2

Table of Contents

EXECUTIVE SUMMARY ................................................................................................... 3

I. BACKGROUND ................................................................................................................... 7

II. INERT INGREDIENT PROFILE ......................................................................................... 7

A. Summary of Uses....................................................................................................... 7

B. Physical Chemical Properties .................................................................................... 7

III. HUMAN HEALTH ASSESSMENT..................................................................................... 8

A. Summary of Toxicity Data......................................................................................... 8

B. Toxicity Endpoint Selection .................................................................................... 19

C. Special Considerations for Infants and Children ..................................................... 21

IV. EXPOSURE ASSESSMENT .............................................................................................. 21

A. Dietary Exposure: .................................................................................................... 22

i. Acute exposure ..................................................................................................... 22

ii. Chronic exposure................................................................................................. 22

iii. Cancer exposure ................................................................................................. 23

B. Dietary Exposure from Drinking Water: ................................................................. 24

C. Residential (Non-Occupational, Non-Dietary) Exposure:....................................... 24

V. AGGREGATE RISK ASSESSMENT ................................................................................ 24

i. Acute Dietary Risk................................................................................................ 24

ii. Chronic Dietary Risk. .......................................................................................... 24

iii. Aggregate Cancer Risk for U.S. Population....................................................... 25

VI. OCCUPATIONAL EXPOSURE/RISK PATHWAY.......................................................... 25

A. Occupational Handler Risk...................................................................................... 25

B. Occupational Post-Application Risk........................................................................ 29

VII. CUMULATIVE EXPOSURE ............................................................................................. 29

VIII. ENVIRONMENTAL JUSTICE STATEMENT.................................................................. 29

IX. ENVIRONMENTAL FATE CONSIDERATIONS ............................................................ 30

X. ECOTOXICITY................................................................................................................... 31

XI. RISK CHARACTERIZATION........................................................................................... 32

REFERENCES ...................................................................................................................... 35

APPENDIX...................................................................................................................................... 37
3

EXECUTIVE SUMMARY

In August 2013 Exponent on behalf of Clariant Corporation submitted a petition to the 

EPA to amend 40 CFR 180.920 by establishing an exemption from the requirement of a tolerance 

for the use of secondary alkane (C13-C17) sulfonates (SAS) (CAS Reg. Nos. 85711-69-9 and 

97489-15-1) as pesticide inert ingredients (surfactants) for use in food crops in accordance with 40 

CFR 180.920 (pre-harvest pesticide applications) with a limitation of 40% in formulation.

Secondary alkane (C13-C17) sulfonates (which will be hereby referred to as SAS) are 

widely used surfactants in detergents and in industrial chemicals. SAS are currently not approved 

for use as inert ingredients in non-food or food-use pesticide formulations in the US. There are 

currently no FDA approved cosmetic or food uses. There is a Human and Environmental Risk 

Assessment on ingredients of household cleaning products by HERA (2005).SAS are synthetic 

anionic surfactants that can be described as sodium salts of secondary C13-C17 alkane (paraffin) 

sulfonic acids. 

The acute oral LD50 for SAS in rats is between 500 and 2000 mg/kg bw. The acute dermal 

exposure to mice did not indicate any potential for acute or systemic toxicity. SAS is a mild eye 

irritant based on a primary eye irritation study in rabbits (Tox Category III). SAS is not dermally 

irritating based on primary skin irritation study in rabbits (Tox Category IV). SAS is not a dermal 

sensitizer in guinea pigs and no acute inhalation studies were available in the database however,

due to the low vapor pressure, inhalation is not expected to be a major exposure route of concern. 

A chronic toxicity study (52 weeks) was conducted on SAS (60%) in rats and demonstrated 

a No Observed Adverse Effect Level (NOAEL) of 4,000 ppm (about 168 mg/kg bw/day in males 

and 227 mg/kg bw/day in females), and a Lowest Observed Adverse Effect Level (LOAEL) of 

20,000 ppm (about 920 mg/kg bw/day in males and 1281 mg/kg bw/day in females) based on 

reduced body weight, body weight gain and the clinical signs of reduced grooming in males and 

females. 

Developmental and reproductive toxicity was examined in a two-generation reproduction 

study in rats dosed with SAS (60%). There was no indication that offspring were more susceptible 

to test substance toxicity than the parental adults. The parental systemic LOAEL was 3000 ppm

(177 mg/kg bw in males and 181 mg/kg bw in females), based on decreased body weight gain 

during premating and on reduced organ weight. The parental NOAEL was 1000 ppm (58.2 mg/kg 

bw for males and 66 mg/kg bw for females). The offspring LOAEL was 3000 ppm (177 mg/kg 

bw) based on decreased pre- and post-implantation loss and decreased weight gain in offspring. 

The offspring NOAEL was 1000 ppm (58.2 mg/kg bw). 

SAS (93%) was not mutagenic when tested in the in vitro mammalian cell gene mutation 

assay, and SAS (30%) was not mutagenic in the Salmonella typhimurium reverse mutation assay.

SAS (60%) was administered in the diet to rats in a combined chronic 

toxicity/carcinogenicity study at concentrations (adjusted for the active ingredient content of 60%) 

of 0.0, 0.08, 0.40, or 2.0% (about 0.0, 27.9, 145.3, and 805 mg/kg bw/day for males and 0.0, 36.5, 

182.9, and 1032 mg/kg bw/day for females, respectively) for 104 weeks. There were no treatment-
4

related neoplastic or non-neoplastic microscopic effects observed up to 2.0% (M/F: 805/1032 

mg/kg/day). A LOAEL was not identified. However, body weights of high-dose males and 

females were lower by about 20% relative to controls throughout most of the study. The decreased 

body weights were attributed to decreased food intake. Although decreased body weight is 

typically viewed as an adverse effect, in this study survival of males and females from the high 

dose group was substantially higher than that of the control group. The improved survival was 

attributed to the leaner body conformation, so the decreased body weight was not viewed as an 

adverse effect. 

SAS (60%) was tested in a dermal carcinogenicity study in mice No indication of increased 

incidence relative to controls of malignant neoplasms was observed. No LOAEL was 

demonstrated. The NOAEL was 1.0% (about 0.6 mg/treatment), the highest concentration applied 

to the skin. 

SAS was rapidly absorbed and excreted. Primary routes of excretion were feces and urine. 

There was no bioaccumulation. Metabolites were not identified. Dermal application on male rats 

demonstrated low penetration potential of 14C-radiolabled SAS. The elimination half-life averaged 

about 41 hours (15% elimination in air, 18% in urine and about 31% in feces). About 2.2% of the 

radioactivity was found in the treated skin and 35% in the bandage used to cover the treated area. 

SAS has a low potential for dermal absorption.

No immunotoxicity or neurotoxicity studies on SAS were available in the database.

However, evidence of immunotoxicity or neurotoxicity was not observed in the submitted studies. 

EPA has also determined that reliable data show the safety of infants and children would be 

adequately protected if the FQPA SF were reduced to 1X. 

An acute dietary risk assessment was not conducted because no endpoint of concern 

following a single exposure was identified in the available studies. A chronic dietary exposure 

assessment was completed and performed using the Dietary Exposure Evaluation Model DEEMFCIDTM, Version 3.16. The chronic Reference Dose (cRfD) of 58.2 mg/kg/day was determined on 

the basis of the reproductive toxicity study in rats. The LOAEL of 177 mg/kg/day SAS was based 

on decreased body weight gain during premating and on reduced organ weight. This study 

provided the lowest NOAEL in the database (most sensitive endpoint) and will also provide the 

most protective limits for human effects. An UF of 100X (10-fold for interspecies extrapolation 

and 10-fold for intra species variability) was applied to the NOAEL of 58.2 mg/kg/day to derive 

the cRfD. The FQPA safety factor of 1X is applicable for chronic dietary risk assessment. 

Therefore, the chronic population-adjusted dose (cPAD) is 0.582 mg/kg/day. This endpoint of

concern was also used for all dermal and inhalation exposure scenarios. Dermal absorption was 

determined to be 50% based on the dermal absorption study and inhalation absorption was 

assumed to be 100%. 

Based on analyses of estimated dietary risks for the general U.S. population and various 

population subgroups, the chronic dietary exposure estimates for SAS are below the Agency’s 

level of concern. The chronic dietary exposure estimate for the highest exposed population 
5

subgroup, children 1-2 years old is 97.1% of the chronic population adjusted dose (cPAD) and 

26.0% of the cPAD for the general population. 

The Agency’s level of concern (LOC) for SAS occupational and residential dermal and 

inhalation exposures is 100. The LOC is based on a 10X uncertainty factor (UF) to account for 

interspecies extrapolation to humans from the animal test species and 10X UF to account for 

intraspecies sensitivity.

Short-term aggregate exposure takes into account short-term residential exposure plus 

chronic exposure to food and water (considered to be a background exposure level). SAS is an 

inert ingredient in pesticide products that is not expected to result in short-term residential 

exposure since the proposed uses are for commercial agricultural seed treatment and possible foliar 

applications. Therefore the Agency has determined that aggregating chronic exposure through food 

and water with short-term residential exposures is not required. 

Intermediate-term aggregate exposure takes into account intermediate-term residential 

exposure plus chronic exposure to food and water (considered to be a background exposure level). 

SAS is an inert ingredient in pesticide products that is not expected to result in intermediate-term 

residential exposure since the proposed uses are for commercial agricultural seed treatment and 

possible foliar applications. Therefore the Agency has determined that aggregating chronic 

exposure through food and water with intermediate-term residential exposures is not required. 

Occupational handler risks are not expected to be of concern for all scenarios evaluated. It 

is noted that this occupational handler assessment assumes that mixer/loader/applicators are not 

wearing protective respirators when using open pour in support of aerial and groundboom 

application. The estimated MOEs are greater than 100 based on 100% inhalation absorption and 

50% dermal absorption except for mixer/loader aerial/chemigation which had a combined 

herbicide inhalation and dermal MOE of 64.3. However based on the amount of conservatism built 

into the model (i.e. liquid aerial/chemigation with no respirator, maximum application rate on corn 

and treating 1200 A/day) the estimated combined occupational herbicide MOEs are not expected 

to be of concern. Additional, SAS is expected to be used in seed treatments and the occupational 

handler dermal/inhalation exposure and MOEs are calculated for this application method. The 

lowest estimated combined seed treatment MOE was 620 for “multiple activities” exposure 

scenario, therefore the estimated combined occupational seed treatment MOEs are also not 

expected to be of concern. This assessment is considered to be a screening level estimate, 

demonstrating that there are minimal potential risks to workers re-entering fields treated with 

pesticides containing SAS as inert ingredients. Therefore an occupational post application risk 

assessment was not performed.

Once SAS is released into the environment, it is expected to partition between soil and 

water. Based on fugacity modeling, SAS should partition primarily to the soil compartment. 

Therefore SAS used in either seed or foliar applications can be expected to have limited mobility 

in the environment. SAS is not expected to bioconcentrate or bioaccumulate based on a low 

logKow of 0.2.
6

Based on studies conducted with various aquatic species, SAS is considered highly toxic to 

aquatic organisms. Based on a 9 day chronic fish toxicity study, the NOEC was 0.9 mg/ml and a 

21 day chronic daphnia toxicity study, the NOECrepro was 0.4 mg/ml. SAS is not expected to be 

toxic to birds based on the lack of bioconcentration and bioaccumulation.

