Di(2-ethylhexyl) terephthalate (DEHT) (CAS # ) GreenScreen Assessment. October 11 th, 2012

Transcription

1 Di(2-ethylhexyl) terephthalate (DEHT) (CAS # ) GreenScreen Assessment Octber 11 th, Cnnecticut Ave., N.W., Suite 300 Washingtn, D.C

2 TABLE OF CONTENTS GreenScreen Summary Rating fr DEHT... 1 Transfrmatin Prducts and Ratings:... 2 Intrductin... 2 Grup I Human Health Effects (Grup I Human)... 3 Carcingenicity (C) Scre... 3 Mutagenicity/Gentxicity (M) Scre... 3 Reprductive Txicity (R) Scre... 3 Develpmental Txicity incl. Develpmental Neurtxicity (D) Scre... 4 Endcrine Activity (E) Scre... 4 Grup II and II* Human Health Effects... 5 Acute Mammalian Txicity (AT) Grup II Scre... 5 Systemic Txicity/Organ Effects incl. Immuntxicity (ST)... 5 Grup II Scre (single dse)... 5 Grup II* Scre (repeated dse)... 5 Neurtxicity (N)... 6 Grup II Scre (single dse)... 6 Grup II* Scre (repeated dse)... 6 Skin Sensitizatin (SnS) Grup II* Scre... 6 Respiratry Sensitizatin (SnR) Grup II* Scre... 6 Skin Irritatin/Crrsivity (IrS) Grup II Scre... 6 Eye Irritatin/Crrsivity (IrE) Grup II Scre... 7 Ectxicity (Ectx)... 7 Acute Aquatic Txicity (AA) Scre... 7 Chrnic Aquatic Txicity (CA) Scre... 7 Envirnmental Fate (Fate)... 8 Persistence (P) Scre... 8 Biaccumulatin (B) Scre... 8 Physical Hazards (Physical)... 8 Reactivity (Rx) Scre... 8 Flammability (F) Scre... 8 References... 9 APPENDIX A: Hazard Benchmark Acrnyms Authrized Reviewers... 11

3 TABLE OF FIGURES Figure 1: GreenScreen TM Hazard Ratings fr Di(2-ethylhexyl) terephthalate (DEHT)... 2

4 GreenScreen Assessment fr Di(2-ethylhexyl) terephthalate (DEHT) (CAS # ) GreenScreen Versin 1.2 Verified Assessment Date f Verificatin: Octber 17, 2012 Expiratin Date: Octber 17, 2015 Uses: Restrictins: This cmplete reprt may be freely published and distributed by the Green Chemistry and Cmmerce Cuncil (GC3). Clean Prductin Actin des nt cnfer licensing rights r authrize the use f the GreenScreen trademark n public r prmtinal materials fr individual prducts cmprised f the chemical assessed in this reprt. Any prmtinal use f the GreenScreen trademarks must be cvered under a separate license agreement. Chemical Name: Di(2-ethylhexyl) terephthalate (DEHT) (CAS # ) GreenScreen Assessment Prepared By: Name: Chris Schlsser, M.F.S. Title: Assciate Txiclgist Organizatin: TxServices LLC Date: February 27, 2012 Updated: April 18, 2012; Octber 10, 2012 Quality Cntrl Perfrmed By: Name: Dr. Margaret H. Whittaker, Ph.D., M.P.H., CBil., F.S.B., E.R.T., D.A.B.T. Title: Managing Directr and Chief Txiclgist Organizatin: TxServices LLC Date: February 29, 2012 Updated: April 29, 2012; May 30, 2012; Octber 11, 2012 Cnfirm applicatin f the de minimus rule 1 : N/A Chemical Structure(s): Identify Applicatins/Functinal Uses: (e.g. Cleaning prduct, TV casing) 1. Plasticizer GreenScreen Summary Rating fr DEHT 2 : DEHT was assigned a GreenScreen Benchmark Scre f 3 DG as it des nt meet the data gap requirements fr a Benchmark scre f 4. Data gaps (dg) exist fr Neurtxicity (N) and Respiratry Sensitizatin (SnR). As utlined in CPA (2011c) Sectin III(1)(Benchmarking Chemicals With Data Gaps), DEHT meets requirements fr a 1 Every chemical in a material r frmulatin shuld be assessed if it is: 1. intentinally added and/r 2. present at greater than r equal t 100 ppm 2 Fr inrganic chemicals with lw human and ectxicity acrss all hazard endpints and lw biaccumulatin ptential, persistence alne will nt be deemed prblematic. Inrganic chemicals that are nly persistent will be evaluated under the criteria fr Benchmark 4. Page 1 f 11

