Document ID: EPA-HQ-OPP-2004-0302-0020
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-02-21T05:00Z

PINE OIL 

Risk Assessment

Office of Pesticide Programs

Antimicrobials Division

U.S. Environmental Protection Agency

1801 South Bell Street

Arlington, VA 22202

Jaunuary 26, 2006

 TOC \f 

1.0 	EXECUTIVE SUMMARY	3

2.0	PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION	9

2.1  	Chemical Identification	9

2.2	Physical/Chemical Properties	9

3.0	HAZARD CHARACTERIZATION	10

3.1	Hazard Profile	10

3.2	FQPA Considerations	12

3.3	Dose-Response Assessment	13

3.4	Endocrine Disruption	14

4.0	EXPOSURE ASSESSMENT AND CHARACTERIZATION	15

4.1	Summary of Registered Uses	15

4.2	Dietary Exposure/Risk Pathway	15

4.3	Drinking Water Exposure/Risk Pathway	17

4.4	Residential Exposure/Risk Pathway	17

4.4.1	Residential Handler Scenarios	17

4.4.1.1	General Purpose Cleaner Scenario	18

4.4.1.2	Dog Bath	20

4.4.2	Residential Postapplication Exposure	20

5.0 	AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION	24

5.1 	Acute and Chronic Dietary Aggregate Risk. . . . . . . . . . . . . .
. . . . . . . . . . . . . 24

5.2	Short-, Intermediate-, and Long-Term Aggregate Risk. . . . . . . . .
. . . . . . . . .24

5.3	Dermal Aggregate Risk. . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . .  27

6.0	OCCUPATIONAL EXPOSURE AND RISK	28

6.1	Occupational Handlers	28

6.2	Occupational Postapplication Exposure	30

7.0	INCIDENTS	30

8.0	ENVIRONMENTAL FATE ASSESSMENT	30

9.0	ECOTOXICOLOGY ASSESSMENT	32

10.0	REFERENCES	34

 

1.0 	EXECUTIVE SUMMARY tc \l1 "1.0 	EXECUTIVE SUMMARY 

Pine oil is a complex combination of terpenes produced by high
temperature distillation of oil of turpentine or by catalytic hydration
of terpenes.  Pine oil contains a minimum of 60% isomeric secondary and
tertiary cyclic terpene alcohols and a maximum of 40% non-terpene
alcohol components consisting of terpene hydrocarbons, terpene ether,
and ketones.

Pine oil is registered for use as a disinfectant, sanitizer,
microbiocide/microbiostat, virucide, and insecticide for indoor food
use, indoor non-food use, indoor residential use, indoor medical use,
and aquatic non-food industrial use.  Some of these formulations are
allowed for use as hard surface disinfectants in eating establishments
where there may be the potential for indirect transfer to food.  	

Hazard:  The acute toxicity of pine oil is relatively low 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).  

Subchronic toxicity testing of pine oil in rats showed no systemic
toxicity by the dermal route (90-day dermal toxicity study).  No studies
are available regarding subchronic toxicity by the oral route. The
Agency recommends that a subchronic oral toxicity study with
neurotoxicity evaluation be performed for adequate evaluation of the
hazard from repeated oral exposure. 

In a developmental toxicity study in rats, maternal toxicity was
observed at doses of 600 and 1,200 mg/kg/day. Maternal deaths at the
dose level of 1,200 mg/kg/day indicated a potential neurotoxic effect.
In fetuses, increased fetal and litter incidence of depressed eye bulge 
were observed at the 1,200 mg/kg/day dose.  Dilation of the lateral
ventricles was present at 1,200 mg/kg/day, and increased incidence of
micropthalmia was also noted. Increased fetal and litter incidence of
non-ossified or incompletely ossified skull, vertebrae, manubrium,
sternebrae, and pelvis were also reported in the study.  The maternal
and developmental toxicity NOAEL for this study is 50 mg/kg/day. This
value is considered somewhat conservative based on the lack of any other
studies available for non-acute toxicity of pine oil. 

Toxicity Endpoints:  The toxicity endpoints used in this document to
assess potential risks include acute and chronic dietary reference doses
(RfDs), short- and intermediate-term incidental oral doses,
intermediate- and long-term dermal doses and short-, intermediate-, and
long-term inhalation doses. These endpoints were selected in 2004 by the
Antimicrobials Division’s Toxicology Endpoint Selection Committee
(ADTC) for use as appropriate in occupational/residential exposure
assessments.		

Acute and Chronic RfDs: The aRfD for females of child bearing age
(13-50 years)  and the general population is 0.05 mg/kg/day. The female
(13-50 year) aRfD is based on adverse developmental effects (decreased
fetal weight, fetal malformations, retardation of ossification) at 600
mg/kg/day  in the rat developmental study, while the aRfD for the
general population is based on clinical observations of toxicity,
decreased body weight, weight gain, food consumption in maternal rats at
600 mg/kg/day in the same study.    Uncertainty factors were included
for inter-species extrapolation (10x), intra-species variation (10x),
and lack of an adequate hazard database for FQPA safety assessment(3x).

The chronic RfD is 0.016 mg/kg/day based on adverse maternal effects at
600 mg/kg/day in the rat developmental study. Uncertainty factors were
included for inter-species extrapolation (10x), intra-species variation
(10x),  lack of an adequate hazard database (10x), and lack of a
long-term study (3x).   

Incidental oral endpoints:    The short-term, and intermediate-term
incidental oral endpoint of 50 mg/kg/day is based  on clinical
observations of toxicity, decreased body weight, weight gain, and food
consumption at 600 mg/kg/day in maternal animals in the rat
developmental study.  Uncertainty factors were included for
inter-species extrapolation (10x), intra-species variation (10x), and 
lack of an adequate hazard database (10x).  Thus, the target margin of
exposure (MOE) is 100 for short-term exposures and 1,000 for
intermediate-term exposures.

Dermal endpoints:   A short-term dermal endpoint was not needed for pine
oil.  This conclusion was based on the results of a 14-day dermal
toxicity study (submitted with the 90-day dermal toxicity study)    in
which no adverse dermal effects were observed at a dose near a limit
dose (940 mg/kg/day). For intermediate- and long-term dermal exposure,
the highest dose tested in the 90-day dermal toxicity study was selected
as the endpoint (NOAEL of 226 mg/kg/day).  Uncertainty factors were used
for inter-species extrapolation (10x) and intra-species variation (10x).
 The target MOE is 100.  Extra uncertainty factors were not applied to
the dermal endpoint based on the conservative nature of the dose level
(i.e. 226 mg/kg/day vs. 940 mg/kg/day in the 14 day dermal study) and
the observation that higher dose levels could not be tested dermally.

Inhalation endpoints:  The inhalation endpoint for all exposure
durations is 50 mg/kg/day and is based on clinical observations of
toxicity, decreased body weight, weight gain, and food consumption at
600 mg/kg/day in maternal animals in the rat developmental study. 
Uncertainty factors were included for inter-species extrapolation (10x),
intra-species variation (10x), and lack of an adequate hazard database
including a route-specific inhalation study (10x) for the short-term
inhalation endpoint.  For the intermediate and long-term endpoint, an
additional uncertainty of 3x was applied for the  lack of a long-term
study from which to determine a long-term exposure endpoint. Thus, the
MOE is 1,000 for short- and intermediate-term exposures and 3,000 for
long-term exposures.

FQPA Safety Factor:  On February 24, 2004 , the ADTC reviewed the
available toxicology data for pine oil and recommended that the
hazard-based  special FQPA safety factor be removed (1X) when assessing
dietary risks resulting from the uses of pine oil.  

With respect to adequacy of the database, in the case of pine oil, the
toxicology data are deficient in needed areas, specifically
neurotoxicity and and reproductive toxicity. In addition, the data
available for assessing pre- and post-natal toxicity are limited to one
developmental toxicity study. While the one developmental study showed
no apparent sensitivity of offspring, as just noted, a better hazard
characterization should be performed to adequately address pre- and
post-natal toxicity by inclusion of the reproductive and neurotoxicity
data. Therefore on the basis of this analysis, the ADTC applied a
database  uncertainty factor of 10x for pine oil.  

Based on Agency policy, a RfD modified by a FQPA safety factor is a
population adjusted dose (PAD).  The Agency calculated an acute PAD and
a chronic PAD, and uses this value to estimate acute and chronic dietary
risk.  The acute PAD is the acute RfD divided by the FQPA safety factor.
 The chronic PAD is the chronic RfD divided by the FQPA safety factor.

Dietary Exposure and Risk:  AD considered potential dietary exposure to
pine oil residues in food.  When assessing acute and chronic
(non-cancer) dietary risk, AD considered potential dietary exposure to
the U.S. population including infants and children as well as to females
13-50 years, based on the developmental toxicity potential of this
active ingredient.  AD expresses dietary risk estimates as a percentage
of the aPAD or chronic PAD.  Dietary exposures that are less than 100%
of the aPAD or cPAD are below the Agency’s level of concern. 

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 did not request nor was any data
received on the residue chemistry of pine oil.  Therefore, the Agency
has relied upon the models developed by the Food and Drug Administration
(FDA) to estimate dietary exposure through the indirect food contact
uses of pine oil. The results of the dietary exposure and risk analysis
indicated that of the five product formulations registered for indirect
food uses, there is only one dietary exposure scenario of concern, that
of children’s dietary exposure to the El-Pinol 60 formulation, where
the dietary risk was estimated at 248% of the aPAD and cPAD. 

Water Exposure and Risk: Pine oil is registered for indoor uses only and
it is not likely to contaminate surface or ground water. In the event
that  Pine oil is released into a waste stream, the three major
constituents (alpha-pinene, beta pinene and alpha terpineol) volatilize
rapidly from surface water, are  highly biodegradable, have short half
lives in water, and have low mobility in soils. Hence there is low
probability of  surface or ground water contamination.

Residential (Non-Occupational) 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 residential exposure assessment were developed to encompass
multiple uses but still represent a high end exposure scenario for all
uses represented.   The residential handler scenarios considered in this
assessment include handling of liquid general purpose cleaner and dog
bathing.  These scenarios were selected because they are believed to
yield the greatest amount of handler exposure to pine oil. 



