Document ID: EPA-HQ-OPP-2007-0556-0017
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-07-02T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, DC 20460

			OFFICE OF  PREVENTION, PESTICIDES,  AND TOXIC SUBSTANCES

 

MEMORANDUM:							September 18, 2007

Subject:	Revised Risk Assessment Chapter for Copper 8-Quinolinolate
(Oxine-Copper) in Support of the Reregistration Eligibility Decision
(RED) Document for the Copper Salts (RED Case 4026). 

To:	Kathryn Jakob, Chemical Review Manager

	Regulatory Management Branch II

Antimicrobials Division (7510P)

		

From: 		Timothy McMahon, PhD., Risk Assessor

	Senior Toxicologist

Antimicrobials Division (7510P)	 

 

DP Barcode: 	D336552

							CAS

Chemical Name:			PC Code:	Registry No.: 	Common Names:

Copper, bis(8-quinolinolato-N1,O8)-,	024002		10380-28-6	Copper
8-Quinolinolate;										Oxine-Copper; Oxine-Cu; 									Copper-8

Attached is the draft Preliminary Risk Assessment for Copper
8-Quinolinolate in support of the RED assessment for the Copper Salts
(RED Case 4026). 



Copper-8-quinolinolate

Risk Assessment 

DP Barcode (336552)

Office of Pesticides Program

Antimicrobials Division

U.S. Environmental Protection Agency

2777 South Crystal Drive

Arlington, VA 22202

Date: 

September 18, 2007

TABLE OF CONTENTS

1.0	EXECUTIVE
SUMMARY………………………………………………………
………………..3

2.0	PHYSICAL AND CHEMICAL
PROPERTIES………………………………………………..14

3.0	HAZARD
CHARACTERIZATION……………………………………….………
…………....14

   	 3.1	HAZARD
PROFILE………………………………………………………
……………..14

    	 3.2	FQPA
CONSIDERATIONS…………………………………………………
…………..15

   	 3.3	DOSE-RESPONSE
ASSESSMENT..............................................................
....................16

     	 3.4	ENDOCRINE
DISRUPTION……………………………………………………
……....18

.

4.0	EXPOSURE ASSESSMENT AND
CHARACTERIZATION………………………………........18

     	 4.1	SUMMARY OF REGISTERED
USES....................................................................
.........18

    	 4.2	DIETARY EXPOSURE AND
RISK....................................................................
.............29

     	 4.3	DRINKING WATER EXPOSURES AND
RISKS...................................................... ....31

    	 4.4	RESIDENTIAL EXPOSURES/RISK
PATHWAYS.........................................................31

5.0	AGGREGATE RISK ASSESSMENT AND
CHARACTERIZATION………………………32

	5.1	ACUTE AND DIETARY AGGREGATE
RISK...............................................................32

	5.2	SHORT AND INTERMEDIATE TERM AGGREGATE EXPOSURE AND RISKS.....33

6.0	CUMULATIVE EXPOSURE AND
RISK……………………………………………………...34

7.0	OCCUPATIONAL EXPOSURE
ASSESSMENT……………………………………………...34

     	 7.1	SUMMARY OF REGISTERED
USES....................................................................
........34

     	 7.2	OCCUPATIONAL HANDLER
EXPOSURES...............................................................
37

     	 7.3	OCCUPATIONAL POST-APPLICATION
EXPOSURES..............................................40

	 7.4	WOOD
PRESERVATION............................................................
....................................43

     	 7.5	DATA
LIMITATIONS/UNCERTAINTIES...............................................
......................52

8.0
ENVIRONMENTALRISKS.……………………………………………..
..................................53

    	 8.1	ECOLOGICAL
HAZARD..................................................................
..............................53

    	 8.2	ENVIRONMENTAL FATE
ASSESSMENT..............................................................
.....62

    	 8.3	ENVIRONMENTAL EXPOSURE AND ECOLOGICAL RISK
ASSESSMENT..........62

    	 8.4	ENDANGERED SPECIES
CONSIDERATIONS..........................................................
..63

	 8.5	DATA LIMITATIONS AND
UNCERTAINTIES...........................................................
64

9.0	INDCIDENT
REPORTS………………………………………………………
………………...65

10.0
REFERENCES..............................................................
.................................................................66

11.0	APPENDIX
A.……………………………………………………………
……………………....75

1.0	EXECUTIVE SUMMARY

Hazard Characterization

	Copper 8-quinolinolate is a greenish solid that is practically
insoluble in water and most organic solvents.   SEQ CHAPTER \h \r 1
Copper 8-quinolinolate is a fungicide, mildewcide and wood preservative
chemical.  In addition, Copper 8-quinolinolate is approved for use as a
wood preservative for control of sapstain, mold and decay in unfinished
wood and wood products such as millwork, siding, decks, outdoor
furniture, shingles, structural lumber, boats, decks and baseboards. 
Treated wood materials may be used in contact with fruit, vegetables and
other foodstuffs in an area such as greenhouses and greenhouse items,
produce picking boxes, mushroom trays and vegetables stakes. Copper
8-quinolinolate is also used as a disinfectant to control potato ring
rot in planters, seed handling equipment, seed cutters, storage areas
and transportation equipment.  Copper 8-quinolinolate is used in the
manufacturing of kraft paper, paperboard, adhesives, paints, and
textiles as a fungicide and mildewcide.  Copper 8-quinolinolate is
additionally used to control mold and mildew on industrial textiles such
as canvas, burlap, rope, leather and nets (non-aquatic uses only). 
Clearances exist in 21 CFR 176.170 and 21 CFR 178.3800 for the use of
copper 8-quinolinolate as a component of the food contact surface of
paper and paperboard (as a preservative for coating formulations) and as
a preservative on wooden articles that are used or intended for use in
packaging, transporting, or holding raw agricultural commodities.

The acute toxicity database for Copper 8-quinolinolate is complete.
Copper 8-quinolinolate has a low order of acute toxicity via the oral
route of exposure (Toxicity Category IV).  Copper 8-quinolinolate has a
moderate order of toxicity via the dermal route of exposure (Toxicity
Category III), whereas the inhalation exposure route produced a higher
order of exposure (Toxicity Category II).  Copper 8-quinolinolate is
classified as corrosive to the eye (Toxicity Category I).  For dermal
irritation, Copper 8-quinolinolate is a low irritant (Toxicity Category
IV).  Copper 8-quinolinolate is not a dermal sensitizer.

For subchronic toxicity, several studies were submitted to the Agency.
Three of the five studies were considered acceptable (MRIDs 42986801,
42986802, 42957802). The other two studies were supplementary (MRID
42937301) and range-finding (MRID 42957801) respectively.

  SEQ CHAPTER \h \r 1 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.

  SEQ CHAPTER \h \r 1 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.

The database for developmental toxicity is considered complete 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 carboxymethylcellulose 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 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),  K37
(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, K37 was also orally administered to two groups of 5 non-mated
female New Zealand White rabbits per dose using the following dose
scheme: dosing began at 5 mg/kg/day and was increased every 5 days to 10
mg/kg  (days 6-10), 20 mg/kg (days 11-15), and 40 mg/kg (days 16-20).  
The maternal LOAEL in the first study was determined to be 45 mg/kg
bw/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 bw/day.  In the non-mated female study, the
LOAEL was 40 mg/kg bw/day, based on clinical signs of toxicity, reduced
body weight and body weight gains, and reduced food consumption.  In
non-mated females, the NOAEL is 20 mg/kg bw/day. There were no
treatment-related effects observed in developmental parameters.  

	In a developmental toxicity study (MRID 41063702), K37 (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.  

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: 0,
1.8, 18.2, and 181 mg/kg/day for males and 0, 2, 20.8, and 203 mg/kg/day
for females; in the F1 generation: 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 and
the parental (systemic) toxicity LOAEL was determined to be 2500 ppm
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 rat subchronic feeding study
(MRID No. 42986801), and 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 oxine-copper 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 F1 generation.

In a chronic toxicity study in the dog, (MRID 00099606), Copper
8-quinolinolate (96%) was administered to 4 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.

The database for carcinogenicity consists of three submitted studies
(MRID 00083777, 42957801 and 43267201) for copper 8-quinolinolate and 2
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, 2 unilateral and 1 bilateral were observed in
three 2000 ppm males 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 (approximately 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 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 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. 

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 incidence 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).

The database for mutagenicty consists of three studies that are
considered adequate with three studies (MRID 42962301, 42962302,
42962303). One gene mutation study (MRID 42962301) concluded that there
was a weak positive response for reverse gene mutation in S9-activated
bacterial strains TA97, TA100, TA102 of S. typhimurium exposed unto
toxic doses. An in vivo mammalian cytogenetics study (MRID 42962302)
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 42962303) 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].

	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 co-ordination 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 examined the effects of oral administration at 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.

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 oxine copper at oral doses of 30 or 1000
mg/kg and at repeated oral doses (14 daily doses) of unlabeled oxine
copper at 30 mg/kg followed by administration of a single oral dose of
14C-labeled oxine copper 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 air as
CO2 accounted for 0.4-2.2% of the administered dose and less than 8% was
excreted via bile, mainly as glucuronide conjugate.

Dose-Response Assessment	

For acute dietary risk assessments, no appropriate endpoints were
identified that represent a single dose effect.  Hence this risk
assessment is not required. For chronic dietary risk assessments, a
NOAEL value of 5 mg/kg/day was selected, based on clinical signs of
toxicity (vomiting, decreased plasma protein and albumin, and reddened
mucosa and hyperemia in the stomach and small intestine) at a dose of 50
mg/kg/day in a subchronic toxicity study in the dog (MRID 42986802). An
uncertainty factor of 100 is assigned (10x inter-species extrapolation,
10x intra-species variation) and the hazard-based FQPA safety factor of
1 applied in this case. The resulting acute and chronic Reference Dose
value is 0.05 mg/kg/day. 

For short-term (1-30 days) and intermediate-term (30 days-6 months)
incidental oral risk assessments, a NOAEL of 200 mg/kg/day was selected,
based on clinical signs of toxicity and decreased body weight gain in
maternal rats, at a dose of 800 mg/kg/day in a prenatal developmental
toxicity study in the rat. An uncertainty factor of 100 is assigned (10x
inter-species extrapolation, 10x intra-species variation) and the
hazard-based FQPA safety factor of 1 applied in this case. 

For short-term (1-30 days) and (30 days-6 months) intermediate-term
dermal risk assessments, a NOAEL of 200 mg/kg/day was selected, based on
necrosis of thymic lymphocytes, at a dose of 1000 mg/kg/day. An
uncertainty factor of 100 (10x inter-species extrapolation, 10x
intra-species variation) was assigned to this endpoint. 

	For long-term (> 6months) dermal risk assessments no appropriate
endpoint was identified in the database for copper-8-quinolinolate.

For inhalation risk assessments, a NOAEL of 5 mg/kg/day was selected,
based on clinical signs of toxicity (vomiting, decreased plasma protein
and albumin, and reddened mucosa and hyperemia in the stomach and small
intestine), at a dose of 50 mg/kg/day in a subchronic toxicity in the
dog (MRID 42986802). An uncertainty factor of 1000 (10x inter-species
extrapolation, 10x intra-species variation, 10x route extrapolation) was
assigned to this endpoint. 

FQPA Considerations

There was no evidence for a primary developmental effect of oxine copper
in either the rat or rabbit developmental toxicity study. There was no
evidence of a primary reproductive effect of oxine copper in this study.
The ADTC concluded that the special hazard-based FQPA factor can be
reduced to 1x. The available developmental and reproductive toxicity
data for oxine copper show no evidence of teratogenicity or reproductive
toxicity. The studies are conducted according to guidelines and show no
evidence of increased susceptibility of offspring. There is no evidence
for neurotoxicity of oxine copper.  A developmental neurotoxicity study
for oxine copper is not needed at this time.

Dietary Exposure and Risk

Dietary exposure and risk were assessed 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, Food and Drug Administration (FDA) methodology
was utilized. A detailed explanation is found within the dietary risk
assessment chapter for copper-8-quinolinolate. It was concluded that
there are no chronic dietary concerns (% cPADadults = 0.3%, % cPADchild
= 0.9%) from the migration of Cu-8 from paper to food. No acute dietary
end points exist, and therefore, the Agency does not have any acute
exposure from the use of Cu-8 by migration into foods. Adhesive use was
treated as an indirect food use and assessed using FDA methodology. The
Agency has no chronic dietary concerns (% cPADadults = 0.6%, % cPADchild
= 1.4%) from the use of Copper-8 Quinoloate in adhesives. Another
scenario which may likely pose some concerns is the use of copper-8
treated wooden trays which are used to store or transfer foods. No data,
laboratory or monitoring, were submitted. It is therefore a data gap for
the dietary risk assessment for copper-8.

Drinking Water Exposure and Risk

Oxine-Copper is not used for potable water treatment, nor are effluents
containing this chemical expected in fresh water environments. Hence a
drinking water exposure assessment for copper-8-quinolinolate was not
conducted. 

Residential Handler Exposure and Risk

	Residential handler dermal and inhalation (aerosol particles) exposure
scenarios are best represented by short-term exposures that include
using wood preservative coatings/water repellents (applied via brush,
roller and low-pressure coarse spray) and application of manufactured
paint products containing Oxine-Copper as a preservative (paint
brush/roller and airless sprayer). The calculated short-term (ST)
Margins of Exposures (MOEs) were above the target dermal MOE of 100 for
all scenarios.  The high-end scenario developed for airless sprayer
yielded a ST inhalation MOE below the target of 1000, as 278, indicating
a potential risk concern. Confirmatory inhalation toxicity study data
may be required to address this. 

Residential Post-application Exposure and Risk

Representative post-application scenarios were assessed for child
contact with surface residues from oxine-copper treated wood (dermal and
incidental oral exposure) and residues remaining on treated outdoor hard
surfaces (dermal and incidental oral exposure to children).  Scenarios
were also developed for contact with residues on treated textiles such
as tents and tarps (dermal exposure to adults and children and
incidental oral exposure to children). Post-application exposures in
residential settings are assumed to occur over a short-term duration (1
to 30 days) as episodic, not daily events.  The Agency has determined
that the use patterns for oxine-copper will not result in any
intermediate-term residential exposures and hence these were not
assessed. For treated outdoor surfaces the calculated short-term dermal
MOE of 4,484 is above the target MOE of 100 and is therefore not of
concern. The calculated short-term incidental oral MOE of 36,765 is
above the target MOE of 100 and is therefore not of concern. For dermal
exposure to adults and toddlers from contacting treated textiles (canvas
tents) are all below the target MOE of 100, denoting potential risk
concerns. For incidental oral exposure to mouthing treated textiles for
toddlers, the target MOE of 735 is well above the target MOE of 100 and
hence not a concern. 

In addition to the above mentioned post-application exposure scenarios
certain oxine-copper end-use products are labeled for wood preservative
uses in pressure and non-pressure treatments of wood products intended
for residential applications.  The Agency is therefore concerned that
there are potential post-application exposures to individuals exposed to
Oxine-Copper-treated wood in residential settings (home and farm) and
hence exposure scenarios were considered for children (dermal contact
with wood product, incidental ingestion of wood product, inhalation of
wood dusts, incidental ingestion of contaminated soil, dermal contact
with contaminated soil and inhalation of contaminated soil dusts)
exposed to treated lumber.

 For adults the exposure scenarios assessed were dermal contact with
wood dusts, incidental ingestion and inhalation of wood dusts from
construction of decks and playsets. Currently, there are no study data
that can be used to estimate either exposure to adults from inhalation
of wood dusts during construction of wood decks or to children exposed
to treated wood.  Incidental ingestion exposure for adults is expected
to be negligible and dermal contact for adults is expected to be lower
than children for crawling on wood decks. t present, there are no
available data to assess the levels of Oxine-Copper residues in soil
contaminated from Oxine-Copper-treated wood (above ground fabricated
components of decks or playsets).  Because of this data gap, EPA was not
able to estimate residential post-application dermal and incidental
ingestion exposures to soil contaminated with Oxine-Copper.  In this
assessment, incidental ingestion and dermal exposures to children from
contact with treated wood were estimated using surrogate data. For
outdoor residential dermal contact with oxine-copper-treated wood
products the dermal MOEs for toddlers are greater than the target MOE of
100 (MOEs = 1156 and 129) and therefore are not of concern. For   SEQ
CHAPTER \h \r 1 outdoor residential hand-to-mouth contact with
oxine-copper-treated wood products, the estimated short-term MOEs for
the hand-to-mouth exposure are above the target MOE of 100 (MOEs = 7143
and 794) and therefore are not of concern.  A detailed explanation is
found within the residential post-application section of the
Occupational and Residential Exposures (ORE) chapter of the risk
assessment for copper-8-quinolinolate. 

 Aggregate Exposure and Risk

	In order for a pesticide registration to continue, it must be shown
“that there is reasonable certainty that no harm will result from
aggregate exposure to pesticide chemical residue, including all
anticipated dietary exposures and other exposures for which there are
reliable information.”  Aggregate exposure is the total exposure to a
single chemical (or its residues) that may occur from dietary (i.e.,
food and drinking water), residential, and other non-occupational
sources, and from all known or plausible exposure routes (oral, dermal,
and inhalation).  

	The use patterns of the products and probability of co-occurrence were
taken into account for the selection of which scenarios to incorporate
into the aggregate assessment.    SEQ CHAPTER \h \r 1 The following list
summarizes all of the potential sources of oxine-copper exposures for
adults and children that were considered for aggregate assessment:

Adult Oxine-Copper exposures sources:

Dietary exposure from pulp/paper treated with oxine-copper

Dietary exposure from adhesives containing oxine-copper

Child Oxine-Copper exposure sources:

Dietary exposure from pulp/paper treated with oxine-copper

Dietary exposure to oxine-copper containing adhesives 

Incidental oral exposure to outdoor surfaces treated with oxine-copper

Incidental oral exposure to treated tents/tarps

Dermal exposure to outdoor hard surfaces treated with oxine-copper

Dermal exposure to treated wood products 

Acute and Chronic Dietary Aggregate Risk:

	  For copper-8-quinolinolate, an aggregate dietary exposure and risk
assessment was performed for the pulp and paper use as well as the
adhesive use of copper 8-quinolinolate.  This however, may be an under
estimation of the risk due to a lack of data on the exposure from use of
copper 8-quinolinolate in wooden trays which are used to store or
transfer foods. The results indicate that for adults, 5% of the cPAD
(chronic RfD) is occupied from all dietary exposure sources, while for
children, 11% of the cPAD is occupied from all dietary sources.  These
percentages are below 100% of the cPAD and are thus not of concern to
the Agency.  

Short- and Intermediate-term aggregate risk:

A short-term aggregate assessment for adults was not performed for
copper-8-quinolinolate due to the varying toxicity endpoints for the
oral, dermal and inhalation studies concerned. The episodic nature of
likely exposures and the low probability of co-occurrence also supported
this decision. There are no intermediate-term scenarios for adults and
therefore, adult exposures were not aggregated.   

	For toddlers, aggregation of incidental oral, dermal, and inhalation
exposures is not performed across routes of exposure as toxicity
endpoints of concern were derived from separate toxicity studies. 
However, it is possible to aggregate exposures within a route of
exposure to the extent reasonable. Thus, incidental oral and dermal
exposures of children from mouthing of treated textiles with
hand-to-mouth activities and from exposure to treated outdoor hard
surfaces and lumber can be performed. The total MOEs for incidental oral
exposure (MOE = 373) and for dermal exposure (MOE = 125) are above the
target MOE of 100 and hence are not of concern. 

Occupational Exposure

	Occupational Handler Exposures

	Potential occupational handler exposure can occur in various use sites,
which include food handling premises, commercial/industrial premises,
and even applications done in residential sites. For handlers, the
representative uses assessed include various materials preservative and
wood preservative applications: mixing and loading of product
concentrates for materials 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 were all above the target MOE of 100 with
the use of 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
of concern are as follows:

General wood preservative brush applications: ST/IT MOE = 47.

Painting (professional) wood coatings, low pressure sprayer: ST/IT MOE =
35.

Painting (professional) treated paint, airless sprayer: ST/IT MOE = 74.

Paper preservation, liquid pump: ST/IT MOE = 12.

Paint preservation, liquid pour: ST/IT MOE = 14.

Textile preservation, liquid pour: ST/IT MOE = 3.

	Most inhalation MOEs were above the target MOE of 1000, except for the
scenarios indicated below. 

General wood preservative brush applications: ST/IT/LT MOE = 758.

Paper preservation, liquid pump: ST/IT/LT MOE = 500.

Painting (professional) treated paint, airless sprayer: ST/IT/LT MOE =
83 / 833 (PPE).

	Occupational Post-application Exposures

	With the exception of the post-application scenarios assessed for wood
preservatives, occupational post-application exposures are assumed to be
negligible. 	

	Wood Preservation

	

	Oxine-Copper is used in several wood preservative treatments as wood
surface coatings (e.g., water repellents applied via brush, roller or
spray) and impregnation into wood via non-pressure (e.g., non-pressure
dipping/immersion) and pressure techniques (vacuum/empty-cell).  The
products can be used on many different types of wood including 1) green
or fresh cut/debarked lumber, poles, posts, and timbers; 2) manufactured
wood products such as logs (including for log home construction),
plywood, and particle board (wood composites); 3) dry lumber; and 4)
finished wood products such as millwork, shingles, shakes, siding,
plywood and structural lumber.

	

	For wood preservation, the exposures were assessed as non-pressure and
pressure treatment related scenarios. For the non-pressure treatment
exposure, assessments were carried out based on worker function:
Handler: Blender/spray operators, chemical operators, diptank operators
and Post-application: Graders, trim saw operators, millwrights, clean up
crews, construction workers.

For Blender/spray operators, the dermal ST/IT MOE was 540 which is above
the target MOE of 100 and therefore not of concern.  The inhalation
ST/IT/LT MOE was below the Agency target of 1,000, as 212, denoting a
potential risk concern.  For inhalation MOEs below 1,000 the Agency may
request a confirmatory inhalation toxicity study since the current
inhalation endpoint is based on an oral NOAEL. For diptank operators the
dermal ST/IT MOE was 2.037 which is above the target MOE of 100 and
therefore not of concern.  The inhalation ST/IT/LT MOE exceeded the
Agency target of 1,000, as 3,311, and is also not of concern. 
Therefore, a confirmatory inhalation toxicity study is not warranted
based on the results of this exposure scenario.  

	For chemical operators, graders, millwrights, clean-up crews, and trim
saw operators, the dermal MOEs are above the target MOE of 100 for ST/IT
durations assessed.  For all worker functions, the inhalation MOEs are
above the target MOE of 1000 for ST/IT/LT durations, and therefore are
not of concern. Therefore, a confirmatory inhalation toxicity study is
not warranted based on the results of this assessment. Not enough data
exists to estimate the amount of exposure associated with construction
workers who install treated wood. Values for the transfer coefficient
associated with a construction worker handling the wood could not be
determined although it is believed that the construction worker using a
trim saw will have larger dermal and inhalation exposures than the
installer, due to the amount of sawdust generated and the greater amount
of hand contact that would be necessary to handle the wood when using a
saw compared to installing the wood.

	For pressure treatment scenarios (handler and post-application)
chemical-specific exposure data are not available on Oxine-Copper for
assessment of pressure treatment exposure.  Therefore, the assessment
relies on surrogate chromated copper arsenate (CCA) data (ACC, 2002) and
was based on the approach used in a previous Agency exposure assessment
(USEPA, 2003).  Dermal and inhalation exposures for pressure treatment
uses are derived from information in the exposure study sponsored by the
American Chemistry Council (2002) entitled “Assessment of Potential
Inhalation and Dermal Exposure Associated with Pressure Treatment of
Wood with Arsenical Wood Products” (ACC, 2002). Assessments were
conducted based on worker function: Handler: Treatment operator (TO),
Treatment assistant (TA); Post-application: Tram setter, stacker
operator, loader operator, supervisor, test borer, tallyman. The
calculated ST/IT dermal MOEs are all above the target MOE of 100 and do
not pose a risk concern.  Also, the inhalation ST/IT/LT MOEs for all
scenarios and durations are above the target MOE of 1000, therefore, a
confirmatory inhalation toxicity study is not warranted based on the
screening-level results.