5 GreenScreen Benchmark Scre f 3. In a wrst-case scenari, if DEHT were assigned a High scre fr N r SnR, it wuld be assigned a GreenScreen Benchmark Scre f 2. Figure 1: GreenScreen TM Hazard Ratings fr Di(2-ethylhexyl) terephthalate (DEHT) Grup I Human Grup II and II* Human Ectx Fate Physical C M R D E AT ST N SnS* SnR* IrS IrE AA CA P B Rx F single repeated* single repeated* L L L L L L dg L dg dg L dg L L L L vl L L L Nte: Hazard levels (Very High (vh), High (H), Mderate (M), Lw (L), Very Lw (vl)) in italics reflect estimated values and lwer cnfidence. Hazard levels in BOLD fnt reflect values based n test data (See Guidance). Nte: Please see Appendix A fr a glssary f hazard acrnyms. Transfrmatin Prducts and Ratings 3 : Identify relevant fate and transfrmatin prducts (i.e., dissciatin prducts, transfrmatin prducts, valence states) and/r mieties f cncern 4 Functinal Use N/A N/A Life Cycle Stage End f Life End f Life Transfrmatin Pathway Cmbustin Cmbustin Transfrmatin Prducts Carbn mnxide Carbn dixide CAS # On CPA Red List 5? Reprductive/develpmental txicant, neurtxicant (CPA 2009) Nt present n the Red List f chemicals (CPA 2009) Green Screen Rating 6 End f Life End f Life Intrductin Di(2-ethylhexyl) terephthalate (DEHT) is a phthalate alternative. DEHT is nt cnsidered t be a part f the cmmn phthalate ester class as it is nt rth-substituted. DEHT is cmpatible with use in cellulse acetatebutyrate, cellulse nitrate, plymethyl methacrylate, plystyrene, plyvinyl butyral, and PVC resins (CPSC 2010). GreenScreen List Translatr Screening Results The GreenScreen List Translatr identifies specific authritative r screening lists that shuld be searched t identify GreenScreen Benchmark 1 chemicals (CPA 2012). Phars (Phars 2012) is an nline list-searching tl that is used t screen chemicals against the List Translatr electrnically. The utput indicates benchmark r pssible benchmark scres fr each human health and envirnmental endpint. N utput was identified in Phars fr DEHT. 3 Prducts that cntain phthalates r phthalate alternatives are ften plastics. Plastics are ften dispsed f via incineratin. Therefre, health and envirnmental effects assciated with cmbustin byprducts are f particular cncern. 4 A miety is a discrete chemical entity that is a cnstituent part r cmpnent f a substance. A miety f cncern is ften the parent substance itself fr rganic cmpunds. Fr inrganic cmpunds, the miety f cncern is typically a dissciated cmpnent f the substance r a transfrmatin prduct. 5 The CPA Red List refers t chemicals: 1) flagged as Benchmark 1 using the GreenScreen List Translatr, r 2) flagged as Benchmark 1 r 2 using the GreenScreen List Translatr and further assessed and assigned as Benchmark 1. The mst recent versin f the GreenScreen List Translatr shuld be used (CPA 2011b). 6 GreenScreen TM reviews f transfrmatin prducts depend n the GreenScreen TM Benchmark Scre f the parent chemical (See Guidance in CPA 2011c). Page 2 f 11

