9/13/10 UNITED STATES ENVIRONMENTAL PRO T ECTION AGENCY

WASHING T ON

, D

. C

. 20460

OFFICE OF

CHEMICAL SAF E TY AND

POLLUTION P REVENTION

MEMORANDUM

SUBJECT:

FROM:

TO:

THRU:

Int r oduction Copper 8-quinolinolate. Human Health Effects Scoping

Document for the Regi s tration Review Decision

. PC Code:

024002. Registration Review Case No.: 5118

. CAS No.:

10380-28-6. DP Barcode : D380656.

William J

. Hazel

, Ph

. D

. , Chemist

Risk Assessment and Science Support Branch (

Antimicrobials Division (751 OP)

Rebecca von dem Hagen

, Chemical Review Manager Regulatory Management Branch II (RMB II)

Antimicrobials Division (7510P) 

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# C2..

Nader Elkassabany

, Ph

. D

. , Chief 

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# CRisk Assessment and Science Support Branch ( RASSB)

Antimicrobials Division (7510P )

The Antimicrobials Division (AD) has evaluated the status of the human health

assessments for Copper 8-quinolinolate

. Copper 8-quinolinolate is an organic

copper chelate registered for use as an ant i microbial pesticide to prevent the growth of algae

, bacteria

, and fungi inIon textiles

, wood products

, paper

, adhes i ves

, etc. The Agency examined the hazard and human exposure databases for Copper 8-quinolinolate to determine whether current science policies

, use patterns

, or available data ma t erially affect the overall risk p i ctu r e

. Copper 8

- quinolinolate was first registered 9 /

9/94

. A Reregistration Eligibility

Decision (RED) was i ssued for Copper 8-quinolinolate September

, 2007. A

Generic Data Call-in associated w i th the RED was issued June 8

, 2010 requiring

subm i ssion o f studies to characterize inhalation toxicity

, leaching of residues

from treated wood

, residues in honey

, applicator e x posure and postapplication

exposure

. Consequently

, no addit i onal human hazard or exposure data are likely

to be needed in association with this Copper 8-quinolinolate Registration Review.

Copper 8-quinolinolate is an algaecide

, bactericide and fungicide. It is used as a material preservative in industrial textiles in t ended for the treatment of webbing

,tenting, rope, canvas, leather, industrial cotton, industrial fabrics and clothing for industrial and govern ment (e.g ., military) use. Other material preservation uses include in-can paint preservation; pulp, paperboard, and kraft paper; and adhesives and glues. Copper 8-quinolinolate is also used as a wood preservative intended for treatment of w ood to be used as beams for indoor use, mushroom trays, produce picking trays/cont ainers that may contain fruit (indirect food contact use), interior boat applicat ions, wood used in greenhouse premises, equipment and containers, l og homes, roofing shingles, siding, fences, decks, furniture, playground equipment, sills and baseboards, and structural building

lumber.

There are three manufacturing-use products (MP). The Osmose, Inc. MP (EPA Reg. No. 3008-93) contains 96% ai and is labeled to formulate products to treat cement and wood products. Tanabe U.S.A ., Inc. has registered a 98% MP (EPA Reg. No. 10829-8) to formulate EPs us ed to treat textile s, cement, pulp and paper ingredients, paper, wood products, paint, polymeric plastics, adhesives, and glue. James Hardie Building Produc ts, Inc. has registered a 98% MP (EPA Reg. No. 83515-1) labeled to formulat e products to treat cement, pulp, and

paper.

There are 26 end-use products (EP) formulated into soluble concentrate/liquids (SC/L), emulsifiable concentrates (EC), and ready-to-use (RTU) products from

these three MPs. The EPs contain Copper 8-quinolinolate at 0.25-34.18% ai. Copper 8-quinolinolate is used to tr eat wood and wood products in commercial