Ecological/Environmental Risk 

The wood treatment uses of copper 8 have high potential for
environmental exposure and thus require an ecological risk assessment. 
Uses in rope, webbing, and roofing shingles are likely to provide for
environmental exposures as well; however, the wood treatment uses have
been examined in this assessment.  All other uses are considered indoor
and have minimal to no environmental exposure potential following use.  

Copper 8-quinolinolate is hydrolytically stable at pH 5, 7 and 9 but
photolytically it is not stable. More than 80% of it is stable in
aerobic and anaerobic soils. In aerobic soils its half-life is about
four months, but it may be over one year in anaerobic soils.  It does
not show any tendency to migrate from top soil. It is therefore likely
to contaminate surface water through surface water run-off. Its
degradation pathway appears to be aqueous photolysis with a half-life of
60 to 96 hours. Leaching from (sapstain use) treated Douglas fir wood is
666 mg/1000 board feet while for Hemlock it is 229 mg/1000 board feet
after 8 stimulated rain cycles. The estimated log Kow for copper
8-quinolinolate is 2.5, which indicates that it is not likely to
bioaccumulate in aquatic organisms like fish. It is persistent in water
and soils. 

EPA performed an environmental risk assessment using estimated
environmental concentrations (EECs) for copper-8 developed by modeling
its release from a dock into water and toxicity values from the tables
in section 8.1 to develop risk quotients (RQs) and compare them to
levels of concern (LOCs) for copper-8.  LOCs were not exceeded for fish,
freshwater invertebrates, the eastern oyster or aquatic plants in bodies
of water 6 acre feet in size or greater, whereas risks to endangered
freshwater fish and the eastern oyster as well as risks to aquatic
plants were of concern in bodies of water 1 acre foot in size or less. 
Since it is unlikely that a dock of the size used in the calculations
for EEC will be present on a body of water less than 6 acre feet in
size, the risks to aquatic organisms from copper 8 in this assessment
appear to be small.  There were no acceptable acute toxicity studies for
other estuarine and marine organisms nor were there any acceptable
chronic toxicity studies available for aquatic organisms.  Therefore,
risk to these species could not be assessed.

Endangered Species

For certain use categories, the Agency assumes there will be minimal
environmental exposure, and only a minimal toxicity data set is required
(Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04, Appendix A, Section
IIB, pg.81).  Chemicals in these categories therefore do not undergo a
full screening-level risk assessment, and are considered to fall under a
“No Effect” determination.  The materials preservative uses of
copper 8-quinolinolate fall into this category.

	The preliminary analysis for wood treatment uses indicates that there
is a potential for copper-8 use to overlap with listed species and that
a more refined assessment is warranted, to include direct, indirect and
habitat effects.  The more refined assessment should involve clear
delineation of the action area associated with proposed use of copper 8
and best available information on the temporal and spatial co-location
of listed species with respect to the action area.  This analysis has
not been conducted for this assessment.  An endangered species effect
determination will not be made at this time.  The wood runoff label
statement is expected to provide some level of mitigation until such
time as a full endangered species assessment is possible.

Incident Reports

Some incidences associated with exposure to end-use products containing
copper-8-quinolate, have been reported. Dermal and eye exposure are the
primary routes of exposure associated with these incidences. No severe
incidences associated with copper-8-exposure have been reported.

2.0	PHYSICAL AND CHEMICAL PROPERTIES

 

www.generalchem.cn/images/crop/Oxine%20Copper.jpg

Table 2.2 Physical/Chemical Properties for Copper-8-quinolinolate

Parameter	Copper-8-quinolinolate

Molecular Weight	351.851

Color	Olive Green

Physical State	Crystalline Powder

Odor	Odorless

Melting Point	270 o C (decomposes below MP)

Boiling Point	Not determined

Specific Gravity	1.63

Solubility	0.7 mg/L at 25 o C

Vapor Pressure	Can not be calculated even at 270 o C*

Log Kow	3.14

Henry law Constant	7.849 x 10—13 atm-m3/mole

Half Life in Air	0.642 Hours (measured against OH radical reaction)

Log Koc	6.69

* EPISuite Program estimated the vapor pressure of copper-8 as: 6.3 x
10-12 mm Hg

3.0	HAZARD CHARACTERIZATION

	3.1	Hazard Profile

Acute Toxicity

	Adequacy of Database for Acute Toxicity: The acute toxicity database
for Copper 8-quinolinolate and salts is considered complete. Copper
8-quinolinolate has a low order of acute toxicity via the oral route of
exposure (Toxicity Category IV).   Copper 8-quinolinolate has a moderate
order of toxicity via the dermal route of exposure (Toxicity Category
III), whereas the inhalation route of exposure yielded a higher order
(Toxicity Category II).   The primary eye irritant study classified
oxine copper as corrosive (Toxicity Category I).  For dermal irritation,
Copper 8-quinolinolate is a low irritant (Toxicity Category IV).  
Copper 8-quinolinolate is not a dermal sensitizer. The acute toxicity
data for Copper 8-quinolinolate is summarized below in Table 3.1.

Table 3.1 Acute Toxicity Profile for Copper 8-quinolinolate and Salts

Guideline Number	Study Type/Test substance (% a.i.)	MRID Number/

Citation	Results	Toxicity Category

870.1100

(§81-1)	Acute Oral- Rat

Copper 8-quinolinolate

purity 99.5%	42921501	LD50 > 5000 mg/kg M/F	IV

870.1200

(§81-2)	Acute Dermal- Rabbits

Copper 8-quinolinolate

 purity 99.5%	42921502, 43558501	LD50 = 2000 mg/kg M/F	III

870.1300

(§81-3)	Acute Inhalation- Rat

Copper 8-quinolinolate

purity 96%	43611901	LC50 = 0.089 ± 0.031 mg/L M/F	III

870.2400

(§81-4)	

Primary Eye Irritation- Rabbit, Copper 8-quinolinolate 

purity 98%	41678402	Corrosive	I

870.2500

(§81-5)	Primary Dermal Irritation- Rabbit Copper 8-quinolinolate 

purity 99.7%

	42921503	Non-Irritant	IV

870.2600

(§81-6)	Dermal Sensitization - Guinea pig

Copper 8-quinolinolate purity 99.7%	42921504	Not a sensitizer.	N/A

N/A = NOT APPLICABLE

3.2	FQPA CONSIDERATIONS

		3.2.1	Developmental Toxicity Study Conclusions

There are two acceptable developmental toxicity studies available for
oxine copper. There was no evidence for a primary developmental effect
of oxine copper in either the rat or rabbit developmental toxicity
study.

		3.2.2	Reproductive Toxicity Study Conclusions

There is one acceptable reproductive toxicity study available for oxine
copper. There was no evidence of a primary reproductive effect of oxine
copper in this study.

The ADTC concluded that the special hazard-based FQPA factor can be
reduced to 1x. The available developmental and reproductive toxicity
data for oxine copper show no evidence of teratogenicity or reproductive
toxicity. The studies are conducted according to guidelines and show no
evidence of increased susceptibility of offspring. There is no evidence
for neurotoxicity of oxine copper.  

		3.2.3	Recommendation for a Developmental Neurotoxicity Study

	A developmental neurotoxicity study for oxine copper is not needed at
this time.

3.3	Dose-Response Assessment

3.3.1	Summary of toxicology endpoint selection for oxine copper. Table
3.2

Table 3.2 Summary of Toxicological Doses and Endpoints for
Copper-8-quinolinolate                    

  SEQ CHAPTER \h \r 1 Exposure

Scenario	Dose Used in Risk Assessment

(mg/kg/day) 	Target MOE, UF, 

Special FQPA SF* for Risk Assessment	Study and Toxicological Effects

Dietary Risk Assessments

Acute Dietary

(general population and females 13-49) 	No appropriate endpoints were
identified that represent a single dose effect.  

Therefore, this risk assessment is not required.

Chronic Dietary

(all populations)	NOAEL = 

5 mg/kg/day

	FQPA SF = 1

UF = 100 (10x inter-species extrapolation, 10x intra-species variation)

Chronic RfD (cPAD) = 0.05 mg/kg/day	Subchronic Toxicity in the Dog

MRID 42986802

LOAEL = 50mg/kg/day, based on vomiting, decreased plasma protein and
albumin, and reddened mucosa and hyperemia in the stomach and small
intestine.

Non-Dietary Risk Assessments

Incidental Oral Short-Term 

(1-30 days)

Intermediate-term

(30-days – 6months) 

	NOAEL (maternal)  =  200 mg/kg/day	Target MOE = 100

(10x inter-species extrapolation, 10x intra-species variation) 

FQPA SF = 1

	Prenatal Developmental Toxicity Study in the Rat 

LOAEL = 800 mg/kg/day, based on clinical signs of toxicity and decreased
body weight gain in maternal rats.   

Dermal

Short-Term (1 to 30 days) and Intermediate-term (30 days- 6 months)
NOAEL = 

200 mg/kg/day  

	Target MOE = 100 

(10x inter-species extrapolation, 10x intra-species variation)

	28-day dermal toxicity study in the rat  

MRID 42957802

LOAEL(systemic)  = 1000 mg/kg/day, based on  necrosis of thymic
lymphocytes

No evidence of dermal irritation from either this study or the acute
dermal study

Dermal

Long-Term (>6 months)	A long-term dermal endpoint is not required for
oxine copper. 

Inhalation

(all durations)	NOAEL = 5 mg/kg/day  

	UF = 1000

(10x inter-species extrapolation, 10x intra-species variation, 10x route
extrapolation)	Subchronic Toxicity in the Dog

MRID 42986802

LOAEL = 50mg/kg/day, based on vomiting, decreased plasma protein and
albumin, and reddened mucosa and hyperemia in the stomach and small
intestine.

Cancer	Oxine Copper has not been formally classified as to
carcinogenicity.  

3.3.2	Dermal Absorption

Dermal Absorption Factor:  A route-specific study is available for
dermal risk assessments. Therefore, a dermal absorption factor is not
required.

		3.3.3	Classification of Carcinogenic Potential

	Oxine copper has not been formally classified for carcinogenicity by
the Office of Pesticide Programs.   Oxine copper has been examined for
carcinogenicity in the rat (MRID 00083777) and in the mouse (MRID
43267201) in studies reviewed by the Office of Pesticide Programs.   The
National Toxicology Program has examined the 8-hydroxyquinoline moiety
for carcinogenicity (NTP Technical Report no. 301).  Additional studies
not reviewed by the EPA but reviewed by Health Canada, Pest Management
Regulatory Agency include a 3 week gavage plus 50 week dietary
carcinogenicity study in mice, a 2 year carcinogenicity study in B6C3F1
mice, and a 2 year carcinogenicity study in Fischer 344 rats.   

In the mouse carcinogenicity study with oxine copper, Health Canada
noted in their review that the lymphomas noted in the mouse study were
discounted based on the observations that (a) the tumors were not
dose-related (also noted in the EPA’s own review, HED document number
011915), (b) the tumors occurred in only one sex, and (c) the tumors
were not increased further at the next highest dose.  With regard to the
uterine tumors, although Health Canada noted that these tumors were
outside historical control at the high dose, the EPA notes that the
incidence of the tumors that were outside historical control occurred at
a dose above the limit dose (1000 mg/kg/day) for carcinogenicity
studies. Therefore, the biological significance of the tumors is
questionable. 

In the rat carcinogenicity study with oxine copper, interstitial cell
tumors of the testes, 2 unilateral and 1 bilateral were observed in
three males at the 761 mg/kg/day dose level. The study report indicated
that this incidence was within historical control range for ‘rats of
this age in this laboratory.’ However, only one set of historical
control data were submitted that indicated benign interstitial cell
tumor incidence of 10% (from examination of 70 male rats). In addition,
only 10 rats at the high dose in the present study were examined
histologically. 

As noted by both the EPA and by Health Canada, this rat study had
several significant deficiencies, including high mortality rates in all
treatment groups, assessment of too few rats for carcinogenicity (only
30 animals/sex/dose), and inadequate historical control data. 
Therefore, the significance of the interstitial cell tumors are not
known and cannot be determined from these data. 

	3.4	Endocrine Disruption

	EPA is required under the Federal Food, Drug and Cosmetic Act (FFDCA),
as amended by the Food Quality Protection Act (FQPA), to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) “may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other endocrine effects as the Administrator may designate.” 
Following recommendations of its Endocrine Disruptor Screening and
Testing Advisory Committee (EDSTAC), EPA determined that there was a
scientific basis for including, as part of the program, the androgen and
thyroid hormone systems, in addition to the estrogen hormone system. 
EPA also adopted EDSTAC’s recommendation that EPA include evaluations
of potential effects in wildlife.  For pesticides, EPA will use FIFRA
and, to the extent that effects in wildlife may help determine whether a
substance may have an effect in humans, FFDCA authority to require the
wildlife evaluations.  As the science develops and resources allow,
screening of additional hormone systems may be added to the Endocrine
Disruptor Screening Program (EDSP).

When the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, Copper-8-quinolinolate
may be subject to additional screening and/or testing to better
characterize effects related to endocrine disruption.

4.0	EXPOSURE ASSESSMENT AND CHARACTERIZATION

 

4.1 Summary of Registered Antimicrobial Uses

	Based on a review of product labels, Copper-8-quinolinolate is the
active ingredient in products used in the following Use Site Categories:

(II)   SEQ CHAPTER \h \r 1  Food handling/storage establishments,
premises and equipment,

(VII)   SEQ CHAPTER \h \r 1 Material preservatives

(X) Wood preservatives

The majority of registered products are intended for
industrial/commercial uses in the preservation of materials/wood during
manufacture, or through impregnation and surface treatments against
fungicidal decay in non-residential use sites.  However, some end-use
products containing Oxine-Copper are for protection of wood found in
residential sites as well as residential application of wood coatings
and water repellents.  Some are ready-to-use RTU products sold to
consumers for home/farm uses to protect outdoor wood surfaces (e.g.,
fencing, wood siding/shingles/roofs, log homes).

	Also, the Oxine-Copper-treated wood itself is used for fabrication of
residential structures (e.g., outdoor above-ground fencing, playsets,
decks) and in home renovation (interior sub-flooring and framing
lumber).  Material preservation of textiles are intended for mainly
industrial/government-specified (i.e., military-issued) end-use
applications (USEPA, 2006b).  However, the Agency cannot rule out the
possibility of consumers coming in contact with treated textiles (e.g.,
obtaining Army-grade canvas tents treated with Oxine-Copper). Commercial
remediation treatments to outdoor environmental surfaces in residential
sites (e.g., brick, concrete and tile) may also contribute to
residential post-application exposure.  Table 4.1 identifies the
representative residential exposure scenarios considered for assessment
in this document.

Table 4.1. Representative Uses Associated with Residential Exposure 

Representative Use	

Exposure Scenario	

Application Method	

EPA Reg. No.	

Maximum Application Rate

Using Wood Preservative Coatings/ Water Repellents 	ST Handler: Adult
Dermal and Inhalation	Paint brush,

Roller and Low-pressure coarse sprayer 

	1022-514; 81819-1	0.675% ai ready-to-use (RTU) oil-based exterior
coating for log homes, wood roofs, siding, fences, rough sawn lumber,
new/old wood. 150-300 sq ft/gal. as one coat application.

Using Treated Paints/Coatings             (in-can preservative)	

ST Handler: Adult Dermal and Inhalation 

(aerosol particulates)6

	

Paint brush,

Roller,

Airless sprayer	

Commercially-treated article preserved with 2829-136 (e.g., exterior
house paint) 	

Solvent-based paint containing 1% a.i. incorporation to inhibit
mold/mildew. (Paint use applications unspecified).

Contact with treated Textiles (i.e., outdoor-use treated tents/tarps,
canvas exposed to the elements and prone to decay)

Note: Textiles are not Clothing Apparel, Bedding or Home-goods 	ST
Post-application: Adult dermal; Child Incidental oral ingestion and
Dermal

	NA	Commercially- treated articles preserved with 2829-42;     2829-49;
and 2829-112	0.7-1.0% a.i. used to treat canvas fabric

Environmental Outdoor Hard Surface Treatments 

(i.e., mold and mildew control treatments to exterior environmental
surfaces ) 	ST Post-application: Child incidental oral ingestion and
Dermal

	

NA	

Commercial application done 

via Brush/Spray at residential sites with 

1022-489;

1022-490;

75675-1

	

0.1% a.i. treatment solution used on paint/varnish, concrete, brick,
glass, tile, metals, plastic, wood, (paper)*, (leather)*, textiles and
asphalt shingles.

* - Treatments to these materials may indicate potential indoor uses.
Clarification of labeling is needed. 

Contact with treated Wood products (i.e., outdoor playsets, decks, wood
structures)

	ST Post-application: Child incidental oral ingestion and Dermal	NA	

Commercially- treated wood preserved with 2829-135 and 2829-136, used
for above-ground applications (via pressure and non-pressure methods)	

1.0% ai used to treat wood via pressure methods resulting in an active
ingredient retention of 0.02 lb/ft3.

Note: Only EPA registered products with specified use directions/use
applications are included in this table. 

Products listed were selected based on maximum use rates by application
method.

ST = Short-term exposure

6 Handler dermal and inhalation (to the particulates) exposure were
assessed for Oxine-Copper using PHED unit exposures. 

	

		4.1.1	Residential Handler Exposures

	The residential handler scenarios described in Table 4.1 were assessed
to determine dermal and inhalation exposures.  The majority of the
scenarios were assessed using CMA data.  These scenarios were assessed
using the Pesticides Handler Exposure Database (PHED).  Residential
handlers using Oxine-Copper-treated paint (as an in-can preservative)
may have inhalation exposures to aerosol particulates during airless
spray applications.  Aerosols are not anticipated for the wood coatings
applications using a low-pressure sprayer (non-misting).  In the case of
Oxine-Copper, the technical-grade chemical has a low vapor pressure (6.3
x 10-12 mm Hg) and therefore it is expected to be non-volatile in end
product formulations.  

  

	The resulting short-term exposures and MOEs for the representative
residential handler scenarios are presented in Table 4.2. The calculated
ST MOEs were above the target dermal MOE of 100 for all scenarios.  The
high-end scenario developed for airless sprayer yielded a ST inhalation
MOE below the target of 1000, as 278, indicating a potential risk
concern. Confirmatory inhalation toxicity study data may be required to
address this. 

Table 4.2 Short-Term Oxine-Copper Residential Handlers Exposures and
MOEs 

Exposure Scenario

	

Method of Application	

Unit Exposure 

(mg/lb a.i.)	

Application Rate	

Quantity Handled/ Treated per day	

Absorbed Daily Dose (mg/kg/day)	

MOE (ST)

Dermala	

Inhalationb

	

Dermalc	

Inhalationd	

Dermal 

(Target = 100)e	

Inhalation (Target = 1000)f

Using

Wood Coatings

	Low Pressure Sprayer

	

100

	

0.030

	

0.675% a.i. by weight

	50 lbs

(5 gal)

	

0.482

	

0.00015

	

415

	

33,333

Using Treated Paint

	

Brush/roller

	

230

	

0.284

	

1.0% a.i. by weight

	

20 lb s

 (2 gal)	

0.657	

0.0008	

304	

6,250

	

Airless sprayer	

79

	

0.83

	

1.0% a.i. by

 weight	150 lbs (15 gal)	

1.69

	

0.018

	

118

	278

a	All dermal unit exposures represent ungloved replicates. The low
pressure sprayer, brush/roller, and airless sprayer unit exposures
represent short sleeve and short pant replicates.

b	No respirator used by exposed individual.

c	Dermal Daily Dose (mg/kg/day) = [dermal unit exposure (mg/lb a.i.) *
application rate (0.00675 or 0.01) * quantity handled * dermal
absorption factor (NA) / body weight (70 kg).

d	Inhalation Daily Dose (mg/kg/day) = [inhalation unit exposure (mg/lb
ai) * application rate (0.00675 or 0.01) * quantity handled * inhalation
absorption factor 100% / body weight (70 kg).

e	Dermal MOE = NOAEL (200 mg/kg/day) / Daily Dose. Target dermal MOE is
100.

f 	Inhalation MOE = NOAEL (5 mg/kg/day) / Daily Dose. Target inhalation
MOE is 1000.

		4.1.2	Residential Post-application Exposures

 	For the purposes of this screening level assessment, post-application
scenarios have been developed to encompass potential high-end exposure
from various wood/materials preservative treatments.  As shown in Table
4.1, representative post-application scenarios assessed include child
contact with surface residues from Oxine-Copper treated wood (dermal and
incidental oral exposure) and residues remaining on treated outdoor hard
surfaces (dermal and incidental oral exposure to children).  Scenarios
were also developed for contact with residues on treated textiles such
as tents and tarps (dermal exposure to adults and children and
incidental oral exposure to children).

	Typically, post-application exposures in residential settings are
assumed to occur over a short-term duration (1 to 30 days) as episodic,
not daily events.  AD does not believe that the use patterns for
Oxine-Copper will result in any intermediate-term residential exposures.

			4.1.2.1   Outdoor Hard Surfaces/Remedial Fungistatic Surface         

                                                  Treatments            
          

Dermal Exposure to Children from Treated Outdoor Surfaces

	There is the potential for dermal exposure to toddlers crawling on hard
outdoor surfaces (e.g., brick/tile or concrete surfaces of
walkways/patios) after periodic surface treatments with Oxine-Copper
products.  Exposures and MOEs were calculated for children contacting
treated hard surfaces in residential sites (short-term exposure).  The
calculated short-term dermal exposure dose and MOE is shown in Table
4.3.  The dermal MOE of 4,484 is above the target MOE of 100 and is
therefore not of concern.

Table 4.3.  Short-term Post-application Dermal Exposure and MOE for
Children 

                   Contacting Treated Outdoor Hard Surfaces

Exposure Scenario	

Application Rate 

(lb ai/sq ft)	

Product remaining after treatment	

Percent Trans. Residue	

Body Area in contact with surface (m2)	

Absorbed potential daily dosea (mg/kg/day)	ST

Dermal MOEb

Target = 100

Treated Outdoor Hard surfaces - residential setting

	

8.34 x10-6

	

25%

	

10%

	

0.657

	

0.0446

	

4,484

a 	Absorbed Potential Daily Dose(mg/kg/day) = [(Application rate, lb
ai/ft2)*(conversion factor, 454 g/lb)* (conversion factor, 1,000 mg/g) *
(conversion factor, 1 ft2/0.093 m2) * (product remaining after hard
surface treatment, 25%) * (dermal transfer factor, 10%) * (body surface
area in contact with floor, 0.657 m2) * (dermal absorption , NA) ] /
(body weight, 15 kg)

b	Dermal MOE  = NOAEL (mg/kg/day) / Absorbed Potential Daily Dose
(mg/kg/day) [Where short-term dermal NOAEL (systemic) = 200 mg/kg/day]. 
Target MOE = 100.

Child Incidental Ingestion Exposure to Treated Floor Residues

	In addition to dermal exposure, toddlers crawling on treated outdoor
hard surfaces will also be exposed to Oxine-Copper residues via
incidental oral ingestion through hand-to-mouth activity.  To calculate
incidental oral ingestion exposure to this chemical via hand-to-mouth
transfer, the methodologies established in the Standard Operating
Procedures (SOPs) for Residential Exposure Assessments (USEPA 2000 and,
2001) were used.  These SOPs use assumptions that are similar to those
used above in calculating the dermal exposure for toddlers crawling on
residential outdoor treated surfaces.  The calculated short-term
incidental oral exposure dose and MOE is shown in Table 4.4.  The oral
MOE is 36,765, which is over the target MOE of 100 and therefore not of
concern.

