9/13/10 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

MEMORANDUM 

SUBJECT: 

FROM: 

TO: 

THRU: 

Introduction 

Copper 8-quinolinolate. Human Health Effects Scoping 

Document for the Registration 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) /V"?/l _~" r? C2.. 

Nader Elkassabany, Ph.D., Chief -I l(.A. a~, ~ 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 antimicrobial pesticide to prevent the 

growth of algae, bacteria, and fungi inIon textiles, wood products, paper, 

adhesives, 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 materially affect the overall risk picture. 

Copper 8-quinolinolate was first registered 9/9/94. A Reregistration Eligibility 

Decision (RED) was issued for Copper 8-quinolinolate September, 2007. A 

Generic Data Call-in associated with the RED was issued June 8, 2010 requiring 

submission of studies to characterize inhalation toxicity, leaching of residues 

from treated wood, residues in honey, applicator exposure and postapplication 

exposure. Consequently, no additional 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 intended for the treatment of webbing, 
tenting, rope, canvas, leather, industrial cotton, industrial fabrics and clothing for 

industrial and government (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 wood to be used as beams for indoor use, 

mushroom trays, produce picking trays/containers that may contain fruit (indirect 

food contact use), interior boat applications, wood used in greenhouse premises, 

equipment and containers, log 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 used to treat textiles, cement, pulp and 

paper ingredients, paper, wood products, paint, polymeric plastics, adhesives, 

and glue. James Hardie Building Products, Inc. has registered a 98% MP (EPA 

Reg. No. 83515-1) labeled to formulate 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 treat 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 commercial sites may also be dipped into a 1% 

ai solution, brushed with a 3.3% ai solution (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, spray, 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 impregnated for government use with Copper 8-

quinolinolate by brushing, spraying, or dipping 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 CFR 175.105(c) for use in food contact 

adhesives as a preservative; 21 CFR 176.170 for use of Copper 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. 

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The primary source of information for this Human Health Scoping Document was 

the Reregistration Eligibility Decision (RED) of 2007 and its associated 

references and sources as per the Docket EPA-HQ-OPP-2007-0556. The 

purpose of this document is to determine whether sufficient data are available to 

support registration review and whether 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 C18H12CuN2O2

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, olive 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 KO/W) of 2.5 at 25 °C. Copper 8-

quinolinolate degrades above the melting point 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 hydrolysis (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 continue although the 90-day inhalation toxicity 

study called in via the 6/8/10 DCI associated with the 2007 RED will permit 

significant refinement of risk estimates associated with applicator and 

postapplication exposure via the inhalation route as a number of use scenarios 

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

studies currently available. 

a. Acute Toxicity 

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 (Toxicity Category IV). It is somewhat toxic via the dermal 

route of exposure (Toxicity Category III) whereas exposure via the inhalation 

route induces moderate toxicity (Toxicity Category II). Copper 8-quinolinolate is 

classified as corrosive to the eye (Toxicity 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 were submitted to the Agency. Three of 

the five studies were considered acceptable in the 2007 RED (MRIDs 42986801, 

42986802, 42957802). The other 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 females, respectively) for 13 weeks. The 

NOAEL was determined to be 5 mg/kg/day (males/females), based on vomiting, 

reduced total plasma protein and albumin, reddened mucosa and hyperemia in 

stomach and/or small intestine observed at the LOAEL of 50 mg/kg/day. 

In a 28-day dermal toxicity study (MRID 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 increased incidence of necrosis 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-quinolinolate (98.5% a.i.) in 0.5% 

aqueous carboxymethyl-cellulose was administered 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 

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toxicity NOAEL is 800 mg/kg/day and the developmental toxicity LOAEL is >800 

mg/kg/day. 

In a range-finding developmental toxicity study (MRID 41063701), Copper 8-

hydroxyquinolate was administered 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 orally dosed using the following scheme: 

began at 5 mg/kg/day and was increased every 5 days to 10 mg/kg/day (days 6-

10), 20 mg/kg/day (days 11-15), and 40 mg/kg/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 observed in developmental parameters. 

