Page 2 of 36

corneas. An eye irritation test with New Zealand white rabbits indicates it to be moderately irritating. 

Two skin sensitization tests with Hartley guinea pigs show it is not a sensitizer to the guinea pig. 

A 28-day repeat dose oral toxicity study was conducted with Wistar rats. In this study, rats were 

treated via gavage with D-glucitol, 1-deoxy-1-(methylamino)- N-C8-10 derivatives at doses up to 500 

mg/kg/day. At the 500 mg/kg/day dose, mortality was observed as well as toxicity reflected as

microscopic findings in the GI tract, trachea, lung, spleen and bone marrow. The NOAEL was 250 

mg/kg/day. 

In a reproduction/developmental toxicity screening test, rats were dosed for 54 days with D-glucitol, 

1-deoxy-1-(methylamino)- N-C8-10 derivatives at doses up to 312.5 mg/kg/day. Neither parental, 

developmental nor reproduction toxicity was observed at 312.5 mg/kg/day, the highest dose tested. 

 

A gene reverse mutation study with Salmonella, an in vitro mammalian cell gene mutation study with 

Chinese hamster V 79 cells, a mammalian micronucleus mutagenicity test of micronuclei in 

polychromatic erythrocytes in the mouse bone marrow, a mammalian micronucleus test with murine 

peripheral blood cells, a mutagenesis assay using L5178Y TK+/- mouse lymphoma cells, an in vivo rat 

bone marrow cytogenicity study all were negative for mutagenic and clastogenic effects. 

There were no neurotoxicity data per se however there were no indications of neurotoxic effects in 

the functional observation battery in the 28-day oral toxicity study in the rat. In addition, the DEREK 

predictive modeling system did not identify any alerts for potential neurotoxicity.

There were no data regarding immunotoxicity. However evidence of potential immunotoxicity was 

observed in the 28 day oral toxicity study in the rat. In this study, atrophy is seen in the spleen and 

bone marrow at 500 mg/kg/day. These effects will be protected since the established chronic 

reference dose (cRfD) is 1.04 mg/kg/day. 

There were no study data presented specifically addressing metabolism. Modeling data using the 

DEREK (Nexus) and METEOR modeling systems indicate 80 % absorption via the gastrointestinal 

system and less than 1 % via dermal absorption. The major route of excretion is via the urine.

The toxicological endpoint selected for use in chronic dietary risk assessment is taken from 

reproduction/developmental toxicity screening study in the rat. In this study, no effects are observed 

up to 312.5 mg/kg/day. The standard uncertainty factors (100x) are applied for intra- and interspecies 

variation and an additional uncertainty factor (3X) is applied to account for extrapolation from 

subchronic to chronic exposures. The Agency considers an uncertainty factor of 3X protective as no 

toxicity was observed up to 312.5 mg/kg/day in an OECD 422 Guideline study. Dermal and 

inhalation absorption are assumed to be 100 %. For all short- and intermediate-term residential and 

occupational risk assessments, the toxicological endpoint selected for use is the assessment is taken 

from reproduction/developmental toxicity screening study in the rat. In this study, no effects are 

observed up to 312.5 mg/kg/day. The level of concern is for margins of exposure (MOEs) of 300 or 

less.
Page 3 of 36

The general public is expected to be exposed via the oral route via dietary residues from treated crops

and from ingestion of drinking water that may contain D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10

acyl derivatives . The Agency has assessed dietary exposure with 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). For D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives, 

aggregate risk include dietary exposure from food and drinking water. Exposures to children 1-2 years

(the most highly exposed population subgroup from dietary sources) include food and water 

exposures. Dietary exposure estimates for food and drinking water are below the Agency’s level of 

concern (<100% cPAD) for the U.S. population and all population subgroups. The total dietary 

exposure for food and drinking water is 14.6 % of the cPAD for the U.S. population and 54.4 % of the 

cPAD for children 1-2 yrs. old, the most highly exposed population subgroup. 

The Agency assessed aggregate exposures to D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10

acyl derivatives by considering potential dietary exposures, as discussed above, as well as potential 

residential applicator and post-application exposures via the oral, dermal and inhalation routes of 

exposure to both adults and children. The Agency’s level of concern is for Margins of Exposure < 

300. The estimated screening level aggregate MOEs (assuming 100 % absorption via the dermal and 

inhalation routes) are > 300 and do not exceed the Agency’s level of concern. Screening level 

occupational exposures resulted in Margins of Exposure (MOE) greater than 300 and thus do not 

exceed the Agency’s level of concern. 

D-Glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives exhibits low levels of toxicity to fish, 

Daphnia, algae and aquatic microorganisms. Study data indicate it is readily biodegradable within 28 

days. The physical nature of the substance and the low vapor pressure indicate minimal concern for 

volatility. It is essentially insoluble in water It is therefore not expected to bioaccumulate or be 

persistent in soil or water. 

Based upon the factors and discussion presented above, an exemption from the requirement of a 

tolerance for D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives as an inert ingredient 

(surfactant) in pesticide formulations applied to growing crops and raw agricultural commodities at a 

maximum concentration of 40% by weight can be established. 

II. BACKGROUND

On 23 December 2014, Keller & Heckman (1001 G Street, N.W., Suite 500 West, Washington, DC 

20001) on behalf of the Clariant Corporation (4000 Monroe Road, Charlotte, NC 28205) submitted a 

request to the U.S. EPA for the establishment of an exemption from the requirement of a tolerance for 

D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives (CAS Reg. No. 1591782-62-5) when 

used as an inert ingredient in pesticide formulations applied growing crops and raw agricultural 

commodities after harvest.. D-Glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives is also 

referred to as C8-10 acyl N-methylglucanamide or C8-10 acyl NMGA in portions of this document. 
Page 4 of 36

The submission relies, to a large degree, upon “read-across” data regarding a structurally similar 

chemical analogue. 1-Deoxy-1-(methyl(C12-C14-(even)-alkanoyl)amino)-D-glucitol (CAS Reg. No. 

287735-50-6) is identified as an analogue to address data gaps for the D-glucitol, 1-deoxy-1-

(methylamino)-, N-C8-10 acyl derivatives The molecular structural difference is distinguished by only 

2 to 4 CH2 units in the alkyl chain. The Agency believes that based on the similarities in structural, 

functional and metabolic behavior of the target and source molecules, it is reasonable and 

scientifically justified to accept the “read-across” approach as the source of effects on mammalian 

systems and on environmental fate and effects. 1-Deoxy-1-(methyl(C12-C14-(even)-alkanoyl)amino)-Dglucitol D-Glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives is also referred to as C12-14

acyl N-methylglucanamide or C12-14 acyl NMGA in portions of this document 

III. PHYSICAL/CHEMICAL PROPERTIES

Table 1.0

Property C8-10 acyl NMGA C12-14 acyl NMGA

State Solid Solid

Molecular Weight 334.1 386.2

Melting Point 59-64 °C 77-113°C

Boiling Point No boiling point under

atmospheric conditions

No boiling point under

atmospheric conditions

Relative Density D4

R = 1.16 @ 20.6°C D420 = 1.14 @ 19.9-20.5° C

Vapor Pressure 1.1 x 10-8 hPa @ 25°C =

~ 8.25 x 10-9 mm Hg

1.4 Pa @ 25°C

Solubility in Water Not applicable: test substance

Is surface active substance

C12 68 mg/L

 @ 20° C (24 hr)

C14 95 mg/L @ 60-70°C 30 minutes

Octanol/Water

Coefficient

Calculated log POW

1.43 @ pH 9.36

Solubility in n-Octanol 47 g/L @ 20°C 28 g/L @ 20°C

Taken from pp 44-47/125 MRID 49537200 (Volume 2)

IV. HAZARD CHARACTERIZATION 

1-Deoxy-1-(methyl(C12-C14-(even)-alkanoyl)amino)-D-glucitol 

Acute Oral Toxicity

In an acute oral toxicity study by Leoni (2013; MRID 49537203) the oral LD50 for Wistar Crl: 

WI(Han) rats was determined to be 500 mg/kg for C8-10 following a single oral dose.

Acute Dermal Toxicity

The acute dermal toxicity of C8-10 was studied by Allingham (2013; MRID 49537206). Five male and 

five female Wistar Crl: WI(aHan) rats were administered a single dermal dose of 2000 mg/kg applied 
Page 5 of 36

to 10% of the body surface area. The dermal LD50 for a single dermal dose of C8-10 was determined to 

be > 2000 mg/kg.

Acute Inhalation Toxicity

Acute inhalation toxicity was evaluated by van Huygevoort (2014; MRID 49537208) using a single 

four hour, nose only exposure to three male and three female Wistar rats. The test was conducted 

according to OECD test guideline 436. The mean actual vapor concentration was 22.2 ± 1.4 mg/L of 

the test substance C8-C10. The Mass Median Aerodynamic Diameter of vapor particles was 2.0 μm. 

Animals were observed on days 1, 2, 4, 8, and 15. There was no mortality and no clinical signs were 

seen. Body weight loss and reduced body weight gain was noted for the females between Days 4 and 

15 which were considered as signs of toxicity. The inhalation LC50, -4-hr value of a 1 % water 

solution of C8-C10 in Wistar rats was established to exceed 20 mg/L. According to the OECD 

Guideline 436 test guideline and considering the effects on body weights of females, the LC50, 4-hr

cut-off value was considered to be 50 mg/L.

In another study by van Huygevoort (2011; MRID49537209), the acute inhalation toxicity was 

evaluated in Wistar rats. Three male and three female rats were exposed for four hours to a 

concentration of 5 mg/L. The mean actual concentration was 5.1 ± 0.13 mg/L. Exposures were noseonly to restrained animals. Animals were observed on days 1, 2, 3, 4, 8 and 15. At the 5 mg/L dose 

two males and one female died within 3 days post-treatment. No further mortality was observed. At 

the 5 mg/L dose, animals showed slow breathing and one animal was restless during the exposure. 

After exposure, lethargy, hunched posture, abnormal gait, labored respiration, rales, 

chromodacryorrhea and/or ptosis was noted for the animals between Days 1 and or 9. One female 

showed hunched posture till Day 14.

After noting the results/observations from the 5 mg/L exposure group, a second group of rats was 

exposed in a similar fashion to 1 mg/L of C8-C10 for four hours. At 1 mg/L no clinical signs were 

noted during exposure. After exposure, hunched posture was seen in all animals between Days 1 and 

4. One male showed labored respiration and ptosis between Days 1 and/or 2. Overall body weight 

gain in males and females was within the historical range expected for rats of that strain and age thus 

not considered toxic effects. The inhalation LC50, 4hr value in Wistar rats was established to be within 

1 – 5 mg/L. According to the OECD Guideline 436 the LC50, 4hr cut-off value was considered to be 5 

mg/L.

In Vitro Skin Irritation 

An in vitro skin irritation study (Lehmeir, 2013; MRID 49537210) was conducted using the human 

skin model test with C8-10. The test was conducted according to OECD Guideline test 404 (OPPTS 

Guideline 870.2500) which uses the Draize scoring method. The test was conducted with the 

reconstituted three-dimensional human skin model, EPISKIN-SMTM (SkinEthic). The skin model 

consists of normal, adult human-derived epidermal keratinocyts (NHEK) which have been cultured to 

form a multilayered, highly differentiated model of the human epidermis. The NHEK are cultured on 

chemically modified, collagen-coated cell culture inserts. A highly differentiated and stratified 

epidermis model is obtained after 13-day culture period comprising the main basal, supra basal, 

spinous and granular layers and a functional stratum corneum.
Page 6 of 36

In this study, C8-10 was applied topically to the EPISKIN SMTM tissue for 15 minutes followed by a 42 

hour post-incubation period and immediate determination of cytotoxic effects via MTT reduction 

assay (MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Irritant potential of the 

test item was predicted from the relative mean tissue viability obtained compared to the corresponding 

negative control tissues concurrently treated with PBS. The test item showed no irritant effects. The 

mean relative tissue viability was > 50 % (100.2%) after 15 minute treatment and 42 hour postincubation. The controls confirmed the viability of the study. The mean Optical Density (OD)550 of 

the six blank values was < 0.1. The mean absolute OD550 of the three negative control tissues was ≥ 

0.6 and ≤ 1.5. The mean relative tissue viability (% negative control) of the positive control was ≤

40% (28.5 %). Under the conditions of this study, the test material showed no irritant effects and was 

classified as non-irritating.