Table 4.4.  Short-term Incidental Oral Post-application Exposure and MOE

                   for Children Contacting Treated Outdoor Hard Surfaces

Exposure Scenario	

Appl. Rate

 (lb ai/

sq ft)	

Product remaining after treatment	

Surface Residuea (µg/cm2)	

Percent transferable residue	

Surface area mouthed (cm2/event) 	

Exposure Frequency (events/hr)	

Saliva Extraction Factor	

Exp. Time (hrs/day)	

Absorbed Potential Daily Doseb (mg/kg/day)	

ST Oral

MOEc

Target = 100 

Treated Outdoor Hard surfaces - residential setting	

8.34 x10-6

	

25%	

1.02	

10%	

20	

20	

50%	

4	0.00544	36,765

a 	Surface residue (µg/cm2) = (application rate, lb ai/ft2)*(product
fraction remaining on surface, 0.25)*(conversion factor to convert lb to
µg, 4.54E+08 µg/lb)*(conversion factor to convert ft2 to cm2, 1.08E-03
ft2/cm2)

b 	Absorbed Potential Daily Dose (mg/kg/day) = [(Surface residue,
µg/cm2)*(transferable residue, 0.10)*(exposure time, 4
hrs/day)*(surface area of hands, 20 cm2/event)*(frequency of
hand-to-mouth activity, 20 events/hr)*(extraction by saliva, 50
%)*(conversion factor to convert µg to mg, 0.001 mg/µg)]/ (body
weight, 15 kg)

c 	MOE = NOAEL (mg/kg/day) / absorbed potential daily dose (mg/kg/day)
[Where short-term oral NOAEL (maternal) = 200 mg/kg/day].  Target MOE =
100.

			4.1.2.2   Treated Textiles

Dermal Exposure to Adults and Toddlers from Contacting Treated Textiles
(Canvas Tents)

	The Agency assumes that there is the remote potential for dermal
exposure to adults and children from contact with fabric (canvas tents)
treated for mildew control at military-specified levels of 1.0%
Oxine-Copper via factory impregnation. From our understanding of
registered use patterns, textiles treated with Oxine-Copper
preservatives meet the needs of niche markets for government
(military-issued) and industrial textiles.  Registrant input is needed
to confirm that residential consumers will have limited contact with
Oxine-Copper-treated textiles.

	This post-application assessment assumes the tent is new (i.e., not
laundered and not yet exposed to rainfall and outdoor elements) as a
conservative measure (i.e., the effect of dislodgeable residues being
diminished over time is not quantifiable).  It should be noted that it
was assumed that contact with these treated textile articles are
infrequent and episodic. Therefore, only short-term duration (1-30 days)
exposure was considered.  The calculations of the short-term dermal
doses and MOEs for adults and toddlers in contact with treated textiles
are shown in Table 4.5.  The dermal MOEs for adults and toddlers are all
below the target MOE of 100, denoting potential risk concerns.

Table 4.5.  Dermal Post-application Exposures and MOEs for Toddlers and
Adults Contacting

                   Treated Textiles                 

Exposure Scenario	W (weight of treated textile per day)a  (g/day)	WFai 

(fraction a.i. in textile)	TF (percent transfer)	PDD (mg/kg/day)b	ST
Dermal MOEc   Target = 100

Toddler	121	0.01	100%	81	3

	5%	4	50

Adult	376	0.01	100%	54	4

	5%	3	67

a.	Weight of treated textile in contact with skin (g/day) = (Density of
shirt 408 g/m2) * (surface area of body covered, cm2 as 2,955 cm2
toddler or 9,220 cm2 adult) * (0.0001 m2/cm2) 

b.	Absorbed Potential Daily Dose (mg/kg/day) = [(weight of treated
textile, g/day) * (weight fraction a.i. in treated cloth) * (percent
transfer) * (conversion factor, 1000 mg/g)] / (body weight, kg, as 15
toddler or 70 adult).

c. 	Dermal MOE = NOAEL (mg/kg/day) /Absorbed Potential Daily Dose [Where
short-term dermal (systemic) NOAEL = 200 mg/kg/day].  Target MOE = 100.

Incidental Oral Exposure to Toddlers Mouthing Treated Textiles (Canvas
Tents/Tarps)

	Based on the dermal scenario developed above, there is the potential
for incidental oral exposure to toddlers from mouthing textiles (e.g.,
canvas tents/tarps) treated with Oxine-Copper. Table 4.6 shows the
calculation of the oral dose and oral MOE for toddlers mouthing treated
textiles. The MOE value is 735 which is above the target MOE of 100 and
is not of concern.

Table 4.6.  Incidental Oral Exposures and MOEs for Toddlers Mouthing
Treated 

                   Textiles (Canvas Tent/Tarp)                      

Weight of textile (g/m2)	Concentration on textilea 

(mg/cm2)	Surface area mouthed (cm2/day)	

Saliva extraction efficiency 

	Potential daily doseb (mg a.i./kg/day)	Incidental Oral MOEc

408	0.408	20	50%	0.272	735

a.	Concentration on textile (mg/cm2) = (Weight fraction a.i. in
clothing, 0.01) * (weight of textile, g/m2) * (1,000 mg/g) * (0.0001
m2/cm2)

b.	Potential Daily Dose (mg/kg/day) = (concentration on textile, mg/cm2)
* (surface area mouthed, cm2/day) * (saliva extraction efficiency 0.50)
/ (body weight, 15 kg).

c 	Oral MOE = NOAEL (mg/kg/day) / Potential Daily Dose [Where short-term
incidental oral (maternal) NOAEL = 200 mg/kg/day].  Target MOE = 100.	

			 

			4.1.2.3   Treated Lumber		

	Certain Oxine-Copper end-use products are labeled for wood preservative
uses in pressure and non-pressure treatments of wood products intended
for residential applications.  The Agency is concerned that there are
potential post-application exposures to individuals exposed to
Oxine-Copper-treated wood in residential settings (home and farm).  

The potential outdoor residential post-application exposure pathways
considered are outlined below for children.

Dermal contact with Oxine-Copper-treated wood products for above-ground
uses [e.g., residential playground equipment (playsets), posts, decks,
shingles, fencing, outdoor lumber, etc.];

Incidental ingestion due to hand-to-mouth contact with
Oxine-Copper-treated wood products;

Inhalation of wood dusts from fabrication of Oxine-Copper-treated wood
products;

Incidental ingestion of soil contaminated with Oxine-Copper;

Dermal contact with soil contaminated with Oxine-Copper (e.g., soil
contaminated by treated decks and playsets); and

Inhalation of soil dusts contaminated with Oxine-Copper (e.g., soil
contaminated by treated decks and playsets).

Other potential outdoor residential post-application exposure pathways
for adults are outlined below:

Dermal contact with wood/wood dusts from construction of decks and
playsets;

Incidental ingestion of wood dusts from construction of decks and
playground equipment; and,

Inhalation of wood dusts from construction of decks and playsets.

	Currently, there are no study data that can be used to estimate either
exposure to adults from inhalation of wood dusts during construction of
wood decks or to children exposed to treated wood.  Incidental ingestion
exposure for adults is expected to be negligible and dermal contact for
adults is expected to be lower than children for crawling on wood decks.
 Because children are more likely than adults to contact wood surfaces
using playground equipment (playsets), and because children have a
higher surface area to body weight ratio, they have been used to
represent the maximum exposed individual.  

At present, there are no available data to assess the levels of
Oxine-Copper residues in soil contaminated from Oxine-Copper-treated
wood (above ground fabricated components of decks or playsets).  Because
of this data gap, EPA was not able to estimate residential
post-application dermal and incidental ingestion exposures to soil
contaminated with Oxine-Copper.  In this assessment, incidental
ingestion and dermal exposures to children from contact with treated
wood were estimated using surrogate data.

Surrogate Data 	

	

	No chemical-specific residential post-application studies conforming to
Series 875 guidelines were available; however, data from the proprietary
study, “Measurement and Assessment of Dermal and Inhalation Exposures
to Didecyl Dimethyl Ammonium Chloride (DDAC) Used in the Protection of
Cut Lumber (Phase III)” (Bestari et al., 1999, MRID 455243-04, SIG
Task Force #73154) can be used as surrogate data to estimate
screening-level exposures for the following pathways: outdoor
residential dermal contact with Oxine-Copper-treated wood products used
in above-ground applications (e.g., residential playsets, posts, decks,
shingles, fencing, outdoor lumber, etc.); and outdoor residential
incidental ingestion due to hand-to-mouth contact with pressure-treated
wood products.  The DDAC study measured dermal and inhalation exposures
for various worker functions/positions for individuals handling
DDAC-containing wood preservatives for non-pressure treatment
application methods and for individuals that could then come into
contact with the preserved wood. 

Outdoor Residential Dermal Contact with Oxine-Copper-treated Wood
Products

Potential dermal doses are calculated as follows:

PDD = R x SA exposed 								

	    BW							

Where: 

PDD	= 	potential daily dose (mg/kg/day);

R 	= 	residue on skin after contact with treated wood (μg/cm2);

SA exposed=	Skin surface area in contact with treated wood (cm2);

BW	=	Body Weight of a toddler (kg)

The value for R used was based on two surrogate data sources: 1)
measured worker residue data for hands that are available in the DDAC
study (maximum concentration 3.0 µg/cm2 ); and, 2) a conservative
(high-end) surrogate value to represent skin residue concentration (as
27 µg/cm2) taken from a chemical-specific leaching study on
Oxine-Copper spray-treated hemlock-fir lumber (MRID 436370-01).  

	DDAC Study (MRID 455243-04)

	The DDAC data in Table 4.7 were used to approximate the residues
transferred from treated wood to skin for contact with
Oxine-Copper-treated wood.  No wood-wipe sampling data are available. 
The data from the following job descriptions in the DDAC study were
chosen because of the possibility of the contact with dry treated wood. 

End Stacker - Operates an automated stacking system at the end of the
conveyor.  Lumber stacked into loads.

Stickman - Places sticks between stacks of wood manually.  At some
mills, this is done automatically by end stacker operator.

Tallyman - Staples information sheet on to wood.  May come in contact
with treated lumber. (Note: there were two reps available for tallyman)

Table 4.7.  Hand Residue Data for DDAC for Handling of Dry Wood

Job Description	Total Hand Residue Data (μg/cm2)

End Stacker	1.2

Stickman	0.6

Tallyman	0.8

Tallyman (Maximum Value)	3.0

Average Hand Residue	1.4

These test subjects handled the dry treated wood from the non-pressure
treatments. Of the 20 test subjects measured for handling “dry” wood
in the DDAC study, 19 had detectable hand values (one value non-detect)
ranging from 0.04 to 3.0 µg/cm2 (DDAC study page 104). The highest
value (most conservative) (3.0 µg/cm2) represents the “Tallyman”
that wore no gloves (DDAC study page 189). This value was used in the
assessment.

	Oxine-Copper Study (MRID 436370-01) 

A non-guideline leaching study is on file with the Agency for this
chemical, “Leaching of Copper Oxinate (Copper 8-Quinolinolate) From
Lumber Spray Treated with Maag Sapstain Control Formulations: Lab
Project Number: 17930425. Unpublished study prepared by Forintek Canada
Corp. 24 p.” (Byrne, A.; Minchin, D., 1991, MRID 436370-01).  It is
unclear if it has been formally reviewed for acceptance by EPA in
registering the end-use product.  However, since it is cited as a data
source in an environmental fate transport memorandum written in support
of Oxine-Copper reregistration (USEPA, 2006c), it is used in this
assessment.

The study included data on the measured wood surface concentration of
Oxine-Copper on hemlock fir samples which were subjected to spray
treatments for sapstain control.  Data indicated that a conventional
spray system achieved a surface sample retention concentration (surface
deposition) of 27 µg/cm2 . For lack of wood wipe sampling data on
Oxine-Copper residues, the 27 µg/cm2 Oxine-Copper retention level is
assumed to represent a maximum surface residue concentration, as a
surrogate for hand residue load. 

SA exposed was determined using the following equation:

SA exposed =  SA total * (X handSA *  X hand,touching+X non-handSA * X
non-hand,touching)		

Where:

SA total 		  =	 total surface area for a 3-year old toddler (cm2)

X handSA		  =	fraction of total toddler surface area that is hand
(unitless)

X hand,touching	  =	fraction of X handSA that contacts treated wood
(unitless)

X non-handSA         =	fraction of total toddler surface area that is
unclothed, other than hands (i.e., legs, arms, head)

X non-hand,touching  =	fraction of X non-handSA that contacts treated
wood (unitless)

The value for SA total used was 6,565 cm2, which is the average surface
area for a 3-year old toddler.  The values X handSA and X non-handSA are
0.0607 and 0.548, also based on the average surface area for a 3-year
old toddler (USEPA, 1997a).  The values for X hand,touching and X
non-hand,touching are 0.74 and 0.158, respectively.  These are the
values used in a USEPA model to determine chromated copper arsenate
(CCA) exposure on treated playground sets (USEPA, 2005a). 

Table 4.8 shows the results of the calculations.  The dermal MOEs are
greater than the target MOE of 100 (MOEs = 1156 and 129) and therefore
are not of concern.

Table 4.8.  Residential Post-application Dermal Exposures to
Oxine-Copper-treated Wood Products

Hand Residue Concentration from DDAC Study (ug/cm2)	Fraction of Hand
Touching Residues: Hand, touching	Fraction of Body Surface that is hand:
Hand SA	Fraction of Unclothed Body (Non-hand) skin touching residues: 

Non-Hand, touching	Fraction of body surface that is unclothed, non-hand
(i.e., legs, arms, head): 

Non-Hand SA	Total surface area of 3-yr old (cm2):

 SA Total	Surface Area in contact with residues

 (cm2): a

SA Exposed	PDD (mg/kg/day)b	ST Dermal MOEc

Target MOE = 100

3.0	0.74	0.0607	0.158	0.548	6565	863	0.173	1156

Surrogate Hand Residue Concentration 

(Maximum Surface Residue) from Oxine-Copper

Spray-treated Lumber

(MRID 436370-01 Study) (µg/cm2)

	1.55	129

27.0

a	SA exposed = (X hand,touching*X handSA+X non-hand,touching*X
non-hand,SA)*SA total

b	PDD=[Residue (either 3 μg/cm2  or 27 μg/cm2) x 0.001 mg/ μg x
SAexposed]/(Body Weight, 15 kg)

c	MOE  = NOAEL (mg/kg/day) / daily dose (mg/kg/day).  For dermal
exposures, the (systemic) NOAEL is 200 	mg/kg/day.  Target MOE = 100.

  SEQ CHAPTER \h \r 1 Outdoor Residential Hand-to-Mouth Contact with
Oxine-Copper-treated Wood Products

	The results of the hand-to-mouth estimates are presented in Table 4.9. 
The estimated short-term MOEs for the hand-to-mouth exposure are above
the target MOE of 100 (MOEs = 7143 and 794) and therefore are not of
concern.  

Table 4.9. Residential Post-application Incidental Oral Exposures to
Oxine-Copper-treated Wood Products

Hand Residue concentration 

from DDAC Study (µg/cm2)	Finger

 Surface Area (cm2)	Exposure Frequency for Outdoor Playing (events/hr) 
Saliva Extraction Factor	Exposure Time (hrs/day)	Average Daily Oral Dose
a (mg/kg/day)	ST Oral MOEb

Target MOE = 100 

3.0

	20	7	50%	2	0.028	7143

Surrogate Hand Residue (Maximum Surface Residue) 

concentration from Oxine-Copper Spray-treated Lumber

 (MRID 436370-01 Study) (µg/cm2)

27.0

	0.252	794

3 μg/cm2  or 27 μg/cm2 ) x Hand SA (20 cm2) x SEF (50% as 0.50) x
Frequency (7 events/hr) x Exposure Time (2 hrs/day) x 0.001 mg/μg] / BW
(15 kg)

b     MOE  = NOAEL (mg/kg/day) / daily dose (mg/kg/day).  For incidental
oral exposures, the ST/IT (maternal) NOAEL is 200 mg/kg/day.  Target MOE
= 100.

		

		4.1.3	Data Limitations/Uncertainties

	There are several data limitations and uncertainties associated with
the residential handler and post-application exposure assessments. 
These include the following:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handler Exposure Database (USEPA, 1998) (See Appendix A for summaries of
these data sources). Most of the CMA data are of poor quality,
therefore, AD may request that confirmatory monitoring data be generated
to support the values used in these assessments. 

 

The quantities handled/treated were estimated based on information from
various sources, including HED’s Standard Operating Procedures (SOPs)
for Residential Exposure Assessments (USEPA 2000, and 2001) and the AD
Draft SOP use table.  In certain cases, no standard values were
available for some scenarios.  Assumptions for these scenarios were
based on AD estimates and could be further refined from input from
registrants. 

The low pressure spray unit exposure data from PHED were used to assess
outdoor applications of wood preservative coatings (exterior of homes). 
As the low pressure spray data are representative of treating low to mid
level range targets (shrubs/greenhouse benches) and the scenario
assessed in this document represents treatments that may also occur
above the waist, the unit exposure value may underestimate exposure to
the head and the upper body.

The methods used to estimate child and adult exposures to treated
textiles are highly conservative and based on approaches from the
Residential SOPs (USEPA 2000, and 2001) for contact with porous treated
surfaces (clothing, mattresses and carpets). Without data on actual
treated textile residues, dissipation or dermal transfer coefficients,
these scenarios have a high degree of uncertainty associated with them.
The registrants input will assist in refining the MOEs and confirming
the Oxine-Copper textile use patterns.    

In this assessment, incidental ingestion and dermal exposures to treated
wood were estimated using surrogate DDAC data (3 (g/cm2).  The degree of
uncertainty (under- or overestimation) associated with using the DDAC
hand residue data for dermal and oral exposure from contacting treated
lumber are unknown.  The amount of residue measured on the test
subjects’ hands is variable and may be influenced by the duration of
exposure, how often wood is contacted, and the degree of contact (i.e.,
do the hand residues from the DDAC study mimic a child’s play activity
on decks and playsets?). In comparison, measured wood retention data
from a chemical-specific leaching study (MRID 436370-01) were used as a
surrogate to represent potential residue load for child contact. The
maximum surface retention (surface deposition) measured from lumber
spray-treated with Oxine-Copper (27 (g/cm2) was used as a conservative,
high-end estimate. There is a high degree of uncertainty associated with
this value as well.

Data are not available to assess the levels of Oxine-Copper in soil
contaminated from Oxine-Copper-treated wood (e.g., above ground
fabricated components of decks or playsets). Because of this data gap,
EPA was not able to estimate residential post-application dermal and
incidental oral ingestion exposure to soil contaminated with
Oxine-Copper residues.  It is assumed that any soil residues attributed
to weathering of in-service wood (playsets) will remain near these
structures for potential child exposure. [Note: Soil migration study
data (MRIDs 429255-03, 429255-04) on file with the Agency for
Oxine-Copper indicate that between 88-90% of the applied active remained
in 0-6 cm of the tested soil columns, indicating limited leaching and
migration from soil matrices (USEPA, 2006c).]

	4.2	Dietary Exposure 

	AD has assessed the exposure and risk assessment of copper-8 quinoloate
for its uses in pulp/paper and adhesives. AD has determined that % aPAD
and or % cPAD for copper-8 quinolinolate uses in pulp/paper (% a PAD and
cPAD less than one percent for adults and children) and adhesives (%
cPAD less than one percent for adults and a little over one percent for
children) pose no dietary concerns for US populations.

FDA METHODOLOGY FOR DETERMINING ESTIMATED DAILY INTAKE (EDI) OF A
PESTICIDE USE IN A FOOD CONTACT PAPER.

For the determination of the amount of a pesticide migrating into food
when the food is in contact with the treated paper, FDA makes the
following assumptions:

	

Table 4.10 Dietary Use Pattern and Assumptions for
Copper-8-quinolinolate

Parameter	Assumption/Value

1.Paper slurry, prior to entering paper manufacturing machine	1%: 99%
water, 1% pulp

2.Concentration of slurries entering driers	33% pulp, 67% water

Table 4.10 Dietary Use Pattern and Assumptions for
Copper-8-quinolinolate

Parameter	Assumption/Value

3.Standard paper wt.	50 mg/in2

4.Finished paper	8% water, 92% pulp

5. Mass of food in contact with surface area of treated paper	10 g/in2

6. Consumption factor (CF)*	0.10

7. Daily  average food intake (adult)	3000 g

8. Daily average food intake (child)	1500 g

Note: *FDA1, 2, 3 Method makes a number of assumptions for calculating
migration of active (in this case copper-8-quinolinoate)) from food
contact surfaces (paper): 1. Food contact surface (paper) can be a one
time use/day or a repeat use material; 2. Consumption factor (CF) or
fraction of daily food which comes in to contact with the packaging
surface (paper). CF represents the actual weight of food that comes into
contact with the paper to the weight of all food packaged with paper; 3.
The CF varies from one type of packaging (type of paper) to the other
(type of paper). FDA methodology of migration of active assumes a 100%
migration to the food commodities (This represents a worst case
scenario).

Note:	Label search indicates that copper-8-quinolinoate is used in pulp
and paper in more than one formulation. : 1) PQ-56 (EPA Reg#: 1022-489);
2) PQ-57 (EPA Reg#: 1022-490); 3) Cunilate 2174-NO (EPA Reg#: 2829-44);
4) Cunilate 2002 (EPA Rg#: 707-302); 5) Cu-8 (EPA Reg#: 10827-5). In all
applications for pulp and paper maximum active is 10% and in all
application dilutions are made. The minimum dilution is 0.5% active or
0.5 lb of active per 1000 lbs of paper. This also translates into 1.0
lbs active per 2000 lbs.  A short ton = 2000 lbs.  This rate of
application was used to determine the exposure of this active to food
through indirect contact with paper.

AD’s End Points Selection Committee determined that: cPAD (chronic
RfD) for Copper-8 quinolinolate is 0.05 mg/kg/day. Table 4.11 summarizes
the estimations for % cPAD. 

Table 4.11  Estimations for % cPAD for Copper-8-quinolinolate

Dietary Conc. Of Cu-8	Estimated Daily Intake (EDI)	Daily Dietary Dose
(DDD): mg/kg/day	% cPAD

(cPAD = 0.05 mg/kg/day)

10.0 µ g	

Adult: 13.8 µg

	

Adult: 0.00197 mg/kg/day ∕ 0.05 mg/kg/day x 100

= 0.3%

	

Child: 6.9 µg	

Child: 6.9µg/70 kg/day = 0.0046 mg/kg/day	Child: 0.0046 mg/kg/day ∕
0.05 mg/kg/day = 0.9% 

The calculations of % cPAD show that there are no chronic dietary
concerns from the migration of Cu-8 from paper to food. No acute dietary
end points exist, and therefore, Agency does not have any acute exposure
from the use of Cu-8 by migration into foods.

	AD has assessed adhesive use as an indirect food use.  Since it is
likely that adhesives may end up in the food packaging materials, and
this may result in the migration of the pesticide into the food
indirectly.  For the indirect food dietary assessment, AD has adopted
Food & Drug Administration (FDA) methodology.  For adhesive use, FDA has
provided guidance for dietary estimation that a maximum of 7 ppb of a
pesticide is likely to migrate from the food packaging materials into
the food. The quantity of 7 ppb can be used to calculate the Estimated
Daily Intake (EDI), Daily Dietary Dose (DDD), and using the acute and
dietary end points from toxicity data, one calculates the overall risks
to general and subgroups of populations (% aPAD, and % cPAD).

Table 4.12 gives estimates of % cPAD for adhesive use of
Copper-8-quinolinolate.

Table 4.12   Estimates of % cPAD for adhesive use of
Copper-8-quinolinolate

Use	Dietary Conc. (ppb)	Estimated Daily Intake (EDI) µg/p/day	Daily
Dietary Dose (DDD) mg/kg/day

 

	% aPAD	% cPAD

( cPAD) = o.05 mg/kg/day

Adhesive	

7	

Adult: 7µg/kg x 3000g = 21
µg/p/d祡഍桃汩㩤㜠딠⽧杫砠ㄠ〵‰⁧‽〱㔮딠⽧⽰慤ݹ
䄍畤瑬›ㄲ딠⽧〷欠⽧慤⁹‽⸰〰㌰洠⽧杫搯祡഍桃汩
㩤ㄠ⸰‵딠⽧㔱杫搯祡㴠〠〮〰‷杭欯⽧慤ݹ䄍畤瑬›
潮搠瑡⹡丠⁯潣据牥獮മ䌍楨摬›潮搠瑡⹡丠⁯潣据牥
獮ܮ

Adult:  0.0003 mg/kg/day ∕ 0.05 mg/kg/day x100 = 0.6%

Child: 0.0007 mg/kg/day ∕ 0.05 mg/kg/day x 100  = 1.4 %

These calculations assume that the adhesive use is 100% of the chemical
produced, which is not a likely scenario. The actual % cPAD is going to
be much lower than the estimated one. The Agency has no chronic dietary
concerns from the use of Copper-8 Quinoloate in adhesives.