wood treatment facilities at a use concentration of 2.3% ai in a diptank or 1% ai by pressure treatment. Wood in commerc ial sites may also be dipped into a 1% ai solution, brushed with a 3.3% ai soluti on (for ground-contact only), or brushed, rolled, or sprayed using a 0.675-0.8% ai RTU preservative coating. Paints and coatings are preserved (in-can) using 1% ai (v:v) and adhesives are preserved by incorporating Copper 8- quinolinolate at 0.1% ai (v:v). Paper and paperboard are preserved at the sheet stage using 0.24% ai (w:w) applied at the size press by liquid pump or 0.4% ai (w:w) applied by brush, spra y, or dip. Textiles are treated at the padder using liquid pump or liquid pour to incorporate Copper 8- quinolinolate at 0.7% ai (w:w) for industrial use or 1% ai (w:w) for government use. Textiles may also be impr egnated for government use with Copper 8- quinolinolate by brushing, spraying, or di pping at 0.2-1% ai. Mold and mildew may be treated on virtually any porous or nonporous outdoor hard surface by brushing or spraying with a 0.1% ai (v:v ) solution of Copper 8-quinolinolate. Indoor hard surfaces of potato seed piece handling, storage, or shipping facilities and equipment may be treated by spraying with a 0.05% ai (v:v) solution to

control Corynebacterium sepedonicum which causes potato ring rot. Clearances have been established by FDA at: 21 CF R 175.105(c) for use in food contact adhesives as a preservative; 21 CFR 176. 170 for use of C opper 8-quinolinolate as a component of the food contact surface of paper and paperboard (as a preservative for coating formulations); and 21 CFR 178.3800 as a preservative of

wooden articles used or intended for use in packaging, transporting, or holding raw agricultural commodities. There is no EPA-established tolerance or tolerance exemption associated with the use of Copper 8-quinolinolate.

2The primary source of information for th is Human Health Scoping Document was the Reregistration Eligibility Deci sion (RED) of 2007 and its associated references and sources as per th e Docket EPA-HQ-OPP-2007-0556. The purpose of this document is to determine whether sufficient data are available to support registration review and whet her new human health assessments are needed to reflect current use patterns, regulations, and policies.

Section 1. Chemical Identity

Table 1.1 Chemical Identity

Common Name Copper 8-quinolinolate

Chemical Name Copper, bis(8-quinolinolato-N1,O8)-, Synonyms Copper 8-quinolinolate

Molecular Formula C 18 H 12 CuN 2 O 2 Molecular Weight 351.851

PC Code 024002 CAS Registry Number 10380-28-6 Registration Review Case No. 5118

Chemical Structure

Copper 8-quinolinolate is an odorless, oliv e green solid at room temperature (25 C) that melts at 270 °C. It has low solubility in water (0.07 mg/L) and an octanol/water partition coefficient (log K O/W ) of 2.5 at 25 °C. Copper 8- quinolinolate degrades above the melting poi nt but below the temperature at which it boils. It has a very low vapor pressure of 6.3 x 10 -12 . Copper 8- quinolinolate is fairly stable to hydrolysi s (at pHs of 5-9), microbial metabolism, and photodegradation.

Section 2. Toxicology

The Copper 8-quinolinolate toxicology database is considered adequate to permit the registration review process to conti nue although the 90-day inhalation toxicity study called in via the 6/8/10 DCI a ssociated with the 2007 RED will permit significant refinement of risk esti mates associated with applicator and postapplication exposure via the inhalat ion route as a number of use scenarios

3will result in the generation of aerosols. Summarized below are the toxicology studies currently available.

a. Acute Toxicit y

The acute toxicity database for Copper 8- quinolinolate was considered complete in the 2007 RED. Copper 8- quinolinolate has a low order of acute toxicity via the oral route of exposure (Toxic ity Category IV). It is so mewhat toxic via the dermal route of exposure (Toxicity Category II I) whereas exposure via the inhalation route induces moderate toxicity (Toxicity Category II). Copper 8-quinolinolate is classified as corrosive to the eye (Toxic ity Category I). Copper 8-quinolinolate is

considered to be a mild dermal irritant (Toxicity Category IV) and not to be a

dermal sensitizer.

b. Subchronic Toxicity

For subchronic toxicity, several studies we re submitted to the Agency. Three of

the five studies were considered a cceptable in the 2007 RED (MRIDs 42986801, 42986802, 42957802). The ot her two studies were supplementary (MRID 42937301) and range-finding (MRID 42957801), respectively. In a 90-day oral toxicity test (MRID 42986802), Copper 8-quinolinolate (>99.5% purity) was administered in feed via capsules to 4 dogs /sex/dose at concentrations of 0, 5, 50, or 250 mg/kg/day for males and fema les, respectively) for 13 weeks. The NOAEL was determined to be 5 mg/kg/day (males/females), based on vomiting, reduced total plasma protein and album in, reddened mucosa and hyperemia in
stomach and/or small intestine observ ed at the LOAEL of 50 mg/kg/day.

