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`

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

 AND TOXIC SUBSTANCES

August 22, 2005

MEMORANDUM

SUBJECT: Exemptions from the Requirement of a Tolerance for 

C9 Rich Aromatic Hydrocarbons, PC Code 886810, PP# 4E6935, DP Barcode

316616

C10-11 Rich Aromatic Hydrocarbons, PC Code 806602, PP# 4E6934, DP

Barcode 316615

C11-12 Rich Aromatic Hydrocarbons, PC Code 806602 & 806501, PP# 4E6937; 

DP Barcode 316617

MRIDs 46369812, 46369813, 46398901, 46398902, 46398903, 46398904,

46398905, 46398906, 46398907, 46398908, 46398909, 46398910, 46398911

FROM: Becky Daiss

Environmental Health Scientist

Reregistration Branch 4

Health Effects Division (7509C)

THRU: Susan V. Hummel 

Branch Senior Scientist

Reregistration Branch 4

Health Effects Division (7509C)

TO: Pauline Wagner, 

Inerts Coordinator

Registration Division (7505C)

This provides a science assessment for C9 Rich Aromatic Hydrocarbons, C10-11 Rich

Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons based on data submitted for

the corresponding Exxon Mobil trade name products, Aromatic 100 Fluid, Aromatic 150 Fluid,

and Aromatic 200 Fluid respectively. The attached assessment summarizes available

information on the use, physical/chemical properties, toxicological effects, exposure profile, and

environmental fate of these three pesticide inert ingredients. The purpose of this document is to

evaluate the proposed exemptions from the requirement of a tolerance for residues of the three
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inert ingredients as required under the Food Quality Protection Act (FQPA) section 408. This is

a conservative risk assessment in which high-end assumptions were used for most key

parameters. HED is confident that this analysis does not underestimate the risk associated with

exposure to C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12

Rich Aromatic Hydrocarbons.

1.0 EXECUTIVE SUMMARY

This assessment evaluates potential risks from use of C9 Rich Aromatic Hydrocarbons,

C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons. These three

inert ingredients have been considered to be included under the existing tolerance exemptions for

petroleum oils and xylene. ExxonMobil submitted dietary and residential exposure/risk

assessments for the trade name products Aromatic 100 Fluids, Aromatic 150 Fluids, and

Aromatic 200 Fluids; the generic names for these products are C9 Rich Aromatic Hydrocarbons,

C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons respectively. 

ExxonMobil has petitioned to have these chemicals exempted from the requirement of a

tolerance. HED has evaluated ExxonMobil’s submissions and has incorporated information

from those assessments into its risk assessment. Toxicological data submitted by ExxonMobil

provide the primary basis for HED’s hazard identification evaluation. 

Aromatic 100, 150, and 200 Fluids are ExxonMobil’s trade names for C9 Rich Aromatic

Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons

which are a multi-constituent group of related hydrocarbon compounds with closely controlled

and defined physicochemical parameters. The C9, C10-11, and C11-12 Rich Aromatic

Hydrocarbons consist of a mixture of aromatic hydrocarbons. C9 Rich Aromatic Hydrocarbons

consist primarily of alkylated benzenes that have a predominant carbon number in the range of

C9 to C10. C10-11 Rich Aromatic Hydrocarbons consist primarily of alkylated benzenes with

some alkylated naphthalenes that have a predominant carbon number in the range of C10 to C11. 

C11-12 Rich Aromatic Hydrocarbons consist primarily alkylated benzenes with some alkylated

naphthalenes that have a predominant carbon number in the range of C10 to C12. C9, C10-11, and

C11-12 Rich Aromatic Hydrocarbons are created as part of the crude oil refining process and are

widely used as pesticide inert ingredients.

Sufficient toxicity data and information on Aromatic 100, 150, and 200 Fluids are

available from the petitioner. As noted, Aromatic 100 Fluid consists primarily of linear alkyl

benzenes; Aromatic 150 and 200 Fluids consist primarily of primarily alkylated benzenes with

some alkylated naphthalenes. Both EPA and OECD have expressly identified linear alkyl

benzenes as an example of appropriate Structural Activity Relationship (SAR) categories of

chemicals. Based on common functional substructure, common metabolic pathways/kinetics of

metabolism, and comparable molecular properties, the aromatic fluids can be considered valid

analogues of each other for purposes of predicting toxicity. C9 Rich Aromatic Hydrocarbons,

C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons are therefore

considered toxicologically equivalent and are assessed together in this document. HED also

assessed potential risks from naphthalene, which comprises up to 10% of Aromatic 150 and 200
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Fluids. The toxicological data base is adequate to assess risks from exposure to naphthalene as a

component of these Aromatic Fluids. 

Based on data submitted by the petitioner on the trade name products, Aromatic 100, 150,

and 200 Fluids exhibit low acute toxicity by oral, inhalation and dermal routes (toxicity Category

III or IV by all exposure routes). They are minimally irritating to eyes and skin and negative for

dermal sensitization effects. Subchronic oral and inhalation toxicity studies indicate these

Aromatic Fluids to be relatively non-toxic except at relatively high doses. Reversible effects to

the liver, thyroid, stomach, spleen, and urinary bladder were reported at mid- and high doses in a

subchronic oral toxicity study in rats. A developmental inhalation study in mice indicates severe

maternal and developmental toxicity at the high dose (1500 ppm) and reduction in fetal weight

gain at the next lowest dose (500 ppm) but no other evidence of developmental effects nor any

adverse effects in maternal animals. An oral developmental study in rats indicates maternal

effects (decreased body weight gain and food consumption) at the mid-dose (150 mg/kg/day) but

no developmental effects at the highest dose tested (450 mg/kg/day). An inhalation reproduction

study in rats indicates reduced body weight gain in parents and off-spring at mid and high doses

(500 and 1500 ppm). Based on neurotoxicity studies, Aromatic 100, 150, and 200 Fluids are not

expected to cause any nervous system damage. Due to their complex, multi-constituent nature,

there are no substance-specific absorption, metabolism, distribution and excretion studies done

specifically on Aromatic 100, 150, and 200 Fluids. However, sufficient data are available on

aromatics to show that they are typically well absorbed, widely distributed between tissues,

extensively metabolized and rapidly excreted. Aromatic 100, 150, and 200 Fluids are of low

toxicological concern for developmental and reproductive effects, based on the available toxicity

data. Based on this finding, it is recommended that the Food Quality Protection Act (FQPA)

tenfold safety factor be reduced to 1x for this risk assessment.

The assessments of C9, C10-11, and C11-12 Rich Aromatic Hydrocarbons have been

grouped together in this document because they are toxicologically equivalent, and share similar

use patterns and potential routes of exposure. HED conducted screening level dietary and

residential exposure and risk assessments for the Rich Aromatic Hydrocarbons. HED did not

aggregate estimated exposure/risk for these chemicals, however, because it is unlikely that

products containing C9, C10-11, and C11-12 Rich Aromatic Hydrocarbons will be used

concurrently. HED also assessed potential risks from naphthalene, which comprises up to 10%

of C10-11, and C11-12 Rich Aromatic Hydrocarbons. Based on HED’s screening level

quantitative assessment, C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic

Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons do not pose dietary risks of concern. A

screening level quantitative assessment of inhalation and dermal exposures to residential

applicators indicates no risks of concern. A qualitative exposure assessment of incidental oral

exposures indicates that these compounds also do not pose risks of concern for this route of

exposure. In addition, ecological risk concerns are not likely to occur from the use of C9 Rich

Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic

Hydrocarbons as pesticide inert ingredients based on available toxicity data on aquatic and

terrestrial organisms. Therefore, it is recommended that C9 Rich Aromatic Hydrocarbons, C10-
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11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons in/on raw

agricultural commodities can be considered safe under section 408(q) of the FFDCA.

2.0 USE INFORMATION

C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12

Rich Aromatic Hydrocarbons have many uses as a pesticide inert ingredients. Most commonly,

these compounds are used as solvents for a wide variety of fungicides, herbicides and pesticides. 

The pesticide is usually dissolved in C9, C10-11, and C11-12 Rich Aromatic Hydrocarbons and

other solvents, and later is applied as an emulsion after dilution with water. Other common

solvent uses include use in ultra low volume pesticides where the pesticide is dissolved in C9,

C10-11, and C11-12 Rich Aromatic Hydrocarbons or a solvent mixture and applied at low

volumes with no addition of water. The exemptions from the requirement of a tolerance for C9

Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic

Hydrocarbons Fluids are provided in Table 1 below. 