In a developmental toxicity study (MRID 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 toxicity study (MRID 43267202), Copper 8-

quinolinolate was administered to Cr1 CD rats, 32/sex/dose for the F0 generation 

and 28/sex/dose for the F1 generation, in the diet at concentrations of 0, 25, 250, 

or 2500 ppm. In the F0 generation, 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. Although 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 (MRID No. 43267201). No significant 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 birth (87% of controls; p<0.05) and at 

day 4 pre-cull (85% of controls; p<0.01) and decreased litter weights observed at 

day 0 and during lactation in the F1 generation. 

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e. Chronic Toxicity 

In a chronic toxicity study in the dog, (MRID 00099606), Copper 8-quinolinolate 

(96%) was administered to four 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 females, 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 the 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 mixture. The nominal doses received were 0, 5, 20, 100, 

500, and 2000 ppm. Estimates of compound intake 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 exsanguination under sodium pentobarbital 

anesthesia. Interstitial tumors 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 control 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 increased incidence of pigment deposition 

observed in the spleens and small intestines 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 males and 229 mg/kg/day for females). 

A supplementary study (MRID 42957801) utilized 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 treatment with copper 8-quinolinolate. No 

treatment –related increase in the incidence of epithelial hyperplasia of the 

glandular mucosa of the stomach 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 multiple of the expected human exposure 

level. This study was conducted as a range-finding study and does not satisfy a 

guideline requirement. 

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In a carcinogenicity study (MRID# 43267201), Cr1:CD-1 mice (50/sex/dose 

group) received copper 8-quinolinolate (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-related 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 control, 1500 and 6000 ppm groups, 

respectively) although there was no clear 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. Other tumor occurrences were within the 

range of spontaneous incidences 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 females), 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 systemic toxicity NOAEL is 400 ppm (57.1 

mg/kg/day in males, 66.2 mg/kg/day). 

g. Mutagenicity 

The database for mutagenicty was considered adequate in the 2007 RED with 

three studies (MRID 429623-01, 429623-02, 429623-03). One gene mutation 

study (MRID 429623-01) concluded that there 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 for micronucleus induction in bone 

marrow cells of mice treated once at doses up to 7500 mg/kg, (non-toxic but 

limiting dose). A third study (MRID 429623-03) reported negative results for 

induction of unscheduled DNA synthesis in primary rat hepatocyte cultures 

isolated from male rats that were treated 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 compared to the vehicle-treated control 

group. Little or no such effect was observed 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 observed in males (9.2-14.8%). A third study 

7
examined the effects of oral administration of the above mentioned-doses on 

hexobarbital-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 consists of two studies (MRID 42962304, 

42962305). These metabolism studies in male and female Wistar rats dosed the 

animals with 14C-labeled Copper 8-quinolinolate 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 administration of a single oral dose of 14Clabeled 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 within 48 hours of dosing. Saturation 

of absorption following high dose was indicated by large amounts (23%) of 

radioactivity in the feces. Radioactivity in tissue residues was very low in all 

tissues including blood (<0.05%). The potential for bioaccumulation was 

considered to be minimal even after high dose or low dose (single or repeated) 

exposures. In urine, radioactivity was associated with the parent (5 to 16% of 

dose), sulfate (12 to 18%) and glucuronide 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 conjugate of the parent (0.1 to 4%). Expired CO2 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 inhalation toxicity study called in via the 

6/8/10 DCI associated with the 2007 RED will permit significant refinement of risk 

estimates associated with applicator and postapplication exposure via the 

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

aerosols and contaminated sawdust. 

Section 3. Dietary Exposure 

a. Food Exposure 

Dietary exposure and risk were assessed 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 methodology 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 adverse systemic effects resulting from a 

single dose; therefore, there is no basis for the Agency to assess acute dietary 

risk. 

8
Another scenario that may pose dietary risk concern is the use of Copper-8-

quinolinolate-treated wood products to store or transport foods. These may 

include beehives, mushroom trays, fruit and vegetable crates, etc. No data were 

available to estimate migration from treated wood into food. The lack of a 

treated-wood migration study was, therefore, determined 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-quinolinolate could result in 

contamination of surface water and groundwater because the compound is 

expected to gradually transfer/leach from dried paint and coating 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 products, textiles, paints, 

coatings, building materials, etc. formulated with Copper 8-quinolinolate. 

