Page 2 of 19 

also used as an ingredient in personal care products such as shampoos, conditioners, and 

moisturizers. 

DBS is not expected to pose a hazard when used for its proposed use pattern. A skin 

sensitization study on guinea pigs determined that DBS is not a sensitizer. A primary dermal 

irritation study in rats determined that DBS is not irritating. The combined LD50 of DBS in an 

acute oral toxicity study in mice was 12,800 mg/kg/day. The dermal LD50 in mice (males only) 

was 6400 mg/kg/day. 

In a 90-day subchronic oral toxicity study in mice and rats, the NOAEL was determined to be 

3200 mg/kg/day for mice and 2000 mg/kg/day for rats. No treatment-related clinical signs of 

toxicity were noted during the 90-day test period at the highest dose tested. In a 90-day 

subchronic oral toxicity study in dogs the NOAEL was determined to be 92.1 mg/kg/day for 

males and 91.5 mg/kg/day for females. No evidence of systemic toxicity was observed at doses 

as high as 2500 ppm (92.1 and 91.5 mg/kg/day in males and females, respectively). In a 13-

week oral toxicity study in rats there were no significant treatment-related effects noted and the 

NOAEL was determined to be 20,000 ppm (1261.3 for males and 1479.2 mg/kg/day for 

females). 

In a mammalian cell gene mutation assay at the TK locus, mouse lymphoma L5178Y cells 

cultured in vitro were exposed to Millad 3905. The study concluded that Millad 3905 was 

negative in the in vitro mammalian cells in culture gene mutation assay in mouse lymphoma 

L5178Y cells, both with and without S9-mix under the conditions of testing. 

In a mouse bone marrow micronucleus assay mice were treated orally by gavage with Millad

3905. There were no signs of toxicity during the study and the test substance is considered 

negative in the mouse bone marrow micronucleus test. 

In a reverse gene mutation assay in bacteria of S. typhimurium were exposed to Millad 3905. It 

was negative for mutagenicity in both the presence and absence of metabolic activation. 

Based on the results from these studies, EPA concluded that DBS is not likely to be genotoxic. 

No carcinogenicity studies are available on DBS. Based on the lack of any systemic toxicity at 

high doses in rats and mice in a 90-day study and the lack of mutagenicity, EPA concluded that 

DBS is not likely to be carcinogenic. It is also likely that DBS will be metabolized into sorbitol 

and benzaldehyde in the body. Sorbitol is a natural constituent and is considered noncarcinogenic and benzaldehyde has been shown to be non-carcinogenic in rats at doses up to 400 

mg/kg/day. (Bishop, 1990) 

No neurotoxicity studies are available on DBS; however, there were no clinical signs of 

neurotoxicity were observed in the database. 

Residues of concern are not anticipated for dietary exposure (food and drinking water) or for 

residential exposure from the use of DBS for the proposed use pattern as an inert ingredient in 

pesticide products. EPA expects aggregate exposure to DBS to pose no appreciable dietary risk 
Page 3 of 19 

given that the data on DBS shows a lack of any systemic toxicity at doses of up 3200 mg/kg/day. 

There was also a lack of any apparent developmental effects in the database. 

The toxicity database is sufficient for DBS and potential exposure is adequately characterized 

given the low toxicity of the chemical. In terms of hazard, there are low concerns and no 

residual uncertainties regarding prenatal and/or postnatal toxicity. DBS has low subchronic 

toxicity. Although no developmental or reproductive studies, per se, were identified, subchronic 

90-day studies in dogs, rats and mice have not demonstrated any systemic toxicity or effects on 

the reproductive organs. No acute or subchronic neurotoxicity studies are available, but there 

were no signs of neurological effects observed in the database at high doses. Therefore, the 

Agency concluded that the developmental neurotoxicity study is not required. No 

immunotoxicity study is available, however, no systemic toxicity was observed in mice, rats and 

dogs at high doses. In addition, no hazard has been identified following exposure to DBS. 

Based on this information, there is no concern at this time for increased sensitivity to infants and 

children to DBS when used as an inert ingredient in pesticide formulations and a safety factor 

analysis has not been used to assess risk. For the same reason, EPA has determined that an 

additional safety factor is not needed to protect the safety of infants and children.

The values for melting point and boiling point of DBS are high. These two factors, along with 

the vapor pressure indicate that DBS exists primarily as a solid. The low vapor pressure and 

Henry’s Law Constant estimates indicate that DBS is unlikely to volatilize from dry surfaces or 

moist surfaces or moist soils or sediments. The Koc values for DBS indicate that sorption to 

soils and sediments may occur and is not likely to enter groundwater. DBS also has low 

bioconcentration potential and is considered to be nonvolatile. 

