UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D

. C

. 20460



### ME MO RAN D UM D a t e: 02-FE B- 2016 OF F I CE O F C HEMI C AL SAFE TY AND P OL LUTION PREV E NTI O N

SUBJEC T : d-Lim o n e n e. R e vi se d Human Health Risk Assessment in Support of R eg istrati on Review
. P C Codes: 07970 I , 87970 I DP B a r co d e: 0429982 Decis i o n No. : 510766 Reg i st r at io n Nos.: NA P e ti tio n No.: NA R eg ul ato r y Act io n : Regi s tration Review Ri sk Assessment R is k Assessme n t Ty p e : Single Chemical Case N o.: 3083 TX R No.: NA C A S No.: 5989-27-5 MRID No.: NA 40 CF R: § 180.539 , § 180.910 , § 180.930 

### F RO M : George F. Kramer, Ph.D. , Senior

# Chemis**~ ~** **~** - Mon iq ue M. P erron, Sc.D. , Tox icologist

## ~**~** Risk Assessment B ranch 1 (RABI) Health Effects Division (HED, 7509P) 

### T HR O UGH: C harl es W. Smith III, Branch C h ic - -- - RAB 1/HED (7509P) 

### T O : Caitlin Newcamp, Chemical Review Manager Risk Management and Implementation Branch I Pesti cide Re-Evaluation D i v ision (PRD/7508P) 

### N O TE: This document supersedes "d

- Limonene. Human Health Risk Assessment in Support of Registration Re v iew ," G. Kramer and M. Perron , D411403 , dated 04-DEC

- 2014. This assessment has been revised to add a tole rance exemption for ag r icultura l uses of d-limonene when used as an active ingredient.

PageloflOd-Limonene R egistration R eview Hum an Health Ri sk Assessment 0429982 Table of Contents 1.0 Executive Swnmary
........... ........... ........................................................... .. . .. ........................ .......... ............ 3 2.0 H E D Recommendation s ............................................................................................................................ 3 2. 1 Data Deficiencie s ............. . ....................... . ... .. ........................... .. ..................................... 3 2.2 Tolerance Considerations
................................................................................................. 3 2.3 Label Recomm endations
.................................................................................................. 4 3.0 lntroduction
.............................. .. .................................................................................................................. .4 3.1 C hemical I dentity
........................ ............ .................... ........... ................. ......................... 4 3.2 Ph ysical/Chemic al Characteristics
................................................................................... 5 3.3 Pesticid e Use Panern
........ .. .............................................................................................. 5 4.0 Hazard C har acterization and Dose-Re sponse Assessment...
................................................. .... ...... 6 4.1 Toxico l ogy Analysis
................................................. . ....... . ...... ........ .. . ......... . . . .. . .. . ........... 6 4.2 Safety Facto r for infants and Chi ldren (FQP A SF)
.......................................................... 6 4.2.1 Completeness of the Toxicolo gy Database
...................... . .. .. ....................... .. ... . ....... 7 4.2.2 Evidence ofNeurotox icity
... .. .. ......................... ....... .................... .... ..................... .... 7 4.2.3 Evidence of Sens itivi ty/ Susceptibility in the Developing or Young Animal
........... 7 4.2.4 Residual Uncertainty in the Exposure Databa se ....................................................... 7 5.0 Dietary Exposure and Risk Assessme n t ........... .. ... .. ....................... . .. ...... ........................ .. . .. . . .. . ........... 8 6.0 Re s id ent ial (No

_ n-Qccupational) Ex po sure/Risk Characterization
................................................ 8 6.1 Spray Drift. : ......... : ............................................................................................................ 8 6.2 Residential B ys tander Post-Application Inhalation Exposure
......................................... 8 7.0 Agg regate Expo sure/ Risk Characterization
........... ....................... ............ ..................... ....... ............... 8 8.0 Cum ul ative Exposure/ Risk Characterization
........ .................. ...... . .......... . .. .................. . . .. . .. . .... .......... 8 9.0 Public H ealth and Pesticide Ep id e mi ology Data
....................... .. .. .. ............................... ....... ............. 9 10.0 Occupational Expos ure/ Risk Characterization
.. ................... .. .................................... ............. ........... 9 11.0 References ............................................. . ................... ........ ............ . ............. ........ ....................... .......... ......... 9

