Page 2 of 25

(CAS No. 112

- 18

- 5) and other closely relate d alkyl dimethyl amines in assessing CADA. These substances, along with other related dimethyl amines were included in a cluster of chemicals

submitted to EPA as part of the High Production Volume (HPV) Test Challenge Program by the American Chemistry Council (ACC) Fatty Nitrogen Derivatives Panel Amines Task Group (2003).

CADA exhibit s low toxicity via the acute oral, dermal and inhalation routes of exposure. In rats

the acute oral LD 50 is > 1000 mg/kg bw/day

. The acute dermal LD 50 is > 3385 mg/kg bw/day in

rabbits. It is corrosive to the skin and irritating to the eyes of rabbits

. An acute inhalation study was not available with the coco alkyl dimethyl amines, however data are available for an acceptable surrogate compound , n

- tallow alkyl derivatives of 2,2’

- iminobis ethanol CAS Reg.

No

. 61791

- 44

- 4). The acute inhalation LC 50 is > 0.6 mg/L in rats.

A 28

- day toxicity study was conducted according to Organization for Economic Co

- operation and Development ( OECD ) Test Guideline 407 using N, N

- dimethyl

- 1

- dodecanamine (CAS Reg.

No. 112

- 18

- 5). Sprague

- Dawley rats received a n oral ga vage dose of 0, 50, 150, or 300 mg/kg bw/day (OECD 2001). At 150 mg/kg bw/day, animals displayed mild adverse behavior, including snout rubbing. A NOAEL of 50 mg/kg bw/day was observed in this study.

Regarding genotoxicity

, the ACC HPV submission provided data on three dimethyl alkyl amines that together comprise a large portion of coco alkyl dimethyl amines. These compounds
are: N,N

- dimethyl 1

- tetradecanamine (CAS Reg. No. 112

- 75

- 4), N,N

- dimethyl 1

- hexadecanamine (CAS Reg. No. 112

- 69

- 6) and N,N

- dimethyl 1

- octadecanamine (CAS Reg. No.

124

- 28

- 7) (ACC 2003 )

. There was no evidence of mutagenicity under the conditions of the test in any of the three compounds

. In addition, N,N

- dimethyl

- 1

- dodecanamine was not clastogenic

in an in vivo mammalian ery throcyte micronucleus test (OECD 2001).

The OECD (2001) reported a reproductive/developmental toxicity screening study (OECD TG 421) of N,N

- dimethyl

- 1

- dodecanamine (CAS Reg. No. 112

- 18

- 5) administered via gavage to Sprague

- Dawley rats. At 150 mg/kg bw/day, mortality, increased mean i m plantation loss, decreased mean viability index and abnormal maternal behavior was observed in the dams and reduced weight in pups. The maternal, developmental and reproduction NOAEL was 50 mg/kg bw/day.

None of th e amines discussed in an HPV challenge document were mutagenic. Greim et al (1998) stated “The vast majority of the in vitro and in vivo genotoxicity tests gave no indication of genotoxic potential for primary aliphatic amines” (which includes CADA). Gre im et al further state “Carcinog e nicity studies (cyclohexylamine and 2

- year feeding studies that do not completely meet the curr e nt standards (sec

- butylamin and octadecylamine) sho w ed no

tum o rigenic potential.”

The Agency further evaluated the carcinogenic potential of coco alkyl dimethyl amines by conducting a probability analysis using the Nexus DEREK model (Appendix 2) . The model

results are based on a proprietary data set of 731 chemicals, classified on the basis of the presence or absence of histopathologic lesions in the liver in oral rat repeat dose studies mostlyPage 3 of 25

of 28

- days duration. The model results indicated that there were no “ALERTS” for

car cinogenicity or other pathology.

Dermal absorption is based upon surrogate data for 1

- dodecanamine. The dermal absorption of

1

- dodecan amine was determined to be 60% (Euro pean Chemicals Agency. 2011). Based on this information, it can be assumed that the dermal absorption of the coco alkyl dimethyl amines is not more than 60%. The CADA is a larger molecule than 1

- dodecanamine therefore it is not expected to be absorbed at a greater rate. For risk assessment purpose s , dermal absorption is

assumed to be 6 0%.

No studies were found specific to the metabolic pathway or toxicokinetic properties of coco alkyl dimethyl amines in mammalian systems. Parkinson ’s (1996) stud y of structurally similar compounds suggested that for structurally similar compounds in ma mmals, hepatic dealkylation readily occurs with secondary and tertiary amines, with the methyl groups leaving preferentially. Oxidation of the alpha carbon via cytochrome P450, forms a ca r b inolamine intermediate that will spontaneously cleave to form a se condary amine and a carbonyl compound. Subsequent dealkylation of the secondary amine will take place at a slower rate. In a more minor pathway, hydroxylation of the nitrogen atom by hepatic oxidases may take place. Fatty acids are primarily

excreted as CO 2 (ECHA 2011).

No acute endpoint of concern was identified in the available database, therefore there is no need to conduct an acute dietary exposure assessment. The NOAEL for risk assessment for all exposure scenarios is based on surrogate data from co

- critical studies: a 28 day repeat dose feeding study and a reproduction/developmental screening study in rats. A t 150 mg/kg bw/day, animals displayed mild adverse behavior and snout rubbing in the 28

- day oral toxicity study. In the reproduction/devel opmental screening study in rats, dam mortality and abnormal behavior, increased implantation loss, decreased viability index and reduced pup weight were observed at 150 mg/kg bw/day. The NOAEL in both studies was 50 mg/kg bw/day. The uncertainty factor of 1000X was used for chronic dietary assessment (10X for intra

- individual variability and 10X for interspecies extrapolation and 10X FQPA factor). No appropriate dermal or inhalation toxicity studies are available for the exposur e assessment. Therefore, the oral studies selected for the chronic RfD were used as a conservative approach. Dermal absorption is assumed to be 60% and inhalation absorption is assumed to be 100%.

Special Consideration for Infants and Children (FQPA Safety Factor) : The database is

considered in adequate for FQPA assessment. The FQPA factor of 10X is retained due to severity of effects in the reproduction/developmental screening study in the rat and uncertainty regarding long term studies evaluating gu ideline parameters

.

The chronic analysis was based on a NOAEL of 50 mg/kg bw/day. The uncertainty factor of

100 0 (10x for intraspecies variability and 10x for inter species extrapolation and 10x FQPA ) was used for the chronic endpoints. One hundred per cent crop treated was assumed, default processing factors and tolerance

- level residues for all foods and use limitations of not more than

0.5 % by weight in pesticide formulations. Drinking water (100 ppb) was incorporated directly into the dietary assessm ent. The chronic dietary risk assessment shows that the chronic dietary risk estimates are not of concern (i.e., <100% cPAD). For the Total U.S. population, thePage 4 of 25

exposure for food and water utilized 3.8 % of the cPAD. The chronic dietary risk estimate for the highest exposed population subgroup, children 1

- 2 years old is 14.1 % of the cPAD.