Table 1. Chemicals Included in this Risk Assessment

Chemical Name

(Trade Name)

CAS Reg No. 40 CFR § Use 

(Pesticidal)

List

Classification

C9 Rich Aromatic

Hydrocarbons

( Aromatic 100 Fluid)

64742-95-6 180.9051

180.9102

180.9203

180.9304

solvent/co-solvent 2

C10-11 Rich Aromatic

Hydrocarbons

( Aromatic 150 Fluid) 

64742-94-5 180.9051

180.9102

solvent/co-solvent 2

C11-12 Rich Aromatic

Hydrocarbons

( Aromatic 200 Fluid)

64742-94-5 

68477-31-6

180.9203

180.9304

solvent/co-solvent 2

1. Pesticide Chemicals: Residues listed in 40 CFR §180.905 [formerly 40 CFR§ 180.1001(b)] are exempted from

the requirement of a tolerance when applied to growing crops, in accordance with good agricultural practice. 

2. Inert Ingredients: Residues listed in 40 CFR §180.910 [formerly 40 CFR§ 180.100(c)] are exempted from the

requirement of a tolerance when used in accordance with good agricultural practice as inert or occasionally active

ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest. 

3. Inert Ingredients: Residues listed in 40 CFR §180.920 [formerly 40 CFR§ 180.100(d)] are exempted from the

requirement of a tolerance when used in accordance with good agricultural practice as inert or occasionally active

ingredients in pesticide formulations applied to growing crops only. 

4. Residues listed in 40 CFR §180.930 [formerly 40 CFR§ 180.100(e)] are exempted from the requirement of a

tolerance when used in accordance with good agricultural practice as inert or occasionally active ingredients in

pesticide formulations applied to animals. 

3.0 PHYSICAL AND CHEMICAL PROPERTIES
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Table 2. Physical and Chemical Properties of Aromatic 100, 150, and 200 Fluid and Naphthalene

Aromatic 100

Fluid

Aromatic 150 Fluid Aromatic 200 Fluid Naphthalene

PC Code 886810 806602 806602 & 806501 055801 & 855801

CAS # 64742-95-6 64742-94-5 64742-94-5 

68477-31-6

91-20-3

Chemical name C9 Rich Aromatic

Hydrocarbons

C10-11 Rich Aromatic

Hydrocarbons 

C11-12 Rich Aromatic

Hydrocarbons

naphthalene

Molecular formula alkylated benzenes

C9-C10

alkylated benzenes C10-

C11

alkylated benzenes C10-

C12

C10H8

Molecular weight NA NA NA 128.18

Physical state Liquid Liquid Liquid Liquid

Vapor Pressure (20C) 2.09 mm Hg 0.62 mm Hg 0.043 mm Hg 0.085 mm Hg

Density 0.873 g/cm3

 15.6 C 0.899 g/cm3 15 C 0.995 g/cm3 15 C

Boiling Point 161-171 C at 1013

hPa

184-205 C at 1013 hPa 232-275 C at 1013 hPa 217.9 

Freezing Point 7 F -18 C -19 C NA 

Flash Point 46 C closed cup 63 C closed cup 95 C closed cup NA

Water Solubility 11-69 mg/L 4.8-55 mg/L 4.8-55 mg/L 31 mg/L

Henry’s Law constant 6E-03 to 33E-03 

atm-m3

/mole

4E-04 to 4.6E-04 

atm-m3/mole

4E-04 to 4.6E-04 atmm3

/mole

4.4E-04 

 atm-m3/mole

Log P (octanol-water) >3.0 >3.0 >3.0 3.3

Table 3. Fugacity Modeling (Mackay Level 1)

Aromatic 100 Fluid Aromatic 150 Fluid Aromatic 200 Fluid

Air 98.6-99.8% 78.1-96.1% 78.1-96.1%

Soil 0.1-0.5% 1.8-6.9% 1.8-6.9%

Water 0.1-0.5% 0.5-9.8% 0.5-9.8%

4.0 HAZARD ASSESSMENT

4.1. Hazard Profile

This hazard assessment was developed using toxicity data provided by the petitioner. 

The toxicity data base for the trade name products Aromatic 100, 150, and 200 Fluids is

adequate for the selection of doses and endpoints for use in risk assessment of C9, C10-11, and

C11-12 Rich Aromatic Hydrocarbons. HED evaluated the available studies and established

acute and chronic RfDs, as well as doses and endpoints for inhalation and dermal exposure

scenarios. Endpoints were not selected for residential incidental oral exposure routes based on

use and physical chemical property data which indicates that these scenarios are not likely to be
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of concern. The Acute RfD is an estimate of a single day oral exposure level for the human

population that is likely to be without an appreciable risk of deleterious effects. The chronic RfD

is an estimate of a daily oral exposure level that is likely to be without an appreciable risk of

deleterious effects during a lifetime. Acute and chronic RfDs are calculated by dividing the No

Observable Adverse Effect Level (NOAEL) by the Uncertainty Factors (UF). UFs are used to

account for differences between humans (intraspecies variability) and for differences between

the test animals and humans (interspecies extrapolation). For the residential inhalation

exposures assessed, UFs are used to determine adequate margins of exposure (MOEs). The

MOE is the ratio of the route appropriate NOAEL to the estimated exposure. HED also

evaluated available studies to determine if there was a special sensitivity for infants and children. 

The toxicological data for Aromatic 100, 150, and 200 Fluids are summarized in Tables 4 and 5. 

The toxicity data base for naphthalene is adequate for the selection of doses and

endpoints for use in risk assessment. The toxicological data for naphthalene are summarized in

Sections 4.2 and 4.3 below. 

Table 4. Acute Toxicity Profile for AF100, 150, and 200

Study Species AF100 (CAS # 64642-95-6) AF150 (CAS # 64642-94-5) AF200 (CAS # 64642-94-5)

Results Classification Results Classification Results Classification

oral rat LD50 = 3.4 g/kg Category III LD50 = 7.1 g/kg

(m) 

LD50 = 5.6 g/kg

(f)

Category IV LD50 = 10.7 g/kg

(m) 

LD50 = 5 g/kg (f) 

Category IV

Inhalation rat LC50 = >1192

ppm

Category IV LC50 = >809

ppm

Category IV LC50 = 726 ppm Category IV

dermal rabbit LD50 = >3.16 g/kg Category III LD50 = >2 g/kg Category III LD50 = >3.16 g/kg Category III

skin irritant

rabbit

moderate moderate mild

eye irritation

rabbit

minimal no irritation slight no irritation minimal no irritation

skin

sensitization

human

no not a

sensitizer

no not a sensitizer no not a sensitizer

Table 5. Toxicity Profile for AF100, 150, and 200

Study Type Publication Doses Results

3 day inhalation neurotoxicity male

rat 

(C10-C11 aromatics)

Nessel et al 2000 0, 35, 110, 365

ppm

NOAEL = 110 ppm (600 mg/m3

;156 mg/kg/day)

LOAEL = 365 ppm low to moderate gait

abnormalties 

90 day oral gavage rat 

(1,3,5-trimethylbenzene)

IIT Research

Institute, 1995

0, 50, 200, 600

mg/kg/day

NOAEL = 600 mg/kg/day

no effects at highest dose tested
Table 5. Toxicity Profile for AF100, 150, and 200

Study Type Publication Doses Results

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90 day oral gavage rat 

(Aromatic 200 Fluid)

EMBSI 1991 0, 300, 600, 1000

mg/kg/day

NOAEL = 300 mg/kg/day

LOAEL = 600 mg/kg/day reversible effects to

liver, thyroid, stomach, spleen, and bladder

90 day neurotoxicity inhalation rat

(C9AHM)

Douglas et al 1993 0, 101, 452, 1320

ppm

NOAEL = 1320 ppm

no effects highest dose tested

1 year inhalation rat 

(50/50 mixture AF100 & Shellsol)

Clark et al 1989 0, 450, 900, 1800

mg/m3

NOAEL = 1800 mg/m3 ( 340 ppm)

no effects highest dose tested

3-generation reproduction inhalation

rat(C9AHM)