Another scenario which may likely pose some concerns is the use of
copper-8 treated wooden trays which are used to store or transfer foods.
No data, laboratory or monitoring, were submitted. It is therefore a
data gap for the dietary risk assessment for copper-8.

	4.3	Drinking Water Exposure 

Oxine-Copper is not used for potable water treatment, nor are effluents
containing this chemical expected in fresh water environments.
Oxine-Copper is not used for potable water treatment, nor are effluents
containing this chemical expected in fresh water environments. Hence a
drinking water exposure assessment for copper-8-quinolinolate was not
conducted.

	4.4	Residential Exposure/Risk Pathway

	The exposure scenarios assessed in this document for the representative
uses selected by AD are shown in Table 4.1. The table also shows the
maximum application rate associated with the representative use and the
EPA Registration number for the corresponding product label.  For
handlers, the representative uses assessed include treatments to wood
surfaces (e.g., water repellents and coatings applied via brush, roller
and low-pressure coarse spray). Additionally, handler exposures were
assessed for the application of manufactured paint products containing
Oxine-Copper as a preservative (paint brush/roller and airless sprayer).

5.0	AGGREGATE RISK ASSESSMENT AND CHARACTERIZATION

	In order for a pesticide registration to continue, it must be shown
“that there is reasonable certainty that no harm will result from
aggregate exposure to pesticide chemical residue, including all
anticipated dietary exposures and other exposures for which there are
reliable information.” Aggregate exposure is the total exposure to a
single chemical (or its residues) that may occur from dietary (i.e.,
food and drinking water), residential, and other non-occupational
sources, and from all known or plausible exposure routes (oral, dermal,
and inhalation).  

In performing aggregate exposure and risk assessments, the Office of
Pesticide Programs has published guidance outlining the necessary steps
to perform such assessments (General Principles for Performing Aggregate
Exposure and Risk Assessments, November 28, 2001; available at
http://www.epa.gov/pesticides/trac/science/aggregate.pdf).  Steps for
deciding whether to perform aggregate exposure and risk assessments are
listed, which include: identification of toxicological endpoints for
each exposure route and duration; identification of potential exposures
for each pathway (food, water, and/or residential);  reconciliation of
durations and pathways of exposure with durations and pathways of health
effects; determination of which possible residential exposure scenarios
are likely to occur together within a given time frame; determination of
magnitude and duration of exposure for all exposure combinations;
determination of the appropriate technique (deterministic or
probabilistic) for exposure assessment; and determination of the
appropriate risk metric to estimate aggregate risk

	

	5.1	Acute and Chronic Dietary Aggregate Risk

	In general, acute and chronic dietary aggregate risks are represented
by dietary (direct, indirect, and inert exposures) and drinking water
exposures.  For copper-8-quinolinolate, an aggregate dietary exposure
and risk assessment could be performed for the pulp and paper use as
well as the adhesive use of copper 8-quinolinolate.  This may be an
under estimation of the risk due to a lack of data on the exposure from
use of copper 8-quinolinolate in wooden trays which are used to store or
transfer foods.    

    	Total aggregate dietary exposure and risk from
copper-8-quinolinolate is shown below in Table 5.1.  The results
indicate that for adults, 5% of the cPAD is occupied from all dietary
exposure sources, while for children, 11% of the cPAD is occupied from
all dietary sources.  These percentages are below 100% of the cPAD and
are thus not of concern to the Agency.  

Table 5.1 Aggregate Dietary Exposures and Risks (direct, indirect, and
inert  uses)

Population	Indirect Dietary Exposure (mg/kg/day)	

cumulative

/kg/day ∕ 0.05 mg/kg/day x 100 = 4.6%

Children	0.0046 (paper) + 0.0007 (adhesive) = 0.0053	0.0053 mg/kg/day
∕ 0.05 mg/kg/day x 100 = 10.6%

5.2	  SEQ CHAPTER \h \r 1 Short- and Intermediate-Term Aggregate
Exposures and Risks 	Acute and Chronic Dietary Aggregate Risk

For copper-8-quinolinolate, a short-term aggregate assessment for adults
is not performed.  Toxicity endpoints of concern involving oral, dermal,
and inhalation were selected from separate studies with differing
toxicological effects.  In addition, the nature of the exposures from
painting activities, mold remediation, and contact with textiles (which
are limited to industrial/government use items) are episodic in nature
and probability of co-occurrence is unlikely.  There are no
intermediate-term scenarios for adults. Therefore, adult exposures are
not aggregated.   

For toddlers, aggregation of incidental oral, dermal, and inhalation
exposures is not performed across routes of exposure as toxicity
endpoints of concern were derived from separate toxicity studies. 
However, it is possible to aggregate exposures within a route of
exposure to the extent reasonable. Thus, incidental oral exposures of
children from mouthing of treated textiles with hand-to-mouth activities
and from exposure to treated outdoor hard surfaces and lumber can be
performed.   

Results of the short-term aggregate assessment for toddlers or children
to incidental oral post applicator exposures are presented in Table 5.2.

Table 5.2. Short-term Aggregate  Risk Assessment for Incidental Oral
Exposures in  

                  Children                                              
                                           

Exposure Routes	Exposure (mg/kg/day)	Margin of Exposure	Total MOE

Incidental oral aggregate

     -treat outdoor surfaces

     -mouthing textile (tent/tarp)

     -surrogate hand residue	

0.00544

0.272

0.252	

36,765

735

794	

373

	

a: Aggregate MOE = 1/((1/MOE incid,oral) + (1/MOEincid,oral) +  (1/MOE
incid,oral)) where MOE = NOAEL (mg/kg/day) / absorbed daily dose
(mg/kg/day) [Incidental oral NOAEL (maternal): 200 mg/kg/day].

Table 5.3 presents the results of short-term dermal aggregate exposure
and risk for children from dermal contact with outdoor treated hard
surfaces, textiles, and treated wood.  The Margin of Exposure from
children’s dermal exposure from contact with treated textiles is alone
of concern (MOE = 50 assuming 5% residue transfer), and thus is not
included in the aggregate assessment.  Refinement of this exposure
scenario is necessary to arrive at a better estimate of risk.   

Table 5.3. Short-term Aggregate  Risks from  Dermal Exposures in
Children

Exposure Routes	Children

	Exposure (mg/kg/day)	Margin of Exposure

Treated Outdoor hard surface	0.0446	4,484

Wood Products	1.55	129

TOTAL MOE

125

a: Aggregate MOE = 1/ ((1/MOEtreated hard)  + (1/MOE wood products))
where MOE = NOAEL (mg/kg/day) / absorbed daily dose (mg/kg/day) [Dermal 
NOAEL (systemic): 200 mg/kg/day].

6.0	CUMULATIVE EXPOSURE AND RISK

	

Risks summarized in this document are those that result only from the
use of Copper-8-quinolinolate. The Food Quality Protection Act (FQPA)
requires that the Agency consider “available information” concerning
the cumulative effects of a particular pesticide’s residues and
“other substances that have a common mechanism of toxicity.” The
reason for consideration of other substances is due to the possibility
that low-level exposures to multiple chemical substances that cause a
common toxic effect by a common toxic mechanism could lead to the same
adverse health effect as would a higher level of exposure to any of the
substances individually. Unlike other pesticides for which EPA has
followed a cumulative risk approach based on a common mechanism of
toxicity, EPA has not made a common mechanism of toxicity finding for
Copper-8-quinolinolate. For information regarding EPA’s efforts to
determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the policy
statements released by EPA’s Office of Pesticide Programs concerning
common mechanism determinations and procedures for cumulating effects
from substances found to have a common mechanism on EPA’s website at  
HYPERLINK "http://www.epa.gov/pesticides/cumulative/_" 
http://www.epa.gov/pesticides/cumulative/ .

7.0	OCCUPATIONAL EXPOSURE ASSESSMENT

	7.1	Summary of Registered Uses

	Potential occupational handler exposure can occur in various use sites,
which include food handling premises, commercial/industrial premises,
and even applications done in residential sites.  The exposure scenarios
assessed in this document for the representative uses selected by AD are
taken from Table 7.1. The table also shows the maximum application rate
associated with the representative use and the appropriate EPA
Registration number for the product label.  For handlers, the
representative uses assessed include various materials preservative and
wood preservative applications: mixing and loading of product
concentrates for materials 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).

	The “preservation of materials” refers to the scenario of a worker
adding the preservative to the material being treated through either
liquid pour or liquid pump methods.  Liquid pour refers to transferring
the antimicrobial product from a small container to an open vat.  Liquid
pump refers to transferring the preservative by connecting/disconnecting
a chemical metering pump from a tote or by gravity flow.  For the
preservation of wood at treatment plants and lumber mills, the methods
for treatment can vary (pressure/non-pressure), such that multiple
worker functions were analyzed.  Due to the complexity of the wood
preservative analysis, the results for handler and post-application
exposures are presented in a separate section, 7.4.



Table 7.1.  Representative Exposure Scenarios Associated with
Occupational Exposures to Oxine-  

                   Copper                                             

Representative Use	

Method of Application	

Exposure Scenario	

EPA Reg. No.	

Maximum Application Rate

Wood Preservatives (Use Site Category X)

Non-pressure treatment of wood and wood products in wood treatment
facilities 

	Handler Worker Functions

Diptank Operators

Blender/spray operators

Chemical operators

Post-Application Worker Functions

Graders

Trim saw operators

Clean-up crews

Construction Workers	

ST/IT/LT Handler & Post-application: Dermal and inhalation	3008-91

	Diptank operators and Blender/spray operators:

2.3 % ai water-borne treatment solution used (1:15 v/v dilution of
34.18% ai product)

Chemical operators and all other worker functions:

34.18% ai in water-borne product concentrate handled.

 

Pressure treatment of wood and wood products in wood treatment
facilities 

	Handler Worker Functions

Treatment assistant

Treatment operator

Post-Application Worker Functions

Tram setter, stacker operator, loader operator, supervisor, test borer,
and tallyman	ST/IT/LT Handler & Post-application: Dermal and inhalation
2829-135;

2829-136	1.0 % ai solvent-borne treatment solution used (10% w/w
solution of 10% ai product) via vacuum/empty-cell methods

General Preservation of wood in commercial sites (non-pressure treatment
applications to wood including indirect food contact wood) 

	Brush/Spray and Dip methods employed for this use pattern 	ST/IT
Handler: Dermal and Inhalation 

	2829-135;

2829-136

	Dip 1.0 % a.i. solvent-based treatment solution (applied at a rate of
10% w/w of 10 % a.i. product)

	1022-489;

75675-1	Brush  3.3% ai water-based treatment solution (1:3dilution of
10% ai product) for ground-contact wood

Wood Preservative Coatings/ Water Repellents

	Paint brush,

Roller and Low-pressure coarse sprayer 

	ST/IT Handler: Dermal and Inhalation	1022-504;  1022-514; 81819-1
0.675%-0.8% ai ready-to-use (RTU) water and oil-based exterior coatings
for log homes, wood roofs, siding, fences, rough sawn lumber, new/old
wood. 150-300 sq ft/gal. as one coat application.

Material Preservatives (Use Site Category VII)

Paints/Coatings 

(in-can preservative incorporation)	

Preservation of paint

Liquid pour

Liquid pump

Commercial/

Professional painter

Brush/Roller

Airless sprayer

	

ST/IT/LT Handler: Dermal and Inhalation

ST/IT Prof Painter:

Dermal and Inhalation (aerosol particulate) 6	

2829-136

Treated article preserved with 2829-136 (e.g., exterior house paint) 	

1.0 % a.i. incorporation by volume of the material to be treated (10 %
product by volume treated x 10 % a.i. in product) Note: Adhesives are
incorporated at 0.1 % ai 

[Solvent-based]

Paper and Paperboard 

	Liquid pump

(i.e., incorporation at the size press during manufacture of paper and
paperboard sheets)

	

ST/IT/LT Handler: Dermal and Inhalation	

2829-112

	

0.24% a.i. incorporation by weight of the material to be treated (3.2%
product by weight of material treated x 7.5% a.i. in product)

[Water-based]

	Brush/Spray and Dip impregnation methods employed for this use pattern

1022-489;

75675-1

	0.4% ai water-based treatment solution impregnation (1:25 dilution of
10% ai products)

Textiles

[Industrial-use and government-specified (e.g., military-issued)
cloth/webbing/ropes used for tents/tarps, cotton duck/canvas, paper,
paperboard for shoe construction]	

Liquid pour

Liquid pump

(i.e., incorporation at the padder during textile processing)

	

ST/IT/LT Handler: Dermal and Inhalation

	2829-42;

2829-49;

2829-112

	

0.7% ai (industrial-use) to

 1.0 % ai (government-use) incorporation by weight of the material to be
treated (10 % w/w  of 10 % a.i. products for 2829-42 and 2829-49)

[Solvent- & Water-based]

	

Brush/Spray and Dip impregnation methods employed for this use pattern 

2829-135;

2829-136;

60061-22

	Mildew inhibitor to cotton duck, canvas, cotton webbing and rope

Dip: 

0.2% ai to 1.0 % ai (government-use);

1.0% ai as RTU (60061-22)

[Solvent-based]

Material Preservatives (Use Site Category VII)

Environmental Outdoor Hard Surface Treatments 

(i.e., mold and mildew control treatments to exterior environmental
surfaces )	

Brush/Spray

Tank-type garden sprayer  (i.e., Low pressure sprayer)	

ST/IT Handler: Dermal and Inhalation

	

1022-489;

1022-490;

75675-1

	

0.1% ai water-based treatment solution (1:100 dilution of 10% ai
product; 1:50 dilution of 5% ai product) used on paint/varnish,
concrete, brick, glass, tile, metals, plastic, wood, (paper)*,
(leather)*, textiles and asphalt shingles.

* - Treatments to these materials may indicate potential indoor uses.
Clarification of labeling is needed. 

Food Handling/Storage Establishments, Premises and Equipment (Use Site
Category II)

Indoor Hard Surfaces Disinfection for Potato Ring Rot

  

(e.g., potato processing planters, seed handling equipment, seed
cutters, storage areas, truck/railcar transportation equipment.)

	

Spray- Low pressure spray non-mist nozzle 20 psi	

ST/IT Handler: Dermal and Inhalation	

1022-489;

1022-490; and 

75675-1	

0.05% ai water-based treatment solution (1:200 dilution of 10% ai
product; 1:100 dilution of 5% ai product)

Note: Only EPA registered products with specified use directions/use
applications are included in this table.  Products listed were selected
based on maximum use rates by application method.  

ST = Short-term exposure, IT = Intermediate-term exposure, LT= Long-term
exposure. 

6 Handler dermal and inhalation  exposure (to aerosol  particulates)
were assessed for Oxine-Copper using PHED unit exposures. 

	       7.2   Occupational Handler Exposures

	Certain occupational handler scenarios included in Table 7.1 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 general assumptions and
equations that were used to calculate occupational handler risks are
provided in Section 4.0, Criteria for Conducting the Risk Assessment.
The majority of the scenarios were assessed using CMA data and Equations
1-3.  However, for the occupational scenarios in which CMA data were
insufficient, other data and methods were applied. 

	

Unit Exposure Values (UE):  Dermal unit exposure values were taken from
the proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handlers Exposure Database (USEPA, 1998).  

For the liquid pour scenarios for materials preservatives, the unit
exposure depends on the material being treated.  The following CMA unit
exposures were available and used for the assessment of the risk
associated with the treatment of the specified materials.

 Paint and Textiles: CMA preservative gloved data.  The dermal UE is
0.135 mg/lb a.i. and the inhalation UE is 0.00346 mg/lb a.i.. The values
are based on 2 replicates where the test subjects were wearing a single
layer of clothing and chemical resistant gloves. Since no baseline
dermal (ungloved) unit exposure data are available for preservative uses
in paints or textiles, the baseline dermal exposures were evaluated
using the cooling tower CMA data (50.3 mg/lb ai). 

For the liquid pump scenarios, the unit exposure depends on the material
being treated. The following CMA unit exposures were available and used
for the assessment of the risk associated with the treatment of the
specified materials.

 Paint and Textiles:  CMA preservative gloved data.  The dermal UE is
0.00629 mg/lb a.i. and the inhalation UE is 0.000403 mg/lb a.i.  The
values are based on two replicates where the test subjects were wearing
a single layer of clothing and chemical resistant gloves. Since no
baseline dermal (ungloved) unit exposure data are available for
preservative uses in paints or textiles, the baseline dermal exposures
were evaluated using the cooling tower CMA data (0.454 mg/lb ai). 

Pulp and Paper:  CMA pulp and paper gloved data.  The dermal UE is
0.00454 mg/lb a.i. and the inhalation UE is 0.000265 mg/lb a.i. The
values are based on 7 replicates where the test subjects were wearing a
single layer of clothing and chemical resistant gloves. Since no
baseline dermal (ungloved) unit exposure data are available for
preservative uses in adhesives, paint, or textiles, the baseline dermal
exposures were evaluated using the cooling tower CMA data (0.454 mg/lb
ai). Only closed application methods were assessed for pulp/paper based
on industrial practices. Therefore, a liquid pour scenario for
preservation of paper/paperboard with Oxine-Copper was not developed.

For the low pressure sprayer (course spray) scenarios, the occupational
PHED dermal and inhalation unit exposure values for a handler pouring a
pesticide and applying it via a low pressure sprayer (hand wand) were
used (PHED scenario 32).  The unit exposure values of 100 mg/lb a.i. for
ungloved dermal, 0.43 mg/lb a.i. for gloved replicates, and 0.030 mg/lb
a.i. for inhalation represent a handler treating low and mid-level
targets, generally below the waist (greenhouse benches and shrubs) while
wearing a single layer of clothing. 

For roller/brush scenarios, the occupational PHED dermal and inhalation
unit exposure values for paintbrush applications (PHED scenario 22) were
used (single layer of clothing).  The inhalation exposure value is 0.28
mg/lb a.i. The dermal unit exposures are 180 mg/lb a.i. for ungloved
replicates and 24 mg/lb a.i. for gloved replicates. 

For the airless sprayer scenario, the occupational PHED dermal and
inhalation unit exposure values for airless sprayer application (PHED
scenario 23) were used (single layer of clothing). The inhalation
exposure value is 0.83 mg/lb a.i. The dermal unit exposures are 38 mg/lb
a.i. for ungloved replicates and 14 mg/lb a.i. for gloved replicates. 

Quantity handled/treated: The quantity handled/treated values were
estimated based on information from various sources.  The following
assumptions were made:

For the liquid pour scenarios, the quantity of the chemical that is
handled depends on the material that is being treated.  The following
values were used for the different materials:

Paint:  2,000 lbs (approximately 200 gallons, weight based on a density
10 lb a.i./gal) (USEPA, 2005).	

Textiles:  10,000 lbs (USEPA, 2005).

For the liquid pump scenarios the quantity that is handled depends on
the material that is being treated.  The following values were used for
the different materials:

Paint:  10,000 lbs (approximately 1,000 gallons, weight based on a
density of 10 lb a.i./gal) (USEPA, 2005).

Textiles:  10,000 lbs (USEPA, 2005).

Paper/Paperboard:  These applications are expected to be similar to
textile treatments, but a standard value of 500 tons is used as a
high-end assumption (500 tons x 2204.622 lb/ton = 1102311 lbs). 

For the low pressure sprayer (course spray) scenarios, it was assumed
that 100 lbs (approximately 12 gallons of water-based treatment solution
having a density of water 8.34 lb/gal) are used for the outdoor hard
surface treatments (Agency assumption); and for the wood coating
scenario it was assumed that 500 lbs (approximately 50 gallons of paint
with a density of 10 lb/gal) of treated paint are used. (USEPA, 2005).

For the roller/brush painting scenario, it was assumed that 50 lbs
(approximately 5 gallons of paint with a density of 10 lb/gal) of
treated paint are used (USEPA, 2005).

For the airless sprayer scenario, it was assumed that 500 lbs
(approximately 50 gallons of paint with a density of 10 lb/gal) of
treated paint are used. (USEPA, 2005).

Duration of Exposure: The MOEs were calculated as ST/IT dermal and
ST/IT/LT inhalation based on end-point selection in Table 3.2.  It is
assumed however, that occupational handlers will have exposures of
short- and intermediate-term durations only.   

Exposure Calculations and Results

	The resulting exposures and MOEs for the representative occupational
handler scenarios are presented in Table 6.2. The calculated dermal MOEs
were all above the target MOE of 100 with the use of glove PPE. Baseline
dermal estimates for workers without gloves indicated risk concerns for
certain scenarios listed below.   It should be noted that the 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 CMA data set because data for baseline
dermal unit exposures were not available for preservative scenarios.   

General wood preservative brush applications: ST/IT MOE = 47.

Painting (professional) wood coatings, low pressure sprayer: ST/IT MOE =
35.

Painting (professional) treated paint, airless sprayer: ST/IT MOE = 74.

Paper preservation, liquid pump: ST/IT MOE = 12.

Paint preservation, liquid pour: ST/IT MOE = 14.

Textile preservation, liquid pour: ST/IT MOE = 3.

	Most inhalation MOEs were above the target MOE of 1000, except for the
scenarios indicated below.  It should be noted that for MOEs below 1,000
the Agency may request a confirmatory inhalation toxicity study to
refine the potential risks since the current inhalation endpoint is
based on an oral NOAEL.  

General wood preservative brush applications: ST/IT/LT MOE = 758.

Paper preservation, liquid pump: ST/IT/LT MOE = 500.

Painting (professional) treated paint, airless sprayer: ST/IT/LT MOE =
83 / 833 (PPE).

	7.3  	Occupational Post-application Exposures

	Except for the post-application scenarios assessed for wood
preservatives in Section 7.4, occupational post-application exposures
are assumed to be negligible. 	

	

Table 7.2  Short-, Intermediate-, and Long-Term Risks Associated with
Occupational Handlers

Exposure Scenario	

Method of Application	

Unit Exposure (mg/lb a.i.)	Application Rate (% a.i. by weight)	

Quantity Handled/ Treated per day	

Absorbed Daily Dose (mg/kg/day)c	

MOEd

Baseline Dermala	

PPE-Gloves Dermalb	

 Inhalation

	

Baseline Dermala

	

PPE-

Gloves Dermalb

	Inhalation

	

Baseline Dermal

 (Target MOE = 100)a	

PPE-Gloves Dermal

 (Target MOE = 100) b	Inhalatione

 

(Target MOE = 1000)

ST/IT	

ST/IT	ST/IT/LT

Wood Preservatives (Use Site Category X) *

General Wood Preservative Application by Professionals	Brush	180	24	0.28
0.033	50 lbs	4.24	0.566	0.0066	47	353	758

Application of Wood Coatings by Professionals	

Brush/ Roller	180	24	

0.28	0.008	

50 lbs	1.03	0.137	0.0016	194	1,460	3,125

	

Low Pressure Sprayer	100	0.43  	0.030	0.008	

500 lbs	5.71	0.025	0.0017	35	8,000	2,941

Material Preservatives (Use Site Category VII)

Preservation of  Paper and Paperboard

	

Liquid Pump	0.454	0.00454	0.000265	0.0024	

(500 tons) 

1,102,311 lbs	17.16	0.172	0.01	12	1,163	500

	Brush

	180	24	0.28	0.004	50 lbs	0.514	0.069	0.0008	389	2,898	6,250

Preservation of Paint

(in-can preservative)

	

Liquid Pour

	50.3	

0.135	

0.00346	

0.01	

2,000 lbs	14.37	0.039	0.001	14	5,128	5,000

	

Liquid Pump	0.454	

0.00629	

0.000403	

0.01	

10,000 lbs	0.649	0.0089	0.0006	308	22,472	8,333

Preservation of Textiles

	

Liquid Pour

	50.3	

0.135	

0.00346	

0.01	

10,000 lbs	71.86	0.193	0.005	3	1,036	1,000

	

Liquid Pump	0.454	

0.00629	

0.000403	

0.01	

10,000 lbs	0.649 	0.0089 	0.0006	308	22,472	8,333

Material Preservatives (Use Site Category VII)

Application of Treated Paint by Professionals

	

Brush/ Roller	

180	

24	

0.28	

0.01	

50 lbs	1.29	0.17	0.002	155	1,176	2,500

	

Airless Sprayer	

38	

14	

0.83	

0.01	

500 lbs	2.71	1.0	0.060	74	200	83	833

PPE

Commercial application to outdoor hard surfaces 	Low Pressure Sprayer
100	0.43	0.030	0.001	100 lbs	0.143	0.00061	0.000043	1,399	327,869
116,280

	

	* Note:  Other Occupational scenarios for Wood Preservatives are
assessed separately in Section 6.4.