The term “residential exposure” is used in this document to refer to non

- occupational, non

dietary exposure (e.g., for lawn and garden pest control, indoor pest contr ol, termiticides, and flea and tick control on pets). Based upon the request to use CADA on growing crops, the Agency does not expect non

- occupational (i.e., residential) pesticide handler exposure.

Therefore an assessment of residential pesticide handlers is not necessary.

Since the proposed use of CADA is not expected to result in “residential” exposures, it is not necessary to conduct an aggregate exposure assessment with estimated dietary post

- application

exposures. Based on the expectations d escribed above, EPA has concluded that the aggregated food and water exposures result in aggregate MOEs > 100.

CADA is toxic to freshwater fish and other freshwater organisms. Environmental modeling suggests volatilization and hydrolysis are not like ly to be important for CADA. The modeling data suggest ready biodegradability. Also according to the modeling, CADA ha s a low potential to persist (P1) and bioaccumulate (B1) in the environment.

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

- Income Populations.” http://www.eh.doe.gov/oepa/guidanc e/justice/eo12898.pdf.

This assessment does not rely on any studies in which human subjects were intentionally exposed to a pesticide. There are no international limits for CADA.

Based on the information presented above, the Agency approves of the proposed use of coco alkyl dimethyl amines as an inert ingredient under 40 CFR § 180.920 for use pre

- harvest on growing crops at a maximum end

- use concentration not to exceed 0.5%.

II. BACKGROUND

The firm Technology Sciences Group Inc. (1150 18 th Street S.W., Washington, D.C. 20036) has submitted a request to exempt coco alkyl dimethyl amines (CASRN 61788

- 93

- 0) from the requirements of a tolerance when used as an inert ingredient. Spe cifically, the request is to use coco alkyl dimethyl amines (hereafter may be termed CADA) as an inert ingredient which serves as an emulsifier in liquid pesticide products and acts to enhance spray application and deposition. The requested end

- use concen tration of a spra y mix is less than 0.5% . Coco alkyl dimethyl amines are currently permitted for use in non

- food pesticide products.

C oco alkyl dimethyl amine is one of 23 fatty nitrogen derived (FND) amines submitted to the EPA by the American Chemical Council (ACC) as part of the EPAs High Production Volume (HPV) Chemical Challenge Program. The submission clustered the FND amines on the basis of their structural similarity for the purposes of allowing data on members of the cluster to be

utilized for “r ead

- across or bridging data.” Deleted:

Deleted:Page 5 of 25

III. PHYSICAL /CHEMICAL PROPERTIES

Chemical Structure of Coco Alkyl Dimethyl Amines

Characterization of coco alkyl dimethyl amines

Characterization of Coco alkyl group Chain length Degree of unsaturation

C6: 0

- 1% None

C8: 5

- 9% None

C10: 5

- 10% None

C12: 44

- 53% None

C14: 13

- 19% None

C16: 8

- 11% None

C16: 0

- 1% 1

C18: 5

- 8% 1

C18: 1

- 3% 2

Commercial Names Armeen DMCD, Genamin CS 302D

Molecular Weight (average) 228

Taken from the American Chemistry Council. 2003. Fatty Nitrogen Derived Amines Category, HPV Chemicals Challenge. 29DEC.Page 6 of 25

Physical/Chemical Properties Property Value Source Physical state Liquid ACC 2003 Water Solubility Mg/L @ 25oC Not soluble ECB 2000

Density (g/cm 3 @ 25oC 0.79 ECB 2000 Vapor Pressure (hPa @ 100oC <1 ECB 2000 LogK OW 5.44 EPI Suite/KOWWIN v1.68 BP(oC) >150 ECB 2000 MP (oC)

- 10 ECB 2000 Flash point (oC) >1000 ECB 2000 Henry’s Law Constant (atm

- m 3 /mole @

25oC 5.2x10

- 4 EPI Suite HENRYWIN v3.2

Log K OC (soil sorption coeff.) 3.751

- 3.869 EPI Suite/KOWIN v 2.0 Biodegradability Readily ACC 2003, ECB 2000 BCF (L/kg wet

- wt) 76.29 EPI Suite/BCFBAF

Bioaccumulation Factor 280 EPI Suite/BCFBAF

Volatilization from Water:

Half

- life (days) 5.9 EPI Suite/Volatilization

Fugacity Model Compartment/Mass Amount % Soil: 79.8

Water: 16.8

Sediment:

2.9

Air: 0.5 EPI Suite/Level III fugacity

model

The proposed use of CADA is an emulsifier in pesticide formulations that aids in spray deposition and retention. The final end

- use concentrations will be < 0.5%. Coco alkyl dimethyl amines and similar alkyl tertiary amines are primarily used in commercial surfactants, corrosion inhibitors, detergents, ore floating agents, fabric softeners, anti

- static agents, germicides, insecticides, dispersants, anti

- caki ng agents, lubricants and water treatment agents.Page 7 of 25

IV TOXICOLOGICAL PROFILE

Summary of Acute Toxicity

Route Value Source

Acute oral

t oxicity (rat) LD 50

1300 mg/kg F 1500 mg/kg M

>1000 > 1250 mg/kg

1247 mg/kg ACC

Acute dermal Toxicity 3384 mg/kg HPV report

Acute inhalation (surrogate) LC 50

> 0.6 mg/L TSG submission

Pg 9/16

Irritation skin Corrosive OECD 2001 Irritation eye Corrosive EPA 2010

Acute Oral Toxicity

Three acute oral toxicity studies were identified in the HPV submission . In one study, Sprague

Dawley rats were administered an oral dose of 1.0

- 2.5 g/kg coco alkyl dimethyl amines (purity not stated). The LD 50 was determined to be 1500 mg/kg for males and 1300 mg/kg for females. The study was determined to be reliable with out restrictions by the ACC.

The second study was a GLP acute oral toxicity study using Wistar rat s (5/dose). An LD 50 of >1000 and >1250 mg/kg bw/day (100% purity) were determined.

The third acute oral toxicity study was conducted on albino rats (st rain not specified) (10 rats/dose). The LD 50 was determined to be 1.58 mL/kg (equivalent to approximately 1247 mg/kg).

Acute Dermal Toxicity

An acute dermal toxicity study of CADA is listed in the HPV submission in the Fatty Nitrogen Derivatives ( FN D ) ether amines category. No standard guideline was listed however the study was deemed reliable without restrictions by the ACC. Four New Ze a land white rabbits/dose were dermally exposed to undiluted test material at concentrations of 4.0 6.0 or 8.0 mL/ kg (equivalent to 3156 mg/kg, 4734 mg/kg and 6312 mg/kg respectively) . The applied substance was covered with impervious plastic for 24 hours and the rabbits observed for 14 days. The

LD 50 was determined to be 4.29 mL/kg equivalent to about 3385 mg/kg.

