d-Limonene Registration -Review Human-Health Assessment Seeping Document

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POL LUTION PREVENTION

MEMORANDUM

Date: 13-AUG-20 10

SUBJECT: d-Limonene. Human-Health Assessment Seoping Document in Support of Registration

Review.

PC Codes: 079701,879701

Decision No.: 428346

Petition No.: N/A

Risk Assessment Type: N/A

TXR No.: N/A

MRID No.: N/A

DP Barcode: D374492

Registration No.: N/A

Regulatory Action: Registration Review Seoping Document

Case No.: 3083

CAS No.: 5989-27-5

40 CFR: §180.539, §180.910, §180.930

- FROM: George F. Kramer, Ph.D., Senior <)7rnist..... 1" ,...<:5S:(

Allison Nowotarski, Biologist p.

Robert Mitkus, Ph.D., DABT, Toxicologist

Risk Assessment Brauch I (RAB I) f::,. ...5' - 0'

Health Effects Division (HED, 7509P) "------,-

Office ofPesticide Programs (OPP)

THROUGH: Dana M. Vogel, Branch Chief

RABI /HED/OPP (7509P)

TO: Russell Wasem/Niel Anderson

Pesticide Re-Evaluation Division (PRD)/OPP (7508P)

Attached is HED's human -health risk assessment scoping document for d-limonene to support

Registration Review.

Executive Summary

d-Limonene has a lemon-like flavor and smell, and occurs naturally in citrus and certain fruits,

vegetables, meats, and spices. d-Limonene is used as both an active and inert ingredient in

pesticide products, and as an ingredient in food products, soaps, and perfumes. As an active

ingredient, it is used as an insecticide, herbicide, insect repellent, and animal (dog and cat)

repellent. As a pesticide inert ingredient, it is used as a solvent or fragrance. FDA considers dlimonene to be Generally Recognized as Safe (GRAS) as a food additive when used as a

synthetic flavoring substance and adjuvant (21 CFR §182.60). d-Limonene is not registered for

terrestrial food or feed crop uses as an active ingredient, but can be used in insect-repellent

tablecloths and in insect-repellent strips used in food or feed-handling establishments. Since the

Pagelof31
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d-Limonene Tolerance Reassessment Eligibility Decision (TRED) was completed in 2004, a 

non-food herbicidal use has been assessed and registered. No new food uses have been assessed 

or registered. The most recent human-health risk assessment for d-limonene was completed in 

2004 (d-Limonene TRED, EPA-HQ-OPP-2004-0335-0003). HED has evaluated the status of 

the human-health assessments for d-limonene to determine whether sufficient data are available 

and whether any updates are needed to support Registration Review. HED has considered the 

most recent human-health risk assessment for d-limonene (d-Limonene TRED, EPA-HQ-OPP2004-0335-0003); updates to its toxicity, exposure, and usage databases that have occurred since 

the last registration; and the most recently updated Agency science policy and risk assessment 

methodologies to determine the scope of work necessary to support Registration Review. No 

residue chemistry or toxicology data requirements have been identified for d-limonene to 

support registration review. 

Background 

The toxicology database is sufficient to support the current registrations. Overall, the database 

supports the conclusion that high doses of d-limonene (≥500 mg/kg/day) are needed to 

induce any form of relevant toxicity in laboratory animals. d-Limonene is a skin and eye 

irritant, as well as a dermal sensitizer, with air-oxidized (vs. unoxidized) d-limonene shown to be 

the sensitizing agent. d-Limonene is essentially non-toxic following single doses via the oral or 

dermal routes (LD50 ≥4400 mg/kg) and inhalation routes (LC50 >4.8 mg/L) and non-toxic in 

repeat-dose oral animal studies up to relatively high doses (500 mg/kg/day). In addition, a 2-

week preliminary study for a 90-day dermal toxicity study in the rat indicated that d-limonene 

produced excessive dermal irritation at doses ≥500 mg/kg/day, but no systemic toxicity. Oral 

doses ≥75 mg/kg/day of d-limonene elicit effects in the livers of rats; however, these effects are 

considered adaptive (non-adverse). The kidney was also identified as a target organ in rodent 

toxicity studies, but only in male rats and not in any other sex or species. Extensive evaluation 

of the effects in the kidney of male rats determined that they are not predictive of kidney toxicity 

in humans. In addition, d-limonene was negative in several mutagenicity and clastogenicity 

assays. There was no evidence of developmental toxicity with d-limonene in rabbits and no 

evidence in rats, except at very high doses and in the presence of maternal toxicity. A clear noobserved adverse-effect level (NOAEL) of 250 mg/kg/day was obtained for both maternal and 

developmental effects in rats. There was no evidence of possible neurotoxicity following 

exposure to d-limonene, except in a 13-week oral study in mice in which decreased motor 

activity was observed at a very high dose (1000 mg/kg/day); however, this observation could 

have been due to general systemic toxicity. A published 9-week immunotoxicity study in mice 

yielded no clear evidence of immunotoxicity with d-limonene. 

In the Agency’s TRED (2004), EPA chose endpoints for short- and long-term dermal and 

inhalation exposure scenarios, as well as chronic dietary exposure. The points of departure for 

the short- and long-term dermal and inhalation exposure scenarios are considered overly 

conservative and inconsistent and should be updated in future risk assessments. In addition, 

based on expected exposure patterns, the need for acute dietary and incidental oral toxicity 

endpoints should be addressed in future risk assessments as part of Registration Review.

The most recent chronic dietary-exposure assessment for d-limonene was completed in 2004 (dLimonene TRED, EPA-HQ-OPP-2004-0335-0003). Screening-level assessments were 

performed using the Dietary Exposure Evaluation Model (DEEMTM) to determine the potential 

exposure for d-limonene in the food supply as a result of applications of a pesticide product 
d-Limonene Registration-Review Human-Health Assessment Scoping Document

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containing d-limonene as an inert ingredient. Residues in drinking water were not included in 

the dietary risk assessments. For chronic dietary risk assessments, a NOAEL of 150 mg/kg bw/d 

was selected, based on a 103-week oral gavage study in the male rat. For all populations 

addressed, the margins of exposure (MOEs) for d-limonene were greater than HED’s MOE of 

concern of 100; the most highly exposed subgroup was children (1-2 years old) with an MOE of 

360. An acute assessment was not performed because no toxic effects attributable to a single 

(i.e., acute) exposure were identified. 

The residue chemistry database is sufficient to support the current registrations. No new residue 

chemistry data requirements have been identified for d-limonene to support registration review. 

There is sufficient information available to assess residential exposure. The residential 

assessment may need to be updated to incorporate any changes in short-term dermal and 

inhalation endpoints. Additionally, handler inhalation exposure may also need to be assessed for 

the outdoor residential uses of limonene. A revised residential assessment may also need to be 

performed to include residential handler dermal risks from use of pet shampoos and dips, as 

policies have recently changed. HED/OPP is currently revising the Residential Standard 

Operating Procedures (SOPs), including those used to determine exposure associated with pet 

treatments and impregnated bracelets/clothing/pest strips. Residential exposure to d-limonene as 

an inert ingredient may also need to be re-assessed due to changes in methodologies since the 

2004 TRED. 

 

Because the indoor crack and crevice use of d-limonene as an active ingredient is limited to 

inaccessible areas (applied under cabinets and behind appliances) and because of its high 

volatility, post-application residential dermal and incidental oral exposures are not expected for 

the indoor or outdoor residential uses. However, post-application inhalation exposure may also 

need to be assessed for residential indoor and outdoor uses. Post-application dermal, inhalation, 

and hand-to-mouth exposure assessments for pet shampoo and dip scenarios are recommended. 

Post-application exposure may also need to be assessed for impregnated clothing, bracelet, and 

strips uses that were not previously evaluated in the TRED. Representative residential handler 

scenarios and use sites are listed in Attachment 5. 

The 2004 aggregate risk assessment found short-term risks of concern; however, the exposures 

are considered to be over-estimated due to (1) the volatile nature of d-limonene, (2) the overly 

conservative and inconsistent points of departure for the short- and long-term dermal exposure 

scenarios, and (3) the conservative nature of the exposure assessment. A new acute and chronic 

aggregate risk assessment may also need to be conducted if a dietary risk assessment 

incorporating drinking water residues and updated endpoints is performed. Short-, intermediate-, 

and long-term aggregate risk estimates may also need to be updated once a revised residential 

assessment is available. 

Occupational post-application exposure to d-limonene has not been assessed. Because of the 

volatile nature of d-limonene (vapor pressure of 2 mm Hg), post-application dermal exposure is 

not expected. However, there is the potential for post-application inhalation exposures from the 

use pattern and associated sites (i.e., applied as a spray at a high application rate). Postapplication inhalation exposure may also need to be assessed during Registration Review. 

