### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , D.C. 20460

MEMORANDUM OFFI CE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### DATE: 20 May 20 1 5 

### SUBJECT: Furfural. Human Health Scoping Do c um e nt in Support o f Reg istration R eview. 

### PC Code: 04330 I 

### DP Barcode: 424668 

### Deci s ion No

. : 498470 

### Ref!istration Nos.: Petition No.: NA 

### Regulatory Action: Registration Rev iew 

### Case No.: Risk Assessment Type: NA 

### TXRNo.: NA 

### CAS No.: MRIDNo.: NA 

### 40 CFR: FROM: K e ll y O ' Rourke , Biol og i st/R isk

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# 1 ·**fYfl~lA...­** T hur sto n Morton , Chem is t

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TO : J ess ica Kid we ll , Tox icolog is t

### ~**l** Ri s k Assess me nt Bran ch 4 () Health Effects Di vision (7509 P) Eli ssa Reaves, Ph.D

. , Branch

# hi**ef C~**  Ri s k Assessme nt Branch 4 H ea lth Effect s Divi s ion (7509 P) Jolene Trujillo , C hemica l R eview Manager Ri s k Management and Im pleme ntation Bran c h 5 Pe s tic id e Re-Evaluation Division (7508 P ) A ttac hed i s HED ' s human health ri sk assess me nt sco ping docum e nt fo r furfural to support Reg i s tration R ev iew .Furfural Scoping Document 0424668


### Exec uti ve S u m m ary This document summarizes the review of the Health Effects Division ' s (HED's) human health assessments to support the Registration Review of furfural. To determine the scope of work necessary to support Registration Review, H E D has considered updates to agency science policy and risk assessment methodologies and to the toxicity, exposure , and usage databases. The most recent risk assessment for furfural , dated August 8, 2012, was conducted for the use on athletic fie lds and outdoor ornamentals (D389907, D395132). Furfural (2-furancarboxaldehyde), a heterocyclic aromatic aldehyde, is a non-systemic nematicide and fungicide. It is currently registered for use to control root infesting plant parasitic nematodes and s uppress fungal plant diseases on turf and ornamentals. Furfural has a vapor pressure of 2.6 mm Hg and is considered volatile relative to typical insecticides / fungicides. Therefore , the inhalation route is expected to be a significant component of overall exposure. For the general public , inhalation exposure is expected to be the major route of exposure . Occupational workers have potential for both inhalation and dermal exposure. The currently registered use patterns (golf courses , sod farms , athletic fields, and ornamentals) are considered non-food uses. However, because of the high application rate of furfural, and the large amounts of water used during and after application, furfural may inadvertently be transported into drinking water sources. Th e refore, to be health protective, the H ED evaluated the potential dietary exposure associated with drinking water. The hazard database for furfural is complete. Severa l inhalation studies are available and include a special acute portal-of-entry study as well as repeat dosing inhalation studies. Re s piratory effects, both at the portal of entry (the nose) and in the deep lung (pulmonary effects) were observed across the inhalation studies. The portal-of-entry effects (e.g. nasal inflammation as indicated by infiltration of inflammatory cells , hyperplasia , and degeneration) occur at lower concentrations than the pulmonary effects (breathing abnormalities that can progress to mortality at high doses) , and so protecting for portal-ofentry effects protects for pulmonary effects. Importantly , portal- of-entry effects of low severity (e.g., slight nasal inflammation) that occur after a single exposure are completely reversible within two weeks. Acute or repeated ora l exposures of rats to concentrations of furfural higher than those that cause portal-of-entry effects results in pulmonary effects (e .g. , breathing abnormalities) and mortality that likely resulted from respiratory distress. For the oral route only , liver toxicity is also observed, but at lower doses than those that cause pu lmonary toxicity; therefore , protecting for liver effects also protects for pulmonary effects and mortality. Clinical signs of toxicity that could be neurotoxic and/or agonal are also observed at concentrations /dose levels of furfural that cause pulmonary toxicity and mortality by the oral and dermal routes
. There was no evidence of qualitative or quantitative susceptibility seen in the deve lopmental rat and rabbit studies or in the 2- generation reproduction study in rats. In 2013, the Cancer Assessment Review Committee (CARC) re-classified furfural and furfuryl alcohol (soil degradate of furfural) each as
" Likely to Be Carcinogenic to Humans ". The CARC recommended the low dose extrapolation method (Q 1*) for quantification of human cancer risk. Page 2 of20

### Furfural Scoping Documen t 0 424668
Acute and chronic dietary risk assessments for water only were prev iously conducted for furfural u sed on non-food s ites (i.e. , turf and ornamentals). No dietary risks of concern were id e ntified. The cancer dietary risk was not evaluated , because furfural and furfuryl alcohol had not been classified at the time of the 2012 ri sk assessment. Updated dietary exposure and risk assessments will be necessary to reflect changes to the acute dietary endpoint and point of departure (POD) as well as th e cancer re-classification. The residentia l and occupational exposure databases for furfura l are adequate for Re g istration Review. A ltho ug h no res ident ia l ris ks of concern were ide ntified in previous risk assessments, u pdated r es i de nt ia l bystander risk est im ates resulti ng from off

- site transp ort (i.e., vo l atilizati on) associated with occ up at io n a l app li cati ons are like l y to be necessa ry g i ve n t he cance r r e - cl ass ificatio n . Althoug h n o occupatio na l ri sks of concern were iden tified in p r ev ious ri s k assessments , updated occupational ex p osure and risk assessme n ts are li ke l y to be necessary give n th e cancer re- cl ass i ficat io n , and any changes to PODs and un ce rt ai nty factors. 

### Use Pro file Furfu ra l is cu rrently registered fo r u se on golf courses (i.e., tees a nd greens, a nd as a spot treatment on fairways and roughs ), athletic field s and so d farms at application rates ranging from 47.7 lb ai/ A to 69.5 lb ai/A , up to 6 times per season, at 14- to 28-day intervals. Application equipment/methods for these existing u ses include groundboom sprayer, chemigation , mechan ically

- pressurized handgun , manuall y -pressurized handwand and backpack s praye r. It is also registered fo r ornamenta ls; post-plant application rates range from 19.5 lb a i / A to 47.7 lb ai/A, up to 8 times pe r crop , at 14

- to 28-day i nterval s , by chemigation o nl y (drip tubes/ tap es)

. D re nch appl ication rates range from 0.174 lb ai/ 100 ga l to 0.339 lb ai / l 00 gal, at 7- to 28-day intervals. T here is a proposed new u se th at is c urre nt ly un de rgo in g eva l uatio n for reg i stratio n . 