McKee et al 1990 0, 100, 500, 1500

ppm

Parental LOAEL = 100 ppm reduced weight gain

F2 (143 mg/kg/day)

Offspring NOAEL = 100 ppm

LOAEL = 500 ppm reduced mean pup weight F3

Developmental inhalation mouse

(C9AHM)

McKee et al 1990 0, 100, 500, 1500

ppm

Developmental NOAEL = 100 ppm

LOAEL = 500 ppm reduction in fetal weight gain

Maternal NOAEL = 100 ppm (207 mg/kg/day)

LOAEL = 500 ppm reduced maternal weight gain

Developmental oral gavage rat

(Aromatic 200 Fluid)

EMBSI1

 1992 0, 75, 15, 450

mg/kg/day

Maternal NOAEL = 150 mg/kg/day

LOAEL = 450 mg/kg/day decreased body weight

gain and food consumption 

Developmental NOAEL = 450 mg/kg/day

Bacterial reverse mutation assay

(C9AHM)

EMBSI 1991 not mutagenic

In vitro cytogenetic Assay (CHO)

(C9AHM)

EMBSI 1992 negative

Rat bone marrow cytogenetics assay

(C9AHM)

EMBSI 1992 negative

CHO/HGPRT Forward Mutation

Suspension Assay (C9AHM)

EMBSI 1992 negative

Chronic/Cancer - No Studies

available 

NA NA Not likely to be carcinogenic in humans based on

SAR 2

1

 ExxonMobil Biomedical Sciences, Inc.

2

 EPA, Review of Mutagenicity Testing Results on C9 Aromatic Hydrocarbon Fraction, “The negative results of these studies do

not trigger additional mutagenicity or carcinogenicity testing as specified in the C9 test rule.” (April 1, 1992)

4.2 Hazard Characterization

Aromatic 100, 150, and 200 Fluids exhibit low acute toxicity by oral, inhalation and

dermal routes (toxicity Category III or IV by all exposure routes). These compounds are

minimally irritating to eyes and skin and negative for dermal sensitization effects.

C9 Rich Aromatic Hydrocarbons (Aromatic 100 Fluid) consists primarily of linear alkyl

benzenes. Aromatic 150 and 200 Fluids (C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich

Aromatic Hydrocarbons) consist primarily of linear alkyl benzenes with some alkylated

naphthalenes. Both EPA and OECD have expressly identified linear alkyl benzenes as an

example of appropriate SAR categories of chemicals. C9 Rich Aromatic Hydrocarbons tend to
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contain higher concentrations of trimethylbenzenes and C10-11 Rich Aromatic Hydrocarbons

contain higher concentrations of tetramethylbenzenes. However, both have common functional

substructure, common metabolic pathways/kinetics of metabolism, and comparable molecular

properties. Therefore, C9 Rich Aromatic Hydrocarbons can be considered an appropriate analog

for predicting the toxicity of C10-11 Rich Aromatic Hydrocarbons. Both C10-11 Rich Aromatic

Hydrocarbons and C11-12 Rich Aromatic Hydrocarbons contain chemical constituents largely

with carbon numbers between C10 and C12. While C10-11 Rich Aromatic Hydrocarbons tend to

have more of C10 and C11 constituents and C11-12 Rich Aromatic Hydrocarbons tend to have

more of the constituents in the C11 to C12 range, the two compounds also share a common

functional substructure (alkyl group on an aromatic), common metabolic pathways and kinetics of

metabolism, and similar molecular properties. Thus, these Aromatic Hydrocarbons can be

considered valid analogues of each other for purposes of predicting toxicity. Furthermore, C9

aromatic hydrocarbon materials (C9AHM) can be considered a valid analog for the Aromatic

Hydrocarbons. C9 Rich Aromatic Hydrocarbons are structurally similar to C9AHM which is

predominantly composed of C9 aromatic hydrocarbon materials such as propylbenzenes, methylethylbenzenes and trimethylbenzenes. On average, C9 Rich Aromatic Hydrocarbons contain 94

percent C9 aromatic hydrocarbons. Consequently, since aromatic fluids can be considered valid

analogues of each other for purposes of predicting toxicity as discussed above, C9AHM can be

considered a valid analog for C9, C10-11, and C11-12 Rich Aromatic Hydrocarbons.

Subchronic oral and inhalation exposure studies indicate Aromatic 100, 150 and 200

Fluids to be relatively non-toxic except at high doses. Reversible effects to the liver, thyroid,

stomach, spleen, and urinary bladder were reported mid- and high doses in a subchronic oral

toxicity study in rats. A developmental inhalation study in mice indicates severe maternal and

developmental toxicity at the high dose (1500 ppm) and reduction in fetal weight gain at the next

lowest dose (500 ppm) but no other evidence of developmental effects nor any adverse effects in

maternal animals. An oral developmental study in rats indicates maternal effects (decreased body

weight gain and food consumption) at the mid-dose (150 mg/kg/day) but no developmental

effects at the highest dose tested (450 mg/kg/day). An inhalation reproduction study in rats

indicates reduced body weight gain in parents and off-spring at mid and high doses (500 and 1500

ppm) and reduced parental weight gain at 100 ppm in the F2 generation. Based on neurotoxicity

studies, Aromatic 100, 150, and 200 Fluids are not expected to cause any nervous system damage.

Naphthalene was subject to an EPA IRIS assessment in 1998. In that assessment, EPA

adopted a chronic reference dose health benchmark based on a subchronic oral toxicity study and

a reference concentration for chronic inhalation exposure based on a chronic mouse inhalation

study. EPA’s IRIS assessment for naphthalene does not include an acute health benchmark

because no effect attributable to a single day oral exposure was observed in animal studies. 

Naphthalene is currently classified by EPA/IRIS as a “possible” (Group C) human carcinogen (no

cancer quantification required) and by IARC as “possibly carcinogenic to humans” (Group 2B).

It should be noted that the carcinogenicity classification of naphthalene is currently being

reviewed as part of EPA’s ongoing update of the Integrated Risk Information System (IRIS)

program.
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Aromatic 100, 150, and 200 Fluids are of low toxicity for endpoints of concern for

developmental and reproductive effects, based on the available information. Reproductive and

developmental studies show no sensitivity issues of concern. Therefore, the tenfold FQPA safety

factor for the protection of infants and children may be reduced to 1 for these compounds. 

4.3 Summary of Toxicity Studies

4.3.1 Aromatic 100, 150, and 200 Fluids

Metabolism

Due to their complex, multi-constituent nature, there are no absorption, metabolism,

distribution and excretion studies done specifically on these Aromatic Fluids. However,

sufficient data on other aromatic solvents – such as alkylbenzenes and alkylnaphthalenes – exist

to describe the absorption, distribution, metabolism and excretion of Aromatic 100, 150, and 200

Fluids (Hissink et al. 1999; Snyder 1987; Patty’s Toxicology 2001; European Union 1999). 

Typically, aromatics are well absorbed, widely distributed between tissues, extensively

metabolized and rapidly excreted. The efficiency of dermal absorption varies depending on the

molecular weight and structure of the compounds.

Following absorption, aromatic hydrocarbon solvents distribute throughout the body and

are extensively metabolized and eliminated. Typically, the solvents will be found at higher levels

in the organs of metabolism and excretion, although they can distribute to other tissues as well,

particularly those with high lipid content.

The most common metabolic pathway for aromatic hydrocarbon solvents is oxidation

followed by conjugation. Cytochrome P450 catalyzes the oxidation of the solvents to alcohol or

acidic forms. For compounds with side chains – including the trimethylbenzenes,

propylbenzenes, and methyl-ethylbenzenes that are the predominant constituents of Aromatic 100

Fluid – side chain oxidation is the first step in metabolism. Glucuronidation and sulfation are

both common Phase II reactions in the metabolism of heavy aromatic hydrocarbon solvents, and

these reactions typically occur in the liver. Other conjugation reactions also may occur. This

conjugation typically serves to detoxify the heavy aromatic hydrocarbon solvent metabolites, and

the conjugates often can be found in the urine.