6 Hazard Classificatin Summary Sectin: Grup I Human Health Effects (Grup I Human) Carcingenicity (C) Scre (H, M r L): L DEHT has been assigned a scre f Lw fr carcingenicity based n n evidence f carcingenic effects r statistically significant increases in tumrs fllwing a tw-year carcingenicity assay in rats. Nt listed as a knwn carcingen by IARC, NTP, U.S. EPA, r CA Prp 65. Dey 2007 A GLP cmpliant 104 week chrnic txicity/carcingenicity study (EPA OPPTS ) was cnducted using male and female Fischer 344 rats (50/sex/dse). Rats were administered dses f 0, 79, 324, and 666 mg/kg in males and 0, 102, 418, and 901 mg/kg (> 98% purity) in females daily in the diet. There was n evidence f a treatment-related effect n the incidence f any tumr type fr any grup f rats. There were n statistically significant dse-related differences in incidences f specific tumrs between treated and cntrl grups. Txic respnses were limited t reduced bdy weight gain and fd cnversin efficiency in the tp tw dse grups. A NOEL fr tumrigenicity f 666 mg/kg in males and 901 mg/kg in females was established by the study authrs. Mutagenicity/Gentxicity (M) Scre (H, M r L): L DEHT was assigned a scre f Lw fr mutagenicity based n negative in vitr mutagenicity and clastgenicity assays. A lw cnfidence scres was assigned as n in viv assays were identified. Barber 1994 A nn-glp cmpliant bacterial reverse mutatin assay (methd nt reprted) was cnducted utilizing Salmnella typhimurium tester strains TA98, TA100, TA1535, TA1537 and TA1538 at cncentratins f up t 10,000 μg/plate with and withut metablic activatin. N mutagenic activity was bserved under the tested cnditins and DEHT was reprted as negative fr mutagenicity. A GLP cmpliant chrmsmal aberratin assay (similar t OECD 473) was cnducted utilizing Chinese Hamster Ovary (CHO) cells at cncentratins up t 1,000 nl/ml with and withut metablic activatin. N increases in aberratins were identified and DEHT was reprted as negative fr clastgenicity. A GLP cmpliant HGPRT assay (similar t OECD 476) was cnducted utilizing CHO cells at cncentratins f up t 20 nl/ml with and withut metablic activatin. N statistically significant increases in mutatin frequencies were reprted when cmpared t cntrls. DEHT was reprted as negative fr mutagenicity under the tested cnditins. Reprductive Txicity (R) Scre (H, M, r L): L DEHT was assigned a scre f Lw fr reprductive txicity based n n effects n reprductive parameters fllwing a tw-generatin (OECD 416) reprductive txicity study. Faber et al. 2007a A GLP cmpliant tw generatin reprductive txicity study (OECD 416) was cnducted using male and female Sprague-Dawley rats (30/sex/dse). Rats were administered dses f 0, 0.3, 0.6, and 1.0% (0, 258, 516, and 860 mg/kg in males, and 0, 294, 588, and 980 mg/kg in females 7 ) f DEHT (purity nt reprted) in the diet frm 70 days pre-mating t terminatin in the F0 generatin and frm PND 22 until terminatin in the F1 generatin. Reprductive parameters (fertility, mating, days between pairing and citus, gestatin, parturitin, and estrus cycling). Mean litter sizes, numbers f pups brn, percentages f males per litter at birth and pstnatal survival were unaffected. Female rats displayed systemic txicity in the 516 and 860 mg/kg grups including decreased fd cnsumptin. Slight decreases in rgan weights in the tp dse F1 grup were cnsidered t be secndary t maternal txicity. Additinally, n dse-respnse culd be established. Based n available data, a NOAEL f 1.0% (860 mg/kg) was established by study authrs. Study authrs nly reprted abslute rgan weights, and n evaluatin r values fr relative rgan weights were identified. N evaluatins 7 Dse cnversin estimates are based n default male and female Sprague Dawley fd factr values frm x 98,000 mg/kg (Fd Factr fr Females) = ~294 mg/kg x 86,000 mg/kg (Fd Factr fr Males) = ~258 mg/kg Page 3 f 11