Acute Inhalation Toxicity

No acute inhalation toxicity studies were identified for the coco alkyl dimethyl amines. However an acute inhalation toxicity study with a structurally similar compound was conducted.Page 8 of 25

The compound is hydroxylated FMN amin e , N

- tallow alk y l derivatives of 2,2

- imino bis ethanol (CAS 61791

- 44

- 4). Five Sprague

- Dawley rats/sex/dose received 0.6 mg/L aerosolized compound via whole body inhalation for four hours. No deaths were observed. The LC 50 was determined to be >0.6 mg/L theref ore this compound is classified in Acute Inhalation Toxicity Category III.

Irritation

Numerous GLP studies indicate that coco alkyl dimethyl amines are corrosive to rabbit skin (ECB 2000). Rabbits exposed to commercial products containing CADA such as Genamin LA 302D (70% C12, 25% c12

- 14 and 5% C16 dimethylalkylamin e s) or Genamin 12 r 302 D (95% C12 dimethyldodecylamine) had corrosive skin effects after 4 hour or 3 minute exposures via the OECD TG 404 test (OECD 2001).

N,N

- dimethyl1

- hexadecanamin, N,N

- dimethyl

- 1

- tetradecanamine, and N,N

- dimethyl

- 1

- tetradecanamine are comp o unds that are the primary constitu ents of coco alkyl dimethyl amines. All three compounds are irritating to the rabbit eye (US EPA 2010).

Repeat Dose Toxicity

Data were not availab le on CADA, however, data are available on the N,N

dimethy ldodecylamine (CAS Reg. No. 112

- 18

- 5) also known as N,N

- dimethyl

- 1

- dodecanamine

. The SIDS Initial Assessment Report for SIAM 11 (OECD 2001) presented toxicity data on CAS Reg. No. 112

- 18

- 5.

In a 28

- day subchronic toxicity study (OECD Guideline 407) dimethyl dodecy l amine was administered daily by gavage to four groups of 5 Sprague

- Dawley rats in test concentrations of 0 (control), 50, 150 or 300 mg/kg bw/day. Toxicological examinations were carr ied out on mortalities, clinical signs, body weight, food consumption, examination of eyes, hematology

, clinical biochemistry, urinalysis, organ weights, macroscopic post mortem findings and histopathology.

The highest dose group (300 mg/kg bw/day) was within the lethal range. Three of five females died between test day 5 and 28. None of the males died. No substance

- related changes were found at histopathology in surviving animals. No mortalities occurred in the 50 and 150 mg/kg bw/day group. No subs tance

- related influence on behavior and external appearance was evident in the 50 mg/kg bw/day group. In the 150 mg/kg bw/day group all animals showed rubbing of the snouts in the bedding material between test days 2 and 28 immediately after dosing for a

duration of about 5 minutes.

Body weight, food consumption, hematology , clinical biochemistry, urinalysis and organ weights

showed no substance

- related influence in animals after dosing of 50 or 150mg/kg bw/day . The LOAEL was 150 mg/kg bw/day based on mild adverse behavior including snout rubbing. The NOAEL of 50 mg/kg bw/day was determined in this study.Page 9 of 25

Genotoxicity

Data from an Ames assay are presented in the ACC HPV submission . The HPV submission discussed three dimethyl alkyl amines that to gether comprise a large portion of coco alkyl dimethyl amines. These compounds are: N,N

- dimethyl 1

- tetradecanamine (CAS Reg. No. 112

- 75

- 4), N,N

- dimethyl 1

- hexadecanamine (CAS Reg. No. 112

- 69

- 6) and N,N

- dimethyl 1

- octadecanamine (CAS Reg. No. 124

- 28

- 7) (AC C 2003). The study was not conducted in

accordance with OSCPP Harmonized Test Guidelines as two 2 bacterial strains were studied. As such, the ACC rated the studies reliable with restrictions. Four pour

- plate type assays used

co ncentrations of 0.5, 1.6 , 5.0, 15.8 and 50 μg/plate (purity 100%). Salmonella typhimurium strains TA98 and TA 100 were plated with and without metabolic activation using Aroclor 1254

- induced rat liver S

- 9 from male CD rates. There was no evidence of mutagenicity under the

condi tions of the test in any of the three compounds

.

In an in vitro study, Genamin 12 R 302 D (>95% C12

- Dimethyldodecylamin e ) was tested for mutagenicity with Salmonella typhimurium strains TA100, TA1535, TA1537, TA1538 and TA98 (the Ames test) and with Escherichia coli WP2 u vrA. The mutagenicity studies were conducted in the absence and presence of a metabolizing system derived from rat liver homogenate. A dose range from 0.16 μg/plate to 500 μg/plate was used. Genamin 12 R 302 D

did not show a dose de pendent increase in the number of revertants in any of the bacterial strains testes. Based on the results it can be stated the Genamin 12 R 302 D is not mutagenic in these

test systems

.

An in viv o mammalian erythrocyte micronucleus test was conducted acc ording to OECD TG 474) with the product Genamin LA 302D (about 70% C12

- 25% C12

- 14 and 5% C16 dimethylalkylamine) using male and female HsdWi n NMRI mice. The doses were administered by oral gavage at 0, 120, 400, or 1200 mg/kg N,N

- dimethyl

- 1

- dodecanamine. There were no statistically significant increases in the percentage of micronucleated polychromatic erythrocytes in treated mice compared to the controls. The study indicates that N,N

- dimethyl

- 1

- dodecanamine is not clastogenic under the conditions of the test (OECD 2001).

Carcinogenicity

None of the amines discussed in an HPV challenge document were mutagenic. Greim et al (1998) stated “The vast majority of the in vitro and in vivo genotoxicity tests gave no indication of genotoxic potential for pri mary aliphatic amines” (which includes CADA). Greim et al further state “Carcinog e nicity studies (cyclohexylamine and 2

- year feeding studies that do not completely meet the currant standards (sec

- butylamin and octadecylamine) sho w ed no

tum o rigenic potenti al.”

The Agency further evaluated the carcinogenic potential of coco alkyl dimethyl amines by conducting a probability analysis using the Nexus DEREK model. The model results are based

on a proprietary data set of 731 chemicals, classified on the basi s of the presence or absence of histopathologic lesions in the liver in oral rat repeat dose studies mostly of 28

- days duration. The model results indicated that there were no “ALERTS” regarding carcinogenicity or other pathology.Page 10 of 25

Reproductive/Developmental Toxicity

The OECD (2001) reported a reproductive/developmental toxicity screening study (OECD TG 421) of N,N

- dimethyl

- 1

- dodecanamine (CAS Reg. No. 112

- 18

- 5) that was conducted using Sprague

- Dawley rats. Ten animals/sex/group we re used. Dosing was administered by oral gavage. The administered doses were: 0, 50, 150, 300, and 450 mg/kg bw/day for 14 days prior to mating, 14 days during mating and for females, during pregnancy and lactation. Animals were examined for mortality, clinical signs, body weight, and food consumption, as well as reproductive histopathology. During the study course, 1 male and 2 females from the highest dose group died by day 5 and the rest of the high dose group was discontinued. In the 300 mg/kg

bw/d ay group, one male and six females died and only one p up was born alive. A t the 150 mg/kg bw/day do se , two dams died and two dams did not deliver pups. The mean implantation loss was significantly higher than the controls ( 50.4 % v s 13.3% ) and the mean vi ability index was significantly lower (36.9 % v s 99.3% ) . The birth weight of male pups was significantly

lower than that of controls. M aternal behavior was also affected as evidenced by an unsevered umbilical cord, cannibalization, and lack of care of pup s. No reproductive or developmental effects were observed in the absence of maternal toxicity. The NOAEL for systemic toxicity and for reproductive/developmental toxicity was determined to be 50 mg/kg bw/day. The LOAEL was 150 mg/kg bw/day based on mort ality in the dams, increase mean implantation loss, decreased mean viability index, reduced pup weight and abnormal maternal behavior.