Therefore, there is the potential for human exposure to Copper 8-quinolinolate 

residues in drinking water to occur. However, the need for a drinking water 

exposure assessment will be revisited 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. 

Section 4. Residential Exposure

Residential handler dermal and inhalation (aerosols) exposure scenarios were 

determined in the 2007 RED to be best represented 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 calculated ST Margins of Exposure (MOEs) were 

above the target dermal MOE for all scenarios and were, therefore, not of 

Agency concern. The high-end scenario (use of an airless sprayer) had an 

associated ST inhalation MOE 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 postapplication scenarios were assessed in the 2007 

RED for child contact with surface residues of Copper 8-quinolinolate from 

treated wood (dermal and incidental oral exposure) and residues remaining on 

treated outdoor hard surfaces (dermal and incidental oral exposure to children). 

Postapplication exposures in residential settings 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 Copper 8-quinolinolate will not result in 

any intermediate-term (IT) or long-term (LT) residential exposures and, hence, 

these exposure durations were not assessed. 

9
In the case of treated outdoor surfaces, the ST dermal MOE was well above the 

target MOE and, therefore, not of concern. The ST incidental oral exposure 

MOE was far above the target MOE and was also not of concern. When adults 

contact treated textiles, dermal exposure was estimated to result in risks below 

the target MOE, indicating a risk of potential Agency concern. 

In addition to the above-mentioned postapplication exposure scenarios, certain 

Copper 8-quinolinolate end-use products are 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 individuals to wood treated with Copper 8-

quinolinolate in residential settings (home and farm). Consequently, dermal 

contact with wood products and inhalation of wood dust scenarios were 

considered for children. Adult scenarios included dermal, incidental oral, and 

inhalation exposure to wood dust generated during construction of decks and 

playsets. Currently, there are no data available 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 with Copper 8-quinolinolate-treated wood 

products, the dermal MOEs for toddlers were greater than the target MOE and, 

therefore, not of concern. For outdoor residential hand-to-mouth contact with 

Copper 8-quinolinolate-treated wood products, the estimated ST MOEs were 

above the target MOE and, therefore, were not of concern. 

Section 5. Aggregate Risk 

Aggregate human exposure associated with 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 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. 

 

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, the representative uses assessed in the 

2007 RED included various materials preservative and wood preservative 

applications: mixing and loading of product concentrates for materials 

10
preservative 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 coatings (low pressure sprayer); and 

applications to outdoor hard surfaces for mold remediation (brush/roller and low 

pressure sprayer). Certain occupational handler scenarios were assessed to 

determine dermal and inhalation exposures. If application methods were similar 

across use patterns, then only those scenarios with maximum application rates 

were assessed as representative of potential exposure for the other handler 

scenarios. 

The calculated dermal MOEs for occupational handlers were all above the target 

MOE, i.e., not of Agency concern, with the use of the glove PPE. Baseline 

dermal estimates for workers without gloves indicated risk concerns for certain 

scenarios listed below. Baseline (ungloved) dermal MOEs for the material 

preservation of paints, textiles, and paper were calculated using unit exposure 

values (liquid pour/liquid pump) from the cooling tower Chemical Manufacturers 

Association (CMA) data set because data for baseline dermal unit exposures 

were not available for preservative scenarios. The scenarios resulting in 

exposure estimates (MOEs) found to be of concern in the 2007 RED were as 

follows: general wood preservative brush applications; painting (professional) 

wood coatings, low pressure sprayer; painting (professional) with treated paint, 

airless sprayer; paper preservation, liquid pump; paint preservation, liquid pour; 

and textile preservation, liquid pour. 