For the general purpose cleaner scenario, the calculated dermal MOEs are
not of concern for any of the scenarios (MOE = 570 and 2,900, for wiping
and mopping, respectively; where the target MOE is 100 for
intermediate-term exposures).  The calculated inhalation aerosol MOEs
for the wiping and mopping are also not of concern.  The wiping MOE is
5,300 and the mopping MOE is 20,000 where the target MOE is 1,000 for
short- and intermediate-term exposures.  In addition, inhalation MOEs
from the vapor of pine oil are not of concern (MOE = 1,400).

Residential exposure to pine oil products used for washing dogs (i.e.,
specified on label as a “dog bath”) was also evaluated.  This
scenario is believed to be best represented by the short-term exposure
duration.  Because there is no short-term dermal endpoint, dermal risks
were not evaluated.  However, a short-term inhalation exposure and risks
to pine oil vapors were estimated using  the methodology outlined in the
 Standard Operating Procedures (SOPs) for Residential Exposure
Assessments (U.S. EPA 2000) for calculating handler inhalation doses
from treating pets with shampoo is based on a percentage of the
application rate.  Because pine oils have a relatively high vapor
pressure, the model EFAST was used.  However, EFAST does not contain an
exposure scenario for bathing a dog.  Therefore, to determine the
potential inhalation exposure to pine oil when used to bath a dog, the
air concentration estimate for general purpose cleaners was used as a
screening-level assessment.  The application rate for a dog bath (EPA
Reg. No. 62644-1) is 3 teaspoons of a 19.9 % ai formulation per gallon
of water.  Therefore, the weight fraction is determined to be 0.00078
(i.e., 3 tsp/768 tsp per gallon x 8 lb/gal x 0.199 = 0.0062 lb ai per
gallon of dog bath.  Weight fraction is 0.0062 lb ai per gallon / 8 lb
per gallon wash solution density = 0.00078).  The weight fraction used
for the general purpose cleaner assessment above was higher at 0.009. 
Therefore, the estimated inhalation risk for the dog bath is less than
that posed by the cleaner use (i.e., higher MOE than the 1,400 estimated
above for vapor exposures) and not of concern. 

The residential post-application scenario considered in this assessment
is exposure to residue from hard surfaces (i.e., floors) that have been
mopped with a product containing pine oil.  At this time the
Antimicrobials Division has not developed a methodology to assess
exposure to pets after treatment.  This is considered a data gap that
needs to be addressed by the registrant.

 

Dermal and incidental oral exposures of toddlers crawling on floors
treated with pine oil products were assessed as part of the
post-application exposure and risk assessment.  The dermal MOE from this
scenario (570) does not indicate a risk of concern for toddlers (target
MOE (100). Additionally, the short- and intermediate-term incidental
oral MOEs for toddlers are 960 and 2,200, respectively (target MOE (100
for short-term and 1000 for intermediate term).  Therefore, the
incidental oral MOEs from this scenario does not indicate a risk of
concern.

In addition, short-term postapplication inhalation exposures to vapors
are not of concern for adults for cleaning products (MOE = 1,400 versus
target MOE (1000), but are of concern for children (MOE = 450) for the
80% ai cleaning products.  However, the postapplication inhalation
(vapor) MOE for the dog bathing scenario is below the Agency’s level
of concern (MOE = 7,400 versus  target MOE of  (1000).  

Aggregate Exposure and Risk: For the short-term aggregate assessment,
adult exposures from dietary exposure and cleaning could be aggregated. 
In the case of pine oil, the dietary exposure is aggregated with the
inhalation exposures from cleaning.  The dermal exposure is not included
as the study and endpoint defining the toxicity by the dermal route
differ from the oral and inhalation route. 	

For toddlers, only the short-term  incidental oral exposure from the
floor cleaning (postapplication) are aggregated with dietary exposure.
Dermal exposures are not aggregated for the same reason as stated for
adults. In addition, there are no aggregate intermediate-term scenarios
for toddlers, although there are intermediate-term exposure scenarios. 

The total MOE method is used to aggregate the above scenarios for
adults, as the uncertainty factor from chronic dietary exposure (1000)
is similar to the uncertainty factors for the short- and
intermediate-term inhalation exposure (1000). However, for children, the
Aggregate Risk Index method (ARI) is used to aggregate exposures as the
uncertainty factor for incidental oral (100) is dissimilar to the
chronic dietary uncertainty factor (1000). 

 Based on this approach, total MOEs for adult aggregate exposures were
above the level of concern (MOE of > 1000) for all scenarios. For
children’s aggregate exposure using the ARI method, ARIs ranged from
0.17-0.4, indicating a risk of concern for children’s aggregate
exposures. 

Occupational Exposure and Risk:  Worker exposure to pine oil is expected
to occur through the use of pine oil-containing products in
commercial/institutional settings (e.g., janitors).  Dermal and
inhalation exposures from contact with pine oil were assessed for
handling pine oil-containing cleaning products through low pressure
spray, wiping, and mopping application methods. While pine oil products
have other listed uses, these additional exposure scenarios are not
expected to result in higher exposures than the selected scenario. 
Therefore, exposures to pine oil from cleaning was considered
representative of a high end exposure.  

Occupational handler exposures were assessed for low pressure spray,
wiping, and mopping application methods using surrogate data obtained
from the Chemical Manufacturers Association (CMA) antimicrobial study
(U.S. EPA, 1999).  In addition, product label maximum application rates,
related use information, and Agency standard values were used to
evaluate occupational handler exposures.  The dermal and inhalation risk
estimates for all 3 scenarios are not of concern (dermal MOEs range from
280 to 1,500 and the inhalation MOEs range from 2,600 to 9,800, with
target MOEs of 100 and 1,000, respectively).

Occupational postapplication dermal and aerosol- and vapor-generated
inhalation exposures to pine oil are likely to be minimal compared to
handler exposure because of dilution with water.  (Note: postapplication
exposure from cleaning products are assessed for residents in the
residential section.)  Therefore, a separate screening-level assessment
was not conducted for occupational postapplication scenarios.

Environmental Fate: No data are available regarding the fate
characteristics of pine oil, which is a complex mixture of terpenes. The
fate properties of the major components of pine oil, namely
alpha-terpineol and alpha- and beta-pinene, were used instead to assess
the environmental fate of this complex blend.  Based on alpha- and
beta-pinene’s bioconcentration factors of 2,800 and 440 (estimated), 
respectively, and high log Kow values, bioaccumulation or
bioconcentration in aquatic organisms is possible. Likewise,
alpha-terpineol’s bioconcentration factor of 110 suggests   a low to
moderate  potential for bioconcentration.  However, alpha- and
beta-pinene are expected to undergo rapid biodegradation and
volatilization in water. Alpha-terpineol, on the other hand, is not
likely to biodegrade as rapidly as pinenes, alpha-terpineol is not
persistent in water.

Alpha- /beta-pinene and alpha-terpineol have been shown to be readily
biodegradable in soil by microorganisms. In addition, the Henry’s Law
Constants for these chemicals indicate that they will volatilize from
most moist soils. However, they are expected to absorb with a high
degree to suspended particles and sediments in the water column based on
estimated Koc values (1,000 for alpha-pinene and alpha-terpineol and
1,200 for beta-pinene). 

In general, the rapid volatilization and biodegradation and low
half-lives in water of alpha-/beta-pinene and alpha-terpineol indicate a
low probability for contamination of water systems.  Due to their
volatilization, biodegradation and low mobility in soils, contamination
of  ground or surface water systems is not likely.  

Ecological Hazard and Environmental Risk: Ecological effects data
indicate that pine oil is practically non-toxic to avian species and
only slightly toxic to freshwater fish and invertebrates on an acute
basis. Chronic toxicity testing for freshwater organisms is not required
for pine oil and no information is currently available. Likewise, plant
toxicity information on pine oil is not available; however, terrestrial
and aquatic plant testing is not required to support the indoor uses of
pine oil.

The indoor uses of Pine Oil considered in this RED make it unlikely that
any appreciable exposure to terrestrial or aquatic organisms would occur
when it is used according to label directions. The low toxicity to
birds, mammals, and aquatic organisms makes it even more unlikely that
the indoor uses of this chemical pose a risk to these species.  Risk to
plants cannot be addressed due to a lack of phytotoxicity data; however,
exposure to plants is unlikely from the indoor uses of this chemical.		

Endangered species considerations:  Based on the low likelihood of
environmental exposure from the registered indoor uses, coupled with the
low toxicity of pine oil to fish, aquatic invertebrates, mammals, and
birds, adverse impacts to endangered birds, fish and aquatic
invertebrate species are not expected from the registered uses of pine
oil.  Risk to endangered plants cannot be addressed due to a lack of
phytotoxicity data; however, exposure to endangered plants is unlikely
from the indoor uses of this chemical. 

DATA GAPS / REQUIREMENTS

For the uses of Pine oil in the RED, data gaps exist for a
two-generation reproduction toxicity test and a 90-day oral toxicity
test with neurotoxic endpoint  These aspects of Pine oil toxicity are
not adequately addressed by the current toxicology database, and a
database uncertainty factor has been used in the absence of these data. 

In addition, the dermal sensitization assay and the in vitro mammalian
cells in culture assay must be repeated. The sensitization assay used an
inadequate number of animals to make a determination of sensitization,
and the CHO assay had significant problems with the integrity of the
cell cultures that compromised the results of the study. 

The residential post-application scenario considered in this assessment
is exposure to residue from hard surfaces (i.e., floors) that have been
mopped with a product containing pine oil.  At this time the
Antimicrobials Division has not developed a methodology to assess
exposure to pets after treatment.  This is considered a data gap that
needs to be addressed by the registrant

2.0	PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION tc \l1 "2.0
PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION 

2.1  	Chemical Identification tc \l2 "2.1  	Chemical Identification 

Chemical identification parameters, including chemical and common/trade
names, chemical family, CAS Number, and molecular formula are provided
in Table 1.

Table 1. Chemical Identification

Chemical Name	

1-Methyl-4-isopropyl-1-cyclo-hexen-8-ol

Common/Trade Names	

Pine Oil 80

Chemical Family	

alpha-Terpineol and Terpinolene (Terpene alcohol)

CAS Number	

8002-09-3

Molecular Formula	

C10H18O

2.2	Physical/Chemical Properties tc \l2 "2.2	Physical/Chemical
Properties 

The physical and chemical properties of Pine Oil are shown in Table 2.