There are currently no established Codex or Mexican maximum residue limits (MRLs) for dlimonene. Harmonization is thus not an issue. 
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Introduction 

HED has evaluated the status of the human-health assessments for d-limonene to determine if 

sufficient data are available for Registration Review and whether any updates are required to 

support Registration Review. HED has considered the most recent human-health risk assessment 

for d-limonene (d-Limonene TRED, EPA-HQ-OPP-2004-0335-0003); updates to its toxicity, 

exposure, and usage databases that have occurred since the last registration; and the most 

recently updated Agency science policy and risk assessment methodologies to determine the 

scope of work necessary to support Registration Review. In addition, HED conducted an open 

search to look for new literature relevant to the human-health risk assessment of d-limonene. 

d-Limonene has a lemon-like flavor and smell, and occurs naturally in citrus and certain fruits, 

vegetables, meats, and spices. d-Limonene is used as both an active and inert ingredient in 

pesticide products, and as an ingredient in food products, soaps, and perfumes. As an active 

ingredient, it is used as an insecticide, herbicide, insect repellent, and animal (dog and cat) 

repellent. As a pesticide inert ingredient, it is used as a solvent or fragrance. FDA considers dlimonene to be GRAS as a food additive when used as a synthetic flavoring substance and 

adjuvant (21 CFR §182.60). d-Limonene is not registered for terrestrial food or feed crop uses as 

an active ingredient, but can be used in insect-repellent tablecloths and in insect-repellent strips 

used in food or feed-handling establishments. Since the d-Limonene TRED was completed in 

2004, a non-food herbicidal use has been assessed and registered. No new food uses have been 

assessed or registered. The most recent human-health risk assessment for d-limonene was 

completed in 2004 (d-Limonene TRED, EPA-HQ-OPP-2004-0335-0003). 

The established tolerances and exemptions, with the respective CFR citation, and the use patterns 

as an active and inert ingredient are listed in Table 1. 

Table 1. Established Tolerances and Exemptions for d-Limonene. 

Tolerance 

Exemption 

Expression 

CAS No. 40 CFR § PC 

Code Use Pattern List Classification 

Active Ingredient

180.539 079701

Used in insect-repellent 

tablecloths and in insectrepellent strips used in food- or 

feed-handling establishments 

NA 

Inert Ingredient

d-Limonene 5989-27-5 

180.910 and 180.930 (formerly 

180.1001(c) and (e))a, b 879701 “Solvent, fragrance” 4Bc

a

 Residues listed in 40 CFR §180.910 are exempt from a tolerance when used as inert ingredients in pesticide formulations applied to growing 

crops or to raw agricultural commodities after harvest and those listed in 40 CFR §180.930 are exempt from a tolerance when used as inert 

ingredients in pesticide formulations applied to animals. b

 In both sections, the inert ingredient is listed as “d-Limonene (CAS Reg. No. 5989-27-5).” c

 Inert ingredients are categorized into four lists as described in the 1987 and 1989 Policy Statements. List 4B inert ingredients are those inerts 

for which EPA has sufficient information to reasonably conclude that the current use pattern in pesticide products will not adversely affect public 

health or the environment.

Data needs and risk assessment updates required under registration review for d-limonene are as 

follows: 

• Formal review of both the 1992 developmental toxicity study in rat (MRID 42316301) 

and the 1994 2-week dermal toxicity range finding study (MRID 43117001). 
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• Reevaluation of endpoints for short- and long-term dermal and inhalation exposure 

scenarios, as well as chronic dietary exposure. 

• The need for acute dietary and incidental oral toxicity endpoints should be addressed as 

part of Registration Review. 

• A new chronic dietary risk assessment incorporating drinking water residues and 

reevaluation of the dietary endpoints may be required. An acute dietary risk assessment 

also may be required. 

• A new residential risk assessment may be required. 

• A new occupational risk assessment may be required. 

• A new aggregate risk assessment may also be required if revised dietary and residential 

exposure risk assessments have been performed. 

Hazard Identification/Toxicology 

d-Limonene has been evaluated extensively in a number of short- and long-term toxicity assays 

since the 1950s. Overlapping summaries of these studies can be found in the EPA RED (1994) 

and TRED (2004), in reviews published by the World Health Organization (WHO; 1993, 1998), 

and in the technical report for d-limonene issued by the National Toxicology Program (NTP, 

1990), which performed the carcinogenicity studies for d-limonene as well as several subchronic 

toxicity studies. The following hazard characterization summarizes the toxicology of d-limonene 

that is described in these reports and assessments, with additional information from the published 

literature where appropriate. 

d-Limonene is a skin and eye irritant, as well as a dermal sensitizer, with air-oxidized (vs. 

unoxidized) d-limonene shown to be the sensitizing agent (WHO, 1998). d-Limonene is 

essentially non-toxic following single doses via the oral or dermal routes (LD50 ≥4400 mg/kg) 

and inhalation routes (LC50 >4.8 mg/L) and non-toxic in repeat-dose oral animal studies up to 

relatively high doses (500 mg/kg/day). In addition, a 2-week preliminary study for a 90-day 

dermal toxicity study in the rat indicated that d-limonene produced excessive dermal irritation at 

doses ≥500 mg/kg/day, but no systemic toxicity. Oral doses ≥75 mg/kg/day of d-limonene elicit 

effects in the livers of rats; however, these effects are considered adaptive (non-adverse) and 

were correctly identified as such in the EPA TRED, since they were limited to increased relative 

liver weights and/or liver enzyme induction in the absence of evidence of histopathology in the 

liver in short-term studies, lack of progression to liver histopathology with longer-term 

exposures and/or higher doses, and the absence of changes in clinical chemistry parameters in 

rodent studies that would be indicative of liver toxicity (summarized in TRED 2004). The 

changes in liver parameters are therefore considered to reflect the increased functional capacity 

of the liver to detoxify d-limonene. This interpretation is consistent with the 2002 HED 

guidance document on “Hepatocellular Hypertrophy.” The only evidence of possible 

hepatotoxicity in the database for d-limonene was an increase (35%) in serum alkaline 

phosphatase and cholesterol and slightly increased absolute and relative liver weights in dogs 

treated orally with d-limonene for 6 months, as reported in WHO (1998). However, the findings 

were observed at a very high dose (1000 mg/kg/day), and the increased serum cholesterol was 

contradicted by the observation of decreased cholesterol levels in an earlier toxicity study in dogs 

at the same dose, as reported by NTP (1990), and decreased serum and liver cholesterol levels in 

rats exposed to d-limonene (WHO, 1993). 
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The kidney was also identified as a target organ in rodent toxicity studies, but only in male rats 

and not in any other sex or species. Extensive evaluation of the effects in the kidney of male 

rats, which were characteristic of hyaline droplet nephropathy, led to the conclusion by EPA, 

WHO, and NTP that the effects were associated with the increased production of the urinary 

protein, α2u-globulin, which is produced and excreted at high levels by the male rat only, and 

therefore not predictive of kidney toxicity in humans. This conclusion was supported by the 

observations that the concentration of d-limonene was approximately 3 times higher in male rats 

than in female rats and approximately 40% was reversibly bound to α2u-globulin (WHO, 1998). 

Renal tubular cell tumors were also observed in male rats in the 2-year carcinogenicity study 

performed with d-limonene. As was the case for the α2u-globulin nephropathy, the renal tumors 

were observed only in male rats, not in female rats, nor in mice of either sex in chronic 

bioassays. Several independent assessments determined that the kidney tumors observed in male 

rats do not pose a risk to humans, since they were observed only in animals with α2u-globulin 

nephropathy (a male rat-specific phenomenon) and humans do not synthesize α2u-globulin 

(WHO, 1998; Hard and Whysner, 1994; Whysner and Williams, 1996). In addition, d-limonene 

was negative in several mutagenicity and clastogenicity assays. 

WHO (1998) reported that there was no evidence of developmental toxicity with d-limonene, 

except at very high doses and in the presence of maternal toxicity. This conclusion was 

consistent with results from a developmental toxicity study in rats that was described in the 1994 

RED and 2004 TRED. It was stated that an increased number of litters and fetuses with 14th rib 

(“extra rib”) was observed in this study at the same dose (500 mg/kg/day) as reduced body 

weight gain in maternal animals. A clear NOAEL of 250 mg/kg/day was obtained for both 

maternal and developmental effects. This study should be formally reviewed for future 

regulatory actions for d-limonene. WHO (1998) and NTP (1990) also discussed the results of a 

developmental toxicity study in rabbits, in which effects in dams, but not offspring, were 

observed at ≥500 m/kg/day. There was no evidence of possible neurotoxicity following 

exposure to d-limonene, except in a 13-week oral study in mice in which decreased motor 

activity was observed at a very high dose (1000 mg/kg/day) (WHO, 1998). However, as pointed 

out by WHO (1998), the effects may have been due to general systemic toxicity and not a 

neurotoxic effect at this high dose. Mention was also made in WHO (1998) of a study in which 

various immune parameters were measured in mice exposed to d-limonene by gavage for 9 

weeks (Evans, et al.; 1987). However, this study is of questionable reliability for several 

reasons, including (1) the doses to which the animals were exposed were unreported, (2) there is 

a concern over the purity of the d-limonene that was tested, and (3) effects were negative or 

equivocal. Overall, the database supports the conclusion that high doses of d-limonene 

(≥500 mg/kg/day) are needed to induce any form of relevant toxicity in laboratory animals. 