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.

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

reasonable certainty that no harm to any population subgroup will result from aggregate exposure 

to SAS when considering residential, occupational, dietary exposure and all other nonoccupational 

sources of pesticide exposure for which there is reliable information. Therefore, the establishment 

of an exemption from tolerance under 40 CFR 180.920 for residues of Secondary Alkane (C13-

C17) Sulfonates (CAS Reg. No. 85711-69-9 and 97489-15-1) when used as a pesticide inert 

ingredient applied to pre-harvest crops with a limitation of 40% in formulation, can be considered 

assessed as safe under section 408(q) of the FFDCA.
7

I. BACKGROUND

Exponent on behalf of Clariant Corporation (EPA Company Number 8340, 4000 Monroe 

Road Charlotte, NC 28205) is requesting that EPA establish a tolerance exemption for secondary 

alkane (C13-C17) sulfonates (CAS Reg. No. 85711-69-9 and 97489-15-1) as pesticide inert 

ingredients under 40 CFR 180.920 (pre-harvest for seed treatment and foliar applications in food 

crops). Secondary alkane (C13-C17) sulfonates also referred to as (C13-C17 SAS) is currently not 

approved for use as inert ingredients in non-food or food-use pesticide formulations in the US. 

There are currently no FDA approved cosmetic or food uses. Toxicology, environmental and 

use/exposure data reported by the Human and Environmental Risk Assessment on ingredients of 

household cleaning products (HERA 2005) for CAS Reg. No. 85711-69-9 are referenced in this 

document as well as data provided by REACH Chemical Safety Report (2010) for CAS Reg. No. 

97489-15-1. 

SAS are synthetic anionic surfactants that can be described as sodium salts of secondary 

C13-C17 alkane (paraffin) sulfonic acids, which will be used as surfactants in pesticide

formulations applied to growing crops only under 40 CFR 180.920. It is proposed that because 

CAS Reg. No. 97489-15-1, sulfonic acids, C14-C17 secondary alkane, has an alkyl carbon chain 

length that falls within the carbon chain length range of sulfonic acids, C13-C17 secondary alkane 

(CAS Reg. No. 85711-69-9) it is appropriate to bridge data for the SAS surfactant CAS Reg. No. 

85711-69-9 to CAS Reg. No. 97489-15-1. 

II. INERT INGREDIENT PROFILE

A. Summary of Uses

SAS surfactants are currently used in detergents and for industrial chemical use in the EU.

B. Physical Chemical Properties

Some of the physical and chemical characteristics of SAS, along with its structure and 

nomenclature, are found in Table 1.

Table 1. Physical and Chemical Properties of Secondary Alkane (C13-C17) Sulfonates (SAS)

Parameter Value Source

Structure Various

CAS # 85711-69-9

97489-15-1

Molecular Formula Various

Molecular Weight (g/mol) ~328.0

Common Names

Sulfonic acids, C14-C17 sec-alkane, 

sodium salts; secondary alkane sulfonate 

sodium salts; Sec-alkane sulfonatesodium salts

Submitted petition

Color yellowish HERA 2005

Physical State waxy HERA 2005

Odor

Flash Point

pH 7 (at 20°C 10g/L) HERA 2005
8

Table 1. Physical and Chemical Properties of Secondary Alkane (C13-C17) Sulfonates (SAS)

Parameter Value Source

Viscosity (dynamic)

Melting Point <200°C (softening) HERA 2005

Boiling Point (°C) @ 19 hPa Not determined HERA 2005

Specific Gravity

Bulk Density 600 kg/m3 HERA 2005

Dissociation Constant (pKa) pKa <0 estimated for C16 SAS (at 25°C) HERA 2005

Octanol/water Partition Coefficient 

(Kow)

Log Kow = 0.2 (at 20°C)

Log Kow = 2.76 (at 20°C) calculated for 

C16 SAS

EPISuite 4.1 by Clariant (2010)

HERA 2005

Soil organic carbon/water Partition 

coefficient (Koc) Log Koc = 2.181 (Kow method) EPISuite 4.1 by Clariant (2010)

Solubility (at 25°C) 115.6 mg/L water (at 25°C) EPISuite 4.1 by Clariant (2010)

Vapor Pressure 

1.97 x 10-11 mg/HG (at 25°C)

5.3 x 10-11 Pa (at 25°C) calculated for 

C16 SAS

EPISuite 4.1 by Clariant (2010)

HERA 2005

Henry's Law Constant 3.6 x 10-5calculated for C16 SAS HERA 2005

III. HUMAN HEALTH ASSESSMENT

A. Summary of Toxicity Data 

Clariant Corporation has submitted studies on SAS at varying concentrations. 

Acute Oral Toxicity

The following summary is cited from 2010 REACH Chemical Safety Report on SAS.

The acute oral toxicity of sec-alkane sulfonate-sodium salts SAS (93%) was 

investigated in rats using water as vehicle. 5 male and 5 female rats per dose group 

were administered the test compound by single-dose gavage at dose levels of 500 or 

2000 mg/kg body weight. The observation period was 14 days. After administration 

of 2000 mg/kg body weight all animals died within 24 hours p.a. Fatal intoxicated 

animals showed the following symptoms: bristled coat, squatting posture, stilted 

gait, irregular respiration and decreased spontaneous activity. At necropsy the 

following findings were revealed: stomach full of reddish-black mass (haemoccult 

positiv), intestinal tract filled with reddish mucous (haemoccult positv), lungs partly 

filled with blood. After administration of 500 mg/kg body weight no mortalities 

occurred. Unspecific clinical symptoms (bristled coat, squatting posture, stilted 

gait) were present up to 24 hours p.a. No clinical symptoms were observed from 

day 1 until the end of the observation period. Based on the findings of this limit-test 

the median lethal dosage (LD50) of sec-alkane sulfonate-sodium salts SAS (93%) 

in rats is between 500 and 2000 mg/kg body weight. (Hoechst AG 1988)

Dermal Toxicity

The following summary is referenced from 2010 REACH Chemical Safety Report on SAS. 
9

In an acute dermal toxicity study, female CD-1 mice were dosed with SAS (60%). Acute 

dermal exposures to mice (non-GLP) did not indicate any potential or acute and/or 

systemic toxicity. The LD50 is > 2000 mg/kg bw (Life Science Research 1975).

Inhalation Toxicity

No inhalation studies were available in the database.

Primary Eye Irritation

The following summary is cited from 2010 REACH Chemical Safety Report on SAS. 

Sec-alkane sulfonate-sodium salts SAS (30%) was tested for primary eye irritation 

according to OECD 405 and GLP. Based on the observed skin irritating potential in 

rabbits, testing for eye irritation was conducted in only one rabbit. 0.1 mL of 

undilauted Hostapur SAS 30 was applied into the left conjunctival sac of this rabbit. 

The right eye served as a control. Assessments were made 1, 24, 48 and 72 hours 

p.a. as well as 7 days after treatment. From one hour up to seven days moderate 

irritations including corneal and iridial effects were observed. After seven days a 

clear vascularisation of the cornea was observed. Based on the results of this study, 

sec-alkane sulfonate-sodium salts SAS (30%) when tested according to OECD 

guideline 405 was considered to be severely irritating to eyes and thus no further 

animals were included in the test.

In a primary eye irritation study (MRID 49146412), 10 μL of undiluted SAS [30% purity; 

Batch No. 04665 (September 93); liquid; pH ~7] was instilled as received directly on the 

cornea between its center and the superior limbus of the left eye of one male and two 

female young adult New Zealand White rabbits (CRL:KBL (NZW) BR; age: 15 weeks; 

body weight: male: 2.7 kg and female: 2.9-3.0 kg; source: Charles River, Stolzenseeweg 

32-36, D-88353 Kisslegg). The untreated eye served as a control. The animals were 

observed at 1, 24, 48, and 72 hours and 7 days post-instillation.

No iritis was noted on any animal during the study. Corneal opacity was noted on one 

animal 48 and 72 hours after test material instillation with clearance by day 7. Positive 

conjunctival irritation was noted on three animals one hour after test material instillation 

with clearance on two rabbits by 24 hours and on one rabbit by day 7. The highest 

maximum mean total score was 13.3, recorded one hour after test material instillation.

Based on highest maximum mean total score and no irritation by day 7, SAS (30%) was 

mildly irritating. This study as indicated that only 0.01 mL instead of 0.1 mL of test 

material was instilled into the rabbit eye. If 0.1 mL of test material was used, the test 

material likely would have caused cause further irritation/damage. 

All available OECD 405 studies conducted with C13-C17 SAS aqueous solutions were 

consistent and demonstrated concentration dependent irritant effects. Results demonstrate 

that C13-C17 is slightly irritating to the eye at 15% and that irritation increases with 

increasing concentrations, i.e., irritating to eye at concentrations of 30% and above. 

However, when the low-volume technique (LVET) is utilized even a 30% aqueous solution 
10

does not cause significant eye irritation. Based on the results of the available studies, C13-

C17 SAS up to 30% is moderately irritating to the eye (EPA Category III).

Primary Skin Irritation

In a primary dermal irritation study (MRID 49146409), three male young adult New 

Zealand White rabbits (age: not reported; body weight: at least 1.5 kg; source: Paulistee, 

Mairipora, SP) were dermally exposed to 0.5 g of undiluted SAS (93%) (concentration not 

reported; Batch No. 2703061; pH 7.5) for 4 hours on a 6 cm2area of the clipped flank skin 

that was covered with a semi-occlusive gauze patch and held in place with non-irritating 

tape. The patch was removed and the residual test material was removed with water at the 

end of a 4-hour exposure. The animals were observed and irritation was scored at 1, and 

24, 48, and 72 hours and 7 days after patch removal. 

All animals survived the study. Very slight erythema was noted on three animals one hour 

after removal of the patch with clearance on one animal by 72 hours and on two animals by 

day 7. One animal had very slight edema one hour after patch removal with clearance by 

48 hours. Another animal had very slight edema one hour after patch removal that became 

slight edema then reduced to very slight edema with clearance by day 7.

In this study, the test material was slightly irritating and the Primary Irritation Index (PII) 

was 1.5. 

Dermal Sensitization

The following summary is cited from 2010 REACH Chemical Safety Report for SAS. 

Sec-alkane sulfonate-sodium salts SAS (60%) was examined for its capacity to 

cause contact allergy by the maximization test according to Magnusson and 

Kligman with guinea pigs. Based on a screening study using groups of 6 male 

guinea pigs the highest non-irritating concentration of sec-alkane sulfonate-sodium 

salts SAS (60%) was established to be 5% in water. In the main study 15 male 

guinea pigs were used. Induction exposure included 10 intracutaneous injections of 

0.05 mL of a solution of 500 mg sec-alkane sulfonate-sodium salts SAS (60%) in 

10 mL of Freund`s complete adjuvant. Challenge was made 14 days after the last 

injection using 0.1 mL of sec-alkane sulfonate-sodium salts SAS (60%) at 5% test 

concentration. Readings performed 24 and 48 hours after the challenge treatment 

revealed no signs of skin reactions (sensitization incidence = 0%). Additionally, 

also a second challenge treatment using the same test conditions like in the first 

challenge revealed no signs of skin reactions (sensitization incidence = 0%). Thus it 

was concluded that sec-alkane sulfonate-sodium salts SAS is not a skin sensitizer.