Aromatic hydrocarbon solvents are rapidly excreted. Both rodents and humans show

similar clearance kinetics of hydrocarbons from blood. Typically, they are excreted as various

metabolites in the urine, although some parent compound may still be present. Urine is the

primary route of excretion for hydrophilic conjugates from both oral and inhalation exposure to

aromatic hydrocarbon solvents, although a much smaller fraction of metabolite excretion can also

occur through the feces. Some lower molecular weight components of heavy aromatic

hydrocarbon solvents – including some of the compounds in Aromatic 100 Fluid – may also be

excreted through the lung. In radiotracer experiments, most heavy aromatic hydrocarbon solvents
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are almost completely eliminated from the body within 48 hours, although small amounts may

reside in organs with high lipid content for slightly longer periods of time. 

Subchronic Toxicity

In a subchronic oral gavage study, Solvesso® 200 Fluid was administered to SpragueDawley rats at concentrations of 300, 600 or 1000 mg/kg/day, 7 days/week for 13 weeks (MRID

46398905, EMBSI 1991). A satellite group received 1000 mg/kg/day for 13 weeks, followed by

a 4-week recovery period. Body weights and food consumption were significantly decreased in

male rats at 1000 mg/kg/day; this effect was not seen in female rats. Hematologic and serum

chemistry changes were observed in both male and female rats at 600 and 1000 mg/kg/day dose

levels and correlated with effects seen in the liver and spleen. Kidney and liver weights increased

in both sexes and all dose levels but the organ weights for animals in the recovery group were

similar to those of control animals, indicating that this was a reversible effect. No treatment

related histopathological effects were observed in the kidney. Treatment related microscopic

changes were observed in the liver, thyroid, stomach, spleen and urinary bladder of rats. 

Histopathologic effects included liver hypertrophy that was observed in the females at all dose

levels and sporadically in males. The effects had reversed completely in the recovery group

animals. Thyroid hyperplasia and hypertrophy of the follicular epithelial cells were observed in

male and female rats at all doses. The effects were also observed in the control animals at a

similar severity level, but at a lower incidence rate. After the recovery period, the severity and

incidence of the effects were comparable in control and test animals. Hemosiderosis was

observed in the spleen of males and females at 600 and 1000 mg/kg/day. Hyperplasia of the

urinary bladder mucosa was observed in male rats at all doses and in female rats at 600 and 1000

mg/kg/day. The effects in the spleen and urinary bladder were reduced in the recovery group

animals. Inflammation and necrosis of the stomach were observed in some treated animals and

were attributed to the effects of intubation of a locally irritating substance on the gastrointestinal

tract. The effects had reversed completely after the 4-week recovery period. The NOAEL is 300

mg/kg/day based on reversible treatment-related microscopic changes observed in the liver,

thyroid, stomach, spleen, and urinary bladder in both male and female rats at 600 and 1000

mg/kg/day.

The subchronic toxicity of 1,3,5-trimethylbenzene (which may be present in high

concentrations in some aromatic hydrocarbons) was evaluated in a 90-day oral gavage study in

rats (IIT Research Institute 1995). Sprague Dawley rats were dosed at levels of 0, 50, 200 and

600 mg/kg/day. A satellite groups received 600 mg/kg/day and was held for a 28-day recovery

period. There were no treatment-related deaths during the study. (Two animals died due to

dosing errors.) There was a statistically significant decrease in body weight gain in the high dose

males at the end of Week 5; although weight gain in the high dose males was still decreased

compared to controls at the end of the treatment period, cumulative body weight gain was not

significantly different in treatment versus control animals. In addition, cumulative body weight

gain in the recovery animals at the end of the 28-day recovery period was similar to control

animals. The only significant changes observed were increased phosphorous levels and

alterations in liver and kidney weights in high dose animals. At the end of the 28-day recovery
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period, these effects were no longer observed, indicating that they are reversible. These effects

were considered an adaptive response and therefore not an adverse effect from exposure to the

test material. Based on the results of this study, the NOAEL was 600 mg/kg/day, the highest dose

tested.

In one study, rats were exposed via inhalation to a 50/50 mixture of Solvesso® 100 Fluid

and Shellsol® A at 450, 900, and 1800 mg/m3

 for 6 hours/day, 5 days/week for twelve months

(Clark et al. 1989). Transient changes in hematologic and plasma clinical chemical parameters

and increased liver and kidney weights were observed at the highest dose only. No corresponding

histopathological differences or evidence of exposure-related kidney dysfunction were observed,

leading the study researchers to conclude that the observed effects were physiological adaptive

responses and not biologically significant. The study NOAEL was greater than 1800 mg/m3

.

Developmental and Reproductive Toxicity

C9AHM was evaluated in a mouse inhalation developmental toxicity test (McKee et al.

1990). Pregnant mice were exposed to 100, 500, or 1500 ppm for 6 hr/day from days 6-15 of

gestation. Exposure to 1500 ppm produced severe maternal toxicity - 44% mortality. At 500

ppm there was significantly reduced maternal weight gain and one unexplained death. There was

no maternal toxicity at the 100 ppm level. Exposure to 1500 ppm produced fetal effects including

mortality, reduced body weight, delayed ossification and an increased incidence of cleft palate. 

Exposure to 500 ppm resulted in a significant reduction in fetal weight gain, but no other

evidence of developmental effects. No developmental toxicity occurred at the lowest dose level

(100 ppm). On this basis, the NOAEL for both maternal and developmental effects is 100 ppm. 

The maternal and developmental LOAELs are 500 ppm based on reduction in maternal weight

gain and reduced fetal weight gain respectively. 

Solvesso® 200 Fluid was evaluated in a Sprague Dawley rat developmental study (EMBSI

1992). Pregnant dams were dosed by oral gavage with 75, 150 or 450 mg/kg/day during

gestational days 6 through 15. At 450 mg/kg/day, maternal body weight gain and food

consumption were significantly decreased during the first three days of treatment. Mean body

weight change was comparable between treated animals and controls during the overall study

period, and there were no statistically significant differences in organ weights and uterine

implantation data between treated groups and controls. There were no adverse fetal effects at any

dose. There were no differences in mean fetal body weight, nor were there any significant

differences in the incidences of fetal variations or malformations in treated groups as compared to

controls, either on a per fetus or a per litter basis. Based on the study results, the maternal

NOAEL is 150 mg/kg/day. The maternal LOAEL is 450 mg/kg/day based on decreased body

weight gain and food consumption. The developmental NOAEL for this study is greater than 450

mg/kg/day, the highest dose tested.

C9AHM was evaluated in a three-generation reproduction inhalation study in rats at 0,

100, 500, or 1500 ppm (McKee et al. 1990). Male fertility was significantly reduced in the F1

males in the 1500 ppm group. However, as fertility was not affected in the first and third
Page 12 of 33

generation, this effect was not considered by the study authors to have been related to exposure. 

Exposure at the mid- and high-dose levels resulted in reduced parental weight gain in both the F0

and F1 generations. For F2 rats, weights of both males and females were initially below control

values in the 100 and 500 ppm group. F1 and F2 litters showed significant reductions in mean pup

weights at the high dose only; similar effects were seen in the F3 litters at both mid and high dose. 

However, when parental exposure was stopped just prior to delivery on gestational day 20, birth

weights as well as postnatal weight gain were similar to control values even in the 1500 ppm

exposure group. Postnatal weight gain was also similar to control values early in weaning, but if

maternal exposure was reinitiated, weight gain was reduced in the high exposure group. When

exposure was continued until delivery, pups in the high exposure group exhibited reduced litter

size, birth weight and poor survival. There was no increase in developmental variations for

offspring at any dose level. Based on the foregoing, the NOAEL and LOAEL for reproductive

effects are 500 and 1500 ppm respectively. The LOAEL for parental system toxicity is 500 ppm

in the F0 and F1 and generations and 100 ppm in the F2 generation based on reduced parental

weight gain. The NOAEL for F0 and F1 generations is 100 ppm. The parental NOAEL for the F2

generation is below the lowest dose tested of 100 ppm. The NOAEL for offspring toxicity is 500

ppm in the F1 and generations, and 100 ppm in the and F3 generation. The LOAEL for offspring

toxicity is 500 ppm based on significant reductions in mean pup weights at both mid and high

doses. 

Neurotoxicity

A subchronic neurotoxicity test exposed Sprague Dawley rats to 0, 101, 452 or 1320 ppm

C9AHM 6 hours per day, 5 days per week for 90 days (Douglas et al. 1993). Body weights of the

high dose group were depressed as compared to controls for much of the exposure period. 