Orally administered d-limonene is rapidly and almost completely absorbed in humans and 

animals. d-Limonene is also well-absorbed via the dermal and inhalation routes (WHO, 1998). 

The distribution (primarily to liver, kidney, and blood) and metabolism of d-limonene is rapid; 

negligible amounts remain in the tissues of rats 48 hours after exposure. d-Limonene is 

metabolized primarily to the water-soluble metabolites, d-limonene-8,9-diol and its glucuronic 

acid conjugate, as well as perillic acid. Human and animal studies indicate that when 

administered orally, 75-95% of d-limonene is eliminated in the urine and <10% in feces within 

2-3 days (NTP 1990). 
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Endpoint Selection and Food Quality Protection Act (FQPA) Considerations 

In the Agency’s TRED (2004), EPA chose endpoints for short- and long-term dermal and 

inhalation exposure scenarios, as well as chronic dietary exposure. These endpoints are 

summarized in Attachment 2. The short-term dermal and inhalation endpoints were based on 

increases in liver weight and liver enzymes (enzyme induction) in a 30-day short-term toxicity 

study in the rat. No adverse effects were observed in any of the chronic studies. However, the 

highest dose tested from a 2-year chronic rat study (150 mg/kg/day) was used as a NOAEL and 

provided a highly conservative endpoint for the long-term risk assessment because there was no 

toxicity identified in this study. The points of departure for the short- and long-term dermal and 

inhalation exposure scenarios are considered overly conservative and inconsistent and should be 

updated in future risk assessments for the following reasons: 1) the short-term endpoint was 

based on adaptive (non-adverse) effects in the liver, 2) long-term and chronic risks were assessed 

based on a study with no identified toxicity, and 3) the extrapolated NOAEL for short-term 

exposures (400/3X=133.3) is lower than the NOAEL chosen for long-term exposures (150 

mg/kg/day), thereby implying that the short-term toxicity of d-limonene is greater than its longterm toxicity, which is unlikely. However, based on the lack of systemic toxicity at doses above 

the limit dose in a range-finding dermal toxicity study in rats, a dermal risk assessment may not 

be necessary in the future. In addition, based on expected exposure patterns, the need for acute 

dietary and incidental oral toxicity endpoints should be addressed in future risk assessments as 

part of Registration Review. Currently, the study that provides the smallest lowest-observed 

adverse-effect level (LOAEL)/NOAEL in the database is a Good Laboratory Practice (GLP) 

developmental toxicity study in the rat that was submitted to the Agency in 1992 and 

summarized in both the RED (1994) and TRED (2004). It provides the lowest point of departure 

that is not based on adaptive (non-adverse) effects in the liver or kidney effects in male rats only 

(which is an endpoint that is not relevant to humans). However, as noted above, the 

developmental toxicity study in the rat, as well as the range-finding dermal toxicity study, should 

first be formally reviewed by the Agency. The magnitude of the FQPA Safety Factor (SF) will 

also need to be determined in regulatory review and should reflect the low toxicity and lack of 

offspring susceptibility with d-limonene. 

Endocrine Disruption 

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

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by 

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may 

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

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

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

This list of chemicals was selected based on the potential for human exposure through pathways 
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such as food and water, residential activity, and certain post-application agricultural scenarios. 

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

d-Limonene was not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. 

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

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

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

Conclusions

The toxicity database is adequate to support existing registrations and registration review. dLimonene does not cause repeat-dose toxicity in laboratory animals except at high doses (≥500 

mg/kg day), and there was no evidence of immunotoxicity in a published immunotoxicity study 

with d-limonene. In addition, d-limonene occurs naturally in citrus fruits and spices and is 

classified as GRAS by the FDA when used as a food additive. Therefore, although oral 

immunotoxicity, acute neurotoxicity, subchronic neurotoxicity, and reproductive toxicity studies 

are now required, as specified in the most recent 40 CFR Part 158 data requirements, the Agency 

does not believe that conducting these studies will provide any additional relevant information 

for human-health risk assessment. 

A 90-day dermal toxicity study is not a requirement for food-use chemicals, as specified in 40 

CFR Part 158. This study was only requested as “confirmatory” data in the 1994 RED. Due to 

the low toxicity of d-limonene via the oral route and the lack of systemic toxicity when tested up 

to 1500 mg/kg/day in a 2-week range-finding dermal toxicity study (summarized in the RED), 

systemic toxicity via the dermal route is not expected, except perhaps at doses above the limit 

dose. Therefore, HED does not believe that conducting a 90-day dermal toxicity study will 

provide additional relevant information for human-health risk assessment. In addition, a full 90-

day dermal toxicity study may not be feasible, since mild to severe irritation, which was 

observed at the dose site at all doses tested in the 2-week range-finding dermal study in rats, may 

preclude a meaningful interpretation of the results. 

The toxicity profile table for d-limonene, which can be found in the 2004 TRED, should be 

updated to incorporate the results of an acute inhalation toxicity study with d-limonene technical 

(LC50 >4.8 mg/L, MRID 00150433). In addition, both the 1992 developmental toxicity study in 

rat (MRID 42316301) and the 1994 2-week dermal toxicity range finding study (MRID 

43117001) should be formally reviewed by the Agency in order to verify the results of these 

studies, which have been summarized in the RED and/or TRED. 

Residue Chemistry

No residue chemistry studies have been submitted or are required to support the currently 

registered food uses of d-limonene. HED notes that a study on the magnitude of residues 

resulting from foliar application of d-limonene to mustard greens has been submitted to the 

Agency (MRID# 47548301). Review of this study is not required to support the currently 

registered food uses of d-limonene. 
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Conclusions 

The residue chemistry database is sufficient to support the current d-limonene registrations. 

Dietary Exposure 

The most recent chronic dietary-exposure assessment for d-limonene was completed in 2004 (dLimonene TRED, EPA-HQ-OPP-2004-0335-0003). Screening-level assessments were 

performed to determine the potential exposure for d-limonene in the food supply as a result of 

applications of a pesticide product containing d-limonene as an inert ingredient. This assessment 

would also cover any residues resulting from the d-limonene food uses (i.e., food additive and 

food-handling establishments). The following assumptions were used for the DEEMTM modeling: 

• 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; i.e., 100% of all crops are “treated” with inert 

ingredients; 

• No adjustment made for % of inert in formulation, application rate, or multiple 

applications of different active ingredient formulations; 

• Considers only preharvest applications. 

For chronic dietary risk assessments, a NOAEL of 150 mg/kg bw/d was selected, based on a 

103-week oral gavage study in the male rat. For all populations addressed, the MOEs for dlimonene were greater than the MOE of concern of 100; the most highly exposed subgroup was 

children (1-2 years old) with an MOE of 360 (0.12 mg/kg body). By comparison, the intake of 

d-limonene from food sources for the general population was estimated to be 0.27 mg/kg body 

weight per day (Flavor and Extract Manufacturers Association (1991) d-Limonene Monograph). 

An acute assessment was not performed because no toxic effects attributable to a single (i.e., 

acute) exposure were identified. 

d-Limonene is only somewhat soluble in water (13.8 mg/L) and has an estimated octanol/water 

partition coefficient of 4.2. d-Limonene is expected to rapidly volatilize from water to the 

atmosphere, with an estimated half-life for volatilization from a model river of 3.4 hours, 

although adsorption to sediment and suspended organic matter may attenuate the rate of this 

process. Based on these data, it is unlikely that d-limonene will occur in drinking water sources 

resulting from any of the registered uses at the time the d-Limonene TRED was completed in 

2004. Residues in drinking water were thus not included in the dietary risk assessments. As new 

herbicidal uses of d-limonene with significantly higher use rates have been recently registered, 

actual estimated drinking water residues should be requested from the Environmental Fate and 

Effects Division (EFED) and, if finite values are provided, incorporated in any future dietary risk 

assessments. 

Conclusions 

A new chronic dietary risk assessment incorporating drinking water residues and reevaluated 

endpoints may be required. An acute dietary risk assessment also may be required. 
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Residential Exposure

d-Limonene can be used as both an active and an inert ingredient in products registered for use in 

residential environments. It is registered for use on many residential sites, including pets (as a 

shampoo or dip), outdoor premises (spot treatment), indoor treatments (crack and crevice and 

cleaning uses), impregnated materials (repellant clothing, bracelets, strips), roads and sidewalks 

(spot treatment), and professional applications to wooden structures (applied as a wood 

injection). Additional exposure may occur naturally through different foods, soaps, and 

perfumes. These uses are FDA-approved and generally regarded as safe. The representative 

residential use patterns, application rates and formulations of pesticide products are provided in 

Attachment 5. 

Residential Handlers

HED has determined that residential handlers are likely to be exposed to d-limonene residues via 

dermal and inhalation routes during mixing, loading, and application activities. HED expects the 

duration of the handler exposures to be short-term for the pet, the indoor crack and crevice, and 

outdoor residential uses, and long-term for the indoor cleaning uses of d-limonene. No handler 

exposure is expected to result from the wood injection treatment or repellant uses of d-limonene. 