(Hoechst AG 1974)

Sec-alkane sulfonate-sodium salts (60%) (Marlon PS 60) was tested for skin 

sensitization according to OECD guideline 406 but without GLP using the 

maximaization test protocol of Magnusson and Kligman. Based on prescreening, 
11

the primary irritating as well as non-irritating concentration was 5% and 1% 

respectively. 20 guinea pigs in the test group and 10 guinea pigs as control were 

used. Intradermal induction was performed using 0.1 mL of a 0.05% solution of 

Marlon PS 60 in Freund`s complete adjuvant. Dermal induction was performed one 

week later by dermal exposure with a 5% solution of Marlon PS 60 in water. 14 

days after the dermal induction phase challenge treatment was conducted using a 

1% solution of the test material in water. Readings performed after 24 and 48 hours 

after challenge treatment revealed no signs of skin reactions (sensitization incidence 

= 0%). Based on the test results, the authors concluded that sec-alkane sulfonatesodium salts (Marlon PS 60) is not a skin sensitizer. (Huls AG 1986).

The results of the available acute toxicity studies are summarized in Table 2.

Acute Toxicity

Table 2. Acute Toxicity Profile of Secondary Alkane (C13-C17) Sulfonates (SAS)

Study Type Results MRIDs # /Reference

Acute Oral - rat LD50 =500 - 2000 mg/kg bw Hoechst AG 1971, 1977, 1979, 1988 and Life 

Science Research 1975

Acute Dermal –

rats/rabbits

No potential for acute/systemic 

toxicity

Life Science Research 1975

Acute Inhalation - N/A N/A N/A

Primary Eye Irritation -

rabbit

Moderately irritating Hoechst AG 1989; RCC 1990, 1995; Huls AG 

1986

Mildly irritating MRID 49146412

Primary Skin Irritation -

rabbit Slightly irritating MRID 49146409

Dermal Sensitization Not a dermal sensitizer Hoechst AG 1974 and Huls AG 1986

Chronic Toxicity -

A chronic toxicity study was conducted on SAS (60%) in Sprague-Dawley rats (MRID 

49146406). The test material was administered to 20 rats/sex/dose in the diet for 52 weeks

at dose levels of 0, 800, 4,000, or 20,000 ppm (calculated as equivalent to 0, 34, 168, and 

920 mg/kg bw/day in males, respectively; and 0, 45, 227, and 1281 mg/kg bw/day in 

females, respectively and corrected for purity). Groups of 10 rats/sex/dose served as 

satellite animals and were fed diet containing the same dose levels followed by interim 

sacrifice after 26 weeks of treatment. Hematology (10 rats/sex/group) and clinical 

chemistry (5 rats/sex/group) analyses were conducted on blood drawn at 26 and 52 weeks. 

Urinalysis was conducted on urine from 5 rats/sex/group after 26 and 52 weeks. 

Ophthalmoscopic examinations were conducted on all rats prior to the study and all rats 

scheduled for sacrifice at 26 or 52 weeks. All animals that died and those sacrificed at 26 

or 52 weeks were subjected to gross pathological examination, selected organs were 

weighed, and selected tissues examined histologically. 

A lack of grooming activity was observed throughout the study in rats given 20,000 ppm

(not verifiable since the incidence data for clinical signs were not provided). The study 

authors reported only mean absolute body weight, but the study reviewer subsequently 

calculated body weight gains and conducted comparative statistics. In males at 20,000 ppm, 

mean absolute body weight from Weeks 1-4 was 91-94% of controls, and from week 5 to 
12

study termination was 77-89% of controls. The final mean body weight in males at the high 

dose was 82% of controls (p≤0.01). Body weight gain at the high dose was reduced to 85% 

of controls over weeks 0-13 and to 58% of controls over weeks 13-25, but was comparable 

to control over weeks 25-52. However, overall body weight gain (weeks 0-52) in high dose 

males was 80% of controls (p≤0.01). A similar pattern was seen in females at the high 

dose. Mean absolute body weight was decreased to 91-93% of controls for weeks 3-5. 

From week 6 to study termination, mean absolute body weight was reduced to 81-91% of 

controls. Body weight gain was reduced to 84% of controls over weeks 0-13 and to 51% of 

controls over weeks 13-25. Although not attaining statistical significance, body weight 

gain over weeks 25-52 was reduced to 73% of controls. Overall body weight gain for 

weeks 0-52 was 77% of controls (p≤0.01). No statistically significant or biologically 

significant decreases in mean body weight or body weight gain were observed in males or 

females at 800 ppm (34 mg/kg bw/day for males and 45 mg/kg bw/day for females) or 

4000 ppm (168 mg/kg bw/day for males and 227 mg/kg bw/day for females).

The reductions in body weight at the high dose were not accompanied by concomitant 

reductions in food consumption in females. Food consumption was statistically reduced in 

males, but only over the first few weeks of the study (food consumption at weeks 2, 3, 4, 5, 

and 11 was 85, 80, 81, 77, and 86% of controls, respectively); by 12 weeks, food 

consumption was generally comparable to controls. No other adverse effects on food 

consumption were observed in high-dose males or females, indicating that food efficiency 

was compromised.

A total of eight animals died during the course of the study, but the deaths were not related 

to treatment. No definitive, treatment-related effects were observed in hematology, clinical 

chemistry, ophthalmoscopic findings (data not included so this could not be verified), 

organ weights, or macroscopic or microscopic pathology. No tumors were related to 

treatment.

Based on these findings, the LOAEL was 20,000 ppm (calculated as equivalent to 920 

mg/kg bw/day in males and 1281 mg/kg bw/day in females) based on reduced body weight 

and body weight gain and the clinical signs of reduced grooming in males and females. 

The NOAEL is 4,000 ppm (calculated by reviewer as equivalent to 168 mg/kg bw/day in 

males and 227 mg/kg bw/day in females). This chronic oral study was conducted prior to 

the current Guideline (OCSPP 870.4100, OECD 452) without the indication that it was 

conducted to GLP requirements (40 CFR 160). No data on the concentration, homogeneity, 

and stability of the test diet preparations were provided. However considering these 

deficiencies, they do not have a significant impact on the overall toxicity of the chemical.

Genotoxicity

SAS (93%) was evaluated for mutagenicity in the in vitro mammalian cell gene mutation 

assay (MRID 49146410). Chinese hamster V79 cell cultures were exposed in a 

preliminary toxicity assay for 4 hours at concentrations of 0, 0.158, 0.5, 1.58, 5, 15.8, 50, 

158, and 500 μg/mL and for 20 hours at concentrations of 0, 5, 10, 15, 20, 25, 35, and 50 

μg/mL without activation, and they were also exposed for 4 hours with activation at 
13

concentrations of 0, 0.316, 1, 3.16, 10, 31.6, 100, 316, and 1000 μg/mL. Activation was 

carried out using S-9 from male Wistar rat liver induced with phenobarbital and βnapthoflavone. The cultures treated for 4 hours without S-9 activation showed no cell 

survival at concentrations of 15.8 μg/mL or higher, while the 20-hour exposures showed no 

toxicity up to 50 μg/mL, the highest concentration tested. This discrepancy in the pre-test 

results was not considered important because significant toxicity was seen at the highest 

concentrations used in subsequent mutagenicity tests without activation. Based on the 

results of that pre-test, the first mutation assay used a 4-hour exposure and concentrations 

of 0, 0.2, 0.5, 1.0, 3.0, 4.5, 5.5, 6.5, 7.5 and 8.25 μg/mL without activation and 

concentrations of 0, 30, 35, 40, 47, 50.2, 52.6, 53.8 and 55.0 μg/mL with activation. In the 

confirmatory assay, concentrations of 0, 10.0, 80.0, 90.0, 92.5, 95.0, 100.4, 102.2 and 104.0 

μg/mL were used without activation for a 20-hour exposure, and concentrations of 0, 20.0, 

42.5, 45.0, 49.6, 50.8, 52.0, 53.2 and 54.4 μg/mL were used with activation for a 4-hour 

exposure. Without activation, the relative growth was 6.4% for the highest concentration 

(8.25 μg/mL) in Exp. I and 19.3% for the highest concentration (104.0 μg/mL) in Exp. II. 

With activation, the relative growth was 20.2% for the highest concentration (55.0 μg/mL) 

in Exp. I and 18.8% for the highest concentration (54.4 μg/mL) in Exp. II. These results 

demonstrate that SAS (93%) was tested up to toxic levels without and with activation.

Either without or with activation, SAS (93%) did not induce a mutagenic response in 

Chinese hamster V79 cells at any concentration level. All of the positive controls gave 

appropriate responses, without and with activation, and the concurrent negative controls 

were in agreement with historical laboratory background values. Therefore, SAS (93%)

was not mutagenic in the in vitro mammalian cell gene mutation assay under the conditions 

of this testing using Chinese hamster V79 cell cultures (OCSPP 870.5300, OECD 476).

SAS (30%) A 297 T3/131 was tested in a reverse gene mutation assay (MRID 49146413) 

using Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 without and 

with S9 activation at concentrations of 0, 0.001, 0.01, 0.1, 1, and 5 μL/plate. Cytotoxicity 

was indicated in all strains at 5 μL/plate based on zero revertants at that concentration 

under all test conditions. The number of revertants per plate was not increased over the 

concurrent solvent control value at any test substance concentration, without or with S9-

mix, in any tester strain. Because no historical data were presented, it is unknown whether 

solvent controls gave appropriate responses. There were no positive controls. There was no 

evidence of induced mutant colonies over background up to the maximum concentration 

tested. However, no confirmatory mutagenicity assay was conducted and there were no 

positive controls. Major deficiencies of the study were that there were no positive controls, 

only four or fewer concentrations were tested at which revertants were found, and three of 

the four concentrations with revertants were far below cytotoxic levels (OCSPP 870.5100). 

Carcinogenicity

SAS (60%) was tested in a combined chronic toxicity/carcinogenicity study (MRID 

49146408). The test material was administered to groups of 50 Sprague Dawley 

rats/sex/dose in the diet at concentrations (adjusted for the active ingredient content of 

60%) of 0.0, 0.08, 0.40, or 2.0% in the diet (calculated as equivalent to 0.0, 27.9, 145.3, 
14

and 805 mg/kg bw/day for males and 0.0, 36.5, 182.9, and 1032 mg/kg bw/day for females, 

respectively and corrected for purity) for 104 weeks. 

Treatment did not induce long-term toxicity. Although rats of both sexes displayed a lack 

of grooming activity exacerbated by adherence of diet particles from the start of treatment 

through the end of the first year; the effect disappeared during the second year of treatment. 