	

	ST= Short-term;  IT = intermediate-term, NA= No data available (or not
applicable for dermal absorption factor).

	Unit Exposure (UE) Data from CMA for most scenarios. PHED data used for
Brush/Roller and Airless Sprayer.

	a	Baseline Dermal:  Long-sleeve shirt, long pants, no gloves. It should
be noted that the baseline dermal unit exposures for the preservation of
paper, paint and textiles were from the cooling tower CMA data set
because baseline (ungloved) dermal unit exposures are not available for
the CMA data set on preservatives. 

 	b	PPE Dermal with gloves: baseline dermal plus chemical-resistant
gloves.  No gloved replicates available for CMA Low Pressure Spray
scenario.

	c	Absorbed Daily dose (mg/kg/day) = [unit exposure (mg/lb a.i.) *
absorption factor (NA for dermal; 100% (1.0) for  inhalation) *
application rate * quantity treated / Body weight (70 kg).

	d	MOE = NOAEL  (mg/kg/day) / Absorbed Daily Dose [Where ST/IT Dermal
NOAEL (systemic)  = 200 mg/kg/day; ST/IT/LT Inhalation NOAEL = 5
mg/kg/day].

	e	For PHED data, a protection factor of 90% can be applied to UE values
to represent use of organic vapor respirators as PPE.  Any PHED Baseline
inhalation painting scenarios (Brush/Roller or Airless Sprayer) with
MOEs below the target of 1000 were also assessed for use of PPE.

	7.4 	Wood Preservation

	Oxine-Copper is used industrially as a stand-alone preservative to
control sapstain, and protect against mold/mildew in softwood or
hardwood lumber.  It can also protect against insect damage for wood
used in mainly above-ground use applications.  Where ground- contact
protection is needed, usually higher concentrations of preservative
treatment solutions are used and applied via non-pressure methods  Wood
treated with Oxine-Copper has a greenish-brown color, and little or no
odor.

	Registered uses for Oxine-Copper include several wood preservative
treatments as wood surface coatings (e.g., water repellents applied via
brush, roller or spray) and impregnation into wood via non-pressure
(e.g., non-pressure dipping/immersion) and pressure techniques
(vacuum/empty-cell).  The products can be used on many different types
of wood including 1) green or fresh cut/debarked lumber, poles, posts,
and timbers; 2) manufactured wood products such as logs (including for
log home construction), plywood, and particle board (wood composites);
3) dry lumber; and 4) finished wood products such as millwork, shingles,
shakes, siding, plywood and structural lumber. The majority of the
products are intended for use at wood treatment facilities, 

	The exposure scenarios assessed in this document for the representative
wood preservation uses selected by AD are shown in Table 7.1.  Section
7.4.1 presents the exposure analysis for the handler and
post-application scenarios for non-pressure treatment scenarios and
Section 7.4.2 presents the exposure analysis for the handler and
post-application scenarios for pressure treatment scenarios. 

		7.4.1 	Non-Pressure Treatment Scenarios (Handler and Post-application)

			7.4.1.1   Scenarios Assessed by Worker Function 

	Handler and post-application scenarios that have been identified and
assessed using surrogate data.  The proprietary study, “Measurement
and Assessment of Dermal and Inhalation Exposures to Didecyl Dimethyl
Ammonium Chloride (DDAC) Used in the Protection of Cut Lumber (Phase
III)” (Bestari et al., 1999, MRID 455243-04) identified various worker
functions/positions for individuals that handle DDAC-containing wood
preservatives for non-pressure treatment application methods and for
individuals that could then come into contact with the preserved wood.
Representative worker functions/positions identified in the DDAC study
are presented below. It was assumed that the workers at facilities using
Oxine-Copper wood preservatives, and handling the treated wood are
performing similar tasks as those monitored in the DDAC study. This
study was sponsored by an industry consortium [Sapstain Industry Group
(SIG) Task Force # 73154]; therefore, data compensation issues apply for
use of these data as a surrogate source in assessing exposure.  

Handler:

Blender/spray operators are workers that add the wood preservative into
a blender/sprayer system for composite wood via closed-liquid pumping.

Chemical operators for a spray box system consist of chemical operators,
chemical assistants, chemical supervisors, and chemical captains.  These
individuals maintain a chemical supply balance and are assigned the task
of flushing and cleaning spray nozzles. 

Diptank Operators can be in reference to wood being lowered into the
treating solution through an automated process (i.e.: elevator diptank,
forklift diptank).  This scenario can also occur in a small scale
treatment facility in which the worker can manually dip the wood into
the treatment solution.

Post-application: 

Graders are expected to be positioned right after the spray box
sequence, where they grade the dry lumber by hand (i.e. detect faults). 
In the DDAC study, graders graded wet lumber; therefore, the exposures
to graders using Oxine-Copper are assumed to be the worst-case
scenarios.    

Trim saw operators operate the hula trim saw and consist of operators
and strappers.  In the DDAC study, hula trim saw operators handled dry
lumber. 

Millwrights repair all conveyer chains and are involved in a general
up-keep of the mill.  

Clean-up crews perform general cleaning duties at the mill.

Construction workers install treated plywood, oriented strand board,
medium density fiberboard, and others.  

	In lieu of chemical-specific data available regarding typical exposures
to Oxine-Copper as a wood preservative, surrogate data were used to
estimate exposure risks. The blender/spray operator position was
assessed using CMA unit exposure data and the remaining handler and
post-application positions were assessed using data from the DDAC study
(Bestari et al., 1999). 

Blender/Spray Operators

	Exposures and risks to the blender/spray operators were assessed using
Equations 1 through 3 in Section 4.0.  The surrogate unit exposures were
taken from the CMA study (USEPA, 1999).  Specifically, the liquid pump
preservative unit exposures for gloved workers were used in this
assessment.  The dermal unit exposure was 0.00629 mg/lb ai and the
inhalation unit exposure was 0.000403 mg/lb ai. These values are based
on two replicates where the test subjects were wearing a single layer of
clothing and chemical resistant gloves.  The quantity of the wood being
treated was derived from other wood preservative estimates (USEPA, 2004)
for the amount of wood slurry treated because no chemical specific data
were available for Oxine-Copper.  It was assumed that batches of wood  
SEQ CHAPTER \h \r 1 slurry are treated in 10,000 gallon tanks, and that
eight batches of wood slurry are treated per day (one per hour for an
8-hr work shift).  Additionally, it was assumed that each batch requires
3,000 gallons of preservatives and the remainder volume of the tank
consists of wood slurry (7,000 gallons of wood slurry per batch).  Since
wood chips have a density of approximately 380 kg/m3 (SIMetric, 2005),
the total amount of wood slurry treated per day would be 178,000 lbs
(i.e., 8 batches/day * 7,000 gallons/batch * 0.003785 m3/gallon * 380
kg/m3 * 2.2 lb/kg).    SEQ CHAPTER \h \r 1 The assumptions used for
batch sizes and the quantity of preservative needed are consistent with
an assessment performed previously by the EPA. The Oxine-Copper
assessment was conducted based on use-application of a 2.3 % ai
solution.  This represents the maximum application rate for both diptank
and spray methods for sapstain treatment as per product labeling for EPA
Reg. No. 3008-91.  This product is a 34.18 % ai concentrate used to make
water-based treatment solutions of up to 2.3% ai [i.e., 1:15 v/v use
dilution (0.0666) x 34.18 % ai in product = 2.3 % ai].  Product labeling
cites use of eye protection and rubber gloves as PPE.

	Table 7.3 provides the short-, intermediate-, and long-term doses and
MOEs for the blender/spray operators adding the preservative to the wood
slurry.  The dermal ST/IT MOE was 540 which is above the target MOE of
100 and therefore not of concern.  The inhalation ST/IT/LT MOE was below
the Agency target of 1,000, as 212, denoting a potential risk concern. 
For inhalation MOEs below 1,000 the Agency may request a confirmatory
inhalation toxicity study since the current inhalation endpoint is based
on an oral NOAEL.

Table 7.3. Short-, Intermediate-, and Long-term Exposures and MOEs for
Wood Preservative Blender/Spray Operators

Exposure Scenario

	Dermal Unit Exposurea

(mg/lb ai)	Inhalation Unit Exposureb

(mg/lb ai)	Application Ratec

(% ai in solution/

day)	Wood Slurry Treatedd

(lb/day)	Absorbed Daily Dosee 

(mg/kg/day)	MOEsf

	Dermal	Inhalation	Dermal

ST/IT

Target=100	Inhalation

ST/IT/LT

Target = 1000

Occupational Handler

CMA Liquid Pump	0.00629	0.000403	2.3	178,000	0.37	0.0236	540	212

ST =	Short-term duration; IT =Intermediate-term duration; and LT =
long-term.

Dermal unit exposure: Single layer clothing with chemical resistant
gloves.

Inhalation unit exposure: Baseline, with no respirator.	

c.	The maximum application rate for both diptank and sapstain spray
application methods is 2.3% ai solution based on product labeling
(3008-91).  

d.	Wood slurry treated = (8 batches/day * 7,000 gallons/batch * 0.003785
m3/gallon * 380 kg/m3 * 2.2 lb/kg)	

e.	Absorbed Daily Dose = unit exposure (mg/lb ai) x App Rate (% ai/day
as 2.3%; the ai weight fraction is 0.023) x Quantity treated (lb/day) x
absorption factor (NA for dermal and 100% for inhalation) / BW (70 kg)

f.	MOE = NOAEL (mg/kg/day) / Daily dose [Where ST/IT (systemic) NOAEL =
200 mg/kg/day for dermal and 

	ST/ /IT/LT NOAEL = 5 mg/kg/day for inhalation].  Target MOE is 100 for
dermal exposure and 1000 for inhalation 	exposure.

Chemical Operators, Graders, Millwrights, Clean-up Crews, and Trim Saw
Operators

	Exposures to chemical operators, graders, millwrights, trim saw
operators, and clean-up crews were assessed using surrogate data from
the DDAC study (Bestari et al., 1999). This study examined
individuals’ exposure to DDAC while working with anti-sapstains and
performing routine tasks at 11 sawmills/planar mills in Canada.  Dermal
and inhalation exposure monitoring data were gathered for each job
function of interest using dosimeters and personal sampling tubes. 
These sample media were then analyzed for DDAC, and the results were
reported in terms of mg DDAC exposure per person per day.  The study
reported average daily exposures for workers in various categories. 
Exposure data for individuals performing the same job functions were
averaged together to determine job specific averages.  Total exposures
from 2 trim saw workers, 13 grader workers, 11 chemical operators, 3
millwrights, and 6 clean-up staff were used. 

	The individual dermal and inhalation exposures from the DDAC study are
presented in Table B-1 in Appendix B.  To determine Oxine-Copper
exposures, the average DDAC exposures measured on individuals (in terms
of total mg DDAC) were multiplied by a modification factor of 0.427 to
account for the difference in percent active ingredient between
Oxine-Copper and DDAC (34.18 % Oxine-Copper in the wood preservative
product versus 80% DDAC in the comparative wood preservative product).
The pound (lb) active ingredient handled by each person or the percent
(%) active ingredient in the treatment solution was not provided for
these worker functions. 

The following equation was used to calculate daily dose for
Oxine-Copper: 

Daily Dose = DDAC UE x CR x AB 

           	         BW

Where

DDAC UE	=	DDAC dermal or inhalation unit exposure (mg/day);

CR		=	Conversion ratio (34.18 % Oxine-Copper / 80% DDAC) ;

AB	=	Absorption factor (NA for dermal, 100% for inhalation); and

BW		=	Body weight (70 kg).

In using this methodology, the following assumptions were made:

DDAC and Oxine-Copper end products will be used in similar quantities. 

The procedures for applying both chemicals are similar. 

The physical-chemical properties that affect the transport of the
chemical are similar. (This assumes similar product densities for the
DDAC and Oxine-Copper water-borne solutions).

The limits of detections (LOD) for inhalation residues from   SEQ
CHAPTER \h \r 1 chemical operators, graders, mill wrights, and clean-up
staff replicates were not provided in the DDAC report.  For lack of
better data, it was assumed that the inhalation LODs for these worker
positions are equal to the LOD of the diptank operator replicates (5.6
(g).  For all measurements below the air concentration associated with
this detection limit, half the detection limit was used.  The dermal LOD
for all operators is also 5.6 (g.

In the DDAC study, dermal exposures to hands were measured separately
from the rest of the body.  For each replicate, the body dose
measurements and hand dose measurements were summed for a total dermal
dose.

Air concentrations were reported in the DDAC study. To convert air
concentrations ((g/m3) into terms of inhalation unit exposure (mg/day),
the air concentrations were multiplied by an inhalation rate of 1.0
m3/hr for light activity (EPA 1997a), sample duration of 8 hrs/day, and
a conversion factor of 1 mg/1000 (g.  Table B-1 in Appendix B presents
the inhalation and dermal DDAC exposures.

Average DDAC dermal and inhalation exposures were multiplied by a
conversion ratio of 0.427 to account for the differences in Oxine-Copper
and DDAC concentrations [i.e., (34.18 % Oxine-Copper / 80% DDAC)].  

Table 7.4 provides the short-, intermediate-, and long-term doses and
MOEs for chemical operators, graders, millwrights, clean-up crews, and
trim saw operators.  For all worker functions, the dermal MOEs are above
the target MOE of 100 for ST/IT durations assessed.  For all worker
functions, the inhalation MOEs are above the target MOE of 1000 for
ST/IT/LT durations, and therefore are not of concern. Therefore, a
confirmatory inhalation toxicity study is not warranted based on the
results of this assessment.

Table 7.4. Short-, Intermediate- and Long-Term Exposures and MOEs for
Wood Preservative Chemical Operators, Graders, Trim Saw Operators, and
Clean-Up Crews

Exposure Scenarioa 

(number of volunteers)	Dermal UEb 

(mg/day)	Inhalation UEb 

(mg/day)	Conversion Ratioc 	Absorbed Daily Dosesd 

(mg/kg/day)	MOEse

Dermal	Inhalation	Dermal

ST/IT

Target = 100	Inhalation

ST/IT/LT

Target = 1000

Occupational Handler

Chemical Operator (n=11)	9.81	0.0281	0.0427	0.060	0.00017	3,333	29,412

Occupational Post-application

Grader (n=13)	3.13	0.0295	0.0427	0.019	0.00018	10,526	27,778

Trim Saw (n=2)	1.38	0.061	0.0427	0.0084	0.00037	23,809	13,513

Millwright (n=3)	12.81	0.057	0.0427	0.078	0.00035	2,564	14,286

Clean-Up (n=6)	55.3	0.60	0.0427	0.337	0.0037	593	1,351

ST = 	Short-term duration; IT = Intermediate-term duration; and LT =
long-term

a.	The exposure scenario represents a worker wearing either long-sleeved
or short-sleeved shirts, cotton work trousers, and cotton glove
dosimeter gloves under chemical resistant gloves. Volunteers were
grouped according to tasks they conducted at the mill.

b.	Dermal and inhalation unit exposures are from Bestari et al (1999). 
Refer to Table B-1 in Appendix B for the calculation of the dermal and
inhalation exposures. Inhalation exposure (mg/day) was calculated using
the following equation: air concentration ((g/m3) x inhalation rate (1.0
m3/hr) x sample duration (8 hr/day) x unit conversion (1 mg/1000 (g). 
The inhalation rate is from USEPA, 1997a. 

c.	Conversion Ratio = 34.18% Oxine-Copper / 80% DDAC

d.	Absorbed Daily dose (mg/kg/day) = exposure (mg/day) * conversion
ratio (0.427) * absorption factor (NA for dermal and 100% for
inhalation)/body weight (70 kg). 

e.			MOE = NOAEL (mg/kg/day) / Daily dose [Where ST/IT (systemic) NOAEL
= 200 mg/kg/day for dermal and ST/IT/LT NOAEL = 5 mg/kg/day for
inhalation]. Target MOE is 100 for dermal exposure and 1000 for
inhalation exposure.

Diptank Operators

	Exposures to diptank operators were also assessed using surrogate data
from the DDAC study (Bestari et al., 1999). The diptank scenario
assessment was conducted differently than for the other job functions
because the concentration of DDAC in the diptank solution was provided. 
Typical registered product use rates for dip treatments (dipping,
diptank, immersion) are at levels of 0.11% to 1.25% ai. Non-pressure dip
treatment of wood intended for ground contact is usually specified for
levels of 1.0% ai or more. The exposures were estimated based on the
maximum application rate for dipping treatment to control sapstain cited
on product labeling for EPA Reg. No. 3008-91 which is a 34.18 % ai
concentrate used to make water-based treatment solutions of up to 2.3%
ai [i.e., 1:15 v/v use dilution (0.0666) x 34.18 % ai in product = 2.3 %
ai].  Product labeling cites use of eye protection and rubber gloves as
PPE.

	The exposure data for diptank operators wearing gloves were converted
into “unit exposures” in terms of mg a.i. for each 1% of
concentration of the product. The calculation of the dermal and
inhalation unit exposures (2.99 and 0.046 mg/1% solution, respectively)
is presented in Table B-2 in Appendix B.  The air concentrations
presented in the DDAC study were converted to unit exposures using an
inhalation rate of 1.0 m3/hr (light activity) and sample duration of 8
hrs/day.

The following equations are used to estimate dermal and inhalation
handler exposure: 

Daily Dose = DDAC UE x AI x AB 

		BW

Where

DDAC UE	=	DDAC dermal unit exposure (mg/ 1% in solution);

AI		=	AI (2.3% ai in solution/day);

AB	=	Absorption factor (NA for dermal, 100% for inhalation); and

BW		=	Body weight (70 kg).

	Table 7.5 provides the short-term and the intermediate- and long-term
doses and MOEs for diptank operators. The dermal ST/IT MOE was 2.037
which is above the target MOE of 100 and therefore not of concern.  The
inhalation ST/IT/LT MOE exceeded the Agency target of 1,000, as 3,311,
and is also not of concern.  Therefore, a confirmatory inhalation
toxicity study is not warranted based on the results of this exposure
scenario.

Table 7.5.  Short-, Intermediate-, and Long-Term Exposures and MOEs for
Diptank Operator 

Exposure Scenarioa

(number of replicates)	Dermal Unit Exposureb 

(mg DDAC/1% solution)	Inhalation Unit Exposureb 

(mg DDAC/1% solution)	App Rate 

(% a.i. in solution/ day)c 	Absorbed Daily Dosesd 

(mg/kg/day)	MOEse

Dermal	Inhalation	Dermal

ST/IT

 

Target MOE = 100	Inhalation

ST/IT/LT 

Target MOE = 1000

Occupational Handler

Dipping, with gloves (n=7)

	2.99	0.046	2.3	0.0982	0.00151	

2,037

	3,311

ST = 	Short-term duration;  IT =Intermediate-term duration; and LT =
long-term.

a. 	The exposure scenario represents a worker wearing long-sleeved
shirts, cotton work trousers, and gloves. Gloves were worn only when
near chemical, not when operating the diptank.

b.	Dermal and inhalation unit exposures are from DDAC study (MRID
455243-04). Refer to Table B-2 in Appendix B for the dermal and
inhalation unit exposure calculations. Inhalation exposure (mg) was
calculated using the following equation: Air concentration (mg/m3) x
Inhalation rate (1.0 m3/hr) x Sample Duration (8 hr).  The inhalation
rate is from USEPA, 1997a.

c.	The maximum application rate for sapstain control dip application
method is 2.3% ai solution (3008-91).  

d.	Absorbed Daily dose (mg/kg/day) = unit exposure (mg/1% ai solution) *
percent active ingredient in solution (2.3) * absorption factor (NA for
dermal and 100% for inhalation) / body weight (70 kg).

e.			MOE = NOAEL (mg/kg/day) / Daily dose [Where ST/IT (systemic) NOAEL
= 200 mg/kg/day for dermal and ST/IT/LT NOAEL = 5 mg/kg/day for
inhalation]. Target MOE is 100 for dermal exposure and 1000 for
inhalation exposure.

Construction Workers

	Not enough data exists to estimate the amount of exposure associated
with construction workers who install treated wood.  In particular,
values for the transfer coefficient associated with a construction
worker handling the wood could not be determined. However, it is
believed that the construction worker using a trim saw will have larger
dermal and inhalation exposures than the installer, due to the amount of
sawdust generated and the greater amount of hand contact that would be
necessary to handle the wood when using a saw compared to installing the
wood.

7.4.2	Pressure Treatment Scenarios (Handler and Post-Application)

	

	Oxine-Copper wood preservatives may be used to treat wood and wood
products using pressurized application methods, specifically empty-cell
vacuum pressure techniques.  Pressure treatment solutions of solubilized
Oxine-Copper are predominantly oil or solvent-based. However, there are
a few water-borne products registered as well. Typical registered
product use rates for pressure treatment are at levels of 0.25% ai. The
maximum rate of application used in this assessment is 1% ai solution
based on product labeling for EPA Reg. Nos. 2829-135 and 2829-136 which
are 10% ai concentrates, and indicate that pressure treatment use
solutions of up to 1% ai can be made [i.e., 10% w/w use dilution (10) x
10% ai in product (0.10) = 1% ai].  

	 Oxine-Copper is listed in the American Wood-Preservers’Association
(AWPA) Book of Standards for treatment of several softwood species used
in exposed, above-ground applications. AWPA has standardized oil-borne
treatments using solubilized Oxine-Copper in their AWPA Standard P8 for
oil-borne preservatives.  The minimum specified retention (as
Oxine-Copper active ingredient) for these applications is 0.32 kg/m3
(0.02 lb/ft3).

	Chemical-specific exposure data are not available on Oxine-Copper for
assessment of pressure treatment exposure.  Therefore, the assessment
relies on surrogate chromated copper arsenate (CCA) data (ACC, 2002) and
was based on the approach used in a previous Agency exposure assessment
(USEPA, 2003). 

Surrogate Unit Exposure Data

	

	Dermal and inhalation exposures for pressure treatment uses are derived
from information in the exposure study sponsored by the American
Chemistry Council (2002) entitled “Assessment of Potential Inhalation
and Dermal Exposure Associated with Pressure Treatment of Wood with
Arsenical Wood Products” (ACC, 2002).  In this study, a treatment
solution of CCA was approximately 0.5 percent active ingredient.  The
CCA exposure monitoring study has been reviewed by the Agency and is
considered a valid surrogate source of data for pressure treatment
applications and is therefore used in estimating exposure to
Oxine-Copper. 

small (5 ≤ n ≤ 15).  

	The measured CCA dermal and inhalation exposure values were normalized
by the treatment solution concentration used at each of the 3 facilities
(i.e., unit exposure reported as µg arsenic/ppm treatment solution). 
The normalization by treatment solution concentration was performed to
extrapolate the measured exposures in the CCA study (monitored at ~0.5%
ai solution) to the maximum Oxine-Copper treatment solution
concentration (1% ai solution).  Table 6.6 presents the dermal and
inhalation unit exposure values normalized to the treatment solution
concentration in ppm for (1) all sites, (2) treatment operator (TA
handler), (3) treatment assistant (TA handler), and (4) all
post-application job functions (TS, SO, LO, S, TB, TM).  

	Note: The U.S. and Canadian sites indicate a 7x difference in the mean
dermal exposures (US site mean is 0.40 µg As/ppm compared to the
Canadian site mean of 2.84 µg As/ppm).  It is recommended that
additional analysis be performed to determine if the increased exposure
levels at the Canadian site can be attributed to differences in
site-specific engineering controls or facility design.

