Page 2 of 25

(CAS No. 112-18-5) and other closely related 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 exhibits low toxicity via the acute oral, dermal and inhalation routes of exposure. In rats 

the acute oral LD50 is > 1000 mg/kg bw/day. The acute dermal LD50 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 LC50 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. 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 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 implantation 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 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). Greim et al 

further state “Carcinogenicity studies (cyclohexylamine and 2-year feeding studies that do not 

completely meet the current 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 (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 mostly 
Page 3 of 25

of 28-days duration. The model results indicated that there were no “ALERTS” for 

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 (1996) 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, 

hydroxylation of the nitrogen atom by hepatic oxidases may take place. Fatty acids are primarily 

excreted as CO2 (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. At 150 mg/kg bw/day, 

animals displayed mild 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, 

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 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 assumed to be 100%. 

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

considered inadequate 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 guideline parameters.

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

1000 (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 ppb) 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 
Page 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, nondietary 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.

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 described 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 likely to be important for CADA. The modeling 

data suggest ready biodegradability. Also according to the modeling, CADA has 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/guidance/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 18th 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. Specifically, 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 concentration of a spray mix is less than 0.5%. Coco alkyl dimethyl 

amines are currently permitted for use in non-food pesticide products.

Coco 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 “read-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.

N

CH3

CH3

Coco Alkyl
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/cm3 @ 25oC 0.79 ECB 2000

Vapor Pressure (hPa @ 100oC <1 ECB 2000

LogKOW 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-m3/mole @ 

25oC

5.2x10-4 EPI Suite HENRYWIN v3.2

Log KOC (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-caking agents, lubricants and water treatment agents. 
Page 7 of 25

IV TOXICOLOGICAL PROFILE

Summary of Acute Toxicity

Route Value Source

Acute oral

toxicity (rat)

LD50

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)

LC50

> 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, SpragueDawley rats were administered an oral dose of 1.0-2.5 g/kg coco alkyl dimethyl amines (purity 

not stated). The LD50 was determined to be 1500 mg/kg for males and 1300 mg/kg for females. 

The study was determined to be reliable without restrictions by the ACC. 

The second study was a GLP acute oral toxicity study using Wistar rats (5/dose). An LD50 of 

>1000 and >1250 mg/kg bw/day (100% purity) were determined. 

The third acute oral toxicity study was conducted on albino rats (strain not specified) (10 

rats/dose). The LD50 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 (FND) ether amines category. No standard guideline was listed however the study 

was deemed reliable without restrictions by the ACC. Four New Zealand 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 

LD50 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 amine, N-tallow alkyl derivatives of 2,2-iminobis 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 LC50 was 

determined to be >0.6 mg/L therefore 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 dimethylalkylamines) 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 compounds that are the primary constituents of coco alkyl dimethyl amines. 

All three compounds are irritating to the rabbit eye (US EPA 2010).

Repeat Dose Toxicity

Data were not available on CADA, however, data are available on the N,Ndimethyldodecylamine (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) dimethyldodecylamine 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 carried 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 substance-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 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). 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 

concentrations 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 

conditions of the test in any of the three compounds.

In an in vitro study, Genamin 12 R 302 D (>95% C12- Dimethyldodecylamine) was tested for 

mutagenicity with Salmonella typhimurium strains TA100, TA1535, TA1537, TA1538 and 

TA98 (the Ames test) and with Escherichia coli WP2uvrA. 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 dependent 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 vivo mammalian erythrocyte micronucleus test was conducted according to OECD TG 

474) with the product Genamin LA 302D (about 70% C12- 25% C12-14 and 5% C16 

dimethylalkylamine) using male and female HsdWinNMRI 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 primary aliphatic amines” (which includes CADA). Greim et al 

further state “Carcinogenicity studies (cyclohexylamine and 2-year feeding studies that do not 

completely meet the currant 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 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 were 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/day group, one male and six females died and only one pup was born alive. At the 150 

mg/kg bw/day dose, two dams died and two dams did not deliver pups. The mean implantation 

loss was significantly higher than the controls (50.4% vs 13.3%) and the mean viability index 

was significantly lower (36.9% vs 99.3%). The birth weight of male pups was significantly 

lower than that of controls. Maternal behavior was also affected as evidenced by an unsevered 

umbilical cord, cannibalization, and lack of care of pups. 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 mortality 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 neurotoxicity or immunotoxicity.