Table 2. Physical/Chemical Properties

Parameter	

Value

Molecular Weight	

154.0

Molecular Structure	

CH3-C6H9-(OH)-C3H5

Color	

Colorless to pale yellow

Physical State	

Liquid

Specific gravity	

0.952 at 20 oC

Boiling Point	

~ 210 o C at 750 mm Hg

Dissociation Constant	

NA (insoluble in water)

pH	

NA (insoluble in water)

Stability	

30-day accelerated storage study showed the substance is stable

Melting point	

N/A

Water Solubility	

Insoluble in water (immiscible)

Solubility in organic solvents	

Isopropyl alcohol  >90%

Toluene >90%

Octanol-water Partition Coefficient	

Can not be determined (insoluble in water)

Vapor Pressure	

0.2 mm Hg at 20(C

3.0	HAZARD CHARACTERIZATION tc \l1 "3.0	HAZARD CHARACTERIZATION 

3.1	Hazard Profile tc \l2 "3.1	Hazard Profile 

A detailed hazard assessment for pine oil is presented in the attached
appendix (Toxicology Disciplinary Chapter for the Reregistration
Eligibility Decision Document).  

Acute Toxicity.  In acute toxicity studies, pine oil has been shown to
have low toxicity by the oral route (Toxicity Category III), inhalation
route (Toxicity Category IV) and dermal route (Toxicity Category III). 
Pine oil is a moderate skin irritant (Toxicity Category III), but shows
a stronger response as an eye irritant (category II).  No dermal
sensitization has been observed with pine oil; however, the available
dermal sensitization assay is considered unacceptable because an
inadequate number of animals was used to make the determination of
sensitization.  Table 3 presents the acute toxicity data for pine oil. 
Table 4 highlights results of key toxicological studies with pine oil.  
 

Subchronic Toxicity. The database for subchronic toxicity of pine oil
consists of one 14-day dermal toxicity test and one 90-day dermal
toxicity test in rats.  In the 14-day dermal toxicity test no
significant adverse effects were observed up to a dose of 940 mg/kg/day.
In the 90-day dermal toxicity study, no significant adverse dermal or
systemic effects were observed due to treatment. The systemic
no-observed-adverse effect level (NOAEL) was (226 mg/kg/day (the highest
dose tested); a lowest-observable-adverse effect level (LOAEL) could not
be determined due to a lack of treatment-related effects. 

Developmental Toxicity.  In a prenatal developmental toxicity study in
rats, maternal toxicity in the form of excess salivation, alopecia, and
ungroomed coat was observed at doses of 600 and 1,200 mg/kg/day. In
addition, adrenal gland weight was significantly increased in maternal
animals at the 1,200 mg/kg/day dose level. Maternal deaths were also
increased at the 1,200 mg/kg/day; animals exhibited  ataxia, decreased
motor activity, and impaired righting reflex prior to death, raising the
possibility of a neurotoxic effect.  External examination of fetuses
showed an increased fetal and litter incidence of depressed eye bulge at
the 1,200 mg/kg/day dose. Visceral examination showed dilation of the
lateral ventricles at 1,200 mg/kg/day, and increased incidence of
micropthalmia. Skeletal examination showed increased fetal and litter
incidence of non-ossified or incompletely ossified skull, vertebrae,
manubrium, sternebrae, and pelvis.  The maternal and developmental
toxicity NOAEL for this study is 50 mg/kg/day. This value is considered
somewhat conservative based on the lack of any other available studies
for non-acute toxicity of pine oil. 

Reproductive Toxicity.  Studies with pine oil were not available to
satisfy the data requirements for reproductive toxicity for this
chemical. As there are indirect food uses for this chemical, and in
accordance with the interim working policy of AD regarding indirect food
use data requirements, a reproductive toxicity study is required in
order to properly characterize these risks. 

Carcinogenicity.   Pine oil has not been classified as to its
carcinogenicity. However, carcinogenicity data are not required at this
time. 

Mutagenicity.  Acceptable mutagenicity studies including an Ames
Salmonella assay, a micronucleus assay, and a UDS assay were conducted
with pine oil. No mutagenic response was observed in these studies. In
an unacceptable in vitro cytogenetics assay, a negative mutagenic
response was also observed for this chemical.  This study was deemed
unacceptable due to problems with the integrity of the cell cultures. 

Neurotoxicity.  Studies with pine oil were not available to satisfy the
data requirements for neurotoxicity for this chemical.  The Agency
recommends that a subchronic oral toxicity study with neurotoxicity
evaluation be perform to address the neurotoxicty of pine oil. 

Metabolism.  Metabolism data are not required at this time.

Table 3.  Acute Toxicity of Pine Oil

Guideline No./ Study Type	

MRID No.	

Results	

Toxicity Category

870.1100 Acute oral toxicity-Rat	

40253502 	

LD50(combined) = 2.7 g/kg	

III

870.1200 Acute Dermal toxicity-Rat	

40253503	

LD50 > 2000 mg/kg	

 III

870.1300 Acute inhalation toxicity-Rat	

 43375208	

 LC50  > 3.67 mg/L	

IV

870.2500 Dermal irritation-Rabbit	

 43375210	

Erythema/edema up to 7 days post dose	

III

870.2400 Primary Eye Irritation	

43375209	

Irritation lasting up to 16 days	

II

870.2600 Skin sensitization-Guinea pig	 	                       Not a
sensitizer. Study unacceptable

Table 4.  Toxicity Profile of Pine Oil 

Guideline No./ Study Type	

MRID No. (year)/ Classification/ Doses	

Results

870.3250

90-day Dermal Toxicity in Rats	

40515401 (1988)/

acceptable/non-guideline

Doses:

0, 50, 113, 226 mg/kg/day to shaved skin, 6 hrs/day, 5days/wk, 13 weeks

	

Systemic Toxicity NOAEL = >226 mg/kg/day

Systemic Toxicity LOAEL = >226 mg/kg/day  

 

NOAEL can be estimated from a 14-day range-finding study that showed a
dermal NOAEL of 940 mg/kg/day. 

870.3700

Developmental Toxicity in Rats	

40515201 (1988)/

Acceptable-guideline/

Doses: 0, 50, 600, 1200 mg/kg/day	

Maternal/Developmental Toxicity NOAEL = 50 mg/kg/day

Maternal/Developmental  Toxicity LOAEL = 600 mg/kg/day  

The dose spacing in this study (i.e. 50, 600, 1,200 mg/kg/day) along
with the appearance of effects mainly at 1200 but also at 600 mg/kg/day
suggests that effects could have arisen at doses lower than 1,200
mg/kg/day but greater than 600 mg/kg/day.  This leads to a conservative
assumption of 50 mg/kg/day as the NOAEL for maternal and developmental
toxicity. 

Mutagenicity

Gene Mutation

870.5100 Ames Salmonella Assay	

43375212 (1994)/

Acceptable/

concentrations of 0.1, 1.0, 10, 100, 1,000, 10,000 µg/plate	

No evidence of an increase in induced mutant colonies over background in
the absence or presence of metabolic activation.

In vitro Cytogenetics 

870.5300

 	

40341403 (1987)/

Unacceptable/

100, 130, 170, 200, 250 ng/mL (-S9); 50, 100, 200, 300, 400 nL/mL (+S9)	

No evidence of induction of mutant colonies over background. 

Study not acceptable and must be repeated. Cells not checked for
mycoplasma contamination, and several cultures were lost to
contamination during conduct of the assay.   

 

870.5395 

Micronucleus Assay	

40341403 (1987)/

Acceptable/

 i.p. doses of 0, 116, 578, 1155 mg/kg  	

No significant increase in frequency of micronucleated polychromatic
erythrocytes in bone marrow at any test concentration or harvest time.

870.5550

UDS Assay	

40341404 (1987)

Acceptable

concentrations of 0.03, 0.01, 0.003, 0.001, 0.0003 ul/ml	

No evidence of a positive response at dose levels up to and including
0.03 ul/ml.  

Neurotoxicity

870.6300

Developmental neurotoxicity	

Not required

3.2	FQPA Considerations tc \l2 "3.2	FQPA Considerations  

Under the Food Quality Protection Act (FQPA), P.L. 104-170, which was
promulgated in 1996 as an amendment to the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug and
Cosmetic Act (FFDCA), the Agency was directed to "ensure that there is a
reasonable certainty that no harm will result to infants and children"
from aggregate exposure to a pesticide chemical residue.  The law
further states that in the case of threshold effects, for purposes of
providing this reasonable certainty of no harm, "an additional tenfold
margin of safety for the pesticide chemical residue and other sources of
exposure shall be applied for infants and children to take into account
potential pre- and post-natal toxicity and completeness of the data with
respect to exposure and toxicity to infants and children. 
Notwithstanding such requirement for an additional margin of safety, the
Administrator may use a different margin of safety for the pesticide
residue only if, on the basis of reliable data, such margin will be safe
for infants and children."

 On February 24, 2004 , the Antimicrobials Division Toxicology Endpoint
Selection Committee (ADTC) reviewed the available toxicology data for
pine oil and recommended that the hazard-based  special FQPA safety
factor be removed (1x) when assessing dietary risks resulting from the
uses of pine oil. This conclusion is based on the use of conservative
NOAEL values from the developmental toxicity study for calculation of
dietary and non-dietary endpoints. The ADTC also concluded that there is
no evidence for susceptibility to exposure to pine oil from the limited
data available.  The ADTC however included a database uncertainty factor
of 10x for risk assessments involving pine oil.  As noted in the OPP
guidance document Determination of the appropriate FQPA Safety Factor(s)
in Tolerance Assessment (USEPA, 2002), “Determination of the magnitude
of the overall safety factor or margin of safety involves evaluating the
completeness of the toxicology and exposure databases and the potential
for pre- and post-natal toxicity.” In the case of pine oil, the
toxicology data are deficient in needed areas, specifically
neurotoxicity and and reproductive toxicity. In addition, the data
available for assessing pre- and post-natal toxicity are limited to one
developmental toxicity study. While the one developmental study showed
no apparent sensitivity of offspring, as just noted, a better hazard
characterization should be performed to adequately address pre- and
post-natal toxicity by inclusion of the reproductive and neurotoxicity
data. Therefore on the basis of this analysis, the ADTC applied a
database  uncertainty factor of 10x for pine oil. 

3.3	Dose-Response Assessment tc \l2 "3.3	Dose-Response Assessment  

The doses and toxicological endpoints selected for various exposure
scenarios are summarized in Table 5. 			