The ecotoxicity of DBS was estimated using Ecological Structure Activity Relationships 

(ECOSAR). The results indicate that the ecotoxicity of DBS ranges from practically nontoxic to 

slightly toxic. 

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.gove/oepa/guidance/justice/eo12898.pdf. This assessment does not rely in 

part on data from studies in which adult human subjects were intentionally exposed to a 

pesticide. 

Taking into consideration all available information on DBS, EPA concludes that there is a 

reasonable certainty that no harm will result to the general population or to infants and children 

from aggregate exposure to DBS. Therefore, the establishment of an exemption from tolerance 

under 40 CFR 180.920 for residues of DBS when used as an inert ingredient in pesticide 

formulations applied pre-harvest can be considered safe under section 408 of the FFDCA. 
Page 4 of 19 

I. Background 

Inert ingredients are those ingredients that are added to end use products that are not active 

ingredients. The terms "active ingredient" and "inert ingredient" are defined under the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA). An active ingredient is one that prevents, 

destroys, repels or mitigates a pest, or is a plant regulator, defoliant, desiccant or nitrogen 

stabilizer. The statute defines the term "inert ingredient" as an ingredient that is not active. 

Dow Agrosciences submitted a petition dated June 11, 2009 proposing to establish an exemption 

from the requirement of a tolerance under 40 CFR §180.920 (pre-harvest only) limited to 

herbicides only with a 3% formulation cap for: 

 

 Dibenzylidene sorbitol (CAS Reg. No. 32647-67-9) 

The proposed use of DBS is as an inert ingredient in pesticide formulations (herbicide only) 

applied to growing crops under 40 CFR §180.920 with a limit of 3% in pesticide formulations. 

EPA published a Notice of Filing for this petition in the Federal Register of September 4, 2009 

(71 FR 45848, FRL-8434-4). The Agency did not receive any substantive comments in response 

to this notice. 

This document provides an assessment of DBS for the requested tolerance exemption and is 

based on information and data submitted by the petitioner and information found in the public 

literature. 

II. Use Information 

DBS is an organic molecule capable of inducing gelation in a variety of organic solvents and 

polymers at low concentrations. (Wilder, et. al.) Its purpose in formulation is as a clarifying 

agent or nucleating agent. (Milliken) DBS has reported uses in antiperspirant and deodorant 

products. (EWG) According to the US Department of Health and Human Services, Household 

Products Database, DBS is used as an ingredient in personal care products such as shampoos, 

conditioners, and moisturizers. 

DBS is also approved for use as a Food Additive under 21 CFR 178.3295, for use only as a 

clarifying agent for olefin polymers complying with 177.1520 (c) 1.1, 3.1, and 3.2 of this chapter 

under conditions of use C, D, E, F, and G, described in table 2 of 176.170 (c) of this chapter at a 

level not exceeding 0.25 percent by weight of the polymer. 

(http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=178.3295) 
Page 5 of 19 

III. Structural Information 

Table 1: Structural Information for Dibenzylidene Sorbitol (CAS Reg. No. 32647-67-9) 

Structure: Chemblink 

SMILES 

Code: 

OC(CO)C1C2C(OC(C3=CC=CC=C3)O1)COC(C4=CC=CC=C4)O2 As cited in 

PP#9E7581 
Page 6 of 19 

IV. Physical and Chemical Properties 

Table 2. Physical and Chemical Properties of DBS 

Parameter Value References 

Systemic Name: D-Glucitol, bis-O-

(phenylmethylene)- 

Common Name: Dibenzylidene sorbitol 

Molecular Formula: C20-H22-O6 

CAS # 32647-67-9 

Synonyms: Bis-O-(phenylmethylene)-

D-glucitol; D-Sorbitol, diO-benzylidene-; 

Dibenzalsorbitol; 

Dibenzylidene-D-sorbitol 

ChemIDplus Lite 

Appearance White to off-white powder 

Boiling Point 548.7 oC at 760 mmHg 

Flash Point 285.6 oC 

LookChem 

Molecular Weight 358.39 

Density 1.272 

Melting Point 224-228 oC 

ChemBlink 

Log Kow 1.98 (+/-) 0.35) MRID 47777901 

Reactivity The product is stable at 

ambient conditions. 

Hazardous polymerization 

will not occur. 