In a 28-day dermal toxicity study (MRI D 42957802), Tif: RAIF (SPF) Albino rats (5/sex) were administered Copper 8-quinolinolate (99.7% a.i.) at doses of 0, 50, 200, or 1000 mg/kg/day for 6 hours per day, for 4 weeks. Histopathologic

examination revealed an in creased incidence of nec rosis of the thymic lymphocytes in male rats exposed to 1,000 mg/kg/day of test material. The systemic toxicity NOAEL is 200 mg/kg/day , and the systemic toxicity LOAEL is 1000 mg/kg/day based on necrosis of thymic lymphocytes. The dermal toxicity NOAEL is 1000 mg/kg/day; the LOAEL could not be determined for dermal toxicity.

c. Developmental Toxicity

The database for developmental toxicity was considered complete in the 2007

RED and consists of three studies (MRID 41063701, 41063702 and 42986803). In one study (MRID 42986803), Copper 8-qui nolinolate (98.5% a.i.) in 0.5% aqueous carboxymethyl-cellulose was admin istered via oral gavage to mated

female Fu-Albino rats at dose levels of 0, 50, 200, or 800 mg/kg/day from gestation day (GD) 6 to 15 inclusive. Maternal toxicity was noted at 800 mg/kg/day (clinical toxicity, decreased body weight gain). No developmental toxicity was noted at any dose level tested in this study. The maternal toxicity NOAEL is 200 mg/kg/day and the LOAEL is 800 mg/kg/day. The developmental

4toxici ty NOAEL is 800 mg/kg/day and the developmental toxicity LOAEL is >800 mg/kg/day.

In a range-finding developmental toxi city study (MRID 41063701), Copper 8- hydroxyquinolate was adminis tered orally to 5 timed-mated female New Zealand White rabbits per dose at dose levels of 0, 7, 18, or 45 mg/kg bw/day from days 6 through 18 of gestation. In a concurrent study, two groups of five nonmated

female New Zealand White rabbits were or ally dosed using the following scheme: began at 5 mg/kg/day and was increased ev ery 5 days to 10 mg/kg/day (days 6- 10), 20 mg/kg/day (days 11-15), and 40 mg/k g/day (days 16-20). The maternal LOAEL in the first study was determined to be 45 mg/kg/day based on clinical signs of toxicity, reduced body weight and body weight gain, and reduced food consumption. The maternal NOAEL was determined to be 7 mg/kg/day. In the nonmated female study, the LOAEL was 40 mg/kg/day based on clinical signs of toxicity, reduced body weight and body weight gain, and reduced food consumption. In non-mated females, the NOAEL was 20 mg/kg/day. There

were no treatment-related effects obser ved in developmental parameters.

In a developmental toxicity study (MR ID 41063702), Copper 8-hydroxyquinolate (96.5% a.i., lot 382) was administered to 64 New Zealand White rabbits by gavage at dose levels of 0, 7, 15, or 30 mg/kg/day from days 7 through 19 of gestation (i.e., GD 7-19). In this study, a maternal LOAEL was not established. The Maternal NOAEL was 30 mg/kg/day (highest dose tested). There was no evidence of developmental toxicity in this study.

d. Reproductive Toxicity

In a 2-generation reproductive toxi city study (MRID 43267202), Copper 8- quinolinolate was administer ed to Cr1 CD rats, 32/sex/ dose for the F0 generation and 28/sex/dose for the F1 generat ion, in the diet at conc entrations of 0, 25, 250, or 2500 ppm. In the F0 generatio n, actual doses were equivalent to: 0, 1.8, 8.2, and 181 mg/kg/day for males and 0, 2, 20.8, and 203 mg/kg/day for females. In the F1 generation, actual doses were equivalent to: 0, 2, 19.8 and 196 mg/kg/day for males and 0, 2.2, 22.8 and 218 mg/kg/day for females. The parental (systemic) toxicity NOAEL was determined to be 250 ppm (about 20 mg/kg/day) and the LOAEL 2500 ppm (about 200 mg/kg/day) based on increased liver weight in F1 males. Alt hough the liver toxicity occurred only in F1 males, this effect is expected to be real since the liver was reported as a target organ in a rat subchronic feeding study (MRID No. 42986801) and in a mouse carcinogenicity study (MRI D No. 43267201). No signi ficant compound-related effects were noted in the pregnancy rate, pre-coital time, duration of pregnancy, and implantation sites/litter for rats fed Copper 8-quinolinolate for two successive generations. The reproductive toxicity NOAEL was determined to be 250 ppm and the reproductive toxicity LOAEL was determined to be 2500 ppm based on decreased mean number of live pups at birt h (87% of controls; p<0.05) and at day 4 pre-cull (85% of cont rols; p<0.01) and decreased litter weights observed at day 0 and during lactation in the F1 generation.

