Aq u a s hade ® Human H ea lth Ri s k Assessment DP No. 0425777

UNITED S T ATES ENV IR ONM ENTAL PROTECTION AGENCY

WASH I NGTON

, D.C. 20460

M E MORAND U M

Date: Se ptemb e r 1 5

, 20 15 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

SUB J ECT : Aqua s h a d e ®

. Sco pin g Document and Dr a ft Risk Assess m e nt for R eg i st r at ion

Review

P C Co d e: I I 0 303, I I 030 I

, 11 0302

D ec i s i o n No.: 5002 1 I DP Bar code: 425777

R eg i s tr a ti o n No.: NA

P elilion No.: NA R eg ul alor y Ac ti on: R egistratio n R eview

Case No.: 4010 Ri s k A ss e ss ment T y p e: Scoping D ocumen t
TXR No.: NA CAS No.: 26 50-18- 2; 19 34-2 1- 0

40CFR: 1 80.1074 ; 1 80.910 MR ID N o.: NA

FROM:

THROUGH:

TO: U ma Habiba

, Ri s k A ssesso r

## ~ 

# Ii

Ronnie Bever

, Ph

. D

. , Toxicolo g i s t /{., 

## /l**~ ~**  

## . Katel y nn Kin g, C hemi s t

### ~ 

# U

Ri s k A ssess m e nt Branch 5/7 

### 'I

H

ea lth Effects Di vis i on (750 )

1 (**(~**

Michael Met zge r , Chief 

# VJA (} /() ·**~** A l exa ndra Gavclck

, Bi o og t ";) ; 

# kr

7 

### "'-li' L •
Pete Savo ia

, C h e mi s t (**~'--{""** (___**~--** Risk As sess ment Branc 5/7 /

H ea l th E ffects Di vis i on (75 09P )

C hri st ina Motilall

, CRM
Ri s k M a n ag em e nt and Impl e m e ntation Br a nch ( RMIB I )

P est icid e R e

- evalua tion D i vision ( PRD )

P age I of 35

### Aquashade ® Hum an He alt h Ri sk Assessment DP No. 0425777

1.0 E xecutive S un1m ary

. . .. .. .. . ... . ... . ... .... . . .. ....... .. ...... ... .................. .. . .. .. .... . . . ..... . ...... . ......... . ...... 3
2

. 0 H E D Recommen d a ti on s

.. ...... .... ... ...... .. ....... ... ..... ... ...... .. ............................................. .. .... 6

2.1 Data D efic i e n c i e s

. . .. .. .. . .. ....... . ....... . ............. . ............... .. ...... .. . .. .. ... .. ...... .. . ... .. . . ... ..... .. ...... 7

2.3.2 Recommend at i on s from Occupational As s e ss ment..

.. ..... ..... .. ........................... .. . .. . 7
2.3.3 R ecom mend at ion s from R es id e nti a l Assess m ent

.. ...... ...... ...... .... ...... .. ..... .. . .......... ... 7

3.0 Introduction

. ...... ....... . ...... ... ............................. .. ...... .. .............. .. ...... .. . .. .. .. . .. ....................... 7

3.1 C h e 1ni ca l Id e ntity

.. .. .. . .. ...... .. . ... .. ................... ... ...... ... ... . ..... . .. ...... .. . ... . ...... .. .. . .. ............... 7

3.2 Ph ys ical /C h emica l Cha r ac t e ri s t i c s

...................................... .. ..... ... ..... ... . .. .. ...... .... ... .... . 8

3.3 Pest icide Use Pattern

.. .... . . .. .. . ... . ... . . .. . ...... .. ...... .. . .. ......... .......... ......... ..... ... ..... .. . .. .. .. . .. ..... 8

3.4 An ti ci p ated E xpo s ur e Pathwa ys

............. .... ..... ..... ... ....... .. .. ................. . ..... ..... .............. 8

3.5 Co n s id era tion of E n v ironm enta l Ju s tice

. . ... .. .. .. .. .. ... . .. .. .. . . .. . ..... . .... .. . .. .. ... . ... . . .. ..... .. ..... 9
4.0 H a zard C h a r acterizat i o n and Do se -Re s p o n se Assess m e nt

...................... .. ..... .. ..... . . . ..... 9

4.1 Sum m ary of To x icological Effects

..... ... .. .. .. .. .... . .. . ... . .. . . .... .. ...... . .. . ... .. ............. . ...... .. ..... 9
4.2 Sa fety Factor for In fants and C hildr e n (FQPA S afe ty Factor)

................. .. ............ 

### 11

4

. 2.1 Co mpl ete n es s o f the Toxicolo gy D ataba s e

................. .... ....... .. .. .. . ... ..... . .... .. ...... . ..... 11

4

. 2.2 Ev iden ce of Ne urotoxicit y

... ............................. . ....... . ............... . ........ ... ..... .. ............. l l

4.2.3 Ev iden ce of Se n s itiv ity/S u s ceptibility in the Developing o r Yo un g A nimal..

.... .. 11
4.2.4 Re s idual U ncertainty in the Ex p os ur e Datab ase

............................ .. .. .. . .... ....... . .... 11

4.3 Tox icity End p oi nt a nd Point of Departure Se le c tion s

.. ... .. ...... .. ... .. ... .. ...... . . ......... .. .. 12
5

. 0 Dieta ry E x p os ur e an d Ri s k A ss essme nt

.... ... ............................................................. . .... 14

6.0 Re s id e nti a l (No n

- Occupational) E xposure/Ri s k C h a r acte ri zat i o n

.......... . ..... ... .... ... ... 15

6.1 Re s identi a l Handler E xpo s ure

...... ... ...... .. ................. .. ..... ... .... ... ......... . ........ .... ..... .. .... 15

6 .5 Residenti a l Bystander Post-application Inh a la t i o n Ex p os ur e

.. .. ..... . .. . ... . .. ... .. ...... ... 20

6.6 S pra y Drift

........... . ....... . ...................................................... ... ........ .. .... .... .... .. . . .......... ... 20

7. 0 Agg r ega t e Expos ur e/ Ri s k C h aracter i zatio n

.. .. ... . ... .. .. . ... .. ... .. ..... .. .... .. .. .. . ................. . . .. . 20
8.0 C umul a ti ve E xpo s ure / R i s k C h aracte riz a ti o n

........................................ . ........ .. ..... .... ... 23

9.0 Occupational Expos ur e/ Ri s k C har acteriza ti o n

.... .. ...................... .. .. .. .. .. .... . .. . .. .. .. . .. ..... 23

9

. 1 S h o r t- a nd Intermedi a te

- Pos t -Ap pli cat i o n Ri s k

. ...... ..... ..... ... .... ..... .... ... .. ................ 

### 25

9. 1

. 1 Dermal Po st

- a ppli ca ti o n Ri s k

. . .... . .. .. ....... . . .. .... .. .. . . . . ...... .. . ................ . .. .. .. ... . . . .. . ..... .. 25

9.1.2 Inh a l at i o n Po s t -a pplication Ri s k

.................................... .... ..... .. ...... ... ..... .. .............. 

### 25
10

. 0 E pidemiolo gy

. . .. .. . ... . .. .. ..... .. .. .. ... ..... ... ...... .. .. .. ... .. .. . ... .. .... .. ...... .. . .. .. . . ........ . . .......... . .... .. ...... 25

11

. 0 R e ference s

..... . .......... . ...... ..... ..... ... ...... ...... ... ... ...... ...... .. ..... ...... . ............................ . ...... .... .. 

### 25

A pp en dix A. To x i co lo gy Profile a nd E x ecutive Su mm ar i es

.. .. ...... ... . . ... . .. . . .. . ... . .. . . . ..... .. ..... 

### 27
A.l Tox i co lo gy Data Requir e ment s

.... .. .................. .. .... .... ....... . ......................................... 

### 27

A

. 2 Toxicity Profile s

...... .. . .......... .. ...... .. ....................................... .. .. .. . . .. . .. .. ...... . .. . . . . . ......... .. 28

A pp en di x B. Ph ys ical/ C h e mic a l Propert i es

......... .. ....... ... ..... .. ....... .... ........................... .. ..... .... 32 Append i x C. S ummary o f Occupational and Residential No n -ca n cer Al go rithm s

.. . ..... ... . . 33



### P age 2o f 35

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 3 of 35 1.0 Executive Summary

The Health Effects Division (HED) of EPA's Office of Pesticide Programs has evaluated the toxicity and exposure data bases for the aquatic algaecide/herbicide Aquashade® also known as
Admiral ® , containing the dyes e rioglaucine (Acid Blue 9 or FD&C Blue No. 1) and tartrazine (Acid Yellow 23 or FD&C Yellow No. 5); and has conducted a human health ri sk assessment in support of the registration review for these active ingredients.