### Ha z ard ld entificationffox ico logy T h e haza rd database for furfura l is comp lete. The tox ic ity database cons ists of s i ngle- and repeated-dose ani m al toxicity stud ies from the open li terature that use vario u s species and various rou tes of exposure as we ll as several studies conducted according to agency guidel i nes (See Attachment 2). The previously required studies , whjc h included acute neuroto x icity (M RID 48998502), 2-generation re productio n toxicity (MRID 49139201 ), and immunotoxicity (M RID 48999301) stud ies , have been s ubmitted , re v iewed , and found to be acceptable. The requirement of a subchroruc neurotoxicit y s tud y has been waived by the HASPOC (TX R No. 0056939). This approach considere d all of the available hazard and exposure information for furfural i ncluding: 1) Th e ora l acu t e neurotoxicity (ACN) resulted in systemic effec t s at high doses (200 m g/kg); 2) the inhalation studies suggest portal-of

- entry effects are more sensitive than systemic effects; 3) the PO D s for risk assessment are protective of neurotox ic i ty w h e n considerin g t he s ho rt er du ratio n of exposure assoc iate d with relative ly rapid dissipatio n due to vo latil ization and degradati on Page 3 of 20

### Furfural Scoping Document D424668
and 4) a subchronic neurotoxicity study , either oral or inhalation, will not li kely provide a lower POD or a more sensitive endpoint for the risk assessment. Inhalation exposure to fu r fural vapor in rats results in respiratory effects, both at the portal of entry (the nose) and in the deep lung (pulmonary effects) following both acute and repeated exposures. The portal-of-entry effects (e.g

. nasal inflammation as ind icated by infiltration of inflammatory cells , hyperp l asia, and degeneration) occur at lower concentrations than the pulmonary effects (breathing abnormal iti es that can progress to morta li ty at high doses) , and so protecting for portal-of-entry effects protects for pulmonary effects. Importantly, portal-of-entry effects of low severity (e.g

. s li ght nasal inflammation) that occur after a single exposure are completely reversible within 2 weeks

. Exposure to furfural via the oral and dermal routes also results in pulmonary toxicity indicative of respiratory distress , which likely mediates the mortality observed at high dos e levels of fu rfu ral. For the oral route only , liver tox i city is also observed , but at lower doses than those that cause pulmonary toxicity , and so protecting for li ver effects protects for pulmonary effects and mortality. Liver effects were observed in both rats and mice and increased in severity with dose , ranging from increased liver weights and inflammation at lower doses to necrosis at higher doses. C li nical signs of toxicity that could be neurotoxic and/or agonal are also observed at concentrati ons /dose levels of furfural that cause pulmonary toxicity and mortality by the oral and dermal routes. There was no evidence of quali tative or quantitative susceptibility seen in the gavage developmental rat and rabbit studies or 

### in the gavage two

- generati on reproduction study in rats
. Since the t ime of the 2012 risk assessment , the Cancer Assessment Review Committee (CARC) determined furfural and furfuryl alcohol (soi l degradate of furfural) both to be individually classified as "Likely to Be Carcinogenic to Humans " (TXR No. 0056891)

. Furfural was given this classification based on cholangiocarcinoma 1 

### of the liver , a rare tumor type , observed in male rats, li ver tumors in male and female mice, and hepatocellu lar neoplasms in each sex of mice with compounds structurally very similar to furfural. Furfuryl alcohol ' s classification was based on nasal tumors in male rats and kidney tumors in male mice. The CARC recommended the low dose extrapolation method 

### (Q1*) for quantification of human cancer risk

### 2

. The most potent oral slope factor 

### [Qi* (m g/ k g/dayY 1] , 

### of furfuryl alcohol, based upon male rat nasal combined tumor rates, is 1.31x10- 

### 1 in human equivalents (TXR No. 0056959). The most potent unit risk , 

### Q1* (mg/kg/day)-1 of furfural based on male mouse liver combined tumor rates is 3.49x 10- 2 

### in human equivalents (TXR No. 0056864).

1 Note: The registrant submitted a Patholog y Working Group (PWG) re-read of the cholangiocarcinomas in male rats g iven furfural and identified them as non-neoplastic). Since mode of action (MOA) studies for the furfuryl alcohol tumors are currently on-going , a CARC meeting will be held when all the data are reviewed. 2 Mode of action s tudie s are currently being developed by the registrant for th e tumor types seen in animal s treated with furfural or furfuryl alcohol. 

### Page 4 of 20

### Furfural Scoping Document D424668


### Dose Response /

Endpoint Selection Points of departure (PODs) were selected for both ac u te and chronic dietary (drinkin g water only) and occupational/residential exposure scenarios. Previously , an acute reference dose (RID) for all populations of 0.01 mg/kg/day was selected from a developmental toxicity study in rats based on clinical signs of tox ici ty (bilateral exopthalmia, tremors , head held low) seen at 50 mg/kg/day (POD = l 0 mg/kg/day) with a total uncertainty factor of 1OOOx (I OX intraspecies variation , 1 OX interspecies extrapolation, and I OX database uncertainty factor for missing studies). However, since the 2012 risk assessment, the ACN study was submitted (MRID 48998502) and the registrant submitted a request to reevaluate the acute dietary endpoint and to use the ACN study for the acute dietary endpoint. Part of their rational e was that the previously selected endpoint using the developmental toxicity study in the rat was not the result of a single exposure. The agency considered this information and based on current updated policies , determined that the previous endpoint was not the result of a s in g le exposure and that acute neurotoxicity study is the more appropriate study to be used for the acute dietary endpoint (0419653 , 9/ 23 / 2014) for registration review. The no observed adverse effect leve l (NOAEL) is 80 mg/kg/day and the lowest observed adverse effect level (LOAEL) is 200 mg/kg/day based on mortality and effects on Functional Observational Battery (FOB) parameters and motor activity in both males and females. This study is appropriate for the acute dietary endpoint for the general population since the effects occurred following a single oral dose

. Based on the submission of an acceptab le / guide li ne ACN study , there is no lon ger a data gap, and the 1 OX database uncertainty factor may be removed fo r registration review. The updated aRfD will be 0.8 mg/kg/day with a total uncertainty factor of 100 (lOX intraspecies variation , I OX interspecies). The remaining endpoints have not changed s ince the 2012 risk assessment (See Attachment 3). For registration review, a residential level of concern MOE of 100 , rather than I 000, should be used for the inc id enta l oral endpoint because all data gaps have now been satisfied and the 1 OX database uncertainty factor has been removed. The current uses fo r furfural are non-food (i

. e. , turf and ornamentals); therefore , an FQPA assessment of this chemi cal has not been conducted. 