However, by the end of the post-exposure period, these differences were not statistically

significant. No overt signs of toxicity were observed, and histopathological examination showed

no evidence of neuropathological or degenerative changes in the central and peripheral nervous

system at the highest dose tested. No exposure related effects were seen in any motor activity or

neurobehavioral tests, including quantitative motor activity, startle response, quantitative grip

strength, hindlimb splay or thermal response. The NOAEL for this study was 1320 ppm.

A neurobehavioral testing program on aliphatic, cycloaliphatic and aromatic hydrocarbons

was conducted by the CEFIC Hydrocarbon Solvent Producers Association (Nessel et al. 2000;

TNO Nutrition and Food Research Institute 2001). The purpose of this program was to develop

data on the neurobehavioral effects of hydrocarbon solvent constituents on the central nervous

system. Twelve representative constituents of complex hydrocarbon solvents, with carbon chain

lengths ranging from C5- C11, were evaluated. Most representative for purposes of evaluating the

toxicity of the Aromatic Fluids was the test on C10-C11 Aromatics. Male rats were exposed by

inhalation, 8 hours per day for 3 consecutive days to 0, 35, 110 or 365 ppm (0, 0.2, 0.6 and 2.0

g/m3). Animals were tested for effects on motor activity, functional observation measures, and

learned performance of a visual discrimination task. No remarkable clinical signs were observed

during the testing period. Some low to moderate gait abnormalities were observed during the 3-

day exposure period in rats exposed at the maximum concentration level. In the learned
Page 13 of 33

performance test, the high dose rats had increased latencies to make a correct choice and latencies

to obtain water reinforcement, as well as increases in the variability of the speed of responding. 

A small, but statistically significant, decrease in the number of collected reinforcements also was

observed in the high dose group. Effects of exposure were most clearly observed after the first

eight-hour exposure period. The LOAEL for this test was 365 ppm (2.0 g/m3), and the NOAEL

was 110 ppm (0.6 g/m3). 

These two studies suggest that Aromatic 100, 150, and 200 Fluids can cause slight,

transient central nervous system depression, with related minor neurobehavioral effects. 

However, based on these studies, they are not expected to cause nervous system damage.

Chronic Toxicity/Carcinogenicity

Aromatic 100, 150 and 200 Fluids have not been tested specifically for carcinogenicity. 

However, registrant submitted data on the structure and metabolism, subchronic health effects,

and genotoxicity of these compounds indicate that they are not likely to have carcinogenic

properties. Aromatic 100, 150 and 200 Fluids do not belong to a class of chemicals known to

react with DNA, nor are they metabolized to materials that are likely to react with DNA. 

Materials which are oncogenic for mammals appear to cause cancer either by interacting with the

genetic material (DNA) (that is, they are genotoxic and, therefore, are probably initiators of the

carcinogenic process), or they produce chronic toxic effects which result in increased cell

turnover and, therefore, produce effects by epigenetic mechanisms and are probably promoters of

the carcinogenic process. The data available for Aromatic 100, 150 and 200 Fluids indicate that

these compounds are not genotoxic. Aromatic fluids containing primarily C9AHM have been

tested for mutagenic activity in the following in vitro tests: bacterial reverse mutation assay; CHO

gene mutation assay; CHO sister chromatid exchange assay; and CHO/HGPRT forward mutation

suspension assay (Schreiner et al 1989). In addition, C9AHM was tested in an in vivo bone

marrow chromosomal aberration test (Schreiner et al. 1989). There was no indication of

mutagenic activity in any of the assays, providing strong support for the conclusion that Aromatic

100 Fluid is not likely to be mutagenic. Further, in its evaluation of C9AHM as part of a TSCA

Section 4 test rule, EPA concluded that, based on the negative mutagenicity studies and other

available data, no further mutagenicity or carcinogenicity testing of these compounds was

required. (EPAs “Review of Mutagenicity Testing Results on C9 Aromatic Hydrocarbon

Fraction” April 1, 1992 concluded, “The negative results of these studies do not trigger additional

mutagenicity or carcinogenicity testing as specified in the C9 test rule.”). Based on this data, C9

Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic

Hydrocarbons are considered unlikely to be carcinogenic. 
Page 14 of 33

4.3.2 Naphthalene

Metabolism

The metabolism of naphthalene has been extensively investigated and reported in the

literature (Buckpitt and Franklin, 1989; Wells et al. 1989; Plopper et al. 1992a, b; Xu et al.

1992a,b; Wilson et al. 1996; Chichester et al. 1994; IARC 2002). The initial step in the

metabolism of naphthalene in mammalian species is oxidation, catalyzed by cytochrome P450

oxygenases (CYP2F family), to naphthalene1,2-epoxide (also called naphthalene 1,2-oxide); both

the 1R,2S and 1S,2R enantiomers may be formed, depending on the P450 isoform. The epoxide

may undergo the following transformations: (1) be enzymatically conjugated with glutathione by

glutathione S-transferases to form a variety of glutathione conjugates that are excreted in the urine

as n-acetylcysteine; (2) be enzymatically hydrated by epoxide hydrolase to form naphthalene-1,2-

dihydrodiol, which can be conjugated with sulfate and glucuronic acid, or converted by catechol

reductase, forming naphthoquinone via oxidation; (3) spontaneously rearrange to form naphthols

(primarily 1-naphthol) and eventually form naphthalene diols and naphthoquinones; or (4) react

with nucleophilic cellular constituents (EPA, 1998; Franklin 1987; Klaassen 1996). The first two

pathways generally are considered to detoxify naphthalene 1,2-epoxide. 

Subchronic

The IRIS health assessment of naphthalene (EPA, 1998)cites a subchronic oral toxicity

study in rats as its principal study in determining an reference dose for chronic oral exposure. In

the cited subchronic oral toxicity study, naphthalene was administered by gavage to Fischer 344

rats at dose levels of 0, 25, 50, 100, 200, or 400 mg/kg, 5 days/week for 13 weeks (BCL, 1980).

Animals were evaluated for food consumption and body weight, clinical signs of toxicity and

hematological parameters (hemoglobin, hematocrit, total and differential white blood cell count,

red blood cell count, mean cell volume, mean cell hemoglobin concentration), as well as necropsy

of all rats in the study, and histopathological examination of selected animals. 

At the highest dose level, there were overt signs of toxicity, including death of two

animals, and diarrhea, lethargy, hunched posture, and rough coats at intermittent intervals

throughout the study. Food consumption was not affected by exposure, but mean decreases in

terminal body weight were observed in the 200 and 400 mg/kg/day dose groups. Some

differences in hematological parameters also were observed in the high dose group, and some

histopathological effects were noted in the kidney and thymus of high (and some mid) dose

animals. Decreased body weight was the most sensitive effect and EPA identified this effect as

the most appropriate critical effect for the purposes of RfD derivation. The study NOAEL was

100 mg/kg/day. 

Developmental

Developmental effects were summarized in the IRIS Toxicological Review of

Naphthalene as follows. In developmental toxicity studies, naphthalene was administered by

gavage to pregnant animals during gestation, and little evidence was found of naphthalene fetal
Page 15 of 33

developmental toxicity. Signs of maternal toxicity (e.g., decreased body weight gain, lethargy)

without fetal effects were found in a rat study (NTP, 1991) and a rabbit study (NTP, 1992). Other

studies were conducted at dose levels that either produced increased maternal mortalities (mice:

Plasterer et al., 1985; rabbits: NTP, 1990) or no maternal or fetal effects (rabbits: Naismith and

Matthews, 1985)

Chronic/Cancer

Naphthalene is currently classified by EPA as a “possible” (Group C) human carcinogen

(no cancer quantification required). This is based on the inadequate data of carcinogenicity in

humans exposed to naphthalene via the oral and inhalation routes, and the limited evidence of

carcinogenicity in animals via the inhalation route. Using the 1996 Proposed Guidelines for

Carcinogen Risk Assessment, the human carcinogenic potential of naphthalene via the oral or

inhalation routes "cannot be determined" at this time based on human and animal data; however,

there is suggestive evidence (observations of benign respiratory tumors and one carcinoma in

female mice only exposed to naphthalene by inhalation (NTP, 1992a)). Additional support

includes increase in respiratory tumors associated with exposure to 1-methylnaphthalene. At the

present time the mechanism(s) whereby naphthalene produces benign respiratory tract tumors are

not fully understood, but are hypothesized to involve oxygenated reactive metabolites produced

via the cytochrome P-450 monooxygenase system. However, based on the many negative results

obtained in genotoxicty tests, a genotoxic mechanism appears unlikely. An oral slope factor for

naphthalene was not derived by EPA because of a lack of chronic oral naphthalene studies. An

inhalation unit risk estimate for naphthalene was not derived by EPA because of the weakness of

the evidence (observations of predominant benign respiratory tumors in mice at high dose only)

that naphthalene may be carcinogenic in humans. Naphthalene is classified by IARC as “possibly

carcinogenic to humans” (Group 2B). It should be noted that the carcinogenicity classification of

naphthalene is currently being reviewed as part of EPA’s ongoing update of the IRIS program. 