Reduced body weights (12 – 16%) and body weight gains were seen in rats of both sexes 

receiving diets containing 2.0% test material during the first 13 weeks of treatment. Thereafter, the body weights of high-dose males and females were lower by 18-22% relative to 

controls through the remainder of the study. The decreased body weights were attributed to 

decreased food intake. Although decreased body weight is typically viewed as an adverse 

effect, in this study survival of high-dose males at study termination was 58% compared to 

18% in controls and in female rats, survival was 66% vs. 42% in controls. The improved 

survival was attributed to the leaner body conformation at the high dose. Therefore, the 

decreased body weight observed at the high-dose was not viewed as an adverse effect. The 

growth of both sexes receiving diets containing 0.40 and 0.08% in the diet were similar to 

controls. No treatment-related effects were found on hematology or urinalysis results 

(clinical chemistry, neurotoxicity studies, ophthalmoscopic examinations, and organ 

weights were not measured) and no treatment-related effects were noted at necropsy. 

There were no treatment-related neoplastic or non-neoplastic microscopic effects observed. 

Based on the study results, a LOAEL was not identified. The NOAEL for male and female 

Sprague Dawley rats was > 2.0% SAS (60%) in the diet (calculated by the reviewer as 

equivalent to 805 mg/kg bw/day in males and 1032 mg/kg bw/day in females). This 

chronic/carcinogenicity study in the rat was conducted prior to the current Guideline for a 

combined Chronic Toxicity/Carcinogenicity Oral Study (OCSPP 870.4300) without the 

indication that it was conducted to GLP requirements (40 CFR 160). Deficiencies of the 

study included lack of data on the concentration, homogeneity, and stability of the test diet 

preparations were not provided; statistical analyses as provided were not appropriate; and 

survival was below 25% in the male control group at study termination. However despite of 

all these deficiencies, this study demonstrates that there is no tumorigenic effect of this 

chemical at very high doses.

SAS (60%) was tested in a dermal carcinogenicity study in mice (MRID 49146407). The 

test substance was administered by dermal application (0.1 mL) to groups of 100 CD-1 

mice/sex at dilutions with distilled water of 0 (no treatment), 0 (vehicle control), 0.1%, 

0.5%, or 1.0% three times/week for 80 weeks and observed for an additional 24 weeks.

The amounts estimated by the reviewer that were applied to the skin for the respective 

concentrations were about 0.06, 0.3, and 0.6 mg/treatment. 

No test substance-related clinical finding were observed. The test substance did not alter 

survival relative to controls and there was no treatment-related effect on the distribution of 

factors contributing to death. No differences between treated and control groups were 

apparent in the body weight data, though statistical analyses were not performed. Females 

from the high dose group had slightly increased incidence of enlarged spleen (40/100) 

relative to controls (31/100 and 27/100 vehicle only) and increased incidence of lymph 
15

node enlargement (18/100 vs. 11/100 and 9/100 vehicle only). Similar findings were not 

observed in males. No marked differences were observed between treated and control 

groups in microscopic lesions of the skin. No indication of increased incidence relative to 

controls of malignant neoplasms was observed in males or females from the treated groups. 

The findings were similar with the incidences of benign neoplasms with no differences 

indicated between control and treated groups. No LOAEL was demonstrated in mice 

administered SAS on the skin. The NOAEL was 1.0% (about 0.6 mg/treatment), the 

highest concentration applied to the skin. The study did not meet any OCSPP guideline 

requirement and did not meet GLP requirements (40 CFR 160). The major deficiencies 

relative to the current Guideline (OCSPP 870.4200b) were: the lack of toxicity at any dose, 

including at the site of application; no dose selection rationale was provided; the test 

material was applied only three times per week; no statistical analyses of the data were 

conducted; and the incidence of microscopic lesions was vague, since no indication was 

provided on the number of animals found dead for which microscopic observation of 

tissues was either limited or not possible to perform due to autolysis.

No treatment-related tumors were observed in a chronic dietary toxicity study (52 weeks) 

conducted on Hostapur (SAS 60) in Sprague-Dawley rats (MRID 49146406; details 

presented in “Chronic Toxicity” in Section III of this document).

Reproductive Toxicity

Developmental and reproductive toxicity was examined in a two-generation reproduction 

study conducted in Charles River CD rats (MRID 49146411). For 60 days prior to mating, 

SAS (60%) was administered continuously in the diet to groups of 25 rats/sex/dose at 

dietary levels of 1000, 3000, or 10,000 ppm (equivalent to 58.2, 177, or 570 mg/kg bw/day 

in males, and 66, 181, or 566 mg/kg bw/day in females corrected for purity). Three 

additional groups of 25 female rats were not treated prior to mating, but were given diets 

containing 1000, 3000, or 10,000 ppm SAS during gestation day (GD) 6 to 15; male rats in 

these groups were not treated. Groups of males and females not treated were considered 

control animals for both the continuously treated rats and those treated only during 

gestation. 

Several parameters were evaluated which are not routinely done in reproduction studies. 

Prior to mating, after continuous treatment for 8 weeks with 1000, 3000, or 10,000 ppm 

and non-treatment for 60 days 5 males and 5 females per group were selected for 

hematological evaluation, organ weight, and macroscopic and microscopic evaluation. 

After the third mating (F1C and F2C litters), each litter was divided into two subgroups, one 

subgroup was euthanized at GD 13 and one subgroup was euthanized at GD 21. For each 

female in each subgroup, developmental toxicity parameters were measured. 

Continuous treatment with SAS during premating provided some indication of toxicity. 

Mean body weight of F0 males treated during pre-mating showed a dose-related decrease at 

3000 and 10,000 ppm, and a dose-related and significant decrease in F1 males at 3000 and 

10,000 ppm. The data for F1 males showed a dose-related decrease in body weight for each 

week for all treated groups (1,000-10,000 ppm) and significant decreases for each week at 

3000 and 10,000 ppm. Mean body weight of females in F0 and F1 generations showed a 
16

significant decrease at 10,000 ppm. The F0 data showed a consistent decrease in body 

weight during the 8 weeks of treatment which culminated in significance at 8 weeks in the 

high-dose group, and the F1 data showed a consistent and dose-related decrease in body 

weight for each week for each treated group, although the decreases did not reach statistical 

significance. Of the organ weights measured, relative liver weights were significantly 

reduced at 10,000 ppm in F0 males and absolute liver weight of F1 females at 3000 and 

10,000 ppm. Relative liver weight in females was significantly reduced at 10,000 ppm in F1

premating females. Weight of sex organs was not affected by the compound. The parental 

systemic LOAEL was 3000 ppm, based on decreased body weight gain during premating 

and on reduced organ weight. The parental systemic NOAEL was 1000 ppm (58.2 mg/kg 

bw/day). 

In F1C and F2C litters, there were scattered increases and decreases in pre- and postimplantation losses at both Gestation Day (GD) 13 and GD 21. Some of the increases are 

not significant because of the small number of litters utilized. Looking at F1C, on GD 21, at 

groups of control vs 10,000 ppm, pre-implantation loss increased from 8.3 to 17.8%, and 

the loss was dose-related in all groups. In F2C, at GD 13, there was an increase in preimplantation loss from 3.0 to 10.2%. Looking at dose levels of control vs 10,000 ppm 

dosed during gestation in F1C, on GD 21, there was a significant and dose-related increase 

from 8 to 31.5% in pre-implantation loss. In F2C, at GD 13, there was an increase from 3.0 

to 12.7% in pre-implantation loss and in post-implantation loss from 4.0 to 8.7%. At GD 

21, in F2C, there was an increase in post-implantation loss from 4.8 to 11.8%. Continuous 

treatment with 10,000 ppm SAS produced a significant decrease in pup weights at GD 21 

in F1A, a decrease in F1B not statistically significant, and a statistically significant decrease 

in F2B. The offspring LOAEL was 3000 ppm based on decreased pre- and postimplantation loss and decreased weight gain in offspring. The offspring NOAEL was 1000 

ppm (58.2 mg/kg bw/day).

This two-generation reproduction study was conducted prior to the current Guideline 

(OCSPP 870.3800, OECD 416) and prior to GLP requirements (40 CFR 160). Major 

deficiencies of the study were: 1) pathology results showed that there was widespread 

pneumonia (100% in males) and changes in lung pathology in males and females (eg., 

congestion, hyperplasia) after 60 days of treatment (prior to any mating); 2) there was a 

lack of individual animal data which reduced the robustness of the data; 3) too few litters 

were utilized which decreased the robustness of litter observations; and 4) insufficient 

information was provided on diet preparation (incorporation of the test substance, 

frequency of mixing, diet storage, and diet analyses for homogeneity, stability, and 

concentration. However, this study clearly demonstrates that there is a lack of reproductive 

toxicity and the lack of susceptibility of infants and children.

Immunotoxicity

No immunotoxicity studies were available in the database for SAS. However, evidence of 

immunotoxicity was not observed in the submitted studies.

Neurotoxicity
17

No neurotoxicity studies were available in the database for SAS. However, evidence of 

neurotoxicity was not observed in the submitted studies except decrease in grooming at 

high dose, however there were no incidences provided therefore it is difficult to conclude 

whether the effect is treatment related or not.

Metabolism and Pharmacokinetics

Sections of the following summary are cited directly from Clariant Corporation’s petition. 

HERA (2005) and additional references cited therein, have reported that primary nalkanesulfonates are metabolized to bisulfite and the corresponding aldehyde by 

Pseudomonas sp. By analogy HERA postulated that the proposed metabolic pathway may 

also be applicable to C13-C17 SAS.

Accordingly, the SAS surfactants are initially oxidized to generate a keto-bisulfite, which is 

degraded to bisulfite and an alkyl ketone metabolite. The ketone metabolite may be further 

metabolized through oxidative degradation (presumably to alkyl acetate ester metabolites). 

Ester cleavage would yield acetate and an alcohol, which should be further metabolized by 

β-oxidation fatty acid processes to ultimately generate carbon dioxide and water.

The C13-C17 SAS surfactants toxicokinetic data in rats (Clariant, 2010) substantiated the 

likelihood of a β-oxidation pathway since excretion of radiolabeled CO2 was observed. The 

mammalian toxicokinetics data also confirmed rapid excretion with the absence of 

bioaccumulation. 

14C-radiolabeled C13-C17 SAS administered by gavage to male rats at concentrations of 

0.5, 5.3 or 51 mg/kg was excreted according to a biphasic elimination with a biological 

half-life of 11 hours to 65 hours. Up to 17% of the administered radioactivity was exhaled 

as CO2, approximately 30% was excreted via urine and about 45% with feces. In total more 

than 90% of the applied radioactivity was excreted within the first 24 hours after 

application. There was no indication of bioaccumulation as demonstrated by very low 

residual radioactivity (< 1ppm) in organs after 7 days. Potential metabolites were not

identified.

Dermal application on male rats demonstrated low penetration potential of 14C-radiolabled 

C13-C17 SAS. Elimination half-life averaged about 41 hours (15% elimination in air 18% 

in urine and about 31% in feces. About 2.2% of the radioactivity was found in the treated 

skin and 35% in the bandage used to cover the treated area. All of which indicate a low 

potential for dermal absorption (calculated 50%).
18

Table 3. Toxicology Profile of Secondary Alkane (C13-C17) Sulfonates

Guideline No./ 

Study Type

Doses Levels Results MRID No. 