Table 7.6.  Dermal and Inhalation Exposure Values from a CCA Pressure
Treatment Study (Exposure Data used as Surrogate Unit Exposures for
Oxine-Copper Assessment)

Site	Treatment Solution  	Statistic	Dermal Unit Exposure

((g As/ppm)	Air 

Concentrationb

((g As/m3/ppm)	Inhalation Unit Exposurec

((g As/ppm)

	%	ppma

All sites - All Data

(n = 64)	0.438 to 0.595	4,380 to 5,950	Average ± std	0.97 ± Unknown
0.00013 ± 0.00023	0.00104

	Median	0.36	0.00013	0.00104

	90th percentile	2.07	0.00077	0.00617

	Maximum	7.74	0.0011	0.00882

All sites - Handler Treatment Operator

(n = 15)	0.438 to 0.595	4,380 to 5,950	Average ± std	2.04 ± 2.68
0.00032 ± 0.00038	0.00257

	Median	0.37	0.00013	0.00104

	90th percentile	5.39	0.00092	0.00737

	Maximum	7.74	0.0011	0.00882

All sites - Handler Treatment Assistant

(n = 10)	0.438 to 0.595	4,380 to 5,950	Average ± std	0.24 ± 0.14
0.0001 ± 0.00004	0.000802

	Median	0.23	0.00013	0.00104

	90th percentile	0.40	0.00013	0.00104

	Maximum	0.52	0.00014	0.00112

All sites – Post-application: All job functions (TS, SO, LO, S, TB,
TM)

(n = 39)	--	--	Average ± std	0.74 ± 0.73	0.00020 ± 0.00025	0.00160

	Median	0.42	0.00013	0.00104

	90th percentile	1.81	0.00050	0.00401

	Maximum	3.11	0.0011	0.00882

	a.	ppm = (% treatment solution) * (10,000).

	b.	Air concentration was calculated as (g collected per sample per ppm
/ (480 min per day x 2 L/min).

	c.	Inhalation unit exposure = air concentration ((g As/m3/ppm) *
breathing rate for light activities (0.0167 	m3/min) * sample duration
(480 min).  Values shown in bold are used for the assessment.

Exposure Calculations

The following equation was used to estimate dermal and inhalation
handler exposure: 

Absorbed Daily Dose = 	UE x AI x AB 

	      	       BW

Where

UE	=	Unit exposure (mg As/ppm);

AI	=	Percent active ingredient (1% ai in solution);

AB	=	Absorption factor (Not applicable [NA] for dermal, 100% for
inhalation); and

BW	=	Body weight (70 kg).

Results

	The estimated dermal and inhalation exposures and risks for
Oxine-Copper pressure treatment uses are presented in Table 7.7.  The
calculated ST/IT dermal MOEs are all above the target MOE of 100 and do
not pose a risk concern.  Also, the inhalation ST/IT/LT MOEs for all
scenarios and durations are above the target MOE of 1000, therefore, a
confirmatory inhalation toxicity study is not warranted based on the
screening-level results. 

Table 7.7.  Short-, Intermediate-, and Long-Term Exposures and MOEs for
Pressure Treatment Handler and Post-application Scenarios Related to
Oxine-Copper Use

Exposure Scenarioa	

Unit Exposurea 

((g As/ppm)

	

Application Rate 

(% ai solution) 	Absorbed Daily Dosesb 

(mg/kg/day)	MOEsc

	Dermal	Inhalation

Dermal	Inhalation	Dermal

ST/IT

Target = 100	Inhalation

ST/IT/LT

Target=1000

Occupational Handler

Treatment Operator (TO)	2.04	0.00257	1	0.291	0.000367	687	13,624

Treatment Assistant (TA)	0.24	0.000802	1	0.0343	0.000115	5,831	43,478

Occupational Post-application

All Job Functions

(Tram setter, stacker operator, loader operator, supervisor, test borer,
and tallyman) 	0.74	0.00160	1	0.106	0.000229	1,887	21,834

ST = 	Short-term duration; IT = Intermediate-term duration; and LT =
long-term.

a. 	Unit exposure values are taken from CCA study as shown above and in
Table 6.6.

μg) * absorption factor (NA for dermal; 100% for inhalation) / Body
weight (70 kg).

c.			MOE = NOAEL (mg/kg/day) / Daily dose [Where ST/IT (systemic) NOAEL
= 200 mg/kg/day for dermal and ST/IT/LT NOAEL = 5 mg/kg/day for
inhalation]. Target MOE is 100 for dermal exposure and 1000 for
inhalation exposure.

	7.5	Data Limitations/Uncertainties tc \l2 "6.3	Data
Limitations/Uncertainties 

	There are several data limitations and uncertainties associated with
the occupational handler and post-application exposure assessments. 
These include:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handlers Exposure Database (USEPA, 1998) (See Appendix A for summaries
of these data sources).   Since the CMA data are of poor quality, the
Agency may request that confirmatory data be submitted in order to
support the occupational scenarios assessed in this document.

The low pressure spray unit exposure data from PHED were used to assess
both outdoor environmental surface treatments (materials preservative)
and applications of wood coatings/water repellents (wood preservatives).
 As the low pressure spray data are representative of treating low to
mid level range targets (shrubs/greenhouse benches) and the scenarios
assessed in this document represents treatments that may also occur
above the waist, the unit exposure value may underestimate exposure to
the head and the upper body.

For the wood preservative pressure treatment scenarios, surrogate CCA
exposure data were used for lack of chemical-specific exposure data for
this use pattern. For the wood preservative non-pressure treatment
scenarios, surrogate DDAC exposure data were used for the lack of
chemical-specific exposure data.  Limitations and uncertainties
associated with the use of these data include:

The assumption was made that exposure patterns for workers at treatment
facilities using CCA and DDAC would be similar to exposure patterns for
workers at treatment facilities using Oxine-Copper, and therefore the
exposures could be used as surrogate data for workers that treat wood
with Oxine-Copper based formulations.

For environmental modeling, it was assumed that the leaching process
from wood treated with Oxine-Copper would be similar to that of CCA and
DDAC. However, due to the lack of robust data for Oxine-Copper -treated
wood, it is not possible to verify this assumption. 

The quantities handled/treated were estimated based on information from
various sources, including Agency standard assumptions, HED’s Standard
Operating Procedures (SOPs) for Residential Exposure Assessments (USEPA,
2000 and 2001), and professional judgment based on Agency understanding
of industrial practices.  In certain cases, no standard values were
available for some scenarios.  Assumptions for these scenarios were
based on AD estimates and could be further refined with input from
registrants.  

8.0	ENVIRONMENTAL RISKS 

8.1	Ecological Hazard

	8.1.1	Toxicity to Terrestrial Animals

		8.1.1.1   Birds, Acute

		In order to establish the toxicity of copper-8 to avian species, the
Agency requires an acute oral toxicity study using the technical grade
active ingredient (TGAI).  The preferred test species is either mallard
duck (a waterfowl) or bobwhite quail (an upland game bird).  The results
of two acute oral toxicity studies, submitted for copper-8, are provided
in the following table (Table 8.1).

Table 8.1.  Acute Oral Toxicity of Copper-8-Quinolinolate to Birds

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(mg/kg)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Bobwhite quail

(Colinus virginianus)	Copper-8 99.5%	LD50 = 618

	Slightly toxic	Yes (core)

- 14-day test duration

- 4-5 months of age	42927101

Mallard duck

(Anas platyrhynchos)	Copper-8 99.5%	LD50 = >2000

NOAEL = 2000

	Relatively nontoxic	Yes (core)

- 14-day test duration

- 15 months of age	42927102

		These acceptable acute oral toxicity studies indicate that copper-8 is
slightly toxic to relatively nontoxic to birds on an acute oral basis.
The guideline requirement OPPTS 850.2100/ (71-1) is satisfied.  

			8.1.1.2   Birds, Subacute

		A subacute dietary study using the TGAI may be required on a
case-by-case basis depending on the results of lower-tier ecological
studies and pertinent environmental fate characteristics in order to
establish the toxicity of a chemical to avian species.  This testing was
required for copper-8.  The preferred test species is either the mallard
duck or bobwhite quail.  The results of two subacute dietary toxicity
studies, submitted for copper-8, are provided in the following table
(Table 8.2).

Table 8.2.  Subacute Oral Toxicity of Copper-8 to Birds

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(ppm)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Bobwhite quail

(Colinus virginianus)	Copper-8 99.5%	LC50 (diet) = 3248

NOAEC = 1300	Slightly toxic	Yes (core)

-	8-day test duration

-	14 days of age	42927103

Mallard duck

(Anas platyrhynchos)	Copper-8 99.5%	LC50 (diet) = >5200

NOAEC = 2600	Relatively nontoxic	Yes (core)

-	8-day test duration

-  10 days of age	42927104

		The results from these acceptable studies indicate that copper-8 is
slightly toxic to relatively nontoxic to avian species through subacute
dietary exposure. These studies fulfill guideline requirements OPPTS
850.2100/ (71-2a – Bobwhite quail and 71-2b – Mallard duck). 

	8.1.1.3   Mammals, Acute and Chronic Toxicity

Wild mammal testing is not required by the Agency.  In most cases, rat
toxicity values obtained from studies conducted to support data
requirements for human health risk assessments substitute for wild
mammal testing.  Refer to the human toxicology chapter of this RED for
mammalian toxicity data.

		8.1.2	Toxicity to Aquatic Animals

			8.1.2.1   Freshwater Fish, Acute

		In order to establish the acute toxicity of copper-8 to freshwater
fish, the Agency requires freshwater fish toxicity studies using the
TGAI.  The preferred test species are rainbow trout (a coldwater fish)
and bluegill sunfish (a warmwater fish).  The results of four freshwater
fish acute studies submitted for copper-8, 3 coldwater and 1 warmwater,
are presented in Table 8.3.

Table 8.3.  Acute Toxicity of Copper-8 to Freshwater Fish

		

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(mg/L)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Bluegill Sunfish (Lepomis macrochirus)	Copper-8 100%	LC50 = 0.0216

NOAEC = 0.0108	Very highly toxic	Yes (core)

-	96-hr test duration

-	flow-through test system	42899003

Rainbow Trout (Oncorhynchus mykiss)	Copper-8 100%	LC50 = 0.0089

NOEC = 0.0062	Very highly toxic	Yes (core)

- 96-hr test duration

- flow-through test system	42899002

Rainbow Trout (Oncorhynchus mykiss)	Copper-8 80%	LC50 = 0.0097

NOAEC = 0.0071	Very highly toxic	Yes (core)

- 96-hr test duration

- static renewal test system	43563701

Coho Salmon (Oncorhynchus kisutch)	Copper-8 100%	LC50 = 0.0139

NOAEC = 0.0066	Very highly toxic	Yes (core)

- 96-hr test duration

- flow-through test system	42902401

		Freshwater acute toxicity tests indicate that copper-8 is very highly
toxic to the coldwater rainbow trout and very highly toxic to the
warmwater bluegill sunfish on an acute basis.  Guideline requirement
OPPTS 850.1075 (72-1a&b) is fulfilled.  Because acute toxicity to fish
is <1.0 mg/L the environmental hazard section of copper 8 labels must
state: “This pesticide is toxic to fish.”

		8.1.2.2   Freshwater Invertebrates, Acute

		The Agency requires a freshwater aquatic invertebrate study using the
TGAI to establish the acute toxicity to freshwater invertebrates.  The
preferred test species is Daphnia magna.  The results of one study
submitted for copper-8 is provided in the following table (Table 8.4).

Table 8.4.  Acute Toxicity of Copper-8 to Freshwater Invertebrates

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(mg/L)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Waterflea (Daphnia magna)	Copper-8 

98%	EC50 = 0.162

NOAEC = < 0.036 	Highly toxic	Yes (core)

-	48-hr test duration

-	flow-through test system 	43228401

		The results of MRID 432284-01 indicate that copper-8 is highly toxic
to freshwater invertebrates. This study fulfills guideline requirement
OPPTS 850.1010 (72.2a). Because the acute aquatic invertebrate toxicity
value is < 1.0 mg/L, the environmental hazard section of copper-8 labels
must state: “This pesticide is toxic to aquatic invertebrates.

			8.1.2.3   Estuarine and Marine Organisms, Acute

		Acute toxicity testing with estuarine and marine organisms using the
TGAI is required when the end-use product is intended for direct
application to the marine/estuarine environment or effluent containing
the active ingredient is expected to reach this environment.  The
preferred fish test species is the sheepshead minnow.  The preferred
invertebrate test species are mysid shrimp and eastern oysters.  This
testing is required for copper-8 based on the chemical’s potential to
reach estuarine and marine environments.  The results of two toxicity
studies submitted for copper-8 are presented in Table 8.5.

Table 8.5.  Acute Toxicity of Copper-8 to Estuarine and Marine Organisms

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint

(mg/L)	

Toxicity Category	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Eastern oyster (Crassostrea virginica)	Copper 8 

100%	LC50  = 0.0363

EC50 = 0.0111

NOAEC = 0.003	Very highly toxic	Yes (core)

-	48-hr test duration 

-	static test system	42899004

		The results of the one core study indicate that copper-8 is very
highly toxic to estuarine/marine invertebrates on an acute basis.  The
Eastern oyster study (42899004) fulfills the guideline requirement OPPTS
850.1025/ (72-3b) for an acute estuarine/marine mollusk study. Study
MRID 42902402 for Mysid shrimp is INVALID and must be repeated.  The
guideline requirements OPPTS 850.1075/ (72-3a) for an acute
estuarine/marine fish study and OPPTS 850.1035/ (72-3c) for an
estuarine/marine shrimp study are not fulfilled.  Because
estuarine/marine acute toxicity values are < 1.0 mg/L, the environmental
hazard section of copper-8 labels must state:  “This pesticide is
toxic to oysters and shrimp.”

		8.1.2.4   Aquatic Organisms, Chronic

		Chronic toxicity testing (fish early life stage and aquatic
invertebrate life cycle) is required for pesticides when certain
conditions of use and environmental fate apply.  Preferred freshwater
and estuarine/marine fish and invertebrate species include:  fathead
minnow, rainbow trout, Daphnia magna, and mysid shrimp.  Two studies
were submitted for copper-8, but are INVALID and must be repeated.  The
rainbow trout study (42902403) does not fulfill the guideline
requirement for a fish early life stage toxicity test (72-4a/OPPTS
850.1400) due to the percent RSD of weight in one replicate of the
solvent control being >40%. The study on the waterflea (42899005) also
does not fulfill the guideline requirement for a chronic aquatic
invertebrate because dissolved oxygen concentrations fell to extremely
low levels during the test and the highest measured concentration in one
exposure solution was greater than twice the lowest measured
concentration at the same level. 

		8.1.3	Toxicity to Plants

		Non-target plant phytotoxicity testing is required for pesticides when
certain conditions of use and environmental fate apply.  The use of
copper-8 as a wood treatment may result in chemical leachate from
treated wood into the aquatic environment.  Aquatic plant toxicity data
are necessary for a non-target plant risk assessment.  Testing is
conducted with one species of aquatic vascular plant (Lemna gibba) and
four species of algae:  (1) freshwater green alga, Selenastrum
capricornutum, (2) marine diatom, Skeletonema costatum, (3) freshwater
diatom, Navicula pelliculosa, and (4) bluegreen cyanobacteria, Anabaena
flos-aquae.  The rooted aquatic macrophyte rice (Oryza sativa) is also
tested in seedling emergence and vegetative vigor tests.

		Two marine diatom studies and a saltwater green algae study were
reviewed. Results of these studies are presented in Table 8.6.

Table 8.6.  Toxicity of Copper-8 to Aquatic Plants

Species	

Chemical,

% Active Ingredient

(a.i.)

Tested	

Endpoint 

(mg/L)	

Satisfies Guidelines/

Comments	

Reference

(MRID No.)

Marine diatom (Nitzschia punctata)	Copper-8

100%	EC50 = 0.0073	No (supplemental)

- 5-day test duration

-  static test system

-  NOEC not determined	42902404

Marine diatom (Skeletonema costatum)	Copper-8

98%	EC50 = 0.0019

NOEC = < 0.0007	Yes (core)

- 5-day test duration

- static test system

	43073501

Saltwater Green alga (Dunaliella tertiolecta)	Copper-8

100%	EC50 = 0.0154

NOEC = 0.009	Yes (core)

- 5-day test duration

- static test system 	42902405

		The studies above are classified as acceptable and partially fulfill
the guideline requirements for an algae toxicity test (850.5400, 123-2).
 Three additional algal toxicity tests under 850.5400 are outstanding: 
freshwater diatom (Navicula pelliculosa), blue-green cyanobacteria
(Anabeana flos-aquae), and freshwater green alga (Selenastrum
capricornutum).  Other outstanding non-target aquatic plant toxicity
tests are:  floating freshwater aquatic macrophyte duckweed (Lemna
gibba) – 850.4400 and rooted freshwater macrophyte rice (Oryza sativa)
– 850.4225 and 850.4250 (2 tests on seedling emergence and vegetative
vigor).

		8.1.4	RISK QUOTIENTS

Risk assessment integrates the results of the exposure and ecotoxicity
data to evaluate the likelihood of adverse ecological effects. One
method of integrating the results of exposure and ecotoxicity data is
called the quotient method.  For this method, risk quotients (RQs) are
calculated by dividing exposure estimates by ecotoxicity values, both
acute and chronic:  

       

           RQ = EXPOSURE/TOXICITY 

 

RQs are then compared to levels of concern (LOCs).  These LOCs are
criteria used by OPP to indicate potential risk to nontarget organisms
and the need to consider regulatory action.  The criteria indicate that
a pesticide used as directed has the potential to cause adverse effects
on nontarget organisms.  LOCs currently address the following risk
presumption categories: (1) acute - the potential for acute risk is
high, regulatory action may be warranted in addition to restricted use
classification; (2) acute restricted use - the potential for acute risk
is high, but this may be mitigated through restricted use
classification; (3) acute endangered species - the potential for acute
risk to endangered species is high, and regulatory action may be
warranted, and (4) chronic risk - the potential for chronic risk is
high, and regulatory action may be warranted, (5) non-endangered plant
risk – potential for effects in non-target plants, and (6) endangered
plant risk – potential for effects in endangered plants.   Currently,
EPA does not perform assessments for chronic risk to plants, acute or
chronic risks to nontarget insects, or chronic risk from granular/bait
formulations to birds or mammals.

The ecotoxicity test values (measurement endpoints) used in the acute
and chronic risk quotients are derived from required studies.  Examples
of ecotoxicity values derived from short-term laboratory studies that
assess acute effects are: (1) LC50 (fish and birds), (2) LD50 (birds and
mammals), (3) EC50 (aquatic plants and aquatic invertebrates) and (4)
EC25 (terrestrial plants).  Examples of toxicity test effect levels
derived from the results of long-term laboratory studies that assess
chronic effects are: (1) LOAEC (birds, fish, and aquatic invertebrates),
and (2) NOAEC (birds, fish and aquatic invertebrates). For birds and
mammals, the NOAEC generally is used as the ecotoxicity test value in
assessing chronic effects, although other values may be used when
justified. However, the NOAEC is used if the measurement endpoint is
production of offspring or survival.  Risk presumptions, along with the
corresponding RQs and LOCs are tabulated below.



Risk Presumptions for Terrestrial Animals

Risk Presumption	

RQ	

LOC

Birds and Wild Mammals

Acute Risk	

EEC1/LC50 or LD50/sqft2 or LD50/day3	

0.5

Acute Restricted Use	

EEC/LC50 or LD50/sqft or LD50/day (or LD50 < 50 mg/kg)	

0.2

Acute Endangered Species	

EEC/LC50 or LD50/sqft or LD50/day 	

0.1

Chronic Risk	

EEC/NOAEC	

1

 1  abbreviation for Estimated Environmental Concentration (ppm) on
avian/mammalian food items   

 2    mg/ft2             	3  mg of toxicant consumed/day

   LD50 * wt. of bird             	LD50 * wt. of bird  

Risk Presumptions for Aquatic Animals	 

Risk Presumption	

RQ 	

LOC

Acute Risk	

EEC1/LC50 or EC50	

0.5

Acute Restricted Use	

EEC/LC50 or EC50	

0.1

Acute Endangered Species	

EEC/LC50 or EC50	

0.05

Chronic Risk	

EEC/MATC2 or NOAEC	

1

 1  EEC = (ppm or ppb) in water

 2  MATC = maximum allowable toxicant concentration

Risk Presumptions for Plants	

	

Risk Presumption	

RQ	

LOC

Terrestrial and Semi-Aquatic Plants 

Acute Risk	

EEC/EC25	

1

Acute Endangered Species	

EEC/EC05 or NOAEC	

1

Aquatic Plants

Acute Risk	

EEC1/EC50	

1

Acute Endangered Species	

EEC/EC05 or NOAEC 	

1

EEC = (ppb/ppm) in water 

Maximum Expected Environmental Concentrations:

	EPA calculated the leaching of copper-8 from a dock into water.  It was
assumed that 4% of the total applied copper-8 would leach from the wood
into the water.  The retention rate of the wood was assumed to be 22
(g/cm2.  The length and width of the dock was assumed to be 30 meters
and 10 meters, respectively and the thickness of the wood was assumed to
be 0.1 meters.  The number of poles underneath the dock was assumed to
be 18 and the dimensions of the poles were assumed to be 2 meters
(length) x 0.15 meters (width) x 0.15 meters (height).  The poles were
assumed to be 0.5 meters inserted into the sediment.  Based on these
specifications, copper-8 EECs were calculated for water body sizes
ranging from 1 acre foot to 24 acre feet.  The highest EEC calculated
for the smallest body of water (1 acre foot) was 0.00226 mg copper-8 per
liter of water.  The calculated EEC for a slightly larger body of water
(6 acre feet) is 0.00038 mg copper-8 per liter of water.  For details on
the calculations conducted to arrive at this EEC as well as the
uncertainties and limitations of the calculations, consult Siroos
Mostaghimi’s 4/25/2007 memo “Estimated Environmental Concentrations
for Copper 8-Quinolinolate (Cu8Q) from Treated Wood Used to Build
Docks.”

Maximum Ecotoxicity Values:

From the toxicity tables in section 8.1 above, the highest toxicity in
an acceptable fish study was achieved in a study on the rainbow trout
(Oncorhynchus mykiss).  The LC50 value obtained in this study was 0.0089
mg/L (MRID 42899002).  The EC50 value obtained in the study on the
freshwater invertebrate (Daphnia magna) was 0.162 mg/L (MRID 43228401). 
The EC50 value obtained in the study on the eastern oyster (Crassostrea
virginica) was 0.0111 mg/L (MRID 42899004).  There were no acceptable
acute toxicity studies for estuarine and marine fish or shrimp nor were
there any acceptable chronic toxicity studies available for aquatic
organisms.  Therefore, risk to these species cannot be assessed.  The
highest toxicity in an acceptable aquatic plant toxicity study was
achieved in a study on the marine diatom (Skeletonema costatum).  The
EC50 value obtained in this study was 0.0019 mg/L and the NOEC was <
0.0007 (MRID 43073501).   Due to outstanding plant toxicity studies, the
non-target plant risk assessment is incomplete.

Acute Freshwater Fish LOC’s:

Comparing the maximum calculated EEC (0.00226 mg/L) to the highest
toxicity found in a fish acute study (0.0089 mg/L), an RQ of 0.254 is
obtained.  This is less than the LOCs for acute and chronic risks to
aquatic animals but greater than the LOCs for endangered species and
acute restricted use.  Therefore, there is the potential for copper-8 to
cause adverse effects to endangered freshwater fish and these risks may
need to be mitigated.  The calculated EEC for a slightly larger body of
water (6 acre feet) is 0.00038 mg copper-8 per liter of water.  This EEC
brings the RQ for freshwater fish down to 0.043, therefore the risk to
endangered fish species is no longer considered significant in this size
body of water.  However, as discussed below an endangered species effect
determination will not be made at this time.