An in vitro eye irritation study (Schmitz, 2013; MRID 49537212) was conducted using C8-10 using the 

bovine corneal opacity and permeability (BCOP) method. The bovine corneas were obtained from 

animals freshly sacrificed at the abattoir. Three corneas were used for the test item, three were used as 

positive controls (treated with imidazole 20 % in physiological saline, 0.9 % NaCl, and three were 

used as negative controls treated with physiological saline, 0.9 % NaCl. The BCOP assay is 

considered valid if the in vitro irritation score obtained with the positive control falls within the two 

standard deviations of the current historical mean. The mean in vitro irritation score was calculated to 

be 130.97 therefore the test item is considered to be a severe irritant to the eye.

Skin Sensitization

A skin sensitization study was conducted by van Huygevoort (2013; MRID 49537214) using 10 

female Dunkin Hartley albino guinea pigs. The test article is identified as C8-10. The study followed 

the Magnusson and Kligman protocol. The study was based on findings from a preliminary study. 

The ten animals were intradermally injected with a 0.5 % concentration and epidermally exposed to a 

5 % concentration. Five control animals were similarly treated but with vehicle (water) only. Two 

weeks after the epidermal application all animals were challenged with a 5 % test substance 

concentration and the vehicle. No skin reactions were evident after the challenge exposure in the 

experimental and control animals. There was no evidence that C8 had caused skin hypersensitivity in 

the guinea pig since no responses were observed in the experimental animals in response to a 5 % test 

substance concentration in the challenge phase.

28-Day Repeat Dose Oral Toxicity

In a 28-day oral toxicity study (Stiller, 2014: MRID 49537217), C8/10 was administered by gavage to 

four groups of 5 male and 5 female Crl: WI(Han) rats/group at 0, 100, 250, and 500 mg/kg/day for 28 

consecutive days. Two additional groups of 5 male and 5 female rats were administered the test 

material at 0 and 500 mg/kg/day for 28 days and kept for a 14-day recovery period prior to necropsy.

During the study 1/10 males and 3/10 females were sacrificed in extremis at the high dose and one 

female at the high dose was found dead. The first was a male sacrificed on Day 12 and the last death 

was a female on Day 22. Numerous treatment-related findings were observed that predominantly were 

associated with direct-acting irritating effects of the test material. Immediately after administration, 
Page 7 of 36

moving the nose through cage bedding was observed at all three dose levels in a dose dependent 

manner. Piloerection was observed at the high dose in some females and one male animal on single or 

occasional days of the treatment period. Piloerection was also observed at the high dose during the 

first week of the recovery period. Respiratory sounds were heard at all three doses in a dose-dependent 

manner, but not during the recovery period. No statistically significant or biologically relevant 

findings were observed in the clinical chemistry results, functional observational battery, or urinalysis 

data. There was no statistically significant effect on body weight or weight gain at any dose, although 

female body weight at the high dose was 6.7% lower and weight gain was 27% lower at the end of the 

treatment period. Statistically significant increases (p≤0.001) in neutrophils (20.2% vs. 10.0% in 

controls) and lymphocytes (75.7% vs. 87.2% in controls) were observed in females at the high dose at 

the end of the treatment period, but no microscopic correlate was observed. Somewhat increased 

uterus weight was observed at all three doses at the end of the treatment period (49%, 38% and 58% 

higher at 100, 250 and 500 mg/kg bw/day, respectively) that was related to fluid distension of the 

uterus/cervix, but no microscopic correlate was observed. Females in the recovery group (N = 2) did 

not appear to have substantially higher uterine weight. Gaseous distension of the gastrointestinal (GI) 

tract was observed in one male and four females sacrificed in extremis at the high dose. At scheduled 

sacrifice, gaseous distension of the GI tract was observed in one male at the mid-dose, one female at 

the low dose, and two females at the high dose. This finding was related to direct irritating effects to 

the GI tract observed microscopically. Minimal to moderate granulomatous inflammation in the lungs 

was observed in animals at the high dose that did not survive the treatment period. The high dose 

female found dead also showed minimal alveolar edema and congestion, and marked epithelial 

necrosis of the trachea along with slight bronchiolar necrosis. Minimal basophilic foreign material and 

bronchiolar hyperplasia was observed in the lung of one male at the high dose, and acute 

alveolar/interstitial inflammation and bronchiolar hyperplasia was observed in one female at the high 

dose. One high dose female at terminal sacrifice had moderate amounts of basophilic foreign material 

located in bronchioles and alveoli. Respiratory tract lesions were attributed to direct-acting irritation 

effects of the test material following aspiration of gavage doses. Lung lesions were not observed in 

animals that survived to the end of the recovery period. All premature deaths showed slight to 

moderate lymphoid atrophy in the spleen and minimal bone marrow atrophy and/or myeloid 

hypercellularity. The LOAEL for C8/10 was 500 mg/kg/day in both sexes of Wistar rats based on 

mortality, microscopic findings in the GI tract, trachea, lung, spleen, and bone marrow. The 

NOAEL was 250 mg/kg/day in both sexes. 

Reproduction/Developmental Toxicity in the Rat

In a reproduction/developmental toxicity screening study (Allingham, 2014; MRID 49537220), study, 

D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-C10 acyl derivs; was administered to 10 Wistar 

rats/sex/dose by gavage in water at dose levels of 0, 50, 125, or 312.5 mg/kg/day for at least 14 days 

prior to mating, during mating, after mating (males), throughout gestation, and through lactation day 

(LD) 4. The total treatment period was 54 days. Males were sacrificed on study day 29 and females 

and offspring were sacrificed on lactation day 4. Evaluated parameters included clinical observations, 

parental body weight, parental food consumption, parental organ weights, parental gross necropsy 

observations, parental histopathology, litter size, offspring sex and weight, and offspring gross 

examination. 
Page 8 of 36

There were no treatment-related effects on mortality, body weight, body weight gain, food 

consumption, gross or histopathological findings. Transient clinical signs attributable to local effects 

of the test substance (salivation, moving bedding, piloerection, and abnormal breathing) were 

observed in males and females of the high-dose group. Treatment-related, but non-dose-related, 

increased uterus+cervix weights were noted at all dose levels (absolute weights: +14-20%; relative-tobody weights: +13-24%; not significant). However these increases were not considered adverse due to 

the absence of correlated alterations in histopathology. Therefore, the parental systemic LOAEL is 

not identified, and the parental systemic NOAEL is 312.5 mg/kg/day.

Aside from increased uterus+cervix weights, there were no treatment-related effects on the evaluated 

reproductive parameters, including mating, conception, fertility, precoital interval, gestation length, 

corpora lutea, implantation sites, pre- or post-implantation loss, or pregnancy outcomes, or 

gross/microscopic pathology of the male and female reproductive tracts. Therefore, the 

reproductive LOAEL is not identified, and the reproductive NOAEL is 312.5 mg/kg/day.

There were no treatment-related effects on gestation survival, numbers of litters, litter size and weight, 

sex ratio, live born or born dead, viability indices, or macroscopic findings. Therefore, the 

developmental LOAEL is not identified, and the developmental NOAEL is 312.5 mg/kg/day. 

Reverse Mutation Assay

In 2012, Schreib (MRID 49537223) conducted a gene reverse mutation study to evaluate C8-C10 for 

its ability to induce gene mutations in Salmonella typhimurium test strains TA 98, TA 100, TA 1535, 

TA 1537 and TA 102. In two different experiments several concentrations of the test substance were 

used. The concentrations including the controls were tested in triplicate. The dosing concentrations 

were 3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 μg/plate. No precipitation of the test item was 

observed in any tester strain used in experiment I and experiment II, with and without metabolic 

activation. Toxic effects from the test item were noted in most tester strains used in experiments I 

and II. 

In experiments I and II, toxic effects from the test item were observed at concentrations of 1000 

μg/plate and higher (without metabolic activation) and at concentrations of 2500 μg/plate and higher 

(with metabolic activation), depending upon the particular test strain. 

No biologically relevant increases in revertant colony numbers of any of the five test strains were 

observed following treatment with the test substance at any concentration level, not in the presence or 

absence of metabolic activation in experiments I and II. 

Under the conditions of this study, the test substance did not cause gene mutations by base pair 

changes or frame shifts in the genome of the test strains used. Therefore, the test substance is 

considered to be non-mutagenic in this bacterial mutation assay.

In Vitro Mammalian Cell Gene Mutation

An in vitro mammalian cell gene mutation test was conducted by Wallner (2013, MRID 49537224) 

using Chinese hamster V79 cells exposed to the test substance C8-C10. The test was designed to assess 
Page 9 of 36

the potential for the test substance to induce mutations at the hypoxanthine-guanine-phosphoribosyltransferase (HPRT) locus of V79 Chinese hamster cells. Two tests were conducted with and without 

metabolic activation. The test concentrations were:

Test I: without metabolic activation – 0.5, 0.75, 1.00, 1.50, 1.60, 1.90, 1.95 and 2.05 mM and with

metabolic activation – 0.25, 0.5, 1.0, 2.0, 2.5, 2.7, 2.8, 2.9, 3.0 and 3.1 mM. 

Test II without metabolic activation the concentrations were 0.010, 0.025, 0.05, 0.10, 0.25, 0.50, 1.00, 

1.50, 1.75 and 2 mM. and with metabolic activation the concentrations were 0.20, 0.40, 0.80, 1.5, 

2.10, 2.35, 2.60 and 2.95 mM. No precipitation of the test item was noted in the experiments. 

Biologically relevant growth inhibition was observed in experiment I and II with and without 

metabolic activation. In experiment I without metabolic activation the relative growth was 11.8 % for 

the highest concentration (2.05 mM) evaluated. The highest biologically relevant concentration 

evaluated with metabolic activation was 3.1 mM with a relative growth of 12.7%. In experiment II 

without metabolic activation the relative growth was 15.9 % for the highest concentration (2 mM) 

evaluated. The highest concentration evaluated with metabolic activation was 2.95 mM with a relative 

growth of 10.0 %. 

In both experiments no biologically relevant increase of mutants was found after treatment with the 

test item with or without metabolic activation. No dose-response relationship was observed. 7,12-

dimethylbenz(a)anthracene (DMBA) and ethylmethanesulfonate (EMS) were used as positive controls 

and showed distinct and biologically relevant effects in mutation frequency. Under the conditions of 

these two tests, the test substance is considered to be non-mutagenic in the HPRT locus of V79 

Chinese hamster cells. 

Mammalian Micronucleus Mutagenicity Test

A mammalian micronucleus test of murine peripheral blood cells with C8-C10 was conducted by 

Wessels (2013, MRID 49537225) to investigate the potential of the test substance to induce 

micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse. After a dose 

range finding study, the following doses were selected, 2000 mg/kg/day the maximum tolerated dose 

(MTD), 1,000 mg/kg/day and 400 mg/kg/day. The animals treated with 400 and 1000 mg/kg/day 

showed no signs of systemic toxicity. The animals treated with 2000 mg/kg/day showed mild to 

moderate signs of systemic toxicity such as reduction of spontaneous activity, catalepsis, constricted 

abdomen, piloerection and half eyelid closure. For all dose groups, including positive and negative 

controls, 10000 polychromatic erythrocytes per animal were scored for incidence of micronucleated 

immature erythrocytes. The negative controls (44hr and 68 hr) were within the range of the laboratory 

control data. The mean values noted for the dose groups which were treated with the test substance 

(44 hr and 68 hr) were within the negative control data range. 