(year)/References

Chronic Toxicity Rat 

(diet)

OCSPP 870.4100a

OECD 452

0, 34, 168 and 920 

mg/kg bw/day

(males)

0, 45, 227 and 

1281 mg/kg 

bw/day (females)

Doses were 

reviewer 

calculated

NOAEL 168 mg/kg bw/day (males)

LOAEL 920 mg/kg bw/day (males) based on 

reduced body weight and body weight gain and 

the clinical signs of reduced grooming.

MRID 49146406

Ben-Dyke, R, and 

Newman, A.J. (1977)

In vitro bacterial

gene mutation test –

Chinese hamster V79

cells

OCSPP 870.5300

OECD 476

0, 0.158, 0.5, 1.58, 

5, 15.8, 50, 158, 

and 500 μg/ml 

with metabolic 

activation

0, 5, 10, 15, 20, 

25, 35 and 50 

μg/ml without 

metabolic 

activation

Negative MRID 49146410

Wallner, Barbara 

(2010)

In vitro bacterial 

gene mutation 

(Salmonella 

typhimurium and 

Escherichia coli

OCSPP 870.5100

OECD 471& 472

0, 0.001, 0.01, 0.1, 

1 and 5 μg/plate 

with and without 

metabolic 

activation

Negative MRID 49146413

Gericke, D. (1977)

Carcinogenicity – rat 

(diet)

OCSPP 870.4300

OECD 453

0.0, 0.08, 0.40, or 

2.0% in diet

Equivalent to:

0.0, 27.9, 145.3, 

and 805 mg/kg 

bw/day (males) 

0.0, 36.5, 182.9 

and 1032 mg/kg 

bw/day (females)

NOAEL > 2.0% (805 mg/kg bw/day in males 

and 1032 mg/kg bw/day in females calculated 

by reviewer)

LOAEL was not identified.

MRID 49146408

Ben-Dyke, r, Finn, 

J.P., and Newman, 

A.J. (1978)

Carcinogenicity –

mouse (dermal)

Non-guideline

0 (no treatement), 

0 (vehicle control), 

0.1%, 0.5% or 

1.0% three 

times/week for 80 

weeks.

Equivalent to:

2.4, 12, and 24 mL 

(males)

2.7, 14, and 27 mL 

(females)

NOAEL 1% (24 mL in males and 27 mL in 

females)

LOAEL was not identified.

MRID 49146407

McSheehy, TW, 

Finn, JP, Kiss, I. 

(1978)
19

Table 3. Toxicology Profile of Secondary Alkane (C13-C17) Sulfonates

Guideline No./ 

Study Type

Doses Levels Results MRID No. 

(year)/References

Reproduction and 

Fertility Effects 

Study – rat

OCSPP 870.3800

OECD 416

1000, 3000, or 

10,000 ppm

Equivalent to:

58.2, 177, or 570 

mg/kg bw/day 

(males)

66, 181, or 566

mg/kg bw/day 

(females)

Parental systemic NOAEL is 1000 ppm.

Parental systemic LOAEL is 3000 ppm based 

on reduced body weight gain during premating 

and on reduced organ weight.

Offspring NOAEL is 1000 ppm.

Offspring LOAEL is 3000 ppm based on 

decreased pre- and post-implantation loss and 

decreased weight gain in offspring. 

MRID 49146411

Tesh, J.M., 

Davidson, E.J., 

Newman, A.J. (1978)

Toxicokinetics – rat 

(gavage)

Equivalent to OCSPP 

870.7485 or OECD 

417

0.51, 5.3 or 51 

mg/kg

Blood level reached maximum about 2 to 6 

hours after administration. Elimination from 

blood was biphasic with half-lives of 11 and 65 

hours. 17% was exhaled as Co2, 30% excreted 

via urine and 45% with feces. 90% excreted in 

first 24 hours. No bioaccumulation potential 

based on results.

Hoechst AG (1977a)

Toxicokinetics – rat 

(dermal absorption)

Equivalent to OECD 

427

0.25 mg per 

animal

Blood level reached maximum about 2 to 6 

hours after application. Elimination half-life 

was average of 41 hours (air approximately 

15%, urine 18%, feces 31%). Most 

radioactivity as found in bandage (35%) 

whereas only 2.2% was detected in treated skin 

7 days post application. Low skin penetration 

potential based on results. 50% absorption rate.

Hoechst AG (1977b)

B. Toxicity Endpoint Selection

The two generation reproductive toxicity study in rats was selected for oral, dietary and 

inhalation exposure scenarios (all durations) for this risk assessment. The parental systemic 

NOAEL in this study was 1000 ppm and calculated to be 58.2 mg/kg/day for males. The 

parental systemic LOAEL was 3000 ppm and calculated to be 177 mg/kg/day for males

based on based on reduced body weight gain during premating and on reduced organ 

weight. The rationale for selecting this study for the dietary, oral and inhalation exposure 

scenario is based on the fact that this study provided the lowest and most conservative 

toxicity endpoint. 

A default 100% inhalation absorption will be used for inhalation exposure scenarios. A 

50% dermal absorption rate will be used for dermal exposure scenarios based on the 

toxicokinetic dermal absorption study. The 50% dermal absorption rate was calculated by 

summing and rounding the percent of radiolabeled material found in both the urine and 

feces in the study. 
20

Table 4. Summary of Toxicological Doses and Endpoints of Secondary Alkane (C13-C17) Sulfonates (SAS)

for Use in Human Health Risk Assessment

Exposure/Scenario Point of Departure and 

Uncertainty/Safety Factors

RfD, PAD, 

LOC for Risk 

Assessment

Study and Toxicological Effects

Acute dietary 

(General population 

including infants and 

children)

An acute effect was not found in the database therefore an acute dietary assessment is 

not necessary.

Chronic dietary 

(All populations)

NOAEL= 58.2 mg/kg/day 

UFA = 10 x

UFH = 10 x

FQPA SF = 1 x

Chronic RfD = 

58.2 mg/kg/day

cPAD = 0.582

mg/kg/day

[Repro-toxicity-rat] LOAEL = 

177 mg/kg/day based on 

decreased weight gain during 

premating and reduced organ 

weight.

Incidental oral short-term 

(1 to 30 days)

NOAEL= 58.2 mg/kg/day 

UFA = 10 x

UFH = 10 x

FQPA SF = 1 x

LOC for MOE = 

100

[Repro-toxicity-rat] LOAEL = 

177 mg/kg/day based on 

decreased weight gain during 

premating and reduced organ 

weight.

Incidental oral 

intermediate-term 

(1 to 6 months)

NOAEL= 58.2 mg/kg/day

UFA= 10 x

UFH= 10 x

FQPA SF = 1 x

LOC for MOE = 

100

[Repro-toxicity-rat] LOAEL = 

177 mg/kg/day based on 

decreased weight gain during 

premating and reduced organ 

weight.

Dermal short-term 

(1 to 30 days)

Repro. study NOAEL= 58.2

mg/kg/day (dermal absorption 

rate = 50%)

UFA = 10 x

UFH = 10 x

FQPA SF = 1 x

LOC for MOE = 

100

[Repro-toxicity-rat] LOAEL = 

177 mg/kg/day based on 

decreased weight gain during 

premating and reduced organ 

weight.

Dermal intermediateterm

(1 to 6 months)

Repro. study NOAEL= 58.2

mg/kg/day (dermal absorption 

rate = 50%)

UFA = 10 x

UFH = 10 x

FQPA SF = 1 x

LOC for MOE = 

100

[Repro-toxicity-rat] LOAEL = 

177 mg/kg/day based on 

decreased weight gain during 

premating and reduced organ 

weight.

Inhalation short-term 

(1 to 30 days)

Repro. study NOAEL= 58.2

mg/kg/day (inhalation 

absorption rate = 100%)

UFA = 10 x

UFH = 10 x

FQPA SF = 1 x

LOC for MOE = 

100 

[Repro-toxicity-rat] LOAEL = 

177 mg/kg/day based on 

decreased weight gain during 

premating and reduced organ 

weight.

Inhalation 

(1 to 6 months)

Repro. study NOAEL = 58.2

mg/kg/day (inhalation 

absorption rate = 100%)

UFA = 10 x

UFH = 10 x

FQPA SF = 1 x

LOC for MOE = 

100 

[Repro-toxicity-rat] LOAEL = 

177 mg/kg/day based on 

decreased weight gain during 

premating and reduced organ 

weight.

Cancer (Oral, dermal, 

inhalation)

Based on the lack of increased incidence of tumor formation compared to controls in 

multiple carcinogenicity studies and the lack of mutagenicity, SAS is considered not 

likely to be carcinogenic.

UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of 

the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study 

for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA SF = Food 
21

Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. 

MOE = margin of exposure. LOC = level of concern.

C. Special Considerations for Infants and Children

FFDCA, as amended by FQPA, directs the Agency to use an additional 10X safety factor 

(SF), to account for potential pre- and postnatal toxicity and completeness of the data with 

respect to exposure and toxicity to infants and children. FQPA authorizes the Agency to 

modify the 10X FQPA SF only if reliable data demonstrate that the resulting level of 

exposure would be safe for infants and children. EPA concludes that the FQPA safety 

factor could be reduced to 1X for SAS for the following reasons:

i. The toxicity database for SAS includes a subchronic, developmental/reproductive, 

and chronic/carcinogenicity studies, several mutagenicity studies, and two toxicokinetic

studies. 

ii. Maternal and developmental toxicity was observed at 3000 ppm (177 mg/kg/day) in 

rats based on decreased bodyweight gain during premating and on reduced organ weight.

The parental systemic NOAEL is 1000 ppm (58.2 mg/kg/day). The offspring LOAEL is 

3000 ppm based on decreased pre- and post-implantation loss and decreased weight gain in 

offspring. The offspring NOAEL is 1000 ppm.

iii. There is no indication that SAS is a neurotoxic chemical. Although no 

neurotoxicity studies were available in the database, no clinical signs of neurotoxicity were 

observed in the available subchronic and chronic studies. Therefore, there is no need for a 

developmental neurotoxicity study or additional UFs to account for neurotoxicity. 

iv. There is no indication that SAS is an immunotoxic chemical. Although no 

immunotoxicity studies were available in the database, no signs of immunotoxicity were 

observed in the available studies. Therefore, there is no need for a immunotoxicity study or 

additional UFs to account for immunotoxicity.

v. The dietary food exposure assessment utilizes proposed tolerance level or higher 

residues and 100% crop treated information for all commodities. By using these screeninglevel assessments, chronic exposures/risks will not be underestimated.

Taking into consideration the available information, EPA concludes the additional 10X 

FQPA safety factor can be reduced to 1X.

IV. EXPOSURE ASSESSMENT

The petitioner has requested use of SAS without limitation in pesticide formulations. The 

petitioner requested the ability to use SAS in any type of pesticide i.e., insecticide, 

fungicide or herbicide on seed treatment and foliar applications. 
22

Therefore, the Agency has conducted a “screening-level” assessment of a wide variety of 

sites and use patterns in an effort to obtain a qualitative idea of the possible results of 

human exposures that might result from such combinations of methods of application and 

sites of application. 