Page 2 of JOd-Limonene Registration Re view Human H ealth Risk Assessment 0429982 1.0 Execut ive S u mmary HED has prepar ed a qualitative human-health risk assess ment to support re gistration review for the use of d-limonene [ (4R)- 1

- methyl-4-(1-meth y leth enyl)cyclohexene]. When writing this risk assessme nt , HED primarily considered the following two documents: ( i) d-L i monene. Human Health Assessment Scoping Document in Support of Registration Review (G. Kramer 

### et al., 13- AUG-20 10 ; 0 374492); and (ii) HED's Hazard and Science Policy Council ( HASPOC ) recommendations (J. Yan A l stine; 05-NOY-2013 ; TXR # 0056807). d-Limonene has a lemon-like flavor and sme ll , and occurs naturally in c itru s and certain fruits , vegetables , meats, and sp ices. 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 u sed as a solvent or fragrance. FDA considers dlimonene to be Genera ll y Recognized as Safe (GRAS) as a food additive when used as a synthetic flavoring substanc e and adjuvant (2 1 CFR § 182.60)
. d-Limonene is also registered for terrestrial food or feed crop uses as an active ingredient (herbicide), and can be used in insectrepellent tablecloths and in insect

- repellent strips used in food or feed-handling establishments. No data deficiencies we re identified for the toxicology , residue chemistry , or occupational/ residential exposure databases. No toxicologica l points of departure have been established fordlimonene
. As a result, quantitative risk assessments are not necessary to conclude with reasonable certainty that ex po s ures from the current ly registered u ses of d-limonene do not pose a significant human hea lth ri s k. 2. 0 HE D Recom me nd atio ns HE D has no objection for continued registration of the current d-limonene pesticide products. 2.1 Data De fi c i encies No data deficiencies were identified for the toxicology, residue chemistry , or occupational/ residential exposure database s. 2.2 To l era n ce Co nside rations As no toxicological points of departure have been established for d-limonene, tolerances are not required for residues in/on food/feed commodities. I n a ddition , there are curren tl y no established Codex o r Mexican maximum re sidue limits (MRLs) for d- limonene
. However , to s upport both the herbicidal and insecticidal use s of d-limonene , HED recommend s that the following modifica tion s to 40 CFR 180 Subpart C and Subpart D:

• The following tolerance exe mption be es tabli shed under 40 CFR 180 Sub part DExemption s From Tolerances: (a) An exemption from the requirement of a t o lerance i s established for residues of dlimonene , (4R)-l-me th yl -4- ( 1-methy lethe ny l )cyclohexene , in or on all food commodities when applied as an herbicide used in accordance wi th its label and labeling registered by the U.S. Environmental Protection Agency. (b) An exemption from the requirem e nt of a tolerance is established for residues of dlimonen e, (4R)-1-methyl

- 4

- ( 1-methy letheny l)cyclohexene , in or o n a ll food P

age 3of10d-L i mo n en e Regi stra tion R eview H uman H ealth Risk Assessment 0 429982 co mm od it ies w he n a p p l ied in i n sec t-repe ll ent tab l e cl ot h s and in insect re p e ll e nt stri p s u sed i n food- o r feed

- h an dl ing es t a bli s hm e nt s.
• Th e remov al of s ubp art 180. 53 9 under 40 CF R 180 Subpart C