Erioglaucine and tartrazine have many non

- pesticidal uses, including their use as inert ingredients (dyes) in other pesticide formulations and as approved food coloring additives in a variety of applications. These substances are each Generally Recognized as Safe (GR AS) for general use as food, drug, and cosmetic color additives by the Food and Drug Administration (FDA).

This risk assessment considers only the use of erioglaucine and tartrazine as active ingredients in Aquashade® and similar products. Human health risk estimates associated with their use as inert ingredients were previously assessed by the Office of Pesticide Programs' Registration Division (RD) [ Reassessment of the Requirement of a Tolerance for the FDA

- Certifie d Color Additives FD&C Blue No. 1, FD&C Red No. 40, and FD&C Yellow No. 5 (Tartrazine) , K. Liefer, December 21, 2004 ] and by OPP’s HED [ Aquashade®: Revised HED Chapter of the Reregistration Eligibility Decision Document (RED) , W. Britton, September 9, 2005 ] . HED relied heavily on the information presented in RD’s inert ingredient risk assessment and HED’s revised HED chapter of the RED in this assessment of the human health risk estimates from the pesticidal uses of Aquashade®

.

Use Information

Aquashad e® also known as Admiral ® is registered for use as an aquatic algaecide/herbicide. The two dyes

, erioglaucine and tartrazine

, work by blocking penetration of the portion of the light spectrum required for photosynthesis, thereby limiting the growth of fila mentous algae and submerged aquatic vegetation. Application is recommended early in the growing season while growth is on the bottom of the water body or later in the season after the killing and/or removal of any existent growth. Repeated applications a re allowed to maintain an effective concentration of product in the water body. Aquashade® may be used in natural or manmade ponds, lakes, fountains, fish farms and fish hatcheries; and may be applied by both professional applicators
and home owners . Wate r bodies treated with Aquashade® may not be used for human consumption. However, treated water may be used for irrigation of crops, livestock watering and fishing. Any residues of erioglaucine or tartrazine occurring in foods from the use of Aquashade® as an aquatic algaecide/herbicide would be negligible

.

Toxicology

The toxicology database is sufficient for characterizing toxicity and hazard. The toxicity profile of Aquashade® does not identify a target organ. Systemic toxicity was observed in one study in the toxicity database and was limited to a decrease in mean body weight following long

- term dietary exposure to high doses in rats. No developmental, reproductive, or neurological toxicity

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 4 of 35 was observed in the database. Immunotoxicity was not tested, bu t is not required. There was no evidence of carcinogenicity or mutagenicity in the database. Aquashade® is not acutely (lethal)
toxic via the oral, dermal, and inhalation routes (Toxicity Category III or IV), is not an eye or dermal irritant, but is a derm al sensitizer.

Based on the toxicity, duration of exposure, and uses of Aquashade®, the following toxicity endpoints were selected:

Acute Dietary Endpoint (General Population, including Infants and Children;
Females 13

- 49 years of age): No appropriate endpoint was identified which could be attributed to a single exposure. Chronic Dietary Endpoint: chronic population adjusted dose (cPAD) of 5 mg/kg/day
derived from a no observed adverse effect level ( NOAEL ) of 500 mg/kg/day tartrazi ne in a chronic oral toxicity study in dog. A lowest observed adverse effect level ( LOAEL ) was not identified. A combined chronic toxicity/carcinogenicity study in rat was considered

co

- critical (NOAEL of 631 mg/kg/day erioglaucine; LOAEL of 1262 mg/kg/day based on decreased body weight in females).
Short

- and Intermediate

- Term Incidental Oral, Inhalation, and Dermal (residential and occupational where applicable): The same endpoints were used as in the chronic dietary exposure scenar io. An appropriate guideline, dermal toxicity study was not available for any exposure scenario. There was a non

- guideline, 21

- day dermal study in rabbits with a NOAEL of 5 mg/kg/day (highest dose tested). However, given that all other guideline studies had NOAELs ≥ 500 mg/kg/day and that 5 mg/kg/day was the highest dose tested in the dermal study, selection of an endpoint based on this study will give an extremely conservative endpoint and is unlikely to be near the threshold dose. Therefore, the chroni c oral toxicity study in dogs was selected, assuming 100% dermal absorption (which is expected to be conservative in the absence of a dermal penetration study).

For the occupational and residential risk assessments the level of concern (LOC) is for MOEs less than 100. The FQPA safety factor has been reduced to 1X. The screening exposure assessment for swimmers (SWIMODEL) was developed based upon reliable data and is unlikely to underestimate exposure or risk estimates.

Residue Chemistry

Water bodies t reated with Aquashade® may not be used as a source of drinking water

. However, treated water may be used for irrigation of crops, livestock watering and fishing, which could result in residues of erioglaucine and/or tartrazine in human foods. In addition

, Aquashade® may be used in fish farms/hatcheries. In 1982, based on Aquashade 's ® low toxicity profile, EPA waived residue chemistry data requirements and established an exemption from the requirement of a tolerance for erioglaucine when used as an aquati c plant control agent under 40 CFR 180.1074. Tartrazine, when used as a dye, had previously been exempted from the requirement of a tolerance as an inert (or occasionally as an active) ingredient in pesticide formulations applied to growing crops or to ra w agricultural commodities after harvest under 40
CFR 180. 910 (previously 40 CFR 180.1001 ). HED has determined that the existing exemption

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 5 of 35 for tartrazine as an inert ingredient is not sufficient to satisfy reregistration requirements for the active ingred ient when used as an aquatic plant control agent. Therefore, we are recommending that the exemption for erioglaucine at 40 CFR 180.1074 be revised to include both erioglaucine
and tartrazine.

Residential Exposure

Aquashade® is labeled for consumer use t o control aquatic algae and weeds in ponds and lakes. The anticipated use patterns and current labeling indicate several residential handler scenarios based on the types of equipment and techniques that can potentially be used to make Aquashade® applicati ons. Residents or consumers applying Aquashade® products to ponds or lakes may be exposed for short

- term (1 to 30 days) duration through skin contact or by
inhalation.

All residential handler scenarios assessed resulted in estimated MOEs greater than 100 and, therefore, are not of concern. Residential short

- term dermal MOEs range from 16,000 (pouring liquid) to 1,400,000 (drop in water soluble packets) , and short

- term i nhalation MOEs range from

to 92,000 (pouring liquid) to 110,000 (drop in water soluble packets)

. Combined dermal and inhalation MOEs range from 14,000 (pouring liquid) and 110,000 (drop in water soluble packets).

Post

- application exposures to children an d adults that contact Aquashade®

- treated swimming ponds are anticipated. To address the risk of such exposures, a screening tool from the 2013 Draft Aquatic SOP, the Swimmer Exposure Assessment Model (SWIMODEL) was applied. The
SWIMODEL uses well

- accepte d screening exposure assessment equations to calculate the total

worst

- case exposure for swimmers expressed as a mass

- based intake value (mg/ event). Post

application residential exposure durations are expected to be short

- term in duration. All
residenti al post

- application scenarios assessed (dermal, ingestion, and inhalation routes of exposure) resulted in estimated combined MOEs well above 100 and, therefore, are not of

concern.

Aggregate Risk

In accordance with the FQPA, HED must consider and aggrega te pesticide exposures and risk
estimates from three major sources: drinking water, food and residential exposures. Since Aquashade® is applied to contained water bodies with little or no outflow, and none of the
treated water bodies serves as a source of drinking water, no drinking water exposure is expected. Although water treated with Aquashade® may potentially be used for irrigation of food crops and livestock watering, and Aquashade® is registered for use in fish farms and hatcheries, HED has not qua ntitatively assessed exposures and risk estimates from food sources for several reasons: (1) Aquashade® is used primarily in ornamental and/or recreational lakes and ponds with very little treated water expected to be used for agricultural pu r poses. (2)

E rioglaucine and tartrazine are highly water soluble compounds and, as such, not likely to accumulate in livestock or fish tissues. The results of the rat metabolism study with erioglaucine support this determination, since nearly the entire administered d ose was excreted unchanged in the feces in less than 2 days. (3) Any residues of erioglaucine or tartrazine occurring in foods

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 6 of 35 from the use of Aquashade® as an aquatic algaecide/herbicide would be negligible compared to
residues in food from the common u se of these dyes as food coloring additives. (4) The most significant route of exposure to erioglaucine and tartrazine from the use of Aquashade® is residential exposure, including residential handler and post

- application (swimming) exposure.
HED believe s that the conservative residential exposure and risk estimates discussed above are more than adequate to cover any food exposures that could potentially occur from the use of Aquashade® as an aquatic algaecide/herbicide.

Occupational Exposure

Pesticide handler exposure to Aquashade® is likely to occur during its use in a variety of occupational environments. The anticipated use patterns and current labeling indicate several occupational exposure scenarios based on the types of equipment and te chniques that can be potentially used for Aquashade® applications. Short

- term (1 to 30 days) and intermediate

- term exposures (1 to 6 months) may occur; however, long

- term exposures (greater than 6 months) are not expected.