7 r data n crpra lutea r pre- and pst- implantatin lses were identified. Additinally, data n male rgan weights in the table 4 were nt reprted crrectly and evaluatin f data is nt pssible. Based n the missing and inaccurately reprted data, TxServices cnsiders the endpint evaluatin f DEHT t be f lw cnfidence. Develpmental Txicity incl. Develpmental Neurtxicity (D) Scre (H, M r L): L DEHT was assigned a scre f Lw fr develpmental txicity based n the absence f fetal txicity r teratgenicity fllwing three develpmental txicity studies in rats and mice. Faber et al. 2007b A GLP cmpliant develpmental txicity study (OECD 414) with utertrphic evaluatins was cnducted using female Sprague-Dawley rats (25/grup). Rats were administered dses f 0, 229, 458, and 747 mg/kg (purity nt reprted) f the test substance n days 0 thrugh 20 f gestatin. In the utertrphic examinatins sexually immature rats were administered dses f 20, 200, and 2,000 mg/kg via ral gavage n days pst natal days 19 t 21. Number f viable and nn-viable fetuses, resrptins and implantatin sites, and crpra lutea did nt differ frm cntrls. N visceral r skeletal anmalies and n signs f develpmental txicity were reprted. In the utertrphic assay fr estrgenic activity DEHT expsure did nt affect wet r bltted uterine weight parameters. A NOAEL f 747 mg/kg fr develpmental txicity was established by the study authrs. A GLP cmpliant develpmental txicity study (OECD 414) was cnducted using female CD-1 mice (25/grup). Mice were administered dses f 0, 197, 592 and 1,385 mg/kg f DEHT ( 97.6%) in the diet n days 0-18 f gestatin. N effects were bserved n the number f malfrmatins/skeletal variatins, litter size, fetal bdy weights r sex ratis. N evidence f fettxicity r teratgenicity was bserved even at maternally txic dses. A NOEL f 1,385 mg/kg was identified fr develpmental txicity by the authrs. A (GLP status nt reprted) develpmental txicity limit test (methd nt reprted) was cnducted using female Sprague-Dawley rats (number nt reprted). Rats were administered dses f 0 r 750 mg/kg f DEHT (98% purity) n gestatin day 14 thrugh pstnatal day 3 via ral gavage. N maternal txicity, fettxicity, r teratgenicity was reprted at any dse level. A NOEL f 750 mg/kg was reprted by the study authrs. Liu et al An additinal study was perfrmed t investigate the gene expressin in the fetal testis fllwing in uter expsure t DEHT. While this nt a standard guide-lined study and is nt applicable t the GreenScreen scring criteria, it des prvide insight int the mechanistic nature and mde f actin f phthalate n testicular effects. In this study it was fund that DEHT did nt alter gene expressin fllwing in uter expsure n gestatin days 12 t 19. Endcrine Activity (E) Scre (H, M r L): L DEHT has been assigned a Lw fr endcrine activity. Sufficient data have been prvided t demnstrate that DEHT is nt estrgenic r andrgenic. Althugh n thyrid effects were bserved, limited data were available t fully assess ptential thyrid effects f DEHT and it was assigned a lw cnfidence scre. Nt listed as a ptential endcrine disruptr n the EU Pririty List f Suspected Endcrine Disruptrs. Nt listed as a ptential endcrine disruptr n the OSPAR List f Chemicals f Pssible Cncern. Nt listed as a ptential endcrine disruptr n the Red List f Chemicals (CPA 2011b). Gray et al DEHT was tested fr its ptential t alter sexual differentiatin f the male rat fllwing perinatal expsure. DEHT was rally administered t pregnant dams frm gestatin day 14 t pst natal day 3. Study results indicated that DEHT did nt induce vert maternal txicity r reduced litter sizes. N changes were bserved in angenital distance, testis weights, r nipple retentin. Study authrs cncluded that DEHT was ineffective at 750 mg/kg at altering sexual differentiatin in male rats. A slight decrease in serum teststerne was reprted, but did nt reach statistical significance. Spermatgenic assessment cnducted during the 2-generatin reprductive txicity study appeared nrmal (Faber et al. 2007a). A slight decrease in serum teststerne was reprted, but did nt reach statistical significance. Hwever, the lack f effects n reprductive rgan weights in bth the current Page 4 f 11