- S p ec ifi c T o le rance s 

### 2. 3 L a bel R ec omm e nd a tion s HE D h as n o lab e l r e co mm endatio n s at thi s tim e. 3
. 0 

### Introduct io n d-L imon e ne has a le m o n - lik e fl av or and s m e ll , and occ urs naturall y in c itru s and ce rtain frui ts , vege tabl es, m e at s , a nd s pi ces . d -L imonen e i s u se d as b o th an acti ve and in e rt in gre d ie nt i n p es ticide products, and as an in gre di e nt i n fo od pro du c t s , s oap s, and p e rfum es. A s an act ive in gredi e nt , it i s u se d as an in sec tic ide , h e rb ic id e , in sec t repellent , and a nim a l (do g and cat) re p e ll e nt. A s a pe s ti c id e i ne rt in gredient, it i s u sed as a s ol vent or frag ran ce. F DA co nsiders d 1 im o ne ne to b e GRAS as a foo d a ddi ti ve w he n used as a syn thetic fl avo rin g su b s t ance and ad

j uv ant (2 1 C FR 

### § 1 82.60). The es t ab l i s hed to lerances and e xe mpt io n s, w it h the res p ecti ve CF R c it ation , an d the u s e p atte rn s as an acti ve and i ne rt in gredie nt are li s ted i n Tab le 3
. 0
.

Tab l e 3.0. E stab l is h ed T o lerance s a nd Exe m pt i on s for d- Limonene
.

To l erance PC L i s t Exempt i o n CASNo. 40 CFR § C ode U s e P attern C lass i fica t io n Ex p ressio n Act i ve In e r e di e nt Used i n in sec t
- re p e ll e nt 180.53 9 07 97 0 1 tabl e cloth s and in in s e c t
- N A d -Limon e ne 5 9 8 9

- 27

- 5 re p e llent st rip s u sed i n food- o r feed

- h an dlin g es tabli s hm e nts I nert In 2 r e di e nt 18 0.9 1 0 and 18 0.930 (fo rm e rl y 8 7970 1 ··S o l ve nt. fragra nce ·· 4B c 18 0
. I O O

l ( c ) and (e)) o.b

.. • R es idu es li ste d m 4 0 CF R § 1 80
.9 10 arc ex empt fr o m a to leran ce wh en u ;e d as m e n in g redi ents m pc s 11 c 1d c fo mrn latJ o ns applied to gro wing c r

o p s o r to raw a g ricu l tura l co mm oditie s after harve s t and th ose l is ted i n 40 CF R § 1 8 0
. 9 3 0 arc exempt fr o m a to l e ran ce whe n us ed as in e n in g r e d ients in pe s tici d e fo nnul a ti o n s app l ie d to an imal s. b In bot h s ect ion s , th e in e n in g r

e d ien t is l isted as " d

-Lim on en c (CA S R eg No . 5 989- 27-5 ).' " ' l nen in gre dients are c a t e go ri zed in to fo u r li s t s as d e scribe d i n th e 19 87 and 1 9 89 Po li cy Sta t eme n t s . L is t 4B in c n in g redie n ts are th ose i n e n s fo r wh ich E PA has s uffi c ien t in fo rma t io n to re aso nabl y co n c l ud e drn t th e curre nt use patt e rn in pe s ti c ide pro ducts wi ll n o t adverse l y aff ect publi c h ea lth o r th e en v ir o nm e nt. 

### 3. 1 C h e mic a l Id e nti ty

Tab l e 3. 1. T e st Co m po und No m encl at ure. Co mp o und C hemical Stru c ture 

# '9 '

'

CH 1 C ommon nam e d

- Lim o ne ne I U PAC name ( R ) -4-i sopro pcn y l- 1 -m c th y l cyclo h exe ne C A S name ( 4R)

- l- meth y l

- 4

- ( 1- mc th y l e th e n y l

)cyc lohexen e C A S# 5989-27-5 P age 4of10d-L im onene Registrat io n Review Hum an Hea lth Risk Assessment D4 29982 T a bl e 3. 1. Tes t C omp o und No menclat u r e. PC Codes 07970 1,87970 1 

### 3. 2 Ph ys ical/ C hemic a l C h a racteri st ic s T a b l e 3 .2. P h ys ic oc h e m ica l Pr o p e r t ie s of d

- Lim o nc n c. P aram e ter Va lu e Refe re nce M e ltin g po i nt -75 °°C Boiling point 176 °C N IOSH , 2001; WHO , Solubi li ty in w ater 13.8 mg!L at 25°C 1998 p H Not aoolicable Den sity/ Specific Gravity 0.84 .e./ mL Vapor Density Relative vapo r density= 4.7 (air= I ) Vapo r Pressur e 0.4 kP a at 14.4 °C; 2 mm Hg at 20°C Es timated Octan ol/W ate r Coe ffi c ient log Kow: 4.2 