4.4 Special Considerations for Infants and Children

C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich

Aromatic Hydrocarbons are of low toxicity for endpoints of concern for developmental and

reproductive effects, based on the available information. Therefore an additional tenfold safety

factor for the protection of infants and children is determined to be unnecessary. 

4.5 Endpoint Selection

4.5.1 C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and

C11-12 Rich Aromatic Hydrocarbons

Acute RfD

For acute dietary exposure, an oral NOAEL of 150 was selected from a rat developmental

gavage study based on significantly decreased maternal body weight gain and food consumption 
Page 16 of 33

Acute RfD = 150 mg/kg/day = 1.5 mg/kg/day

 100 (UF)

Chronic RfD = 150 mg/kg/day = 1.5 mg/kg/day

 100 (UF)

during the first three days of treatment at the LOAEL of 450 mg/kg/day. An uncertainty factor

(UF) of 100x (10x for interspecies and 10x for intraspecies is extrapolation) was applied which

results in an RfD of 1.5 mg/kg/day. The study and the end point are considered appropriate for

the route and duration. 

Chronic RfD

For chronic dietary exposure for all populations, the oral NOAEL of 150 was selected

from the rat developmental gavage study based on significantly decreased maternal body weight

gain and food consumption during the first three days of treatment at the LOAEL of 450

mg/kg/day. An uncertainty factor (UF) of 100x (10x for interspecies and 10x for intraspecies is

extrapolation) was applied which results in an RfD of 1.5 mg/kg/day. The study and the end

point are considered as the most appropriate for chronic dietary exposure given that effects in

longer term studies were seen only at higher doses. 

Short Term Inhalation

For short-term inhalation, the toxicology endpoint was selected from a 3 day inhalation

neurobehavioral testing program in rats on twelve representative constituents of complex

hydrocarbon solvents, with carbon chain lengths ranging from C5- C11. The NOAEL for this

study was 110 ppm (156 mg/kg/day) based on low to moderate gait abnormalities observed at the

maximum concentration level of 365 ppm. This inhalation study is considered the most

appropriate for endpoint selection based on the expected duration of exposure (short-term). The

level of concern (LOC) or target margin of exposure (MOE) for inhalation exposures is 100 based

on the conventional uncertainty factor of 100X (10x for interspecies and 10x for intraspecies is

extrapolation). 

Short Term Dermal

For short term dermal exposure, the oral NOAEL of 150 was selected from the rat

developmental gavage study based on significantly decreased maternal body weight gain and food

consumption during the first three days of treatment at the LOAEL of 450 mg/kg/day. The LOC

or MOE) for dermal exposures is 100 based on the conventional uncertainty factor of 100X. 

Dermal Absorption
Page 17 of 33

A dermal absorption estimate of 5% was selected based on the dermal absorption of ethyl

benzene in hairless mice (Susten et al, 1990). Ethyl benzene is a vaporous compound analogous

to the Aromatic Fluids. 

Incidental Oral

No dose or endpoint selected for incidental oral because oral post-application exposure is

expected to minimal. Only a small fraction of the compounds are expected to remain on the

ground or grass because Aromatic Fluids tend to evaporate rapidly. 

Table 6. Summary of Toxicological Doses and Endpoints for C9, C10-11, and C11-12 Rich Aromatic Hydrocarbons 

Exposure

Scenario

Dose Used in Risk

Assessment, UF 

Special FQPA

SF* and Level of

Concern for

Risk Assessment

Study and Toxicological Effects

Acute Dietary

All Populations

NOAEL= 150

mg/kg/day

UF = 100

Acute RfD = 

1.5 mg/kg/day

FQPA SF = 1X

aPAD = 

acute RfD

 FQPA SF

= 1.5 mg/kg/day

Developmental Oral- Rat

Maternal LOAEL = 450 mg/kg/day based on decreased

body weight gain and food consumption

Chronic Dietary

All Populations

NOAEL= 150

mg/kg/day

UF = 100

Chronic RfD =

1.5 mg/kg/day

FQPA SF = 1X

cPAD = 

chronic RfD

 FQPA SF

= 1.5 mg/kg/day

Developmental Oral- Rat

Maternal LOAEL = 450 mg/kg/day based on decreased

body weight gain and food consumption

Inhalation - Short-term NOAEL = 110

ppm 

(146 mg/kg/day)*

Residential LOC

for MOE = 100

3 Day Inhalation Nuerobehavoiral Testing Program - Rat 

LOAEL = 365 ppm based on low to moderate gait

abnormalities

Incidental Oral Endpoints of concern were not selected for incidental oral exposure scenarios based on physicalchemical property data.

Dermal - Short-term NOAEL= 150

mg/kg/day (dermal

absorption rate =

5%)

Residential LOC

for MOE = 100

Developmental Oral- Rat

Maternal LOAEL = 450 mg/kg/day based on decreased

body weight gain and food consumption

Cancer 

Oral, Dermal, Inhalation

Not likely to be carcinogenic in humans

* MW of C9AHM = 129
Page 18 of 33

Chronic RfD = 71 mg/kg/day = 0.02 mg/kg/day

 3000 (UF)

4.5.2 Naphthalene

Acute RfD

EPA’s IRIS assessment for naphthalene does not include an acute health benchmark

because no effect attributable to a single or few day(s) oral exposure was observed in animal

studies. 

Chronic RfD

The chronic RfD for naphthalene was selected based on information provided in IRIS. 

The toxicology endpoint was selected from a subchronic oral gavage study in rats in which the

NOAEL was 71 mg/kg/day based on decreased mean terminal body weight in males at the

LOAEL of 143 mg/kg/day. A UF of 3000x was considered appropriate for deriving the chronic

RfD (10 to extrapolate from rats to humans; 10 to protect sensitive humans; 10 to extrapolate

from subchronic to chronic exposure; and 3 for data base deficiencies to arrive at a chronic RfD

of 0.02 mg/kg/day. 

Dermal and Incidental Oral Endpoints

No dose or endpoints were selected for dermal or incidental oral exposure for naphthalene

because exposures via these routes are expected to minimal due to high and rapid evaporation

rates and predicted low dermal absorption. 

5.0 Exposure Assessment

5.1 Dietary Exposure and Risk Assessment

To assess whether C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic

Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons meet the standard for reissuance of a

tolerance exemption, HED conducted a dietary exposure and risk assessment using the ScreeningLevel Dietary Exposure Model for Inert Ingredients developed jointly by the Inerts Team and

residue chemists in HED. Anticipated residues of C9 Rich Aromatic Hydrocarbons, C10-11 Rich

Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons were compared to modeled

anticipated residues for inerts which were derived based on the inert ingredients screening model.

The Tier 1Inert Ingredient Model assessment is based on the following assumptions:

actual crop-specific residue data for active ingredients can be utilized as surrogate data for inert

ingredient residue levels (including secondary residues in meat, milk, poultry and eggs); inert

ingredients are used on all crops and 100% of all crops are “treated” with inert ingredients; no
Page 19 of 33

adjustment made for percent of inert in formulation, application rate, or multiple applications of

different active ingredient formulations; and only preharvest applications are considered. 

The Inert Ingredient Model exposure estimates are based on highest tolerance level

residues of high-use active ingredients for all food forms, including meat, milk, poultry, and eggs. 