8 study and the 2-generatin study, and lack f effects n the spermatgenic assessment in the 2- generatin study indicate that DEHT is unlikely t affect the endcrine activity in male rats. Additinally, the lack f effects n estrgenic activity fllwing the develpmental txicity and utertrphic assay indicate that DEHT is unlikely t affect endcrine activity in female rats. Based n the available data, TxServices cncludes that there is n evidence f endcrine activity fr DEHT in the available studies. Hwever, limited data were available t assess ptential thyrid effects f DEHT. Therefre, TxServices has assigned a lw cnfidence scre fr this endpint. Grup II and II* Human Health Effects (Grup II and II* Human) Nte: Grup II and Grup II* endpints are distinguished in the v 1.2 Benchmark system. Fr Systemic Txicity and Neurtxicity, Grup II and II* are cnsidered sub-endpints and test data fr single r repeated expsures may be used. If data exist fr single OR repeated expsures, then the endpint is nt cnsidered a data gap. If data are available fr bth single and repeated expsures, then the mre cnservative value is used. Acute Mammalian Txicity (AT) Grup II Scre (vh, H, M r L): L DEHT was assigned a scre f Lw fr acute mammalian txicity based ral and dermal abve 2,000 mg/kg, the GreenScreen cut ff value fr lw txicity (CPA 2011a). UNEP 2003 An ral LD 50 value f greater than 5,000 mg/kg was identified in (strain nt reprted) rats. An ral LD 50 value f greater than 3,200 mg/kg was identified in (strain nt reprted) mice. A dermal LD 50 value f greater than 19,670 mg/kg was identified in (strain nt reprted) guinea pigs. Systemic Txicity/Organ Effects incl. Immuntxicity (ST) Grup II Scre (single dse)( vh, H, M r L): dg N relevant data were identified fr DEHT r structurally related chemicals. Grup II* Scre (repeated dse)(h, M, L): L DEHT was assigned a scre f Lw fr systemic txicity/rgan effects (repeated expsure) based n n significant effects between 10 and 100 mg/kg and nt being classified as a specific target rgan txicant fllwing GHS Criteria. Dey 2007 A GLP cmpliant 104 week chrnic txicity/carcingenicity study (EPA OPPTS ) was cnducted using male and female Fischer 344 rats (50/sex/dse). Rats were administered dses f 0, 79, 324, and 666 mg/kg in males and 0, 102, 418, and 901 mg/kg (> 98% purity) in females, daily, in the diet. Examinatin included clinical signs and mrtality, bdy weight and bdy weight gain, fd cnsumptin and cmpund intake, phthalmscpic examinatin, hematlgy, clinical chemistry, urinalysis, rgan weights, grss pathlgy, and histpathlgy. N treatment related effects were identified n clinical signs and mrtality, fd cnsumptin, clinical chemistry, hematlgy, grss pathlgy, and ne-plastic histpathlgy. Bdy weights and bdy weight gain was significantly lwer in the tp dse grup thrughut the study and in the mid-dse grup during the first-year f the study. In the eyes, a statistically significantly increased incidence f lss f the uter nuclear layer f the retina was seen in females in the mid and tp dse grups. An increased incidence f prminent esinphilic inclusins was bserved in females in the mid and tp dse grups (36/50 ttal and 47/50 ttal, respectively, vs. 29/50 ttal cntrls). ECHA (2012) authrs reprted that this may have been an exacerbatin f an age-related finding. Only the mid-dse was statistically significant. Based n the available data authrs established a NOAEL and LOAEL f 102 and 418 mg/kg, respectively. Barber and Tpping 1995 A GLP cmpliant 90-day txicity study (EPA ) was cnducting using male and female Sprague-Dawley rats (20/sex/dse). Rats were administered dses f 0, 54, 277, and 561 mg/kg f DEHT in males, and 0, 61, 309, and 617 mg/kg f DEHT (98.4% purity) in the feed fr 90-days. Examinatin included clinical signs and mrtality, bdy weight and bdy weight gain, fd cnsumptin and cmpund intake, phthalmscpic examinatin, hematlgy, clinical chemistry, urinalysis, rgan weights, grss pathlgy, and histpathlgy. N effects were reprted n clinical signs and mrtality, bdy weight and bdy weight gain, fd cnsumptin and cmpund intake, Page 5 f 11