Neurotoxicity and Immunotoxicity

No data were presented regarding n eurotoxicity or i mmunotoxicity.

Metabolism

No studies were found specific to the metabolic pathway or toxicokinetic properties of coco alkyl dimethyl amines in mammalian systems. Parkinson ’s (1996) research on structurally similar compounds suggested that for structurally similar compounds in mammals , hepatic dealkylation readily occurs with secondary and tertiary amines, with the methyl groups leaving preferentially.

Oxidation of the alpha carbon via cytochrome P450, forms a ca rb inolamine intermediate that will spontaneously cleave to form a seconda ry amine and carbonyl compound. Subsequent dealkylation of the secondary amine will take place at a slower rate. In a more minor pathway, hydroxylation of the nitrogen atom by hepatic oxidases may take place. Fatty acids are primarily

excreted as CO 2 (E CHA 2011)

.

Dermal Absorption

Dermal absorption is based upon surrogate data for 1

- dodecanamine. The dermal absorption of

1

- dodecanamine was determined to be 60% (Euro pean Chemicals Agency. 2011). Based on this information, it can be assumed that the dermal absorption of the coco alkyl dimethyl amines is not more than 60%. The CADA is a larger molecule than 1

- dodecanamine therefore it is not expected to be absorbed at a greater rate. For risk assessment purposes, dermal absorption is

assumed to be 6 0%.Page 11 of 25

V. Toxicity Endpoint Selection

No acute endpoint of concern was identified in the available database, therefore no need to conduct an acute dietary exposure assessment. The chronic reference dose was based on data

from co

- critical studies, a 28

- day oral toxicity study and a reproduction and developmental screening study on N,N

- dimethyldodecylamine (CAS Reg. No. 112

- 18

- 5) . In the 28

- day repeat dose feeding study in rats, animals displayed mild adverse behavior including snout (150 mg/kg bw/day) . In a reproduction and developmental screening study in rats

, mortality, increased mean implantation loss, decreased mean viability index, reduced pup weight and abnormal maternal behavior were observed at 150 mg/kg bw/day. The NOAEL was 50 mg/kg bw/day in bo th

studies . The uncertainty factor of 1000 X was used for chronic dietary assessment (10x for intra

individual variability, 10X for interspecies extrapolation and 10 X FQPA factor). No appropriate dermal or inhalation toxicity studies are available for th e exposure assessment. Therefore, the oral studies selected for chronic RfD was use as a conservative approach. Dermal absorption was

assumed to be 60% and inhalation absorption is assumed to be 100% oral equivalent. The acceptable MOEs for dermal and inha lation exposure are 1000 (10x for intra

- individual variability, 10X for interspecies extrapolation and 10 X FQPA factor).

Special Consideration for Infants and Children (FQPA Safety Factor)

Section 408 (b)(2)(c) of the FFDCA provides that EPA shall apply an additional margin of safety for infants and children in the case of threshold effects to account for prenatal and post natal toxicity and the completeness of the database on toxicity and exposure

unless EPA de termines that a different margin of safety will be safe for infants and

children. EPA concludes that the 10X FQPA safety factor should be retained for the coco alkyl dimethyl amines for the following reasons:

The database is considered in complete for FQ PA assessment. The following acceptable

studies are available:

28

- day Oral toxicity study in rats Reproduction/Developmental Screening study in rats.

i. In the 28

- day oral toxicity study in rats, toxicity was manifest as mild adverse behavior

and snout rubbing at 150 mg/kg bw/day.

ii. In a reproductive toxicity/developmental screening study in rats, neither qualitative nor quantitative fetal susceptibility was observed. Maternal (mortality and abnormal maternal behavior), developmental and reproduction (increased implantation loss, decreased mean viability index, reduced pup weight) effects were observed at the same dose, 150 mg/kg bw/day.

iii. Neurotoxic i ty and Immunotoxicity studies were not available for review. However, evidence of neurotoxicity or i mmunotoxicity was not observed in the submitted studies. Therefore, an immunotoxicity study or a developmental neurotoxicity study is not required at this time.Page 12 of 25

iv. The dietary food exposure assessment utilizes proposed to lerance level or higher residues and 100% crop treated (CT) information for all commodities. In addition, a conservative drinking water concentration value of 100 parts per billion (ppb) was used to assess the contribution to drinking water. By using these screening

- level assessments, chronic exposures/risks will not be underestimated.

As part of its qua ntitative assessment, the Agency retained the FQPA safety factors for assessing risk to infants and children because the available toxicity studies d o not allow for long

- term assessment of exposure to N,N

- dimethyl

- 1

- dodecanamine. Given the severity of toxicity observed in the present studies and the limited data available in the reproduction/developmental screening study, it cannot be concluded with c ertainty that long

- term post

- natal exposure would be safe. Therefore, the additional 10X FQPA safety factor is retained

.

VI. EXPOSURE

Dietary Exposure/Risk Characterization

Because no acute endpoint of concern was identified, a quantitative acute dietary exposure

assessment is unnecessary. In conducting the chronic dietary exposure assessment using the Dietary Exposure Evaluation Model DEEM

– FCIDTM, Version 3.16, EPA used food consumption information from the U.S. Department of Agriculture’s Nation al Health and Nutrition Examination Survey, What we eat in America, (NHANES/WWEIA). This dietary survey was conducted from 2003 to 2008. The Inert Dietary Exposure Evaluation Model ( I

DEEM) is a highly conservative model with the assumption that the residu e level of the inert ingredient would be no higher than the highest tolerance for a given commodity. Implicit in this assumption is that there would be similar rates of degradation between the active and inert ingredient (if any) and that the concentration of inert ingredient in the scenarios leading to these highest of tolerances would be no higher than the concentration of the active ingredient. The model assumes 100 percent crop treated (PCT) for all crops and that every food eaten by a person each day h as tolerance

- level residues. A complete description of the general approach taken to assess inert ingredient risks in the absence of residue data is contained in the memorandum entitled ‘‘Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic Aggregat e (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.’’ (D361707, S. Piper, 2/25/09) and can be found at http://www.regulations.gov in docket ID

number EPA

– HQ

– OPP

– 2008

– 0738.