Milliken, 2009 

Water Solubility Reported as Nil (6) 

estimated as 6 mg/L (Table 

3) 

As cited in PP#9E7581 

Vapor Pressure 6.31E-013 ((mm Hg, 25 oC) 

Modified Grain Method) 

Henry’s Law Constant 4.959E-014 atm-m3/mole 

(via VP/WSol estimate) 

Koc 3.226-13.44 L/kg 

OH Reaction Rate 98.7E-12 cm3/molecule-sec 

(half-life=1.3 hours) 

BCF 5.22 L/kg 

Level III Fugacity 

Model/Mass Amount (%) 

Air 5.28e-006 

Water 32.6 

Soil 67.3 

Sediment 0.0831 

EPISUITE estimates (*) 

* Estimated from EPISUITE version 4 based on Log Low=1.98, Melting point=220, water solubility of 6 mg/L and SMILES code 
Page 7 of 19 

V. Hazard Assessment 

Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the available scientific data 

and other relevant information in support of this action and considered its validity, completeness 

and reliability and the relationship of this information to human risk. EPA has also considered 

available information concerning the variability of the sensitivities of major identifiable 

subgroups of consumers, including infants and children. The nature of the toxic effects caused 

by DBS are discussed in this unit. 

Some of the toxicological studies available in the database were conducted with Millad 3905 and 

Millad 3988. These are tradename for the inert ingredient DBS and contains a minimum of 96% 

DBS.

Table 3: Acute Toxicity Profile for DBS 

Study Type Test 

Organism/ 

Strain 

Results Toxicity 

Category 

MRID 

Skin 

Sensitization 

Guinea Pig 

(White 

Hartley) 

Not a sensitizer N/A 47777902 

Primary 

Dermal 

Irritation 

Rat 

(Wistar) 

Not irritating IV 47777903 

Acute Oral 

Toxicity 

Mouse 

(dd-system) 

Oral LD50 

Males= >12,800 mg/kg/day 

Females= >12,800 

mg/kg/day 

Combined= >12,800 

mg/kg/day 

IV 47777904 

Acute Dermal 

Toxicity 

Mouse 

(dd-system) 

LD50 

Males= >6400 mg/kg/day 

Females not tested 

Combined not available 

N/A 47777904 

A. Skin Sensitization 

In a dermal sensitization study (MRID 47777902) with Dibenzylidene-Sorbitol (purity not 

reported , Batch No. not reported), five Hartley guinea pigs were tested with 0.1% water 

suspension of Dibenzylidene-Sorbitol (containing 1% gum Arabic) using intracutaneous 

injection. One control animal was treated with water solution of 1% gum arabic. 

The animals (sex not reported) were induced and challenged with intracutaneous injections. The 

test solution was 0.1% water suspension of dibenzylidene-sorbitol (containing 1% gum Arabic). 

For the induction, the back of the five test animals was treated with 0.05 mL of the test solution 

for the first time, and henceforth, each 0.1 mL for three times a week, “and repeated 10 times.” 

Two weeks after the induction, the back of the animals was challenged with 0.05 mL of the test 
Page 8 of 19 

solution. After 24 hours, the treated site was checked for reactions as compared with the site just 

after the treatment. One animal was induced and challenged with the control liquid (1% gum 

Arabic in water) using the same procedure as the test animals. 

“No specific differences” were noted at the treated site after the induction and challenge. The 

test and control animals had an erythema with a diameter of 1±0.5 cm. There were some cases 

of hair loss at the treated sites with a diameter of approximately 0.5 cm. No specific differences” 

were noted at the treated site after the induction and challenge. Dibenzylidene-sorbitol was not a 

sensitizer. The study author stated that the test material does not dissolve or uniformly disperse 

in physiological salt solution, thus, the test material was injected as a gum arabic suspension. 

The test solution was not isotonic and it was considered the appearance of erythema was due to 

the stimulation caused by the discrepancy of osmotic pressure. No positive control study was 

available to validate the current study. 

B. Primary Dermal Irritation 

In a primary dermal irritation study (MRID 47777903), eight Wistar rats (sex not reported) were 

dermally exposed to 0.08 to 0.12 g of dibenzylidene-sorbitol (purity not reported , Batch No. not 

reported) preparation applied to the shaved back of the rats. The test material preparation was 

prepared as follows: Fifty mL of propyleneglycol was added to 1.5 g of dibenzylidene-sorbitol 

and heated to 150oC. After dissolving, the mixture was cooled down to about 60oC and poured 

into a tube to solidify at room temperature before use. It was not stated whether the treated site 

was covered. The sites were checked for existence of erythema, edema, incrustation and other 

symptoms 24 hour and 72 hours after treatment. Occasional observation was made immediately 

after treatment until 7 hours after treatment. No erythema or other abnormalities were noted on 

any animal during the study. Hair growth was normal. In this study, dibenzylidene-sorbitol was 

not irritating to the skin and is in Toxicity Category IV. This study is classified as 

Acceptable/non-guideline. 