All short

- term occupational sce narios assessed (dermal and inhalation) resulted in estimated MOEs greater than the LOC of 100 and, therefore, are not of concern.

Public Health and pesticide Epidemiology Data

Based on the low severity of incidents involving A quashade® (pc code 110303), acid yellow 23 ( pc code 110302), and a cid blue 9, diammonium salt ( pc code 110301) reported to IDS and the fact that no incidents involving A quashade ®

, acid yellow 23, and a cid blue 9, diammonium salt were reported to SENSOR

- Pesticides, t here does not app ear to be a concern at this time that would warrant further investigation

. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the risk assessment (S. Recore, 2014, D427136).

Conclusions

Aquashade® is a low toxicity algaecide/ herbicide with the potential for occupational, dietary, and residential (non

- dietary) exposure. The label precludes use of treated water bodies as a source of drinking water; and, while treated water ma y be used to irrigate food crops or for livestock watering, resulting food residues are expected to be negligible. Aggregate risk
estimates (including dietary and no n

- dietary residential exposure) are well below HED’s level of

concern. Under the conditions of its current use, human health risk estimates to workers handling the pesticide or to the general population are below HED’s level of concern.

2.0 HED Recommendations

The assessment discussed herein constitutes both the registration review scoping doc ument and
draft risk assessment for Aquashade®. HED concludes that there are no human health risk
estimates of concern associated with the currently registered uses of Aquashade®.

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 7 of 35 2.1 Data Deficiencies

The toxicity, exposure, and residue chemistry dat abases are considered complete for the purpose of registration review. No additional data is required to support the requested registration of Aquashade®.

2.3.2 Recommendations from Occupational Assessment

None.

2.3.3 Recommendations from Residential Assessment

None.

3.0 Introduction

3.1 Chemical Identity

Table 3.1 Aquashade®

Chemical Structure

Empirical Formula C 37 H 34 N 2 Na 2 O 9 S 3 C 16 H 9 N 4 O 9 S 2 Na 3

Common Name Erioglaucine, Acid Blue 9 Tartrazine , Acid Yellow 23
Company experimental name BASF BASF

IUPAC name 

### disodium;2

- [[4

- [ethyl

- [(3

-

sulfonatophenyl)methyl]amino]phenyl ]

- [4

- [ethyl

- [(3

- sulfonatophenyl)methyl]azaniumylide ne]cyclohexa

- 2,5

- dien

- 1

- ylidene]methyl]benzenesulfonate trisodium;5

- oxo

- 1

- (4

- sulfonatophenyl)

- 4

- [(4

- sulfonatophenyl)diazenyl]

- 4H

pyrazole

- 3

- carboxylate

CAS Name disodium bis[4

- (N

- ethyl

- N

- 3

-

sulfonatophenylmethyl)aminophenyl]phe nylmethylium 4,5

- dihydro

- 5

- oxo

- 1

- (4

- sulophenyl)

- 4

- [(4

- sulfophenyl)azo]

- 1H

- pyrazole

- 3

- carboxylic acid trisodium salt
CAS Registry Number 2650

- 18

- 2 1934

- 21

- 0

End

- use product/EP 33068

- 1 12.60% ai 1.04% ai

33068

- 3 30.45% ai 2.45% ai

67064

- 1 49.72% ai 3.27% ai

67064

- 2 15.31% ai 1.00% ai Known Impurities of
Concern N/A N/A

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 8 of 35 3.2 Physical/Chemical Characteristics

Aquasha de ® is composed of two dyes, erioglaucine and tartrazine. Erioglaucine has a vapor pressure of 2.97 x 10

- 42 

### mmHg @ 25°C and tartrazine has a vapor pressure of 7.43 x 10

- 22 

### mmHg @ 25°C. Both dyes are water soluble and have low octanol/water partition coefficients. Aquasha de ® would not partition into fatty tissues. As a result, bioaccumulation would not occur. See Appendix B for detailed information.

3.3 Pesticide Use Pattern

Aquashade® is registered for use in a variety of occupational and residential scenarios and thus
these populat ions could be exposed while performing Aquashade® applications. Aquashade liquids are “ready

- to

- use” formulations and do not require any mixing/loading for preparation. A summary of maximum application rates for registered Aquashade® us es is presented in Table
3.3.

Table 3

. 3 . Summary of Directions for Use of Aquashade®

Applic. Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic.

Rate (lb
ai/A

- ft ) Max. No.

Applic. per
Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Aquatic Areas

Pouring Aquashade®

Liquid (33068

- 1) 0. 75 N/A N/A N/A 80 oz/2.4 L per A

- ft

Pouring Aquashade®

Liquid (33068

- 3) 0.79 N/A N/A N/A 32 oz/0.93 L per A

- ft

Pouring Admiral

Liquid (67064

- 2) 0.73 N/A N/A N/A 64 oz/1.89 L per A

- ft

WSP Admiral

WSP (67064

- 1) 0.58 N/A N/A N/A 2 WSPs per A

- ft



### 3.4 Anticipated Exposure Pathways

Humans are not exposed to Aquashade® in food and drinking water, since Aquashade® is applied directly to aquatic areas application it does not result in Aquashade® leaching and infiltrating into ground sources of drinking water . In an occupational setting, applicators may be exposed while handling the pesticide during application. There is no potential for post

application exposure for workers. Residential and occupational handlers may be exposed via dermal and inhalation routes. Residential post

- application scenarios may results in dermal, inhalation, and oral routes of exposure.

A human health assessment to support a registration e ligibility document (RED) (W. Britton, 2005, D 321912 ) has been previously completed for Aquashade®, but no new toxicity data have been received since the previous risk assessment. This risk assessment considers all of the

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 9 of 35 aforementioned exposure pathways of Aquashade® for the dietary and residential risk

assessments.

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance wi th U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," ( http://www.eh.doe.gov/oepa/guidance/justice/eo128 98.pdf

. As a part of every pesticide risk assessment, OPP considers a large variety of consumer subgroups according to well

- established procedures. In line with OPP policy, HED estimates risk estimates to population subgroups from pesticide exposures tha t are based on patterns of that subgroup’s food and water consumption, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing
Sur vey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the countr y. Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non

- dietary exposures based on home use of pesticide products and associated risk estimates for adult applicators and for toddlers, youths, and adults entering o r playing on treated areas post

application are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose

- Response Assessment

No new toxicity and/or metabolism data have been received by HED since the last risk assessment (W. Britton, 2005, D 321912 ).

4.1 Summary of Toxicological Effects

A combination of erioglaucine (Acid Blue 9 or FD&C Blue No. 1) and tartrazine (Acid Yellow
23 or FD &C Yellow No. 5) is commonly referred to as Aquashade®. Five currently registered pesticide products, which are used as aquatic algaecides/herbicides, contain a combination of erioglaucine and tartrazine. These substances are each Generally Recognized as Safe (GRAS) for general use as food, drug, and cosmetic color additives by the Food and Drug Administration (FDA).

The mode of action for Aquashade® as an aquatic herbicide is through sunl ight filtration, inhibiting photosynthesis. Tartrazine and erioglaucine each have very low toxicity potentials.

Erioglaucine and tartrazine are rapidly metabolized, and excreted in rats, rabbits, and dogs. Erioglaucine is poorly absorbed; however, this is not the case for tartrazine. The presence of the dye was found in the bile. The parent compounds are excreted unchanged mainly in the feces

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 10 of 35 with a small amount excreted by the urine. Erioglaucine was administered orally to rats as a 2% aqueous solutio n at a level of 200 mg/rat. Almost the entire amount was excreted unchanged in the feces within 40 h after administration. In a later investigation, the presence of the color in the bile was observed in rats, rabbits, and dogs after oral administration. In the case of the dog, the amount did not exceed 5% of the dose administered (Hess, 1953; 1954; 1955). Administration of an aqueous solution of the color by stomach tube resulted in 89% excretion in the feces; none
was found in the urine. After subcutaneous injection of 80

- 100 mg some 79% was excreted; 77% appeared in the feces and 2.5% in the urine (Imperial Chemical Industries, 1958).

An acceptable, guideline dermal absorption study was not submitted. A dermal toxicity study was submitted, but the highes t dose tested was only 5 mg/kg/day (no adverse effects observed).

A definitive target organ has not been identified, and clinical signs were not observed in any study performed using these dyes. Systemic toxicity was observed in one study in the toxicity database and was limited to a decrease in mean body weight following long

- term dietary exposure to high doses in rats. There were no adverse effects observed in mice or dogs. All NOAELs were reported to be ≥500 mg/kg/day with the exception of a non

- guide line 21

- day dermal study in rats. The NOAEL for this dermal study was 5 mg/kg/day; however, this was the highest dose tested.