Acute Freshwater Aquatic Invertebrate LOC’s:

Comparing the maximum calculated EEC to the toxicity value found in the
study on the freshwater invertebrate (0.162 mg/L), an RQ of 0.014 is
obtained.  This is less than all LOCs for aquatic organisms, therefore
the potential for risks from copper-8 to aquatic invertebrates is not
high.  The calculated EEC for a slightly larger body of water (6 acre
feet) is 0.00038 mg copper 8 per liter of water.  The calculated RQ is
less than 0.00 and therefore no risk is triggered for a larger water
body.  However, as discussed below an endangered species effect
determination will not be made at this time.

Acute Aquatic Estuarine/Marine Species:

For the eastern oyster, the RQ is 0.204.  This is less than the LOCs for
acute and chronic risks to aquatic animals but greater than the LOCs for
endangered species and acute restricted use.  Therefore, there is the
potential for copper-8 to cause adverse effects to endangered estuarine
and marine organisms and these risks may need to be mitigated.  The
calculated EEC for a slightly larger body of water (6 acre feet) is
0.00038 mg copper-8 per liter of water.  This EEC brings the RQ for the
eastern oyster down to 0.034 and the RQ for aquatic plants down to 0.2
so the risks to endangered estuarine/marine organisms and aquatic plants
are no longer considered significant either.  This risk assessment is
incomplete due to outstanding fish and shrimp toxicity studies.

Chronic Aquatic Toxicity Studies:

	Chronic freshwater fish and invertebrate studies are triggered based on
acute toxicity.  No valid studies are available for copper-8.
Estuarine/marine chronic toxicity studies for fish and invertebrates are
required.  This risk assessment is incomplete.

Plant Toxicity Studies:

Comparing the maximum calculated EEC (0.00226 mg/L) to the highest
toxicity value found for aquatic plants (0.0019 mg/L), an RQ of 1.189 is
obtained. This is greater than the LOC of >1.0 and therefore there is
the potential for acute risk to aquatic plants, including endangered
species, from copper-8. The calculated EEC for a slightly larger body of
water (6 acre feet) is 0.00038 mg copper-8 per liter of water. This EEC
brings the RQ for aquatic plants down to 0.2 so the risks to endangered
estuarine/marine organisms and aquatic plants are no longer considered
significant for the larger body of water. This risk assessment is
incomplete due to outstanding plant toxicity studies.

Avian and Mammalian Species:

Based on available avian toxicity data for copper-8, the various wood
treatments are not expected to be acutely toxic.

	8.2	Environmental Fate Assessment

	Copper 8-quinolinolate is hydrolytically stable at pH 5, 7 and 9 but
photolytically it is not stable. More than 80% of it is stable in
aerobic and anaerobic soils. In aerobic soils its half-life is about
four months, but it may be over one year in anaerobic soils.  It does
not show any tendency to migrate from top soil. It is therefore likely
to contaminate surface water through surface water run-off. Its
degradation pathway appears to be aqueous photolysis with a half-life of
60 to 96 hours. Leaching from (sapstain use) treated Douglas fir wood is
666 mg/1000 board feet while for Hemlock it is 229 mg/1000 board feet
after 8 stimulated rain cycles. The estimated log Kow for copper
8-quinolinolate is 2.5, which indicates that it is not likely to
bioaccumulate in aquatic organisms like fish. It is persistent in water
and soils.

8.3	Environmental Exposure and Ecological Risk Assessment

	

	LOCs were not exceeded for fish, freshwater invertebrates, the eastern
oyster or aquatic plants in bodies of water 6 acre feet in size or
greater, whereas risks to endangered freshwater fish and the eastern
oyster as well as risks to aquatic plants were of concern in bodies of
water 1 acre foot in size or less.  Since it is unlikely that a dock of
the size used in the calculations for EEC will be present on a body of
water less than 6 acre feet in size, the risks to aquatic organisms from
copper 8 in this assessment appear to be small. There were no acceptable
acute toxicity studies for other estuarine and marine organisms nor were
there any acceptable chronic toxicity studies available for aquatic
organisms. Therefore, risk to these species could not be assessed.

	

8.4	Endangered Species Considerations

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2),
requires all federal agencies to consult with the National Marine
Fisheries Service (NMFS) for marine and anadromous listed species, or
the United States Fish and Wildlife Services (FWS) for listed wildlife
and freshwater organisms, if they are proposing an "action" that may
affect listed species or their designated habitat.  Each federal agency
is required under the Act to insure that any action they authorize,
fund, or carry out is not likely to jeopardize the continued existence
of a listed species or result in the destruction or adverse modification
of designated critical habitat.  To jeopardize the continued existence
of a listed species means "to engage in an action that reasonably would
be expected, directly or indirectly, to reduce appreciably the
likelihood of both the survival and recovery of a listed species in the
wild by reducing the reproduction, numbers, or distribution of the
species." 50 C.F.R. ( 402.02.

To facilitate compliance with the requirements of the Endangered Species
Act subsection (a)(2) the Environmental Protection Agency, Office of
Pesticide Programs has established procedures to evaluate whether a
proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed
species in the wild by reducing the reproduction, numbers, or
distribution of any listed species (U.S. EPA 2004).  After the
Agency’s screening-level risk assessment is performed, if any of the
Agency’s Listed Species LOC Criteria are exceeded for either direct or
indirect effects, a determination is made to identify if any listed or
candidate species may co-occur in the area of the proposed pesticide
use.  If determined that listed or candidate species may be present in
the proposed use areas, further biological assessment is undertaken. 
The extent to which listed species may be at risk then determines the
need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.

For certain use categories, the Agency assumes there will be minimal
environmental exposure, and only a minimal toxicity data set is required
(Overview of the Ecological Risk Assessment Process in the Office of
Pesticide Programs U.S. Environmental Protection Agency - Endangered and
Threatened Species Effects Determinations, 1/23/04, Appendix A, Section
IIB, pg.81).  Chemicals in these categories therefore do not undergo a
full screening-level risk assessment, and are considered to fall under a
“No Effect” determination.  The materials preservative uses of
copper 8-quinolinolate fall into this category.

	The preliminary analysis for wood treatment uses indicates that there
is a potential for copper-8 use to overlap with listed species and that
a more refined assessment is warranted, to include direct, indirect and
habitat effects.  The more refined assessment should involve clear
delineation of the action area associated with proposed use of copper 8
and best available information on the temporal and spatial co-location
of listed species with respect to the action area.  This analysis has
not been conducted for this assessment.  An endangered species effect
determination will not be made at this time.  The wood runoff label
statement is expected to provide some level of mitigation until such
time as a full endangered species assessment is possible.

8.5	Data Uncertainties and Limitations

	Fate and Environmental Modeling: There are a number of uncertainties
and limitations with this preliminary environmental risk assessment.
Extrapolating risk conclusions from the pond scenario used in the
environmental modeling may either underestimate or overestimate
potential exposures and risks. Numerous uncertainties exist with the
modeling used since environmental properties are likely to be regionally
specific because of local hydrogeological conditions. Further, any
alteration in water quality parameters may impact the environmental
behavior of the pesticide.  Additionally, there are pertinent data (wood
leaching) lacking; such data would be useful in refining this
preliminary risk assessment.

	Eco-Toxicity Data:  This screening level risk assessment relies on
selected toxicity endpoints from, what is believed to be, the most
sensitive species tested, but it does not necessarily mean that the
selected toxicity endpoints reflect sensitivity of the most sensitive
species existing in a given environment. Surrogates were used to predict
potential risks for various species, and data for several species are
lacking. Submission of additional non-target organism data will refine
this screening level assessment.

	Stakeholder Modeling Efforts:  The American Chemistry Council (ACC)
Biocides Panel Copper Reregistration Task Force is presently developing
modeling pertinent to the wood preservative and roofing uses of various
copper products. This modeling effort is intended to provide estimated
environmental exposures which can be used by the Agency to refine
environmental assessments. Such data would be useful in refining this
screening level assessment.

Confirmatory data listed below is required to support the wood treatment
use of 

copper-8-quinolinolate:

Estuarine/marine fish acute study (850.1075),

Estuarine/marine shrimp acute study (850.1035),      

Acute sediment toxicity to freshwater invertebrates (850.1735),

Acute sediment toxicity to estuarine invertebrates (850.1740),

Aquatic invertebrate (freshwater) life-cycle study (850.1300),

Fish early life-stage (freshwater) study (850.1400),1

Fish early life-stage (estuarine/marine) study (850.1400),1

Chronic mysid shrimp study (850.1350),1

Freshwater diatom (850.5400),

Blue-green cyanobacteria (850.5400),

Freshwater green alga (850.5400),

Freshwater floating macrophyte duckweed (850.4400),

Freshwater rooted macrophyte rice seedling emergence (850.4225),

Freshwater rooted macrophyte rice vegetative vigor (850.4250),

Wood leaching study (AWPA E11-06),

Environmental runoff monitoring study (None).  This test can be waived
provided labels are amended as outlined below for wood preservative
labels,

Residues in honey/beeswax and toxicity of treated wood residues to bees
– combination of Guideline 860.1500 and 850.3030 (“Honey Bee
Toxicity of Residues on Foliage.”).  The toxicity portion of this
study is in lieu of the honeybee contact LD50 test 850.3020.  The
residue and toxicity test can be waived provided the label is amended to
prohibit the use of treated wood for beehive construction, with a
statement such as, “Wood treated with copper 8-quinolinolate shall not
be used in the construction of beehives.”

 

9.0	INCIDENT REPORTS

The Agency reviewed the following information for human poisoning
incidents related to copper-8-quinolinolate use: (1) OPP Incident Data
System (IDS) – The Office of Pesticides Programs (OPP) Incident Data
System contains reports of incidents from various sources, including
registrants, other federal and state health and environmental agencies
and individual consumers, submitted to OPP since 1992; (2) California
Department of Pesticide Regulation (1982-2004) - The California
Department of Pesticide Regulation pesticide poisoning surveillance
program consists of reports from physicians of illness suspected of
being related to pesticide exposure since 1982. (3) National Pesticide
Information Center (NPIC) – NPIC is a toll-free information service
supported by OPP that provides a ranking of the top 200 active
ingredients for which telephone calls were received during calendar
years 1984-1991. (4) National Poison Control Centers (PCC) (1993-1996). 

Eight definite or probable relationship cases submitted to the
California Pesticide Illness Surveillance Program (1982-2004) were
reviewed and all the symptoms were irritation type reactions. Dermal and
eye exposure are the primary routes of exposure associated with these
incidences. For eye contact, red, itchy eyes, blurred vision,
photophobia, chemical conjunctivitis, cornea abrasions have been
reported.  For dermal contact, red, rash and contact dermatitis have
been reported. For inhalation exposure, sore and burning throat, and
inhalation infection symptoms have been reported. There was no incidence
requiring hospitalization and no severe incidences associated with
copper-8-exposure have been reported.

10.0	REFERENCES

Toxicology References

00083777	Mulligan, T.; Banas, D.A. (1976). Final Report: Two-year
Dietary Administration in the Rat: Project No. 854-104. (Unpublished
study received May 20, 1981 under 42567-1; prepared by Hazleton
Laboratories America, Inc., submitted by La Quinoleine S.A., c/o Regst.
Consulting, Pacifica, Calif.; CDL: 245397-G).

00099606	Mulligan, T.; Voelker, R. (1976). Final Report: Two-year
Dietary Toxicity Study in Dogs: Project No. 854-103. (Unpublished study
received Dec 8, 1978 under 42567-1; prepared by Hazleton Labo- ratories
America, Inc., submitted by La Quinoleine S.A., c/o Registration
Consulting Associates, Pacifica, CA; CDL:237444-A).

 0079233	Mulligan, T.; Durloo, R. (1975). Final Report: A Two Generation
Reproduction Study in Rats: Project No. 854-105. (Unpublished study
received May 20, 1981 under 42567-1; prepared by Hazleton Laboratories
America, Inc., submitted by La Quinoleine S.A., c/o Regst. Consulting,
Pacifica, Calif.; CDL: 245397-F).

41063701	Ridgway, P. (1987). K37 (Copper 8-Hydroxyquinolate): rabbit
teratology dose ranging study: Project ID: AKJ/5/87. Unpublished study
prepared by Toxicol Laboratories Ltd.

41063702	 Ridgway, P. (1987). K37 (Copper 8-Hydroxyquinolate): Rabbit
Teratology Study: Project ID: AKJ/6/87. Unpublished study prepared by
Toxicol Laboratories Ltd. 106 p.

42921501	Buser, S. (1990). Determination of the Acute Oral Toxicity of
Ro 17-0099/000 (Copper 8-Quinolinolate TGAI) in the Rat: Lab Project
Number: B-157'235: 032A90Z. Unpublished study prepared by F. Hoffmann-La
Roche Ltd. 37 p.

42921502	 Buser, S. (1990). Determination of the Acute Dermal Toxicity
of Ro 17-0099/000 (Copper 8-Quinolinolate TGAI) in the Rat: Lab Project
Number: B-157'234. Unpublished study prepared by F. Hoffmann-La Roche
Ltd. 21 p.

42921503	 Ullmann, L.; Porricello, T. (1993). Primary Skin Irritation
Study with Ro 17-0099/000 (Copper 8-Quinolinolate) in Rabbits (4-Hour
Semi-Occlusive Application on Intact and Abraided Skin): Lab Project
Number: 213344. Unpublished study prepared by Research & Consulting Co.,
AG. 29 p.

42921504	Ullmann, L.; Kups, A. (1988). Contact Hypersensitivity to Ro
17-0099/000 (Copper 8-Quinolinolate) in Albino Guinea Pigs (Maximization
Test): Lab Project Number: 213333. Unpublished study prepared by
Research & Consulting Co., AG. 46 p.

42937301	Buser, S. (1983). A 13-Week Toxicity Study with Ro-17-0099/000
(Copper 8-Quinolinolate) in Mice p.o. (Feed Admix): Lab Project Number:
RRB 104 777: 62 A 81: 104 777. Unpublished study prepared by F.
Hoffmann-La Roche & Co. Ltd. 135 p.

42957801	Coleman, M.; Taupin, P. (1990). K-37 (Copper 8-Quinolinolate):
13-Week Oral (Dietary) Rangefinding Study in the Mouse: Lab Project
Number: TOM/1/90. Unpublished study prepared by Toxicol Labs, Ltd. 211
p.

42957802	Hagemann, C. (1990). 28 Day Repeated Dose Dermal Toxicity Study
in the Rat: Lab Project Number: 911205: CGA 281881: Final Report: Lab
No. 911205. Unpublished study prepared by Ciba-Geigy Limited. 178 p.

42962301	Chetelat, A. (1989). Mutagenicity Evaluation of the Fungicide
Ro 17-0099/000 (Copper 8-Quinolinolate) with Salmonella typhimurium
(Ames test): Lab Project Number: B-116'875. Unpublished study prepared
by F. Hoffmann-La Roche Ltd. 38 p.

42962302	Chetelat, A.; Dresp, J. (1990). Micronucleus Test in the Mouse
Bone Marrow In Vivo After Oral Administration of the Fungicide Ro
17-0099/000 (Copper 8-Quinolinolate): Lab Project Number: B-116'890.
Unpublished study prepared by F. Hoffman-La Roche Ltd. 20 p.

42962303	Strobel, R. (1990). In vivo/in vitro Rat Hepatocyte DNA Repair
Test with the Fungicide Ro 17-0099/000 (Oxine Copper-Copper
8-Quinolinolate) (Unscheduled DNA Synthesis Test: Lab Project Number:
B-154'904. Unpublished study prepared by F. Hoffmann-La Roche Ltd. 158
p.

42962304	Dennis, S. (1991). Ro 17-0099/022 (Carbon 14)-Copper
8-Quinolinolate): Metabolism of Ro 17-0099/022 in the Rat Tissues and
Excreta after Single Oral, Repeated Oral Administrations and After a
Single Oral Administration to Bile Duct Cannulated Rats: Lab Project
Number: RES-MET Q14. Unpublished study prepared by Dr. R. MAAG AG. 48 p.

42962305	Van Dijk, A., Baranowski, D. (1991). Ro 17-0099/022 (Carbon
14)-Copper 8-Quinolinolate): Absorption, Distribution and Excretion
after Single Oral, Repeated Oral Administration to the Rat and After
Single Oral Administration to Bile Cannulated Rats: Lab Project Number:
276118. Unpublished study prepared by RCC UMWELTCHEMIE AG. 95 p.

42986801	Buser, S.; Mettler, F. (1990). 13-Week Oral (Dietary) Toxicity
in the Rat with the Fungicide Ro 17-0099/000 (Oxine Copper): Lab Project
Number: B-157'249: 269302: 026A90. Unpublished study prepared by F.
Hoffmann-La Roche & Co. Ltd. 465 p.

42986802 	Schlappi, B.; Jovanovic, B. (1990). Ro 17-0099/000: 13-Week
Oral Toxicity Study (by Capsules) on Dogs with the Fungicide Ro
17-0099/000 (Copper 8-Quinolinolate): Lab Project Number: B-154'807:
024A90: RRB 154'807. Unpublished study prepared by F. Hoffmann-La Roche
& Co. Ltd. 306 p.

42986803 	Bacchus, C. (1992). Ro 17-0099/000 (Copper 8-Quinolinolate):
Oral (Gavage) Embryo Toxicity Study in the Rat with the Fungicide Ro
17-0099/000: Segment II Study with Post Natal Evaluation: Lab Project
Number: B-154'980: 284027: 273677. Unpublished study prepared by F.
Hoffmann-La Roche Ltd. 155 p.

43267201 	Husband, R. (1994). K-37 (Copper 8-Quinolinolate): 80-Week
Oral (Dietary) Carcinogenicity Study in the Mouse: Lab Project Number:
TOM/2B/93. Unpublished study prepared by Toxicol Laboratories Ltd. 2279
p.

43267202 	Bryson, A. (1994). Technical CGA 281881 (Copper
8-Quinolinolate): A Study of the Effect on Reproductive Function of Two
Generations in the Rat: Lab Project Number: 911382: CBG/576/931390:
567/931390. Unpublished study prepared by Huntingdon Research Centre
Ltd. 323 p.

43558501 	Driscoll, R. (1993). Oxine Copper Technical (K-37): acute
dermal toxicity (limit test) in the rat. Safefarm Laboratories Limited,
Derby, UK. Laboratory Prokject Identification 386/39. October 8, 1993.
Unpublished.

43572401 	Coleman, M. and P. Taupin (1990). K-37 133 week oral (dietary)
rangefinding study in the mouse. Toxico Laboratories Limited, Bromyard
Road, Ledbury, Herefordshire, HR8 1LH, England. Toxicol Report Reference
No. TOM/1/90. November 1990. Unpublished.

43611901        Jackson, G. (1987) K-37 (Copper 8-Quinolinolate): Acute
Inhalation Toxicity in the Rat: Lab Project Number: AGK 1/87926.
Unpublished study prepared by Huntingdon Research Centre Ltd. 54 p.

Open Literature

Algate, D.R., P.L. Munt. and C.Mejer-Aspell. (1990). Copper
8-Quinolinolate Technical Assessment of Effects on Hexobarbital Induced
Sleeping Time in the Mouse. Unpublished report prepared by Huntington
Research Centre, Ltd. Huntington, Cambridgeshire, England. 

Algate, D.R., P.L. Munt. and C.Mejer-Aspell. (1990). Copper
8-Quinolinolate Technical Assessment of Effects On Motor Coordination in
the Mouse. Unpublished report prepared by Huntington Research Centre,
Ltd. Huntington, Cambridgeshire, England.

Algate, D.R., P.L. Munt and C.Mejer-Aspell. (1990). Copper
8-Quinolinolate Technical Investigation of Possible Neurological Effects
on the Rat Using The Tilting Plane Test. Unpublished report prepared by
Huntington Research Centre, Ltd. Huntington, Cambridgeshire, England.

National Toxicology program (NTP) (1985). NTP Technical report on the
Toxicology and Carcinogenesis of 8-Hydroxyquinoline (CAS No. 148-24-3)
in F344/N Rats and B6C3F1 Mice (feed Studies). EG&G Mason Research
Institute, Rockville, MD. NTP TR 276 (NIH Publication No. 85-2532;
NTP-83-029), April, 1985. Published by the U.S. Department of Health and
Human Services. 

Dietary References

Food and Drug Administration (FDA), 2003, “Guidance for Industry:
Preparation of food Contact Notifications and food Additive Petitions
for Food contact Substances: Chemistry Recommendations, Final
Guidance”

FDA, 2003,   HYPERLINK "http://www.cfsan.fda.gov/~opa2pmmne.html" 
http://www.cfsan.fda.gov/~opa2pmmne.html 

FDA, 2003, “Sanitizing solutions: Chemistry Guidelines for Food
Additive Petitions, January 1993.   HYPERLINK "http://www/"  http://www.
Cfsan.fda.gov/~dms/opa-cg3a.html. 

Environmental Fate References

42899001        A. Kesterson, B.A. and Brenda Lawrence. (1993).
Hydrolysis of [14C] Oxine Copper at pH 5, 7 and 9, Study performed by
PTRL East Inc., Richmond, KY. Final Report # 1244.

42925501        Dr. S. Dennis. (1991). Ro 17-0099/022 (14C-Copper
8-Quinolinolate) Photodegradation Studies in Aqueous Solution. Study
Performed by Metabolism Section (RES), Switzerland, Project #: RES-MET
Q13.

42925503        Dr. S. Sack. (1991). Ro 17-0099/022: Laboratory Non-Aged
Leaching              Study. Study Performed by Metabolism Section
Department of Registration and Environmental Studies (RES), Switzerland.
Project #: RES-MET Q102.

42925504        Dr. S. Sack. (1991). Ro 17-0099/022: Laboratory Non-aged
Leaching Study. Study Performed by Metabolism Section Department of
Registration and Environmental Studies (RES). Switzerland. Project #:
RES-MET Q103.

43620602        Electrostatic Application of NYTEK 10BL: Leaching of
Copper 8-Quinolinolate From Hemlock Wood.

Study Author: Matthew Crowe, PhD

Submitted by: Maag Agrochemicals, Inc. Vero Beach, Florida

Performing Waste Management Group: Applied Biology Division, British
Columbia Research Corporation, Vancouver, BC V6S 2 L2

Laboratory Report #: 2-51384-HEM

43620603        Electrostatic Application of NYTEK 10BL-PUR: Leaching of
Copper 8-Quinolinolate From Douglas Fir Wood

Study Author: Matthew Crowe, PhD

Submitted by: Maag Agrochemicals, Inc. Vero Beach, Florida

Performing Waste Management Group: Applied Biology Division, British
Columbia Research Corporation, Vancouver, BC V6S 2 L2

43667001	Leaching of Copper Oxinate(Copper 8-Quinolinolate) From Lumber
Spray Treated With Maag Sapstain Control Formulations, 1991

Study Authors: A. Byrne and D. Minchin

Submitted by: Maag Agrochemicals, Inc. Vero Beach, Florida

Performing Laboratory:Forintek Canada Corporation, Vancouver, BC V6T 1W5

Laboratory Report #: 17930425

43677301       Y. Esumi. (1995). Oxine Copper Technical (K-37):
Metabolism in Aerobic Soil. Study performed by Tokai Research
Laboratories Daiichi Pure Chemicals Co., Ltd., Shizuoka City, Japan.
Project#: AE-976-1.

Product Chemistry References

42922701C  Oxine Copper, 1990 by J. Freyre and G. Griffon. LA Quinoleine
S.A, Usine   D’Oissel, France

43532901  Product Chemistry of Copper-8-Quinoinolate, 1994, by Tomio
Katoh. Chemical Research Lab, Lab ID#: TOM-EPA-1.

43563001  Product Chemistry of Copper-8 Quinoinolate, 1994, by Tomil
Katoh. Chemical Research Lab. ID# TOM-EPA-1.

46346401C and 46346401  Product Identity and Composition of Q8 Log Oil
by Michael Kellog. 2004. Study #: 200401.

46438601C and 46438601  Product Chemistry Data on Osmose ORD-X378, 2004.
By Teri Muchow. Study ID#:  OSMOSE-2004-6.

46835201C and 46835201   Product Chemistry Data,
Cooper-8-Hydroxyquinoline (COX), 2006 by Bruce Bernard, PhD. Lab: SRA
International. Sonsor ID#: COX 2006-2.