9 phthalmscpic examinatin, clinical chemistry, urinalysis, grss pathlgy and histpathlgy. Mean hemglbin, hematcrit, Mean Crpuscular Hemglbin (MCH) and Mean Crpuscular Vlume (MCV) were significantly lwer than cntrls in the tp dse male grup (4-5% decreases). Mean MCH values were als lwer in the mid-dse male rat grup (2%). MCV and MCH values were significantly in mid- and tp-dse female rats (3%). Authrs cncluded that changes in hematlgy were minimal in severity, and nt clearly dse-dependent and were therefre nt f bilgical significance. Abslute liver weight increases (9%) and liver weights relative t bdy weights rati increase (11%) were bserved in males in the tp-dse grup. Only relative liver weight changes reached statistical significance. In females, the abslute liver weight was increased by 7% and the relative liver weight was increased by 9% in the tp-dse grups. Again nly relative liver weight changes reached statistical significance. Based n the available data, study authrs established a NOEL and LOEL f 277 and 561 mg/kg based n hematlgical and liver weight changes. DEHT is nt classifiable as a GHS Specific Target Organ Txicant as n significantly txic effects were reprted within the recmmended guidance values f 10 t 100 mg/kg (UN 2011). Neurtxicity (N) Grup II Scre (single dse)(vh, H, M r L): dg DEHT has been assigned a data gap fr neurtxicity. Althugh it is nt a knwn neurtxicant, neurtxicity testing has nt perfrmed n the chemical. Nt classified as a develpmental neurtxicant (Grandjean and Landrigan 2006). Nt listed as a ptential neurtxicant n the Red List f Chemicals (CPA 2011b). N relevant data were identified fr DEHT r structurally related chemicals. Grup II* Scre (repeated dse)(h, M, L): dg DEHT has been assigned a data gap fr neurtxicity. Althugh it is nt a knwn neurtxicant, neurtxicity testing has nt perfrmed n the chemical. Nt classified as a develpmental neurtxicant (Grandjean and Landrigan 2006). Nt listed as a ptential neurtxicant n the Red List f Chemicals (CPA 2011b). N relevant data were identified fr DEHT r structurally related chemicals. Skin Sensitizatin (SnS) Grup II* Scre (H, M r L): L DEHT was assigned a scre f Lw fr skin sensitizatin based n negative sensitizatin data fllwing a human repeat patch test and a guinea pig sensitizatin study. UNEP 2003 A nn-glp cmpliant dermal sensitizatin study (methd nt reprted) was cnducted using guinea pigs (strain/sex nt reprted, n=5). Guinea pigs were expsed t a 1% slutin f DEHT (purity nt reprted) via injectin int the ftpad fllwed by a 1% dermal applicatin challenge dse. N signs f sensitizatin were bserved and DEHT was reprted as nn-sensitizing under the tested cnditins. A dermal sensitizatin (mdified Draize methd) was cnducted using human vlunteers (9/sex) fllwing gd clinical practices. Humans were expsed nine dermal applicatins f 0.5% DEHT in acetne under semi-cclusive cnditins ver a three-week inductin perid. Fllwing a tw week rest perid a challenge dse f 0.5% was applied t the skin. DEHT was nn-irritating and nnsensitizing in all vlunteers. Respiratry Sensitizatin (SnR) Grup II* Scre (H, M r L): dg DEHT was assigned a data gat fr respiratry sensitizatin. N relevant data were identified fr DEHT r structurally related chemicals. Skin Irritatin/Crrsivity (IrS) Grup II Scre (vh, H, M r L): L DEHT was assigned a scre f Lw fr skin irritatin/crrsivity based n nt being classified as an Irritant fllwing GHS Criteria. A GLP cmpliant skin irritatin/crrsin study (OECD 404) was cnducted using male and female New Zealand white rabbits (2 male/1 female). Rabbits were expsed t 0.5 ml f undiluted test Page 6 f 11