In both the prenatal developmental toxicity study in rats and the 3

- generation reproduction study in rats with tartrazine, adver se effects were not observed at any levels below the limit dose. Both of the two dyes, tartrazine and erioglaucine, show a similar lack of toxicity, and it is considered unlikely that erioglaucine would demonstrate quantitative or qualitative susceptibilit y. No adverse effects have been associated with exposure resulting from the FDA

- approved uses of either tartrazine or erioglaucine.

There was no evidence of neurotoxicity reported in any study. No evidence of carcinogenicity was observed in carcinogenici ty studies in mice and rats with erioglaucine, (Borzelleca and Hallagan, 1988a, 1988b) and tartrazine (Borzelleca et al, 1990). Aquashade ® is classified as not likely to be a carcinogen. These substances are not mutagenic in the standard Ames assay with or without metabolic activation (Brown et al, 1978).

The end

- use products each have a different ratio of the dyes. A product containing 68% erioglaucine and 4.5% tartrazine was used in the acute studies. It has a low acute toxicity with no
deaths occurr ing near the limit dose in oral studies (Category IV). The acute toxicity in dermal
studies is Category III. Based on the uses, the requirement for the acute inhalation study has been historically waived. There were no clinical signs of systemic toxicit y in the acute oral and dermal studies. No significant differences exist between males and females. The tested product caused slight eye irritation (Category III). It was negative for dermal irritation (Category IV); however, it is a dermal sensitizer.

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 11 of 35 4.2 Safety F actor for Infants and Children (FQPA Safety Factor)

The Aquashade® risk assessment team has recommended that the FQPA Safety Factor be reduced to 1X because there is an adequate toxicity database, and exposure data are complete or
are estimated based on data that will not underestimate potential exposures. The toxicological database for Aquashade® is considered complete with regard to pre

- and postnatal toxicity, neurotoxicity, and immunotoxicity. The dietary and residential assessments are based on reliable data and will not underestimate exposure.

4.2.1 Completeness o f the Toxicology Database

The database of toxicology studies for Aquashade® is complete and considered adequate for risk assessment (see Appendix A.1). Developmental toxicity studies in rats and a reproductive toxicity study in rats are av ailable for tartrazine. The Hazard and Science Policy Council (HASPOC; Schlosser, 2014, TXR # 0053946) recommended waiving all outstanding studies, including: 90

- day oral in rodent, 90

- day oral in non

- rodent, 90

- day inhalation, prenatal developmental stud y in rat (erioglaucine or Aquashade®), prenatal developmental study in rabbit (erioglaucine or Aquashade®), reproduction and fertility effects (erioglaucine or Aquashade®), bacterial reverse mutation assay (erioglaucine or Aquashade®), in vitro mammalian c ell assay,

in vivo cytogenetics, acute neurotoxicity, subchronic neurotoxicity, metabolism and pharmacokinetics (tartrazine or Aquashade®), dermal penetration, and immunotoxicity

This risk assessment takes a weight of the evidence approach, considering th e available data from a variety of sources, including studies submitted and reviewed by the agency, the Food and Drug Administration (FDA) and the Joint Expert Committee on Food Additives of the Food and Agriculture Organization/World Health Organization ( JECFA). This information is sufficient to evaluate the toxicity of Aquashade® and related compounds. Based on the information available from these sources, the toxicity database is complete, and there are no data gaps.

4.2.2 Evidence of N eurotoxicity

N eurotoxicity studies have not been conducted on either erioglaucine or tartrazine. However, no evidence of neurotoxicity was observed in any study. No clinical signs indicative of neurotoxicity were noted in subchronic and chronic studies in dogs or rats

.

4.2.3 Evidence o f Sensitivity/Su sceptibility in the Developing o r Young Animal

There was no evidence of increased sensitivity in the developing animal. Two developmental studies in rats were conducted using tartrazine and no adverse effect was observe d at the limit dose in dams and fetuses. In the reproduction study in rats, no adverse finding was noted at the highest dose tested (750 mg/kg/day tartrazine) in parents, offspring, or reproductive parameters.

4.2.4 Residual Uncertainty in the Exposure Datab ase

There are no residual uncertainties in the exposure database for Aquashade® based on the following considerations : (1 ) adequate exposure data are available to assess the residential and

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 12 of 35 occupational exposures resulting from the se use s and (2 ) ex posures are not expected to be
underestimated.

4.3 Toxicity Endpoint and Point of D eparture Selections

Since the last risk assessment, no new guideline toxicity study has been submitted to HED. The endpoints and points of departures have not changed from the previous risk assessment. There is no change in the prior recommendations for combining routes of ex posure nor for the cancer classification. Endpoints and points of departure are provided in Table 4.3.1 below.

Table 4.3.1. Summary of Toxicological Doses and Endpoints for Aquashade® for Use in Dietary and Non

Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty/

FQPA Safety
Factors RfD, PAD,

Level of
Concern for
Risk
Assessment Study and Toxicological Effects

Acute Dietary (General Population, including
Infants and Children) - - - No appropriate endpoint for the general population attributable to a single

exposure

Acute Dietary (Females 13

- 49 years of age) - - - No appropriate endpoint for females age
13

- 49 attributable to a single exposure

Chronic Dietary NOAEL = 500

mg/kg/day (Tartrazine)

Co

- critical:
NOAEL = 631 mg/kg/day (Erioglaucine) UF A =10x

UF H =10x
FQPA SF=1x Chronic RfD

= cPAD =
5 mg/kg/day Chronic oral toxicity in dogs (Tartrazine)

LOAEL was not identified

Combined chronic toxicity/ carcinogenicity study in rats (Erioglaucine)

LOAEL = 1262 mg/kg/day based on decreased body weight in females

Incidental
Oral Short

and
Intermediate Term (1

- 30 days and 1

- 6 months) NOAEL = 500

mg/kg/day (Tartrazine)

Co

- critical:
NOAEL = 631 mg/kg/day (Erioglaucine) UF A =10x

UF H =10x
FQPA SF=1x Residential

LOC for
MOE = 100 Chronic oral toxicity in dogs (Tartrazine)

LOAEL was not identified

Combined chronic toxicity/ carcinogenicity study in rats (Erioglaucine)
LOAEL = 1262 mg/kg/day based on decreased body weight in females

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 13 of 35 Table 4.3.1. Summary of Toxicological Doses and Endpoints for Aquashade® for Use in Dietary and Non

Occupational Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty/

FQPA Safety
Factors RfD, PAD,

Level of
Concern for
Risk
Assessment Study and Toxicological Effects

Dermal Short

and
Intermediate

Term (1

- 30 days and 1

- 6 months) NOAEL = 500

mg/kg/day (Tartrazine)

Co

- critical:
NOAEL = 631 mg/kg/day (Erioglaucine)

Dermal absorption rate
= 100% UF A =10x

UF H =10x
FQPA SF=1x Residential

LOC for
MOE = 100 Chronic oral toxicity in dogs (Ta rtrazine)

LOAEL was not identified

Combined chronic toxicity/ carcinogenicity study in rats (Erioglaucine)
LOAEL = 1262 mg/kg/day based on decreased body weight in females

Inhalation
Short

- and
Intermediate

Term (1

- 30 days and 1

- 6 months) NOAEL = 500

mg/kg/day (Tartrazine)

Co

- critical:
NOAEL = 631 mg/kg/day (Erioglaucine)

Inhalation absorption rate
= 100% UF A =10x

UF H =10x
FQPA SF=1x Residential

LOC for
MOE = 100 Chronic oral toxicity in dogs (Tartrazine)

LOAEL was not identified

Combined chronic toxicity/ carcinogenicity study in rats (Erioglaucine)
LOAEL = 1262 mg/kg/day based on decreased body weight in females

Cancer (oral, dermal, inhalation) Not likely to be carcinogenic to humans.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk estimates associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest o bserved adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a
NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence of key data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. DAF = dermal absorption factor.

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 14 of 35 Table 4.3.2. Summary of Toxicological Doses and Endpoints for Aquashade® for Use in Occupational
Human Health Risk Assessments

Exposure/
Scenario Point of

Departure Uncertainty

Factors Level of

Concern for
Risk
Assessment Study and Toxicological Effects

Dermal Short

and
Intermediate

Term (1

- 30 days and 1

- 6 months) NOAEL = 500

mg/kg/day (Tartrazine)

Co

- critical:
NOAEL = 631 mg/kg/day ( Erioglaucine)

Dermal absorption rate
= 100% UF A =10x

UF H =10x Occupational

LOC for
MOE = 100 Chronic oral toxicity in dogs (Tartrazine)

LOAEL was not identified

Combined chronic toxicity/ carcinogenicity study in rats (Erioglaucine)
LOAEL = 1262 mg/kg/day based on decreased body weight in females

Inhalation
Short

- and
Intermediate

Term (1

- 30 days and 1

- 6 months) NOAEL = 500

mg/kg/day (Tartrazine)

Co

- critical:
NOAEL = 631 mg/kg/day (Erioglaucine)

Inhalation absorption rate
= 100% UF A =10x

UF H =10x Occupational

LOC for
MOE = 100 Chronic oral toxicity in dogs (Tartrazine)

LOAEL was not identified

Combined chronic toxicity/ carcinogenicity study in rats (Erioglaucine)
LOAEL = 1262 mg/kg/day based on decreased body weight in females

Cancer (oral, dermal, inhalation) Not likely to be carcinogenic to humans.