### Conclusions: T here are no outstanding toxicology data requirements. The Agency does not antic ipate the need to update any endpoints , PODs, or uncertainty factors during Registration Review, wi th the possible exception of the cancer slope factor 

### (Q1 *).

Page 5 of20Furfural Scoping Document D424668


### Res i due C h em istry The currently registered uses (golf courses , sod farms , ath let ic fields , and ornamentals) are considered non-food ; therefore , the need for residue chemistry data had previously not been applicab l e . However, s ince the 2012 risk assessment , the registrant submitted a request to classify uses on a ll food/feed crops as non - food , and provided data in association with the proposed use that is current ly under evaluation

. HED ' s ChemSAC discussed thi s request and concluded that add it ional metabolism data on a root crop (and potentially on o i lseed) will be needed in order for the Agency to make a determination on whether or not uses of furfural on food/feed crops should be considered non-food uses . 

### Conclusions: Additi ona l metabo li sm data are recommended to be required in order for use on all food/feed crops to be considered non- food. 

### Die t ary E x pos ur e I nclu di n g D r inkin g Wate r Previously , acute and chronic dietary exposure analyses (dri nking water only) were performed in order to support a Section 3 request for the use of furfural on turf and ornamenta ls 

### (T. Morton , D372769 , 1/27/10). The dietary exposure analyses were based on residues in drinking water on ly. The maximum acute dietary exposure (water onl y) was estimated to be 0.059 mg/kg/day. This is approximate ly 7.4% of the updated aRfD discussed previously , which is below HED ' s LOC ( < 100% of the aRfD). The chronic dietary exposure analysis (water only) indicated that the most high ly exposed population subgroup is All Infants ( < l year old) , which utilized < l % of the cRID

. The risk estimate s for the general U.S

. population and all other regulated population subgroups are below HED ' s l eve l of concern ( < 100% of the cRfD)

. As d i scussed previously , at the time of the 2012 risk assessment, the agency had not classified the human carcinogenic potential of furfural ; subsequently, furfural and furfuryl alcohol (soi l degradate of furfural) were both individually classified as " Like l y to Be Carc i nogenic to Humans". 

### Conclusions: Updated d ietary exposure and risk assessments will be necessary to r e flect changes to the acute dietary endpoint and po int of departure (POD) , the cancer re-classification, and possible revisions of the esti m ated drinking water concentrations (EDWCs)

. The assessments will use the newest version of DEEM and reflect updated consumption information. 

### Res id e nti a l Ex p os ur e Residential handler exposure is not expected for the registered uses on turf and ornamentals. However, bystander inhalation exposure via volatilization is possible for individuals living/working nearby th e application sites

. Adequate field volatility data are available to estimate flux values ; these we re entered into the Probabilistic Exposure and Risk model for Fumigants (PERFUM) for use in estimating air concentrations and buffer Page 6 of2 0

### Furfural Scoping Document D424668

zones for bystander inhalation exposure. The term " buffer zone " equates to the distance downwind at which a specific concentration of concern (i.e. , COC 

## = HEC / UF) is met , based on the desired stat i stical paramete rs. The bystander inhalation assessment indicated that when a I -acre field has been treated , whole field buffer zones were estimated to range from 0 to 140 meters for th e 75th through 95•h percentiles , respectively , depending on the flux data set used. For a 40-acre field, they range from 140 to 1 230 meters for the 75th through 95th percentiles, respec ti vely. It 

### should be noted that the use of the term "buffer zo ne " does not imply any regulatory decision. In the context of ri sk assessme nt , it is only considered as the predicted distance for a specific COC. T he current l abel lists buffer zones for a I- acre field to be 1 5 feet (approximately 5 meters) fo r irrigation via in

- ground pop-up sprinkler systems and 75 feet (approx imatel y 25 meters) for all other types of sprinkler syste m s. For a 40-acre field, the label indicates a buffer zone of 725 feet (approximately 220 meters). These labe l -required buffer zones are within the ranges calcu lated based on the COC. Buffer zones are a lso required for other non-greenhouse uses of furfural, and there also are restrictions regarding how close furfura l can be used near facilities such as hospital s and schools. The requirement for a chemical- specific turf transferrable residue (TTR) study was waived becau s e a dislodgeab le foliar residue (OFR) study (MRlO # : 47146202) was provided to s upport use in greenhouses. These DFR data were used to estimate turf transferable residues , and are considered protective because the results of the DFR study indicate that residues decline to neglig i ble levels within 4 hours of app li cation. Therefore, post application exposure to furfural residues on treated athletic fields / go l f courses is expected to be neg l igible for recreational athletes/golfers , and a quantitative assessment was not conducted. Whi le spray drift may occur as a result of applications of furfural , exposure to furfural residues is expected to be neg li g ible based on the prev io u s discussion (i.e., expos ure from direct co ntact with treated areas is expecte d to be neglig i b le). Therefore, potential for exposu re assoc iated wi th spray drift w ill n ot be quantit a tiv e ly eva lu ated during the Reg i strat ion Review. 

### Co nclu s ion s: The residential exposure database i s adequate to support the Registration Review process for furfural. Although no residential risks of concern were identified in previous risk assessments , updated residential bystander risk estimates resulting from off-site transport (i.e. , volati li zation) assoc iated with occupational applications are likely to be necessary given the cancer re-classification and any changes to uncertainty factors.

Page 7 of 20Fu rfural Scoping Document 0424668 

### Agg re g ate Ri s k Ass ess ment In accordance with the Food Quality Protection Act (FQPA), HED must consider and aggregate pesticide exposures and risks from three major sources: food , drinking water, and residential exposures. T he aggregate risk assessment evaluates the combined risk from dietary exposure (food and water) and any non-occupational (residential) uses. While there is a common effect identified in the toxic i ty stud ies selected to assess oral and dermal exposure (neurotoxicity), postapplication exposure to furfura l residues is expected to be neglig i ble based on the results of the DFR study. The inhalation e ndpo int i s based on a portal of en try effects w hi c h are not appropriate to aggregate with the oral exposure. Thus , an aggregate risk assessment from exposure to fu r fu ral i s not ex p ecte d under Reg istrat ion Review. 