C. Acute Oral Toxicity 

In an acute oral toxicity study (MRID 47777904), groups of dd-system mice (10/group/sex) were 

given a single oral dose of water suspension (containing 10% gum Arabic) of DibenzylideneSorbitol (Purity not reported, batch No. not reported) at 0%, 8%, 10%, or 32% (w/v) (equivalent 

to 0; 3200; 6400; or 12,800 mg/kg, respectively) and observed for 7 days. 

All animals survived the study. No abnormal clinical signs were noted from any male animal. 

The food intake was decreased for all females, including the controls, on the first day of dosing. 

The average body weight of the males dosed at 12,800 mg/kg decreased (1.2 g) on day one with 

gradual recovery, but the mice did not regain their initial body weight. The average body weight 

of the males dosed at 6400 mg/kg decreased (0.7 g) on day 1 with recovery by day 3 and the 

mice gained weight thereafter. The control males and the males dosed at 3200 mg/kg showed no 

difference in body weight gains. A slight decrease in body weight was seen in the females dosed 

at 6400 and 12800 mg/kg with gradually recovery. No necropsy was reported. The Oral LD50

for males, females and combined was greater than 12,800 mg/kg body weight. DBS is in EPA 

Toxicity Category IV. This acute oral toxicity study is classified as Acceptable/Non-guideline. 
Page 9 of 19 

D. Acute Dermal Toxicity 

In an acute dermal toxicity study (MRID 47777904), groups of dd-system male mice (10/group) 

were subcutaneously injected at doses of 0, 1600, 3200, or 6400 mg/kg body weight with water 

suspension (containing 10% gum Arabic) of Dibenzylidene-Sorbitol (Purity not reported, batch 

No. not reported) of 0%, 3.2%, 6.4%, or 12.8% (w/v) and observed for 7 days. 

All animals survived the study. “The change of the lie of hair for the worse was seen in 1-4 

animals of both the test groups and control group, however, it was almost recovered after 7 

days.” No other abnormalities were noted in the study. The food intake of the test group 

animals was decreased (30-40%) as compared to the control group, and was noted on the first 

day of treatment with recovery within 3-4 days in the low and medium dose group and later in 

the high dose group. Body weight gain was normal for all groups. No necropsy was reported. 

The Oral LD50 for males was greater than 6400 mg/kg body weight. Females were not tested. 

EPA Toxicity Category cannot be assigned for Dibenzylidene-Sorbitol, since the females were 

not tested. This acute oral toxicity study is classified as Unacceptable/Non-guideline. 

E. Subchronic Oral Toxicity in Rats and Mice 

In a 90-day oral toxicity study (MRID 47777905), dibenzylidene sorbitol (purity not reported , 

Batch No. not reported) was administered to groups of 10 male and 10 female ICR mice and SD 

rats/sex/dose in the diet at concentrations of 0.0, 0.5, 1.0, or 2.0% (equivalent to a theoretical 

concentration of 0, 800, 1600, and 3200 mg/kg bw/day for mice and 0, 500, 1000, and 2000 

mg/kg bw/day for rats). 

No treatment-related clinical signs of toxicity or toxicologically relevant effects on body weight, 

food and water intake, urinalysis, hematology or clinical chemistry were noted. The absolute 

and relative liver weights of treated male and female mice and rats were increased, but the 

increases were unrelated to dose. No microscopic treatment-related effects were noted in the 

liver. The absolute but not the relative-to-body weight of kidney from female mice in the lowdose and high-dose groups was statistically increased, but the increases were unrelated to dose. 

In this study, no significant treatment-related effects were noted during 90-days of treatment with 

the test material. Based on the results, the NOAEL for male and female mice was 3200 mg/kg 

bw/day and 2000 mg/kg bw/day for male and female rats. 

 

F. Subchronic Oral Toxicity in Dogs 

In a 90-day oral toxicity study (MRID 47777910), Millad 3905 (assumed to be 100% a.i., Batch

# X3005) was administered to six beagle dogs/sex/group in the diet at dose levels of 0, 500, 1000 

or 2500 ppm (equivalent to 0, 17.2, 36.2 and 92.1 mg/kg bw/day for males and 0, 17.6, 36.5 and 

91.5 mg/kg bw/day for females). 

No deaths or clinical signs of toxicity were observed. No treatment-related effects on body 

weight, body weight gain, food consumption, clinical pathology (hematology and clinical 

chemistry) or post-mortem examination were observed. The animals could have tolerated a 

higher dose. 
Page 10 of 19 

No evidence of systemic toxicity was observed at doses as high as 2500 ppm (92.1 and 

91.5 mg/kg/day in males and females, respectively) when Millad 3905 was administered in the 

diet of beagle dogs for 90 days. Since no treatment-related effects were found, the NOAEL for 

beagle dogs was 92.1 mg/kg bw/day for males and 91.5 mg/kg bw/day for females (highest dose 

tested). A LOAEL was not identified. 