Based on anticipated used patterns and information provided on the product labels, the TRED 

(2004) assessed residential dermal risks from exposure to products containing d-limonene as an 

active ingredient (Table 5.1) examining the following scenarios: loading/applying granulars by 

hand, mixing/loading/applying emulsifiable concentrates with a watering can, applying ready-touse (RTU) formulations via pump-trigger spray, applying RTU formulations via shampoo, and 

applying RTU formulations via dip. (An assessment of handler inhalation exposure was not 

included in the TRED and, therefore, may need to be conducted during Registration Review). 

The only scenario which exceeded HED’s level of concern (MOEs were ≤LOC = 300) was the 

application of pet dips (MOE = 81). HED is not concerned with risk estimated in the TRED as 

the assessment is considered to be over-estimated due to the conservative nature of the hazard 

and exposure assessment. The pet handler assessment will be revisited during Registration 

Review to incorporate modifications in policy since the 2004 TRED, as well as potential changes 

is endpoint selection. 

Residential handler dermal risks from exposure to products containing d-limonene as an inert 

ingredient (Table 3.2) were also assessed in the EPA TRED. Exposure was assumed to be from 

application of pressurized liquid, RTU liquids, and emulsifiable and soluble concentrates. The 

EPA TRED assessed residential inhalation exposure from long-term consumer use of general 

purpose cleaner and aerosol spray (crack and crevice only) products (Table 3.3), which was 

assumed to represent the highest exposures expected for indoor uses. A revised assessment of 

residential handler inhalation exposure is recommended for other exposure durations of indoor 

and outdoor residential use scenarios of products containing d-limonene as an inert. The 

residential handler assessment may also need to be updated to incorporate potential changes in 

the hazard assessment, as well as changes in methodologies that have occurred since the 2004 

TRED. 

Residential Post-Application

HED expects post-application dermal exposure to adults and children from the residential 

applications of d-limonene, with the exception of the pet uses, to be negligible because of the use 

pattern and high volatility (2 mm Hg) of the chemical. (Note: The EPA TRED did not examine 

post-application exposure). For the outdoor residential uses, chemical residues are expected to 
d-Limonene Registration-Review Human-Health Assessment Scoping Document

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quickly volatilize after application and therefore are not expected to be available for contact. 

Additionally, because the indoor crack and crevice uses of limonene is limited to inaccessible 

areas (such as, under cabinets and behind appliances), dermal and/or incidental oral exposure are 

not expected. However, due to the high vapor pressure of limonene, there is the potential for 

post-application inhalation exposure from both the indoor and outdoor uses of limonene. Postapplication inhalation exposure may need to be assessed for indoor and outdoor residential uses 

during the Registration Review process. Post-application dermal, inhalation, and hand-to-mouth 

exposures may need to be assessed for pet treatment scenarios. Post-application exposure may 

also need to be assessed for impregnated clothing, bracelet, and strips uses that were not 

previously evaluated in the TRED. 

Conclusions 

There is sufficient information available to assess residential exposure. The residential 

assessment may need to be updated to incorporate potential changes in short-term dermal and 

inhalation endpoints. Additionally, handler inhalation exposure may also need to be assessed for 

the outdoor residential uses of limonene. A revised residential assessment may also need to be 

performed to include residential handler dermal risks from use of pet shampoos and dips, as 

policies have recently changed. HED/OPP is currently revising the Residential SOPs, including 

those used to determine exposure associated with pet treatments and impregnated 

bracelets/clothing/pest strips. Residential exposure to d-limonene as an inert ingredient may also 

need to be re-assessed due to changes in methodologies since the 2004 TRED. 

 

Because the indoor crack and crevice use of d-limonene as an active ingredient is limited to 

inaccessible areas (applied under cabinets and behind appliances) and because of its high 

volatility, post-application residential dermal and incidental oral exposures are not expected for 

the indoor or outdoor residential uses. However, post-application inhalation exposure may need 

to be assessed for residential indoor and outdoor uses. A post-application dermal, inhalation, and 

hand-to-mouth exposure assessments for pet shampoo and dip scenarios are recommended. 

Post-application exposure may also need to be assessed for impregnated clothing, bracelet, and 

strips uses that were not previously evaluated in the TRED. Representative residential handler 

scenarios and use sites are listed in Attachment 5. 

Aggregate Risk Assessment

In the most recent human-health risk assessment (d-Limonene TRED, EPA-HQ-OPP-2004-0335-

0003), aggregate risk assessments were performed for short- and long-term exposures. A cancer 

risk assessment was not conducted because d-limonene has been classified as negative for 

carcinogenicity in humans and an acute assessment was not performed because no toxic effects 

attributable to a single (i.e., acute) exposure were identified.. 

As the residential handler dermal risks from the application of pet dips exceeded HED’s LOC, 

this scenario was not included in the aggregate risk assessment. To judge the potential aggregate 

exposures for d-limonene the Agency performed an aggregate assessment for two other 

residential scenarios: use in a cleaning product, and use in RTU pet shampoo formulations. The 

cleaning product represents the use of d-limonene as an inert ingredient in a product that could 

be used in and around the home. Cleaning products also tend to be used in a repetitive manner, 

and are more of a chronic type of scenario. The RTU pet shampoo formulation represents the 

use of d-limonene as an active ingredient in a product that could be used in and around the home. 
d-Limonene Registration-Review Human-Health Assessment Scoping Document

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The RTU formulation also represents a very short-term scenario that could be measured in 

minutes that is of a non-repetitive nature. 

Given that these two scenarios bracket the inert and active uses, as well as the short-term and 

more chronic types of scenarios, and that these two scenarios have the lowest residential MOEs 

estimated for d-limonene, all other aggregate MOEs should be greater than the target MOE. 

The short-term aggregate MOE is 290 (which combines dietary exposure with residential 

exposure from the RTU pet shampoo formulations) and is less than the target MOE of 300. 

However, as previously discussed, the dietary exposures are considered to be over-estimated due 

to the volatile nature of d-limonene. The driver for the aggregate exposure is the residential 

exposure, which is also considered to be over-estimated. The long-term aggregate MOE (which 

combines dietary exposure with residential exposure from the cleaning products) is 170 and is 

greater than the target MOE of 100. 

Conclusions

The 2004 aggregate risk assessment found short-term risks of concern; however, the exposures 

are considered to be over-estimated due to (1) the volatile nature of d-limonene, (2) the overly 

conservative and inconsistent points of departure for the short- and long-term dermal exposure 

scenarios, and (3) the conservative nature of the exposure assessment. To more realistically 

characterize risk, new acute and chronic aggregate risk assessments may need to be conducted 

once a dietary risk assessment incorporating drinking water residues and updated endpoints is 

available. Short-, intermediate-, and long-term aggregate risk estimates may also need to be 

updated once a revised residential assessment is available. 

Occupational Exposure 

d-Limonene is registered for use on tree, nut, vine, berry, vegetable, and flavoring/spice crops; 

and non-crop areas such as borders, driveways, sidewalks, patios, wood injection uses, and 

ornamental plants. 

Occupational Handlers

Occupational handler exposure is not assessed in the EPA TRED. An occupational handler 

exposure/risk assessment for proposed uses of d-limonene on tree, nut, vine, berry crops, and 

non-crop areas was conducted in February of 2008 (Memo, M. Dow, 2/25/08, D348549). Based 

on the use pattern, the most likely methods of application for tree, nut, vine, berry crops, and 

non-crop uses are by ground-boom spray machinery, low-pressure hand-wand sprayer, backpack 

sprayer, and hand-held pump-up sprayer at a maximum application rate of 61.5 lbs ai/Acre. All 

assessed MOEs were not of concern to HED (MOEs were ≥LOC = 100), provided handlers wear 

protective gloves. (It should be noted that currently registered labels do not listed gloves as the 

required personal-protective equipment (PPE)). 

Occupational handler assessments have not been assessed for mixer/loader/applicators for wood 

protection treatments using injection equipment and package applicators; however, based on the 

label rate and use pattern, they are not expected to exceed HED’s LOC. In addition, a revised 

occupational handler assessment may be needed for the occupational use of aerosol cans. The 

assessment of occupational exposure and risk may also need to be updated based on potential 

changes to the hazard assessment. 
d-Limonene Registration-Review Human-Health Assessment Scoping Document

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Occupational Post-Application

Occupational post-application exposure to d-limonene has not been assessed. Because of the 

volatile nature of d-limonene (vapor pressure of 2 mm Hg), post-application dermal exposure is 

not expected. However, there is the potential for post-application inhalation exposures from the 

use pattern and associated sites (i.e., applied as a spray at a high application rate). Postapplication inhalation exposure may need to be assessed during Registration Review. 

Conclusions

There is sufficient information available to assess occupational handler exposure. There are 

occupational handler scenarios that have not been assessed; however, based on label rates and 

use patterns, they are not expected to exceed HED’s LOC. A post-application inhalation 

exposure assessment is recommended for indoor and outdoor uses. The assessment of 

occupational exposure and risk may also need to be updated based on potential changes to the 

hazard assessment. Representative occupational handler scenarios and use sites are listed in 

Attachment 5. 