A. Dietary Exposure:

 i. Acute exposure. No adverse effects attributable to a single exposure of SAS were seen 

in the toxicity databases. Therefore, acute dietary risk assessment for SAS is not required.

 ii. Chronic exposure. 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. As to residue levels in food, no residue data 

were submitted for SAS. 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-HQOPP-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 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 concentration of 

active ingredients in agricultural products is generally at least 50 percent of the product and 

often can be much higher. Further, 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.
23

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, and then 

use 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.

The additional adjustment factor 2 of 0.8 was utilized in this analysis to account for the 

40% limitation in formulation.

Table 5. Summary of Chronic Dietary Exposure and Risk of Secondary Alkane (C13-C17) Sulfonates (SAS)

Population Subgroup cPAD (mg/kg/day) Chronic

Exposure (mg/kg/day) %cPAD

General U.S. Population

0.582

0.151474 26.0%

All Infants (<1 year old) 0.315542 54.2%

Children 1-2 years old 0.564993 97.1%

Children 3-5 years old 0.388507 66.8%

Children 6-12 years old 0.200443 34.4%

Youth 13-19 years old 0.107838 18.5%

Adults 20-49 years old 0.115792 19.9%

Adults 50+ years old 0.121430 20.9%

Females 13-49 years old 0.117067 20.1%

Based on analyses of estimated dietary risks for the general U.S. population and various 

population subgroups, the chronic dietary exposure estimates for SAS are below the 

Agency’s level of concern for all supported commodities. The chronic dietary exposure 

estimate for the highest exposed population subgroup, children 1-2 years old is 97.1% of 

the chronic population adjusted dose (cPAD). The chronic dietary exposure estimate for the 

general U.S. population is 26.0% of the cPAD.

iii. Cancer exposure. SAS is not expected to be carcinogenic based on multiple 

carcinogenicity studies which showed no increase in incidence of tumors when compared 
24

to the controls. Also all mutagenicity studies on SAS were negative. Therefore, a cancer 

dietary exposure assessment is not necessary to assess cancer risk.

B. 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 SAS, 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 

SAS. These values were directly entered into the dietary exposure model.

C. Residential (Non-Occupational, Non-Dietary) Exposure:

The term ‘‘residential exposure’’ is used in this document to refer to non-occupational, 

non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, 

termiticides, and flea and tick control on pets). However, residential exposure is not 

expected for SAS as the use is for agricultural applications only.

V. AGGREGATE RISK ASSESSMENT

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

aggregate exposure estimates to the acute population adjusted dose (aPAD) and chronic 

population adjusted dose (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 (i.e. toxicological endpoint) 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. 

i. Acute Dietary Risk. 

An acute aggregate risk assessment takes into account exposure estimates from acute 

dietary consumption of food and drinking water using the exposure assumptions discussed 

in Section IV for acute exposure. However there was no hazard attributable to a single 

exposure seen in the toxicity database for SAS; therefore there is no concern for an acute 

dietary risk and an acute aggregate risk assessment was not conducted.

ii. Chronic Dietary Risk. 

A chronic aggregate risk assessment takes into account exposure estimates from chronic 

dietary consumption of food and drinking water using the exposure assumptions discussed 

in Section IV from chronic exposure. The chronic analysis was based on a 2-generation 

reproductive toxicity study with a NOAEL of 58.2 mg/kg/day based on decreased weight 

gain during premating and reduced organ weight. The chronic dietary exposure from food 
25

and water to SAS is 26.0% of the cPAD for the U.S. population and 97.1% for children 1-2 

yrs old, the most highly exposed population subgroup.

iii. Aggregate Cancer Risk for U.S. Population. 

The Agency has not identified any concerns for carcinogenicity relating to SAS; therefore, 

a cancer dietary exposure assessment was not performed and an aggregate cancer risk is not 

a concern.

VI. OCCUPATIONAL EXPOSURE/RISK PATHWAY

The representative occupational scenarios selected by the Agency for assessment are

evaluated based on likely maximum application rates for products which may contain the inert 

ingredient for the short-term exposure assessment, and average application rates for products likely 

to contain the inert ingredient for the intermediate- and long-term exposure durations. Active 

ingredient application rates are corrected for the maximum amount of inert ingredient likely to be 

in the final formulations to determine exposure and risk from exposure to the inert ingredient by 

fungicide/insecticide or herbicide. 

The Agency traditionally considers a level of concern (LOC) for these risk assessments to 

be an MOE of 100 based on the standard 10X inter and 10X intra species extrapolation safety 

factors. 

A. Occupational Handler Risk

Exposure Scenarios

Dermal and inhalation exposure are estimated using the Pesticide Handlers Exposure 

Database (PHED) and Outdoor Residential Exposure Task Force (ORETF) data. The 

analytical techniques are those developed by the Science Policy Council on Exposure 

(ExpoSAC), Heath Effects Division, Office of Pesticide Programs, US Environmental 

Protection Agency. The quantitative exposure/risk assessment developed for occupational 

handlers to support the requested exemption for the inert ingredient based on scenarios to 

represent the highest potential exposure. 

The algorithm used to estimate exposure is:

U.E. * AR * Units Treated/day * absorption factor ÷ body weight.

UE Unit Exposure in mg of material per lb of material handled. Unit Exposures 

are derived in the Pesticide Handlers Exposure Database (PHED) and are 

recently summarized in the “Occupation Pesticide Handler Unit Exposure 

Surrogate Reference Table” US EPA Office of Pesticide Programs, March 

2012 (unpublished)

AR Application Rate in lbs of material per unit (acres).
26

Units Treated/day - - In this case acres treated per day taken from the Antimicrobials 

Division (AD) assessment tool developed to assess Amine Oxide (“900439, 

(C10-16); C10-C18-Alkyldimethylamine oxides; Human Health Risk 

Assessment and Ecological Effects Assessment to Support Proposed 

Exemption from the Requirement of a Tolerance When Used as Inert 

Ingredients in Pesticide Formulations.” 22 SEPT 2009

AF Absorption factor - - 100% default for inhalation routes of exposure and 

50% for dermal routes of exposure based on dermal absorption study.

BW Body Weight - - 80 kg for combined adults in the U.S. Taken from “Use of 

New Human Body Weight Data as Presented in the EPA’s Exposure Factors 

Handbook: 2011 Edition” HED “HotSheet” No. 31. Although due to 

limitations of the assessment tool, the calculations provided below used the 

older default 70 kg.

In this case occupational exposures are presented for aerial applicators, ground applicators 

and for mixer/loaders preparing and applying liquid formulations diluted for use in 

applications. These are the occupational activities believed to be associated with the highest 

exposures use patterns. The occupation exposure assessment utilized the baseline values for 

highest exposure herbicide, insecticide and fungicide. Only the herbicide data is provided 

below because it provided the lowest and most conservative MOEs.

Table 10. Summary of Exposure & Risk to Occupational Handlers From Secondary Alkane (C13-C17) 

Sulfonates (SAS)

Scenario Unit Exposure1

mg inert/lb 

handled

Application Rate1

lb inert/unit

Units 

Treated1

Avg. Daily 

Exposure2

mg inert/kg 

bw/day

MOE3

Herbicide Mixer/Loaders

Liquids: Aerial / 

Chemigation

Dermal:

Single layer

with glove 

0.023

Inhalation: 

No respirator 

0.0012

4.16 lb ai/A

(Corn)

1200 A/day Dermal:

Single layer with

gloves

0.82011

Inhalation: 

No respirator 

0.08558

Dermal:

70.97

Inhalation:

680.1

Combined:

64.3

Liquids: Airblast Dermal:

Single layer

with glove 

0.023

Inhalation: 

No respirator 

0.0012

2.88 lb ai/A

(Nut Trees)

40 A/day Dermal:

Single layer with 

gloves

0.01893

Inhalation: 

No respirator 

0.001975

Dermal:

3100

Inhalation:

29000

Combined:

2800

Liquids: 

Groundboom

Dermal:

Single layer

with glove 

0.023

Inhalation: 

No respirator 

0.0012

5.2 lb ai/A

(Corn)

200 A/day Dermal:

Single layer with 

gloves

0.13669

Inhalation: 

No respirator 

0.01426

Dermal:

430

Inhalation:

4100

Combined:

390
27

1. Default values are taken from Antimicrobials Division (AD) assessment tool developed to assess Amine Oxide (“900439, (C10-

16); C10-C18-Alkyldimethylamine oxides

2. Average Daily Exposure = Unit Exposure * Application Rate * Units Treated * Absorption Rate (Dermal 50%; Inhalation 100%) ÷ 

70 kg Body Weight

3. MOE = Margin of Exposure = NOAEL  ADE. NOAEL = 97 mg/kg bw/day. Combined MOE = 1/(1/Dermal MOE+1/Inhalation 

MOE)

The inhalation absorption was default at 100%. The inhalation toxicity was also assumed to 

be equivalent to oral toxicity (NOAEL 58.2 mg/kg/day). The dermal absorption was set to 

50% based on the dermal absorption study. Risks were calculated using the MOE approach, 

which is a ratio of the exposure to the toxicological PoD. Occupational handler risks are 

not of concern. The Agency’s level of concern for inhalation and dermal exposure is for 

MOEs <100. Although the lowest estimated combined herbicide MOE was 64.3, based on

amount of conservatism build into the model (i.e. liquid aerial/chemigation with no

respirator, maximum application rate on corn and treating 1200 A/day) the estimated 

combined occupational MOEs are not expected to be of concern.

Additional, SAS is expected to be used in seed treatments and the occupational handler 

dermal and inhalation exposure and MOEs are calculated for this application method. The 

Occupational Exposure and Risk from Commercial Seed Treatment Margin of Exposure 

(MOE) Calculator was created in 2004 by Gustafson with guidance from EPA. The seed 

treatment calculated used an example pyraclostrobin label as a conservative seed treatment 

scenario with a high application rate (1.67 lbs per gallon of product). The crop selected was 

Soybean with a default value of 720,000 lbs of seed treated per day and 12,000 lb of seed 

planted per day. The toxicological end point of 58.2 mg/kg/day was selected and the 

dermal absorption rate of 50% and inhalation absorption rate of 100%.