10 UNEP 2003 material under cclusive cnditins fr 4 hurs with a 72 hur bservatinal perid fllwing expsure. Average scres f 0.0 were reprted fr erythema and edema, and DEHT was reprted as nn-irritating under the tested cnditins. A nn-glp cmpliant skin irritatin/crrsin study (methd nt reprted) was cnducted using Male Duncan-Hartley guinea pigs (n=3). Guinea pigs were expsed t 0, 4,920, 9,840, and 19,680 mg/kg f DEHT (purity nt reprted) under cclusive cnditins fr 24 hurs. Tw weeks after expsure the high dse animal shwed mderate edema and slight desquamatin and severe edema was reprted in the lw and mid- dse animals. DEHT was reprted as slightly irritating under the tested cnditins by the authrs. Hwever, current guidelines nly specify a 4-hur expsure time and require at least 3 animals per expsure grup. Therefre, the reliability f this study is limited. A primary dermal irritatin study (methd nt reprted) was cnducted using human vlunteers (9/sex) fllwing gd clinical practices. Humans were expsed t 0.01, 0.05, 0.1, 0.2 and 0.5% f the test substance under semi-cclusive cnditins fr three 24-hur perids. Overall irritatin scres ranged frm 0.00 t 0.11 and the test substance was reprted as nn-irritating under the tested cnditins. Eye Irritatin/Crrsivity (IrE) Grup II Scre (vh, H, M r L): L DEHT was assigned a scre f Lw fr eye irritatin/crrsivity based n nt being classified as an Irritant fllwing GHS Criteria UNEP 2003 A GLP cmpliant eye irritatin/crrsin study (OECD 405) was cnducted using male and female New Zealand white rabbits (1 male/2 female). Rabbits were expsed t 0.1 ml f in ne eye fr 4 hurs with a 72 hur bservatinal perid fllwing expsure. N crneal pacity r iritis was bserved during the study. Cnjunctivitis and redness were reprted up t 48 hurs after administratin. All reprted effects were fully reversible within 72 hurs and DEHT is nt classifiable as a GHS eye irritant. A nn-glp cmpliant eye irritatin/crrsin study (methd nt reprted) was cnducted using New Zealand white rabbits (n=6, sex nt reprted). Rabbits were expsed t 0.1 ml f the test substance in ne eye. At 24 hurs after expsure ne rabbit shwed adnexal staining f the nictitating membrane. At 48 hurs after expsure all animals appeared nrmal. Fllwing GHS criteria, DEHT is nt classified as an irritant as all effects were reversible within a 48-hur time perid. Ectxicity (Ectx) Acute Aquatic Txicity (AA) Scre (vh, H, M r L): L DEHT was assigned a scre f Lw fr acute aquatic txicity based n n effects being expected at saturatin levels f DEHT. An LC 50 value f > 0.25 mg/l was identified in Oncrhynchus mykiss (fish, 7-day). UNEP 2003 A LC 50 value f 984 mg/l was identified in Pimephales prmelas (fish, 96-hr). An EC 50 value f > 1.4 μg/l was identified in Daphnia magna (aquatic invertebrate, 48-hr). An EC 50 value f > mg/l was identified in Selenastrum capricnutum (algae, 72-hr). DEHT has a reprted waster slubility f 0.4 μg/l (ECHA 2012). Based n the available data, n effects are predicted at saturatin levels fr DEHT. Therefre, DEHT is assigned a Lw hazard scre fr acute aquatic txicity. Chrnic Aquatic Txicity (CA) Scre (vh, H, M r L): L DEHT was assigned a scre f Lw fr chrnic aquatic txicity based n n effects at the highest cncentratins tested in fish and daphnid. Additinally, DEHT is bth rapidly bidegradable and nt biaccumulative fllwing GHS Criteria (UN 2011). Chemicals with lw acute txicity which are rapidly bidegrade and d nt biaccumulate are nt cnsidered chrnic aquatic txicants. A NOEC f 0.28 mg/l was established in Oncrhynchus mykiss (fish, 60-day). A NOEC f 0.76 μg/l was established in Daphnia magna (daphnid, 21-day). Page 7 f 11

11 Envirnmental Fate (Fate) Persistence (P) Scre (vh, H, M, L, r vl): vl DEHT was assigned a scre f Very Lw fr persistence based n meeting the ready bidegradable criteria fllwing a GLP cmpliant OECD 301 B bidegradatin study under mdern guidelines. A GLP cmpliant bidegradatin study (OECD 301B Ready Bidegradatin: CO 2 Evlutin Test ) was cnducted under aerbic cnditins at a cncentratin f 10 mg/l. DEHT was fund t have a ttal f 73.05% bidegradatin within 28 days and met the 10-day bidegradatin windw. DEHT was reprted as readily bidegradable by study authrs. UNEP 2003 A (GLP status nt reprted) 28-day shake flask bidegradatin test (similar t OECD 301 B) was cnducted under aerbic cnditins at a cncentratin f 1.04 mg/l. DEHT was fund t have 40.2% bidegradatin after 28 days and was nt cnsidered t be readily bidegradable. Data frm ECHA were cnsidered preferable fr this endpint as the study is well-dcumented, prvides sufficient details, was perfrmed accrding t GLP, and did nt deviate frm OECD guidelines. Therefre, TxServices assigned a hazard scre f Very Lw fr persistence as DEHT is expected t meet the 10-day ready bidegradability windw. Biaccumulatin (B) Scre (vh, H, M, L, r vl): L DEHT was assigned a scre f Lw fr biaccumulatin based n a measured BCF f 396, which is within the 100 t 500 range classified by GreenScreen as lw fr biaccumulatin. DEHT has a measured BCF f 393 in Crasstrea virginica fllwing EPA OPPTS (Oyster Bicncentatin Test). Fllwing GreenScreen criteria, chemicals with a BCF < 500 are cnsidered t have lw ptential fr biaccumulatin. Physical Hazards (Physical) Reactivity (Rx) Scre (vh, H, M r L): L DEHT was assigned a scre f Lw fr reactivity based n the absence f functinal grups cntaining high energy bnds r xidizing species, which may cause reactivity. DEHT wuld nt be classified as an xidizing chemical as its chemical structure des nt cntain halgens, and xygen atms are nly bnded t carbn r hydrgen (UN 2011). In additin, DEHT is nt expected be explsive as it des nt cntain structural grups that wuld cause cncern fr explsin. Furthermre, the high flashpint (212 C) supprts that cnclusin that DEHT is nt a reactive chemical. Flammability (F) Scre (vh, H, M r L): L DEHT was assigned a scre f Lw fr flammability based n nt being classified as a GHS Flammable Liquid. DEHT has a flash pint f 212 C, which is abve the 93 C cut-ff criteria t be classified as flammable by GHS (UN 2011) 8. 8 Table f the GHS Purple Bk. Page 8 f 11