5e. Chronic Toxicity

In a chronic toxicity study in the dog, (MRID 00099606), Copper 8-quinolinolate (96%) was administered to f our Beagle dogs/dose/ sex at dose levels of 0, 10, 40, 200, or 1000 ppm (equivalent to 0, 0.2, 1.30, 6.49, or 32.98 mg/kg/day for males, and 0, 0.30, 1.12, 7.29, or 30.67 mg/kg/day for female s, respectively) for 104 weeks. A fifth treatment group initially receiving concentrations of 4000 ppm (3000 ppm from weeks 10-104) was also used. The LOAEL is 1000 ppm (32.98 and 30.67 mg/kg/day for males and females, respectively) based on changes in liver enzymes, total blood albumin, body weight, body weight gain, and food consumption. The NOAEL is 200 ppm (6.49 and 7.29 mg/kg for males and females, respectively). This study was classified Unacceptable-Nonguideline.

f. Carcinogenicity

The database for carcinogenicity consists of three submitted studies (MRID 00083777, 42957801 and 43267201) for copper 8- quinolinolate and two studies on 8-hydroxyquinolone conducted by t he National Toxicology program (NTP, 1985). In a carcinogenicity study (MRID 00083777), Copper-8-quinolinolate (96%) was orally administered to 180 male rats and 180 female rats (30 animals/ sex/group) via dietary mixtur e. The nominal doses received were 0, 5, 20, 100, 500, and 2000 ppm. Estimates of compound in take were 0, 2, 8, 38, 188, and 761 mg/kg/day for males and 0, 2, 9, 46, 229, and 922 mg/kg/day for females. Five animals/sex/group were sacrificed at 52 weeks and all surviving rats were sacrificed at 102 weeks via exsangui nation under sodium pentobarbital

anesthesia. Interstitial tumo rs of the testes, two unilateral and one bilateral, were observed in three males dosed at 761 mg/kg/ day but this rate is consistent with

historical data for rats of this age in the laboratory. The incidence of neoplasia was considered comparable between cont rol and treated animals. The LOAEL was determined to be 2000 ppm (about 761 mg/kg/day for males and 922 mg/kg/day for females) based on incr eased incidence of pigment deposition observed in the spleens and small intesti nes of males and females at 52 weeks;

and increased incidence of hemosiderin deposition in the spleens, small intestines, livers, and kidneys of males and females at 102 weeks). The NOAEL is 500 ppm (188 mg/kg/day for male s and 229 mg/kg/day for females).

A supplementary study (MRID 42957801) ut ilized 42 day old male and female Crl:CD-1 (ICR)BR strain (VAF plus) mice (10/sex/group) and exposed them orally to concentrations of 0, 300, 1000, 3000, or 6000 ppm in the diet for 13 weeks.

There were no deaths attributable to tr eatment with copper 8- quinolinolate. No

treatment –related increase in the inci dence of epithelial hyperplasia of the glandular mucosa of the st omach was seen in either sex compared to controls. Follicular cysts were seen in 2/10, 1/10, and 3/10 female mice at 300, 3000, and 6000 ppm, respectively. 1000 ppm was considered to be the NOAEL in this study. A dose below 1000 ppm was recommended for the low dose level for a long-term study to represent a low mult iple of the expected human exposure level. This study was conducted as a range-finding study and does not satisfy a guideline requirement.