G. 90-Day Oral Toxicity in Rats 

In a 13-week oral toxicity study (MRID 47777909), Millad 3988 (97.3% a.i.; Batch No. 9236-

23) was administered to ten Sprague Dawley rats/sex/dose in the diet at dietary concentrations of 

0, 2000, 6500, or 20,000 ppm (equivalent to 0, 123.1, 406.5, or 1261.3 mg/kg bw/day for males 

and 0, 146.9, 478.5, or 1479.2 mg/kg bw/day for females) for 13 weeks. An additional group of 

five animals/sex/dose was treated at dietary concentrations of 0 or 20,000 ppm for 13 weeks, 

followed by a 4-week recovery period. 

There were no significant treatment-related effects on mortality, clinical signs, body weight or 

body weight gain, food consumption, food efficiency, ophthalmology, hematology, clinical 

chemistry, organ weight, or gross or microscopic pathology. The LOAEL for Millad 3988 in 

Sprague Dawley rats is not identified, and the NOAEL is greater than or equal to 20,000 ppm 

(1261.3 for males and 1479.2 mg/kg/day for females). 

H. In Vitro Mammalian Cells in Culture Gene Mutation 

In a mammalian cell gene mutation assay at the TK locus (MRID 47777906), mouse lymphoma 

L5178Y cells cultured in vitro were exposed to Millad 3905 (unreported % a.i., lot # U2097) 

dissolved in dimethyl sulfoxide at concentrations of 0, 200, 400, 600, 800, 900, or 1000 μg/mL 

in the absence and presence of mammalian metabolic activation (S9-mix with S9 fraction from 

livers of Aroclor 1254 induced male rats) for 4 hours. 

Millad 3905 was tested up to concentrations limited by solubility. Concentrations higher than 

1000 μg/mL were not tested because of the insoluble nature of the test material. The abstract 

stated that the test material formed a white gelatinous precipitate in media at and above 250 

μg/mL. At the highest concentration tested, there was moderately high cytotoxicity, with 

approximately 30% relative growth both with and without S9-mix. The positive controls did 

induce the appropriate response. There was no evidence of induced mutant colonies over 

background. 

The study concluded that Millad 3905 was negative in the in vitro mammalian cells in culture 

gene mutation assay in mouse lymphoma L5178Y cells, both with and without S9-mix under the 

conditions of testing. 

I. In Vivo Mammalian Cytogenetics – Erythrocyte Micronucleus 

In a mouse bone marrow micronucleus assay (MRID 47777907), five CD-1 (ICR) mice/sex/dose 

were treated orally by gavage with Millad 3905 (unreported % a.i., lot # U2097) at doses of 0, 

1250, 2500, or 5000 mg/kg bw. Bone marrow cells were harvested at 24, 48, and 72 hours posttreatment. The vehicle was 10% gum arabic. Animals received a single dose. 
Page 11 of 19 

There were no signs of toxicity during the study. One thousand polychromatic erythrocytes 

(PCEs) were examined for micronuclei in all animals at all harvest times. Millad 3905 was tested 

at an adequate dose based on exceeding the limit dose for the assay by 2.5 fold. The positive 

control induced the appropriate response. There was not a significant increase in the frequency 

of micronucleated polychromatic erythrocytes in bone marrow after any treatment time. 

The study concluded that Millad 3905 did not induce a significant increase in micronuclei in 

bone marrow PCEs under the conditions of the study and that this test article is thus considered 

negative in the mouse bone marrow micronucleus test. Furthermore, the test substance gave no 

indication of general toxicity. 

J. Salmonella/Escherichis/Mammalian Activation Gene Mutation Assay 

In a reverse gene mutation assay in bacteria (MRID 47777908), strains TA98, TA100, TA1535, 

TA1537, and TA1538 of S. typhimurium were exposed to Millad 3905 (unreported % a.i., lot # 

U2097), dissolved in DMSO at concentrations of 100, 333, 667, 1000, 3330, or 5000 μg/plate in 

the presence and absence of mammalian metabolic activation in the plate incorporation 

procedure using triplicate plating. The S9 fraction was obtained from Aroclor 1254-induced male 

Sprague-Dawley rat liver. 

Millad 3905 was tested up to the limit concentration for the assay. Neither the mutagenesis assay 

nor the preliminary cytotoxicity assay, which was conducted only on strain TA100, showed any 

evidence of cytotoxicity. In both instances there was moderate precipitation of the test article at 

the two highest concentrations tested and slight precipitation at the two concentrations tested 

below them. The positive controls induced the appropriate responses in the corresponding 

strains. There was no evidence of induced mutant colonies over background. 