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk estimates assoc iated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variat ion in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a
NOAEL. UF S = use of a short

- term study for long

- term risk assessment. UF DB = to account for the absence of key data (i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. N/A = not applicable.



### 5.0 Dietary Exposure and Risk Assessment

Since Aquashade® is applied to contained water bodies with little or no outflow, and labels preclude us in treated water bodies that serve as a source of drinking water, no drinking water exposure is expected. Although water treated with Aquashade® may potentially be used for irrigation of food crops and livestock watering, and Aquashade® is registered for use in fish
farms and hatcher ies, HED has not quantitatively assessed exposures and risk estimates from food sources for several reasons: (1) Aquashade® is used primarily in ornamental and/or recreational lakes and ponds with very little treated water expected to be used for agricult ural purposes. (2) Erioglaucine and tartrazine are highly water soluble compounds and, as such, not likely to accumulate in livestock or fish tissues. The results of the rat metabolism study with erioglaucine support this determination, since nearly the e ntire administered dose was excreted

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 15 of 35 unchanged in the feces in less than 2 days. (3) Any residues of erioglaucine or tartrazine occurring in foods from the use of Aquashade® as an aquatic algaecide/herbicide would be negligible compared to residues in fo od from the common use of these dyes as food coloring
additives.

6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

Aquashade® is labeled for consumer use to control aquatic algae and weeds in ponds and lakes. The anticipated use patterns and current labeling indicate several residential handler scenarios based on the types of equipment and techniques that can potentia lly be used to make tartrazine and erioglaucine applications. Residents or consumers applying tartrazine and erioglaucine products to ponds or lakes may be exposed for short

- term (1 to 30 days) duration through dermal contact or by the inhalation route.

Post

- application exposures to children and adults that contact tartrazine and erioglaucine treated swimming ponds are anticipated. To address the risk estimates of such exposures, a screening tool called the Swimmer Exposure Assessment Model (SWIMODEL) from the 2013 Draft Aquatic Use SOP was used to estimate risks. Post

- application residential exposure durations are expected to be short

- term (1 to 30 days) in duration.

The previous residential exposure assess ment was conducted in 2005. The current ass essment updates the previous assessment using the 2012 Residential SOPs and the 2013 Draft Aquatic
Use SOP to recalculate risk estimates.

6.1 Residential Handler Exposure

HED uses the term “handlers” to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct tasks related to applications and that exposures can vary depending on the specifics of each task. Residential handlers are addressed somewhat differently by HED as homeowners are assu med to complete all elements of an application without use of any protective equipment.

Aquashade® is labeled for consumer use to control aquatic algae and weeds in ponds and lakes; therefore, pesticide handler exposure to Aquashade® is likely to occur du ring its use. The anticipated use patterns and current labeling indicate several residential handler exposure scenarios based on the types of equipment and techniques that can be potentially used for consumer Aquashade® applications. The quantitative ex posure/risk assessment developed for residential handlers is based on the following scenarios.

Mixer/ Loader/ Applicators: (1) Liquids for Pouring Applications (using PHED mixer/ loader data) (2) Water Soluble Packets (using PHED mixer/ loader data)

Non

- cancer risk estimates were calculated using the Margin of Exposure (MOE). The overall uncertainty factor applied to Aquashade® handler risk assessments is an MOE of 100, which is
based on 10X for inter

- species extrapolation and 10X for intra

- species va riation. No surrogate

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 16 of 35 data was available to assess the open pour scenario in the Residential SOP, therefore, occupational unit exposures from mixer/loader/applicators data were modified to be representative of residential handlers to better represent the s cenario. 16.85 acre

- ft was used as the volume treated, which is representative of an acreage of 2.5 acres an d a depth of 2 m (6.74 ft) based on the 2013 Draft Aquatic Use SOP.

Risk Summary : A summary of the short

- term risk estimates (dermal and inhalation) for each exposure scenario is presented below in Table 6.1. All residential handler scenarios assessed resulted in estimated MOEs greater than 100 and, therefore, are not of concern. Re sidential
short

- term dermal MOEs range from 16,000 (pouring liquid) to 1,400,000 (drop

- in water soluble packets) , and short

- term inhalation MOEs range from to 92,000 (p ouring liquid) to 110,000 (drop

- in water soluble packets)

. Combined dermal and inhalati on MOEs range from 14,000 (pouring liquid) to 110,000 (drop

- in water soluble packets).

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 17 of 35 Table 6.1: Short

- Term Residential Handler Exposure and Risk Estimates for Aquashade®

Exposure Scenario Level of

Concern Dermal Unit

Exposure (mg/ lb ai) Inhalation Unit

Exposure (mg/lb ai) Application

Rate 1 Amount Treated or

Handled Daily Dermal Inhalation Total

Dose (mg/kg/day)

2 MOE 3 Dose

(mg/kg/day) 4 MOE 5 MOE 6

Mixer/Loader/Applicator

Liquids for pouring applications 100 0.187 0.219 0.79 lb
ai/A

- ft 16.85 A

- ft

(2.5 A 6.74 ft deep) 0.031 16,000 0.0054 92,000 14,000

Water Soluble Packet 100 0.02 0.24 0.58 lb
ai/A

- ft 16.85 A

- ft

(2.5 A 6.74 ft deep) 0.0036 1,400,000 0.0044 110,000 110,000

1 Based on register ed or proposed label (Reg. No. 33068

- 1 and 67064

- 1 )

2 Dermal Dose = Dermal Unit Exposure (mg/kg) x Application Rate (lb ai/acre or gal) x A mount Treated or Handled (A or gallons /day) x DAF (%)/BW ( 80 kg)

3 Dermal MOE = Dermal NOAEL (mg/kg/day)/Dermal Dose (mg/kg/day)

4 Inhalation Dose = Dermal Unit Exposure (mg/kg) x Application Rate (lb ai/acre or gal) x A mount Treated or Handled (A or gallons /day) /BW (kg)

5 Inhalation MOE = Inhalation NOAEL (mg/kg/day)/ Inhalation Dose (mg/kg/day)

6 Total MOE = NOAEL (mg/kg/day)/(Dermal Dose + Inhalation Dose) OR Total MOE = 1/[(1/Dermal MOE) + (1/Inhalation MOE)

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 18 of 35 6.2 Post

- Application Exposure

There is the potential for post

- application exposure for individuals as a result of being in an
environment th at has been previously treated with Aquashade® products. In order to assess
short

- term post

- application risk estimates for children and adults exposed to Aquashade®

- treated residential swimming ponds, the 2013 Draft Aquatic Use SOP was applied.

The lif e stages selected for each post

- application scenario are based on an analysis provided as an Appendix in the 2012 Residential SOPs 1 

### and in the 2013 Draft Aquatic Use SOP

. While not the only lifestage potentially exposed for these post

- application scenarios , the lifestage that is included in the quantitative assessment is health protective for the exposures and risk estimates for any other potentially exposed lifestage.

Risk estimates were calculated for residential handler and post

- application exposures using the MOE approach

. All short

- term residential post

- application scenarios assessed (dermal, ingestion, and inhalation ) resulted in estimated combined MOEs greater than 100 and, therefore,
are not of concern. A summary of these MOEs are pre sented in Table 6.2.

1 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Aquashade® Human Health Risk Assessment DP No. D425777

Page 19 of 3 5 P ost

- A pplication Non

- cancer Risk Estimates

Table 6.2: Short

- Term Residential Post

- A pplication Exposure and Risk Estimates for Aquashade®

Life stage Post

- application Exposure

Scenario Water

Concentration 1 (mg/L) Dose 2 MOEs 3 Combined Routes (X indicates included in Combined MOE) Combined MOEs 4

Adult

Aquatic Dermal 0.291 3 .4 x 10

- 5 1.5 x 10 7 X

9.52 x 10 6 Inhalation 0.291 9.7 x 10

- 14 5.2 x 10 15 X Ingestion 0.291 1.8 x 10

- 5 2.7 x 10 7 X

Child (3 to <6 years old) Dermal 0.291 1.0 x 10

- 5 3.5 x 10 7 X

1.50 x 10 7 Inhalation 0.291 6.7 x 10

- 15 7.5 x 10 16 X Ingestion 0.291 1.9 x 10

- 5 2.6 x 10 7 X

1 Based on registered or proposed label (Reg. No. 3 3 068

- 1 and 67064

- 1 )

. 2 DOSE (mg/kg/day) : equations provided in appendix
3 MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day).
4 Combined MOE = 1 ÷ (1/dermal MOE) + (1/inhalation MOE) + (1/inciden tal oral MOE), where applicable

### Aquashade® Human Health Risk Assessment DP No. 425777

Page 20 of 35 6.5 Residential Bystander Post

- application Inhalation Exposure

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The agency sought expert advice and input on issues related to volatilization of pesticides from its Fe deral Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has evaluated the SAP re port and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219). During Registration Review, the agency will utilize this analysis to determine i f data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required

.