No biologically relevant increase of micronuclei was fond after treatment with the test substance in 

any of the dose groups evaluated. The nonparametric Mann-Whitney Test was performed to verity the 

results. No statistically significant increases/decreases (p<0.05) of cells with micronuclei were noted 

in the dose groups of the test item evaluated.

Cyclophosphamide (40 mg/kg/day) was administered i.p. as a positive control which induced a 

significant increase in micronucleus frequency. This demonstrates the validity of this assay. Based on 
Page 10 of 36

the evidence obtained under the conditions of this study, the test substance did not induce structural 

and/or numerical chromosomal damage in the immature erythrocytes of the mouse. The test substance 

is not mutagenic. 

Neurotoxicity – There were no data presented regarding neurotoxicity per se. However, there were 

no indications of neurotoxic effects in the negative findings in the functional observation battery 

(FOB) in the repeat-dose toxicity studies. The predictive modeling system DEREK Nexus (v 3.0) did 

not identify C8-10 glucamide as being potentially neurotoxic. The C8-10 molecule lacks the phosphate 

or carbamate functionality which is typically expected to induce neurotoxic effects. 

Immunotoxicity – A weight of evidence approach suggests the lack of concern regarding the potential 

for C8-10 to induce immunotoxicological effects. The glucamides in general do not induce delayedtype hypersensitivity responses which is demonstrated by the absence of sensitization potential in the 

guinea pig maximization tests. The data presented regarding standard toxicology endpoints (i.e. 

hematology organ weights macroscopic and microscopic pathology of immune organs) suggest 

minimal concern for Immunotoxicity from exposure to C8-10.

Metabolism – There were no metabolism study data presented. The submission notes that a combined 

analysis using “METEOR” for the prediction of metabolic fate and subsequent evaluation through 

DEREK (Nexus) for structural alerts, metabolites of toxicological significance are not believed to be 

expected. The submission states that C8-10 is expected to undergo enzymatic hydrolysis of the amide 

linkage catalyzed by fatty acid amide hydrolase. The resulting metabolites are meglumine, an amino 

sugar (normally derived from sorbitol) and fatty acids. Meglumine would be expected to be rapidly 

excreted in the urine and the fatty acids are metabolized via the general β-oxidation pathway to 

generate acetyl-CoA. The projected metabolism was evaluated using accepted in silico programs. In 

addition, data are available regarding absorption, distribution, metabolism and elimination (ADME) of 

a surrogate Glucamide (C12). These data indicate oral absorption of over 80% and dermal absorption 

of less than 1 % of the administered dose. The major route of excretion is via the urine.

Surrogate

Acute Oral Toxicity 

Holalagoudar (2014; MRID 49537204) reported the LD50 of 5000 mg/kg for Wistar Crl: WI(Han) rats 

from a single oral dose.

Decker (1991; MRID 49537205) reported “the acute oral toxicity” of E-4086.01 was reported to be 

“greater than 2000” mg/kg. It was not reported as an LD50.

Acute Dermal Toxicity

The acute dermal toxicity in the rabbit was evaluated by Baldrick and McRae (1991; MRID 

49537207). The hair was removed from the dorso-lumbar region of five male and five female New 

Zealand White rabbits equivalent to 10% of the body surface area. A single dose of 2 g/kg C12-C14

was applied and then covered with gauze and backed by a non-irritating dressing which was bound 
Page 11 of 36

around the body trunk. At the end of 24 hours, the dressing was removed and the treated area washed 

with warm water and blotted dry with absorbant paper. The animals were observed from 2 to 12 days. 

There were no signs of systemic reaction to the treatment. There was well defined erythema in all ten 

animals following removal of the dressings. After days 14 and 15 the skins showed minimal irritation 

and appeared normal at termination. The acute lethal dermal dose to rabbits was determined to be > 2 

g/kg bw (not stated as LD50).

Primary Skin Irritation

A primary skin irritation study on three New Zealand White rabbits (one female, two male) was 

conducted by Decker et al., (1991; MRID 49537211). The test was conducted according to OECD 

Test Guideline number 404 adopted 12 May 1981. A single dose of 0.5 g/animal was applied for four 

hours under a 100 cm2 occlusive patch where the hair had previously been removed with clippers. The 

test substance was 98 % pure C10-C16. After four hours the patch was removed and the skin was 

flushed with luke-warm tap-water. Observations were conducted a 1, 24, 48, 72 hours and 7 and 14 

days after removal of the patch. Local signs (mean values from 1 hour to 14 days) consisted of grade 

0.78 erythema and grade 0.39 edema. They were reversible within 14 days. No corrosive effect 

occurred on the treated skin of any animal. Under the conditions of this experiment, C10-C16 was 

found to cause a primary irritation score of 1.5 when applied to intact rabbit skin. Thus, the test article 

is classified as not being an irritant to rabbit skin.

Eye Irritation

An eye irritation study (Liggett and McRae, 1991; MRID 49537213) was conducted using three New 

Zealand White rabbits. The test substance was C10-16. One eye of each of two rabbits received 6.3 mg 

directly onto the corneal surface, the other eye of each rabbit remained untreated. A third rabbit 

received a single dose of 4.6 mg placed onto the cornea of one eye. Treated eyes were examined 1, 2, 

3, 4, 7, 14, 21, 28 and 35 days after treatment. Scoring was according to the Draize method of 

appraisal. Corneal opacities were present in two animals the day following instillation. An opacity 

was still evident in one animal 35 days after treatment. It resolved 14 days after treatment in the other 

animal. Vascularisation of the corneal epithelium was recorded in one animal 14, 21, 28 and 35 days 

after instillation. Iridial inflammation was seen at Day 3 in one animal and for the first four days in a 

second animal. Transient mild conjunctival inflammation only was observed in the remaining animal. 

All conjunctival reactions had resolved 7, 14 or 35 days after treatment. The study authors concluded 

that under the conditions of the study, C10-16 is moderately irritating to the rabbit eye.

Skin Sensitization

Another skin sensitization study was conducted by Ullman et al. (1991; MRID 49537215) using the 

modified Beuhler method. Ten male and female albino guinea pigs (GOHI, SPF-quality = Himalayan 

spotted) were tested, five male and female guinea pigs were untreated and served as controls. The test 

substance was identified as C10-C16 with a physical state of being a white gel of 45 % purity for the test 

substance. Hair was closely clipped from the dorsal aspect of the animals. Approximately 3 ml of 

10% test material was applied with a spatula and then quickly covered with a cloth patch which was in 

turn covered with a rubber dental dam and the animals were restrained for 6 hours. After the exposure 

the dams and patches were removed and the skin flushed with lukewarm tap-water and padded dry. 
Page 12 of 36

Responses were graded at 12 hours and 24 hours post-treatment. According to the European 

Economic Community classification system in Guideline B3/457 16 SEPT 1983, the test article is 

considered not to be a sensitizer to this guinea pig strain.

Bouds (1999; MRID 49537216) conducted a dermal sensitization study with Hartley-derived guinea 

pigs and followed the same basic protocol as outlined above. The potential for dermal sensitization 

from exposure to the test article C10-C16 was evaluated using ten male and 10 female guinea pigs. The 

test animals received intradermal injections of 5 % w/v of the test substance in distilled water along 

with injections of Freund’s Complete Adjuvant (FCA) and the test substance in FCA. One week later, 

the test animals received a topical application of 25 % w/v test substance C10-C16 in distilled water. 

Challenge and re-challenge control animals received similar intradermal and topical treatments except 

distilled water was used in place of the test substance. Following a two-week rest period, a challenge 

was performed whereby the nineteen test and ten previously untreated (naïve) challenge control guinea 

pigs were topically treated with 5 % w/v test substance in distilled water. One female (animal number 

7838/F) was found dead on study day 16. The cause of death was not considered a result of test 

treatment. Challenge responses in the test animals were compared with those of the challenge control 

animals. Following a seven-day rest period, a re-challenge was performed whereby the nineteen test 

animals and ten previously untreated (naïve) re-challenge control animals were topically treated with 1 

% w/v test substance in distilled water. Re-challenge responses in the test animals were compared 

with those of the re-challenge control animals. Based on the results of this study, the test substance 

produced a 10 % (2/19) sensitization rate at re-challenge versus a clean control thus was classified as a 

non-sensitizer in guinea pigs (according to European Union labeling regulations (Annex VI of the 

Council Directive 67/548/EEC). 

In a 28-day oral toxicity study (Schulze, 1991; MRID 49537218) D-Glucitol, 1-deoxy-1-

(methylamino)-, N-C8-10 acyl derivs was administered by gavage to five groups of 10 male and 10 

female Crl:CDF F344 rats/group at 0, 10, 100 (mid-1), 500 (mid-2), and 1000 mg/kg/day for 28 

consecutive days.

During the study, 4/10 females were sacrificed in extremis at the high dose and five males and three 

females in the high dose groups were found dead (most during Week 1). The first death was a female 

on Day 3 and the last death was a male on Day 30. Only two high dose females survived to terminal 

sacrifice, therefore minimizing the effectiveness of statistical analysis. Several treatment-related 

clinical findings were observed, primarily associated with direct irritating effects of the test material. 

Salivation after dosing was observed beginning on Day 1 in all animals at the mid-2 and high doses. 

Wheezing and/or dyspnea were observed sporadically in the mid-2 and high dose groups beginning on 

Day 1. Statistically significant differences (relative to control values) in mean clinical pathology 

parameters were generally limited to the mid-2 and high dose groups and were considered to be 

secondary to decreased food consumption and body weight. ALT levels were increased (p≤0.05) at the 

mid-2 (37.0% in males, 29.7% in females) and high (119.6% in males, 146.0% in females) dose levels. 

Alkaline phosphatase was increased in females at the mid-2 (16.4%) and high doses (24.3%). No 

microscopic correlates were observed for these findings. No statistically significant differences were 

noted in urinalysis parameters in either sex. Average body weight was statistically significantly 

decreased in the mid-2 (9.2%-13% in males; 9.8-11% in females) and high dose (20.3-27.4% in males; 

11.5-13.5% in females) groups in a dose-dependent manner beginning at Week 1. Average body 

weight gains were also decreased (p≤0.05) in the mid-2 (32.9% in males; 31% in females) and high-
Page 13 of 36

dose (84% in males; 55% in females) groups. Hematological changes included a decrease (p≤0.05) in 

lymphocytes in males at the high dose (57%) which correlated with microscopic changes in the 

thymus. At the mid-2 dose, lymphoid depletion was observed in 1/10 males and 3/10 females. One 

high dose female exhibited moderate anemia accompanied by an erythrocytic regenerative response, 

and lymphocytosis with a minimal left shift in neutrophils. The other high dose female exhibited mild 

lymphopenia. These findings were consistent with the presence of inflammatory lesions and focal 

hemorrhaging in the stomach in the mid-2 and high dose groups. Absolute stomach weights were 

increased (p≤0.05) in both sexes at the mid-2 (24.8% in males; 29.1% in females) and high (30.7% in 

males; 43.0% in females) doses, as were relative (to body weight) stomach weights (38.4% in males 

and 38.6% in females at the mid-2 dose; 74.8% in males and 59.9% in females at the high dose) and 

relative (to brain weight) stomach weights (25.1% in males and 12.5% in females at the mid-2 dose; 

36.0% in males and 24.7% in females at the high dose). Decreases (p≤0.05) in absolute thymus 

weights (26.3-38.9% in males; 44.2-47.4% in females) and relative (to brain weight) thymus weights 

(29.2-50.6% in males; 36.3-44.2% in females) were observed at the mid-2 and high doses, and thymus 

to body weight was decreased (p≤0.05) in mid-2 and high dose females (36.7-41.8%). The primary 

treatment-related gross lesions were found in the stomach and were consistent with direct-acting 

irritant effects of the test material. Thickened and/or rough mucosa in the nonglandular region of the 

stomach was observed in three female and six male animals in the high dose group and seven male and 

four female animals in the mid-2 dose group. A dark area in the nonglandular region of the stomach 

was observed in three animals (one low dose female, one mid-2 and one high dose male). The 

nonglandular stomach of all animals in the mid-2 and high dose groups demonstrated acanthosis, and 

parakeratosis was also observed at the mid-2 (9/10 males, 3/9 females) and high (10/10 males, 8/10 

females) doses. Varying incidences of acute inflammation, ballooning degeneration of surface 

epithelium, erosion, ulceration, and focal hemorrhage were noted at the two highest doses. 