12 References Barber, E.D Genetic Txiclgy Testing f Di(2-ethylhexyl) Terephthalate. Envirnmental and Mlecular Mutagenesis 23: Barber, E.D., and D.C. Tpping Subchrnic 90-Day Oral Txiclgy f Di(2-ethylhexyl) Terephthalate in the Rat. Fd and Chemical Txiclgy. 33(11): Clean Prductin Actin (CPA). 2011a. The GreenScreen fr Safer Chemical Versin 1.2. Available: Clean Prductin Actin (CPA). 2011b. Red List f Chemicals. Available: Cnsumer Prduct Safety Cmmissin (CPSC) Review f Expsure and Txicity Data fr Phthalate Substitutes. Available: Dey, James A Carcingenicity and Chrnic Txicity f Di-2-Ethylhexyl Terephthalate (DEHT) fllwing a 2-year Dietary Expsure in Fischer 344 Rats. Fd and Chemical Txiclgy. 46: Eurpean Chemicals Agency (ECHA) Online substance infrmatin fr DEHT. Available: 9eb0e894-2a e f67d031_DISS-9eb0e894-2a e f67d031.html Faber, W.D., James A. Dey, Dnald G. Stump, and Karen Ruble. 2007a. Tw-Generatin Reprductin Study f di-2-ethylhexyl Terephthalate in Crl:CD Rats. Birth Defects Research (Part B) 80: Faber, W.D., James A. Dey, Dnald G. Stump, and Karen Ruble. 2007b. Develpmental Txicity and Utertrphic Studies with Di-2-Ethylhexyl Terephthalate. Birth Defects Research (Part B) 80: Grandjean, P. and P.J. Landrigan Develpmental neurtxicity f industrial chemicals. Lancet 368: Gray Jr, E. L., J. Ostby, J. Furr, M. Price, D.N. Ra Veermachaneni, and L. Parks Perinatal Expsure t the Phthalates DEHP, BBP, and DINP, but Nt DEP, DMP, r DOTP, Alters Sexual Differentiatin f Male Rat. Txiclgical Sciences 58: Liu, K., K. P. Lehmann, M. Sar, S. S. Yung, and K..W. Gaid Gene Expressin Prfiling Fllwing In Uter Expsure t Phthalate Esters Reveals New Gene Targets in the Etilgy f Testicular Dysgenesis. Bilgy f Reprductin 73: United Natins (UN) Glbally Harmnized System f Classificatin and Labeling f Chemicals, Furth Revised Editin. United Natins Envirnmental Prgramme (UNEP) Screening Infrmatin Dataset (SIDS) fr DEHT. Organisatin fr Ecnmic Develpment (OECD). Available: Page 9 f 11

13 APPENDIX A: Hazard Benchmark Acrnyms (in alphabetical rder) (AA) (AT) (B) (C) (CA) (Cr) (D) (E) (F) (IrE) (IrS) (M) (N) (P) (R) (Rx) (SnS) (SnR) (ST) Acute Aquatic Txicity Acute Mammalian Txicity Biaccumulatin Carcingenicity Chrnic Aquatic Txicity Crrsin/ Irritatin (Skin/ Eye) Develpmental Txicity Endcrine Activity Flammability Eye Irritatin/Crrsivity Skin Irritatin/Crrsivity Mutagenicity and Gentxicity Neurtxicity Persistence Reprductive Txicity Reactivity Sensitizatin- Skin Sensitizatin- Respiratry Systemic/Organ Txicity Page 10 f 11

14 Authrized Reviewers DEHT GreenScreen Evaluatin Prepared By: Christpher E. Schlsser, M.F.S. Assciate Txiclgist TxServices LLC DEHT GreenScreen Evaluatin QC d By: Margaret H. Whittaker, Ph.D., M.P.H., CBil., F.S.B., E.R.T., D.A.B.T. Managing Directr and Chief Txiclgist TxServices LLC Page 11 f 11