K. Carcinogencity 

There are no carcinogenicity studies available on DBS. Based on the lack of any systemic 

toxicity at high doses in mice and rats in a 90-day study and the lack of mutagenicity, EPA 

concluded that DBS is not likely to be carcinogenic. It is also likely that DBS will be 

metabolized to sorbitol and benzaldehyde in the body. Sorbitol is a natural constituent and is 

considered to be non-carcinogenic. Benzaldehyde has been shown to be non-carcinogenic in 

F344/N rats at doses up to 400 mg/kg/day. In an NTP bioassay, “there was some evidence of 

carcinogenic activity of benzaldehyde for male and female B6C3F1 mice, as indicated by 

increased incidences of squamous cell papillomas and hyperplasia of the forestomach.” (Bishop, 

1990) Based on the above information, EPA concluded DBS is not likely to be carcinogenic. 

L. Neurotoxicity 

No neurotoxicity studies are available on DBS, however, there were no clinical signs of 

neurotoxicity were observed in the database.

 
Page 12 of 19 

Table 4: Toxicology Profile for DBS 

Guideline No./Study 

Type 

Test Organism/ 

Strain 

Doses Results MRID 

OPPTS 870.3100 

Subchronic Oral 

Toxicity 

Rats – JCL-SD 

Mice – JCL-ICR 

0.0, 0.5, 1.0, or 2.0% 

(equivalent to a theoretical 

concentration of 0, 800, 

1600, and 3200 mg/kg 

bw/day for mice and 0, 500, 

1000, and 2000 mg/kg 

bw/day for rats) 

Rats 

NOAEL=2000 

mg/kg/day 

Mice 

NOAEL=3200 

mg/kg/day 

47777905 

OPPTS 870.3905 

Subchronic Oral 

Toxicity 

Dogs – Beagles 0, 500, 1000 or 2500 ppm 

(equivalent to 0, 17.2, 36.2 

and 92.1 mg/kg bw/day for 

males and 0, 17.6, 36.5 and 

91.5 mg/kg bw/day for 

females) 

NOAEL/Males=

92.1 mg/kg/day 

NOAEL/Females

=91.5 mg/kg/day 

47777910 

OPPTS 870.3100 

90-Day Oral Toxicity 

Rats – Sprague 

Dawley 

0, 2000, 6500, or 20,000 

ppm (equivalent to 0, 123.1, 

406.5, or 1261.3 mg/kg 

bw/day for males and 0, 

146.9, 478.5, or 1479.2 

mg/kg bw/day for females) 

Males=1261.3 

mg/kg/day 

Females=1479.2 

mg/kg/day 

47777909 

OPPTS 870.5300 

In Vitro Mammalian 

Cells in Culture Gene 

Mutation Assay 

Mouse Lymphoma 

L5178Y Cells 

0, 200, 400, 600, 800, 900 or 

1000 μg/ml 

Negative with 

and without S9 

Activation 

47777906 

OPPTS 870.5395 

In Vivo Mammalian 

Cytogenetics – 

Erythrocyte 

Micronucleus Assay 

Mice – CD-1 

(ICR) 

0, 1250, 2500 or 5000 

mg/kg/day 

Negative 47777907 

OPPTS 870.5100 

Salmonella/Escherichi

a/ 

Mammalian 

Activation Gene 

Mutation Assay 

TA98, TA100, 

TA1535, TA1537, 

and TA1538 

strains of S. 

typhimurium

100, 333, 667, 1000, 3330, 

or 5000 μg/plate 

No evidence of 

induced mutant 

colonies over 

background 

47777908 
Page 13 of 19 

VI. FQPA Safety Factor Considerations 

Section 408 of the FFDCA provides that EPA shall apply an additional tenfold (10X) 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. This additional 

margin of safety is commonly referred to as the FQPA safety factor (SF). In applying this 

provision, EPA either retains the default value of 10X or uses a different additional safety factor 

when reliable data to EPA supports the choice of a different factor. 

The toxicity database is sufficient for DBS and potential exposure is adequately characterized 

given the low toxicity of the chemical. In terms of hazard, there are low concerns and no 

residual uncertainties regarding prenatal and/or postnatal toxicity. DBS has low subchronic 

toxicity. Although no developmental or reproductive studies, per se, were identified, subchronic 

90-day studies in dogs, rats and mice have not demonstrated any systemic toxicity or effects on 

the reproductive organs. No acute or subchronic neurotoxicity studies are available, but there 

were no signs of neurological effects observed in the database at high doses. Therefore, the 

Agency concluded that the developmental neurotoxicity study is not required. No 

immunotoxicity study is available, however, no systemic toxicity was observed in mice, rats and 

dogs at high doses. In addition, no hazard has been identified following exposure to DBS. 