Additionally, an increased number of goblet cells and/or mucus on the mucosal surface of the 

glandular region of the stomach was observed in seven mid-2 and four high dose males and in three 

mid-2 females. Microscopic changes in the thymus included necrosis at the high dose (2/9 males, 5/10 

females) and lymphoid depletion at the mid-2 (1/10 males, 3/9 females) and high (7/10 males, 5/10 

females) doses. All animals examined (except two high-dose females found dead or moribund) 

demonstrated peribronchial/perivascular lymphoid infiltration with or without alveolar macrophages. 

Two males and three females at the high dose and one mid-2 female exhibited necrosis of tracheal 

epithelium with acute inflammation. Focal hemorrhage was present in the lungs of three of the 

affected rats. Respiratory effects were attributed to inadvertent aspiration or instillation of the test 

material into the trachea.

The LOAEL for C10-C16 in Fischer 344 rats was 500 mg/kg/day in both sexes based on gross and 

microscopic findings in the stomach and thymus. The NOAEL was 100 mg/kg/day in both sexes.

13-Week Oral Toxicity Study

In a 13-week oral toxicity study, (Isaacs, 1994; MRID 49537219), C12-C14 was administered by 

gavage to five groups of 10 male and 10 female HanIbm: WIST (SPF) rats/group at 0, 10, 50, 200, and 

500 mg/kg/day for 13 weeks (main group). An additional ten male and ten female rats per dose level 

were administered the test material and kept for a 28-day recovery period prior to sacrifice and 

necropsy (recovery group). Histopathology was conducted on tissues from rats in the control and high 
Page 14 of 36

dose groups as part of the original study (1991). A follow-up pathology study (1994) was conducted to 

examine respiratory tract tissues. This examination was more comprehensive than the original 

pathology study, since respiratory tissues from the control and all four treatment groups were included.

Dose-related increases in the incidence and severity of respiratory clinical signs (rales, dyspnea, and 

labored respiration) were observed. Rales were most prominent with incidences of 2/10, 3/10, and 

17/20 at 50, 100, and 500 mg/kg/day, respectively in males, and 0/10, 5/10, and 11/20, in females. 

Rales were observed at the high dose beginning Week 4 in both sexes and dyspnea was observed early 

as Week 2. Ruffled fur was a common finding among all animals at the high dose beginning Week 4. 

These clinical signs at the high dose persisted only into the first week of the recovery period. There 

were eight unscheduled (premature) mortalities during the study. These included 4/20 males and 2/20 

females at the high dose between Days 27 and 91 (of these, intubation error was the cause of death for 

one male and one female, leaving four unexplained mortalities). In addition, one male at the low dose 

and one male at the mid-high dose died of intubation errors.

Body weight was statistically less in males at the mid-high (beginning Week 9) and high dose 

(beginning Week 2). At the end of the treatment period, body weight in males was 7% lower at the 

mid-high dose and 12% lower at the high dose and the respective weight gains were -14% and -26%. 

At the end of the 4-week recovery period, body weight in males at both of these doses was 6% to 7% 

lower, but the differences were not statistically significant. Food consumption was statistically lower 

at the high dose in males for Week 2 (-17%), and was statistically lower by 9% to 15% during weeks

5-10. In females, food consumption was significantly lower by 13% at the high dose for Week 2, but 

closely tracked with controls thereafter. During the recovery period food consumption was similar to 

controls in both sexes at all dose levels.

Relative (to body weight) food consumption was statistically lower at the high dose during the first 

week of treatment in males (-11%) and females (-16%). Both sexes at the high dose were generally 

similar to controls thereafter. Slight, but statistically significant, increases in hematocrit and RBCs in 

both sexes at the high dose indicated some shift in fluid balance (not biologically significant). No 

treatment-related findings were observed in the clinical chemistry results or in ophthalmology 

examinations. The overnight mean urinary output in the main group was 43% higher in males and 

63% higher in females at the high dose (p≤0.01). 

Several organ weight parameters at the high dose (main group, but not the recovery group) were 

observed that reflect treatment-related stress and adaptation by the animals. For example, the 

adrenal:body weight ratio was elevated in main group males by 22% relative to controls; the absolute 

and relative liver weight in females was higher by about 30%. No histological correlates were 

observed in these organs. No treatment-related macroscopic findings were observed in animals that 

survived to terminal sacrifice. In main group males, a total of 7/10 animals (including all four 

decedents) at the high dose and 1/10 at the mid-high dose were observed with lesions in the nasal 

cavity. The lesions were generally widespread, but large areas of affected epithelia (respiratory, 

transitional, and olfactory) were unaltered, an observation that led to the conclusion that test material 

entered the nasal cavity during dosing and caused direct adverse effects (as opposed to those effects 

being caused by systemic toxicity). The types of lesions included acute inflammation, epithelial 

degeneration/regeneration, and focal squamous metaplasia. Typically, these lesions at the high dose 

were slight to moderate, except for epithelial degeneration which was moderate to severe. The one 
Page 15 of 36

lesion observed at the mid-high dose in males (focal fused turbinates) was minimal. In females, a total 

of 6/10 animals (including both decedents) at the high dose and 3/10 at the mid-high dose were 

observed with similar types of lesions in the nasal cavity as males and with similar dose-dependent 

severity (test material concentrations increased with dose as the dosing volume was held constant). 

The incidence and severity of nasal cavity lesions in the recovery groups of both sexes were somewhat 

lower, although 3/10 males were affected at the mid-high dose, while only one was affected from the 

main group. Bedding material was observed in the nasal cavity of one control male from the recovery 

group and in one high dose female from the main group, showing that the nasal lesions were not 

caused by inhalation of bedding material. No treatment-related findings in the nasal cavity were seen 

in either sex at the low and mid-low dose levels. No findings were observed in the larynx or trachea of 

the control and high dose animals, and none was observed in the decedents. The lungs of animals that 

survived to terminal sacrifice were generally unremarkable. In the original pathology report, no 

treatment-related lesions were observed in organs other than those of the respiratory tract.

The LOAEL for C12-C14 was 500 mg/kg/day in both sexes of Wistar rats based on mortality, 

body weight effects, and the clinical observation of ruffled fur. The NOAEL was 200 mg/kg/day 

in both sexes.

Prenatal Developmental Toxicity

In a developmental toxicity study (Saylor, 1991; MRID 49537221), C10-16 was administered to 25 

female Crl:CD VAF/Plus® rats/dose by gavage in deionized water at dose levels of 0, 15, 150, or 363 

mg/kg/day (constant dosing volume of 10 mL/kg) on days 6 through 15 of gestation. On gestation day 

(GD) 20, the females were sacrificed and the fetuses removed by cesarean section. The evaluated 

parameters included clinical signs, mortality, body weight, body weight gain, embryo-fetal death, and 

fetal body weight. All fetuses were examined for external malformations and variations; half of all 

fetuses were examined for visceral malformations and variations, and the remaining half were 

examined for skeletal malformations and variations. 

No mortalities occurred during the study. Increased salivation was observed post-dosing in all females 

of the high-dose group on one or more occasions (starting on GD 6). Material around the mouth 

and/or nose and decreased activity were observed post-dosing in 4/25 and 2/25, respectively, of the 

females of the high-dose group. Post-dosing salivation was also seen in 5 mid-dose females, on 1-2 

occasions each. There were no observations of post-dosing salivation in control or low-dose animals. 

Although mean absolute body weights were similar among the groups, females of the high-dose group 

did not gain weight during the first three days of the treatment period (0 g vs. +5 g for controls 

(p<0.05). Body weight gain in the high-dose group over the duration of the treatment period was 

decreased by 32%, compared with controls (p<0.01). The adjusted (for gravid uterus) GD 0-20 body 

weight gain for females in the high-dose group was decreased by 11%, compared with controls (n.s.). 

Although treatment-related effects (post-dose salivation and decreased body weight gain) were 

observed, there was no indication that the effects were adverse. Therefore, the maternal LOAEL is 

not established. The maternal NOAEL is 363 mg/kg/day.

There were no treatment-related effects on developmental parameters. The developmental LOAEL 

is not established. The developmental NOAEL is 363 mg/kg/day.
Page 16 of 36

The developmental toxicity study is classified Unacceptable/Guideline and satisfies the guideline 

requirement for a developmental toxicity study (OCSPP 870.3700; OECD 414) in rats. Based on the 

absence of maternal systemic toxicity and/or developmental effects, it is not clear that dose selection 

was appropriate. The OCSPP 870.3700 requirement is that the highest dose level should be chosen 

with the aim of causing toxic effects without inducing death or severe suffering, or the highest dose 

should be set at 1000 mg/kg/day. In this study, the highest dose was less than the limit dose and did 

not result in maternal systemic toxicity. The study may be ungraded if the results of the range-finding 

study are reviewed and the dose selection for this study found to be appropriate. 

Reproduction Toxicity

York (2000; MRID 49537222) conducted a study designed to provide information concerning the 

effects of the test substance C10-C16 on the male and female reproductive systems in Crl:CD®(SD)IGS 

BR VAF/Plus® rats. Evaluations included gonadal function, estrous cycles, mating behavior, 

conception, parturition, lactation, weaning and the growth and development offspring. The study also 

provides information regarding neonatal morbidity, mortality and preliminary data on potential 

developmental toxicity.

One hundred male and female rats were randomly assigned to four dosage groups (Groups I through 

IV), 25 rats per sex per dose group. The test substance and the vehicle (processed deionized water), 

was administered orally, via gavage, one time daily beginning 70 days before sacrifice at doses of 0 

(vehicle), 15, 150 and 350 mg/kg/day respectively. 

All P generation rats were observed for viability at least twice each day of the study. The rats were 

also examined for clinical observation of effects of the test substance, abortions, premature deliveries 

and deaths daily before and approximately one hour after administration. Body weights were recorded 

daily during dosage period and at sacrifice. Feed consumption values for male rats were recorded 

weekly until cohabitation and weekly during the post-cohabitation period. Feed consumption values 

for female rats were recorded weekly until cohabitation, on gestation day (DG) 0, 6, 10, 15, 18, 20 and 

25 (if necessary) and on lactation day (DL) 1, 4, 7, 10 and 14. Because pups begin to consume 

maternal feed on or about DL 14, feed consumption values were not tabulated after DL 14. 