### Occupational E xpo s ure Occupationa l han dler and post-app li cat ion exposures are expected based on the reg istered uses of furfural. The most recent occupati ona l a nd residential exposure (ORE) risk assessment was conducted in 2012 to evaluate use on athlet ic fields and ornamentals. The LOC is for dermal and inhalation MOEs less than I 00. Handler The results of the handler occupational exposure and risk assessment indicate that dermal risks are not of concern when g loves are worn , as well as coveralls for hand

- held spraying ac t ivities (which are required on the label) ; dermal MOEs range from 190 to 1,400. Inhalation risks are not of concern when a respirator is worn for mixing/loading and applying as a drench to ornamentals (not currently specified on the label); inha lation MOEs range from 130 to 2,200. Postapp l ication The occ upational postapp l ication inha l atio n assess m e n t in dicates th at w he n a 1

- acre field has been treated, w ho l e fie ld bu ffer zones were es ti mated to range from 0 to 140 m eters for the 75Lh through 95L1 1 per centiles, respectively, depending on the fl u x data set used. For a 40-acre field , they range from 140 to 1230 mete rs for the 75Lh throug h 95th percenti les, respectively. The current label li sts buffer zones for a I -acre fie ld to be 15 feet (approximately 5 meters) for irrigation via in-ground pop-up sprinkler systems and 75 feet (approximately 25 me t ers) fo r all other types of sprinkler systems. For a 40-ac re field, the label indicates a b uffer zone of 725 feet (approximately 220 meters). These label

- required buffer zones are within the ranges calculated based on the COC. As d iscussed previously, the results of the DFR study indicate that furfural residues decline to negligible levels within 4 hours of application. Therefore , occupational postapplication exposure to furfura l residues on treated turf is expected to be neglig i ble , and a quantitative assessment was not conducted. The furfural technical material has been classified in Toxicity Category III for acute dermal toxicity , Category IV for acute dermal irritation , and Category II for primary eye irritation. Per the Worker Protection Standard (WPS) , a 24-hr restri cted entry interval (REI) is requ ired for chemicals classified under Toxicity Category II and a 12-hr RE I is req ui red fo r chemica ls c lassified under Toxicity Category Page 8 of 20

### Furfural Scoping Docum en t D424 668
III and IV . T he propo se d furfural labe l indic ates a n RE I of 12 hours, which i s adequate g i ven the res ult s o f the DFR stud y . This product is intended fo r use on outdoo r orname nt a l s, sod and seed farms , whic h are within the sco pe of th e WPS , therefore, the RE l on th e labe l is appropriate. Furfural i s a l so inte nd ed for a thl etic fi e ld s and go l f cou rses, to whic h the WPS does not apply ; the labe l co rrec tl y con ta in s langua ge cautioning unprotected pe rsons to keep out of treated areas un ti l sprays ha ve dried. The REI for most greenhouse post-application activities is 12 hours; th e REI fo r c uttin g flowers is 9 da ys. Co nclu s i o n s: Th e occ upational ex posure database is ad e quate to s upport the Reg is tration Rev i ew pro cess for furfural. A l though no occupational risks of concern were id e nt ified in pre v iou s ri s k assessments, updated occupational exposure and ris k assessme nt s are li ke ly to be necessa ry g ive n the cancer re - classification. Publi c He alth a nd Pes ti c id e E p i d e mi o lo gy D a t a Both the O PP Inc ident Data System ( ID S) and the Ce nt e rs fo r Disease Co ntrol and Prevention/Nat io na l In stitute for Occupational Safety and H ea lth (CDC/N IOSH ) Sentinel Event Notificat io n Sys te m for Occupationa l R isk

- Pes ti cides (SENSO R ) databa ses were cons ult ed for pesticide incid e nt data on the act i ve i ngredient fur fural (D4 263 6 2)

. Furfural is not included in the Agricultural H ealth Study (AHS). The purpose of the datab ase search was to identify potential patt erns in the frequency and severity of the health effects attri but ed to furfural exposure. 

### Conclusion: The Age nc y has re v ie wed the ava il ab l e incident data and co nclud es t hat there does not appear to be a co ncern that wou ld warrant furt he r in ves ti gatio n , since there we re no in c id e nt s in vo lv ing furfural r eported to e ithe r ID S o r SENSO R-P esti c id es. The Agency w i ll co nt i nu e to monitor th e i nc ident information and i f a concern is triggered, additional anal ysis will b e included i n the ri sk a ssess me n t. To l eranc e Assess m e nt and Inte rn ational H a rm o niz ati o n No tolerances are es tabli s hed for re s idue s of furf u ral , and a re not neede d for the currently regist e red u ses of furfural. E n v iro nm e nt a l Ju s ti ce Potential areas of env iro nm e ntal ju stice concerns , to the ex te nt possible , were considered in this human health ri sk assessmen t , in accordance w ith U.S. Exec ut i ve O rd er 12898 , "Federal Ac t ions to Address Environment a l Ju stice in M in ority Populations and Lowl ncome Populations ," (http: //epa.gov/complia nce/ ej /resources/ policy/ exec orde r 12898.pdD

. As a part o f every pe s t ic id e risk assess ment , OPP considers a large var i e ty of consumer su b grou p s according to well-established proce dures

. In lin e wi th OPP policy , H ED es timates ri sks to population s ub gro up s from pes ticid e exposures that are ba sed on patterns of that s ubgroup's food and wate r co n s umpti o n , and activities i n and around the hom e that invo lve pesticide use in a Pag e 9 o f 20

### Furfural Scoping Document 

### 0424668
residential setting. Extensive data on food consumption patterns are compiled by the United States Department of Agriculture ' s (USDA ' s) National Health and Nutrition Examination Survey (NHANES) , What We Eat in America (NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group . Additionally , OPP is able to assess dietary exposure to small er , special ized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate , non-dietary exposures based on home use of pesticide products and associated risks for adult applicators and for children, youths, and adults entering or playing on treated areas following application are evaluated. Further considerations are currently in development as OPP has comm itted resources and experti se to the development of spec ialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups. 