Based on this information, there is no concern at this time for increased sensitivity to infants and 

children to DBS when used as an inert ingredient in pesticide formulations and a safety factor 

analysis has not been used to assess risk. For the same reason, EPA has determined that an 

additional safety factor is not needed to protect the safety of infants and children.

Endocrine Disruption 

EPA is required under the Federal Food, Drug and Cosmetic Act (FFDCA), as amended by 

FQPA, to develop a screening program to determine whether certain substances (including all 

pesticide active and other ingredients) “may have an effect in humans that is similar to an effect 

produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” Following recommendations of its Endocrine Disruptor and Testing Advisory 

Committee (EDSTAC), EPA determined that there was a scientific basis for including, as part of 

the program, the androgen and thyroid hormone systems, in addition to the estrogen hormone 

system. EPA also adopted EDSTAC’s recommendation that the Program include evaluations of 

potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that 

effects in wildlife may help determine whether a substance may have an effect in humans, 

FFDCA authority to require the wildlife evaluations. As the science develops and resources 

allow, screening of additional hormone systems may be added to the Endocrine Disruptor 

Screening Program (EDSP). 

When additional appropriate screening and/or testing protocols being considered under the 

Agency’s EDSP have been developed, DBS may be subjected to further screening and/or testing 

to better characterize effects related to endocrine disruption. 
Page 14 of 19 

VII. Exposure Assessment 

The proposed use of DBS is as an inert ingredient in pesticide formulations. For the general 

population, the primary route of exposure to DBS from its use as an inert ingredient in pesticide 

products would most likely be through consumption of food to which pesticide products 

containing it have been applied and possibly through drinking water (from runoff). Dermal and 

inhalation exposures are also possible from residential use of pesticide products containing DBS. 

A quantitative dietary risk or residential risk assessment were not performed since no endpoint of 

concern was identified in the database. 

A. Aggregate Exposure 

In examining aggregate exposure, the Federal Food, Drug, and Cosmetic Act (FFDCA) section 

408 directs EPA to consider available information concerning exposures from pesticide residue 

in food and all other non-occupational exposures, including drinking water from ground water or 

surface water and exposure through pesticide use in gardens, lawns, or buildings (residential and 

other indoor uses). 

In addition to pesticide use, DBS has reported uses in personal care products, such as 

antiperspirants, shampoos, conditioners, and moisturizers. 

For DBS, a qualitative assessment for all pathways of human exposure (food, drinking water, 

and residential) is appropriate give the lack of human health concerns associated with exposure 

to DBS when used as an inert ingredient in pesticide formulations. 

B. Cumulative Exposure 

Section 408(b)(2)(D)(v) of FFFDCA requires that, when considering whether to establish, 

modify, or revoke a tolerance, the Agency consider “available information” concerning the 

cumulative effects of a particular pesticide’s residues and “other substances that have a common 

mechanism of toxicity.” 

Unlike other pesticide ingredients for which EPA has followed as cumulative risk approach 

based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity 

finding as to DBS and any other substances and, DBS does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that DBS has a common mechanism of toxicity with other substances. For 

information regarding EPA’s efforts to determine which chemicals have a common mechanism 

of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements 

released by EPA’s Office of Pesticide Programs concerning common mechanism determinations 

and procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/. 

VII. Environmental Fate 
Page 15 of 19 

The values for melting point and boiling point of DBS are high. These two factors, along with 

the vapor pressure indicate that DBS exists primarily as a solid. The low vapor pressure and 

Henry’s Law Constant estimates indicate that DBS is unlikely to volatilize from dry surfaces or 

moist surfaces or moist soils or sediments. The Koc values for DBS indicate that sorption to 

soils and sediments may occur and is not likely to enter groundwater. DBS also has low 

bioconcentration potential and is considered to be nonvolatile. 

VIII. Ecological Effects 

The ecotoxicity of DBS was estimated using Ecological Structure Activity Relationships 

(ECOSAR). ECOSAR is a computerized predictive system that estimates the aquatic toxicity of 

industrial chemicals. The program estimates a chemical's acute (short-term) toxicity and chronic 

(long-term or delayed) toxicity to aquatic organisms such as fish, aquatic invertebrates, and 

aquatic plants by using Structure Activity Relationships (SARs). 