No P (parental) generation male rats died as a result of treatment with C10-C16. Clinical observation 

considered test substance-related in male rats in the 150 and 350 mg/kg/day dose groups included 

excess salivation, rales, chromorhinorrea, a red or dried red perioral substance and chromodacryorrhea 

in the 350 mg/kg/day only. Reduced body weight gains in the 350 mg/kg/day dose group were 

considered related to the test substance. Absolute and relative feed consumption values were 

unaffected by dosages as high as 350 mg/kg/day. Totals of 24 (96.0 %), 25 (100 %), 21 (100 %) and 

25 (100 %) male rats mated. Dosages of the test substance as high as 350 mg/kg/day did not affect the 

fertility index, mating index, precoital index or the number of male rats that mated in the first or 

second week of cohabitation. 

All necropsy observations were considered unrelated to the test substance. Terminal body weights 

were significantly reduced in the 350 mg/kg/day dose group. No biologically significant differences 

occurred among the four dose groups for weights of epididymides, left cauda epididymis and testes, 
Page 17 of 36

seminal vesicles, pituitary and brain or the ratios of these organ weights to the terminal body weights 

or brain weights. No statistically significant or biologically significant differences occurred in the 

number or the percentage of motile sperm, the number of nonmotile sperm and the sum of the motile 

and non-motile sperm.

No parental generation female rats died as a result of treatment with the test article. Clinical 

observations considered test article related during the precohabitation, gestation and lactation periods 

included excess salivation and rales in the 150 and 350 mg/kg/day dosage groups. Average body 

weights, body weight gains and absolute and relative feed consumption values during the 

precohabitation period were comparable among the four dose groups. Maternal body weight gains 

and absolute feed consumption values were significantly reduced in the 350 mg/kg/day dose group for 

the entire gestation period. Although absolute maternal body weights were reduced or significantly 

reduced in the 350 mg/kg/day dose group on each day of the lactation period, maternal body weight 

gains were increased over the vehicle control group value for the entire lactation period. Absolute and 

relative feed consumption values during the lactation period were comparable among the four dose 

groups. 

Doses as high as 350 mg/kg/day did not affect estrous cycling or natural delivery and litter parameters. 

All female rats were mated. Pregnancy occurred in 23 (92 %), 23 (92 %), 21 (100 %) and 22 (88 %) 

female rats in the four respective dose groups. Terminal body weights were unaffected by doses as 

high as 350 mg/kg/day. The weights of the pituitary, brain, left and right ovary and uterus and the 

ratios of these organ weighs to the terminal body weight or absolute brain weight of parental 

generation female rats were comparable among the four dose groups and did not differ significantly. 

Natural delivery and litter parameters were unaffected by doses of the test material as high as 350 

mg/kg/day. 

All clinical and necropsy observations in the F1 generation pups were considered unrelated to the test 

substance. There were no test substance-related microscopic changes observed in the brain, pituitary 

or reproductive tissues of male or female rats in the 350 mg/kg/day dose group. 

Based upon the data and findings in this study, the no observable adverse effect level (NOAEL) for the 

test substance is 15 mg/kg/day. The 150 and 350 mg/kg/day dose groups caused adverse clinical 

observation and the 350 mg/kg/day dose group caused reduced body weight gains and slight 

reductions in feed consumption values. The reproductive and developmental NOAEL is greater than 

350 mg/kg/day. No adverse effects on fertility or development occurred at the highest dose tested 

(350 mg/kg/day). 

Mutagenesis Assay

Bigger and Clarke (1991, MRID 49537226) conducted a L5178Y TK+/- mouse lymphoma 

mutagenesis assay with the test article C10-C16 in the presence and absence of Aroclor induced rat 

liver S9. The non-activated cultures selected for cloning in the initial assay were treated with doses of 

2.3 to 36 μg/ml and exhibited Total Growths from 16% to 93%. The S9 activated cultures selected for 

cloning in the initial assay were treated with doses of 2.3 to 50 μg/ml which produced from 18% to 

107% Total Growths. 
Page 18 of 36

In the confirmatory assay, the non-activated cultures selected for cloning were treated with doses of 

2.3 to 32 μg/ml and exhibited Total Growths from 10% to 106%. The S9 activated cultures selected 

for cloning in the confirmatory assay were treated with doses of 13 to 45 μg/ml which produced from 

12 to 109% Total Growths. 

None of the non-activated cultures that were cloned exhibited a mutant frequency which was at least 

twice the mean mutant frequency of the solvent controls. A dose-dependent response was not noted in 

the treated cultures. None of the S9 activated cultures that were cloned exhibited a mutant frequency 

which was at least twice the mean mutant frequency of the solvent controls. A dose-dependent 

response was not noted in the treated cultures. Therefore under the conditions of this study the test 

material was negative in both the presence and absence of exogenous metabolic activation. 

Cytogenicity

An in vivo rat bone marrow cytogenicity study was conducted by Putman and Young (1991, MRID 

49537227). Male and female Sprague-Dawley rats were treated with the test article C10-C16

administered by a single oral gavage dose in 20 ml/kg of vehicle (water). Males received doses of 

180, 600 or 1800 mg/kg and females received a single dose of 210, 700 or 2100 mg/kg/day. Bone 

marrow cells arrested in metaphase and collected 8 and 12 hours after treatment, were examined 

microscopically for structural chromosome aberrations. No statistically significant increase in 

percentage of aberrant cells were observed in the test article treated groups, regardless of sex or one 

marrow harvest time. Under the conditions of this study the test article did not induce chromosomal 

aberrations in bone marrow cells of male or female rats. 

V. TOXICITY ENDPOINT SELECTION 

The toxicological endpoint selected for use in risk assessment is taken from the

reproduction/developmental toxicity screening study in the rat. In this study, no toxicological effects 

are observed up to 312.5 mg/kg/day. The lowest NOAEL (250 mg/kg/day) in the database is observed 

in a 28 day oral toxicity study in the rat. The LOAEL is 500 mg/kg/day based on mortality, 

microscopic findings in the GI tract, trachea, lung, spleen and bone marrow. Since similar effects are 

not observed in the reproduction/developmental toxicity screening study in which treatment occurred 

for 54 days, it was concluded that the lower NOAEL (250 mg/kg/day) is simply due to dose spread. 

Therefore, the higher NOAEL (312.5 mg/kg/day) is selected for risk assessment. The standard 

uncertainty factors (100x) are applied for intra-and interspecies variation and an additional uncertainty 

factor (3X) is applied to account for extrapolation from subchronic to chronic exposures. Dermal and 

inhalation absorption are assumed to be 100 %. 

VI. 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 

postnatal 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 
Page 19 of 36

concludes that the10X FQPA safety factor should be retained for D-glucitol for the following 

reasons:

The database is considered adequate for FQPA assessment. The following acceptable 

studies are available:

A Reproduction/Developmental study in rats

A Prenatal Developmental Toxicity study in the rat

A Reproduction Study in the rat

i. Fetal susceptibility was not observed in the reproduction/developmental toxicity screening test

in the rat. Neither parental, developmental, nor reproduction toxicity were observed at doses up 

to 312.5 mg/kg/day. No susceptibility was seen in the developmental toxicity study in rats at 

doses up to 300 mg/kg/day; the highest dose tested.

ii. There were no data specific to neurotoxicity. However there were no indications of neurotoxic 

effects in the functional observation battery tests in the 28 day oral toxicity study in the rat.

iii. Immunotoxicity studies were not available for review. However evidence of potential 

immunotoxicity was observed in the 28 day oral toxicity study in the rat. In this study, atrophy 

is seen in the spleen and bone marrow at 500 mg/kg/day. These effects will be protected since 

the established chronic reference dose (cRFD) is 1.04 mg/kg/day. 

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 of exposure via pesticide use and via exposure through food and 

water, the Agency reduced the FQPA safety factors for assessing risk to infants and children to 3X.

The toxicological database for D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives is 

considered adequate.

VII. EXPOSURE

Based upon information provided in the submission, human exposures are expected from several

sources. The general public may be exposed via residues that may exist on treated crops. The Agency 

has conducted a “screening level” assessment of hypothetical exposures and risks based on typical 

end-use product information. The Agency’s level of concern is for Margins of Exposure < 300. The 

estimated screening level MOEs (assuming 100 % absorption via the dermal and inhalation routes) are 

> 300 and do not exceed the Agency’s level of concern.

Finally, human exposure is expected to agricultural workers involved primarily in the preparation and 

delivery of pesticide applications in agricultural settings, in this case sprays as opposed to dusts or 

granules etc. 
Page 20 of 36

Dietary exposure -

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 

Ingredient Dietary Exposure Evaluation Model 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 312.5 mg/kg/day. The uncertainty factor of 300 (10x 

for intraspecies variability and 10x for inter species extrapolation and 3X for subchronic to chronic 

extrapolation) 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 0.50% 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 14.6 % of the cPAD. The chronic dietary risk estimate for the highest exposed 

population subgroup, children 1-2 years old, is 54.4 % of the cPAD. It is important to note that the 

Inert Ingredient Dietary Exposure Model assumes a default value of 100 ppb for the concentration of 

the inert in all sources of drinking water. Based on the physical and chemical properties of this 

chemical and the intended use pattern, exposure through drinking water is unlikely; therefore, these 

results are highly conservative in regards to the exposure through drinking water. 

The proposed use of this chemical as an inert ingredient in food-use pesticide product formulations is 

40%. Using the Inert Ingredient Dietary Exposure model to estimate the exposure to all 

subpopulations (see the attachment), it was determined that the exposure from the use of this inert 

ingredient at the proposed concentration (including exposure through drinking water) would result in 

acceptable exposure to all subpopulations. 
Page 21 of 36

Table 3.0

Summary of Dietary (Food and Drinking Water) Exposure and Risk for CAS 1591782-62-5 

Results Taken from I-DEEM Model

Population Subgroup

Acute Dietary

(95th Percentile)

Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

General U.S. Population

No acute endpoint selected

0.151893 14.6

All Infants 0.316622 30.4

Children 1-2 years old 0.565597 54.4

Children 3-5 years old 0.389016 37.4

Children 6-12 years old 0.200810 19.3

Youth 13-19 years old 0.108143 10.4

Adults 20-49 years old 0.116210 11.2

Adults 55+ years old 0.122555 11.8

Females 13-50 years old 0.117539 11.3

The most highly exposed subgroup is bolded. 

Residential Pesticide Handler Exposure. 

Residential pesticide handler exposure is estimated using Standard Operating Procedure derived by the 

Science Advisory Council for Exposure (ExpoSAC), Health Effects Division/OPP. The algorithm 

used to estimate exposure is: 

Unit Exposure * Application rate * Units Treated ÷ Body weight

Factors used in residential exposure assessment:

Assumed product density 9.0 lb gal.

Assumed 5.0% of formulation = inert. RD reviewed a number of residential product labels –

solvents typically comprised 1.0-5.0 % of the product formulation.

Assumed typical rate of application 3 fl oz formulation per gallon of finish spray

5 gallons spray per day applied to typical 1⁄2 acre lot from HED SOP

Body weight 80 kg from HED SOP

Dermal and inhalation absorption 100 %

Unit Exposures from Standard Operating Procedures for Residential Pesticide Exposure Assessment 

Health Effects Division/ OPP January 2012. 

Toxicological Endpoint NOAEL 312.5 mg/kg/day 

Margin of Exposure = NOAEL mg/kg/day ÷ Average Daily Dose mg/kg/day. Since the same 

toxicological endpoint is used for dermal and inhalation exposure and was identified from the same 

study, the dermal and inhalation exposures are summed prior to dividing into the NOAEL. HED 

SOP.
Page 22 of 36

9 lb/gallon formulation * 0.05 (per cent inert) = 0.45 lb inert/gallon formulation

0.45 lb inert/gal formulation ÷ 128 fl oz /gal formulation = 0.0035 lb inert/fl oz

3 fl oz/gallon finish spray * 0.0035 lb inert/ fl oz = 0.0105 lb inert per gallon finish spray

For five gallons finish spray per day = 0.0525 lb inert per day

Margin of Exposure = NOAEL/Average Daily Exposure (dermal and inhalation exposures are 

summed prior to division into the NOAEL).