Public Health and Pesticide Epidemiology Data 

For this evaluation, both the OPP Incident Data System (IDS) and the Centers for Disease 

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

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

consulted for pesticide incident data on the active ingredient d-limonene. Additionally, the 

Agency is looking to include findings from the Agricultural Health Study (AHS), beginning with 

the problem formulation phase of registration review. The purpose of the database searches is to 

identify potential patterns on the extent and severity of the health effects attributed to d-limonene 

exposure. The IDS includes reports of alleged human-health incidents from various sources, 

including mandatory FIFRA Section 6 (a) (2) reports from registrants, other federal and state 

health and environmental agencies, and individual consumers. Since 1992, OPP has compiled 

these reports in IDS. IDS contains reports from across the U.S. and most incidents has all 

relevant product information recorded. Reports submitted to the IDS represent anecdotal reports 

or allegations only, unless otherwise stated in the report. The NIOSH SENSOR database covers 

12 states from 1998-2006, although reporting varies from state to state (the database includes a 

total of 10,659 cases). Pesticide-related incidents are collected from Department of Labor 

workers’ compensation claims when reported by physicians, reports from State Departments of 

Agriculture, from poison-control centers, and from State Departments of Health based on reports 

by physicians suspecting pesticide exposure. Although both occupational and non-occupational 

incidents are included in the database, SENSOR focuses on occupational pesticide incidents, and 

is of particular value in providing that information. A state SENSOR contact specialist does 

follow-up with workers and obtains medical records to verify symptoms, circumstances 

surrounding the exposure, severity, and outcome. Using standardized protocol and case 

definitions, derived from poison center reporting, SENSOR coordinators at State Departments of 

Health enter the incident interview description provided by the worker, medical report, 

physician, and patient into the SENSOR data system, accessible to participating states and EPA. 

The AHS is a high-quality, prospective epidemiology study evaluating the link between pesticide 

use and various health outcomes, including cancer. The AHS includes private and commercial 

pesticide applicators and their spouses. If there are AHS findings relevant to a particular 

pesticide going through registration review, the Agency will ensure they are considered in the 

problem-formulation/scoping phase of the process and, if appropriate, fully reviewed in the risk-
d-Limonene Registration-Review Human-Health Assessment Scoping Document

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assessment phase of the process. The AHS includes information on the use of 50 different 

pesticide active ingredients commonly used in agriculture. 

For IDS, HED identified 39 cases reported for d-limonene in the United States from 2002 to the 

present. Of these cases, five were reviewed because in these cases d-limonene was used as a 

single chemical only and, therefore, these cases provide more certain information about the 

potential effects of d-limonene exposure. Three of the cases appeared to involve exposure from 

using a flea and tick shampoo containing d-limonene in residential settings, and the remaining 

two cases involved postapplication exposure in residential settings (after professional 

application). The most frequently reported symptoms were neurological (38%), followed by 

dermal (25%); gastrointestinal, ocular, and miscellaneous symptoms were reported equally 

(13%). Proportions relate to the total number of symptoms, not the total number of cases; i.e., an 

individual may report multiple symptoms to the database. See Attachment 7 for further details. 

For NIOSH SENSOR, HED identified 4 cases reported that involve the active ingredient dlimonene. Of these cases, only one was reviewed because, in this case, d-limonene was used as a 

single chemical only and had a certainty classification of definite, probable, or possible. The 

case was an unknown age male who had a postapplication exposure to d-limonene when he 

entered an office that had just been treated. He experienced ocular, respiratory, neurological and 

gastrointestinal symptoms. This case was ranked low severity. 

Limonene is not included in the AHS, and therefore not considered in this report. 

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

at this time that would warrant further investigation. Although there are incidents reported that 

resulted in moderate outcomes, the symptoms and settings were varied and do not indicate a 

trend or pattern that would trigger follow-up analyses. The Agency will continue to monitor the 

incident information and if a concern is triggered, additional analysis will be included in the risk 

assessment. 

Tolerance Assessment and International Harmonization 

U.S. permanent tolerances (listed in 40 CFR §180.539) are summarized in Attachment 6. There 

are currently no established Codex or Mexican MRLs for d-limonene. Harmonization is thus not 

an issue. 

Environmental Justice 

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

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

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

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The OPP 

typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who may be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information. 
d-Limonene Registration-Review Human-Health Assessment Scoping Document

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Human Studies 

Past d-limonene risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide to determine their dermal and inhalation 

exposure. Many such studies, involving exposure to many different pesticides, comprise 

generic pesticide exposure databases such as the Pesticide Handlers Exposure Database 

(PHED), the Outdoor Residential Exposure Task Force (ORETF) Database, and the 

Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies 

supporting these multi-pesticide generic exposure databases, and has found no clear and 

convincing evidence that the conduct of any of them was either fundamentally unethical or 

significantly deficient relative to the ethical standards prevailing at the time the research was 

conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of 

Research (40 CFR Part 26) have been satisfied, and there is no regulatory barrier to continued 

reliance on these studies. 

Data Requirements 

Toxicology 

No toxicology data requirements have been identified for d-limonene to support registration 

review. 

Residue Chemistry 

No residue chemistry data requirements have been identified for d-limonene to support 

registration review. 

Occupational and Residential Exposure 

No new occupational exposure or residential exposure data requirements have been identified for 

d-limonene to support registration review. 

References 

Table 2. Memoranda Relevant to Registration Review. 

Author Barcode Date Title 

USEPA 

EPA-HQOPP-2004-

0335-0003 

2003 Exposure and Risk Assessment on Lower Risk 

Pesticide Chemicals. d-Limonene. 

USEPA EPA 738-R94-034. 1994 Reregistration Eligibility Decision (RED): 

Limonene. 

Dow, M. D348549 25-FEB-2008 

Occupational Exposure/Risk Assessment for 

Proposed New Uses of d-Limonene on Tree, Nut, 

Vine, Berry Crops and Non-Crop Areas. 

Winfield, S., et al. D374493 20-MAY-2010 Limonene: Review of Human Incidents. 

Evans DL, Miller DM, Jacobsen KL, Bush PB. 1987. Modulation of immune responses in mice 

by d-limonene. J. Toxicol. Environ. Health 20(1-2):51-66. 

Flavor and Extract Manufacturers Association (1991) d-Limonene 

Monograph. Washington, DC, pp. 1–4. 
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Hard GC, Whysner J. 1994. Risk assessment of d-limonene: an example of male rat-specific 

renal tumorigens. Crit. Rev. Toxicol. 24(3):231-54. 

National Toxicology Program (NTP). 1990. Toxicology and Carcinogenesis Studies of dLimonene (CAS No. 5989-27-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP TR 

347. U.S. Department of Health and Human Services, Public Health Service, National Institutes 

of Health. NIH Publication No. 90-2802. 

Whysner J, Williams GM. 1996. d-Limonene mechanistic data and risk assessment: absolute 

species-specific cytotoxicity, enhanced cell proliferation, and tumor promotion. Pharmacol. 

Ther. 71(1-2):127-36. 

World Health Organization (WHO). 1993. Toxicological Evaluation of Certain Food Additives 

and Naturally Occurring Toxicants. International Programme on Chemical Safety. 39th Meeting 

of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Accessed: 4/29/2010. 

Website: http://www.inchem.org/documents/jecfa/jecmono/v30je05.htm 

World Health Organization (WHO). 1998. Concise International Chemical Assessment 

Document No. 5: Limonene. International Programme on Chemical Safety. Prepared by: Dr. A. 

Falk Filipsson, National Institute for Working Life; Mr. J. Bard; Ms. S. Karlsson, National 

Chemicals Inspectorate. Accessed: 4/22/2010. Website: 

http://www.inchem.org/documents/cicads/cicads/cicad05.htm

Attachments 

Attachment 1: Chemical Identity Table 

Attachment 2: d-Limonene Endpoint Selection Tables 

Attachment 3: Residential Use Patterns/Exposure Scenarios for d-Limonene 

Attachment 4: Exposure Potential for Adult and Child Aggregate Risk Estimates 

Attachment 5: Occupational Use Patterns/Exposure Scenarios for d-Limonene 

Attachment 6: d-Limonene International Residue Limit Status 

Attachment 7: IDS Report 

cc: G. Kramer (RAB1), A. Nowotarski (RAB1), R. Mitkus (RAB1) 

RDI: RAB1 (5/19/10) 

G.F. Kramer:S10781:PY-S:(703)305-5079:7509P:RAB1
d-Limonene Registration-Review Human-Health Assessment Scoping Document

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Attachment 1: Chemical Identity Table 

Chemical Identity of d-Limonene.

Structure 

Molecular formula C10H16

Molecular weight 136.2 g/mole 

Physical state colorless liquid, with characteristic mild citrus odor 

Melting point -75 °°C 

Boiling point 176 °C 

Solubility in water 13.8 mg/L at 25oC 

pH Not applicable 

Density/Specific Gravity 0.84 g/mL 

Vapor Density Relative vapor density = 4.7 (air = 1) 

Vapor Pressure 0.4 kPa at 14.4oC; 2 mm Hg at 20oC 

Estimated Octanol/Water Coefficient log Kow: 4.2 

Dissociation Constant Not applicable 

References: 

NIOSH, 2001; 

WHO, 1998 
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Attachment 2: d-Limonene Endpoint Selection Table 

Table 2. Summary of Toxicological Endpoints for Use in Human Risk Assessment – from the TRED (2004).