The chronic analysis was based on a NOAEL of 50 mg/kg bw/day. The uncertainty factor of

100 0 (10x for intraspecies variability and 10x for inter species extrapolation and 10x FQPA ) was used for the chronic endpoints. One hundred percent crop treated was assumed, default processing factors and tolerance

- level residues for all foods and use limitations of not more than

0.5 % by weight in pesticide formulations. Drinking water (100 p pb) was incorporated directly into the dietary assessment. The chronic dietary risk assessment shows that the chronic dietary risk estimates are not of concern (i.e., <100% cPAD). For the Total U.S. population, the exposure for food and water utilized 3. 8 % of the cPAD. The chronic dietary risk estimate for the highest exposed population subgroup, children 1

- 2 years old is 14.1 % of the cPAD.Page 13 of 25

Residential (Non

- Occupational) Exposure/Risk Characterization

From non

- dietary exposure . The term “residential exposure” is used in this document to refer to

non

- occupational, non

- dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Based upon the request to use CADA

pre

- harvest on growin g crops, as an emulsifier that aids in the spray application of pesticide s
, the Agency does not expect non

- occupational (i.e., residential) pesticide handler exposure . Since the dietary Total Exposure for the Total U.S. population is 3.8% of the RfD, the Agency believes it is not probable that any possible residential exposure from handler use would fill the risk cup and exceed levels of concern. Therefore a quantitative assessment of residential handlers was

not conducted.

Occupational Exposure

The application to use coco alkyl dimethyl amines is not specific in terms of the ultimate intended use(s). Since the application requests use CADA pre

- harvest on growing crops, the Agency assumes the request is for use in commercial agricultural settings , not homeowner/residential settings. Lacking more specific information regarding anticipated human exposure, the Agency has conducted a screening level occupational exposure assessment.

The screening

- level assessment was conducted using an Antimicrobi als Division/Office of Pesticides Programs assessment tool developed to assess Amine Oxide (“ 900439

, (C10

- 16);

C10

- C18

- Alkyldimethylamine oxides ; Human Health Risk Assessment and Ecological Effects Assessment to Support Proposed Exemption from the Require ment of a Tolerance When Used as Inert Ingredients in Pestic ide Formulations

. ” 22 SEPT 2009; Memorandum L. Austin to P. Shah; Reg. Div./OPP/EPA). The assessment tool uses standard assessment methodology developed by

the Antimicrobials Division and the Sc ience Advisory Council for Exposure (EXPOSAC), Health Effects Division/Office of Pesticide Programs. The methodology can also be found in

part at: http://www.epa.gov/pest icides/science/residential

- exposure

- sop.html http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html http://www.epa.gov/pesticides/science/handler

- exposure

- data.html

.

In its simplest form, exposure is assessed as follows:

Unit Exposure * Amount applied/Unit * Units treated/day * absorption Factor ÷ Body Wt. (mg/lb handled) (lb applied/unit) (acres etc) 60% dermal kg

100% inhalation

The result is an estimated average daily dose (ADD or “exposure”) expressed as mg material/kg bw/day. That value is used then to calculate the Margin of Exposure (MOE) (estimated measure of risk). An MOE is calculated by dividing the value of the average daily dose into the toxicological endpoint of concern (also expressed in mg material/kg bw/day). MOEs ≥ than

100 0 do not exceed the Agency’s level of concern.Page 14 of 25

The end

- use concentration is assumed to be 0.5% the toxicological endpoint is 50 mg/kg bw/day

and dermal a bsorption is assumed to be 60 % inhalation absorption is assumed to be 100%.

The results of the screening level exposure assessmen t for occupationally exposed individuals,

are presented in the attachment. In summary, all Margins of Exposure (MOE) are > 100 0

. Therefore, under the conditions described above, the proposed hypothetical use(s) do not exceed the Agency’s level of concern . Estimates of exposure are presented for mixer/loaders using liquid formulations, for applicators representing several methods of application and for mixer/loader/applicators where that is appropriate for certain application equipment.

VII. AGGREGATE R ISK

Acute Aggregate Risk

. There was no hazard attributable to a single exp o sure seen in the toxicity database for CADA. Therefore, CADA is not expected to p ose an acute risk.

Short

- term Aggregate risk

. Short

- term aggregate exposure takes into account short

- term residential exposure plus chronic exposure to food and water (considered to be a background exposure level). Since the proposed use of CADA is not expected to result in “residential” exposures, it is not necessary to conduct an aggregat e exposure assessment with estimated dietary post

- application exposures.

Based on the expectations described above, EPA has concluded that the aggregated food and water exposures result in aggregate MOEs > 100 0

.

Residential Post

- application Exposure

Assessments of r esidential p ost

- application exposure are not necessary since the proposed use pattern is not expected to result in residential post

- application exposures.

VIII. CUMULATIVE EXPOSURE

Cumulative effects from substances with a common mechanism of toxicity . Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide's re sidues and “other substances that have a common mechanism of toxicity.”

EPA has not found CADA to share a common mechanism of toxicity with any other substances, and CADA does do not appear to produce a toxic metabolite produced by other

substances. For the purposes of this tolerance action, therefore, EPA has assumed that the CADA

do es not have a common mechanism of toxicity with other substances. 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 EPA's website at http://www.epa.gov/pesticides/cumulative

.Page 15 of 25

IX. ENVIRONMENTAL FATE & EFFECTS

A study of toxicity to zebra fish was present ed as well as results from EPI Suite TM ECOSAR modeling program (version 1.11).

Coco alkyl dimethyl amines (purity 100 %) were tested using OECD TG 203 with zebra fish ( Brachydanio rerio ). The 48 hr and 96 hr LC 50 values were > 0.1 mg/L and < 1 mg/L respectively (ACC, 2003.)

The EPI Suite TM ECOSAR modeling program (version 1.11) calculated aquatic toxicity based on structure and physical properties. ECOSAR results follow:

Test System LC 50 or Chronic Value (mg/L)

96 hr fish 0.225

48 hr Daphnid 0.04 96 hr algae 0.015

Chronic fish 0.004 Chronic algae 0.007

Other characteristics were presented earlier under Physical/Chemical Properties. Those

characteristics were based on EPI Suite TM EPIWIN modeling. Based on those results,

volatiliz ation and hydrolysis are not likely to be important for CADA. EPA (2010) indicates chemicals in the FND amines category have low mobility in the soil. Zahn

- Wellens activated sludge studies found a high potential for CADA adsorption onto sludge. The biod egradation of

CADA was 69

- 81 % after 28 days under aerobic conditions (OECD guideline 301D). This suggests readily biodegradability. According to the EPA (Federal Register. 1999), the CADA have a low potential to persist (P1) and bioaccumulate (B1).

X. DETERMINATION OF SAFETY

Based upon the proposed use pattern, upon the maximum limit on use rate and upon the physic al/chemical characteristics of CADA as discussed above, the EPA concludes that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to residues of CADA when used as an inert ingredient in pesticide

formulations under 40 CFR 180. 920

.