6In a carcinogenici ty study (MRID# 43267201), Cr1:CD-1 mice (50/sex/dose group) received copper 8-quino linolate (97.2% a.i.; Lot# 777) in the diet for 80 weeks at dose levels of 0, 100, 400, 1500 and 6000 ppm. (0, 14. 49, 57.15, 207.7, and 855.8 mg/kg/day for males; and 0, 16.3, 66.18, 246.2 and 1051.7 mg/kg/day for females). A satellite group of ten animals/sex/dose group were sacrificed at

12 months. There was no treatment-relat ed difference in the overall tumor incidence (22 and 23 for control and high dose animals, respectively) seen in

male mice. More variation was seen in the tumor incidence in females with different dose levels; however, the tumor incidence tended to be higher at 1500 and 6000 ppm (18, 28, 26 for the c ontrol, 1500 and 6000 ppm groups, respectively) although there was no cl ear dose effect. The incidence of lymphomas in female mice at 1500 ppm was higher than expected from historic controls (2/50-11/50) with no dose effect and the high dose resulting in no

increase over the control incidence. Ot her tumor occurrences were within the range of spontaneous incidenc es for the tumor types and the age and strain of mice. The systemic toxicity LOAEL was determined to be 1500 ppm (207.7 mg/kg/day males, 246.2 mg/kg/day in fe males), based on an increased incidence of stomach ulcers in males; and mild anemia and adverse lever effects including

increased incidence of abnormal liver coloration and increased alkaline phosphatase activity in females. The syst emic toxicity NOAEL is 400 ppm (57.1 mg/kg/day in males, 66.2 mg/kg/day).

g. Mutagenicity

The database for mutagenicty was cons idered adequate in the 2007 RED with three studies (MRID 429623-01, 429623- 02, 429623-03). One gene mutation study (MRID 429623-01) concluded that ther e was a weak positive response for reverse gene mutation in S9-activated bacterial strains TA97, TA100, TA102 of S. typhimurium exposed to toxic doses. An in vivo mammalian cytogenetics study (MRID 429623-02) showed negative results fo r micronucleus induction in bone

marrow cells of mice treated once at dos es up to 7500 mg/kg, (non-toxic but limiting dose). A third study (MRI D 429623-03) reported negative results for induction of unscheduled DNA synthesis in primary rat hepatocyte cultures

isolated from male rats that were treat ed orally up to 3000 mg/kg, as determined by radioactive tracer procedures [nuclear silver grain counts].

h. Neurotoxicity

The database for neurotoxicity consists of three studies (MRID not assigned). One study used the accelerating rotarod test to assess the effects of oral administration of Copper 8- quinolinolate at doses of 100, 300 and 1000 mg/kg on

motor coordination in mice. There was little or no effect on performance on the accelerating rotarod. A second study examined for possible neurological effects of oral doses at 100, 300 and 1000 mg/kg using the tilting plate test. This study

used 20 male and 20 female Wistar rats . Male animals exhibited small decreases in mean angle of slip when co mpared to the vehicl e-treated control group. Little or no such effect was obser ved in females treated at 1000 mg/kg. The effect on bodyweight gain observed over days 4-8 was less severe in females (4.2-6.5% inhibition) than observ ed in males (9.2-14.8% ). A third study

7examined the effects of oral administr ation of the above mentioned-doses on

hexobarbita l-induced sleeping time in mice. No statistically significant effect on hexobarbital-induced sleeping time was noted at the doses tested in the study.

i. Rat Metabolism

The database for metabolism consis ts of two studies (MRID 42962304, 42962305). These metabolism studies in ma le and female Wistar rats dosed the

animals with 14 C-labeled Copper 8-qui nolinolate at oral doses of 30 or 1000 mg/kg and at repeated oral doses (14 daily doses) of unlabeled Copper 8- quinolinolate at 30 mg/kg followed by admin istration of a single oral dose of 14 Clabeled Copper 8-quinolinolate at 30 mg/kg. Major routes of excretion were urine (62-86%) and feces (8-26%) over a 4-7 day period. Most (54-59%) of the compound was excreted in urine and feces wit hin 48 hours of dosing. Saturation of absorption following high dose was i ndicated by large amounts (23%) of radioactivity in the feces. Radioactivit y in tissue residues was very low in all tissues including blood (<0.05%). T he potential for bioaccumulation was considered to be minimal even after high dose or low dose (single or repeated) exposures. In urine, r adioactivity was associated with the parent (5 to 16% of dose), sulfate (12 to 18%) and glucuroni de conjugates (36 to 66%) of the parent

while in the feces it was associated with the parent (4 to 23% of the dose) and the glucuronide conjugat e of the parent (0.1 to 4%). Expired CO 2 accounted for

0.4-2.2% of the administered dose and less than 8% was excreted via bile, mainly as a glucuronide conjugate.

j. Toxicology Data Needs

The Copper 8-quinolinolate toxicology database is considered adequate for registration review although the 90-day inhal ation toxicity study called in via the
6/8/10 DCI associated with t he 2007 RED will permit significant refinement of risk estimates associated with applicator and postapplication exposure via the

inhalation route as a number of use sc enarios will result in the generation of

aerosols and contam inated sawdust.