EXPOSURE 

SCENARIO 

DOSE 

(mg/kg/day) ENDPOINT STUDY 

Short-Term 

Dermal and 

Inhalation 

LOAEL = 400 

(only dose tested) 

MOE = 300 

increased relative liver weights and enzymes (nonadverse effects) 30-day rat oral 

(gavage) study 

[Ariyoshi, et al. 

(1975) in WHO 

(1998)] 

Long-Term 

Dermal and 

Inhalation, and 

Chronic dietary 

NOAEL = 150 

(highest dose tested) 

MOE = 100 

A LOAEL was not observed. 103-week oral 

gavage study in 

the male rat 

(NTP, 1990) 

NOAEL = no-observed adverse-effect level, LOAEL = lowest-observed adverse-effect level. 
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Attachment 3: Previous Residential Assessment for d-Limonene 

(from d-Limonene TRED, EPA-HQ-OPP-2004-0335-0003) 

Table 3.1. Residential Handler Risks Due to Exposure to d-Limonene as an Active Ingredient.

Exposure Scenario

Assumptions for 

estimating 

product 

application rate

Percent 

active 

ingredient

Calculation 

of product 

application 

rate (AR)

Application 

Rate

Area Treated 

or Amount 

Handled 

Dailya

Baseline Dermal 

MOEb

Loading/Applying 

Granulars by Hand 

From product 

label – 

apply 1 lb/800 

ft2

4 

AR = (1 

lb/800 

ft2

)*0.04 

0.00005 lb 

ai/ft2 1000 ft2

/day 1,300 

Mixing/loading/app

lying emulsifiable 

concentrates with a 

watering can 

From product

label, max 

application rate 

is 8 fl. oz and 

5.6 lb ai/gallon 

78.2 

AR = 5.6 lb 

ai/gal *1 

gal/128 oz * 

8 oz/1000 ft2

0.00035 lb 

ai/ft2 1000 ft2

/day 7,300 

Applying RTU 

(Ready-to-Use) 

Formulations via 

Pump-Trigger 

Spray 

Assume 0.125 

gallons of 

product applied 

per day and 

assume density 

is 1.0 g/mL 

5.8 

AR = (1.0 

g/mL * 

0.0022 lb/g * 

3785 mL/gal) 

* 0.058 

0.48 lb 

ai/gallon 0.125 gal/day 2,100 

Applying RTU 

Formulations via 

Shampoo 

Average size of 

shampoo bottle 

is 12 oz; use 1⁄2 

bottle when 

shampooing pet; 

assume density 

is 1.0 g/mL 

5 

AR = (1.0 

g/mL * 

1000mL/L * 

1L/33.8 oz * 

1000 mg/g * 

6 oz/day) * 

0.05 

8,876 mg 

ai/day NA 320 

Applying RTU 

Formulations via 

Dip 

From product

label – 

 use 1.5 

oz/gallon of 

water; assume 

density is 1.0 

g/mL 

78.2 

AR = (1.0 

g/mL * 

1000mL/L * 

1L/33.8 oz * 

1000 mg/g * 

1.5 oz/day) * 

0.782 

34,704 mg 

ai/day NA 81 

a Amount handled per day values are EPA estimates of amount treated based on revised Residential SOPs (2/01). 

b Baseline Dermal MOE = LOAEL (400 mg/kg/day) / dermal daily dose (mg/kg/day), where dermal dose = daily 

unit exposure (μg/lb ai) x application rate x amount handled per day x conversion factor (if needed) / body weight 

(70 kg adult). 

LOC = MOEs ≤300. 
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LOC = MOEs ≤300. 

Table 3.2. Residential Handler Risks Due to Exposure to d-Limonene as an Inert Ingredient.

Formulation 

Type

Application 

method Crop Treated Application Rate

Area treated or 

Amount Used Dermal MOE

Turf, Garden, Trees, Outdoor 

Perimeter Treatment 

0.00023 

lb/ft2 1000 ft2 Low-pressure 170,000 

handwand 

Crack and Crevice 0.12 lb/gal 0.5 gal/day 660,000 

Backpack Turf, Garden, Trees, Outdoor 

Perimeter Treatment 

0.00023 

lb/ft2 1000 ft2

 3,300,000 

Turf 20000 ft2 28,000 

Emulsifiable 

Concentrate 

Hose-end 

sprayer Garden and Trees 

0.00023 

lb/ft2 1000 ft2

 550,000 

Crack and Crevice 0.094 

gal/day Pressurized 56,000 

liquid Aerosol 

Outdoor paint and stain 0.28 gal/day 

NA 

8,100 

Turf and Garden 1.0 gal/day NA 2,300 Pump-trigger Crack and Crevice 0.50 gal/day NA 10,000 

Paintbrush Trees and Outdoor Paint and Stains 1.0 gal/day NA 2,200 

Airless 

sprayer 15 gal/day NA 420 

Backpack 5 gal/day NA 20,000 Outdoor Paint and Stains 

Low-pressure 5 gal/day NA 1,000 

handwand Crack and Crevice 0.50 gal/day NA 10,000 

Pump-trigger 0.13 gal/day NA 18,000 

RTU liquid 

Low-pressure 

handwand 

Crack and Crevice 

0.50 gal/day NA 10,000 

Turf 410,000 

Garden and Trees 120,000 Low-pressure 

handwand 

Crack and Crevice 

0.00023 

lb/ft2 1000 ft2

490,000 

Backpack Turf, Garden, Trees and Outdoor 

Perimeter Treatment 

0.00023 

lb/ft2 1000 ft2

 2,400,000 

Turf 20000 ft2 21,000 

Hose-end 

sprayer Garden and Trees 

0.00023 

lb/ft2

1000 ft2

 410,000 

Crack and Crevice 0.12 lb/gal 0.5 gal/day 490,000 

Soluble 

Concentrate 

Low-pressure 

handwand Outdoor Perimeter Treatment 0.00023 

lb/ft2 1000 ft2

 120,000 
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Table 3.3. Summary of Consumer Dermal and Inhalation Exposure.

Scenarioa Weight 

Fractions 

Dermal Doseb

(mg/kg-day) 

Dermal 

MOEc

Inhalation 

Doseb

(mg/kg-day) 

Inhalation 

MOE 

General Purpose 

Cleaner 0.125 5.77e-02 2,600 7.53E-01 200c

Aerosol Spray Can 0.000734 NAe NA 3.22E-03 124,200d

a This model run was developed using the Office of Pollution, Prevention, and Toxics (OPPT). The general 

purpose cleaner scenario was run with Standard New Chemicals Program assumptions and defaults. The aerosol 

spray can scenario was modified to assess 60 days of use over a year. 

b Modeled for chronic dose rates. 

c MOE = NOAEL (150 mg/kg-day) / Average Daily Dose (mg/kg/day). 

d MOE = LOAEL (400 mg/kg-day) / Average Daily Dose (mg/kg/day). 

e NA = Not available. EFAST Consumer Exposure Module does not have a dermal exposure scenario for aerosol 

paint.
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Attachment 4: Exposure Potential for Adult and Child Aggregate Risk Estimates 

(from d-Limonene TRED, EPA-HQ-OPP-2004-0335-0003) 

Dietary Risk Calculations 

Estimated Chronic Dietary Exposurea and Riskb for a Generic Inert Ingredient. 

Population Subgroupc Estimated Exposure, mg/kg/day MOE 

U.S. Population (total) 0.120 1250 

All infants (<1 year old) 0.245 610 

Children (1-2 years old) 0.422 360 

Children (3-5 years old) 0.310 480 

Children (6-12 years old) 0.174 860 

Youth (13-19 years old) 0.100 1500 

Adults (20-49 years old) 0.087 1720 

Adults (50+ years old) 0.086 1740 

Females (13-49 years) 0.087 1720 

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

including meat, milk, poultry, and eggs. 

b MOE = NOAEL (150 mg/kg/day) / Estimated Exposure (mg/kg/day). 

c Only representative population subgroups are shown.

Short- and Long-Term Aggregate Risk Calculations 

Aggregate MOEs. 

Scenario Type of Assessment Exposure 

(dietary + residential) (mg/kg/day) MOE 

RTU via 

shampoo 

short-term 

LOAEL = 400 mg/kg/day 

target MOE is 300 

0.12 + 1.25 = 1.37 290 

general 

cleaner 

long-term 

NOAEL = 150 mg/kg/day 

target MOE is 100 

0.12 + 0.753 = 0.873 170 

 
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Attachment 5: Occupational/Residential Use Patterns/Exposure Scenarios for d-Limonene 

Table 5.1. Summary of Representative Use Patterns, Formulations, and Application Rates for d-Limonene. 

Use Site Scenario 

Covered? 

