from the floor, based on the Residential SOPs, it was assumed that 10% 

of the amount of product on the hard surface is available for dermal transfer. 

c) For textiles (laundering), the chemical specific quantity of transfer of residues from clothing to skin to confirm 

dermal exposures was identified as a data gap. 

d) Toys being cleaned with pine oil containing products have not been assessed previously and will be assessed as 

part of registration review. 

e) It was assumed that 10% of the available pesticide migrates to the food commodity and is available for ingestion; 

this value will need to be supported or revised. 

 

Practical Utility of the Data 

1. How will the data be used? 

The data would be used to determine the leachability and/or migration of the active ingredient as a percentage of the 

original retention. 

2. How could the data impact the Agency’s future decision-making? 

If levels of pine oil transfer from cleaned surfaces (floors and countertops) or soaked materials (textiles), it may result 

in human exposure and risk. Chemical specific assessments have not been completed due to the absence of data. 

This information will permit a determination of which use patterns are expected to result in exposures less than the 

Agency’s level of concern, which ones must be supported by additional data, and which ones are likely to have risks 

of concern and, therefore, must be mitigated. 

 
Page 29 of 29 

Guideline Number: 875.2800 Study Title: Descriptions of Human Activity 

Rationale for Requiring the Data 

Very limited worker activity data are available for antimicrobial pesticides. Worker application parameters are 

generally defined by the physical nature of the formulation (e.g., formula and packaging), by the equipment required 

to deliver the chemical to the use site, and by the application rate required to achieve an efficacious dose. The risk 

assessment noted that many of the use parameters used (e.g., amount handled and duration of use) were based on 

professional judgments judgment and general use information from the registered product labels, and product 

chemistry data, as well as from communication with the registrants of registered products. These data are needed to 

fill this data gap and provide information needed to refine the risk assessment. 

Practical Utility of the Data 

1. How will the data be used? 

The discussion of human activity would be used to define the exposure scenarios to be assessed in the risk 

assessment. Additionally, a complete description of activity patterns would ensure that the risk assessment is 

inclusive of the types of exposures occurring during residential and occupational use. 

2. How could the data impact the Agency’s future decision-making? 

This information will allow the Agency to assess, with greater confidence, the risks that may result from contact with 

or use of antimicrobial products containing pine oil. This information will also permit appropriate label warnings, 

PPE, and any necessary risk mitigation.