6.6 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is particularly the case with aerial appli cation, but, to a lesser extent, spray drift can also be a potential source of exposure from the ground application methods (e.g., groundboom and airblast) which are not employed for Aquashade®. The agency has been working with the Spray
Drift Task Force (a task force composed of various registrants which was developed as a result
of a Data Call

- In issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (se e the agency’s Spray Drift website for more information). The agency has also developed a policy on how to appropriately consider spray drift as a potential source of exposure in risk assessments for pesticides. The potential for spray drift is qua li tativ ely evaluated for each pesticide during the Registration Review process which ensures that all uses for that pesticide will be considered concurrently. The approach is outlined in the revised (2012) Standard Operating Procedures For
Residential Risk Asses sment (SOPs)

- Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift.

There is no potential for spray drift exposure for Aquashade ® as liquids are poured in directly and water soluble packets are dropped in directly in to water bodies.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and
risk estimates from three major sources: food, drinking water, and residential exposures. I n an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risk estimates themselves can be aggregated. When aggregating exposures and risk estimates from v arious sources, HED considers both the route and duration of exposure. HED has not quantitatively assessed exposures and risk estimates from food sources for several reasons: (1) Aquashade® is used primarily in ornamental and/or recreational lakes and ponds with very little treated water expected to be used for agricultural pu rposes. (2) tartrazine and erioglaucine are highly water soluble compounds and, as such, not likely to accumulate in livestock or fish tissues. The results of the rat metabolism study with erioglaucine support this determination, since nearly the entire

### Aquashade® Human Health Risk Assessment DP No. 425777

Page 21 of 35 administered dose was excreted unchanged in the feces in less than 2 days. (3) Any residues of erioglaucine or tartr azine occurring in foods from the use of Aquashade® as an aquatic algaecide/herbicide would be negligible compared to residues in food from the common use of these dyes as food coloring additives. (4) The most significant route of exposure to erioglaucine and tartrazine is residential exposure, including residential handler and post

- application (swimming) exposure. HED believes that the conservative residential exposure and risk estimates discussed above are more than adequate to cover any food exposures that could potentially occur from the use of Aquashade® as an aquatic algaecide/herbicide. Therefore, the aggregate risks are equivalent to the short

- term residential risks described in Section 6 of this document, which are also protective for intermediat e

- term exposure since the same toxicological endpoint and point of departure are used for both durations of exposure. These aggregate risks are not of concern. Acute and chronic aggregate assessments are not required since there are no significant dietary exposures.

### Aquashade® Human Health Risk Assessment DP No. 425777

Page 22 of 35 Table 7.0

. Recommendations for the Short

- Term Residential Exposures for the Aquashade® Aggregate Assessment 1

Lifestage Handler Exposure

(mg/kg/day) 2 Residential

Handler Total Exposure (mg/kg/day) 3 Residential

Handler
Total MOE 4 Post

- application Exposure (mg/kg/day)

5 Residential
Post

application Total Exposure (mg/kg/day) Residential Post

application MOE 6 Dermal Inhalation Dermal Inhalation Oral

Short

- Term
Adult 0.031 0.0054 0.0364 14,000 3

. 43 x 10

- 5 9.70 x 10

- 14 1.82 x 10

- 5 5.25 x 10

- 5 9.52 x 10 6 Child (3 to <6 years old) N/A N/A N/A N/A 1.00 x 10

- 5 6.70 x 10

- 15 1.91 x 10

- 5 3.32 x 10

- 5 1.50 x 10 7

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment.

2 Handler exposure represents high

- end handler exposure from WSP , where the exposure duration is appropriate to assess.

3 F or adults, r esidential handler total exposure combines the highest d ermal and inhalation exposures, where applicable. For young children, total residential exposure combines high

- end post

- application incidental oral AND der mal exposure, where applicable.

4 Residential Handler Total MOE = 1 / (1/Dermal MOE) + (1/Inhalation MOE). Dermal NOAEL = 500 mg/kg/day; Inhalation NOAEL = 500 mg/kg/day

5 Post

- application exposure represents high

- end dermal, inhalation and/or incidental oral exposure for the relevant exposure duration

6 Tot al MOE = 1/ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental oral MOE). Dermal NOAEL = 500 mg/kg/day, Inhalation NOAEL = 500 mg/kg/day; Incidental oral
NOAEL = 500 mg/kg/day.

### Aquashade® Human Health Risk Assessment DP No. 425777

Page 23 of 35 8.0 Cumulative Exposure/Risk Characterization

Unlike ot her pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as

to Aquashade® and any other substances and Aquashade® does not appear to produce a toxi c metabolite produced by other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that Aquashade® has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemic als 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 http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event. Occupational applicatio n methods assessed include

pour

- in liqu ids and drop

- in water soluble packets.

Pesticide handler exposure to Aquashade® is likely to occur during its use in a variety of occupational environments. The anticipated use patterns and current labeling indicate several occupational exposure scenarios based on the types of equipment and te chniques that can be potentially used for Aquashade® applications. Short

- term (1 to 30 days) and intermediate

- term exposures (1 to 6 months) may occur; however, long

- term exposures (greater than 6 months) are not expected.

The previous occupational exposu re assess ment was conducted in 2005. The current assessment updates the previous assessment recalculating risk estimates. A water body size of 30 acres by 5ft (6.74 ft) deep, a total of 150 A

- ft was used to conduct the occupational assessment based on
info rmation fr om the Army Corp of Engineers (E ndothall RED, D319373, 8/12/05; 2,4

- D RED, D316596, 5/4/05).

All short

- and intermediate

- term occupational scenarios assessed (dermal and inhalation) resulted in estimated MOEs greater than 100 and, therefore, are not of concern. Short

- and intermediate

term dermal MOEs range from 1500 (liquids for pouring applications) to 47,000 (water soluble packets), and short

- and intermediate

- term inhalation MOEs range from 1,500,000 (liquids for pouring applications) to 1,9 00,000 ( drop

- in water soluble packets). The combined MOEs range from 1500 (liquids for pourin g applications) to 46,000 (drop

- in water soluble packets).

### Aquashade® Human Health Risk Assessment DP No. 425777

Page 24 of 35 Table 9.0 Occupational Handler Non

- Cancer Exposure and Risk Estimates for Aquashade®

Exposure Scenario Crop or Target Level of

Concern Dermal Unit

Exposure ( μ g/lb ai) 1 Inhalation Unit

Exposure ( μ g/lb ai) 1 Maximum

Application
Rate 2 Area
Treated or
Amount
Handled Daily Dermal Inhalation Total

Mitigation
Level Mitigation

Level Dose (mg/kg/day) 3 MOE 4 Dose (mg/kg/day) 5 MOE 6 MOE 8

Mixer/loader/Applicator

Liquid (pour on) Aquatic areas (lakes, ponds, etc.) 100 220
(baseline) * 0.219

(baseline) 0.79 lb

ai/Acre

- ft 150 Acre

- ft

(30 A and 5 ft deep) 0.326

(baseline) 1500

(baseline) 0.000325

(baseline) 1,500,000

(baseline) 1500

(baseline)

Water Soluble Packets (drop in) Aquatic areas (lakes, ponds, etc.) 100 9.8 (EC) * 0.24 (EC) 0.58 lb
ai/Acre

- ft 150Acre

- ft

(30 A and 5 ft deep) 0.0107

(EC) 47,000

(EC) 0.000261

(EC) 1,900,000

(EC) 46,000

(EC)

1 Level of mitigation: Baseline, PPE, Eng. Controls.
2 Based on registered or proposed label (Reg. No. 36068

- 3, 67064

- 1 ).
3 Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF (%) ÷ BW ( 80 kg).
4 Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).
5 Inhalation Dose = Inhalation Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai /acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW ( 80 kg).