Max. Rate 

per App 

 Max. Rate 

 Unit/Area 

*UG 

Form Max. App

Rate/ yr 

 Application Equipment 

 //Type 

NON-FOOD/NON-FEED USES

automobiles, taxis, 

limousines, recreational 

vehicles, & tires 

N 1 -- (L) 

*M1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment 

N .0663 lb/1 gal 

*O1 

EC NS Not on label/ Sponge 

//Dip treatment/ Spongeon/ 

Sprinkle 

cats (adults/kittens) 

 

N 1 -- (L) 

*O1 

PRL 

RTU 

NS Aerosol can/ By hand/ 

Pump 

spray bottle 

//Animal treatment 

(spray)/ 

Shampoo 

Christmas tree plantations Y 1 part (L) 

*C1 

L NS Hand held sprayer 

//Spray 

citrus Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast 

commercial 

storages/warehouses 

premises 

N 1 -- (L) 

*C1 M1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment/ Injection 

treatment/ Outdoor general 

surface spray/ Perimeter 

treatment 

commercial transportation 

facilities-nonfeed/nonfood 

N 1 -- (L) 

*M1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment 

N .1654 lb 1K sq.ft 

*M1 

PRL NS Aerosol can 

//Crack and crevice 

treatment 

commercial/institutional/ 

industrial premises/equip. 

(indoor) 

 Y 

(N for 

PRL)

1 -- (L) 

*M1 

EC 

PRL 

NS Aerosol can/ Pressure 

sprayer 

//Contact and/or surface 

treatment/ Crack and 

crevice and/or spot 

treatment/ Crack and 

crevice treatment/ Directed

spray 

Y 

(N for 

PRL)

1 -- (L) 

*C1 

EC 

PRL 

NS Aerosol can/ Pressure 

sprayer 

//Contact and/or surface 

treatment/ Crack and 

crevice and/or spot 

treatment/ Crack and 

crevice treatment/ Directed

spray/ Perimeter treatment 

(a) 

Y 1 part (L) 

*C1 

EC NS Pressure sprayer 

//Mound drench (b) 

commercial/institutional/ 

industrial 

premises/equipment 

(outdoor) 

 

 

N 10 sec location 

(L) 

*C1 

PRL NS Aerosol can 

//Injection treatment/ 

Outdoor general surface 

spray (c) 
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N .0663 lb/1 gal 

*O1 

EC NS Not on label/ Sponge 

//Dip treatment/ Spongeon/ 

Sprinkle (a) 

dogs/canines 

(adults/puppies) 

 

N 1 -- (L) 

*O1 

PRL 

RTU 

NS Aerosol can/ By hand/ 

Pump 

spray bottle 

//Animal treatment 

(spray)/ 

Shampoo (b) 

forest trees (all or 

unspecified) 

Y 1 part (L) 

*J1 

L NS Hand held sprayer 

//Spray (a) 

forest trees (softwoods, 

conifers) 

Y 1 part (L) 

*J1 

L NS Hand held sprayer 

//Spray (a) 

grapes Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y 1.2775 lb/1 gal 

*C1 

EC NS Sprayer 

//Spray (b) 

greenhouses-in use 

 

 

Y 1 -- (L) 

*C1 

RTU NS RTU spray container 

//Spray (c) 

hospitals/medical 

institutions premises 

(human/veterinary) 

N .1654 lb 1K sq.ft 

*N1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

 N 1 -- (L) 

*N1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (b) 

N .1654 lb 1K sq.ft 

*O1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

household/domestic 

dwellings 

 

Y 

(N for 

PRL)

1 -- (L) 

*O1 

EC 

PRL 

RTU 

NS Aerosol can/ Pressure 

sprayer/ 

RTU spray container 

//Aerosol fog or 

fumigation 

application/ Contact and/or

surface treatment/ Crack 

and crevice and/or spot 

treatment/ Crack and 

crevice treatment/ Directed

spray (b) 

N .1654 lb 1K sq.ft 

*O1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

household/domestic 

dwellings contents 

 

N 1 -- (L) 

*O1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (b) 

household/domestic 

dwellings indoor nonfood 

handling areas 

Y 

(N for 

PRL)

1 -- (L) 

*O1 

EC 

PRL 

NS Aerosol can/ Pressure 

sprayer 

//Crack and crevice and/or 

spot treatment/ Directed 

spray (a) 

N .1654 lb 1K sq.ft 

*O1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

household/domestic 

dwellings indoor premises 

 

N 1 -- (L) 

*O1 

IMPR

PRL 

RTU 

NS Aerosol can/ Impregnated 

strip/ Sprayer 

//Crack and crevice and/or 
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spot treatment/ Indoor 

general surface treatment/ 

Insecticidal strip 

treatment (b) 

Y .4015 lb 1K sq.ft 

*K1 

G NS Not on label 

//Sprinkle (a) 

Y 1.2775 lb/1 gal 

*K1 

EC NS Sprayer 

//Spray (b) 

Y 

(N for 

PRL)

1 -- (L) 

*K1 

EC 

IMPR

PRL 

RTU 

NS Aerosol can/ Impregnated 

strip/ Pressure sprayer/ 

Pump 

spray bottle/ RTU 

spray container/ Sprayer 

//Contact and/or surface 

treatment/ Crack and 

crevice and/or spot 

treatment/ Crack and 

crevice treatment/ Directed

spray/ Injection treatment/ 

Insecticidal strip 

treatment/ Outdoor general 

surface spray/ Perimeter 

treatment/ Spray (c) 

N 1 -- nest (L) 

*K1 

PRL NS Aerosol can 

//Directed spray (d) 

Y 1 part (L) 

*K1 

EC NS Pressure sprayer 

//Mound drench (e) 

N 10 sec location 

(L) 

*K1 

PRL NS Aerosol can 

//Outdoor general surface 

spray (f) 

household/domestic 

dwellings outdoor premises 

 

 

 

 

 

 

N 10 sec nest (L)

*K1 

PRL NS Aerosol can 

//Directed spray/ Outdoor 

treatment (g) 

human body/clothing while 

being worn 

N 1 -- (L) 

*O1 

IMPR NS Ankle band/ Cloth/ Wrist 

band 

//Clothing treatment/ Skin 

contact treatment (a) 

manure Y 1 -- (L) 

*C1 

RTU NS Pump spray bottle 

//Spray (a) 

Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y 1.2775 lb/1 gal 

*C1 

EC NS Sprayer 

//Spray (b) 

Y 

(N for 

PRL)

1 -- (L) 

*C1 

EC 

PRL 

RTU 

NS Aerosol can/ Pressure 

sprayer/ 

Pump spray bottle/ 

RTU spray container 

//Directed spray/ Outdoor 

general surface spray/ 

Perimeter treatment/ Spray 

(c) 

nonagricultural outdoor 

buildings/structures 

 

 

 

Y 1 part (L) 

*C1 

EC NS Pressure sprayer 

//Mound drench (d) 

Y 1.2775 lb/1 gal 

*C2 

EC NS Sprayer 

//Spray (a) 

nonagricultural rights-ofway/fencerows/hedgerows 

 Y 1 -- (L) 

*C2 

RTU NS RTU spray container 

//Spray (b) 

nonagricultural uncultivated 

areas/soils 

Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 
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Y .0894 lb/.5 gal 

*C1 

EC NS Pump spray bottle 

//Soil treatment (b) 

Y 1.2775 lb/1 gal 

*C1 

EC NS Sprayer 

//Spray (c) 

Y .3578 lb/2 gal 

*C1 

EC NS Pump spray bottle 

//Soil drench treatment (d) 

 

 

 

 

Y 1 -- (L) 

*C1 

RTU NS RTU spray container 

//Spray (e) 

nursery stock Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y 1.2775 lb/1 gal 

*C2 

EC NS Sprayer 

//Spray (b) 

Y 1 -- (L) 

*C2 

RTU NS RTU spray container 

//Spray (c) 

Y 1 part (L) 

*C2 

L NS Pump spray bottle 

//Spray (d) 

ornamental and/or shade 

trees 

 

 

 

 

Y 1 part (L) 

*C2 I1 

EC 

L 

NS Hand held sprayer/ 

Pressure 

sprayer 

//Mound drench/ Spray (e) 

Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y .4015 lb 1K sq.ft 

*C2 

G NS Not on label 

//Sprinkle (b) 

Y 1.2775 lb/1 gal 

*C2 

EC NS Sprayer 

//Spray (c) 

Y 1 -- (L) 

*C2 

RTU NS RTU spray container 

//Spray (d) 

ornamental herbaceous 

plants 

 

 

 

 

Y 1 part (L) 

*C2 M1 

L NS Pump spray bottle 

//Spray (e) 

ornamental lawns and turf Y .4015 lb 1K sq.ft 

*C2 

G NS Not on label 

//Sprinkle (a) 

Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y 1.2775 lb/1 gal 

*C2 

EC NS Sprayer 

//Spray (b) 

Y 1 -- (L) 

*C2 

RTU NS RTU spray container 

//Spray (c) 

Y 1 part (L) 

*C2 

L NS Pump spray bottle 

//Spray (d) 

ornamental non-flowering 

plants 

 

 

 

 

Y 1 part (L) 