### 3
. 3 Pe s tic i d e U se Patt e rn d-Li m onene can b e u sed as both an active and an in e rt in gre di e nt in products reg i stere d for use in residential environments. It i s reg i stered fo r u se o n many residential s ites, including p ets (as a s hampoo or d ip) , outdoor premises (spot treatme nt ), indoor treatments (crack and crevice and clean ing uses ), impreg n ate d materials (repellant clothing , brace lets , strips ) , roads and sidewalks (s po t tre atme nt) , and profe ss ional appl ication s t o wooden structures (applied as a wood inject ion)
. It is a l so reg i s te red for agric ul tural u se as an herbicide. A d d i tio n a l exposure may occ ur naturally thro ug h differen t foods , soaps, and perfumes
. T h ese use s are FDA-approved and ge nera ll y regard e d as safe. 

### 3.4 C on s id e r at ion of E nv ironmenta l Ju s ti ce Potential areas of e n vironm enta l justice concerns , to the extent po ss ibl e, w ill be considered in future human health ri sk assessments for d-limonene , in accordance with U.S
. Executive Order 1 2 898 , "Federal Actions to Address Environmenta l Ju s tice in Minority Pop u lat ions and L ow 

### J

ncome Popu l at i ons , " http: //www . arch ives .gov / federa l -register / execut ive-orders/ pdf / 12898
.pdf
. As a part of every pe s ticide ri s k assessme nt , OP P co n s iders a l arge variety of co n sumer s ub g roups according to well

- es tablished pro ce dures. In line with OPP policy , HED estimates risks to population s u bgroups from pesticide expos ures that are based o n patterns of that s ub gro up ' s food and wa te r consumption , and activities in and around the home that in volve pesticide u se in a res identi al setting. Extensive d ata on food consumption patte rn s are compil ed by the U nited States Department of Agric u lture (US DA) Na tional Health and N utrit ion Exam ination Survey , What We Eat in America (N H ANES/ WWEIA ; 2003-2008) and are used in p esti ci de risk assessments for all reg i stered food u ses of a pestic ide
. These data are analyzed and categorized by s ub g roup s based o n age , season of the year, ethnic group , and r eg io n of t h e country. Additionally, OPP is able to asse ss dietary exposure to small er, s p ec ia li zed subgroups and exposure assessments are p e rformed when conditions or circumstances warrant. Whenever a ppropriate , non-dietary ex po s ures based on home u se of pestic id e products and assoc iate d ri s k s for a dult applicators and fo r to dd l e rs , yo uth s, and a dults entering o r playing on treated areas post-application are evaluated. Further considerations are currently in development as OPP has committed re sources and expe rtis e to the deve lopment of s pecialized software and models that co n side r exposure to bystanders and farm worke rs as we ll as lifestyle and trad it ional dietary pattern s among s p e cific s u bgroups.
Page 5of 10d-Limonene Registration R ev i ew Human Health Ri sk Assessment 0 429982 4.0 Hazard C h a r ac terization and Do se -R espo nse Assessment 4.1 Toxicology A nalysis d- Limone ne ha s been eva lu ated extensive l y in a number of s hort- and lo ng-te rm tox icity assays s inc e the 1950 s 1 • Overa ll , hi gh doses of d -li monene (2: 50 0 mg/kg/ day) are n eeded to induce any form ofrelevant toxicity in laboratory anim als. Due to it s low toxicity , a r e duced set of gene ri c data requirements we re cons id e red appropriate for d-limonene as di scusse d in the 1994 Re reg i stration Elig i bil ity Document (RE D ) (EPA-738 -R- 94

- 034). In rec ent years, the 40 CFR Toxico lo gy Data Requ i rements have been revised and require pesticid es to have acute neurotoxic ity , s u bchronic neurotoxicity , and immunotoxicity studies. Th e Hazard and Sc i ence Policy Counc il (HASPOC) concl ud ed u sing a weight-of