### C u mu l a ti ve Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity , EPA has not made a common mechanism of toxicity finding as to furfural and any other substances and furfural does not appear to produce a toxic metabolite produced by other substances. For information regarding EPA ' s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals , see the policy statements re l eased by EPA ' s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http: //www.epa.gov/ pesticides/ cumulati v e /

. H um an 

### Stu d ies Past furfural 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. These data, which include studies from the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1 ) ; the Agricultural Handler Exposure Task Force (AHETF) database; the Agricu ltural Re-entry Task Force (ARTF) database; and other registrant-submitted exposure monitoring studies , are subject to ethics review pursuant to 40 CFR 26 , have received that review , and are compliant with applicable ethics requirements

. For certain studies that review may have included review by the Human Studies Review Board. Descriptions of data sources as well as guidance on their use can be found at http: //www.epa.gov/ pesticides /science/handler-exposure-data

. html and http ://www.epa.gov/ pesticides/ science/post-app-exposure

-data

. html.



### Data Deficienci es and Risk Assessment Updates for Registration R evi ew

• Residue Chemistry: The ChemSAC concluded that an exaggerated-rate nature of the residue study in a root crop are recommended to be required , in which both the tuber and leaves would need to be analyzed

. If th is study shows a similar metabolic profile to the Page 10 of2 0

### Furfural Scop ing D ocume n t D 424668
studies previously submitted, then all uses on food/feed could be considered non - food. If it does not , then an additional nature of the residue study in an oilseed would be required. • Toxicology: 

### T here are no outstand ing toxico logy data requirements. The Agency does not anticipate the need to update any endpoints , PODs , o r uncertainty factors during Registration Review with the possible except ion of the cancer s lope factor 

### (Q1 *). • Dietary: 

### Updated dietary exposure and risk assessments will be necessary to reflect changes to the acute dietary endpoint and point of departure (POD) as well as the cancer re-class i ficatio n . The assessment will use the newest version of DEEM and reflect updated co n sumption information. • ORE: 

### Updated occupational/res id e nt ial exposu re a nd r isk assessments w ill li kely need to be conducted to reflect an y s i g ni fican t c hanges to u nce r ta inty fac tors and the cancer reclass i fica ti on.

P age 11 of 20Fu r fura l Scop in g Document D424668


### Reference s
Tabl e I. Memoranda Relevant to Registration Review. Auth or B arcodefIXR Date Title No. Brunsman , TX R No. 12 119 / 2013 Furfural Quantitative Ri s k Assessmen t B ased on L. 0056864 f144/N R ats and B6 C3 FI Mouse Gavage Studies
Bru nsman , T XR No. 6/26/2 014 REV I SED Fur f ura l Alcoho l Q uan titati ve Ri s k L. 0056959 Assess m e nt Based o n F344/N Rat and B6C3FI Mou se I nha lati o n Studies Kidwe ll , J

. 041965 3 9/2/20 1 4 Furfural: Re -eva lu ation of the Ac ute Dietary Endpoint Leshin , J

. D418688 / 6/10/2014 Furfural: S ummary of Hazard and Sc i ence Policy TXR Co uncil (HAS POC) M eeting of April 10, 2014: No.0056939 Recommendations on the R equ irement for a Subchronic Neuro toxic i ty Study Morton. T D372769 1 / 27 /2010 Furfural: Acu te and Chro ni c Dietary (D rinkin g Water Only) Exposure Analysis for the Section 3 R

egis trati on Ac ti on.
Morton , T D405498 11 / 8 / 2012 Furfural. Non-Food Use Determination

O ' R ou rk e , K. 0 3 8990 7; 8 / 8

/2 012 Furf ur al: Hum an- H ea lth Ri s k Assess m e nt for Use e t a l. 0 395 132 o n Athleti c Fi e ld s and O utd oo r O rn ame ntal s; R

evi se d Assessmen t fo r Go l f Cou rse Tu rf and Sod Farm s R eco r e , S 0426362 3 / 25 / 2015 Furfural: Ti e r I Review of Hum an Incident s
Rowland , J T XRNo. 2/6/2014 Furfural a nd Furfu ry l Alcohol: R eport of the 0056891 Cancer Assessme nt R eview Committee



### Attac hm ents Attachmen t 1. Chemical Id entity of F urfural Attac hm ent 2. Toxicity Profile Tables Attac hment 3. Furfural Endpoints and Do ses for Ri sk Assess ment

Page 12 of 20

### Furfural Scop i ng Docu ment

Attachment l

Co mm o n nam e : IU PA C name: CAS nam e : CAS# : Furf u

ra l Tec h nical 2- Furaldeh yde or furfural 2-Fu rancarboxa l de h yde
98-0 1 -0 I 

### H C H -C H

Molecular Weight: Boiling point : Density: W

ater so lubility ( 20°C) : 

## \ II \\ C-C CH 

## II \ I 0 0 FUR FL

96. 1 g/ m

ol 161.7 ° C

Solvent so lubili ty ( m g/Lat 2 0°C): I

. I 6g/mL at 20 ° C 7.8 1 g/ 100 mL alco ho l ( infinit e) e th er ( infinit e)

Vapor pressure: Di ssoc iation constant (pKa) : Octano l / watcr partition coefficient Lo g( K ow): UVNisib le absorpti on : mi sc ibl e in oc tan o l. ace to ne. xy lene

. ethyl acetate. meth y lene ch l oride and m

e th ano l 2.6 mm I lg (a t 20 °C) Docs n ot demon s trat e a di ssoc iation con s tant betwe e n pKa2 and pKalO. 0.35 at 20 ° c 1459 1 .3 cm 2 /mole (p l I 7) 15324.2 cm 2 /m

o lc (p H 1 .94 ) 14 584.8 cm 2 /mole (p ll 10

. 12)



### P age 13 

### o f20 

### 0 424668Furfural Scopi ng D o cume nt 

### D4 24668
Attac hm e nt 2
Ta bl e Al. Ac ut e Toxicity Pro fil e - Furfu ra l Gui d e line No. St u dy T y p e MRID (s) Re s ul ts Toxicity Categ o r y 870.1100 Ac ut e o ra l in rats 46 01100 9 LDso => I 02 mg/kg II ( Ran a, 2002) 870.1200 Acute dermal in rats 46406102 LD so > 2,000 mg/k g 111 * ( Moore