Herbicide Applicator

Liquid: Airblast Dermal:

Open Cab 

0.24

Inhalation:

Open Cab

0.0045

0.64 lb ai/A

(Nut Trees)

40 A/day Dermal:

Open Cab 

0.04389

Inhalation:

Open Cab

0.001646

Dermal:

1300

Inhalation:

35000

Combined:

1300

Liquid:

Groundboom

Dermal:

Open Cab

0.014

Inhalation:

Open Cab

0.00074

4.16 lb ai/A

(Corn)

200 A/day Dermal:

Open Cab

0.08320

Inhalation:

Open Cab

0.008795

Dermal:

700

Inhalation:

6600

Combined:

630

Herbicide Mixer/Loader/Applicator

Liquid: Low 

Pressure handwand

Dermal:

Single layer

with glove 

0.43

Inhalation:

No respirator

0.030

2.88 lb ai/A

(Ornamentals)

5 A/day Dermal:

Single layer with 

gloves

0.04423

Inhalation:

No respirator

0.006171

Dermal:

1300

Inhalation:

9400

Combined:

1200

Table 11. Summary of Exposure & Risk to Occupational Handlers From Secondary Alkane (C13-C17) 

Sulfonates (SAS) when using Seed Treatment
28

1. UE from standard Operating Procedure (SOP) for Seed Treatment, Guidance no. 14, May 1, 2003

2. Label Rate (fl. Oz. per cwt) x Concentration (lbs. ai per gallon) / 128 / 100

3. Daily Exposure (loader, sewers, bagger & multi. activities) = [Rate(lb inert/lb seed) x Amt Seed Treated per Day x 

%Absorption x UE (mg/lb inert)] / [Body Weight (BW) kg]

4. Daily Exposure (Seed Planters) = [Rate(lb inert/lb seed) x Amt Seed Planted per Day x %Absorption x UE (mg/lb inert)] / 

[Body Weight (BW) kg]

5. MOE (unitless) = Toxicological Endpoint (mg/kg/day) / Daily Exposure (mg/kg/day)

6. COMBINED MOE (unitless) = 1 / (1/Dermal MOE) + (1/Inhalation MOE)

The inhalation absorption was default at 100%. The inhalation toxicity was also assumed to 

be equivalent to oral toxicity (NOAEL 58.2 mg/kg/day). The dermal absorption was set to 

50% based on the dermal absorption study. Risks were calculated using the MOE approach, 

which is a ratio of the exposure to the toxicological PoD. Occupational handler risks are 

not of concern. The Agency’s level of concern for inhalation and dermal exposure is for 

MOEs <100. The lowest estimated combined seed treatment MOE was 620 for “multiple 

activities” exposure scenario, therefore the estimated combined occupational seed 

treatment MOEs are not expected to be of concern.

Scenario Unit 

Exposure1

mg inert/lb 

handled

Application 

Rate

lb inert/unit

Units Treated Avg. Daily 

Exposure3, 4

mg inert/kg 

bw/day

MOE5, 6

Loader/Applicator: Dermal:

0.0230

Inhalation: 

0.00034

3.1 fl. oz./100 

lbs. of seed

0.0004045 lbs/ 

lb. of seed2

720,000 lbs seeds 

treated per day

(Soybean)

12,000 lbs seeds 

planted per day

(Soybean)

Dermal:

0.047841

Inhalation: 

0.001414

Dermal:

1200

Inhalation:

41000

Combined:

1200

Sewer: Dermal:

0.0062

Inhalation: 

0.00023

Dermal:

0.012896

Inhalation: 

0.000957

Dermal:

4500

Inhalation:

61000

Combined:

4200

Bagger: Dermal:

0.0091

Inhalation: 

0.00016

Dermal:

0.018928

Inhalation: 

0.000666

Dermal:

3100

Inhalation:

87000

Combined:

3000

Multiple Activities: Dermal:

0.0420

Inhalation: 

0.00160

Dermal:

0.087362

Inhalation: 

0.006656

Dermal:

670

Inhalation:

8700

Combined:

620

Seed Planters: Dermal:

0.2500

Inhalation: 

0.00340

Dermal:

0.008667

Inhalation: 

0.000236

Dermal:

6700

Inhalation:

250000

Combined:

6500
29

B. Occupational Post-Application Risk

Exposure Scenarios

RD uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to 

as re-entry exposure). Such exposures may occur when workers enter previously treated 

areas to perform job functions, including activities related to crop production, such as 

scouting for pests or harvesting. Post-application exposure levels vary over time and 

depend on such things as the type of activity, the nature of the crop or target that was 

treated, the type of pesticide application, and the chemical’s degradation properties. In 

addition, the timing of pesticide applications, relative to harvest activities, can greatly 

reduce the potential for post-application exposure. Inhalation exposures are not typically 

calculated for occupational post-application scenarios because inhalation exposures 

generally account for a negligible percentage of the overall body burden for most pesticide 

chemicals.

This assessment is considered to be a screening level estimate, demonstrating that there are 

minimal potential risks to workers re-entering fields treated with pesticides containing SAS

as inert ingredients. Therefore an occupational post application risk assessment was not 

performed.

VII. CUMULATIVE EXPOSURE

Cumulative effects from substances with a common mechanism of toxicity. Section 

408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke 

a tolerance, the Agency consider “available information” concerning the cumulative effects of a 

particular pesticide's residues and “other substances that have a common mechanism of toxicity.”

EPA has not found SAS to share a common mechanism of toxicity with any other 

substances, and that SAS does not appear to produce a toxic metabolite produced by other 

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

not have a common mechanism of toxicity with other substances. For information regarding EPA's 

efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see EPA's website at 

http://www.epa.gov/pesticides/cumulative.

VIII. 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.
30

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, RD 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 

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

IX. ENVIRONMENTAL FATE CONSIDERATIONS

EPISuiteTM 4.1 was run using CAS Reg. No. 97489-15-1 using C15 alkyl carbon 

chain length since the average carbon chain length was 15.2. SAS is expected to be 

nonvolatile with a vapor pressure of 1.97 x 10-11 mg/Hg @ 25°C. Experimentally it was < 

0.001 Pa @ 20 °C. It is soluble in water (115.6 mg/L @ 25°C). SAS is not expected to 

hydrolyze or undergo direct photolysis. The Log Kow is 0.2 at 20°C and indicates a low 

potential to cross biological membranes. The Log Koc is 2.181 (Kow method) and 3.3 

(MCI Methods) which indicate a moderate soil adsorption. The probability of rapid 

biodgradation (0.82 Biowin1 linear) and (0.99 Biowin non-linear) are consistent with 

experimental environmental degradation data. Atmospheric oxidation indicates a relatively 

rapid oxidation rate with a half-life of 6.6 hours when reacting with hydroxyl radicals. The 

BCF factor is the concentration of a particular chemical in a biological tissue per 

concentration of that chemical in the water surrounding that tissue. EPISuite estimates that 

BCF is 70.79 L/kg wet-wt. BCF lower than 250 are considered low risk. The Primary Level 

III Fugacity Modeling indicates the highest affinity for the soil (70.1%) environmental 

compartment, little affinity for sediment (0.34%) and moderate affinity for water (25.9%). 

The primary degradation persistence is estimated to be 99 hours (about 4 days). The 

Ultimate (complete mineralization) Level IV Fugacity Modeling indicates a high affinity 

for the soil (77.6%) environmental compartment, little affinity for sediment (1.29%) and 

moderate affinity for water (20.5%). The Ultimate Degradation Persistence Time is 

estimated to be 574 hours (about 24 days).

Once SAS is released into the environment, it is expected to partition between soil 

and water, Based on fugacity modeling, SAS should partition mainly in the soil 

compartment. SAS used in either seed or foliar applications can be expected to have limited 

mobility in the environment. Additionally bioaccumulation in mammalian tissues is 

unlikely to occur. 
31

Based on six ready biodegradability (OECD 301) studies, rapid degradation takes 

place over a period of 18-28 days. The most recent OECD Guideline 301B Ready 

Bioavailability; CO2 evolution (Clariant 2001) demonstrated 78% after 28 days.

Four activated sludge (OECD 303A) studies showed rapid and substantial 

degradation over a period of 25 days (98.6%) to 74 days (96.1%). The most recent Hoechst 

(1992) simulated aerobic sewage treatment demonstrated 98.6% after 25 days (DOC 

removal).

Table 11. Summary of Environmental Fate for Secondary Alkane (C13-C17) Sulfonates

Study Results Reference

Aerobic Aquatic 

Biodegradation

Ultimately biodegradable and Readily biodegradable HERA 2005

Anaerobic Aquatic 

Biodegradation

Not biodegraded under strict anaerobic conditions HERA 2005

Hydrolysis Does not hydrolyze in water HERA 2005

Photolysis Does not photolysis in surface water or top soil based on 

molecular structure

HERA 2005

Volatilization Based on Henry coefficient of SAS, volatilization is not a 

relevant elimination factor.

HERA 2005

Bioconcentration Not expected to occur HERA 2005

Bioaccumulation Not expected to occur 

LogKow=0.2

BCFfish=1.4 L/kg wwt

BCFworm=0.9 L/kg wwt

REACH 2010

EUSES: MacKay Fugacity 

Model

<0.003% air

99.98% water

0.014% soil

0.0001% sediment

Dow HPV 

2004

X. ECOTOXICITY

Acute and chronic toxicity data on SAS is available for fish, daphnia and algae. SAS is 

most toxic to Daphnia base on the chronic 21 day Daphnia reproduction study which had a 

NOECrepro of 0.4 mg/L. NOEC of 0.4 mg/L is consider to be highly toxic. 

A chronic 3 day nematode study was carried out resulting in a NOEC reproduction of 939 

mg/kg dw (a.i.). Additional a 56 day Earthworm reproduction study was carried out and 

resulted in a NOEC reproduction of 470 mg/kg dw (a.i.).

Toxicity to birds is not expected due to the lack of expected bioconcentration and 

bioaccumulation based on the low octanol water partitioning coefficient for SAS (Log kow 

= 0.2). 

Table 12. Summary of Aquatic Ecological Toxicity Studies for Secondary Alkane (C13-C17) Sulfonates

Test Type Species Effect Results Units Guideline

Acute fish Leuciscus idus LC50 (96h) 5.5 mg/l OECD 203
32

Acute 

Daphnia

Daphnia 

magna

EC50 (48h) 9.2 mg/l OECD 202

Algae Desmodesmus 

subspicatus

ErC50 (72h) >61 mg/l OECD 201

Cell growth 

inhibition test

Pseudomonas 

putida

NOEC (16h) 1000 mg/l DIN38412, Part 8

Chronic fish Oncorhynchus 

mykiss

NOEC (9d) 0.9 mg/L OECD 212

Chronic 

daphnia

Daphnia 

magna

NOECrepro 

(21d)

0.4 mg/L OECD 211

Chronic 

Algae

Desmodesmus 

subspicatus

ErC10 (72h) 59 mg/L OECD 201

Sediment 

Organism

Caenorhabditis 

elegans

NOEC (96h) 939 mg/kg

Soil MacroorganismEisenia 

fetida(annelids)

NOEC (56d) 470 mg/kg OECD 222

Table data from Clariant 2010 REACH Chemical Safety Report on SAS.

XI. RISK CHARACTERIZATION 

In August 2013 Exponent on behalf of Clariant Corporation submitted a petition to the 

EPA to amend 40 CFR 180.920 by establishing an exemption from the requirement of a tolerance 

for the use of secondary alkane (C13-C17) sulfonates (SAS) (CAS Reg. Nos. 85711-69-9 and 

97489-15-1) as pesticide inert ingredients (surfactants) for use in food crops in accordance with 40 

CFR 180.920 (pre-harvest pesticide applications) with a limitation of 40% in formulation.