Table 5. Toxicological Endpoints

Exposure

Scenario	

Dose used in risk assessment

UF /MOE	

FQPA SF and Endpoint for Risk Assessment	

Study and Toxicological Effects

Dietary Risk Assessments

Acute Dietary

(gen pop)	

NOAEL of 50 mg/kg/day

UF= 100x

DB UF =10x

Acute RfD = 0.05 mg/kg/day	

 FQPA SF = 1x

aPAD=acute RfD

              FQPA 

= 0.05 mg/kg/day	

Developmental toxicity study in rats

Maternal LOAEL of 600 mg/kg/day based on clinical observations of
toxicity, decreased body weight, weight gain, food consumption

Acute Dietary

(females 13+)	

 NOAEL of 50 mg/kg/day

UF= 100x

DB UF = 10x

Acute RfD = 0.05 mg/kg/day	

FQPA SF = 1x

aPAD=acute RfD

              FQPA 

= 0.05 mg/kg/day 	

Developmental toxicity study in rats

Developmental toxicity LOAEL of 600 mg/kg/day based on decreased fetal
weight, fetal malformations, retardation of ossification. 

Chronic Dietary

	

NOAEL= 50

 

UF= 300

DB UF = 10x

Chronic RfD = 

0.016 mg/kg/day

		

FQPA SF = 1x

cPAD=chronicRfD

              FQPA 

= 0.016 mg/kg/day

	

Developmental toxicity study in rats  

Maternal LOAEL of 600 mg/kg/day based on clinical observations of
toxicity, decreased body weight, weight gain, food consumption

Non-Dietary Risk Assessments

Incidental Oral

Short– and Intermediate-Term 

(1 - 30 Days, and 1-6 months)

 	

Maternal NOAEL= 50 mg/kg/day

 

 	

Target MOE= 100 (short-term)

1000 (intermediate-term)	

Developmental toxicity study in rats

Maternal LOAEL of 600 mg/kg/day based on clinical observations of
toxicity, decreased body weight, weight gain, food consumption

Dermal

Short -term 	

Endpoint not required

Dermal intermediate and long-term	

Dermal NOAEL > 226 mg/kg/day	

Target MOE=100

(residential and occupational)	

90-day dermal toxicity study in rats

Dermal NOAEL of > 226 mg/kg/day (highest dose tested)

Inhalation

All durations	

 NOAEL = 50 mg/kg/day 

(assume inhalation and oral absorption are equivalent, i.e., 100%)

	

Target MOE

=1,000 (ST, IT)

= 3,000 (LT)

(residential and occupational)	

Developmental toxicity in rats

Maternal LOAEL of 600 mg/kg/day based on clinical observations of
toxicity, decreased body weight, weight gain, food consumption.

Notes:

UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL
= lowest observed adverse effect level, RfD = reference dose, MOE =
margin of exposure

A short-term dermal endpoint was not needed for pine oil.  This
conclusion was based on the results of a 14-day dermal toxicity study
(submitted with the 90-day dermal toxicity study)  in which no adverse
dermal effects were observed at a dose near a limit dose (940
mg/kg/day). 

Database Uncertainty Factor.  Based on the lack of specific
neurotoxicity and reproductive toxicity endpoints and uncertainty in
chracterization of pre- and post-natal toxicity,  a database uncertainty
factor of 10x applies to pine oil for residents and workers for oral and
inhalation exposures.

 

3.4	Endocrine Disruption tc \l2 "3.4	Endocrine Disruption 

The Agency is required under the Federal Food, Drug and Cosmetic Act
(FFDCA), as amended by FQPA, to develop a screening program to determine
whether certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine
effects as the Administrator may designate."  Following the
recommendations of its Endocrine Disruptor Screening and Testing
Advisory Committee (EDSTAC), EPA determined that there was scientific
bases for including, as part of the program, the androgen and thyroid
hormone systems, in addition to the estrogen hormone system.  EPA also
adopted EDSTAC’s recommendation that the Program include evaluations
of potential effects in wildlife.  For pesticide chemicals, EPA will use
FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA authority to
require the wildlife evaluations.  As the science develops and resources
allow, screening of additional hormone systems may be added to the
Endocrine Disruptor Screening Program (EDSP).

When the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, pine oil may be subjected
to additional screening and/or testing to better characterize effects
related to endocrine disruption.

4.0	EXPOSURE ASSESSMENT AND CHARACTERIZATION tc \l1 "4.0	EXPOSURE
ASSESSMENT AND CHARACTERIZATION 

4.1	Summary of Registered Uses tc \l2 "4.1	Summary of Registered Uses 

Pine oil is the active ingredient in numerous formulations and is used
as a disinfectant, sanitizer, microbicide/microbistat, virucide, and
insecticide.  Products containing pine oil are designated for
occupational and residential use.  The occupational use sites include:
eating establishments (surfaces, equipment, and utensils), food
processing plants/areas, commercial/institutional/industrial premises
and equipment, commercial transportation facilities, refuse and soil
waste transportation and handling equipment, barber and beauty shop
equipment and instruments, laundry, and hospitals and related
institutions.  The residential uses locations include: bathrooms, toilet
bowls, kitchens, non-porous surfaces, garbage cans, household items,
laundry, and pets.  

Concentrations of pine oil in products range < 0.3% to 80%, with two
ready-to-use products containing <1% of the active ingredient. 
Manufacturing-use products contain 99% to 100% pine oil.  All
formulations are in liquid form, and are generally intended to be
diluted with water prior to use.  Label instructions also indicate that
products may be used full strength for heavy-duty cleaning jobs or tough
stains, but areas/items should be rinsed with water immediately. 

4.2	Dietary Exposure/Risk Pathway tc \l2 "4.2	Dietary Exposure/Risk
Pathway 

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 did not request nor was any data
received on the residue chemistry of pine oil.  Therefore, the Agency
has relied upon the models developed by the Food and Drug Administration
(FDA) to estimate dietary exposure through the indirect food contact
uses of pine oil.  In estimating the dietary exposure from the
disinfectant use of pine oil, the Agency has made the following
assumptions: 

1. Residual solution of the formulation on Surface: 1 mg/cm2 (FDA’s
worst Case                           scenario and EPA also has used this
assumption)	

  2. Area of treated surface: 2000 cm2 ( 50% of the FDA worst case
assumption, and  EPA also has used this assumption)

            3. EPA is making the assumption that in all scenarios listed
for the product labels, the maximum exposure of food (indirect contact)
is 2000 cm2, including   drain boards.

4. The Agency recognizes that as a disinfectant use, there will be a
potable water rinse following application of the disinfectant. Although
there are quantitative approaches to measuring the reduction in residue,
the Agency has assumed a 90% reduction in residue level as reasonable. 
Hence the dietary exposure risk assessment is carried out based on the
90% reduction scenario.

Estimation of dietary exposure for the registered pine oil formulation
taking into account the above assumptions yielded exposure estimates
from 0.0034-0.0448 mg/kg/day for adult males, 0.0039-0.0523 mg/kg/day
for adult females, and 0.0158-0.2 mg/kg/day for children (15kg).  The
exposure estimates and resulting dietary risk are summarized in Table 6.
 

                 Table 6. Dietary Exposure and Risk 

 Formulation	

       Exposure (mg/kg/day) (males)	

% aPAD	

%cPAD

Lonza P-13	

0.0035	

      7.0	

7.0

 Lonza P-6	

 0.0035	

      7.0	

7.0

 Lonza P-39	

 0.0034	

      7.0	

7.0

 El-Pinol 60	

0.0267	

      53	

 53

El-Pinol 19.9	

0.0084	

       17	

 17

 Formulation	

       Exposure (mg/kg/day) (females)	

% aPAD	

%cPAD

Lonza P-13	

0.0041	

      8.0	

8.0

 Lonza P-6	

 0.0041	

      8.0	

8.0

 Lonza P-39	

 0.0039	

      8.0	

8.0

 El-Pinol 60	

0.0311	

       62	

 62

El-Pinol 19.9	

0.0098	

     20	

 20

 Formulation	

       Exposure (mg/kg/day) (child)	

% aPAD	

%cPAD

Lonza P-13	

0.0164	

     32     	

  32

 Lonza P-6	

 0.0164	

      32	

 32

 Lonza P-39	

 0.0158	

      32	

 32

 El-Pinol 60	

0.124	

     248	

 248

El-Pinol 19.9	

0.039	

     78	

 78

As is observed from the above calculations, there is only one dietary
exposure scenario, that of children’s dietary exposure from the use of
the El-Pinol 60 formulation, that presents an unacceptable dietary risk.
  

4.3	Drinking Water Exposure/Risk Pathway tc \l2 "4.3	Drinking Water
Exposure/Risk Pathway 

Pine oil is registered for  indoor uses  only and it is not likely to
contaminate surface or ground water. In the event pine oil is released
to a waste stream, the three major constituents (alpha-pinene, beta
pinene and alpha terpineol) volatilize rapidly from surface water, are 
highly biodegradable, they  have short half lives in water, and have low
mobility in soils. Therefore, there is low probability of  surface or
ground water contamination.

4.4	Residential Exposure/Risk Pathway tc \l2 "4.4	Residential
Exposure/Risk Pathway 

A detailed residential and occupational risk assessment for pine oils is
provided in the attached Appendix.  A summary of the exposures and risks
to residential handlers is provided below.

4.4.1	Residential Handler Scenarios tc \l3 "4.4.1	Residential Handler
Scenarios 

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 residential exposure assessment were
developed to encompass multiple uses but still represent a high end
exposure scenario for all uses represented.   The residential handler
scenarios considered in this assessment include handling of liquid
general purpose cleaner and dog washing.  These scenarios were selected
because they are believed to yield the greatest amount of handler
exposure to pine oil.

4.4.1.1	General Purpose Cleaner Scenario tc \l4 "4.4.1.1	General Purpose
Cleaner Scenario 

The following two scenarios were considered for residential handlers of
pine oil-containing cleaning products:

Use of cleaner/disinfectant/deodorizing wipe on hard non-porous
surfaces, and

Use of cleaner/disinfectant/deodorizing mopping on hard non-porous
surfaces.

These potential exposures from a general purpose cleaner are expected to
be best represented by the short-term duration.  However, because no
dermal endpoint has been identified for the pine oil short-term duration
(i.e.,short-term dermal risks are not of concern) the risks for the
intermediate-term duration have been presented to bracket the potential
risks for the regulatory managers.  The dermal portion of the risks
presented (as opposed to short-term inhalation) should not be included
into the aggregate risk because they are not believed to be
representative of the pine oil use pattern.