. 2004) 870.1300 Acute inhalation in rats. 46106302 L Cso = 0.54-1.63 111 (Me rke l, 2003) m g/L 870.2400 Acute eye irritation in rabbits. 4601 101 2 Severe. Irr itant. II (Joseph. 2003) 870.2500 Acute dermal irritation in 46011013 Slight. I rritant. IV rabbits. (Joseph , 2003) 870.2600 Ski n se ns it ization in Guinea 460 11 0 1 4 Non se ns iti zer. Neg. pigs. (Josep h , 2003) 

### * There ha ve been several Acute Dermal L Dso s tudie s subm itted in support of furfural: Joseph , S. A. (2003). Acute Dermal Toxic i ty S tu dy of Fu rfural in R ats. Jai Research Foundation, Department of Toxicology , Valvada , Valsad , G ujr at, India

. Study No. 3950 dated 5-23-03. MRlD 460 1101 0

- Toxicity Categor y I Mukherje e, A. (2003) Acute Dermal Toxicity S tud y of Mu lti guardTM P rotec t in Rats. Jai R esearch Foundation , Dept. of Toxicology , Valvada

- 396108, Di st. Valsad , Gujarat, I ndia. JRF Study No. 4228. Study Completion Date : 12 May 2003. MRlD 46028102. Unpublished

- T oxicity Catego r y I Moo re , G. (2004) Acute D erma l Toxicity Study in Rat s. Laboratory S tud y No.: 15621. Unpub li s hed study prepared by Produ ct Safety Laboratorie s. Sep t e mbe r 27, 2004. MRID 46406102

- To xic ity Catego r y Ill M

oo re, G. (2004) Acute Dermal Toxicity Study in R ats

- D efined LO SO. Laboratory Stu dy No.: 15 139

. U

npubli s hed stud y prepared by Product Safety Laboratories. September 27, 2004. MRJD 46406 103

- Toxicity Category Ill Moore, G. (2004) Acute Dermal Toxicity Study in Rat s - Defined LD50. Laboratory Study No.: 16080. Unpub li s hed s tudy prepared by Prod uct Safety Laboratories. Nove mb er 18 , 2004. MRID 46424 1 0 I

- T ox icit y Ca t ego r y Ill



### Page 14 of 20Furfural Scop in g D oc um ent D424668

Tab le A3

. Subcbron ic, C h ro ni c a n d Oth e r Tox i city P r o fil e fo r F urfu ra l Gu ide li ne No./ MR ID No. (year) / Res u lts

Stu d y Type C l assificat io n /Dose s Non-guideline 4856370 I (20 11 ) LOA EL = Not observed Acceptabl e/No n -g ui de lin e NOA EL= 40 mg/ m 3 Acute inhalation 0, 10, 20, 40 mg/m 3 for 6 with complete hours. Satellite g r oup with 14 recovery day recovery period 870.3100 4601 IOl5 (1990) NTP 1990 Study (pu bli catio n )

. 90-Day oral toxicity Acceptable/ No n -g u ide li ne System ic To x icity NOAEL 

### =45 mg/k g/day rats 0 , 11 , 22, 45, 90 , 180 Systemic Tox icity LOAEL 

### = 90 mg/k g/ da y based on mg/ kg/ day liver pathology

- cytop lasmic vacuolization of (gavage in corn o il ) hepatocytes. Limited p a r a m eters meas ur ed. 870.3100 46011015 (1990) NTP 1990 Study ( pu b li catio n ). 90-Day oral toxicity Acceptable/ Non-g ui deline Systemic Toxicity NOAE L < 75 mg/kg/ day mic e. 0 , 75 , 150 ,3 00 , 600 , 1200 Systemic Toxicity LOAEL < = 75 mg/k g/day based on mg/kg/day relative liver weights. (gavage in corn oil) L imi ted paramete r s measu r e d

. 870.3100 4601 1015 (2001) WHO (p u b li s h ed r ev iew art icle) , Food Additive 90-Day oral toxicity Summary/No n -g ui de lin e Series 46 (200 I) rats. (WHO p ub l is h ed review System ic Tox ic ity NOAEL 

### = 60 m g/kg/day a r t icle) Systemic Toxicity LOAEL 

### = 90 mg/ kg/d a y based on 0 , 30, 60, 90, 180 m g/ kg/day liver effects

. (microencapsulated and mixed into feed) 870.3200 46465501 (2004) Sys temic Tox ic ity NOAEL => I00 m g/kg/day (H OT). 28-Day dermal Unacceptab le / G uid e li ne System ic Toxicity LOAEL > I00 mg/k g/day

. to xic ity in rats. 0 , 25, 50 and I 00 mg/kg Transient effects included drowsiness , d ys pnea, clonic convulsion, hyperactivity , tremor, vocalization, genera li zed effects from exposure to furfural No dem1al irritation noted. 870.3200 4691720 I and 46917202 (2006) System ic Tox ici ty NOAEL 

### =250 mg/kg/day Acceptable/ G ui de l i ne 28-Day dermal 0 , I00 , 250, 500, or I000 Systemic Tox ic ity LOAEL 

### = 500 m g/ k g/day based on toxicity in rats. mg/kg bw/day , 6 hours/day for adverse clinica l s igns ( m a les), an increase in motor 5 days/ week activity (males) and increa sed mortality (males and females). No dermal irritation noted. 870.3250 90-Day dermal 28 day study fulfills this requirement toxicity in rats 870.6200a 48998502 (main) (2012) NOAEL 

### = 80 mg/kg Acute Neurotoxicity Acceptable/Guideline LOA EL = 200 mg/kg based on mortality and effects on

- rat 0 , 30, 80 , 200 mg/kg FOB parameters and motor activity in males and [48998501 (range finding) females (20 12) Page 15 of2 0furfural Scoping Document D424668

Ta bl e A3. S ub c hr o ni c, C hro n ic a nd Ot h e r Tox ici ty Pro fil e fo r F u r fur a l G u ide lin e No./ MRID No. (yea r )/ R es ults

St ud y Ty p e C lass ifi c a t ion /Doses 0, 50 , I 00 , 150 mg/kgj 870.6200b Wa ive d b y H ASPOC (T X R No

. 0 0 56939; Subchronic Neurotoxicity

- rat D4 1 86 88 ; 6 / l 0/201 4) 870.3465 46426504 and 46426505(200 I) NTO (Netherlands) 2001 (stud y publi cat io n ). 28-Day inhalation Acceptab le / G uid e lin e Systemic Toxicity NOAEL < 20 m g/m3

. toxicity in rats 0 , 20 , 40 , 80 , 160,320,640, System ic Toxicity LOA EL =< 20 m g/ m 3