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 carbinolamine intermediate that will 

spontaneously cleave to form a secondary 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 CO2 (ECHA 2011).

Dermal Absorption

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%.
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 both 

studies. The uncertainty factor of 1000 X was used for chronic dietary assessment (10x for intraindividual variability, 10X for interspecies extrapolation and 10 X FQPA factor). No appropriate 

dermal or inhalation toxicity studies are available for the 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 inhalation 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 determines that a different margin of safety will be safe for infants and 

children. EPA concludes that the10X FQPA safety factor should be retained for the coco 

alkyl dimethyl amines for the following reasons:

The database is considered incomplete for FQPA 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. Neurotoxicity and Immunotoxicity studies were not available for review. However, 

evidence of neurotoxicity or immunotoxicity 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 tolerance 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 quantitative assessment, the Agency retained the FQPA safety factors for assessing

risk to infants and children because the available toxicity studies do 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 certainty 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 National 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 (IDEEM) is a highly conservative model with the assumption that the residue 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 has 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 

Aggregate (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 

1000 (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 ppb) 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 growing crops, as an emulsifier that aids in the spray application of pesticides, 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 Antimicrobials 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 Requirement of a Tolerance When Used as 

Inert Ingredients in Pesticide 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 Science 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/pesticides/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 

1000 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 absorption is assumed to be 60 % inhalation absorption is assumed to be 100%.

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

are presented in the attachment. In summary, all Margins of Exposure (MOE) are > 1000. 

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 RISK

Acute Aggregate Risk. There was no hazard attributable to a single exposure seen in the toxicity 

database for CADA. Therefore, CADA is not expected to pose 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 aggregate 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 > 1000. 

Residential Post-application Exposure

Assessments of residential post-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 residues 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

does 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 presented as well as results from EPI SuiteTM 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 LC50 values were > 0.1 mg/L and < 1 mg/L 

respectively (ACC, 2003.)

The EPI SuiteTM ECOSAR modeling program (version 1.11) calculated aquatic toxicity based on 

structure and physical properties. ECOSAR results follow:

Test System LC50 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 SuiteTM EPIWIN modeling. Based on those results, 

volatilization 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 biodegradation 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 

physical/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 concentration 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 12898, "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 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 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 risks 

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 specialized 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. INTERNATIONAL LIMITS: None

XIV. RISK CHARACTERIZATION

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

the acute oral LD50 is > 1000 mg/kg bw/day. The acute dermal LD50 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. The acute inhalation LC50 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 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 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 implantation 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 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). Greim et al 

further state “Carcinogenicity studies (cyclohexylamine and 2-year feeding studies that do not 

completely meet the current 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 studies 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 (1996) 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, 

hydroxylation of the nitrogen atom by hepatic oxidases may take place. Fatty acids are primarily 

excreted as CO2 (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. At 150 mg/kg bw/day, 

animals displayed mild 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 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 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 assumed to be 100%. 

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

considered inadequate 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 long-term

exposure, the 10X FQPA safety factor was retained. 

The term “residential exposure” is used in this document to refer to non-occupational, nondietary 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 the 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 other 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 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 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 Data Availability and Test 

Plan. 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 Assessment Annex 1. Background 

document to the RAC Opinion of amines, 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 European 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-Negele, and K. Ziegler-Skylakakis 1998. 

Toxicity of Aliphatic Amines; Structure-Activity Relationship. 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: Cassaret & Doull’s Toxicology, Fifth 

Edit. CD Klaassen, ed. McGraw-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 SuiteTM for 

Microsoft® Windows. v4.00. 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), Irritation (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, Oestrogenicity, 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), Hepatotoxicity 

(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 prototypes: 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), Rapid 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 toxicity (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 by
Page 23 of 25

Lhasa Limited, Leeds, Yorkshire, UK

Nothing to report

Reasoning glossary:

Certain
Page 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 2735229.8
Page 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