An application rate of 1.5 ounces of liquid pine oil-containing product
diluted in 1 gallon of water has been identified for wiping, and mopping
application methods (EPA Reg. No. 4313-9).  The 80% ai product is the
highest percent ai formulation found, there are, however, many other
labels with lower ai percentages.  The dilution rate for the application
of treated cleaning products is 0.075 lb ai/gallon (1.5 oz/gal x 1
gal/128 oz x 8 lb/gal x 80% ai) for the wiping and mopping application
methods.  CMA data were used to determine the unit dermal and inhalation
exposures.  The inhalation portion of the exposure from CMA is not the
vapor phase but rather resulting from aerosols/splashing of liquid.  
The no gloved CMA unit exposure data for wiping and mopping were used to
determine the dermal and inhalation exposure.  It was assumed that 0.5
liter is used for wiping and 1 gallon for mopping.  The 0.5 liter
assumption for the wiping is a screening-level estimate and should be
refined by the registrant.  

Because pine oil has a relatively high vapor pressure (0.2 mmHg @ 20 C),
there is also the concern for potential vapor inhalation exposure.  To
determine the potential inhalation exposure resulting from the vapor of
pine oil, the model EFAST (Exposure and Fate Assessment Screening Tool)
was used to estimate the air concentration. 	OPPT/EETD has developed the
model, EFAST, to estimate air concentrations.  More information and
access to the EFAST model is available at
http://www.epa.gov/opptintr/exposure/.  In summary, EFAST Version 1.0
bases its air concentration estimates on physical/chemical properties. 
The air concentration estimates for the pine oils are based on the
model’s standard input parameters.  EFAST presents a peak air
concentration as well as a daily air concentration.  The peak air
concentration estimate “... is the highest instantaneous air
concentration that is modeled during the exposure event.”  This peak
air concentration is not expected for any appreciable length of time.

EFAST was used to model the air concentration from general purpose
cleaners using a weight fraction of 0.009 for the pine oil cleaning
solution/water (i.e., 0.9 percent).  EFAST indicates a peak
concentration of 3.94 mg/m3 from this activity. Because the peak
concentration does not represent a daily inhalation exposure, the daily
dose rather than the peak estimate from EFAST is used to compare to the
short-term inhalation toxicological endpoint.  If a short-term
toxicological endpoint of less than one day were to be generated it
should be compared to the peak air concentration estimate.  However,
because the toxicological endpoint of concern is based on greater than
one day of exposure, the daily dose rate of 0.035 mg/kg/day from EFAST
is used in this assessment.  The daily dose rate is based on the average
daily concentration of 0.19 mg/m3. 

The results of the MOE analysis for these scenarios are presented in
Table 6.  The calculated dermal MOEs (intermediate-term) are not of
concern for any of the scenarios (MOE = 570 and 2,900, for wiping and
mopping, respectively).  The intermediate-term dermal risks are
presented to bracket the potential risks as there are no short-term
dermal toxicological concerns.  Using the CMA data, the calculated
inhalation MOEs (all durations) for the wiping and mopping are not of
concern because the estimated MOEs of 5,300 and 20,000, respectively,
are above the target MOE for 1,000.  This estimate is based on the 80
percent active ingredient.  The risks for the lower percent active
ingredient formulations of pine oil will be proportional to the percent
active ingredient.  The results of the EFAST model exposure of 0.035
mg/kg/day indicate an inhalation MOE (all exposure durations) from the
vapor of pine oil to be 1,400.  Therefore, the vapor inhalation portion
of pine oil is not of concern (i.e., above the target MOE of 1,000).



Table 7. Calculation of Dermal and Inhalation MOEs based on CMA Data 

for Residential Handlers a

Exposure Scenario

	

	

Method of Application	

Dermal Unit Exposure (mg/lb ai) b	

Inhalation Unit Exposure   (mg/lb ai) c	

Appl. Rate d

(lb a.i./ gal)	

Amount Treated	

Absorbed Dermal Dose (mg/kg/day)f	

Dermal 

MOE g	

Inhalation Dose (aerosol) (mg/kg/day) (h

	

Inhalation (aerosol) MOE i

Hard Surface Disinfection	

Wiping	

2870

(CMA no glove)	

67.3

(CMA)	

0.075	

0.5

liter of product

(0.13 gal)	

0.40	

570	

0.0094	

5,300

	

Mopping	

71.6	

2.38	

0.075	

1 gallon	

0.077	

2,900	

0.0026	

20,000

a		MOEs rounded to 2 significant figures.

b 		Dermal unit exposures are from CMA (USEPA 1999; long pants,
long-sleeved shirt, no gloves).

c		Inhalation unit exposures are from CMA  (USEPA 1999).

d 		Application rates are based on the pine oil labels (1.5 oz/gal x 1
gal/128 oz x 8 lb/gal x 80% ai) 

f 		Dermal dose (mg/kg/day) = [unit exposure (mg/lb ai) * Appl. rate (
lb ai/gallon) * gallons handled / Body weight (70 kg). 

g  		Intermediate-term Dermal MOE = NOAEL  (mg/kg/day) / Daily Dose
[Where intermediate-term dermal NOAEL = 226 mg/kg/day].  Target MOE is
100.  Note: Short-term not of concern.

h  		Inhalation dose (mg/kg/day) = [unit exposure (mg/lb ai) * max appl
rate ( lb ai/gal) *  gallons handled * 100% inhalation absorption] /
Body weight (70 kg).		

i  		Inhalation MOE = LOAEL  (mg/kg/day) / Daily Dose [LOAEL for all
durations = 50 mg/kg/day].  Target MOE is 1000 for short- and
intermediate-term.

4.4.1.2	Dog Bath tc \l4 "4.4.1.2	Dog Bath 

Residential exposure to pine oil products used for washing dogs (i.e.,
specified on label as a “dog bath”) is believed to be best
represented by the short-term exposure duration.  Therefore, because a
short-term dermal endpoint was not identified (i.e., determined not to
be of concern) no estimates are presented for the dermal exposure to
homeowners bathing a dog (dog shampoo exposure estimates are very crude
and therefore not presented to bracket the risks for the
intermediate-term duration).  However, a short-term inhalation endpoint
has been identified for pine oil.  Because pine oils have a relatively
high vapor pressure, the model EFAST was used TO assess the potential
inhalation exposure.  However, EFAST does not contain an exposure
scenario for bathing a dog.  Therefore, to determine the potential
inhalation exposure to pine oil when used to bath a dog, the air
concentration estimate for general purpose cleaners was used as a
screening-level assessment.  The application rate for a dog bath (EPA
Reg. No. 62644-1) is 3 teaspoons of a 19.9 % ai formulation per gallon
of water.  Therefore, the weight fraction is determined to be 0.00078
(i.e., 3 tsp/768 tsp per gallon x ~ 8 lb/gal x 0.199 = 0.0062 lb ai per
gallon of dog bath.  Weight fraction is 0.0062 lb ai per gallon / 8 lb
per gallon wash solution density = 0.00078).  The weight fraction used
for the general purpose cleaner assessment above was higher – 0.009. 
Therefore, the estimated inhalation risk for the dog bath is less than
that posed by the cleaner use (i.e., higher MOE than the 1,400 estimated
above) and not of concern. 

4.4.2	Residential Postapplication Exposure tc \l3 "4.4.2	Residential
Postapplication Exposure 

Post-application exposures can occur to toddlers from the dermal, oral
(incidental) and inhalation routes from floors that have been mopped 
with a product containing pine oil.  Additionally, adults may be exposed
to inhalation exposures after this use  Although residential floors are
believed to be washed/moped on an intermittent basis (perhaps weekly),
facilities such as day care centers may clean the floors more often. 
Therefore, the intermediate-term dermal risks have been presented (no
short-term dermal endpoints of concern).  In addition, both the short-
and intermediate-term incidental oral endpoints are provided to assess
the potential risks.  The short- and intermediate-term inhalation
exposure to vapors of pine oil after treatment are also of potential
concern.  Finally, there is also the potential exposure to toddlers
playing/sleeping with treated dogs.  The duration of exposure is
expected to be short-term because of the intermittent bathing of dogs
and the relatively high vapor pressure of pine oil.  Although there is
no dermal endpoint of concern for the short-term duration, inhalation
exposure and risks are presented.

Dermal Exposure

There is the potential for intermediate-term dermal exposure to toddlers
crawling on the floors where cleaning occurs more often than in a
residence, such as at day care facilities. To determine toddler exposure
to residues on treated floor, the following equation was used: 

 

where

 	PDD	=	Potential daily dose

FR	=	Flux rate of chemical from material (mg/m2/day)

SA	=	Surface area of the body which is in contact with floor (m2)

BW	=	Body weight (kg)

The following conservative assumptions were made in calculating the
exposures/risks due to limited data:

Toddlers (3 years old) are used to represent the 1 to 6 year old age
group and are assumed to weigh 15 kg, the median for male and female
toddlers (USEPA, 2000).  A body surface area of 0.657 m2 has been
assumed, which is the median value.

1.5 ounces of liquid pine oil-containing product diluted in 1 gallon of
water (water density = 8 lb/gal) is used for mopping.  Additionally,
based on the label for EPA Registration Nos. 4313-9, it is assumed that
products containing 80% a.i. are used per gallon of water.  Therefore,
the use amount for the application of treated cleaning products is 0.075
lb ai/gallon, and that the resulting solution is applied at a rate of
1000 sq. ft. per gallon.

No data could be found regarding the quantity of solution residue left
on the floor after treatment.  As a conservative measure, it has been
assumed that 25% of the cleaner remains after the final mopping.

No transferable residue data were available that could be used to
estimate the skin transfer of pine oil from the floor.  Therefore,
Residential SOPs estimate of 10% of the amount on the hard surface is
available for dermal transfer.

The calculation of the dermal dose and the dermal MOE are presented in
Table 8.  The dermal MOE is estimated to be 570 which is above the
target MOE of 100, and therefore not of concern. 

Table 8. Intermediate-term Risks Associated with Postapplication  Dermal
Exposure on Treated Floors.