The proposed use of CADA is for application to growing crops in commercial agricultural

situations. The final end

- use concen tration is expected to be 0.5 % . Under the proposed conditions of use and the rapidly biodegradability, no harm is expected to the general population

or to infants and children.

XI. ENVIRONMENTAL JUSTICE

Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 128 98, "Federal Actions to Address Environmental Justice in Minority Populations and Low

- Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).Page 16 of 25

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 risks to population subgroups from pesticide exposures that are based on pat terns 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 Survey 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 country. 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 ri sks for adult applicators and for toddlers, youths, and adults entering or 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 spec ialized software and models that consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

XII. HUMAN STUDIES

This assessment does not rely on any studies in which human subjects were intentionally exposed to a pesticide.

XIII

. I NTERNATIONAL LIMITS: None

XIV. RISK CHARACTERIZATION

CADA exhibits low toxicity via the acute oral, dermal and inhalation routes of exposure. In rats

the acute oral LD 50 is > 1000 mg/kg bw/day. The acute dermal LD 50 is > 3385 mg/kg bw/day in rabbits. It is corrosive to the skin and irritating to the eyes of rabbits. An acute inhalation study was not available with the coco alkyl dimethyl amines, however data are available f or an acceptable surrogate compound. The acute inhalation LC 50 is > 0.6 mg/L in rats.

A 28

- day toxicity study was conducted according to Organization for Economic Co

- operation and Development (OECD) Test Guideline 407 using N, N

- dimethyl

- 1

- dodecanamine (CAS Reg.

No. 112

- 18

- 5). Sprague

- Dawley rats received an oral gavage dose of 0, 50, 150, or 300 mg/kg bw/day (OECD 2001). At 150 mg/kg bw/day, animals displayed mild adverse behavior, including snout rubbing. At mid dose, animals displayed mild adve rse behavior, including snout rubbing. A NOAEL of 50 mg/kg bw/day was observed in this study.

Regarding genotoxicity, the ACC HPV submission provided data on three dimethyl alkyl amines that together comprise a large portion of coco alkyl dimethyl amine s. These compounds
are: N,N

- dimethyl 1

- tetradecanamine (CAS Reg. No. 112

- 75

- 4), N,N

- dimethyl 1

- hexadecanamine (CAS Reg. No. 112

- 69

- 6) and N,N

- dimethyl 1

- octadecanamine (CAS Reg. No.

124

- 28

- 7) (ACC 2003). There was no evidence of mutagenicity under the conditions of the test in any of the three compounds. In addition, N,N

- dimethyl

- 1

- dodecanamine was not clastogenic

in an in vivo mammalian erythrocyte micronucleus test (OECD 2001). N,N

- dimethyl

- 1

-Page 17 of 25

dodecanamine (CAS Reg. No. 112

- 18

- 5) was not clastogenic in an in vivo mammalian erythrocyte micronucleus test (OECD 2001).

The OECD (2001) reported a reproductive/developmental toxicity screening study (OECD TG 421) of N,N

- dimethyl

- 1

- dodecanamine (CAS Reg. No. 112

- 18

- 5) administered via gavage to Sprague

- Dawley rats. At 150 mg/kg bw/day, mortality, increased mean implantat ion loss, decreased mean viability index and abnormal maternal behavior was observed in the dams and reduced weight in pups. The maternal, developmental and reproduction NOAEL was 50 mg/kg bw/day.

None of the amines discussed in an HPV challenge docum ent were mutagenic. Greim et al (1998) stated “The vast majority of the in vitro and in vivo genotoxicity tests gave no indication of genotoxic potential for primary aliphatic amines” (which includes CADA). Greim et al further state “Carcinogenicity stud ies (cyclohexylamine and 2

- year feeding studies that do not completely meet the curr e nt standards (sec

- butylamin and octadecylamine) showed no tumorigenic potential.”

The Agency further evaluated the carcinogenic potential of coco alkyl dimethyl amines by conducting a probability analysis using the Nexus DEREK model. The model results are based

on a proprietary data set of 731 chemicals, classified on the basis of the presence or absence of histopathologic lesions in the liver in oral rat repeat dose s tudies mostly of 28

- days duration.

The model results indicate there are no “ALERTS” regarding carcinogenicity or other pathology.

Dermal absorption is based upon surrogate data for 1

- dodecanamine. The dermal absorption of

1

- dodecanamine was determined to be 60% (European Chemicals Agency. 2011). Based on this information, it can be assumed that the dermal absorption of the coco alkyl dimethyl amines is not more than 60%. The CADA is a larger molecule than 1

- dodecanamine therefore it is not expected to be absorbed at a greater rate. For risk assessment purposes, dermal absorption is

assumed to be 60%.

No studies were found specific to the metabolic pathway or toxicokinetic properties of coco alkyl dimethyl amines in mammalian systems. Parkinson’s (19 96) study of structurally similar compounds suggested that for structurally similar compounds in mammals, hepatic dealkylation readily occurs with secondary and tertiary amines, with the methyl groups leaving preferentially. Oxidation of the alpha carbon via cytochrome P450, forms a carbinolamine intermediate that will spontaneously cleave to form a secondary amine and a carbonyl compound. Subsequent dealkylation of the secondary amine will take place at a slower rate. In a more minor pathway, hydroxylat ion of the nitrogen atom by hepatic oxidases may take place. Fatty acids are primarily

excreted as CO 2 (ECHA 2011).

No acute endpoint of concern was identified in the available database, therefore there is no need to conduct an acute dietary exposure ass essment. The NOAEL for risk assessment for all exposure scenarios is based on surrogate data from co

- critical studies: a 28 day repeat dose feeding study and a reproduction/developmental screening study in rats. At 150 mg/kg bw/day, animals displayed mi ld adverse behavior and snout rubbing in the 28

- day oral toxicity study. In the reproduction/developmental screening study in rats, dam mortality and abnormal behavior,Page 18 of 25

increased implantation loss, decreased viability index and reduced pup weight were obs erved at 150 mg/kg bw/day. The NOAEL in both studies was 50 mg/kg bw/day. The uncertainty factor of 1000X was used for chronic dietary assessment (10X for intra

- individual variability and 10X for interspecies extrapolation and 10X FQPA factor). No appro priate dermal or inhalation toxicity studies are available for the exposure assessment. Therefore, the oral studies selected for the chronic RfD were used as a conservative approach. Dermal absorption is assumed to be 60% and inhalation absorption is ass umed to be 100%.

Special Consideration for Infants and Children (FQPA Safety Factor) : The database is

considered in adequate for FQPA assessment. The following acceptable studies are available

, a 28

- day oral toxicity study and a reproduction/developmental toxicity study in rats. However, due to the severity of the effects, the limited data and the uncertainty regarding l ong

- term

e xposure , the 10X FQPA safety factor was retained.

The term “r esidential exposure” is used in this document to refer to non

- occupational, non

dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Based upon the request to use CADA on growing crops, the Agency does not expect non

- occupational (i.e., residential) pesticide handler exposure. Therefore an assessment of residential pesticide handlers is not necessary.