An acute dietary risk assessment was not conducted because no endpoint of concern 

following a single exposure was identified in the available studies. A chronic dietary exposure 

assessment was completed and performed using the Dietary Exposure Evaluation Model DEEMFCIDTM, Version 3.16. The chronic Reference Dose (cRfD) of 58.2 mg/kg/day was determined on 

the basis of the reproductive toxicity study in rats. The LOAEL of 177 mg/kg/day SAS was based 

on decreased body weight gain during premating and on reduced organ weight. This study 

provided the lowest NOAEL in the database (most sensitive endpoint) and will also provide the 

most protective limits for human effects. An UF of 100X (10-fold for interspecies extrapolation 

and 10-fold for intra species variability) was applied to the NOAEL of 58.2 mg/kg/day to derive 

the cRfD. The FQPA safety factor of 1X is applicable for chronic dietary risk assessment. 

Therefore, the chronic population-adjusted dose (cPAD) is 0.582 mg/kg/day. This endpoint of 

concern was also used for all dermal and inhalation exposure scenarios. Dermal absorption was 

determined to be 50% based on the dermal absorption study and inhalation absorption was 

assumed to be 100%. 

Based on analyses of estimated dietary risks for the general U.S. population and various 

population subgroups, the chronic dietary exposure estimates for SAS are below the Agency’s 

level of concern. The chronic dietary exposure estimate for the highest exposed population 

subgroup, children 1-2 years old is 97.1% of the chronic population adjusted dose (cPAD) and 

26.0% of the cPAD for the general population. 
33

The Agency’s level of concern (LOC) for SAS occupational and residential dermal and 

inhalation exposures is 100. The LOC is based on a 10X uncertainty factor (UF) to account for 

interspecies extrapolation to humans from the animal test species and 10X UF to account for 

intraspecies sensitivity.

Short-term aggregate exposure takes into account short-term residential exposure plus 

chronic exposure to food and water (considered to be a background exposure level). SAS is an 

inert ingredient in pesticide products that is not expected to result in short-term residential 

exposure since the proposed uses are for commercial agricultural seed treatment and possible foliar 

applications. Therefore the Agency has determined that aggregating chronic exposure through food 

and water with short-term residential exposures is not required. 

Intermediate-term aggregate exposure takes into account intermediate-term residential 

exposure plus chronic exposure to food and water (considered to be a background exposure level). 

SAS is an inert ingredient in pesticide products that is not expected to result in intermediate-term 

residential exposure since the proposed uses are for commercial agricultural seed treatment and 

possible foliar applications. Therefore the Agency has determined that aggregating chronic 

exposure through food and water with intermediate-term residential exposures is not required. 

Occupational handler risks are not expected to be of concern for all scenarios evaluated. It 

is noted that this occupational handler assessment assumes that mixer/loader/applicators are not 

wearing protective respirators when using open pour in support of aerial and groundboom 

application. The estimated MOEs are greater than 100 based on 100% inhalation absorption and 

50% dermal absorption except for mixer/loader aerial/chemigation which had a combined 

herbicide inhalation and dermal MOE of 64.3. However based on the amount of conservatism built 

into the model (i.e. liquid aerial/chemigation with no respirator, maximum application rate on corn 

and treating 1200 A/day) the estimated combined occupational herbicide MOEs are not expected 

to be of concern. Additional, SAS is expected to be used in seed treatments and the occupational 

handler dermal/inhalation exposure and MOEs are calculated for this application method. The 

lowest estimated combined seed treatment MOE was 620 for “multiple activities” exposure 

scenario, therefore the estimated combined occupational seed treatment MOEs are also not 

expected to be of concern. This assessment is considered to be a screening level estimate, 

demonstrating that there are minimal potential risks to workers re-entering fields treated with 

pesticides containing SAS as inert ingredients. Therefore an occupational post application risk 

assessment was not performed.

Once SAS is released into the environment, it is expected to partition between soil and 

water. Based on fugacity modeling, SAS should partition primarily to the soil compartment. 

Therefore SAS used in either seed or foliar applications can be expected to have limited mobility 

in the environment. SAS is not expected to bioconcentrate or bioaccumulate based on a low 

logKow of 0.2.

Based on studies conducted with various aquatic species, SAS is considered highly toxic to 

aquatic organisms. Based on a 9 day chronic fish toxicity study, the NOEC was 0.9 mg/ml and a 

21 day chronic daphnia toxicity study, the NOECrepro was 0.4 mg/ml. SAS is not expected to be 

toxic to birds based on the lack of bioconcentration and bioaccumulation. 
34

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.

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

reasonable certainty that no harm to any population subgroup will result from aggregate exposure 

to SAS when considering residential, occupational, dietary exposure and all other nonoccupational 

sources of pesticide exposure for which there is reliable information. Therefore, the establishment 

of an exemption from tolerance under 40 CFR 180.920 for residues of Secondary Alkane (C13-

C17) Sulfonates (CAS Reg. No. 85711-69-9 and 97489-15-1) when used as a pesticide inert 

ingredient applied to pre-harvest crops with a limitation of 40% in formulation, can be considered 

assessed as safe under section 408(q) of the FFDCA.
35

REFERENCES

Hoechst AG (1988). Hostapur SAS 93: Akute orale Toxizitat. Testing laboratory: Hoechst AG. 

Report no.: 88.0798. Owner company: Clariant. Study number: 1988.0798. Report date: 1988-06-

13.

Hoechst AG (1974). Hostapur SAS 60: Prufng auf sensibilisierende Eigenschaften an 

Meerschweinchen nach Magnusson und Kligman. Testing laboratory: Hoechst AG. Report no.: 

0294/74. Owner company: Clariant. Study number: 1974.0294. Report date: 1974-11-05.

Huls AG (1986). Prufung auf hautsensibilisierende Wirkung am Meerschweinchen von Marlon 

PS60. Testing laboratory: Huls AG. Report no.: 0636. Owner company: Sasol. Study number:

0636. Report date: 1986-06-24.

Life Science Research (1975). Hostapur SAS 60: Toxicity in dermal application to mice 

(preliminary study). Test laboratory: Life Science Research. Report no.: 75/HAG22/255. 

Laboratory: Life Science Research. Report no.: 75/HAG22/255. Owner company: Clariant. Study 

number: 1975.0650. Report date: 1975-12-31.

MRID 49146406: Ben-Dyke, R., and Newman, A.J. (1977) Hostapur (SAS 60): Toxicity in dietary 

administration to rats for one year. Life Science Research, Stock, Essex Cm4 9PE, England. Study 

Identification Number: Bericht Mr. 0554/78, May 10, 1977. Unpublished.

MRID 49146407: McSheehy, TW, Finn, JP, Kiss, I. (1978) Hostapur SAS 60: Potential 

oncogenicity in dermal application to mice for a period of 80 weeks (final report: 0-104 weeks). 

Life Science Research, Stock, Essex England. Study ID: 76/HAG15/028, March 20, 1978. 

Unpublished.

MRID 49146408: Ben-Dyke, R., Finn, J.P., and Newman, A.J. (1978) Hostapur (SAS 60): 

Toxicology and carcinogenicity in dietary administration to rats for two years. Life Science 

Research, Stock, Essex CM4 9PE, England. Laboratory report number 79/HAG16/045. February 

14, 1978. Unpublished.

MRID 49146409: Alves, C. (2007) Acute Dermal/Corrosion Study in Rabbits (Oryctolagus 

cuniculus) for HOSTAPUR SAS 93. Study Identification No. RL4737-06IC-B. TECAM 

Technologia Ambiental Seo Roque Ltda., Estrada do Carmo, 371, Post Box n 312 – Cep: 18130-

970, Sao Roque, SP - Brasil. May 29, 2007. Unpublished.

MRID 49146410: Wallner, Barbara (2010) In Vitro Mammalian Cell Gene Mutation Test (HPRTLocus) in Chinese Hamster V79 Cells with Hostapur SAS 93. BSL Bioservice, Scientific 

Laboratories GmbH, Behringstrabe 6/8, 82152 Planegg, Germany. Study Identification Number 

(BSL Bioservice Study No.): 092292, January 18, 2010. Unpublished.

MRID 49146411: Tesh, J.M., Davidson, E.J., Newman, A.J. (1978) Hostapur (SAS 60): Effects 

upon Reproductive Function and Intra-Uterine Development of the Rat. Life Science Research, 
36

Stock Essex, CM4 9PE, England. LSR No. 76/HAG19/020, LSR Report No. 78/HAG19/020, 

January 24, 1978. Unpublished.

MRID 49146412: Braun, W. (1995) Primary Eye Irritation Study with HOSTAPUR SAS 30 in 

Rabbits (Low Volume Procedure). Study Identification No. RCC Project 388225. RCC Research 

& Consulting Company, Ltd., Zeigliweg 1, 4452 Itingen, Switzerland. March 10, 1995.

Unpublished.

MRID 49146413: Gericke, D. (1977) Hostapur SAS 30 A 297 T3/131. Test for Mutagenicity in 

Bacteria Strains in the Absence and Presence of a Liver Preparation. Krebsforschungslabor, 

Frankfurt/M, West Germany. Study Identification Number: Bericht Nr. 644/77 A, June 16, 1977. 

Unpublished.

REACH Chemical Safety Report 2010 on Sulfonic acids, C14-C17-sec-alkane, sodium salts. 

http://apps.echa.europa.eu/registered/data/dossiers/DISS-a0017598-8f1c-50d1-e044-

00144f67d031/DISS-a0017598-8f1c-50d1-e044-00144f67d031_DISS-a0017598-8f1c-50d1-e044-

00144f67d031.html
37

APPENDIX

US EPA Ver. 3.16, 03-08-d

DEEM-FCID Chronic analysis for SECONDARY ALKANE (C13-C17) SULFONATES

 NHANES 2003-2008 2-day

Residue file name: E:\DEEM\Secondary Alkane (C13-C17) Sulfonates\Secondary Alkane (C13-C17) 

Sulfonates with 40% Limit Purity Adjusted.R08

 Adjustment factor #2 used.

Analysis Date 01-28-2015/07:08:30 Residue file dated: 01-28-2015/07:07:24

Reference dose (RfD, Chronic) = .582 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 0.151474 26.0%

Hispanic 0.165410 28.4%

Non-Hisp-White 0.148640 25.5%

Non-Hisp-Black 0.140761 24.2%

Non-Hisp-Other 0.178685 30.7%

Nursing Infants 0.198564 34.1%

Non-Nursing Infants 0.367787 63.2%

Female 13+ PREG 0.132191 22.7%

Children 1-6 0.437338 75.1%

Children 7-12 0.181928 31.3%

Male 13-19 0.107010 18.4%

Female 13-19/NP 0.108746 18.7%

Male 20+ 0.112797 19.4%

Female 20+/NP 0.122530 21.1%

Seniors 55+ 0.122150 21.0%

All Infants 0.315542 54.2%

Female 13-50 0.117122 20.1%

Children 1-2 0.564993 97.1%

Children 3-5 0.388507 66.8%

Children 6-12 0.200443 34.4%

Youth 13-19 0.107838 18.5%

Adults 20-49 0.115792 19.9%

Adults 50-99 0.121430 20.9%

Female 13-49 0.117067 20.1%

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