Parameter	

Value	

Rationale   

Application Rate	

1000 ft2/gallon of solution	

USEPA Assumption

Cleaning Solution	

0.075 lb ai/gallon	

Maximum rate listed on label (EPA Reg. No. 4313-9)

Transferable Residues (TR)	

9.2 mg/m2/day

	

((0.075 lb ai/gal)/(1000ft2 per gallon)) * (25% remaining)*  (10%
transfer) * (Conversion Factors)

Surface Area of Body in Contact with Floor	

0.657 m2	

Median surface area of toddler

Body Weight	

15 kg	

Median body weight of toddler

Potential Dermal Exposure	

0.40 mg/kg/day	

TR * SA/ BW

Dermal NOAEL	

226 mg/kg/day	

Dermal MOE	

570	

(Derm. NOAEL) / (Daily Derm. Dose).  Target MOE = 100.

TR = [((0.075 lb ai/gal /1000ft2) x (454 g/lb) x (1000 mg/g) x (1 ft2 /
0.093 m2)) x (0.25 remaining) x (0.1 transferable)]

Incidental Ingestion

In addition to dermal exposure, infants crawling on treated floors will
also be exposed to pine oils via incidental oral exposure.  To calculate
incidental ingestion exposure to pine oils due to hand-to-mouth
transfer, the scenarios established in the Standard Operating Procedures
(SOPs) for Residential Exposure Assessments were used.  These scenarios
use assumptions that are similar to those used in calculating exposures
due to dermal contact of pine oils from toddlers crawling on treated
floors.  The assumptions above in the dermal assessment (Table 8)
estimates the transferable residues as 0.92 μg/cm2 (equivalent to 9.2
mg/m2). 

 The estimated potential ingestion dose rate immediately after
application would be calculated as follows:

PDRnorm= ISRt x SA x FQ x SE x ET x 0.001 mg/μg

BW

where:

PDRnorm	=		Potential dose rate (mg/kg/day);

ISRt		=		Indoor Surface Residue (μg/cm2) at time 0;

SA		=		Surface area of the hands that contact both the treated area, and
the individuals mouth (cm2/event);

FQ		=		Frequency of hand-to-mouth events (events/hr); 

SE		=		Saliva extraction efficiency of 50%; and,

ET		=		Exposure Time (4 hrs/day)

BW		=		Body weight (15 kg)

The surface area used for each hand-to-mouth event is 20 cm2.  It is
assumed that there are 20 hand-to-mouth exposure events per hour (90th
percentile) for the short-term duration and 9.5 events per hour for the
intermediate-term duration (mean).  The short-term incidental oral NOAEL
of 50 mg/kg/day (target MOE = 100) is believed to best represent the
homeowner uses because of the intermittent nature of cleaning the floor
and the intermediate-term duration best represents uses in day care
centers.  The intermediate-term incidental oral NOAEL is the same but
the target MOE is 1,000.  The potential dose rate (PDR) using this
equation for the short-term exposure is 0.052 mg/kg/day and 0.023
mg/kg/day for the intermediate-term, resulting in a hand-to-mouth
short-term MOE for toddlers of 960 and 2,200 for the intermediate-term. 
Therefore, the incidental oral exposure is not of concern for either
exposure duration (i.e., above the target MOE).

Inhalation Exposure

Postapplication inhalation exposure to adults and toddlers after pine
oil use (as a general cleaner and/or dog bath) is concern because of the
relatively high vapor pressure of pine oil (i.e., 0.2 mm Hg @ 20C).  No
postapplication air concentration data have been submitted to determine
potential inhalation risk.  Therefore, EFAST was used to present a
screening-level estimate of the potential inhalation risk.  The
inhalation toxicological endpoint represents both the short- and
intermediate-term exposure durations.  The postapplication estimates are
based on the EFAST results for the air concentration and inhalation dose
from the adult handlers.  The toddler risk estimates are corrected for
the lower body weight (i.e., 15 kg) and breathing rate (i.e., 8.3
m3/day).  

EFAST was used to model the air concentration from general purpose
cleaners using a weight fraction of 0.009 (i.e., 0.9 percent).  EFAST
indicates a peak concentration of 3.94 mg/m3 from this activity. Because
the peak concentration does not represent a daily inhalation exposure,
the daily dose rather than the peak estimate from EFAST is used to
compare to the short-term inhalation toxicological endpoint.  If an
acute (less than one day) toxicological endpoint were to be generated it
should be compared to the peak air concentration estimate.  However,
because the toxicological endpoint of concern is based on greater than
one day of exposure, the daily dose rate of 0.035 mg/kg/day from EFAST
is used in this assessment for adults and 0.11 mg/kg/day for toddlers
(i.e., 0.19 mg/m3 x 8.3 m3/day x (1/15kg)).  The daily dose rate is
based on the EFAST average daily concentration of 0.19 mg/m3.   The
inhalation MOE for adults is not of concern (i.e., MOE = NOAEL of 50
mg/kg/day / 0.035 mg/kg/day = 1,400, target MOE of 1,000).  However,
based on the same scenario, the toddler short-term inhalation risk is of
concern because of the difference in body weight and breathing rate
(i.e., MOE = NOAEL of 50 mg/kg/day / 0.11 mg/kg/day = 450, target MOE of
1,000).  

EFAST was also used to estimate the potential inhalation risks resulting
from the treatment of dogs.  Although EFAST does not provide a scenario
for pets, it does provide a screening-level assessment for cleaning
products.  Based on the cleaning product scenario and a weight fraction
of 0.00078 (pine oil dog wash solution concentration), the acute adult
dose rate is 0.0068 mg/kg/day.  The short-term inhalation MOE is 7,400
which is not of concern (short-term target MOE is 1,000).

5.0 	AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION tc \l1 "5.0 
AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION 

In order for a pesticide registration to continue, it must be shown that
the use does not result in “unreasonable adverse effects on the
environment”.  Section 2 (bb) of FIFRA defines this term to include
“a human dietary risk from residues that result from a use of a
pesticide in or on any food inconsistent with standard under section
408...” of FFDCA.  Consequently, even though no pesticide tolerances
have been established for pine oils, the standards of FQPA must still be
met, including “that there is reasonable certainty that no harm will
result from aggregate exposure to pesticide chemical residue, including
all anticipated dietary exposures and other exposures for which there
are reliable information.”   Aggregate exposure is the total exposure
to a single chemical (or its residues) that may occur from dietary
(i.e., food and drinking water), residential, and other non-occupational
sources, and from all known or plausible exposure routes (oral, dermal,
and inhalation).  

5.1	Acute and Chronic Dietary Aggregate Risk

Aggregate dietary risk includes exposure from food and drinking water. 
Pine oil is used as a hard surface disinfectant, and dietary exposures
from the use of the five products have been noted above in the dietary
exposure and risk section. Pine oil is not expected to impact drinking
water from the registered uses as noted above.  With respect to the five
pine oil formulations noted in the dietary exposure and risk section of
this chapter, only the El-Pinol 60 formulation show a dietary risk of
concern for chronic exposure, and only  in  children.    

5.2	Short-, Intermediate-, and Long-Term Aggregate Risk 

In accordance with the policy of the Office of Pesticide Programs,
short-, intermediate-, and long-term risk typically involves exposure
from dietary sources (food and water) in combination with residential
scenarios that have a reasonable chance of co-occurrence.  In the case
of pine oil, residential scenarios are not felt to be long-term
exposures, only short-term and sometimes intermediate-term. Thus, there
is no long-term aggregate risk assessment. 

For the short-term aggregate assessment, adult exposures from diet  and
cleaning could be aggregated.   In the case of pine oil, the dietary
exposure is aggregated with the inhalation exposures from  cleaning as
the study and endpoint describing the effects from these two routes of
exposure was the same.  The dermal exposure is not included as the study
and endpoint defining the toxicity by the dermal route differ from the
oral and inhalation route. 	

For toddlers, dietary exposure is aggregated with the  incidental oral
exposure from the floor cleaning. Dermal exposures are not aggregated
for the same reason as stated for adults. In addition, there are no
aggregate intermediate-term scenarios for toddlers, although there are
intermediate-term exposure scenarios. 

For adult aggregate exposures, the total Margin of Exposure method is
used to aggregate as the uncertainty factor for the dietary and the
inhalation exposure is similar (1000). Children’s aggregate exposures
are calculated using the Aggregate Risk Index method  as the uncertainty
factor for the chronic dietary endpoint (1000) is dissimilar to the
uncertainty factor for the short- term incidental oral exposure (100). 
Thus, for children’s exposures,  ratios of MOE/UF are calculated to
yield a risk index (RI) for each scenario aggregated, which can then be
inserted into the equation:

ARI =                        1                  

     1    +     1    + ....   1  

                             RI1         RI2           RIn

The result is compared against the number 1.   ARIs greater than 1
indicate no risk of concern while values less than 1 indicate the
potential for risk.   



                                      Aggregate Short-term Risks for
Adult Males

Dietary exposure	

Diet MOE1	

Inhalation exposure2

(mg/kg/day)	

Inhalation MOE	

total MOE

0.0035	

14285	

0.0094	

5300	

4000

0.0035	

14285

	

4000

0.0034	

14705

	

4032

0.0267	

1872

	

1408

0.0084	

5952

	

2941

1Diet MOE = short-term incidental oral NOAEL / food exposure

2inhalation exposure  from cleaning product (wiping).

Target MOE is 1000. 

 

                                      Aggregate Short-term Risks for
Adult Females

Dietary exposure

(mg/kg/day)	

Diet MOE1	

Inhalation exposure3

(mg/kg/day)	

Inhalation MOE	

total MOE

0.0041	

12200	

0.0094	

5300	

3800

0.0041	

12200

	

3800

0.0039	

12800

	

3900

0.0311	

1600

	

160

0.0098	

5100

	

2700

1Diet MOE = short-term incidental oral NOAEL / food exposure

3inhalation exposure from a cleaning product (wiping)

Target MOE is 1000.