Table 4.0 Estimated Residential Pesticide Handler (Outdoor Mixer/Loader/Applicator) Exposure and 

Risk

Table 5.0 Estimated Residential Handler Indoor Exposures and Risks

For the mopping scenario, it was assumed that 1 gallon of diluted solution is used. RD assumes that 

cleaning products are assumed to have the same density as water (8.34 lbs/gallon). While typical product 

concentrate directions indicate that 1 oz concentrated product per 1 gallon of water should be used, RD 

followed the Antimicrobials Division SOP and assumed a dilution factor of 2 oz concentrated product/128 

oz (1 gallon) of water for the residential handler risk assessment to represent heavy-duty cleaning 

formulations. Based on information from RD, the Agency assumed that the maximum percentage by weight 

of the inert ingredient in indoor products would be 5.0%.

1 gallon formulated pesticide solution * (8.34 lb/gal) * (5.0%) * (2 fl oz/128 fl oz dilution factor) =0.0065 lb inert in formulated solution/ day

For wiping scenario 

0.13 gallon formulated solution* (8.34 lb/gal) * (5.0%) * (2 fl oz/128 fl oz dilution factor) = 0.00085 lb inert in formulated solution/ day

For trigger pump spray

Mixer/loader/

applicator

Unit Exposure

mg/lb handled

Application

Rate lb/gal

Units Treated

gal/day

Body weight

kg

Average Daily

Dose mg/kg/day

Margin of 

Exposure

Hose end

 sprayer

Dermal 13.4

Inhal. 0.022

0.0105

lb/gal

5 gal/day

to treat

1⁄2 acre

typical 

lot

80 kg Derm 0.0088

Inhal 0.0000144

35,450

Pump-up handheld sprayerDermal 63

Inhal 0.018

Derm 0.041

Inhal 0.0000118

7,619

Backpack

sprayer

Dermal 130

Inhal 0.14

Derm 0.085

Inhal 0.000092

3,672

Mixer/loader/

applicator

Unit Exposure

mg/lb handled

Amount (lbs)

Handled/day

Body weight

kg

Average Daily

Dose mg/kg/day

Margin of 

Exposure

Mopping Dermal 71.6

Inhal. 2.38

0.0065 80 kg Derm 0.0058

Inhal 0.00019

54,000

1.6M

Wiping Dermal 2870

Inhal 67.3

0.00085 Derm 0.0304

Inhal 0.00072

10,300

43,400

Trigger pump 

spray

Dermal 220

Inhal 2.4

0.05 Derm 0.14

Inhal 0.0015

2230

208,300
Page 23 of 36

0.13 gallon formulated solution* (8.34 lb/gal) * (5.0%) = 0.00085 lb inert in formulated solution/ day

RESIDENTIAL and RECREATIONAL POST-APPLICATION EXPOSURE

Table 6.0 Summary Recreational and Residential Post-Application Exposures and Risks

Activity Exposure (Dose)

mg inert./kg/day

MOE

Toddler short-term oral hand to mouth 

from contacting treated turf

0.018 17,361

Toddler oral object to mouth 

(turfgrass)

0.0011 284,000

Adult dermal post applic turf contact 0.246 1,270

Child dermal post applic turf contact 0.17 1,838

Adult golfer post app turf contact 0.0274 11,405

Child golfer post app turf contact 0.0465 6,270

Toddler combined exposure 0.189 = hand to mouth + object to 

mouth + turf post-application 

exposure

1,653

 MOE = NOAEL ÷ Dose. NOAEL = 110.0 mg inert/kg/day. 

Adult and Adolescent Golfer Post-Application Dermal Exposure may be estimated using the 

convention stated in Science Advisory Council for Exposure draft SOP regarding “Golfer Exposure 

Assessment For Adults and Children” (24 August 2000). The draft policy states that adult and 

adolescent golfer dermal post-application exposure may be calculated as DE(t) (mg a.i./kg bw/day) = 

(TTR(t) (μg/cm2)) * TC (cm2/hr) * hr/day ÷ (CF (1000 μg/mg)) * BW (body weight (kg)) Where:

DE(t) = dermal exposure at time (t) attributable to golfing on previously treated turf (mg a.i./kg 

bw/day).

TTR(t) = turf transferable residue at time t (μg/cm2)

TC = Transfer Coefficient (500 cm2/hr)

hr = exposure period (4 hours)

CF = conversion factor to change μg to mg.

BW = body weight (kg) (80 kg for adult; adjusted (multiplied) by a factor of 1.7 for child golfers) 

and where TTRt = AR * F * (1-D)t * CF2 * CF3
Page 24 of 36

AR = application rate (lb inert/acre); 0.105 lb ai/acre (taken from Table 4.0 above where 

 0.0525 lb is applied to 1⁄2 acre) 

DA = Dermal absorption 100%

F = fraction of inert available on turf/grass (unitless); 5% 

D = fraction of residue that dissipates daily (unitless); 10

t = postapplication day on which exposure is being assessed;

CF2 = weight unit conversion factor to convert the lbs ai in the application rate 

to use for the DFR or GR value (4.54E+8 μg/lb)

CF3 = area unit conversion factor to convert the surface area units (acre) in the 

application rate to cm2 for the TTR or GR value (2.47E-8 acre/cm2 ) 

Therefore, 0.105 lb ai/A * 0.05 (%) * 4.548 μg/lb * 2.47-8 A/cm2 = 0.68 μg/cm2

DE = 0.68 μg/cm2 * 500 cm2/hr * 4 hr/day * 0.001μg/mg ÷ 80 kg bw = 0.017 mg inert/kg /day. 

MOE for adult golfer is 312.5 mg a.i./kg bw/day ÷ 0.017 mg inert/kg bw/day = 18,382.

The adult dose level is adjusted by a factor of 1.7 to estimate child golfer exposure therefore 0.017 mg 

inert./kg/day * 1.7 = 0.0289 mg inert/kg/day. 

MOE for child golfer is 312.5 mg inert/kg/day ÷ 0.0289 mg inert/day = 10,813.

A MOE of 300 is adequate to protect golfers from dermal post-application exposures to treated golf 

course turf. Inhalation exposure is believed to be negligible. The proposed use does not exceed the 

Agency’s level of concern.

Adult and child dermal post-application exposure to treated residential turf is assessed using 

SOP (2.2) which indicates that 

PDR = TTR * TC * ET * conversion factor μg to mg ÷ kg bw where:

Potential Dose Rate (PDR)

Turf Transferable Residue (TTR) (0.68 μg/cm2) 

TC = Transfer Coefficient (TC)(14,500 cm2/hr for adult and 5,200 cm2/hr for child)

ET = exposure time (hours/day) (2) 

CF = 0.001 mg/μg

Dermal absorption = 100%

Body weight = 80 kg for adult, 15 kg for toddler. 

0.68 μg/cm2 * 14,500 cm2/hr * 2 hr/day * 0.001 mg/μg ÷ 80 kg bw = 0.246 mg inert/kg/day for adult.

MOE = NOAEL ÷ Dose and 312.5 mg a.i./kg bw/day ÷ 0.246 mg a.i./kg bw/day = 1,270

0.246 μg/cm2 * 5,200 cm2/hr * 2 hr/day * 0.001 mg/μg ÷ 15 kg bw = 0.170 mg inert/kg/day for toddler

MOE = NOAEL ÷ Dose and 312.5 mg a.i./kg bw/day ÷ 0.170 = 1,838.
Page 25 of 36

Children’s short-term oral hand-to-mouth exposure = 

TTRt * SA * EX * FQ * ET * CF1 where:

PDRt = potential dose rate on day “t” (mg/kg bw/day)

TTRt = turf transferable residue on day “t” (μg/cm2 turf); 0.00056 μg/cm2

SA = surface area of the hand (cm2/event; palmer surface area of 3 fingers = 20 cm2

EX = extraction factor from the hand by saliva = 50 %

FQ = frequency of hand-to-mouth activity (events/hr); 20 events/hr

ET = exposure time (hr/day); 2 hrs/day

CF1 = weight unit conversion factor to convert μg in the TTR value to mg for the daily exposure 

(0.001mg/μg).

0.68 μg/cm2 * 20 cm2/event * 0.50 % extraction factor * 20 events/hr * 2 hr/day * 0.001 mg/μg ÷ 15 

kg bw = 0.018 mg inert/kg/day.

MOE = NOAEL ÷ Dose 312.5 mg inert/kg/day ÷ 0.018 mg inert/day = 17,361.

Children’s object-to-mouth (turfgrass) = Grt * IgR * CF1

PDRt = potential dose rate on day “t” (mg/kg bw/day)

GRt = grass (and plant matter) residue on day “t”; 0.00056 μg/cm2

IgR = mouthing rate of grass (cm2/day); 25 cm2/day

CF1 = weight unit conversion factor to convert μg units of residue on the grass to mg for the daily 

exposure (0.001mg/μg).

0.68 μg/cm2 * 25 cm2/day * 0.001mg/μg ÷ 15 kg bw = 0.0011 mg inert/kg/day

MOE = NOAEL ÷ Dose and 312.5 mg inert/kg/day ÷ 0.0011 mg inert/kg/day = 284,000.
Page 26 of 36

VIII. AGGREGATE EXPOSURE 

In estimating total dietary (food and drinking water) exposures to D-glucitol, 1-deoxy-1-

(methylamino)-, N-C8-10 acyl derivatives as an inert ingredient in pesticide formulations applied to 

growing crops the Agency uses the Dietary Exposures Evaluation Model – Food Commodity 

Intake Database (DEEM-FCID) model for chronic dietary exposures which presented as 

Attachment One. The DEEM analysis was conducted using the NOAEL noted earlier, 312.5

mg/kg/day, with the application of uncertainty factors (300X). 

1. In evaluating dietary exposure to the D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl 

derivatives, EPA considered exposures under the petitioned for exemptions from the requirement 

of a tolerance. EPA assessed dietary exposures as follows:

i. Acute exposure. No adverse effects attributable to a single exposure of D-glucitol, 1-deoxy-1-

(methylamino)-, N-C8-10 acyl derivatives were seen in the toxicity databases. Therefore, an acute 

dietary risk assessment for D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives is not 

necessary.

ii. D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives was not considered to be 

carcinogenic therefore cancer risk assessment was not conducted..

iii. Chronic exposure. In conducting the chronic dietary exposure assessment, EPA used food 

consumption information from the U.S. Department of Agriculture’s (USDA’s) 2003-2008 

National Health and Nutrition Examination Survey, What We Eat in America 

(NHANES/WWEIA). As to residue levels in food, no residue data were submitted for acetic acid. 

In the absence of specific residue data, EPA has developed an approach which uses surrogate 

information to derive upper bound exposure estimates for the subject inert ingredient. Upper 

bound exposure estimates are based on the highest tolerance for a given commodity from a list of 

high use insecticides, herbicides, and fungicides. 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. 

In the dietary exposure assessment, the Agency assumed 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 (if any) between the active and inert 

ingredient and that the concentration of inert ingredient in the scenarios leading to these highest 

levels of tolerances would be no higher than the concentration of the active ingredient. 