Section 3. Dietary Exposure

a. Food Exposure

Dietary exposure and risk were asse ssed in the 2007 RED for Copper-8- quinolinolate for its uses in pulp/paper and adhesives. For the determination of the amount of a pesticide migrating into food when the food is in contact with the treated paper or adhesives, FDA methodolog y was utilized. It was concluded that there are no chronic dietary risks of Agency concern to adults or children due to migration of Copper-8-quinolinolate from paper or adhesives into food. Copper 8-quinolinolate does not cause adver se systemic effects resulting from a single dose; therefor e, there is no basis for the Agency to assess acute dietary

risk.

8Another scenario that may pose dietary risk concern is the use of Copper-8- quinolinolate-treated w ood products to st ore or transport foods. These may include beehives, mushroom trays, fruit and vegetable crates, et c. No data were available to estimate migration from treated wood into food. The lack of a treated-wood migration study was, therefore, determine d to be a data gap in the 2007 RED and the study was included in a DCI dated June 8, 2010.

b. Drinking Water Exposure

A number of the registered uses of Copper 8-quinolin olate could result in

contamination of surface water and groundwater because the compound is expected to gradually transfer/leach from dried paint and coati ng films, treated outdoor surfaces, impregnated materials such as textiles and wood products (including pressure-treated), and from any treated porous or nonporous surface. Also, wastewater containing residues may be discharged from facilities manufacturing paper/paperboard, lumber and wood produc ts, textiles, paints, coatings, building materials, etc. formulated with Copper 8-quinolinolate. Therefore, there is the potential for human exposur e to Copper 8-quinolinolate residues in drinking water to occur. However, the need for a drinking water exposure assessment will be revisit ed upon submission and review of the environmental fate data (wood leaching stud y) the Agency required in the 6/8/10

DCI in association with the 2007 RED.

Section 4. Residential Exposure

Residential handler dermal and inhalation (aerosols) exposure scenarios were determined in the 2007 RED to be best repr esented by short-term (ST) durations of exposure including wood preservative coatings/water repellents (applied via brush/roller and low-pressure coarse spray) and application of manufactured paint products (using paint brush/roller and airless sprayer) preserved in-can with Copper 8-quinolinolate. The calculat ed ST Margins of Exposure (MOEs) were above the target dermal MOE for all sc enarios and were, ther efore, not of Agency concern. The high-end scenario (use of an airless sprayer) had an
associated ST inhalation MO E well below the target and was thus of Agency concern. Confirmatory inhalation toxicity data (90-day rat study) were required in

the 6/8/10 RED DCI to address this.

Representative residential postapplicati on scenarios were assessed in the 2007

RED for child contact with surface re sidues of Copper 8-quinolinolate from treated wood (dermal and inci dental oral exposure) and residues remaining on treated outdoor hard surfaces (dermal and incidental oral exposure to children). Postapplication exposures in residential se ttings are assumed to be episodic, as opposed to daily, and to occur over a ST duration (1 to 30 days). The Agency has determined that the use patterns for C opper 8-quinolinolate wi ll not result in any intermediate-term (IT) or long-term (LT) residential exposures and, hence, these exposure durations were not assessed.

9In the case of treated out door surfaces, the ST dermal MOE was well above the target MOE and, therefore, not of concern. The ST incidental oral exposu re MOE was far above the target MOE and was also not of concern. When adults contact treated textiles, de rmal exposure was estimated to result in risks below the target MOE, indicating a risk of potential Agency concern.

In addition to the above-mentioned postappl ication exposure scenarios, certain Copper 8-quinolinolate end-use products ar e labeled for wood preservative uses in pressure and nonpressure treatments of wood products intended for residential applications. The Agency is, therefore, concerned that there is potential postapplication exposure of indi viduals to wood treated with Copper 8- quinolinolate in residential settings ( home and farm). Consequently, dermal contact with wood products and inhal ation of wood dust scenarios were considered for children. Adult scenarios included dermal, incidental oral, and inhalation exposure to wood dust gener ated during construction of decks and playsets. Currently, there are no data ava ilable to estimate inhalation exposure to wood dust during construction of wood decks or children’s exposure to treated wood. Incidental ingestion exposure of adults is expected to be negligible and dermal contact by adults is expected to be lower than children crawling on wood decks. In the 2007 assessment, incidental ingestion and dermal exposures to

children from contact with treated wood were estimated using surrogate data.