Occupational Residential Exposure Assessment

455021101	American Chemistry Council (ACC). 2002.  Assessment of
Potential Inhalation and Dermal Exposure Associated With Pressure
Treatment of Wood with Arsenical Wood Products.

45524304	Bestari et al., 1999. [Sapstain Industry Group (SIG)-Consortium
Task Force] Measurement and Assessment of Dermal and Inhalation
Exposures to Didecyl Dimethyl Ammonium Chloride (DDAC) Used in the
Protection of Cut Lumber (Phase III). Unpublished Study Prepared by
University of Guelph. 309 p. (SIG Task Force #73154).

Bharat Textiles. 2007. Weight/Density Estimate for Army Duck Canvas
taken from a Specification Chart on the internet site   HYPERLINK
"http://www.tentandcanvas.com/product.htm" 
http://www.tentandcanvas.com/product.htm  of this canvas exporter. Last
viewed April 18, 2007.

  SEQ CHAPTER \h \r 1 Freeman, N , Jimenez M, Reed KJ,Gurunathan S,
Edwards RD, Roy A, Adgate JL, Pellizzari ED, Quackenboss J, Sexton K,
Lioy PJ, 2001.  Quantitative analysis of children’s microactivity
patterns:  The Minnesota Children’s Pesticide Exposure Study.  Journal
of Exposure Analysis and Environmental Epidemiology.  11(6): 501-509.

SIMetric. 2005.    HYPERLINK
"http://www.simetric.co.uk/si_materials.htm" 
http://www.simetric.co.uk/si_materials.htm   Last viewed November 9,
2005.

USEPA.  1997.  Standard Operating Procedures (SOPs) for Residential
Exposure Assessments.  EPA Office of Pesticide Programs(Human Health
Effects Division (HED). Dated December 18, 1997.

USEPA.  1997a.  Exposure Factors Handbook. Volume I-II.  Office of
Research and Development.  Washington, D.C.  EPA/600/P-95/002Fa. August
1997.

USEPA. 1998. PHED Surrogate Exposure Guide. Estimates of Worker Exposure
from the Pesticide Handler Exposure Database Version 1.1.   Washington,
DC:  U.S. Environmental Protection Agency.

  SEQ CHAPTER \h \r 1 USEPA. 1999.  Evaluation of Chemical Manufacturers
Association Antimicrobial Exposure Assessment Study (Amended on December
8,1992).  Memorandum from Siroos Mostaghimi, PH.D., USEPA to Julie
Fairfax, USEPA. Dated November, 4 1999.  DP Barcode D247642.

USEPA.  2000.  Standard Operating Procedures (SOPs) for Residential
Exposure Assessments. Prepared for EPA Office of Pesticide Programs,
Health Effects Division. Dated April 5, 2000.

USEPA.  2001.  HED Science Advisory Council for Exposure. Policy Update,
November 12, 2001.  Recommended Revisions to the Standard Operating
Procedures (SOPs) for Residential Exposure Assessment, February 22,
2001. 

  

USEPA. 2003.  Assessment of the Proposed Bardac Wood Preservative
Pressure Treatment Use.  Memorandum from Tim Leighton and Siroos
Mostaghimi.  February 11, 2003.

USEPA. 2004.  Occupational and Residential Exposure Assessment for
Carboquat WP-50.  Memorandum from Siroos Mostaghimi, USEPA to Velma
Noble, USEPA.   Dated November 4, 2004. DP Barcodes D303714 and D303938.

USEPA.  2005.  Antimicrobials Division’s Draft Standard Operating
Procedures for Occupational and Residential Exposure Assessments.  July,
2005. (Unpublished Internal Guidance).

USEPA.  2005a. A Probabilistic Exposure Assessment for Children Who
Contact CCA-Treated Playsets and Decks.  Final Report, February, 2005. 
US EPA Office of Research and Development, National Exposure Research
Laboratory.

USEPA.  2006.  Coppers: Second Revised Human Health Chapter of the
Reregistration Eligibility Decision Document (RED). Reregistration Case
Numbers 0636, 0649, 4025 and 4026. DP Barcode 319683. Dated January 17,
2006. Document ID: EPA-HQ-OPP-2005-0558-0006. (EPA Docket:
EPA-HQ-OPP-2005-0558; Copper Cases; Coppers Reregistration Eligibility
Decision, Notice of Availability, January 25, 2006.).

USEPA. 2006a. Review Memorandum: Oxine Copper (copper 8-quinolinolate)
– Endpoint Selection Report from T.F. McMahon, Ph.D., Senior
Toxicologist, AD. June 13, 2006.

USEPA. 2006b. Meeting Minutes of SMART Meeting Conference Call for
Copper 8-Quniolinolate. Reregistration Case 4026. November 8, 2006. 
Transmittal from K. Avivah Jakob, Chemical Review Manager, USEPA to
Copper 8-Quniolinolate RED Team Members, USEPA. Dated November 16, 2006.

USEPA. 2006c. Review Memorandum: Environmental Fate Transport Assessment
for Copper 8-Quinolinolate from A. Najm Shamim, Ph.D., Chemist, AD.
November 3, 2006.

Eco-toxicity References

42899002	Ward, G. (1993). Oxine Copper (Copper 8-Quinolinolate): Acute
Toxicity to Rainbow Trout, Oncorhynchus mykiss, Under Flow-Through Test
Conditions: Lab Project Number: J9006014A. Unpublished study prepared by
Toxikon Environmental Sciences.  43p.

42899003  	Ward, G. (1993). Oxine Copper (Copper 8-Quinolinolate): Acute
Toxicity to Bluegill, Lepomis macrochirus, Under Flow-Through Test
Conditions: Lab Project Number: J9006014B. Unpublished study prepared by
Toxikon Environmental Sciences.  44p.

42899004	Ward, G.; Davis, J. (1993). Oxine Copper (Copper
8-Quinolinolate): Acute Toxicity to Embryos and Larvae of the Eastern
Oyster, Crassostrea virginica, Under Static Test Conditions: Lab Project
Number: J9006014I. Unpublished study prepared by Toxikon Environmental
Sciences.  45p.

42899005  	Ward, G. (1993). Oxine Copper (Copper 8-Quinolinolate):
Chronic Toxicity to the Water Flea, Daphnia magna, Under Flow-Through
Test Conditions: Lab Project Number: J9006014F. Unpublished study
prepared by Toxikon Environmental Sciences.  52p.

42902401  	Carr, K.; Ward, G. (1993). Oxine Copper (Copper
8-Quinolinolate): Acute Toxicity to Coho Salmon, Oncorhynchus kisutch,
Under Flow-Through Test Conditions: Lab Project Number: J9006014C.
Unpublished study prepared by Toxikon Environmental Sciences.  44p.

42902402  	Ward, G. (1993). Oxine Copper (Copper 8-Quinolinolate): Acute
Toxicity to the Mysid, Mysidopsis bahia, Under Flow-Through Test
Conditions: Lab Project Number: J9006014J. Unpublished study prepared by
Toxikon Environmental Sciences.  42p.

42902403  	Lintott, D.; Ward, G. (1993). Oxine Copper (Copper
8-Quinolinolate): Toxicity to Embryos and Lavae of the Rainbow Trout,
Oncorhynchus mykiss, Under Flow-Through Test Conditions: Lab Project
Number: J9006014E. Unpublished study prepared by Toxikon Environmental
Sciences.  64p.

42902404  	Ward, G. (1993). Oxine Copper (Copper 8-Quinolinolate):
Toxicity to the Saltwater Alga, Nitzschia punctata, Under Static Test
Conditions: Lab Project Number: J9006014M. Unpublished study prepared by
Toxikon Environmental Sciences.  46p.

42902405 	Ward, G. (1993). Oxine Copper (Copper 8-Quinolinolate): Acute
Toxicity to the Saltwater Green Alga, Dunaliella tertiolecta, Under
Static Test Conditions: Lab Project Number: J9006014L. Unpublished study
prepared by Toxikon Environmental Sciences.  46p.

42927101 	Hakin, B.; Rodgers, M.; Grutzner, I. (1991). Ro 17-0099/000
(Copper 8-Quinolinolate): Acute Oral Toxicity (LD50) to the Bobwhite
Quail: Lab Project Number: HLR 184-901854: RCC 284253. Unpublished study
prepared by Huntingdon Research Centre Ltd.; RCC UMWELTCHEMIE AG. 53p.

42927102  	Hakin, B.; Rodgers, M.; Grutzner, I. (1991). Ro 17-0099/000
(Copper 8-Quinolinolate): Acute Oral Toxicity to Mallard Duck: Lab
Project Number: HLR 185-901733: RCC 284264.  Unpublished study prepared
by Huntingdon Research Centre Ltd.; RCC UMWELTCHEMIE AG. 38p.

42927103  	Hakin, B.; Rodgers, M.; Grutzner, I. (1991). Ro 17-0099/000
(Copper 8-Quinolinolate): Dietary Toxicity (LC50) to Bobwhite Quail: Lab
Project Number: HLR 187-901685: RCC 279854.  Unpublished study prepared
by Huntingdon Research Centre Ltd.; RCC UMWELTCHEMIE AG. 39p.

42927104  	Hakin, B.; Rodgers, M.; Grutzner, I. (1991). Ro 17-0099/000
(Copper 8-Quinolinolate): Dietary Toxicity (LC50) to the Mallard Duck:
Lab Project Number: HLR 186-901684: RCC 274228. Unpublished study
prepared by Huntingdon Research Centre Ltd.; RCC UMWELTCHEMIE AG. 39p.

43073501  	Ward, G. (1993). Oxine Copper (Copper 8-Quinolinolate): Acute
Toxicity to the Freshwater Alga, Skeletonema costatum, Under Static Test
Conditions: Lab Project Number: J9006014K. Unpublished study prepared by
Toxikon Environmental Sciences.  45p.

43228401  	Ward, G. (1994). Oxine Copper (Copper 8-Quinolinolate): Acute
Toxicity to the Water Flea, Daphnia magna, Under Flow-Through Test
Conditions: Lab Project Number: J9006014D. Unpublished study prepared by
Toxikon Environmental Sciences.  44p.

43563701 	Nozaka, T. (1995). Acute Toxicity of Copper 8-Quinolinolate to
Rainbow Trout: English Version: Lab Project Number: 90753:E89-0753.
Unpublished study prepared by Kurume Research Labs.  12p

Incident Report References

Teschke K, Hertzman C, Wiens M, Dimich-Ward H, Hershler R, Ostry A, and
Kelly S. 1992. Recognizing Acute Health Effects of Substitute
Fungicides? Are First- Aid Reports Effective? American Journal of
Industrial Medicine 21: 375-382.

Supporting Documents

AD’s End Point Selection Memo by Tim McMahon, June 13, 2006

Websites/Databases

EPI Suite. US EPA’s Estimation Program of Physical/Chemical
Characteristics of Chemicals.

APPENDIX A

Toxicity Profile for Copper-8-quinolinolate

Table 3.3 Subchronic, Chronic, and other Toxicity Profile for Copper 8- 
                                                   quinolinolate

Guideline number/Study Type/Test Substance

 (% a.i.)

	

MRID number (Year)/Citation/Classification/Doses

	

Results

Copper 8- quinolinolate (case #4026)

Copper 8- quinolinolate (PC code 024002)

870.3100 (§82-1a)

Subchronic oral - rat

99.5% a.i.

	MRID 42986801

Acceptable – Guideline

16/sex/dose at (0, 600 or 1000 mg/kg/day)

10/sex/dose at (30, 100 or 300 mg/kg/day)

for 13 weeks	

NOAEL = 30 mg/kg/day

LOAEL = 100 mg/kg/day, based on statistically significant ALT, AST and
bilirubin in males, increased spleen weights in females, increased
incidence of diffuse degeneration, focal necrosis, extramedullary
hematopoises in liver.

870.3100 (§82-1a)

Subchronic oral - mouse

Oxine Cu purity 99.9%

	MRID 42937301

Supplementary

6/sex/dose

0, 30, 600, or 1000 mg/kg/day

(100 and 300 mg/kg/day for 13 weeks) 	

No signs of toxicity were observed at the highest dose tested. (1000
mg/kg/day) The high dose, which is a mean of three different doses (30,
600 and 1000 mg/kg/day) of only 473 mg/kg/day, was not a limit dose, and
therefore, it therefore, it appeared that the compound was not tested at
a high enough dose.

In the absence of other signs of toxicity, a change in one enzyme level
cannot be used to determine the NOEL and LOEL of this chemical.

870.3100 (§82-1a)

Subchronic oral - mouse

Oxine Cu purity – not given

	MRID 42957801

Range-finding

10 mice/sex/dose

0, 300, 1000, 3000 or 6000 ppm for 13 weeks

	

Tentative NOAEL: 1000 ppm

Tentative LOAEL :  

Apparent treatment-related thickening and pallor of the glandular mucosa
of the stomach in 4/10 females.  Abnormal coloration (pallor) of the
glandular stomach mucosa was seen in 2/10 males at 3000 ppm and 6000,
1/10 was also thickened at the 6000 ppm dose. An increased incidence of
raised, cystic areas in the ovaries at 6000 ppm. The 6000 ppm dose was
recommended as the high level for

the subsequent carcinogenicity

Guideline number/Study Type/Test Substance

 (% a.i.)

	

MRID number (Year)/Citation/

Classification/Doses

	

Results

study.

870.3150 (§82-1a)

Subchronic - dog

99.5% a.i.

	MRID 42986802

Acceptable

4/sex/dose

0, 5, 50, or 250 mg/kg/day

for 13 weeks	NOAEL = 5 mg/kg/day

LOAEL = 50 mg/kg/day, based on vomiting, reduced total plasma protein
and albumin, reddened mucosa and hyperemia in stomach or small
intestine.

870.3200 (§82-2)

28 day dermal - rat

99.7% a.i.

	MRID 42957802

Acceptable - Guideline

5/sex/dose

0, 50, 200, or 1000 mg/kg/day, 6 hours/day for 4 weeks	

Dermal irritation

Tentative NOAEL = 1000 mg/kg/day

Tentative LOAEL > 1000 mg/kg/day, not established

Systemic toxicity

NOAEL = 200 mg/kg/day

LOAEL = 1000 mg/kg/day, based on necrosis of the thymic lymphocytes.

870.4300 (§83-1)

Chronic - rat

96%

	MRID 00083777

Core-Minimum

30/sex/dose

M/F: 0, 5, 20, 100, 500 or 2000 ppm for 102 weeks

            	

Tentative NOAEL: 500 ppm

Tentative LOAEL: 2000 ppm, based on increased concentration of copper in
tissues accompanied by histomorphologic effects.  The incidence of
neoplasia was comparable between the control and treated animals.

When compared to the concentration of copper in the tissues of the
control rats, moderate to marked increases in copper content were noted
in the livers of group 6 

(2000 ppm) rats of both sexes sacrificed at 52 and 102 weeks.  Slight to
moderate increases in copper content were also noted in the kidneys of
group 5 (500 ppm) and group 6 (2000 ppm) males and the group 4 (100 ppm)
group 5 (500 ppm) and group 6 (2000 

ppm) females sacrificed at 52 weeks and in the group 6 males

and the group 2, 4, 5 and 6 females sacrificed at 102 weeks.

The coppe brains of group 5 and group 6 r concentration in the

Guideline number/Study Type/Test Substance

 (% a.i.)

	

MRID number (Year)/Citation/

Classification/Doses

	

Results

males sacrificed at 102 weeks were very slightly increased.  The tissue
copper contents in the rats of the other treated groups weregenerally
comparable to those of the control rats.

There was no evidence of a compound-related effect with regard to
physical appearance and behavior.

870.4100 (§83-1)

Chronic - dog

96%

	MRID 00099606

Core-Minimum

4/sex/dose for 6 groups

M/F: 0, 10, 40, 200, 1000 or 3000 ppm  for 102 weeks

           	

Tentative NOAEL: 200 ppm

Tentative LOAEL: 1000 ppm, based on histological alteration in the liver
and lung correlated with an increase in copper content.

In dogs treated at levels up to 1000 ppm, no effects attributable to
compound administration were noted in evaluations of mortality data,
general appearance and behavior, body weight and food consumption
values, clinical lab values or organ weights and organ/body weight
ratios.

In addition, evaluations of tissue copper analyses values and gross and
histologic pathology data revealed no findings indicative of an effect
from compound in animals treated at levels up to and including 200 ppm. 
At the 1000 ppm level, no compound related-findings were observed in the
one male and one female sacrificed at 52 weeks.  In those dogs
sacrificed at 104 weeks, moderate 

increase in copper content were noted in the livers of all the dogs and
compound-related histomorphologic alterations of the lung (subpleural
inflammation) and liver (focal accumulations of pigment-laden

kupffer cells) were noted in one female dog.

Guideline number/Study Type/Test Substance

 (% a.i.)

	

MRID number (Year)/Citation/

Classification/Doses

	

Results

In the dogs treated with compound at a level of 3000 ppm,
compound-related findings were noted in the majority of the parameters
evaluated.  These findings the following: inappetence resulting from the
impalatibility of the test diet (primarily noted when being treated at a
level of 4000 ppm), mortality in the second year in 4 of the 6 animals
remaining on study after the 52 week interval sacrifice; general
unhealthy appearance in all dogs during the second year; body weight
losses, suppressions in food consumption, hematology findings indicative
of anemia, and blood chemistry findings indicative of hepatoxicity
during both years of the study; marked increase in copper contents of
brain, spleen, livers and kidneys of  the males and females and
histomorphologic alterations involving a variety of tissues examined. 
Principal tissue alterations were liver, kidney, lung, spleen and
anterior mesenteric lymph nodes.

870.4200 (§83-2)

Carcinogenicity-Mouse

97.2%

DER #8	

MRID 43267201

Acceptable – Guideline

50.sex/dose

0,100,400, 1500, or 6000 ppm (M: 0, 14.5, 57,1, 207.7, or 855.8
mg/kg/day, F: 0, 16.1, 66.2, 246.2, or 1051.7 mg/kg/day)

	

NOAEL = 57.1 mg/kg/day (M)

        = 66.2 mg/kg/day (F)

LOAEL  = 207.7 mg/kg/day (M)

               =  246.2 mg/kg/day (F), based on increased incidence of
stomach ulcers in males and mild anemia and adverse liver effects in
females.

No dose-related increases in individual neoplastic lesions were
observed. 

Guideline number/Study Type/Test Substance

 (% a.i.)

	

MRID number (Year)/Citation/

Classification/Doses

	

Results

870.3700 (§83-3)

Carcinogenicity-Mouse

98.5%

DER #9	

MRID  4298603

Acceptable –Guideline

36/dose

0, 50, 200, or 800 mg/kg/day, 

GD 6-15

	

Maternal Toxicity 

NOAEL = 200 mg/kg/day

LOAEL = 800 mg/kg/day, based on increased clinical signs (piloerection,
poor general condition, encrustation of nose and mouth), and decreased
body weight and gain.

Developmental toxicity

No dev. Tox observedentative NOAEL = 800 mg/kg/day

Tentative LOAEL > 800 mg/kg/day, not established

870.3700 (§83-3)

Carcinogenicity-Mouse

96.5%

DER # Not Reviewed

	

MRID 41063702

Not Reviewed

4 groups @ 16/dose

0, 7, 15, or 30 mg/kg/day, GD 7-19	

Maternal Toxicity

Tentative NOAEL= 30 mg/kg/day (HDT) maternal body weight was not
affected as wel as the body weight gain for the treated groups was
similar to the control group.

There was no adverse effecte on food consumption at the HDT (30
mg/kg/day).

Developmental toxicity

Tentative NOAEL = 30 mg/kg/day (HDT)

870.3800 (§83-4)

Reproduction - Rat

> 99.7%

DER # 10

	

MRID 43267202

Acceptable – Guideline

F0: 32/sex/dose

F1: 28/sex/dose

0, 25, 250, or 2500 ppm

(F0: 0, 1.8/2, 18.2/20.8, 181/203 mg/kg/day M/F, F1: 0, 2/2.2,
19.8/22.8, 96/218 mg/kg/day M/F)

	

Parental – Systemic

NOAEL = 250 ppm

LOAEL = 2500 ppm, based on increased liver weight in F1 males.

Reproduction

NOAEL = 250 ppm

LOAEL = 2500 ppm, based on decreased mean number of live pups at birth
(85% of controls) and decreased litter weights at day 0 and during
lactation in F1 generation.

Guideline number/Study Type/Test Substance

 (% a.i.)

	

MRID number (Year)/Citation/

Classification/Doses

	

Results

870.3800 (§83-4)

Reproduction - Rat

> 96%

DER # 11

	

MRID 0079233

Core minimum

P1: 25/sex/dose

P2: 25/sex/dose

P1 & p2: 0, 20, 100 and 500 ppm

	Tentative NOAEL: >500 ppm (HDT) 

Parental:

Food and water consumption showed no treatment-related effects. No
deaths occurred nor were any signs of compound-induced toxicity
observed, during the growth, gestation, or lactation periods of either
parental generation. The pregnancy rates and parturition indices (number
of females delivering viable offspring/total umber of females) of all
the groups were considered comparable at both matings of both parental
generations. Evaluations of the live birth 

	

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n viability between the treated and control group offspring obtained
from either mating trial of the P1 and P2 generations.

No treatment-related findings were observed in gross pathology in the
selected offspring in the F1b generation sacrificed at weaning.

No deaths or signs of compound induced toxicity were observed in the F1b
or F2b generation offspring maintained for 5 weeks and 3 months
postweaning.

870.5100 (§84-2)

Mutagenicity - Ames

Purity not reported 

	

MRID 00248746

Acceptable – Guideline

Strain: TA1535, TA1537,TA1538, TA98 and TA 100

– 0.3 µL/plate (0.2 and 0.3 µL/plate were toxic)

	

Positive

Induced increase in histidine reverants in one strain TA 100, possible
also TA 1538 and TA 98 with metabolic activation (weak mutagen).

Guideline number/Study Type/Test Substance

 (% a.i.)

	

MRID number (Year)/Citation/

Classification/Doses

	

Results

870.5100 (§84-2)

Mutagenicity - Ames

Purity99.7%

	

MRID 42962301

Acceptable – Guideline

TA97, TA98, TA100, TA102,

TA1535, TA1537, TA1538; S. Typhimurium; concentrations: 0.33 – 100
µL/plate (standard assay), 0.51 – 50 µL/plate (pre-incubation)

	

Positive

Dose-related weakly positive reverse gene mutation in S9-activated
bacterial strains TA97, TA100, TA102 of S. typhimyrium exposed up to
toxic doses.

870.5395 (§84-2)

Mutagenicity –Micronucleus test in the Mouse Bone Marrow

Purity 98.5%

	

MRID 42962302

Acceptable – Guideline

Mouse – 5 mice/sex/dose Administered orally at 0, 3750, 7500 mg/kg	

Negative

For induction in bone marrow cells of mice treated once at doses up to
7500 mg/kg, a non-toxic (but limiting) dose. 

870.5550 (§84-2)

Mutagenicity –Unscheduled DNA synthesis 

Purity 99.7%	

MRID 42962303

Unacceptable

Rat – Male 1-3/dose group gvaged once at 100, 500, 1000, 1500,a 2500
and 3000 mg/kg	

Negative

For induction of unscheduled DNA synthesis in primary rat hepatocyte
cultures isolated from male rats treated orally up to 3000 mg/kg, as
determined by radioactive tracer procedures [nuclear silver grain
counts].

870. 7485 (§85-1)

Metabolism – rat

Purity >98.5% (unlabeled); >98% radiolabeled material

	

MRIDs 42962304, 42962305

Acceptable – Guideline

30 or 1000 mg/kg (unlabeled, daily for 14 days) single labeled 30 mg/kg
Major route of excretion via urine (62-68%) and feces (8-26%) within 45
hours. Rapid absorption inferred by rapid excretion of metabolites in
urine. Radioactivity in tissue residues very low in all tissues
including blood (<0.05%). Bioaccumulation is minimal. Radioactivity in
urine associated with parent (5-16%) and sulfate (12-18%) of the parent.
In feces, radioactivity associated with parent (4-23%) and glucuronide
conjugate of the parent (0.1-4%).

  Testing with the more sensitive species (freshwater or
estuarine/marine) based on acute toxicity test results is required.

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