The Agency believes the assumptions used to estimate dietary exposures lead to an extremely 

conservative assessment of dietary risk due to a series of compounded conservatisms. First, 

assuming that the level of residue for an inert ingredient is equal to the level of residue for the 

active ingredient will overstate exposure. The concentrations of active ingredient in agricultural 

products are generally at least 50 percent of the product and often can be much higher. Further, 
Page 27 of 36

pesticide products rarely have a single inert ingredient; rather there is generally a combination of 

different inert ingredients used which additionally reduces the concentration of any single inert 

ingredient in the pesticide product in relation to that of the active ingredient. In the case of Dglucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives, EPA made a specific adjustment to 

the dietary exposure assessment to account for the use limitations of the amount of D-glucitol, 1-

deoxy-1-(methylamino)-, N-C8-10 acyl derivatives,acetic acid that may be in pesticide formulations 

(limited to no more than 40 % final pesticide formulation) present at the maximum limitation 

rather than at equal quantities with the active ingredient. 

Second, the conservatism of this methodology is compounded by EPA’s decision to assume 

that, for each commodity, the active ingredient which will serve as a guide to the potential level of 

inert ingredient residues is the active ingredient with the highest tolerance level. This assumption 

overstates residue values because it would be highly unlikely, given the high number of inert 

ingredients, that a single inert ingredient or class of ingredients would be present at the level of the 

active ingredient in the highest tolerance for every commodity. Finally, a third compounding 

conservatism is EPA’s assumption that all foods contain the inert ingredient at the highest 

tolerance level. In other words, EPA assumed 100 percent of all foods are treated with the inert 

ingredient at the rate and manner necessary to produce the highest residue legally possible for an 

active ingredient. In summary, EPA chose a very conservative method for estimating what level of 

inert residue could be on food, then used this methodology to choose the highest possible residue 

that could be found on food and assumed that all food contained this residue. No consideration 

was given to potential degradation between harvest and consumption even though monitoring data 

shows that tolerance level residues are typically one to two orders of magnitude higher than actual 

residues in food when distributed in commerce.

Accordingly, although sufficient information to quantify actual residue levels in food is not 

available, the compounding of these conservative assumptions will lead to a significant 

exaggeration of actual exposures. EPA does not believe that this approach underestimates 

exposure in the absence of residue data.

iii. Cancer. D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives is not expected to be 

carcinogenic therefore, a cancer dietary exposure assessment was not performed.

2. Dietary exposure from drinking water. For the purpose of the screening level dietary risk 

assessment to support this request for an exemption from the requirement of a tolerance for benzyl 

acetate a conservative drinking water concentration value of 100 parts per billion (ppb) based on 

screening level modeling was used to assess the contribution to drinking water for chronic dietary 

risk assessments for D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives. These values 

were directly entered into the dietary exposure model. The DEEM model indicates the RfD

(chronic population adjusted dose cPAD) is 1.04 mg/kg/day.

Aggregate Exposure for an Adult

0.1519 mg/kg/day the estimated dietary exposure to the “Total U.S. Population” (adult) is

7.3% of the cPAD

0.085 mg/kg/day = highest residential handler exposure
Page 28 of 36

0.246 mg/kg/day = post-application dermal exposure to treated lawn/turf

0.14 mg/kg/day = exposure from antimicrobial trigger pump spray

0.017 mg/kg/day = adult golfer post-applications exposure.

0.639 mg/kg/day thus 312.5 mg/kg/day ÷ 0.639 mg/kg/day = a Margin of Exposure 490 

Aggregate Exposure to Child age 1-2

0.5533 mg/kg/day the estimated dietary exposure to the most highly exposed subpopulation 

(toddlers 1-2 years) = 62.9% of the cPAD.

0.170 mg/kg/day = post-application dermal exposure to lawn/turf

0.018 mg/kg/day = hand to mouth exposure

0.0011mg/kg/day = object (turf grass) to mouth exposure

0.74 mg/kg/day thus 312.5 mg/kg/day ÷ 0.74 mg/kg/day = a Margin of Exposure 420

EPA determines whether acute and chronic pesticide exposures are safe by comparing aggregate 

exposure estimates to the aPAD and cPAD. The aPAD and cPAD represent the highest safe 

exposures, taking into account all appropriate safety factors (SFs). EPA calculates the aPAD and 

cPAD by dividing the POD by all applicable UFs. For linear cancer risks, EPA calculates the 

probability of additional cancer cases given the estimated aggregate exposure. Short-, 

intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate food, 

water, and residential exposure to the POD to ensure that the MOE called for by the product of all 

applicable UFs is not exceeded. An aggregate risk assessment was conducted including exposures 

from food, water, residential handler and residential post-application.

Occupational Exposure 

For purposes of a “screening level” occupational exposure assessment, the Agency has selected a 

number of activities known to result in high levels of occupationally related exposure to 

agricultural workers performing various tasks. Estimates of occupational exposure and risk are 

derived in the same manner described earlier. The rates of application are taken from Davis et al. 

(2009, p 41,42/84) and adjusted for 40 % inert ingredient. Davis et al. assessed 30 % inert 

ingredient formulations.

Occupational Unit Exposures are taken from “Occupational Pesticide Handler Unit Exposure 

Surrogate Reference Table”, Health Effects Division, Office of Pesticide Programs, U.S. 

Environmental Protection Agency, March 2013 and are for a single layer of work clothing (longsleeved shirt, long pants, shoes plus socks) and the use of protective gloves. Pilots in enclosed 

cockpits are considered to be using engineering exposure control mitigation via use of enclosed 

cockpits. 

For occupational assessment the algorithm is:

AR x Units x UE x AF ÷ BW where

AR = Application rate in lb inert/A 

Units = Acres treated/day
Page 29 of 36

UE = Unit Exposure in mg per pound inert handled: Unit Exposures are for workers wearing longsleeved shirt, long pants and shoes plus socks and protective gloves (except for pilots). 

AF = Absorption Factor (100% dermal; 100% inhalation)

BW = body weight (80 kg average adult).

Table 6.0 Estimated Exposure and Risk for Occupational Pesticide Handlers

Exposure 

Scenario 

(Formulation/ 

Application/ 

Crop)

Application 

Rate (lb 

inert/ A)

Area 

Treated 

Daily

(acres)

Dermal 

Unit 

Exposure 

(mg/lb 

inert)

Inhalation 

Unit 

Exposure 

(mg/ lb 

inert)

Baseline 

Dermal Dose 

(mg/kg /day)

Baseline 

Inhalation 

Dose 

(mg/kg/ day)

Baseline 

Dermal 

MOE

Baseline 

Inhalation 

MOE

Liquids/ Aerial 

Application/ High 

Acreage Crops (ST)

Mixer/loader

0.8 1200

0.0376 0.000219

0.45 0.0026 694 120,000

Liquids/ 

Groundboom/ High 

Acreage Crops (ST)

Mixer/loader

0.8 200 0.075 0.00044 4,170 710,230

Liquid/ Aerial 

Applicator/ High 

Acreage Crops (ST)

0.8 1200

Eng 

control 

only: 

0.002

Eng control 

only: 

0.0000049

0.024 0.00006 13,000 5.2M

Groundboom/ High 

Acreage Crops (ST)

applicator

0.8 200 0.0161 0.00034 0.032 0.00068 9,800 459,560

Liquid/ Low Pressure 

Handwand/ Turf (ST)

applicator

2.88 5 0.39 0.0039 0.0702 0.000702 4,450 445,000

Margins of Exposure (MOE) express the Agency’s Level of Concern (LOC). For this review, 

MOE < 100 exceed the Agency’s level of concern. MOEs are the ratio of toxicological endpoint 

(NOAEL) to estimated Dose, both expressed as mg inert/kg/day. 

MOE = NOAEL (mg/kg/day)/Dose (mg/kg/day). The NOAEL is 312.5 mg/kg/day.

Since the estimated MOEs exceed 100, the proposed use patterns do not exceed the Agency’s level 

of concern.

IX. ENVIRONMENTAL FATE AND EFFECTS

The administrative volume of submission IN-10792 (Twaroski, Graham and Novak, 2014; MRID 

49537200 (Volume 2)) contains a “summary” of “available acute and chronic aquatic toxicity data 

for C8-10 Glucamide....” Study citations and details were not provided.

Table 7.0

Test Type C8-10 - Glucamide

Acute fish ()OECD 203) LC50 (96hr) > 100 mg/L

LC100 (96hr) > 100 mg/L

Acute Daphnia (OECD 202) NOEC (48 hr) 100 mg/L

LOEC (48 hr) > 100 mg/L

Algae (OECD 201) ErC50 (72 hr) > 100 mg/L

NOECr (72 hr) 100 mg/L

Chronic fish (OECD 212) NOEC (9d) 200 mg/L

LOEC (9d) > 200 mg/L
Page 30 of 36

Chronic Daphnia (OECD 211) NOEC (21d) 50 mg/L

LOEC (21d) 100 mg/L

Aquatic microorganism (OECD 209) EC50 (3hr) > 1000 mg/L

NOEC (3h) 500 mg/L

A ready biodegradability modified Sturm test was conducted by Fiebig (2013) on C8-10 acyl 

NMGA (CAS No. 85316-98-9 [C8] and CAS No. 85261-20-7 [C10] respectively). The test was 

conducted with a non-adapted activated sludge over a test period of 28 days using the modified 

Sturm test. The test material was tested at a concentration of 19 mg/L with 2 replicates, 

corresponding to a carbon content (TOC) of 10.7 mg C/L in the test vessel. The test vessels were 

incubated at low light conditions at 20-23° C. The biodegradation of the test material was 

followed by titrimetric analysis of the quantity of CO2 produced by the respiration of the bacteria. 

The degradation was stopped on day 28 by acidification of the test solutions. The last titration was 

made on day 29, after residual CO2 had been purged from the test solutions over a period of 24 hr. 

The percentage of CO2 production was calculated in relation to the theoretical CO2 production 

(ThCO2) of the test material. The biodegradation was calculated for each titration time. The test 

functional control was sodium benzoate and the percentage of functional control reached the pass 

level of 60 % within 8 days and a biodegradation of 100 % after 28 days. 

In the toxicity control containing both test and reference material a biodegradation of 67 % was 

determined with 14 days and it came to 90 % after 28 days. The biodegradation of the test 

material was not inhibited by the test material in the toxicity control. Under the conditions of this 

study, the test material is readily biodegradable within 28 days. 

Volatility - As noted earlier, the vapor pressure of C8-10 acyl NMGA is listed as being 1.1 x 10-8

hPa @ 25°C = (~ 8.25 x 10-9 mm Hg). The physical state of most of the test substances were of 

“gel” nature i.e., nearly solid. These two characteristics indicate low levels of volatility thus 

negligible amounts are expected to enter the ambient air. 

Solubility – C8-10 acyl NMGA is essentially insoluble in water as such there is minimal concern 

for persistence in water. The substance is a surface active substance. Results from a Critical 

Micelle Concentration study (ISO 4311) were 1.86 ± 0.23 g/L at pH 9.36 and 20° C based on the 

entire sample: 1.75 ± 0.22 g/L at pH 9.36 and 20° C based on active content (glucamides).

X. DETERMINATION OF SAFETY

For D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives, aggregate risk include dietary 

exposure from food and water. Exposures to toddlers (the most highly exposed population 

subgroup from dietary sources) include food and water exposures. Dietary exposure estimates for 

food and drinking water are below the Agency’s level of concern (<100% cPAD) for the U.S. 

population and all population subgroups. The total dietary exposure for food and drinking water is 

14.6 % of the cPAD for the U.S. population and 54.4 % of the cPAD for children 1-2 yrs old, the 

most highly exposed population subgroup. Aggregate exposures to adults (MOE=490) and 

children (MOE=420) are below the levels of concern of MOE <300. he proposed use of D-
Page 31 of 36

glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives is not expected to induce 

unacceptable adverse effects in any population subgroup and thus is acceptable for use under 40 

CFR §180.910.

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).

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:

There are no international limits on CAS Reg. No. 1591782-62-5.