- evidence approach that these s tudi es are not required at this tim e fo r d-limonene (J. Van A l st in e; 5-N OV- 20 1 3; TXR # 0056807). Th e refo re , th e ava il ab le toxicologica l d at ab ase i s co n s id e r e d comp l e te to s upp o rt ex i s ting regi s trations and r eg i s tration rev iew. d

- Limonene i s a skin and eye irritant, as well as a d e rmal sensitizer. It ha s been found to have low acute to xicity v ia the oral and dermal routes. ln n ume rous stud ie s, d-limone ne re s ulted in liver effects th at are cons id e red a d aptive. Male rats al so exh i bi ted kidney effects (hyaline drop l et nephropath y and renal tumors) that are in dicative of a2μ-g lobul in nephropa thy , whic h is a sex - and spec ies-dependent syndrome. T he refore , t h ese effec t s were not considered predictive of kidney toxicity in hum ans si nc e a2 μ- g l obu li n i s not syn the sized by hum ans. There is no evid e nce of d eve lopm e ntal tox ic ity w ith d- limone ne except at very hi g h do ses ( > 500 mg/kg/day) and in the pr ese nce of maternal tox ic ity. d-Li mone ne was nega tive in severa l mutagenicity and clastoge ni c ity assays. A pub li shed 9 -week imrnun otoxic ity s tud y in mice yield ed no clear evidence of immunotoxici ty from d-limonene. There is no ev id ence of neurotoxicity from ex p os ure to d- lim one ne. A lthou g h dec reased motor act ivity was observed in a 1 3

- week oral to x ic it y s tud y in mice at 10 00 mg/kg/day, the effect is attrib ut ed to ge ne ra l sys te mic toxicity from ex po s u re to s uch a high dose. Prev ious ly, e ndp o int s we r e se lected u si n g a 30- d ay oral rat toxi c it y s tud y w ith li ve r effe cts ( marginal inc reases in li ve r weights and live r e nzy me s) and a 103-wee k gavage rat toxic ity st ud y w i th no effects observed. According to current po li cies , the liver effects wou ld be consi dered adaptive and a study with no effec t s cannot be used for e ndpoint select io n . Given the low t oxi cit y throughout the database, no toxicity endpoint s were selected for d- lim o nene. Therefore, quantitat ive exposure assess ment is not nece ssary . 4.2 Safety Factor for Infant s and C hildre n (FQPA SF) The RAB 1 risk assess me nt team for d-l imon e ne determined tha t the Food Qua li ty Prote cti on Act (F QPA) SF s hould b e re duc e d to 1 X for all expos ure sce narios. There i s a comp l ete toxico logy database , no ev idence of neuroto xicity, and no evide nce of offspring suscep tibility. Ad d itional ly, s inc e no e ndpoints were se le cted for d- limonene give n its low toxicity , a quantitative exposure assessment is not necessary.