. (LDT) all 1280 mg/m3 dose levels showing nasal epithelium pathology. 870.3465 4741910 1 (2008) P o r ta l o f E ntry NOAEL was 8 m g/m 3 (equivalent to 28

- Day inh a lation Acceptable/ G ui de lin e an analytical concentration of 0.007 m g/L). 0 (air) , 2, 4 , 8, or 20 m g/ m 3 Portal of Entry LOAEL was 20 m g/m 3 (equivalent to toxicity in rats (equivalent to ana lytical an analytical concentration of 0.017 mg/L) ba se d on concentrations of 0 , 0.002 , microscopic inflammatory changes in the na sal cavity 0.004, 0.007, and 0.017 mg/ L , Level 3, characterized by transitional respiratory respectively) for 6 hours per epithelial hyperplasia and mixed inflammatory cell day, 5 days/ week for 4 weeks infiltration. This is a portal of entry local adverse effect. 870.3465 90-Day inhalation 28 day study fulfill s this requirement toxicity in rats 870.3700 46147601 (1997) Mate rn a l Systemic Toxicity NOAEL = I0 mg/kg/day Prenatal Acceptable/ G uid e lin e (from rangefinder) deve lopm e ntal in w/ rangefind er Materna l Systemic Toxicity LOA EL = 50 mg/kg/day rats Primary study: 0 , 50 , I00, 150 (from primary) based on clinical signs. mg/kg/day Deve lop m e n ta l Toxicity NOAEL => 150 mg/kg/day Range finder 4662940 I ( 1996) Developmenta l Toxicity LOAEL > 150 mg/kg/day , no 0 , I0, 50 , I 00 , 150 , 250 , 500 , treatment related effects noted in the primary study, no I000 m g/kg/d ay r e leva nt observations in the ran ge findin g s tudy. (gavage in water) 870.3700 46207303 (2004) M ate rn al Systemic Toxicity NOAEL = 225 Prenatal Acceptab le / G u i d e l i ne mg/kg/day developmental in w/ rangefinder Maternal Systemic T oxicity LOA EL = 300 m g/ kg/ da y rabbits Primary study: 0 , 25 , 75, 225 based on decreased bw , bwg

- primar y study combined mg/k g/day with rangefinder study data Rangefinder: 46207302 (2003) Deve l op m e n tal Toxicity NOAEL = 225 mg/kg/day 0 , 25 , 50, I 00, 150 , 300 Developmental Toxicity LOA EL= 300 m g/ k g/day mg/kg/day based on decreased fetal bw

- primary s tudy combined (gavage in water) with rangefind er st udy data 870.3800 49 13920 I (2 013) Parental and Reproductive NOAEL= 60 m g/kg/day Reproduction and Acceptable/ Guideline Parental and Reproductive LOAEL could not be fertility effects determined 0, 20, 40 or 60 mg/k g/day Offspring NOA EL = 60 mg/k g/da y Offspring LOA EL could not be determined.
870.6300 Not required Developmental Page 16 of2 0

### Furfural Scoping Document D424668

Tab l e A3. S ub c hroni c, C hr o ni c an d Other Tox ic i ty Profil e for F urfur a l G uid e lin e No./ MRID No. (yea r)/ R es ults

Study T ype C lass ifi cation / Do ses neurotox1city 870.4100 46011016 (1990) NTP 1990 Study ( publi cat io n ). Chronic toxicity Acceptable/ No n- g ui deline. Systemic Toxicity NOAEL not identified Rats 0, 30 , or 60 mg/kg/day Systemic Toxicity LOAEL = 30 mg/k g/ day based on (gavage in oil) liver histopathology. Limited parameters measured. 870.4100 46011016 ( 199 0) NTP 1990 Study (p ubli catio n) Chronic toxicity

- Acceptable/ Non-guideline. Systemic Toxicity NOA EL = > 1 75 mg/k g/day mice 0 , 50 , 100 , or 1 75 mg/kg/day Systemic Toxicity LOA EL > 1 75 mg/kg/day (gavage in corn oil) Limited parameters measured. 870.4200 460110 16 (1990) NTP 1990 Study (pub li cation). Carcinogenicity Acceptable/ No n- g uid e lin e System ic Toxicity NOAEL = 30 mg/k g/day rat. 0 , 30 , 60 mg/k g/day Systemic Toxicity LOAEL = 60 mg/kg/ day based on (gavage in corn oi l) li ver effects (patholog ical observations). Limited parameters measured. Low in c id e n ce of c h o la n g iocarc inoma s in m a l es 870.4300 46011016 ( 1990) NTP 1990 Study ( publi cation) Carc in ogenicit y Acceptable / Non-guide l ine Systemic Toxicity NOAEL = > 175 mg/kg/day mouse. 0 , 50, I00 , 175 mg/kg/day Systemic Toxicity LOA EL > I 75 mg/k g/day Limited parameters measured. Adenoma s (M / F) and adenocarcinomas (M) of the li ver Gene Mutation 4601 1017 ( 19 99) Negative for bacterial reverse mutation assay 870.5100 Acceptable/ Guideline Gene Mutation 46011018 (2003 ) Negative for in vivo gene mutation 870.5100 Acceptable / Non-g uid e lin e bacterial ge ne in corpo r at ion into genome of transgenic mice C A/ SCE 460 1101 9 (2003) Negat ive and Acceptable/Guideline: 870.5375 , 870.5385 , Compi lat ion of7 reports Reverse Gene Mutation, In vitro mammalian gene 870.5900 , 870.59 I 5 mutation and chromosomal aberrations , In vivo Chromosomal Aberrations , SCE , Gene Mutation

- Drosophilia U n acceptab l e /Guideline

- Expert P ane l Report, SCE in human Lymphocytes , in v itro cytogenetic assays UDS 460 I I020 (2003) Negative for DNA damage/ repair, rec-as s ay , UDS in 870.5500 , 870.5560 Compilation of 9 reports rat hepatocytes

- Accep t ab le / Guideline DNA damage, summary r eports

- U na cce pt ab le 870.7485 47750502 ( 199 2) Furfura l was rapidly absorbed and e l iminated at all M e tabolism and Acceptable/ No n -g uid e lin e dose levels (80 % within 24 hours , 85 % within 72 pharniacokinetics 0.127 , 1.15 , 12.5 mg/kg hours out of a recovery of 90%). The urine was the (gavage in corn oil) major route of elimination (85% within 72 hours). Minor routes were feces (<2%) and exhalation as carbon dioxide (< 7 % ). Furfura l was retained in tissue s 