6 Inhalation MOE = Inhalation NOAEL ( 500 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

7 Total MOE = NOAEL ( 500 mg/kg/day) ÷ Dermal Dose + Inhalation Dose OR Total MOE = 1 ÷ (1/D erma l MOE + 1/Inhalation MOE)

* Baseline includes long pants, long

- sleeve shirt, socks, and shoes *Engineering Controls includes p ackaging of the chemical i.e. WSP

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 25 of 35 9.1 Short

- and Intermediate

- Post

- Application Risk

9.1.1 Dermal Post

- application Risk

Since Aquashade® is an algaecide/ herbicide, HED is not aware of any occupational post

application activities which may result in exposure. No harvesting is required, and while scouting may include identifying any algae or aquatic weed regrowth, these activities should not require contact with the treated water body. For these reasons, occupational po st

- application exposure of workers to previously treated water bodies is expected to be neg ligible and was not assessed quantitatively.

9.1.2 Inhalation Post

- application Risk

Based on the Agency's current practices, a quantitative non

- cancer occupational post

- application inhalation exposure assessment was not performed for Aquashade® at this time. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational
post

- application inhalation exposure assessmen t for Aquashade®.

10.0 Epidemiology

Based on the low s everity of incidents involving A quashade ® (pc code 110303), acid yellow 23 ( pc code 110302), and a cid blue 9, diammonium salt ( pc code 110301) reported to IDS and the fact that no incidents involving A quashade®

, acid yellow 23, or a cid blue 9, diammonium salt were reported to SENSOR

- Pesticides, t here does not appear to be a concern at this time that would warrant further investigation

. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis will be included in the risk

assessment (S. Recore, 2014, D427136)

.

11.0 References

Review of Aquashade® Incident Reports, Chemicals #110303, #110301, and #110302 , DP Barcode: D302184, Jerome Blondell, 08/22/05.

Aquashade®: Occupational and Residential Exposure Assessment and Recommendations for the Reregistration Eligibility Decision Document; DP Barcode: 302180, Wade Britton, 09/13/05.

Aquashade®: Revised Occupational and Residential Exposure Assessment and Recommendations for the Reregistration Eligibility Decision Document; DP Barcode: D321915; W. Britton; 09/27/05.

BIBRA. 1999. BIBRA International Ltd. Toxicity profile: Brilliant Blue FCF, 3 rd 

### ed. Carshalton, Surrey: BIBRA International Ltd., 11 pp.

Borzelleca, J.F. and J.B. Hallagan. 1988a. Chronic toxicity/carcinogenicity studies of FD&C Yellow No. 5 (tartrazine) in rats. Fd. Chem. Toxicol. 26(3):179

- 187.

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 26 of 35 Borzelleca, J.F. and J.B. Hallagan. 1988b. A chronic toxicity/carcinogenicity study of FD&C Yellow No. 5 (tartrazine) in mice. Fd. Chem. Toxicol. 26(3):189

- 194.

Borzelleca, J.F., K. Depukat, and J.B. Hallagan. 1990. Lifetime toxicity/carcinogenicity studies
of FD&C B lue No. 1 (Brilliant Blue FCF) in rats and mice. Fd. Chem. Toxicol. 28:221

- 234.

Brown, J.P., G.W. Roehm, and R.J. Brown. 1978. Mutagenicity testing of certified food colors and related azo, xanthene and triphenylmethane dyes with the Salmonella/microso me system. Mutat. Res. 56:249

- 271.

Collins, T.F.X., T.N. Black, L.H. Brown, et al. 1990. Study of the teratogenic potential of FD&C Yellow No. 5 when given by gavage to rats. Fd. Chem. Toxic. 28(12):821

- 827.

Collins, T.F.X., T.N. Black, M.W. O'Connel l, Jr., et al. 1992. Study of the teratogenic potential of FD&C Yellow No. 5 when given in drinking water. Fd. Chem. Toxic. 30(4):263

- 268.

FDA. 1982. FD&C Blue No. 1.; Final Rule. 47 FR 42563; September 28, 1982

FDA. 1985. FD&C Yellow No. 5.; Fin al Rule; Removal of Stay. 40 FR 35774; September 4, 1985.

IACM. 2004. International Association of Color Manufacturers. Test Plan and Robust Summaries for C.I. Acid Yellow 23 (FD&C Yellow 5). http://www.epa.gov/chemrtk/ciacdylo/c15133tp.pdf

JECFA. 1964. Joint FAO/WHO Expert Committee on Food Additives. Tartrazine. WHO Food
Additive Series. 66.25/NMRS 38B

- JECFA 8/88. http://www.inchem.org/documents/jecfa/jeceval/jec_1936.htm

JECFA. 1969. Joint FAO/WHO Expert Committee on Food Additives. Toxicological
Evaluation of Some Food Colours , Emulsifiers, Stabilizers, Anti

- caking Agents and Certain Other Substances. FAO Nutrition Meetings Report Series No. 46A . World Health Organization, Geneva. http://www.inchem.o rg/documents/jecfa/jecmono/v46aje08.htm

Leifer, Kerry. 2004. United States Environmental Protection Agency. Reassessment of Exemptions from the requirement of a tolerance for the FDA

- certified color additives FD&C Blue No. 1, FD&C Red No. 40, and FD&C Ye llow No. 5.

Sasaki, Y.F., S. Kawaguchi, A. Kamaya, et al. 2002. The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat. Res. 519:103

- 119.

SRC. 2004. Syracuse Research Corporation. Interactive Physical Properties (PHYSPROP) Database Demo. Search terms: FD&C Blue. No. 1, FD&C Red No. 40, FD&C Yellow No. 5. (November 28, 2004) http://www.syrres.com/esc/physdemo.htm

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 27 of 35 Appendix A. Toxicology Profile and Executi ve Summaries

A.1 Toxicology Data Requirements The requirements (40 CFR 158.500) for food

- use for Aquashade® are in Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used.

Study Technical

Required Satisfied

870.1100 Acute Oral Toxicity

................................ ....................... 870.1200 Acute Dermal Toxicity

................................ .................. 870.1300 Acute Inhalation Toxicity

................................ .............. 870.2400 Primary Eye Irritation

................................ .................... 870.2500 Primary Dermal Irritation

................................ .............. 870.2600 Dermal Sensitization

................................ ..................... yes
yes
yes
yes
yes
yes yes a

yes a

yes a

yes a

yes a

yes a

870.3100 Oral Subchronic (rodent)

................................ ............... 870.3150 Oral Subchronic (nonrodent)

................................ ......... 870.3200 21

- Day Dermal

................................ .............................. 870.3250 90

- Day Dermal

................................ .............................. 870.3465 90

- Day Inhalation

................................ .......................... yes
yes
yes

no
yes yes b

yes b

yes c

- yes b

870.3700a Developmental Toxicity (rodent)

................................ .. 870.3700b Developmental Toxicity (nonrodent)

............................ 870.3800 Reproduction

................................ ................................ . yes
yes
yes yes d

yes b

yes d

870.4100a Chronic Toxicity (rodent)

................................ .............. 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200a Oncogenicity (rat)

................................ .......................... 870.4200b Oncogenicity (mouse)

................................ ................... yes

no
yes
yes yes d

- yes e

yes e

870.5100 Mutagenicity

— Bacterial reverse mutation assay

.................... 870.5300 Mutagenicity

— In vitro mammalian cell gene mutation test

....... 870.5375 Mutagenicity

— In vitro mammalian chromosome aberration test 870.5395 Mutagenicity

— Mammalian erythrocyte micronucleus test

........ yes
yes
yes
yes yes d

yes b

yes b

yes b

870.6100a Acute Delayed Neurotoxicity (hen)

............................... 870.6100b 90

- Day Neurotoxicity (hen)

................................ .......... 870.6200a Acute Neurotoxicity Screening Battery (rat)

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

.............. 870.6300 Developmental Neurotoxicity

................................ ....... no

no
yes
yes

no -

- yes b

yes b

-

870.7485 General Metabolism

................................ ...................... 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. yes
yes
yes yes f

yes b

yes b

a Tested Admiral WSP (Erioglaucine : Tartrazine, 68.13% : 4.51%).

b This study was not submitted, but is not required (Schlosser, 2014, TXR # 0053946), The requirement for outstanding studies for Aquashade® were waived including: 90

- day oral in rodent, 90

- day oral in non

- rodent, 90

- day inhalation, prenatal developmental study in rat (erioglaucine or Aquashade®), prenatal developmental study in rabbit (erioglaucine , tartrazine, or Aquashade®), reproduction and fertility effects ( erioglaucine or Aquashade®), bacterial reverse mutation assay (erioglaucine or Aquashade®), in vitro mammalian cell assay, in vivo cytogenetics, acute neurotoxicity, subchronic neurotoxicity, metabolism and pharmacokinetics (tartrazine or Aquashade®), derm al penetration, and immunotoxicity.

c An acceptable, non

- guideline study was submitted. No additional data are required at this time. Erioglaucine was tested

d A study was submitted evaluating tartrazine.

e Guidelines 870.4100 and 870.4200 were satisfied b y Guideline 870.4300 where tartrazine and erioglaucine were tested separately, both in rat and mice.

f A study was submitted evaluating erioglaucine.