Assessments of Residential Post

- application exposure are not necessary since th e proposed use pattern is not expected to result in residential post

- application exposures.

EPA has not found CADA to share a common mechanism of toxicity with any other substances,

and CADA does do not appear to produce a toxic metabolite produced by o ther substances.

CADA is toxic to freshwater fish and other freshwater organisms. Environmental modeling suggests volatilization and hydrolysis are not likely to be important for CADA. The modeling data suggest ready biodegradability. Also according to the modeling data , the CADA have a low potential to persist (P1) and bioaccumulate (B1).

This assessment does not rely on any studies in which human subjects were intentionally exposed to a pesticide. There are no international limits for CADA.

Based o n the information presented above, the Agency approves of the proposed use of coco alkyl dimethyl amines as an inert ingredient under 40 CFR § 180.920 for use on growing crops at

a maximum end

- use concentration not to exceed 0.5%.Page 19 of 25 REFERENCES

American Chemistry Council. 2003. Fatty Nitrogen Derived Amines Category, High Production Volume (HPV) Chemicals Challenge. Assessment of D ata A vailability and T est

P lan. Toxicology/Regulatory Services, Inc. Document 201

- 14978, 29 December 2003

.

European Chemicals Agency. 2011. Annex 1 background document to the Opinion proposing harmonized classification and labeling at Community level of amines, coco alkyl (ECHA/RAC/CLH

- O

- 000002195

- 77

- 01/A1

European Chemicals Agency. 2011. Committee for Risk Assessme nt Annex 1. Background document to the RAC Opinion of amin e s, tallow alkyl. ECHA/RAC/CLH

- O

- 0000002199

- 69

- 01/a1. Adopted 2 DEC 2011.

European Chemical Bureau. 2000. International Uniform Chemical Information Database (IUCLID), Substance ID: 61788

- 93

- 0 ; Amines, coco alkyldimethyl. 18 FEB 2000. Edited by European Chemical Bureau, European Commission.

European Chemical Bureau. 2004. International Uniform Chemical Information Database (IUCLID), Substance ID: 84649

- 84

- 3; 17 August 2004. Edited by Euro pean Chemical Bureau, European Commission.

Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64, Number 213

. 4 NOV 1999 pp 60194

- 60204.

Greim, H., D. Bury, H

- J. Klimisch, M. Oeben

- Ne g ele, and K. Ziegler

- Skylakakis 1998. Toxicity of A liphatic A mine s ; S tructure

- A ctivity R elationship. Chemosphere 36 :(2) 271

- 295.

Organization for Economic Cooperation and Development (OECD). 2001. SIDS Initial Assessment Report for SIAM 11, January 2001. N,N

- Dimethyldodecylamine CAS No.: 112

- 18

- 5. Sponsor: Germany. UNEP Publications. http://www.inchem.org/documents/sids/sids/112185.pdf

Parkinson. A. 1996. Biotransformation of Xenobiotics in: Cas s aret & Doull’s Toxicology, Fifth

Edit. CD Klaassen, ed. McGr aw

- Hill, NY

.

U.S. Environmental Protection Agency. 2010. Screening

- level hazard characterization: Fatty Nitrogen Derived Amines Category> Hazard Characterization Document. September 2010. http://www.epa.gov/chemrtk/hpvis/hazchar/Category FND%20Amines September 2010.pdf

U.S. Environmental Protection Agency> 2013. Estimation Programs Interface Suite TM for

Microsoft ® Windows. v 4.00. http://www.epa.gov/opptintr/exposure/pubs/episuiteedl.htm

.Page 20 of 25 APPENDIX

I

- DEEM ANALYSIS COCO ALKYL DIMETHYL AMINES

US EPA Ver. 3.16,

03

- 08

- d

DEEM

- FCID Chronic analysis for INERTS

- COCA NHANES 2003

- 2008 2

- day

Residue file name:

C: \ Users \ tbloem \ Documents \ INERTS_57ACTIVE_100PPBH2OREV.R08 Adjustment factor #2

used. Analysis Date 03

- 11

- 2014/13:19:15 Residue file dated: 03

- 11

- 2014/13:18:59 Reference dose (RfD, Chronic) = .05 mg/kg bw/day
COMMENT 1: Inert 57 active ingredients + drinking water (100ppb)

====================================================== ====================

===== Total exposure by population subgroup

--------------------------------------------------------------------------

-----

Total Exposure

---------------------------------

-- Population mg/kg Percent of

Subgroup body wt/day Rfd

-------------------------------------- ------------- -------------

--- Total US Population 0.001893 3.8% Hispanic 0.002068 4.1%

Non

- Hisp

- White 0.001858 3. 7%

Non

- Hisp

- Black 0.001760 3.5%

Non

- Hisp

- Other 0.002234 4.5% Nursing Infants 0.002482 5.0%

Non

- Nursing Infants 0.004597 9.2%

Female 13+ PREG 0.001652 3.3%

Children 1

- 6 0.005467 10.9%

Children 7

- 12 0.002274 4.5%

Male 13

- 19 0.001338 2.7%

Female 13

- 19/NP 0.001359 2.7%

Male 20+ 0.001410 2.8% Female 20+/NP 0.001532 3.1%

Seniors 55+ 0.001527 3.1%

All Infants 0.003944 7.9%

Female 13

- 50 0.001464 2.9%

Children 1

- 2 0.007062 14.1%

Children 3

- 5 0.004856 9.7%

Children 6

- 12 0.002506 5.0%

Youth 13

- 19 0.001348 2.7%

Adults 20

- 49 0.001447 2.9%

Adults 50

- 99 0.001518 3.0%

Female 13

- 49 0.001463 2.9%Page 21 of 25 APPENDIX TWO

DEREK ANALYSIS



## Derek Nexus Report

Author

HED Report date

14 March 2014 14:19:48

Prediction date

14 March 2014 14:19:26 Program version Derek Nexus: 3.0.1, Nexus: 1.5.0 Compound name

Structure Species bacterium, mammal Endpoints alpha

- 2

- mu

- Globulin nephropathy, Anaphylaxis, Bladder urothelial hyperplasia, Carcinogenicity, Cardiotoxicity, Cerebral oedema, Chloracne, Cholinesterase inhibition, Chromosome damage in vitro, Chromosome damage in vivo, Cumulative effect on white cell count and immunology, Cyanide

- type effects, Developmental toxicity, Genotoxicity in vitro, Genotoxicity in vivo, Hepatotoxicity, HERG channel inhibition in vitro, High acute toxicity, Irritation (of the eye), Irritati on (of the gastrointestinal tract), Irritation (of the respiratory tract), Irritation (of the skin), Lachrymation, Methaemoglobinaemia, Mutagenicity in vitro, Mutagenicity in vivo, Nephrotoxicity, Neurotoxicity, Occupational asthma, Ocular toxicity, Oestro genicity, Peroxisome proliferation, Phospholipidosis, Photo