(http://www.epa.gov/oppt/newchems/tools/21ecosar.htm) 

The estimated ecotoxicity values for DBS are listed in Table 5. The results indicate that the 

ecotoxicity of DBS ranges from practically nontoxic to slightly toxic 

Table 5: ECOSAR Predicted Calculations for DBS (CAS Reg. No. 32647-67-9) 

Organism Duration End Point Predicted mg/L 

(ppm) 

Fish 96-hr LC50 959.312 * 

Fish 14-day LC50 960.414 * 

Daphnid 48-hr LC50 493.980 * 

Green Algae 96-hr EC50 179.562 

Fish 30-day ChV 95.913 

Daphnid ChV 51.955 

Green Algae ChV 61.933 

Fish (SW) 96-hr LC50 1397.457 * 

Mysid Shrimp 96-hr LC50 1482.969 * 

Fish (SW) ChV 98.148 

Mysid Shrimp (SW) ChV 153.786 

Earthworm 14-day LC50 721.581 * 

* Asterisk designates: Chemical may not be soluble enough to measure this predicted effect 

IX. Environmental Justice Statement 

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. 
Page 16 of 19 

X. Human Health Risk Characterization 

Dow Agrosciences submitted a petition (#9E7581) proposing to establish an exemption from the 

requirement of a tolerance under 40 CFR §180.920 (pre-harvest only) for residues of DBS when 

used as a pesticide inert ingredient, limited to herbicide use only with a 3% formulation cap. 

Based upon review of the data supporting the petition, EPA has modified the requested 

exemption. No limitations are necessary because no hazard was identified. 

DBS is an organic molecule capable of inducing gelation in a variety of organic solvents and 

polymers at low concentrations. (Wilder, et. al.) Its purpose in formulation is as a clarifying 

agent or nucleating agent and has reported uses in antiperspirant and deodorant products. It is 

also used as an ingredient in personal care products such as shampoos, conditioners, and 

moisturizers. 

DBS is not expected to pose a hazard when used for its proposed use pattern. A skin 

sensitization study on guinea pigs determined that DBS is not a sensitizer. A primary dermal 

irritation study in rats determined that DBS is not irritating. The combined LD50 of DBS in an 

acute oral toxicity study in mice was 12,800 mg/kg/day and the LD50 (males only) in an acute 

dermal toxicity study on mice was 6400 mg/kg/day. 

Three subchronic oral toxicity studies, showed no signs of systemic toxicity at high doses. In a 

90-day oral toxicity study of DBS in mice and rats, the NOAEL for mice was 3200 mg/kg/day 

and 2000 mg/kg/day for rats. In a 13-week oral toxicity study of Millad 3988 in rats, the 

NOAEL was 1261.3 mg/kg/day for males and 1479.2 mg/kg/day for females. In a 90-day 

toxicity study of Millad 3905 in dogs, the NOAEL was 92.1 mg/kg/day for males and 91.5 

mg/kg/day for females (highest dose tested). 

Based on the results of mutagenicity studies, DBS is not likely to be mutagenic. No 

neurotoxicity studies are available; however, no signs of neurotoxicity were observed in any of 

the available studies.

The toxicity database is sufficient for DBS and potential exposure is adequately characterized 

given the low toxicity of the chemical. In terms of hazard, there are low concerns and no 

residual uncertainties regarding prenatal and/or postnatal toxicity. DBS has low subchronic 

toxicity. Although no developmental or reproductive studies, per se, were identified, subchronic 

90-day studies in dogs, rats and mice have not demonstrated any systemic toxicity or effects on 

the reproductive organs. No acute or subchronic neurotoxicity studies are available, but there 

were no signs of neurological effects observed in the database at high doses. Therefore, the 

Agency concluded that the developmental neurotoxicity study is not required. No 

immunotoxicity study is available, however, no systemic toxicity was observed in mice, rats and 

dogs at high doses. In addition, no hazard has been identified following exposure to DBS. 

Based on this information, there is no concern at this time for increased sensitivity to infants and 

children to DBS when used as an inert ingredient in pesticide formulations and a safety factor 

analysis has not been used to assess risk. For the same reason, EPA has determined that an 

additional safety factor is not needed to protect the safety of infants and children.
Page 17 of 19 

Residues of concern are not anticipated for dietary (food and drinking water) or for residential 

exposure from the use of DBS for the proposed use pattern as an inert ingredient in pesticide 

products. As discussed above, EPA expects aggregate exposure to DBS to pose no appreciable 

dietary risk, given that the data on DBS show a lack of systemic toxicity at doses up to 3200 

mg/kg/day. 

Taking into consideration all available information on DBS, EPA concludes that there is a 

reasonable certainty that no harm will result to the general population or to infants and children 

from aggregate exposure to DBS. Therefore, the establishment of an exemption from tolerance 

under 40 CFR 180.920 for residues of DBS when used as an inert ingredient in pesticide 

formulations applied pre-harvest can be considered safe under section 408 of the FFDCA. 

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