                                      Aggregate Short-term Risks for
Children/toddlers

Dietary exposure	

Diet MOE1	

Diet MOE/UF2	

Inhalation exposure3 (mg/kg/day)

(MOE)

MOE/UF	

Incidental Oral exposure4 (mg/kg/day) (MOE) MOE/UF	

ARI

0.0164	

3048	

3.0	

0.11

(MOE =450)

0.45	

0.052

(MOE=960)

0.96	

0.4

0.0164	

3048	

3.0

	

0.4

0.0158	

3164	

3.1

	

0.4

0.124	

403	

0.4

	

0.17

0.039	

1282	

1.2

	

0.25

1Diet MOE = short-term incidental oral NOAEL / food exposure

2MOE/UF = calculated MOE / chronic dietary UF [1000]	

3inhalation post-application exposure from cleaning product  

4Incidental oral exposure from treated floors

The above calculations show ARIs of less than 1 for children/toddlers. 
As shown, the ARI for children ranges from 0.17-0.4, which is below the
target ARI of (1, and thus, exceed the Agency’s level of concern.

The post-application exposure from the 80% ai cleaning product is a
primary driver for the risk estimate derived here, except when the
dietary estimate from the El-Pinol formulations contributes
significantly to the ARI value. 

5.3 Dermal Aggregate Risk

Dermal exposures are considered short-term only except for the toddler
dermal scenario from crawling on treated floors. For pine oil, no
short-term dermal endpoint was identified in the available toxicology
database.  As there is only one quantified dermal scenario, no
aggregation of dermal exposure is performed for pine oil.  

 

6.0	OCCUPATIONAL EXPOSURE AND RISK tc \l1 "6.0	OCCUPATIONAL EXPOSURE
AND RISK  

A detailed residential and occupational risk assessment for pine oils is
provided in the attached Appendix.  A summary of the exposures and risks
to occupational handlers is provided below.

6.1	Occupational Handlers tc \l2 "6.1	Occupational Handlers 

The handlers were identified as those individuals who use pine
oil-containing products in commercial/institutional setting (including
industrial and medical uses).  The following short- and
intermediate-term  handler exposure scenario was evaluated for pine oil:

Handling pine oil-containing cleaning products through low pressure
spray, wiping, and mopping application methods.

While pine oil products have other listed uses, these additional
exposure scenarios are not expected to result in higher exposures than
the selected scenario.  Therefore, exposures to pine oil from cleaning
would be considered representative of a high end exposure.  

There are no chemical-specific exposure data to assess cleaning product
applications.  Therefore, dermal and inhalation exposures were assessed
for low pressure spray, wiping, and mopping application methods using
surrogate data.  Specifically, values from the Chemical Manufacturers
Association (CMA) antimicrobial study (U.S. EPA, 1999) were used.  The
dermal and inhalation exposures from these techniques have been
normalized by the amount of active ingredient handled and reported as
unit exposures (UE) expressed as mg/lb ai handled.  In addition, product
label maximum application rates, related use information, and Agency
standard values were used to assess occupational handler exposures. 
Specifically, it was assumed that occupational handlers will use 1.5
ounces of liquid pine oil-containing 80% product diluted in 1 gallon of
water for low pressure spray, wiping, and mopping application methods. 
Therefore, the use amount for the application of diluted cleaning
solutions is 0.075 lb ai/gallon for the low pressure spray, wiping, and
mopping application methods.   For spraying and mopping it is assumed
that 2 gallons (each) are used for daily cleaning and that 1 liter is
used for wiping.

The results of the MOE analysis are presented in Table 9.  The
calculated MOEs indicate that aerosol-generated inhalation exposure
risks are not of concern (i.e., MOEs ( 1,000) for short- and
intermediate- term exposures under all scenarios assessed.  For dermal
exposure, the calculated MOEs indicate that risks do not exceed the
Agency’s level of concern for the low pressure spray and mopping
scenarios (i.e., MOE > 100), but exceed the level of concern for wiping.

The aerosol-generated  inhalation exposure and risk estimates from the
CMA data discussed above do not account for the potential vapor
inhalation exposure to pine oil (pine oil has a relatively high vapor
pressure).  Therefore, the potential vapor inhalation exposure to
handlers are addressed by modeling of the air concentrations.  Because
the occupational handlers use the same weight fraction of pine oil as
the residential handlers, the same type of application techniques (i.e.,
wipes, sprays, mop), and will clean in various rooms to accommodate the
additional amount handled (e.g., moving room-to-room in a hotel), the
air concentrations and vapor-generated inhalation risk estimates will be
similar to those experienced by the residents.  Based on these
assumptions, the short- and intermediate-term vapor-derived inhalation
risks are not of concern (i.e., MOE of 1,400 greater than the target MOE
of 1000 for the average daily dose).		

	Table 9. Estimates of Exposure and Risks to Primary Occupational
Handlers of Pine Oil

Exposure Scenario

	

Dermal Dose (mg/kg/day)a	

Inhalation Dose (mg/kg/day)b	

Dermal 

MOE c	

Inhalation MOE d

Cleaning products - 

Low pressure sprayer	

0.41	

0.0015	

550

	

34,000

Cleaning products - Wiping	

0.81	

0.019	

280	

2,600

Cleaning products - Mopping	

0.15	

0.0051	

1,500	

9,800

a 	Abs. Dermal Dose (mg/kg/day) = [Appl. rate (lb ai/gallon) * Gallons
handled * Unit Exposure (mg/lb ai)] / Body Weight (70 kg)].  Clothing
attire is long pants, long sleeved shirts, and no gloves.

b	Inhalation Dose (mg/kg/day) = [Appl. rate (lb ai/gallon) * Gallons
handled * Unit Exposure (mg/lb ai) * 100% Inhalation Absorption] / Body
Weight (70 kg).	

c  	Dermal MOE= Dermal NOAEL (226 mg/kg/day)/Dermal Dose (mg/kg/day).
Target MOE is 100.

d	Inhalation MOE= Inhalation NOAEL (50 mg/kg/day)/ Inhalation Dose
(mg/kg/day).  Target MOE is 1,000 for short- and intermediate-term
exposure.

6.2	Occupational Postapplication Exposure tc \l2 "6.2	Occupational
Postapplication Exposure 

Occupational postapplication dermal and aerosol-generated inhalation
exposures to pine oil are likely to be minimal compared to handler
exposure because of dilution with water.  Therefore, a screening level
assessment was not conducted for these occupational postapplication
scenarios.  Any residential postapplication exposure resulting from the
occupational/commercial treatments (e.g., cleaning of day care centers)
are assessed in the residential section above.

There is, however, the for potential short- and intermediate-term
postapplication exposures to pine oils based on the relatively high
vapor pressure.  Postapplication inhalation exposure is expected for
bystanders remaining in areas of treatment.  At this time, air
concentration measurements taken after pine oil treatments are not
available.  In addition, modeled results for inhalation exposure are not
specific for occupational postapplication uses.  Therefore, the air
concentration for the 80% product (diluted in water to a weight fraction
of 0.009) that was used in the EFAST model estimate listed in the
residential handler section above is expected to yield similar results
for bystanders.  The average daily air concentration is 0.19 mg/m3. 
Using an 8-hour workday, the dose is estimated to be 0.027  mg/kg/day
(i.e., 0.19 mg/m3 x 1.25 m3/hr breathing rate x 8 hr/day x (1/70 kg
BW)).  The short- and intermediate-term inhalation MOE is 1,900, and
therefore, not of concern (i.e., LOAEL of 50 mg/kg/day / 0.027
mg/kg/day, target MOE = 1,000).  

7.0	INCIDENTS tc \l1 "7.0	INCIDENTS 

The main routes of exposure reported in incident reports are oral,
dermal, and inhalation.  Ingestion incidents have occurred due to:
people have mistaking a container of pine oil as something drinkable,
people trying to commit suicide, or people using a product for its
alcohol content.  Thirty-one cases of ingestion were found in the
databases, 7 of which resulted in death.  Dermal exposure causes
irritation, rash, and allergic reaction.  Inhalation exposures cause
respiratory symptoms–shortness of breath, etc.  Ocular exposure causes
imitation and blurred vision.  There was nothing in the databases
regarding chronic effects, and no evidence of delayed toxicity.  Only a
small fraction of the cases involved something serious enough to involve
medical attention.  

8.0	ENVIRONMENTAL FATE ASSESSMENT tc \l1 "8.0	ENVIRONMENTAL FATE
ASSESSMENT 

No submitted data or open literature are available regarding the fate
characteristics of pine oil, which is a complex mixture of terpenes
produced by high temperature distillation of oil of turpentine or by
catalytic hydration of terpenes. The fate properties of the major
components of pine oil, namely alpha-terpineol and alpha- and
beta-pinene, were used instead to assess the environmental fate of this
complex blend.  Environmental fate properties of these three components
are shown in Table 9.  Alpha- and beta-pinene’s bioconcentration
factors of 2,800 Estimated) and 440 (estimated), respectively, and high
log Kow values suggest that bioaccumulation or bioconcentration in
aquatic organisms is possible.  Likewise, alpha-terpineol’s
bioconcentration factor of 110 suggests that  a low to moderate
potential for bioconcentration.. However, a recent paper by the National
Park Service of Colorado and Colorado State University indicates that
turpentine oil (of which alpha/beta pinenes constitute up to 90%) does
not appear to bioaccumulate possibly due to the fact that turpentine oil
is highly biodegradable (Roy Erwin, National Park Service, Water
Resource Division, Fort Collins, Colorado, July 1997).  Both, alpha- and
beta-pinene undergo rapid biodegradation in water as indicated by
aqueous aerobic degradation studies. Estimated volatilization half-lives
for alpha- and beta-pinene are 4 hours and 1.2 hours, respectively, in a
model river. Alpha-terpineol, on the other hand, does not seem to
biodegrade as rapidly as alpha-/beta-pinene. The estimated half-life for
alpha-terpineol is 4 days in a model river. 

Alpha- /beta-pinene and alpha-terpineol have been shown to be readily
biodegradable in soil by microorganisms. In addition, the Henry’s Law
Constants for these chemicals indicate that they will volatilize from
most moist soils. However, they are expected to absorb with a high
degree to suspended particles and sediments in the water column based on
estimated Koc values (1,000 for alpha-pinene and alpha-terpineol and
1,200 for beta-pinene). 

In general, the rapid volatilization and biodegradation and low
half-lives in water of alpha-/beta-pinene and alpha-terpineol indicate a
low probability for contamination of water systems.  Due to their
volatilization, biodegradation and low mobility in soils, contamination
of ground or surface water systems is not likely.  