1 Sum marized in th e 1994 EPA Reregistration E li gibi l ity Decision (E PA-738-R-94-034) , 2004 E PA Tolerance Reassess ment Eligib ili ty Decision (E P A -H Q-OPP- 2004-0335-0003), published review s by the World Health Organ ization (1993 , 1 998) , and a technical report b y th e Nat io n a l To xi colo gy Pro g r am (1990). Pa ge 6of10d-Limonene Registration Review Human Health Risk Assessment 0429982 4 .2 . 1 C ompl e teness o f th e To xi col ogy Da ta base Limonene was previously classified as a lower-risk pesticide for which a reduced set of generic data requirements are appropr iate for registration. Accordingly, the toxicology database i s cons i de re d comp l ete and in cludes deve lo p menta l st u dies in the rat, mouse , and rabbit. 4.2.2 Ev idenc e of Ne urotoxici ty There is no evidence of neurotoxicity from exposure to d-limonene across the available toxicological studies. Although decreased motor activity was observed in a 13-week oral toxicity study in mice at 1000 mg/kg/ day , the effect is attributed to genera l systemic toxicity from expos u re to such a high dose
. 4.2 . 3 E videnc e o f Se ns itivity /S u s ceptibili ty in th e D ev elopin g or Y o un g A nimal There is no evidence of quant itat ive or qualitat ive susceptibility to offspring from d-limonene exposure. Deve lopmental toxicity with d-l imonene was not observed except at very high doses (> 500 mg/kg/day) and in the presence of maternal toxicity. 4 .2 .4 R es idu a l U n ce rt a in ty in t h e E xpo s ur e D ata base Given its low tox icity, no endpo i nts we re selected for d- l imonene. T herefo re, a q u an titati ve expos ure assessment is not necessary and no res idual uncertainty ex i sts in the exposure database. 4.3 E ndocrin e Di s ruptor Scree ni ng Pr og ra m As required by the Federal Insecticide , Fungicide , and Rodenticide Act (FIFRA) and the Federal Food , Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic, and chronic toxic ity, including assessments of carcinogenicity , n eurotoxicity, developmental , reproductive, and general or systemic toxicity. These studies i ncl ude e ndpoints t hat may be s u scepti b le to endocrine infl uence , includi ng effects on endoc ri ne target organ histopatho l ogy, organ weights, estr u s cyclicity, sexual maturation, ferti li ty, pregnancy rates, reproductive loss , and sex ratios in offspring. For ecological haz.ard assessments, EPA evaluates acute tests and chronic studies that assess growth , deve lopmental and reproductive effects in different taxonomic groups. As part of its reregistration decision for d-limonene , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment sce n arios from the existing haz.ard database. However, as required by FF D CA section 408(p), d-limonene i s subject to th e endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). EPA has developed the EDSP to determine whet her certain substances (including pest i ci d e active and other ingred ients) may have an effect in humans or wildlife simila r 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 r equired 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 l 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 wi ll determine wh ich , if any, of the Tier 2 tests are necessary based on the availab le data. Tier 2 Page7ofl0d-Limonene Regi s tration Review Human Health Risk Assessment 0429982 testing is de signed to identify any adverse e nd ocrine-related effects caused by the substance , and establish a d ose-response re lationsh ip between th e dose and the E , A , or T effect. U nder FFDCA sectio n 

### 408(p) , the Agency must screen all pesticide chemicals. Between October 

### 2009 and February 

### 2010, EPA issued test orders/data call-ins for th e first group of 

### 67 chemicals, which contai ns 

### 58 pesticide active ingredients and 

### 9 inert in g r e dient s. A second list of che micals identified for 

### EDSP screening was published on Jun e 

### 14 , 20 1 32 and includes some pesticides scheduled for registration review and chemicals found in water . Neit her of these lists shou ld be construed 

### as a list of known or like ly e ndocrine disruptors. For further information on the status of the 

### EDSP , the policies and procedures , the lists of chemicals, future l ists , the test guidelines and the Tier 1 screening battery , please visit our website. 3 

### 5.0 Dietary Ex po s ure a nd Risk Assessme nt Quantitative dietary exposure and risk assessments are not required for d-limonene since no toxicological points of departure have been established. ln addition , 

### FDA considers d-lirnone ne to be 

### GRAS as a food additive when used as a s ynthetic flavoring s u bstance and adjuvant 

### (21 CFR 

### § 

### 182.60). 6.0 Residential (Non-Occupational) Ex po sure/Risk Characterization Quantitative residential expos ure and risk assessments are not required for d- limonene since no toxicological point s of departure have been established. 

### 6.1 Sp ra y Drift Q uantitati ve spray drift exposure and risk assessments are not required for d-limonene since no toxicological points of departure have been establ i shed. 

### 6.2 Residential Bystander Post-Application Inhalation Exposure Quantitative residential bystander post-application exposure and risk as s essments are not required for d -lim onene since no toxicological points of departure have been estab li she d. 

### 7.0 Aggregate Exposu re/Ri sk Characterization As quantitative dietary and residential exposure assessments are not required , a quantitative aggregate assessment i s not required eithe r to co nclude w ith reasonable certainty that aggregate exposures to the currently regis te red u ses of d-limonene do not pose a s i gnificant human health ri sk
. 