A group of 57 of the most “significant” active ingredients were considered. These active

ingredients included substances in the insecticide, fungicide, and herbicide class and were

selected based on a overall ranking scheme that included the following components. Overall use

from 1999 data for active ingredient use (in lbs/yr) – all herbicides at >5 million lbs/yr and all

fungicides and insecticides at > 1 million lbs/yr were included. All active ingredients used on

crops that are significant contributors to diet were included (i.e., all which had substantial use on

crops that make up the “Top 25" childrens diet). Crop-by-crop pesticide use information was

evaluated to identify the most frequently used active ingredients. Data from actual residue

monitoring studies from active ingredients with the highest frequency of detection were used. 

Tolerances for the 57 active ingredients were examined for each of the representative crops in the

Agency’s crop group designations [40 CFR 180.41] and for all crops not included in a crop group. 

Where there were multiple tolerances for a given crop or commodity, the highest tolerance was

chosen as the residue level for the model. Non-representative crops within each crop group were

matched to their most-closely related representative crop based on OPP/HED’s standard operating

procedure 2000.1 USEPA, 2000). 

Tier 1 generic inert ingredient acute and chronic dietary exposure assessments were

conducted using the Dietary Exposure Evaluation Model software with the Food Commodity

Intake Database (DEEM-FCIDTM, Version 1.3), which incorporates consumption data from

USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII), 1994-1996 and 1998. The

1994-96, 98 data are based on the reported consumption of more than 20,000 individuals over two

non-consecutive survey days. Foods “as consumed” (e.g., apple pie) are linked to EPA-defined

food commodities (e.g. apples, peeled fruit - cooked; fresh or N/S; baked; or wheat flour -

cooked; fresh or N/S, baked) using publicly available recipe translation files developed jointly by

USDA/ARS and EPA. Consumption data are averaged for the entire U.S. population and within

population subgroups for chronic exposure assessment, but are retained as individual

consumption events for acute exposure assessment.

For acute exposure assessments, individual one-day food consumption data are used on an

individual-by-individual basis. The reported consumption amounts of each food item can be

multiplied by a residue point estimate and summed to obtain a total daily pesticide exposure for a

deterministic (Tier 1 or Tier 2) exposure assessment, or “matched” in multiple random pairings

with residue values and then summed in a probabilistic (Tier 3/4) assessment. For this screeninglevel assessment, only a Tier 1 analysis was performed.

For chronic exposure and risk assessment, an estimate of the residue level in each food

or food-form (e.g., orange or orange juice) on the food commodity residue list is multiplied by the

average daily consumption estimate for that food/food form. The resulting residue consumption

estimate for each food/food form is summed with the residue consumption estimates for all other
Page 20 of 33

food/food forms on the commodity residue list to arrive at the total average estimated exposure. 

Exposure is expressed in mg/kg body weight/day. This procedure is performed for each

population subgroup. A DEEMTM-type analysis was performed utilizing the highest established

tolerance level residue for each commodity. In those cases where DEEM listed a commodity for

which a published tolerance did not exist, the input value was selected based on representative

crops or other “default” values (e.g, use of standard processing factors). A DEEM-FCIDTM,

Version 1.3 analyses were performed for both acute and chronic dietary exposure scenarios and

the results for each are given in Table 7.

The results of this Inert Ingredient Screening Model should represent an upper-bound

estimate of likely potential dietary exposure to an inert ingredient resulting from preharvest use. 

For this assessment of C9 Aromatic Hydrocarbons, C10-11Aromatic Hydrocarbons, and C11-12

Aromatic Hydrocarbons, these values were compared to the selected toxicity endpoints using the

percent of Population Adjusted Dose ( %PAD) approach.

Table 7. Estimated Acute and Chronic Dietary Exposure1 for a Generic Inert.

Population Subgroup Estimated Acute Exposure 

(mg/kg/day)

Est Chronic Exposure

(mg/kg/day)

95th Percentile 99th Percentile 99.9th Percentile Average

U.S. Population (total) 0.336 0.643 1.164 0.120

All infants (< 1 year) 0.701 1.060 2.056 0.245

Children (1-2 years) 0.939 1.382 2.106 0.422

Children (3-5 years) 0.683 1.010 1.476 0.310

Children (6-12 years) 0.395 0.563 0.827 0.174

Youth (13-19 years) 0.239 0.357 0.815 0.100

Adults (20-49 years) 0.199 0.295 0.468 0.087

Adults (50+ years) 0.191 0.263 0.357 0.086

Females (13-49 years) 0.198 0.287 0.415 0.087

1

 Exposure estimates are based on highest-tolerance-level residues of high-use active ingredients for all food

forms, including meat, milk, poultry, and eggs.

The Tier 1screening assessment does not account for evaporative loss which is a

particularly important consideration for volatile compounds such as the Aromatic Hydrocarbons. 

Based on information provided by ExxonMobil, HED conducted a Tier 2/Tier 3 assessment

which still retains conservative assumptions regarding application rates, percent crop treated, etc.,

but which more accurately reflects the evaporative loss of C9 Rich Aromatic Hydrocarbons, C10-

11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons.

To assess the impact of evaporative loss on dietary exposures to C9 Rich Aromatic

Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons,
Page 21 of 33

ExxonMobil conducted an assessment of the evaporative loss of Aromatic 150 and 200 Fluids

using ASTM Method D3539. Following ASTM D 3569 protocol relative evaporation rates (as

compared to n-butyl acetate) result in calculated neat evaporation rates of 7.29E-7 g/s/cm2 and

2.73E-8 g/s/cm2 for Aromatic 150 and 200 Fluids respectively. As noted by ExxonMobil, these

results indicate a significant potential for evaporative loss of Aromatic Hydrocarbons from treated

agricultural surfaces (e.g., foliage). 

Application of a 98% loss factor to the Tier 1 Inerts Model residue values, as proposed by

the registrant based on the ASTM data, results in exposures significantly below OPP’s level of

concern for acute (at 99.9 % of the aPAD) and chronic exposures as shown in Table 8. Use of a

evaporation loss factor as low as 50% would still result in exposures well below the level of

concern. 

Table 8. Estimated Acute and Chronic Dietary Exposure for a C9, C10-11, and C11-12 Rich Aromatic Hydrocarbons

Population Subgroup Acute Dietary Exposure Chronic Dietary Exposure

aPAD

(mg/kg/day)

Exposure

(mg/kg/day)

99.9th ile

% aPAD

cPAD

(mg/kg/day)

Exposure

(mg/kg/day)

Mean 

% cPAD

U.S. Population (total) 1.5 0.0233 1.6 1.5 0.0016 0.2

All infants (< 1 year) 1.5 0.0411 2.7 1.5 0.0033 0.3

Children (1-2 years) 1.5 0.0421 2.8 1.5 0.0056 0.6

Children (3-5 years) 1.5 0.0295 2.0 1.5 0.0041 0.4

Children (6-12 years) 1.5 0.0165 1.1 1.5 0.0023 0.2

Youth (13-19 years) 1.5 0.0163 1.1 1.5 0.0013 0.1

Adults (20-49 years) 1.5 0.0094 0.6 1.5 0.0012 0.1

Adults (50+ years) 1.5 0.0071 0.5 1.5 0.0011 0.1

Females (13-49 years) 1.5 0.0083 0.6 1.5 0.0012 0.1

The results of this assessment indicate that both acute and chronic dietary risks are well

below OPP’s level of concern. This assessment should represent an upper-bound estimate of

likely potential dietary exposure to C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic

Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons as inert ingredients resulting from

preharvest use. As stated in the documentation for the Inert Screening Model, in cases where this

model would yield dietary risk values below the level of concern, no further refinements are

necessary, and the potential dietary exposure and risk are considered adequately characterized. 

A chronic dietary exposure assessment was also conducted for naphthalene using the same

methodology described above for assessment the Aromatic Fluids. Dietary exposure to

naphthalene was assessed using the same assumptions regarding evaporation rates used for the

Rich Aromatic Hydrocarbons dietary assessment. An application rate of 10% of the maximum

rate for Rich Aromatic Hydrocarbons was assumed. Based on this assessment, the chronic dietary
Page 22 of 33

exposure estimate for the highest exposed population subgroup, children 1-2 years of age, is 4%

of the cPAD, and not a of risk concern. 