For outdoor residential dermal contact wit h Copper 8-quinolin olate-treated wood products, the dermal MOEs for toddlers we re greater than the target MOE and, therefore, not of concern. For outdoor residential hand-to-mouth contact with Copper 8-quinolinolate-tr eated wood products, the estimated ST MOEs were above the target MOE and, theref ore, were not of concern.

Section 5. Aggregate Risk

Aggregate human exposure associated wit h the currently-registered Copper 8- quinolinolate uses is expected to be comprised of dietary and residential exposure and, possibly, drinking water exposure. However, the need for a drinking water exposure assessment (and inclusion in an aggregate assessment) will be determined upon submi ssion and review of the environmental fate data (wood leaching study) the Agency required in the 6/8/10 DCI in association with

the 2007 RED.

Section 6. Occupational Exposure

a. Occupational Handlers

Potential occupational handler exposure can occur in various use sites including food handling premises, commercial/industrial premises, and even applications done in residential sites. For handlers, t he representative uses assessed in the 2007 RED included various materials pr eservative and wood preservative applications: mixing and loading of product concentrate s for materials

10preservative incorporation into textile/ paint/paper matrices (liquid pour/liquid pump of soluble concentrates); application of treated paint (paint brush/roller and airless sprayer) and protective wood c oatings (low pressure sprayer); and applications to outdoor hard surfaces for mold remediation (brush/roller and low pressure sprayer). Certain occupationa l handler scenarios were assessed to determine dermal and inhalation exposures. If application methods were similar across use patterns, then only those sc enarios with maximum applic ation rates were assessed as representative of potential exposure for the other handler

scenarios.

The calculated dermal MOEs for occupati onal handlers were all above the target MOE, i.e., not of Agency concern, wit h the use of the glove PPE. Baseline dermal estimates for workers without gloves indicated risk concerns for certain scenarios listed below. Baseline (unglov ed) dermal MOEs for the material preservation of paints, textiles, and paper were calculated using unit exposure values (liquid pour/liquid pump) from t he cooling tower Chemical Manufacturers Association (CMA) data set because dat a for baseline dermal unit exposures were not available for preservative sc enarios. The scenarios resulting in exposure estimates (MOEs) found to be of concern in the 2007 RED were as follows: general wood preservative br ush applications; painting (professional) wood coatings, low pressure sprayer; pai nting (professional) with treated paint, airless sprayer; paper preservation, liqui d pump; paint preservation, liquid pour; and textile preservation, liquid pour.

Most inhalation MOEs for occupationa l handlers were above the target MOE, except for the following scenarios, for wh ich a risk of concern was identified in the 2007 RED as indicated below: general wood preservative brush applications; paper preservation, liquid pump; and pai nting (professional) with treated paint, airless sprayer.

b. Occupational Postapplication

Postapplication exposures were consider ed to be negligible for all scenarios except the wood preserva tive scenarios assessed in the 2007 RED. Copper 8- quinolinolate is used in several wood pr eservative treatments as wood surface coatings (e.g., water repellents applied via brush, roller or spray) and for impregnation into wood using either nonpr essure (e.g., nonpressure dipping/ immersion) and pressure techniques (v acuum/empty-cell). The products can be used on many different types of wood incl uding: (i) green or fresh cut/debarked lumber, poles, posts, and timbers; (ii) m anufactured wood products such as logs (including for log home construction), plywood, and particle board (wood composites); (iii) dry lum ber; and (iv) finished wood products such as millwork, shingles, shakes, siding, plywood and stru ctural lumber. For wood preservation, the exposures were assessed as nonpre ssure and pressure treatment related scenarios. For the nonpressure treatm ent exposure, assessments were carried

out based on worker function as follows: (i) handler - blender/spray operators, chemical operators, dipt ank operators, vacuum chamber operators (pressure

11treatment) and (ii) postapplic ation - graders, trim sa w operators, millwrights, clean-up crews, and construction workers.