Most inhalation MOEs for occupational handlers were above the target MOE, 

except for the following scenarios, for which a risk of concern was identified in 

the 2007 RED as indicated below: general wood preservative brush applications; 

paper preservation, liquid pump; and painting (professional) with treated paint, 

airless sprayer. 

b. Occupational Postapplication 

Postapplication exposures were considered to be negligible for all scenarios 

except the wood preservative scenarios assessed in the 2007 RED. Copper 8-

quinolinolate is used in several wood preservative treatments as wood surface 

coatings (e.g., water repellents applied via brush, roller or spray) and for 

impregnation into wood using either nonpressure (e.g., nonpressure dipping/ 

immersion) and pressure techniques (vacuum/empty-cell). The products can be 

used on many different types of wood including: (i) green or fresh cut/debarked 

lumber, poles, posts, and timbers; (ii) manufactured wood products such as logs 

(including for log home construction), plywood, and particle board (wood 

composites); (iii) dry lumber; and (iv) finished wood products such as millwork, 

shingles, shakes, siding, plywood and structural lumber. For wood preservation, 

the exposures were assessed as nonpressure and pressure treatment related 

scenarios. For the nonpressure treatment exposure, assessments were carried 

out based on worker function as follows: (i) handler - blender/spray operators, 

chemical operators, diptank operators, vacuum chamber operators (pressure 

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treatment) and (ii) postapplication - graders, trim saw operators, millwrights, 

clean-up crews, and construction workers. 

Dermal MOEs associated with all of the postapplication scenarios 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 greater than the Agency’s target MOE (and, 

hence, not of concern) except for those 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 magnitude of dermal and sawdust inhalation 

exposure of construction workers installing treated wood, particularly workers 

using a trim saw. 

Section 7. Cumulative Risk 

EPA does not have, at this time, available data to determine whether Copper 8-

quinolinolate has a common mechanism of toxicity 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 will address the possibility that Copper 

8-quinolinolate shares a common 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 Administrator may designate.” The EDSP 

employs a two-tiered approach to making the statutorily required determinations. 

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

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

T) hormonal systems. Chemicals that go through Tier 1 screening and are found 

to have the potential to interact with E, A, or T hormonal systems will proceed to 

the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 

tests are necessary based on the available data. Tier 2 testing is designed to 

identify any adverse endocrine related effects caused by the substance, and 

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

effect. 

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

for the first group of 67 chemicals, which contains 58 pesticide active ingredients 

and 9 inert ingredients. This list of chemicals was selected based on the 

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potential for human exposure through pathways such as food and water, 

residential activity, and certain post-application agricultural scenarios. This list 

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

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

on the initial list to be screened under the EDSP. Under FFDCA sec. 408(p) the 

Agency must screen all pesticide chemicals. Accordingly, EPA anticipates 

issuing future EDSP test orders/data call-ins for all pesticide active ingredients. 

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

the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, 

please visit our website: http://www.epa.gov/endo/. 

Section 9. Human Incident Data 

A small number of incidents (eight) have been reported that have a likely 

association with exposure to end-use 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 reported as being associated with Copper 8-

quinolinolate exposure. 

Section 10. Overall Conclusions 

The registered uses of Copper 8-quinolinolate are likely to result in risks of 

concern in certain residential and occupational scenarios. Aggregate exposure 

associated with 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 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 inhalation toxicity study, wood leaching study, 

honey/beeswax residue study, and several handler and postapplication exposure 

studies to estimate dermal and inhalation exposures to homeowners and 

occupational workers. It is a conclusion of this Human Health Scoping Document 

to reiterate that the studies 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 additional data on this active ingredient or 

on any of its degradates about which the Agency may have concern, the Agency 

will require such data. 

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Risk Assessments Needed

 A dietary (food) exposure assessment is expected to be needed to 

estimate any dietary risks resulting from migration of Copper 8-

quinolinolate residues from treated wood (trays, beehives, etc.) to raw 

agricultural commodities including fruits, vegetables, mushrooms, 

honey, and beeswax. 

 A dietary (drinking water) exposure assessment may be needed to 

estimate any risk associated with leaching of Copper 8-quinolinolate 

residues into water from preserved building materials, treated wood, 

industry discharges, etc. However, the need for a drinking water 

exposure 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. 

 Assessment of residential handler and postapplication (adult and 

toddler) risks reflecting receipt of the 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 combined to estimate aggregate risks.

 Occupational handler and postapplication risks will need assessment 

reflecting receipt of the 90-day inhalation toxicity study, wood leaching 

study, and dermal and inhalation exposure studies submitted in 

response to the 6/8/10 DCI.

Recommended Label Changes 

None.