5.2 Environmental Fate Characterization Considerations

C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich

Aromatic Hydrocarbons are expected to rapidly volatilize in air. These compounds are expected

to volatilize readily from surface layers of soil and from surface water based on fugacity

modeling. C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12

Rich Aromatic Hydrocarbons readily biodegrade in soil. In a ready biodegradability study in

activated sludge, the biodegradation half-life of 1 week; 78% degradation was observed by day

28. Considering their volatilization from surface soils and ready biodegradation, C9 Rich

Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic

Hydrocarbons are not likely to be present in drinking water sources at substantial concentrations

as a result of their use as pesticide inert ingredients. 

5.3 Residential Exposure and Risk Assessment

Based on the use patterns associated with C9 Rich Aromatic Hydrocarbons, C10-11 Rich

Aromatic Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons as inert ingredients, HED

assessed the following residential handler exposure scenarios as representative of the most highly

exposed residential pesticide handlers. 

1) Mixing, loading, and applying liquid spray formulation to lawns and ornamentals by lowpressure handwand; and

2) Mixing, loading, and applying liquid spray formulation to lawns and ornamentals by hoseend sprayer.

Only outdoor residential exposure scenarios were assessed because, based on information

provided by the petitioner, Aromatic Fluids are unlikely to be used indoors due to odor

characteristics. Only short-term residential exposures are expected based on the anticipated use

pattern. Inhalation and dermal exposures were assessed quantitatively. No dose or endpoints

were selected for incidental oral exposure because these exposures are expected to minimal due to

the expected rapid evaporation of these Aromatic Hydrocarbons. In accordance with HED policy,

data from the Pesticide Handlers Exposure Database (PHED) and or Outdoor Residential

Exposure Task Force was used handler exposures in the absence of chemical-specific monitoring

data (USEPA, 1998, USEPA, 2000). The following assumptions were made for the exposure and

risk calculations:

• Average body weight of an adult handler is 70 kg/day.

• Maximum application rate is 2.2 lb ai per acre based on information submitted by the

registrant. 

• Area treated is 0.5 acres per day

• Residential handlers are expected to have a short-term exposure duration (less than 30
Page 23 of 33

days).

• Baseline inhalation unit exposure - no respiratory protection.

• Baseline dermal unit exposure - long pants, long sleeved shirts, shoes, and socks.

Results of the residential exposure assessment are provided in Table 9. A target MOE of

100 for the inhalation and dermal routes is considered adequate for the handler risk assessment. 

Estimated inhalation and dermal MOEs for both handler scenarios are greater than the target

MOE of 100 and not of concern. 

Table 9. Aromatic 100, 150 and 200 - Short Term Inhalation Exposure & MOEs for Residential Handlers 

Target MOE = 100

Exposure

Scenario 

Dermal Unit

Exposure

(mg/kg/day)1

Inhal Unit

Exposure 

(ug/lb ai)1

Use2 Max

App Rate3

(lb ai/acre)

Daily

Area

Treated4

Dermal

Dose

(m/k/d)5

Inhal

Dose

(m/k/d)6

Dermal

MOE7

Inhal

MOE8

Mixing/Loading/Applying Liquids

Low Pressure

Handwand

100 30 turf/

ornamental

2.2 0.5Acre

/day

0.0236 0.0005 6400 300000

Hose-end

Sprayer

17 11 turf/

ornamental

2.2 0.5Acre

/day

0.0086 0.0002 17000 900000

1

Baseline inhalation unit exposures represent no respirator. Values are reported in the PHED Surrogate Exposure Guide dated August 1998 or are

from data submitted by the Outdoor Residential Exposure Task Force dated May 2000.

Baseline dermal unit exposures represent long pants, long sleeved shirts, shoes, and socks. Values are reported in the PHED Surrogate Exposure

Guide dated August 1998 or are from data submitted by the Outdoor Residential Exposure Task Force dated May 2000. 2

 Use patterns are from information provided by the registrant and product labels 3

Application rates are based on maximum values submitted by the registrant and verified by an HED cursory label review. In most scenarios, a

range of maximum application rates is used to represent the range of rates for different crops/sites/uses. Application rates upon which the analysis

is based are presented as lb ai/A. 

4

Amount treated is based on the area or gallons that can be reasonably applied in a single day for each exposure scenario of concern based on the

application method and formulation/packaging type. (Standard EPA/OPP/HED values). 5

Dermal dose (mg/kg/day) = [unit exposure (mg/lb ai) * Dermal absorption (2%) * Application rate (lb ai/acre or lb ai/gallon) * Daily area treated

(acres or gallons)] / Body weight (70 kg).

6

Inhalation dose (mg/kg/day) = [unit exposure (ug/lb ai) * 0.001 mg/ g unit conversion * Inhalation absorption (100%) * Application rate (lb

ai/acre or lb ai/gallon) * Daily area treated (acres or gallons)] / Body weight (70 kg).

7

Dermal MOE = short-term endpoint for dermal - dermal LOAEL (mg/kg/day) / Daily Dermal Dose. 8

Inhalation MOE = short-term endpoint for inhalation - oral NOAEL (156 mg/kg/day) / Daily Inhalation Dose.

5.4 Aggregate Exposures

In examining aggregate exposure, FFDCA section 408 directs EPA to consider available

information concerning exposures from the pesticide residue in food and all other nonoccupational exposures, including drinking water from ground water or surface water and

exposure through pesticide use in gardens, lawns, or buildings (residential and other indoor uses). 

Only dietary, dermal and inhalation routes of exposure have been assessed for this analysis for

reasons explained above. Inhalation and oral exposures cannot be aggregated for this assessment

because the toxicity endpoints selected for the chronic dietary route of exposure and those

selected for the inhalation route are not based on common effects. Inhalation and dermal

exposures cannot be aggregated for the same reason. Dietary and dermal exposures can be

aggregated because the toxicity endpoints selected for these exposure routes are based on
Page 24 of 33

common effects. Short term aggregate risks from combined dietary and dermal exposure do not

present risks of concern. The aggregate MOE for dietary and dermal exposure is 15000, which

significantly exceeds the target MOE of 100. OPP did not conduct an aggregate assessment of

risk from the Aromatic Fluids because co-occurrence of these compounds is not expected. 

6.0 Cumulative Exposure

Section 408(b)(2)(D)(v) of the FFDCA requires that, when considering whether to

establish, modify, or revoke a tolerance, the Agency consider "available information” concerning

the cumulative effects of a particular pesticide's residues and "other substances that have a

common mechanism of toxicity.”

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 C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich

Aromatic Hydrocarbons and any other substances, and these materials do not appear to produce a

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

therefore, EPA has not assumed that C9 Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic

Hydrocarbons, and C11-12 Rich Aromatic Hydrocarbons have 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/

7.0 Ecotoxicity and Ecological Risk Characterization

There is limited measured toxicity information to characterize the effects of C9 Rich

Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic

Hydrocarbons on aquatic and terrestrial organisms. Data available on Aromatic 100 Fluid show

that toxicity values range from non-toxic to slightly toxic to aquatic and terrestrial organisms. C9

Rich Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic

Hydrocarbons are compositionally comparable products as discussed above. Based on a 96 hour

fish acute static toxicity test on rainbow trout (oncorhynchus mykiss), Aromatic Fluids are

classified as slightly toxic, i.e., the lowest 96-hour LC50 reported 18.0 mg/L based on nominal

values. A 48 hour static daphnid acute toxicity test in the water flea (daphnia magna) indicated a

classification of slightly toxic based on a 48 hour EL50 of 21.3 mg/L (95% Cl 17.2 to 28.9 mg/L). 

Aromatic Fluids are classified as practically non-toxic to birds based on an acute oral gavage

study in Northern Bobwhite Quail, i.e., the acute oral LD50 in birds is > 2250 mg/kg. As

previously discussed, these chemicals will volatilize readily when released. In addition to

volatilization, they will biodegrade readily in soil, which means that run-off into surface water

from pesticidal uses is likely to be low. Therefore, based on potential for exposures and available

toxicity information, ecological concerns for are not likely to occur from the use of C9 Rich

Aromatic Hydrocarbons, C10-11 Rich Aromatic Hydrocarbons, and C11-12 Rich Aromatic

Hydrocarbons as pesticide inert ingredients unless application rates exceed 15 lbs./acre annually.
Page 25 of 33

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and Risk Data in Support of the Registration of [Inert Ingredients]. Transmittal of 2 Studies. 

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