Dermal MOEs associated with all of the postapplication scenario s represented by those above were estimated to be greater than the target MOE for the ST and IT durations, i.e., not of Agency concern. The inhalation MOEs associated with most postapplication scenarios were great er than the Agency’s target MOE (and, hence, not of concern) except for thos e resulting from the activities of blender/spray operators. It is the inhalation risk from this scenario that triggered the need for a 90-day rat inhalation toxicity study in the 6/8/10 DCI associated

with the 2007 RED. Note that it was also determined in the RED that insufficient data existed to estimate the magn itude of dermal and sawdust inhalation exposure of construction workers inst alling treated wood, particularly workers using a trim saw.

Section 7. Cumulative Risk

EPA does not have, at this time, availabl e data to determine whether Copper 8- quinolinolate has a common mechanism of to xicity with other substances or how to include this pesticide in a cumulative risk assessment. At this stage of this Registration Review, EPA has assumed that Copper 8-quinolinolate does not have a common mechanism of toxicity with other substances. During the risk assessment stage, however, the Agency wi ll address the possibility that Copper 8-quinolinolate shares a co mmon mechanism of toxicity with other substances.

Section 8. Endocrine Disruption

As required under FFDCA section 408( p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or

other such endocrine effects as the Admi nistrator may designate.” The EDSP employs a two-tiered approach to making t he statutorily requi red determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will det ermine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine related effects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T

effect.

Between October 2009 and February 2010, EPA i ssued test orders/data call-ins for the first group of 67 chem icals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was selected based on the

12potential for human exposure through pat hways such as food and water, residential activity, and certain post-applicat ion agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors.

Copper 8-quinolinolate is not among the group of 58 pesticide active ingredients

on the initial list to be screened under t he EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemical s. Accordingly, EPA anticipates issuing future EDSP test orders/data call-in s for all pesticide active ingredients.

For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and t he Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/.

Section 9. Human Incident Data

A small number of inci dents (eight) have been repor ted that have a likely association with exposure to end-us e products containing Copper 8- quinolinolate. These occurred in CA between 1982 and 2004. The skin and eyes are the primary routes of exposure and the resulting symptom is irritation. No severe incidents are been report ed as being associated with Copper 8- quinolinolate exposure.

Section 10. Over all Conclusions

The registered uses of C opper 8-quinolinolate are likel y to result in risks of

concern in certain residential and occ upational scenarios. Aggregate exposure associated with the currently -registered Copper 8-quinoli nolate uses is expected to be comprised of dietary and residentia l exposure and, possibly, drinking water exposure. However, the need for a drin king water exposure assessment (and inclusion in an aggregate assessment) will be determined upon submission and

review of the environmental fate data (wood leaching study) the Agency required
in the 6/8/10 DCI in association with the 2007 RED.

Data Needs

In association with the 2007 Copper 8- quinolinolate RED, a 6/8/10 DCI was issued that called in a 90-day rat inhalat ion toxicity study, wood leaching study, honey/beeswax residue study, and severa l handler and postapplication exposure

studies to estimate dermal and inhal ation exposures to homeowners and occupational workers. It is a conclusion of this Human Health Scoping Document

to reiterate that the st udies required in the 6/8/10 DCI are needed to refine assessments completed in the RED and to permit completion of those assessments for which adequate data were not available. Should the Agency

determine at a later date that it needs addi tional data on this active ingredient or on any of its degradates about which the Agency may have concern, the Agency will require such data.

1314 Risk Assessments Needed

 A dietary (food) exposure assessment is expected to be needed to estimate any dietary risks result ing from migrat ion of Copper 8- quinolinolate residues from treated wood (trays, beehives, etc.) to raw agricultural commodities includin g fruits, vegetables, mushrooms, honey, and beeswax.

 A dietary (drinking water) expos ure assessment may be needed to estimate any risk associated with leaching of Copper 8-quinolinolate residues into water from preserve d building materials, treated wood, industry discharges, etc. However, the need for a drinking water exposure assessment will be dete rmined upon submission and review of the environmental fate data (wood leaching study) the Agency required in the 6/8/ 10 DCI in association with the 2007 RED.

 Assessment of residential handle r and postapplication (adult and toddler) risks reflecting receipt of t he 90-day inhalation toxicity study, wood leaching study, and dermal and inhalation exposure studies submitted in response to the 6/8/10 DCI.

 Residential and dietary (and possibly drinking water) sources of exposure will need to be combin ed to estimate aggregate risks.

 Occupational handler and postapplication risks will need assessment reflecting receipt of the 90-day inhal ation toxicity study, wood leaching study, and dermal and inhalation ex posure studies submitted in response to the 6/8/10 DCI.

Recommended Label Changes

None.