Table 10.  Environmental Fate Properties of Alpha- and Beta-Pinene and
Alpha-Terpineol a

Parameter	

Alpha-Pinene	

Beta-Pinene	

Alpha-Terpineol

Vapor Pressure @ 25C (mm Hg)	

4.75	

2.93	

0.0423

Henry’s Law Constant (air/water partition coefficient) (atm-cu-m/mole)

0.107	

0.16	

1.2x10-5

KOC (organic carbon ratio in soil)	

1000	

1200	

1000

Log KOW (octanol/water partition coefficient	

4.83	

4.35	

2.98

BCF	

2800	

440	

110

Note: a) Estimated values, from EPI Suite Program.

9.0	ECOTOXICOLOGY ASSESSMENT tc \l1 "9.0	ECOTOXICOLOGY ASSESSMENT 

Environmental Modeling/Exposure

Environmental exposure modeling was not conducted for the indoor uses of
Pine Oil considered in this RED. Environmental exposure is not expected
to result when registered products are used according to label
directions.

Ecological Hazard and Risk

Results of an acute oral toxicity study with northern bobwhite quail
indicate that pine oil is practically non-toxic to avian species on an
acute oral basis. In an subacute avian dietary study, pine oil was also
found to be practically non-toxic to avian species. The acute toxicity
of pine oils to mammals is defined by rat toxicity values obtained from
studies conducted to support data requirements for human health risk
assessment. Toxicity data for pine oils are presented in Tables 10-12. 
Acute toxicity testing with estuarine and marine organisms is not
required for pine oil.   

Pine oil is slightly toxic to freshwater fish and invertebrates on an
acute basis. Chronic toxicity testing for freshwater organisms is not
required for pine oils and no information is currently available.
Likewise, plant toxicity information on pine oil is not available;
however, terrestrial and aquatic plant testing is not required to
support the indoor uses of pine oil.



Table 11. Acute Oral Toxicity of Pine Oil

Species	

Endpoint	

Toxicity Category

Bird

Bobwhite quail (Colinus virginianus)	

LD50 > 2,250 mg/kg

NOEL = 486 mg/kg	

Practically non-toxic

Mammal

Rat	

LD50 = 2.7 g/kg (combined)	

----

Table 12. Acute Ecotoxicity of Pine Oil

Species	

Endpoints	

Toxicity Category

Freshwater Fish

Rainbow trout (Oncorhynchus mykiss)	

LC50 = 18.4 ppm

NOEC = 10 ppm	

Slightly toxic

Bluegill  (Lepomis macrochirus)	

LC50 = 54.8 ppm

NOEC = 36 ppm	

Slightly toxic

Freshwater Invertebrate

Water flea

(Daphnia magna)	

EC50 = 24.5 ppm

NOEC = 11 ppm	

Slightly toxic

Table 13. Other Toxicity Studies of Pine Oil

Species

	

Endpoint	

Toxicity Category

Subacute Dietary Toxicity

Mallard  (Anas platyrhynchos)	

LC50 >5,620 ppm	

Practically non-toxic

Acute Dermal Toxicity

Rat	

>2,000 mg/kg	

---

Developmental Toxicity

Rat	

NOAEL= 50 mg/kg/day (maternal and developmental)

LOAEL = 600 mg/kg/day (maternal and developmental)	

—

The indoor uses of Pine oil considered in this RED make it unlikely
that any appreciable exposure to terrestrial or aquatic organisms would
occur when it is used according to label directions. The low toxicity to
birds, mammals, and aquatic organisms makes it even more unlikely that
the indoor uses of this chemical pose a risk to these species.  Risk to
plants cannot be addressed due to a lack of phytotoxicity data; however,
exposure to plants is unlikely from the indoor uses of this chemical.			

Endangered Species Consideration

The Agency has developed the Endangered Species Protection Program to
identify pesticides whose use may cause adverse impacts on endangered
and threatened species, and to implement mitigation measures that
address these impacts.  The Endangered Species Act requires federal
agencies to ensure that their actions are not likely to jeopardize
listed species or adversely modify designated critical habitat.  To
analyze the potential of registered pesticide uses to affect any
particular species, EPA puts basic toxicity and exposure data developed
for risk assessments into context for individual listed species and
their locations by evaluating important ecological parameters, pesticide
use information, the geographic relationship between specific pesticide
uses and species locations, and biological requirements and behavioral
aspects of the particular species.  A determination that there is a
likelihood of potential impact to a listed species may result in
limitations on use of the pesticide, other measures to mitigate any
potential impact, or consultations with the Fish and Wildlife Service
and/or the National Marine Fisheries Service as necessary. 

Based on the low likelihood of environmental exposure from the
registered indoor uses, coupled with the low toxicity of pine oil to
fish, aquatic invertebrates, mammals, and birds, adverse impacts to
endangered birds, fish and aquatic invertebrate species are not expected
from the registered uses of pine oil.  Risk to endangered plants cannot
be addressed due to a lack of phytotoxicity data; however, exposure to
endangered plants is unlikely from the indoor uses of this chemical.

10.0	 tc \l1 "10.0	 REFERENCES tc \l1 "REFERENCES 

U.S. EPA.  1997.  Standard Operating Procedures (SOPs) for Residential
Exposure Assessments.  Contract No. 68-W6-0030.  Prepared by the
Residential Exposure Assessment Work Group.  Office of Pesticide
Programs, Health Effects Division and Versar.  July 1997.

USEPA.  1999.  Evaluation of Chemical Manufacturers Association
Antimicrobial Exposure Assessment Study.  Memorandum from Siroos
Mostaghimi, Ph.D., USEPA, to Julie Fairfax, USEPA.  Dated November 4,
1999.  DP Barcode D247642.

USEPA,  2000.  Residential SOPs.  EPA Office of Pesticide
Programs–Human Health Division. Dated April 5, 2000.

USEPA, 2002.  Determination of the Appropriate FQPA Safety Factor(s) in
Tolerance Assessment. Office of Pesticide Programs, February 2002. 

Campbell, S.M. and J.B. Beavers.  1994.  Pine oil: Acute oral toxicity
study with the Northern Bobwhite.  August 31, 1994.  Wildlife
International Ltd., Laboratory Report ID: 274-104.  MRID No. 433752-01.

Campbell, S.M. and J.B. Beavers.  1994.  Pine oil: Acute oral toxicity
with the Mallard.  August 31, 1994.  Wildlife International Ltd.,
Laboratory Report ID: 274-105.  MRID No. 433752-02.

Campbell, S.M. and J.B. Beavers.  1994.  Pine oil: Dietary LC50 study
with the Mallard.  August 31, 1994. Wildlife International Ltd.,
Laboratory Report ID: 274-103.  MRID No. 433752-04.

Graves, W.C. and J.P. Swigert.  1994.  Pine oil: Ninety-six hour
flow-through acute toxicity test with the Bluegill (Lepomis
macrochirus).  August 19, 1994. Wildlife International Ltd., Laboratory
Report ID: 274A-101.  MRID No. 433752-05. 

Graves, W.C. and J.P. Swigert.  1994.  Pine oil: Ninety-six hour
flow-through acute toxicity test with the Rainbow Trout (Oncorhynchus
mykiss).  August 19, 1994. Wildlife International, Laboratory Report ID:
274A-102.  MRID No. 433752-06. 

Graves, W.C. and J.P. Swigert.  1994.  Pine oil: Forty-eight (48) hour
flow-through acute toxicity test with the Cladoceran (Daphnia magna). 
August 19, 1994. Wildlife International, Laboratory Report ID: 274A-103.
 MRID No. 433752-07. 

U.S. Environmental Protection Agency (EPA).  2002.  ECOTOX User Guide:
ECOTOXicology Database System.  Version 3.0.  Available:
http://www.epa.gov/ecotox/

Bonfiglio, JF; Hintze KL.; and Siegell, LT.  1987.  A Multi-Center
Evaluation of the Incidence and Severity of Pine-Oil Ingestion. 
Presented  in the meeting of the American Academy of Clinical Toxicity,
American Association of Poison Control Centers, American Board of
Medical Technology, Canadian Association of Poison Control Centers,
Vancouver, British Columbia, Canada.  September27- October 2, 1987. 
Abstract published in Vet. Hum. Toxicol.  29(6): 481.

Brook, M.;  McCarron, M.; and Mueller, JA.  1989.  Pine Oil Cleaner
Ingestion.  Annals of Emergency Medicine.  18:391-395

Welker, JA and Zaloga, GP.  1999.  Pine Oil Ingestion - A Common Cause
of Poisoning.  Chest:  1822-1826.

EPA, 1997. “Exposure Factors Handbook, Vol III: Activity Factors.”
EPA/600/P-95/002FC

EPA, 1999. “ Available Information on Assessing Exposure from
Pesticides, A User’s Guide,   
http://www.epa.gov/fedrgstr/EPA-PEST/2000/July/Day-12/p17493.htm

FDA, 2003. “ Sanitizing Solutions: Chemistry Guidelines for Food
Additive Petition.”, January,                1993 version,
Http://www.cfsan.fda.gov/~dms/opa-cg3a.html.

Hazard Substances Databank (HSDB), A Database of the National Library of
Medicine’s TOXNET System.

EPI Suite, Version 3.12,
http://www.epa.gov/opptintr/exposure/docs/updates_episuitedl.htm

Roy Erwin, National Park Service, Water Resource Division, Fort Collins,
Colorado, July 1997	

USEPA.  1997.  Exposure Factors Handbook. Volume I-II.  Office of
Research and Development.  Washington, D.C.  EPA/600/P-95/002Fa.

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萏ﾦ葞ﾦ摧₨Aఀ9.  Evaluation of Chemical Manufacturers
Association Antimicrobial Exposure Assessment Study.  Memorandum from
Siroos Mostaghimi, Ph.D., USEPA, to Julie Fairfax, USEPA.  Dated
November 4, 1999.  DP Barcode D247642.

USEPA.  2000.  Residential SOPs.  EPA Office of Pesticide
Programs–Human Health Division. Dated April 5, 2000.

421894-01C		K. Davis, 1992, CSMA Pine Oil Joint Venture, RegWest
Company, Greeley, CO 80632-2220

421894-02		L.S. Desai, 1992,  CSMA Pine Oil Joint Venture, Toxikon
Corporation, Woburn, MA 01801



421894-03		L.S. Desai, 1991, CSMA Pine Oil Joint Venture, Toxikon
Corporation, Woburn, MA 01801

 PAD = Population Adjusted Dose = Acute or Chronic RfD

FQPA Safety Factor

	

	

Pine Oil Risk Assessment

  PAGE  35  of   NUMPAGES  37