*I1 

L NS Hand held sprayer 

//Spray (e) 

Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y 1.2775 lb/1 gal 

*C2 

EC NS Sprayer 

//Spray (b) 

Y 1 -- (L) 

*C2 

RTU NS RTU spray container 

//Spray (c) 

Y 1 part (L) 

*C2 

L NS Pump spray bottle 

//Spray (d) 

ornamental woody shrubs 

and vines 

 

 

 

 

Y 1 part (L) 

*C2 I1 

EC 

L 

NS Hand held sprayer/ 

Pressure 

sprayer 

//Mound drench/ Spray (e) 

Y 1.2775 lb/1 gal 

*K1 

EC NS Sprayer 

//Spray (a) 

paths/patios 

 

Y 1 -- (L) RTU NS Pump spray bottle/ 
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*C2 RTU spray container 

//Outdoor general surface 

spray/ Spray (b) 

Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

Y .4015 lb 1K sq.ft 

*C2 

G NS Not on label 

//Sprinkle (b) 

Y 1.2775 lb/1 gal 

*K1 

EC NS Sprayer 

//Spray (c) 

paved areas (private 

roads/sidewalks) 

 

 

 

Y 1 -- (L) 

*C2 K1 

RTU NS Pump spray bottle/ 

RTU spray container 

//Outdoor general surface 

spray/ Spray (d) 

N .1654 lb 1K sq.ft 

*O1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

pet living/sleeping quarters 

 

Y 

(N for 

PRL)

1 -- (L) 

*O1 

PRL 

RTU 

NS Aerosol can/ Pump spray 

bottle/ Sprayer 

//Animal bedding/litter 

treatment/ Crack and 

crevice and/or spot 

treatment/ Indoor general 

surface treatment (b) 

pome fruits Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

recreational areas Y 

(N for 

PRL)

1 -- (L) 

*C1 

PRL 

RTU 

NS Aerosol can/ Pump spray 

bottle 

//Injection treatment/ 

Outdoor general surface 

spray/ Perimeter treatment 

(a) 

refuse/solid waste 

containers (garbage cans) 

Y 

(N for 

PRL)

1 -- (L) 

*K1 O1 

PRL 

RTU 

NS Aerosol can/ Pump spray 

bottle/ Sprayer 

//Crack and crevice and/or 

spot treatment/ Outdoor 

general surface spray/ 

Spray (a) 

refuse/solid waste sites 

(outdoor) 

Y 1 -- (L) 

*C1 

RTU NS Pump spray bottle 

//Outdoor general surface 

spray (a) 

sewage systems N 1 -- (L) 

*F1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (a) 

ships and boats N 1 -- (L) 

*M1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (a) 

small fruits Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

stone fruits Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

tree nuts Y 34.595 lb A EC NS Hooded sprayer 

//Broadcast (a) 

wide area/general indoor 

treatment 

N 1 -- (L) 

*M1 

PRL NS Aerosol can 

//Contact and/or surface 

treatment (a) 

wide area/general outdoor 

treatment (public health 

use) 

N 1 -- (L) 

*C1 

PRL NS Aerosol can 

//Contact and/or surface 

treatment (a) 

wood protection treatment N 66.5 lb 1K sq.ft RTU NS Package applicator 
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*UG = Use group codes. 

*O1 //Wood surface treatment 

(a) 

N 1 -- (L) 

*O1 

RTU NS Injection equipment 

//Void treatment (b) 

to buildings/products indoor 

 

 

N 1 minute hole 

(L) 

*O1 

RTU NS Injection equipment 

//Injection treatment (c) 

N 66.5 lb 1K sq.ft 

*K2 

RTU NS Package applicator 

//Wood surface treatment 

(a) 

N 1 -- (L) 

*K2 

RTU NS Injection equipment 

//Void treatment (b) 

N 1 minute hole 

(L) 

*K2 

RTU NS Injection equipment 

//Injection treatment (c) 

wood protection treatment 

to buildings/products 

outdoor 

 

 

 

N 10 sec hole (L)

*K2 

PRL NS Aerosol can 

//Injection treatment (d) 

FOOD/FEED USES

N .1654 lb 1K sq.ft 

*L2 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

eating establishments 

 

N 1 -- (L) 

*L2 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (b) 

egg packing plants 

(commercial) 

Y .1538 lb 1K sq.ft 

*L1 

RTU NS Pump spray bottle 

//Crack and crevice 

treatment (a) 

N .1654 lb 1K sq.ft 

*L1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

food processing plant 

premises (nonfood contact) 

 

N 1 -- (L) 

*L1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (b) 

food 

stores/markets/supermarkets 

premises 

N 1 -- (L) 

*L1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (a) 

food/grocery/marketing/ 

storage/distribution facility 

premise 

N 1 -- (L) 

*L1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (a) 

N .1654 lb 1K sq.ft 

*L1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

household/domestic 

dwellings indoor food 

handling areas 

 Y 1 -- (L) 

*L1 

EC 

PRL 

NS Aerosol can/ Pressure 

sprayer 

//Crack and crevice and/or 

spot treatment/ Directed 

spray (b) 

N .1654 lb 1K 

sq.ft*L1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 

meat processing plant 

premises (nonfood contact) 

 

N 1 -- (L) 

*L1 

PRL NS Aerosol can 

//Crack and crevice and/or 

spot treatment (b) 

poultry processing plant 

premises (nonfood contact) 

N .1654 lb 1K sq.ft 

*L1 

PRL NS Aerosol can 

//Crack and crevice 

treatment (a) 
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(L) = The dosage information provided is from the label in terms of product (e.g., ounces, gallons, or pounds of 

product) because there was insufficient information (e.g., missing density, area, or a.i. percentages) to provide 

converted dosage information. 

FORMULATION CODES 

EC : Emulsifiable Concentrate 

G : Granular 

IMPR : Impregnated Material 

L : Liquid 

PRL : Pressurized Liquid 

RTU : Liquid Ready-to-Use 

USE GROUP CODES 

C1 : TERRESTRIAL NON-FOOD CROP 

C2 : TERRESTRIAL NON-FOOD+OUTDOOR RESIDENTIAL 

F1 : AQUATIC NON-FOOD INDUSTRIAL 

I1 : GREENHOUSE NON-FOOD CROP 

J1 : FORESTRY 

K1 : OUTDOOR RESIDENTIAL 

K2 : OUTDOOR RESIDENTIAL + INDOOR RESIDENTIAL 

L1 : INDOOR FOOD 

L2 : INDOOR FOOD+INDOOR NON-FOOD 

M1 : INDOOR NON-FOOD 

N1 : INDOOR MEDICAL 

O1 : INDOOR RESIDENTIAL
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Attachment 6: d-Limonene International Residue Limit Status 

Summary of U.S. Tolerances and International MRLs. 

U.S. Canada Mexico1 Codex

Residue Definition: 

§ 180.539 d-Limonene; tolerances for 

residues. 

(a) General. (1) The insecticide d-limonene 

may be safely used in insect-repellent 

tablecloths and in insect-repellent strips 

used in food- or feed-handling 

establishments. 

(2) To assure safe use of the insect 

repellent, its label and labeling shall 

conform to that registered by the U.S. 

Environmental Protection Agency, and it 

shall be used in accordance with such label 

and labeling. 

None - None 

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

Commodity U.S. Canada Mexico Codex 

 None - None 

 

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes. 
DRAFT d-Limonene Registration Review Human-Health Assessment Scoping Document

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Attachment 7: IDS Report 

Chemical: Limonene Human Incidents 

 

Incident 

Number 

Incident 

Date Product Name 

Registration 

Number City State 

Exposure 

Type* 

018344 001 05-Jan-07 ADAMS FLEA & 

TICK SHAMPOO 

WITH D-LIMONENE 

00475800141 LA HC Adult (18-64 year old

without gloves on 3 s

memory deficit, confu

difficulty expressing 

018666 012 25-Jun-07 ADAMS FLEA & 

TICK SHAMPOO 

WITH D-LIMONENE 

00475800141 NC HC Adult (18-64 year old

dermally 3 days ago. 

top of her foot. She w

were still there and no

ointment, and the sym

019670 002 29-Mar08 PRESCRIPTION 

TREATMENT 

BRAND PROCITRADLTM CONTACT 

00049900497 GA HC Adult (18-64 year old

her home; told her tha

The next day she star

vomiting and diarrhea

and developed vomiti

abnormal liver functi

stopped clotting, and 

gave the dog IV fluid

dog died. 

019849 002 25-Jun-08 PRESCRIPTION 

TREATMENT 

BRAND PROCITRADLTM CONTACT 

00049900497 Anaheim CA HC A 73-year-old male w

professional extermin

product. He develope

He went to his physic

symptoms got better.

021325 020 20-Sep-09 ADAMS DLIMONENE FLEA & 

TICK SHAMPOO 

00272400759 

000270 

 AZ HC Adult (18-64 years ol

forearms, and hands w

next day he develope

forearms. The dog w

* Severity Categories 

H Human 

H-A Human Fatality 

H-B Human Major 

H-C Human Moderate 

H-D Human Minor 

H-E Human Unspecified