### 8.0 Cumulative Expos ure/Ri s k Characterization Unlike other pesticides for which EPA has followed a cumulative risk approach based on a

2 See http: //www.epa.gov/ endocrine-disrupt ion / overview- s econd-I i st-chemicals-tier

- 1- s creen ing-under-endocrinedisruptor for the final second list of chemicals. 3 http: // www.epa . gov/e ndo/ Pa ge 8of10d- Limon ene Re gist ration Rev iew Human Health Risk Assessmen t 042998 2 co mm o n mechani sm of to x ic ity, EPA ha s not m ade a common mechani sm of toxicity finding as to d- limonene and any other substance s and d -lim o ne ne does not appear to produce a toxic metabolite produc ed by o ther su bstances . Fo r the purposes of th i s action , therefore , EPA has assumed that d-limonene doe s not ha ve a common mechanism of toxicity w i th ot h e r substances. For i nformation regarding E PA 's efforts to de t e rmin e which chemicals hav e a common mechanism of tox ic i ty and to eva lu ate the cumu l ativ e effects of suc h c he m ica ls, see the po l icy s tat e ments rel ease d by E PA 's Office of Pe sti cid e Program s concerning common mechanism determinations and procedures for cumulatin g effects from substances found to have a common mechani s m on EPA's webs it e at http: // www . epa . gov/ p es t i c id e - sc i e nce - a nd- assess ing-pe s ti c id er i sks/ cumul ative

- assessme nt-ri s k-p es tic id es . 9 .0 Public Hea lth a nd P esticide E pid e miol ogy Da ta A s ummary report l i stin g incidents for d-limonen e reported to the OPP Inc i de nt Data System ( IDS ) has been previou s ly conducted (W infi e ld , S., et al.; D374493 , 2 0

- MA Y-20 1 0). T he re p ort re pre se nts i ncidents occurring in the U.S. from 2002 to 2009
. Based on the low frequency and seve rit y of incid e nt c ases, there does not a ppear to be a concern at thi s t im e that wo uld warrant further investi gat ion. A lth o u g h the re are in ciden t s re p o rted that resulted in moderate outcomes , the sy mptoms and se ttin gs were varied and do not ind ica t e a trend or p attern that would trigger follow

- up analyse s . 10 . 0 Occup a ti o n a l E xp os ure/Ri s k C h a ract e ri za tion Quantitative occupational h and ler and post-app li cation ex posure and ri s k assessments are not re qui red for d- limo ne ne s inc e no toxicolo g ica l p o int s of departure have been es tab lished. 11.0 R e fer e nc es Memo , S. W infi e ld el al. , D 374493; 20

- MA Y- 20 I 0 Memo , J. Van A l s tine , TXR# 0056807 ; 05-NOY-2013

A ttachment: Summ ary of U.S
. Tolerances and Jnt e m ational MRL s.

cc: G. Kramer(RABI) RDI: RABI ( 11 / 5/14) G.F. Kramer:Sl078 I :PY-S:(703)305-5079:7509 P :RAB I Page 9of 10d-Limonene Registration Review Hum an H ea lth Risk Assessment 0429982 Summary of U.S. Tolerances and International MRLs. U.S. Canada Mexico• Codex Res idue Definition : § 180.539 d-Limonene; to leran ces for None 

## - None residues. (a) Genera l. ( I ) Th e in secticide d- l imonene may be safe l y u sed in in sect-repe ll ent tablecloths and in insect-repellent s trips u s ed in food
- or feed-handling establishments. (2) To assure safe use of th e in sect repellent, its label and labe lin g s hall conform to that registered by the U.S
. Environmental Protection Agency , and it s h a ll be u se d in accordance w ith s uch labe l and labe li ng. Commodity Tolerance (oom)/Maximum R es idue Limit (mg/ke) Com modity U.S. Ca n ada Mexi co C od ex Non e 

## - None

Completed by: M. Negu ss ie ; 10 / 21 / 14 l. Mexico adopts US tolerance s and/or Codex MRLs for it s export purposes.

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