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 28 of 35 A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile

– Admiral WSP a

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral

- Rat 45281101 LD 50 > 5000 mg/kg IV

870.1200 Acute dermal

- Rabbit 45144401 LD 50 > 2000 mg/kg III

870.1300 Acute inhalation None Data requirement
waived -

870.2400 Acute eye irritation

- Rabbit 44902902 No eye irritation III

870.2500 Acute dermal irritation

- Rabbit 45086102 Negative IV

870.2600 Skin sensitization

- Guinea Pig 44902904 Positive NA

a 68.13% Erioglaucine and 4.51% Tartrazine



### Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

- Aquashade®

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870.3100 90

- Day oral

toxicity (rodent) None Not required

870.3150 90

- Day oral

toxicity (non

rodent) None Not required

870.3200 21

- Day dermal

toxicity (rabbit) 43410101 (1962)

Acceptable, non

- guideline ♀: 0, 0.5, 5.0 mg/kg/day
Erioglaucine NOAEL = 5 mg/kg/day
LOAEL was not observed

870.3250 90

- Day dermal

toxicity (species) None Not required

870.3465 90

- Day inhalation

toxicity (species) None Not required

870.3700a Prenatal

developmental (rat) 43408101

Acceptable, guideline 0, 100, 300, 1000 mg/kg/day

Tartrazine Maternal NOAEL = 1000 mg/kg/day
LOAEL was not observed
Developmental NOAEL = 1000 mg/kg/day
LOAEL was not observed

870.3700a Prenatal

developmental (rat) No MRID; Collins, et al.

,

1990 0, 60, 100, 200, 400, 600, 1000 mg/kg/day

Tartrazine Maternal NOAEL = 1000 mg/kg/day
LOAEL was not observed
Developmental NOAEL = 1000 mg/kg/day
LOAEL was not observed

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 29 of 35 Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

- Aquashade®

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870.3700b Prenatal

developmental (non

- rodent) None Not required

870.3800 Reproduction and

fertility effects (rat) 43410901

Acceptable, guideline 0, 7.5, 75, 225, 750 mg/kg/day

Tartrazine Parental/Systemic NOAEL = 750 mg/kg/day
LOAEL was not observed
Reproductive NOAEL = 750 mg/kg/day
LOAEL was not observed
Offspring NOAEL = 750 mg/kg/day
LOAEL was not observed

870.4100a Chronic toxicity

(rat) Not submitted. See

870.4300. -

870.4100a Chronic toxicity

(mouse) Not submitted. See

870.4300. -

870.4100b Chronic toxicity

(dog) No MRID; FDA, 1985

Tartrazine NOAEL = 500 mg/kg/day
LOAEL was not observed

870.4200a Carcinogenicity

(rat) Not submitted. See

870.4300. -

870.4200b Carcinogenicity

(mouse) Not submitted. See

870.4300. -

870.4300 Combined

Chronic Toxicity/ Carcinogenicity (rat) No MRID; Borzelleca,

et al. , 1990 ♂: 0, 54, 536, 1072 mg/kg/day ♀: 0, 63, 631, 1262 mg/kg/day Erioglaucine NOAEL = 631 mg/kg/day LOAEL = 1262 mg/kg/day based on decreased body weight in females

No evidence of carcinogenicity

870.4300 Combined

Chronic Toxicity/ Carcinogenicity (rat) No MRID; Borzelleca,

et al. , 1988a ♂: 0, 67, 1339, 3348 mg/kg/day ♀: 0, 53, 1056, 2641 mg/kg/day

Tartrazine NOAEL = 2641 mg/kg/day
LOAEL was not observed

No evidence of carcinogenicity

870.4300 Combined

Chronic Toxicity/ Carcinogenicity (mouse) No MRID; FDA, 1982

Erioglaucine NOAEL = 1200 mg/kg/day
LOAEL was not identified
No evidence of carcinogenicity

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 30 of 35 Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

- Aquashade®

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870.4300 Combined

Chronic Toxicity/ Carcinogenicity (mouse) No MRID; Borzelleca,

et al. , 1990 ♂: 0, 735, 2206, 7354 mg/kg/day ♀: 0, 897, 2690, 8966 mg/kg/day Erioglaucine NOAEL = 7354 mg/kg/day
LOAEL was not identified
No evidence of carcinogenicity

870.4300 Combined

Chronic Toxicity/ Carcinogenicity (mouse) No MRID; Borzelleca,

et al. , 1988b ♂: 0, 41, 2431, 8103 mg/kg/day ♀: 0, 974, 2912, 9735 mg/kg/day

Tartrazine NOAEL = 8103 mg/kg/day
LOAEL was not observed
No evidence of carcinogenicity

870.5100 Genotoxicity

Bacterial reverse
mutation test No MRID; Hansen, et al.

,

1964, as cited in JEFCA,
1969

Tartrazine Negative

870.5300 Genotoxicity

In vitro
mammalian cell gene mutation test None Not required

870.5375 Genotoxicity

In vitro
mammalian
chromosome
aberration test None Not required

870.5395 Genotoxicity

Mammalian erythrocyte
micronucleus test None Not required

870.6200a Acute

neurotoxicity screening battery None Not required

870.6200b Subchronic

neurotoxicity screening battery None Not required

870.6300 Developmental

neurotoxicity None Not required

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 31 of 35 Table A.2.2 Subchronic, Chronic, and Other Toxicity Profile

- Aquashade®

Guideline
No. Study Type MRID No. (year)/
Classification /Doses Results

870.7485 Metabolism and

pharmacokinetics (rat) No MRID; Imperial

Chemical Industries, 1958
200 mg/rat
Erioglaucine Erioglaucine was administered orally to rats as a 2% aqueous solution at a level of 200 mg/rat.
Almost the entire amount was excreted unchanged in the feces within 40 h after
administration.

870.7600 Dermal

penetration (rat) None Not required

870.7800 Immunotoxicity

(rat) None Not required

All studies that were noted in this table as “Not required” were considered so because the studies were conditionally required and did not meet the conditions for requirement, were considered not required in the previous risk assessment, or were specified as not required by HASPOC ( Schlosser, 2014, TXR # 0053946).

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 32 of 35 Appendix B. Physical/Chemical Properties

Table C1. Physico

- Chemical Properties

Parameter Value Reference

Chemical Tartrazine Erioglaucine

Molecular Weight 534.37 792.86 SRC 2004

Water solubility (20°C) 1.0 x 10 6 m g/L @
25°C 1.45 mg/L @ 25°C BASF, 2003

Vapor pressure (25°C) 7.43 x 10

- 22 mmHg
@ 25°C 

### 2.97 x 10

- 42 

### mmHg

at 25°C EPI Suite, 2004

Dissociation constant, pKa

- 10.7

- 1.50 EPI Suite, 2004 Octanol/water partition coefficient, log K OW (25°C) K ow = 6.3 x 10

- 11 K ow = 0.032 SRC, 2004

Soil Half

- life (or other relevant information from EFED Drinking water assessment) N/A N/A N/A

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 33 of 35 Appendix C. Summary of Occupational and Residential Non

- cancer Algorithms

Occupational Non

- cancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),
AR = maximum application rate according to proposed label (lb ai A or lb ai/gal), and
A = area treated or amount handled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

ADD= E * AF

BW

wh ere:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),
AF = absorption factor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational
h andlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= POD

ADD

where:

MOE = margin of exposure: value used by HED t o represent risk estimates (unitless),
POD = point of departure (mg/kg/day), and
ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).

Occupational Non

- cancer Post

- application Algorithms

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 34 of 35 Potential daily exposures for occupational post

- app lication workers are calculated using the following formulas:

DFR t 

### =AR * F* (1

- D) t 

### * ( 4.54E8 ug
lb ) * ( 2.47E

- 8 A

cm 2 

### )

where:

DFR t 

### = dislodgeable foliage residue on day "t" (μg/cm 2 

### ),
AR = application rate (lb ai/acre),

F = fraction of ai retained on foliage or 25% (unitless),

D = fraction of residue that dissipates daily or 10% (unitless), and

t = number of days after application day (days).

E=TC * DFR t 

### * ET * 0.001 mg

ug

where:

E = exposure (mg ai/day),
TC = transfer coefficient (cm 2 

### /hr),

DFR t 

### = dislodgeable foliar residue on day “t” (μg/cm 2 

### ), and

ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),
AF = absorption factor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure: Non

- cancer risk estimates for each scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicolog ical endpoint to the daily dose of concern. The daily dermal dose received by occupational post

- application workers is compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational post

- application workers. All
MOE values are calculate d using the following formula:

MOE= POD

ADD

where:

### Aquas hade® Human Health Risk Assessment DP No. 425777

Page 35 of 35 MOE = margin of exposure: value used by HED to represent risk estimates (unitless),
POD = point of departure (mg/kg/day), and
ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).