IV. RISK CHARACTERIZATION

D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivatives exhibits low levels of acute 

toxicity by the oral, dermal and inhalation routes of exposure. It is a severe eye irritant. There are 

multiple sub-chronic oral feeding studies in the rat. There is a 13-week oral toxicity study in the 

rat. There is a reproductive/developmental toxicity study, a prenatal developmental study and a 

one-generation reproduction study in the rat. There are multiple genetic/mutagenicity studies in 

various organisms, all with negative effects. There were no specific studies on neurotoxicity, 

immunotoxicity or metabolism. However there were no signs of neurotoxicity in the functional 
Page 32 of 36

observation battery (FOB) observations taken during the subchronic and longer term feeding 

studies. The DEREK (Nexus) and METEOR modeling systems indicate 80% absorption via the 

gastrointestinal system and less than 1.0 % via dermal absorption. The major route of excretion is 

via the urine. There were no data specific to carcinogenicity however the negative findings in the 

mutagenicity and clastogenicity studies indicate minimal levels of concern for carcinogenicity. In 

addition, no structural alerts were identified for the parent C8-10 glucamide or potential metabolites 

using DEREK Nexus (v 3.0) and METEOR (V2.2.2) or the VEGA QSAR models.

The Agency performed screening level exposure/risk assessment for occupational and nonoccupational subpopulations. The margins of exposure did not exceed the Agency’s level of 

concern. The Agency conducted an aggregate exposure assessment (residues from food + water + 

exposure from pesticide use) and Margins of Exposure do not exceed the Agency’s level of 

concern. There are no population subgroups including children with exposures exceeding levels of 

concern. 

Data regarding environmental fate and effects were considered including acute and chronic 

toxicity to fish, daphnids, algae, aquatic micro-organisms, modeled biodegradation, solubility in 

water and volatility. Based upon the proposed use pattern and the available information regarding 

environmental fate and effects, the Agency believes the proposed use would not pose adverse 

effects. 

Having considered the data earlier discussed in detail, the Agency believes it is reasonable to 

approve the exemption from the requirement of a tolerance, under 40 CFR § 180.910 to exempt 

from the requirement of a tolerance for D-glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl 

derivatives (CAS Reg. No. 1591782-62-5) at a maximum concentration in formulations not to 

exceed 40 %.
Page 33 of 36

REFERENCES

Allingham, P. 2014. Reproduction/Developmental Toxicity Screening Test after Oral 

Administration in Wistar Rats with C8-10-Glucamide. Performing Lab. BSL Bioservice. Planegg, 

Germany. Unpublished study. MRID 49537220

Allingham, P. 2013. Acute Dermal Toxicity (Limit Test) with C8/10-Glucamide AC93/13. 

Performing Lab. BSL Bioservice. Planegg, Germany. Unpublished study. MRID 49537206

Baldrick, P. and L. McRae. 1991. Acute Dermal Toxicity to the Rabbit of E-4194.01. Performing 

Lab. Huntington Research Centre Lt., Cambridgeshire, England. Unpublished study. MRID 

49537207.

Bigger, C.A. and J. J. Clarke. 1991. L5178Y TK+/- Mouse Lymphoma Mutagenesis Assay with 

Confirmation Test Article SS 0001.01. Performing Lab. Microbiological Associates, Inc. 

Rockville, MD. Unpublished study. MRID 49537226.

Bouds, D. 1999. A Dermal Sensitization Study in Guinea Pigs with 10000506 – Maximization 

Design. Performing Lab. Springborn Laboratories, Inc. SLI. Spencerville, OH. Unpublished 

study. MRID 49537216.

Daniels, R. and M. Novak. 2014. Physical/Chemical Properties. Unpublished Document 

prepared by Keller and Heckman, LLP. Washington, DC. MRID 49537234.

Davis, D., B-H Chin, A. LaMay, M. Lloyd, C. Olinger, S. Piper. 2009. Alkyl Alcohol Alkoxylate 

Phosphate and Sulfate Derivatives (AAAPDs and AAASDs – JITF CST 2 Inert Ingredients). 

Human Health Assessment to Support Proposed Exemption from the Requirement of a Tolerance 

When Used as Inert Ingredients in Pesticide Formulations. Petition No. 9E7533, PC Code 911339, 

CAS Reg. No. 9046-01-9. Unpublished MEMORANDUM June 8 to K. Leifer U.S. EPA.

Decker, U. 1991. Acute Oral Toxicity Study with E-4086.01 in Rats. Performing Lab. Research 

& Consulting Company AG. Fullinsdorf, Germany. Unpublished report. MRID 49537205

Decker, U., L. Ullman, P. Lucini and N. Hoff. 1991. Primary Skin Irritation Study with E4194.01 in Rabbits. Performing Lab. RCC, Research & Consulting Com. AG. Itingen, 

Switzerland. Unpublished study. MRID 49537211.

Environmental Protection Agency. 2006. Reregistration Eligibility Decision for Alkyl Dimethyl 

Benzyl Ammonium Chloride (ABDAC). Publication EPA739_R-06-009. August 2006.

Fiebig, S. 2013. C8-10 Glucamide AC93/13 Ready Biodegradability Modified Sturm Test. 

Performing Lab. Dr. U.Noack-Laboratorien. Sarstedt, Germany. Unpublished study. MRID 

49537229.

Holalagoudar, S.R., 2014. Acute Oral Toxicity (Acute Toxic Class Method) with Synergen GA. 

Performing Lab. BSL Bioservice. Planegg Germany, Unpublished report. MRID 49537204.
Page 34 of 36

Liggett, M. and L. McRae. 1991. Eye Irritation to the Rabbit of E-4194.01. Performing Lab. 

Huntingdon Research Centre Ltd., Cambridgeshire, England. Unpublished study. MRID 

49537213.

Isaacs, K. 1994. 13-Week Oral Toxicity Study in Rats with E-4086.01 Evaluation of Respiratory 

Tract. Performing Lab. K.R. Isaacs. North Yorkshire, U.K. Unpublished study. MRID

49537219. 

Lehmeier, D. 2013. In Vitro Skin Irritation: Human Skin Model Test with C8-10 Test Article. 

Performing Lab. BSL Bioservice. Planegg, Germany. Unpublished report. MRID 49537210.

Leoni, A. 2013. Acute Oral Toxicity (Acute Toxic Class Method) with C8/10-Glucamide 

AC93/13. Performing Lab. BSL Bioservice, Planegg, Germany. Unpublished study. MRID 

49537203.

Powers, J. 1991. Metabolism Program Report Absorption, Distribution and Elimination 

Following Dermal Dosing Test Article: SS0001.01 and WW0020.02. Performing Laboratory The 

Proctor & Gamble Company Miami Valley Laboratories. Cincinnati, Ohio. Unpublished report. 

MRID 49537202.

Putman, D. and R. Young. 1991. Cytogenicity Study – Rat Bone-Marrow In Vivo Test Article: 

SS0001.01. Performing Lab. Microbiological Associates, Inc. Rockville, MD. Unpublished 

Study. MRID 49537227.

Saylor, J. 1991. Prenatal Developmental Toxicity Study in Rats. Performing Lab. International 

Research and Development Corp. Michigan, USA. Unpublished study. MRID 49537221.

Schmitz, R. 2013. Screening for the Eye Irritancy Potential using the Bovine Corneal Opacity and 

Permeability Assay with C8-10. Performing Lab. BSL Bioservice. Planegg, Germany. 

Unpublished study. MRID 49537212.

Schreib, G. 2012. Reverse Mutation Assay Using Bacteria (Salmonella typhimurium) with 

Glucamide 810 RM. Performing Lab. BSL Bioservice Scientific Laboratories GmbH. Planegg, 

Germany. Unpublished study. MRID 49537223.

Schulze, G. 1991. 4-Week Subacute Oral Toxicity Study in Rats with SS0001.01. Performing 

Lab. Hazleton Washington, Inc. Vienna, VA. Unpublished study. MRID 49537218.

Stiller, S. 28-Day repeated dose oral toxicity study in Wistar rats with C8/10-Glucamide AC93/13 

including a 14-day recovery period. BSL Bioservice Scientific Laboratories GmbH. Study # 

135319, April 30, 2014. Unpublished. MRID 49537217.

Ullman, L., U. Decker, C. Krōling, C. Bōni and M. Hoff. 1991. Contact Hypersensitivity to E4086.01 in Albino Guinea Pigs (Modified Buehler Method). Performing Lab. RCC, Research & 

Consulting Co. AG. Unpublished study. Füllinsdorf, Germany. MRID 49537215.
Page 35 of 36

van Huygevoort, A.H.B.M. 2014. Assessment of Acute Inhalation Toxicity with E-176/2013PC

in the Rat (Acute Toxic Class Method). Performing Lab. WIL Research Europe B.V. 

Hertogenbosch, The Netherlands. Unpublished Study. MRID 49537208.

Van Huygevoort, A.H.B.M. 2013. Assessment of Contact Hypersensitivity to E-185/2012 PC W

in the Albino Guinea Pig (Maximisation-Test). Performing Lab. WIL Research Europe B.V. 

Hertogenbosch, The Netherlands. Unpublished Study. MRID 49537214.

van Huygevoort, A.H.B.M. 2011. Assessment of Acute Inhalation Toxicity with Synergen GA 

(50% Glucamide 810 in Water) in the Rat. Performing Lab. WIL Research Europe B.V. 

Hertogenbosch, The Netherlands. Unpublished Study. MRID 49537209.

Wallner, B. 2013. In Vitro Mammalian Cell Gene Mutation Test (HPRT-Locus) in Chinese 

Hamster V79 Cells with Glucamide 810 RM. Performing Lab. BSL Bioservice Scientific 

Laboratories GmbH. Planegg, Germany. Unpublished study. MRID 49537224.

Wessels, A. 2013. Mammalian Micronucleus Test of Murine Peripheral Blood Cells with 

Glucamide 810 RM. Performing Lab. BSL Bioservice Scientific Laboratories GmbH. Planegg, 

Germany. Unpublished study. MRID 49537225. 

York, R. 2000. Oral (Gavage) Reproduction Study of 10000506.01 in Rats. Performing Lab. 

Argus Research Laboratories, Inc. Horsham, PA. Unpublished study. MRID 49537222.
Page 36 of 36

ATTACHMENT

US EPA Ver. 3.16, 03-

08-d

DEEM-FCID Chronic analysis for INERTS-D-GLUCITOL40% 3X NHANES 2003-2008 2-

day

Residue file name: C:\Users\mdow\MARK\InertsRA\2015 INERTS\IN-10792 DGlucitol\Dglucitol40 3xINERTS_57ACTIVE_100PPBH2OREV.R08

 Adjustment factor #2 used.

Analysis Date 10-22-2015/12:53:36 Residue file dated: 10-22-2015/12:47:04

Reference dose (RfD, Chronic) = 1.04 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 0.151893 14.6%

Hispanic 0.165810 15.9%

Non-Hisp-White 0.149071 14.3%

Non-Hisp-Black 0.141106 13.6%

Non-Hisp-Other 0.179167 17.2%

Nursing Infants 0.198942 19.1%

Non-Nursing Infants 0.369180 35.5%

Female 13+ PREG 0.132585 12.7%

Children 1-6 0.437875 42.1%

Children 7-12 0.182277 17.5%

Male 13-19 0.107298 10.3%

Female 13-19/NP 0.109068 10.5%

Male 20+ 0.113187 10.9%

Female 20+/NP 0.122970 11.8%

Seniors 55+ 0.122555 11.8%

All Infants 0.316622 30.4%

Female 13-50 0.117539 11.3%

Children 1-2 0.565597 54.4%

Children 3-5 0.389016 37.4%

Children 6-12 0.200810 19.3%

Youth 13-19 0.108143 10.4%

Adults 20-49 0.116210 11.2%