### Page 17 of2 0

### Furfural Scoping D ocument 

### 04246 68

Table A 3

. S ub c hronic , Chroni c and Oth e r T ox icit y Profil e fo r Furfu r a l G u id e l i ne No ./ MRID No

. (ye a r) / R es ult s

St u dy T ype C lass ifi cat io n /Doses at low levels oTiess tllan 1 % oTtlle administered dose (range 0.1 ± 0.1% at 0.127 mg/ kg to 0.6 ± 0.1% at 12.5 mg/kg), indicating low potential for bioaccumulation. 870.7600 None. Dermal penetration 870.7800 4899930 I (2012) NOA EL for systemic toxicity = 80 mg/kg/day 28-day Acceptable / Guideline LOA EL for sys temic toxicity could not be determin ed. l mmunotoxiciry in 0 , 20, 40 , 60, 80 mg/kg/day rats NOAEL for immunotoxicity 

### = 80 mg/kg/day LOA EL for immunotox icitv could not be determined

. Non -g uid e lin e = s tudi es e it h e r fr o m t h e o p e n lit e r a tur e, s tu d ies n ot m ee tin g g uid e lin e r e qui re ment s, b u t co n ta in u se ful in fo rm a ti on or r an ge- findin g s tudi es



### Page 18 of 20

### Furfura l/04330 1 

### Scop ing Document 

### D xxxx
Attac hm e nt 3 

### Table X : Summary of Toxicological Do s es and Endpoints for F urfural for Us e in Humanhealth Risk A ss ess ments (to be usedfor Re2i s tratio11 Review) Ex p os ure/ P o in t o f Unce rta in ty Leve l o f C onc e rn S tud y a nd T ox ico log ica l E ff ects Sce nari o D ep a r t ure Fac to r s fo r Ri s k Assess me nt

Acute Neurotoxicity Study Rat Acute Dietary UF A= IOx (M RID 48998502) (genera l NOAEL = 80 UFH = IO x Acute RFD = LOA EL = 200 mg/kg/day based on population) mg/kg/day 0.8 mg/kg/day effec ts o n FOB parameters , motor activity and mortality in mal es and fema les.

UFA= JOx Chronic Rat (M RID 46011016 ) Chronic U F H

= I Ox Chronic RID = Sys temic Toxicity LOAEL = 30 Dietary (All LOAEL = 30 UFL= 3X 0.1 mg/kg/day mg/kg/day based on li ve r Populations) mg/kg/day (LOAEL to path o l ogica l observation s (ce ntri l obular NOA EL necro s is and cy stic degeneration). extrapolation)) NOA EL not estab lished.

I ncidental Deve lopmental Rat (MR ID Oral Short- Re s idential LOC for 46147601 ) Term (1-30 NOAE L= 10 UFA = !Ox MOE = 100 Maternal LOAEL = 50 mg/k g/day d ays) and mg/kg/day U F H

= IO x (T his is also ba sed o n c lini cal s ign s of toxicity I ntermediate app licab l e to the (o ne hour post-dos ing , b il ateral Tenn ( 1- 6 yo un g) exop htha lmia , tremors, and head held month s ) l ow).

Dermal Short

- 28-Day Dermal Rat (M RID Term ( I-30 Occupational LOC 46917 2 0 1 ; 46917202) day s) and NOAEL = 250 UF A= I Ox for MOE = 100 Sys t e mic Toxi ci ty LOAEL 

### = 500 Int ermed iate- mg/k g/day UF H

= I Ox R es id entia l MO E = mg/k g/day , based on adverse clinical Term ( I- 6 1 00 s ig ns (ma le s) , an inc rease in motor months) ac tivity ( ma les) a nd increased mortality (ma les and females). Dermal Lon g -Term No lon g term dermal exposure expe cted ( > 6 months )



### P age 19 of 20

### Furfural / 04330 l Scoping Document 

### Dxxxx

Table X : S u mmary of Tox i colog ica l Doses and Endpoints for F u rfura l for Use 

### in Humanhealth Risk Assessments 

### (to be usedfor Registration Review) Exposure / Point of Uncertai nty Leve l of Concern St udy and Toxico logical Effects Scenario Departur e Factors for Ris k Assessment Port-of-entry NOAEL = 40 Acute Inh a lation Rats (MRlD mg/m3 R esidential and 4856370 I) Port-of-entry LOA EL = I nhalation UFA= 3x Occupational LOC 20 mg/m 3
, based on very sl ight/s li ght Acute Bystander and UFH = IOx for MOE = 30 nasal lesions in males hat were fully Occupational reversible wi thin 2 weeks of a single HEC = 6.63 exposure. mg/m 3 Port-of- entry NOAEL = 8 Inhalati on mg/m 3 Short-Term (2.09 mg/kg/day 1 ) 28- Day Inhalation Rats (MRlD ( 1-30 days) UFA = 3x Residential and 4741910 I) Port-of-entry LOA EL = and Bystander HEC = Occupational LOC 20 mg/m 3 based on nasal epithelial Int ermediate- 0.9Smg/m 3 UFH= l Ox for MOE = 30 pathology seen throughout all of the Term ( 1- 6 treated animal groups. months) Occupational HEC = 1.33 mg/m 3 Inhalation Long-Term No long tenn inhalation exposure expected ( > 6 months) Cancer (ora l, Furfural and Furfuryl Alcohol were both classified by CA R C as "L ikel y to Be Carcino genic to dermal , inhalation) Hum ans" wi th Q 1 *'s (TXR No

. 005689 1 , 2 /6/ 2014)
1 Inhalati on NOAEL = 2.09 mg/ kg/day. The dose in mg/L was converted to mg/kg/day using the following equation: Dose (mg/kg/day) = (NOAE L (0.008 mg/L) * Respiration rate of a young adult Sprague-Dawley rat ( 10.26 L/hr) * Study daily exposure duration (6 hr /day)) I Body weight of a young adult Sprague-Dawley rat (0.236 kg). Point of Departure ( POD ) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beg innin g of extrapolation to determine ri s k associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = low est observed adverse effect level. UF = uncertainty factor. UF" = extrapo lation from animal to human (interspecies). UF11 =potential variation in sensitivi ty among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern. NI A = not applicable

.



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