- induced chromosome damage in vitro, Photoallergenicity, Photocarcinogenicity, Photogenotoxicity in vitro, Photogenotoxicity in vivo, Photomutagenicity in vitro, Phototoxicity, Pulmonary toxicity, Rapid prototypes: adrenal gland toxicity, Rapid prototypes: bladder disorders, Rapid prototypes: blood in urine, Rapid prototypes: bone marrow toxicity, Rapid prototypes: bradycardia, Rapid prototypes: cardiotoxicity, Rapid prototypes: chromosome damage in vitro, Rapid prototypes: hepatotoxicity, Rapid prototypes: kidney disorders, Rapid prototypes: mitochondrial dysfunction, Rapid prototypes: nephrotoxicity, Rapid prototypes: splenotoxicity, Rapid prototypes: testicular toxicity, Rapid prototypes: thyroid toxicity, Respiratory sensitisation, Skin sensitisation, Teratogenicity, Testicular toxicity, Thyroid toxicity, Uncoupler of oxidative phosphorylation Superendpoints Carcinogenicity (SUPER), Chromosome damage (SUPER), Genotoxicity (SUPER), Hepatotoxic ity (SUPER), HERG channel inhibition (SUPER), Irritation (SUPER), Miscellaneous endpoints (SUPER), Mutagenicity (SUPER), Ocular toxicity (SUPER), Rapid prototypes: adrenal gland toxicity (SUPER), Rapid prototypes: bladder disorders (SUPER), Rapid prototype s: blood in urine (SUPER), Rapid prototypes: bone marrow toxicity (SUPER), Rapid prototypes: bradycardia (SUPER), Rapid prototypes: cardiotoxicity (SUPER), Rapid prototypes: chromosome damage in vitro (SUPER), Rapid prototypes: hepatotoxicity (SUPER), Rapi d prototypes: kidney disorders (SUPER), Rapid prototypes: mitochondrial dysfunction (SUPER), Rapid prototypes: nephrotoxicity (SUPER), Rapid prototypes: splenotoxicity (SUPER), Rapid prototypes: testicular toxicity (SUPER), Rapid prototypes: thyroid toxici ty (SUPER),Page 22 of 25

Reproductive toxicity (SUPER), Respiratory sensitisation (SUPER), Skin sensitisation (SUPER), Thyroid toxicity (SUPER)

Constraints

Perceive tautomers true

Perceive mixtures true

Perceive alerts without rules false Average molecular mass 213.4 (Lhasa Limited, version 1.0)

Exact molecular mass 213.2456 (Lhasa Limited, version 1.0) Log Kp 0.12 (Potts & Guy, version 1.0 (LogP: BioByte Corp., version 5.3; Average Molecular Mass: Lhasa Limited, version 1.0)) Log P

5.84 (BioByte Corp., version 5.3)



### Submitted compound



### Predictions

Derek KB 2012 1.0
KnowledgeBase name

Derek KB 2012 1.0 KnowledgeBase version

1.0 KnowledgeBase last modified

29 November 2012 11:56:30 KnowledgeBase location C:/Program Files/Lhasa Limited/Lhasa Knowledge Suite

- Nexus 1.5/KnowledgeBases/org.lhasalimited.pluto.knowledge.derek_1.0.7 KnowledgeBase certified byPage 23 of 25

Lhasa Limited, Leeds, Yorkshire, UK Nothing to report



### Reasoning glossary:

CertainPage 24 of 25 Screening Level Occupational Exposure Assessment 

### ATTACHMENT

Application Method Site/Crop Applic. Rate Units/day Dermal Inhalation Dermal Inhalation Combined lb/acre acre/day mg/kg bw/day mg/kg bw/day MOE MOE MOE

MIXER/LOADERS



### Liquids: Aerial / Chemigation Corn (avg/IT) 0.0035 1200 0.00083 0.0000720 60386.47 694444.4 55555.6 

### Corn (Max/ST) 0.01 1200 0.00237 0.0002057 21135.27 243055.6 19444.4 

### Liquids: Airblast Nut Trees (avg/IT) 0.0125 40 0.00010 0.0000086 507246.38 5833333.3 466666.7 

### Nut Trees (Max/ ST) 0.045 40 0.00035 0.0000309 140901.77 1620370.4 129629.6 

### Liquids: Groundboom Corn (avg/IT) 0.0035 200 0.00014 0.0000120 362318.84 4166666.7 333333.3 

### Corn (Max/ST) 0.01 200 0.00039 0.0000343 126811.59 1458333.3 116666.7 

### Turf/Golf Courses (avg/IT) 0.0035 40 0.00003 0.0000024 1811594.20 20833333.3 1666666.7 

### Turf/Golf Courses (Max/ST) 0.01 40 0.00008 0.0000069 634057.97 7291666.7 583333.3 

### Liquids: Low Press./High Vol.

Turfgun LCO Use on Turf (avg/IT) 0.036 5 0.00004 0.0000031 1409017.71 16203703.7 1296296.3 

### LCO Use on Turf (Max/ST) 0.036 5 0.00004 0.0000031 1409017.71 16203703.7 1296296.3

APPLICATORS 

### Aerial Liquid Application Corn (avg/IT) 0.0035 1200 NA NA NA NA NA



### Corn (Max/ST) 0.01 1200 NA NA NA NA NA



### Airblast Nut Trees (avg/IT) 0.0125 40 0.00103 0.0000321 48611.11 1555555.6 47138.0



### Nut Trees (Max/ST) 0.045 40 0.00370 0.0001157 13503.09 432098.8 13093.9



### Groundboom Corn (avg/IT) 0.0035 200 0.00008 0.0000074 595238.10 6756756.8 547046.0 

### Corn (Max/ST) 0.01 200 0.00024 0.0000211 208333.33 2364864.9 191466.1 

### Turf/Golf Courses (avg/IT) 0.0035 40 0.00002 0.0000015 2976190.48 33783783.8 2735229.8Page 25 of 25 

### Turf/Golf Courses (Max/ST) 0.01 40 0.00005 0.0000042 1041666.67 11824324.3 957330.4

MIXER/LOADER/APPLICATORS 

### Low Pressure/High Volume Turfgun LCO Use on Turf (avg/IT) 0.036 5 0.00100 0.0000170 49857.55 2946127.9 49027.8 

### LCO Use on Turf (Max/ST) 0.036 5 0.00100 0.0000170 49857.55 2946127.9 49027.8 

### Wettable Powder: Low

Pressure Handwand Ornamentals (avg/IT) 0.036 5 0.01327 0.0028286 3768.30 17676.8 3106.1 

### Ornamentals (Max/ST) 0.036 5 0.01327 0.0028286 3768.30 17676.8 3106.1 

### Liquid: Low Pressure

Handwand Ornamentals (avg/IT) 0.036 5 0.00066 0.0000771 75366.06 648148.1 67515.4



### Ornamentals (Max/ST) 0.036 5 0.00066 0.0000771 75366.06 648148.1 67515.4