summary of the data used to reassess this chemical under the current proposed exemption, 

including data from the previous risk assessment along with two studies that were not reviewed 

for the previous tolerance exemption, is provided below. 

For ease of reading, alkyl polyglycosides will be collectively known throughout the document as 

“APGs” with the specific carbon chain length identified as “(Cx-Cx)”, when appropriate. As 

stated in the final rule for alkyl (C10-C16) polyglycosides, “Alkyl (C8-C10) polyglycosides and 

alkyl (C12-C14) polyglycosides are structurally related to the alkyl (C10-C16) polyglycosides also 

known as D-glycopyranose, oligomeric, C10-C16- alkyl glycosides...These chemicals differ from 

one another only in the length of the alkyl chain. Given these structural similarities, these 

chemicals have similar toxicological characteristics.” Therefore, data on alkyl (C8-C16) 

polyglycosides has been used to make a safety finding on D-Glucopyranose, oligomeric, decyl 

octyl glycosides also know as alkyl (C8-C10) polyglycosides. Please note the word 

“polyglucosides” is used throughout the document when the chemical has been derived from 

glucose. 

In addition to their use in pesticide products APGs are used in laundry detergents, hard surface 

cleaners, other house hold cleaners, as rinse aids in dish washers and in personal care products. 

A Generally Recognized As Safe (GRAS) Notice (GRN 000237) was submitted to the Food and 

Drug Administration in 2007 for the use of alkyl polyglycosides in the cleaning of food products, 

the cleaning of equipment used to process food, the manufacture of products that come in contact 

with food, fruits and vegetables including meat and poultry carcasses, the cleaning of materials 

that subsequently come in contact with food, paper, cardboard, plastic or stainless steel lines 

and/or production vessels, and the cleaning and sanitizing of surfaces in food preparation areas. 

It is anticipated alkyl polyglycoside surfactants would be present in most final cleaning product 

formulations at no more than 20% active and at final use levels less than 2% active. The FDA 

had no questions regarding the conclusion that alkyl polyglycosides are GRAS under the 

intended conditions of use. The FDA has not, however, made its own determination regarding 

the GRAS status of the subject use of alkyl polyglycosides.

Acute studies indicate low acute oral and dermal toxicity (Table 1). C10-C16 is likely to be an eye 

and skin irritant; however, studies using C8-C10 did not show evidence of irritation. 

Table 1. Acute Toxicity Studies* 

Study/Species Test Substance Results 

Acute oral toxicity/rat C8-C14 Lethal Dose (LD)50> 5,000 milligrams/kilogram (mg/kg) 

Acute oral toxicity/rat C12-C14 LD50> 5,000 mg/kg 

Acute oral toxicity/rat C12-C14 LD50> 5,000 mg/kg 

Acute dermal toxicity/rabbit C8-C10 LD50> 5,000 mg/kg 

Acute dermal toxicity/rabbit C12-C14 LD50> 5,000 mg/kg 

Primary eye irritation/rabbit C8-C10 No irritating effects 

Primary eye irritation/rabbit C12-C14 Irritating to the eye 

Primary dermal irritation/rabbit C8-C10 No irritating effects 

Primary dermal irritation/rabbit C12-C14 No irritating effects at concentrations of up to 30% 

Irritating to the skin at concentrations > 30% to 100% 

Dermal sensitization/ guinea pig C8-C10 Not a dermal sensitizer 

Dermal sensitization/ guinea pig C12-C14 Not a dermal sensitizer 

*Adopted directly from FR(citation) 
Repeat dose studies (Table 2) for APGs include a 90-day gavage study, a 14-day dermal, a 

reproduction study, and a developmental study. In the 90-day rat oral (gavage) study, APG (C12-

C14) was administered at dose levels of 0, 250, 500, or 1,000 mg/kg/day for 5 days/week. (MRID 

46090901) There were no treatment-related adverse effects on body weight, body weight gain, 

food consumption, hematological or clinical chemistry parameters or organ weights in any 

group. Adverse treatment-related effects were limited to the forestomach in both males and 

females receiving 500 or 1,000 mg/kg/day. After 27 days, it was observed that forestomach 

effects were reversible following the cessation of treatment, but not reversible during treatment. 

The no observed adverse effect level (NOAEL) in the 2005 Final Rule (FR) was determined to 

be 250 mg/kg/day and the lowest observed adverse effect level (LOAEL) was 500 mg/kg/day 

based on acanthosis, subepithelial inflammatory edema, and hyperkeratosis (females only) of the 

forestomach. However, “Humans do not have a forestomach which serves as a storage reservoir 

in rodents; therefore effects seen in the rat forestomach are likely to be significantly more severe 

than what would be expected from the compound in the glandular stomachs in humans and 

therefore, have less relevance to humans.”(EPA 2009) The Toxicology Science Advisory 

Committee (ToxSAC), one of Office of Pesticide’s Health Effect Division’s scientific peer 

review committees, recently concluded that these effects are local effects and not systemic and 

therefore, should not be the basis for the study LOAEL. Therefore, EPA concluded that the 

NOAEL for the systemic toxicity is 1,000 mg/kg/day. A LOAEL was not observed in this study. 

A 14-day dermal study was conducted on APGs (C8-C10). The information contained in this 

document was taken from a summary of the study which was published in the Handbook of 

Detergents, Part B. (Willing, 2004) While skin irritation was observed at doses above 180 

mg/kg/day and changes in hematological and clinical parameters and testicular degeneration 

were observed at the dose levels of 1,500 and 3,000 mg/kg/day, these effects are likely 

attributable to stress and inflammation due to the severe irritation caused by the test substance 

and therefore a NOAEL for systemic effects was not established. 

...study for subacute toxicity is available for C8–10 APG. The test substance (60% active 

substance) was applied openly to the intact skin of rabbits (New Zealand white) at doses 

between 0.06 and 3 g/kg b.w./day, respectively. Each dose group consisted of six male 

and six female animals, which received aliquots of 2 mL/kg once daily over a treatment 

period of 14 days. After each daily 6-h exposure time, the application sites were wiped. A 

control group was treated with only water. The rabbits were observed daily for clinical 

signs and skin irritation. Body weights were determined on days 5 and 9 of treatment, 

whereas hematological and clinical chemical parameters were determined prior to dosing 

and on termination of the study. Absolute and relative organ weights, necropsy 

observations, and histopathology of the testes and accessory sex glands were evaluated at 

the end of treatment. Doses at and above 1.5 g/kg b.w./day induced severe skin irritation 

after repeated application as well as several changes in hematological and clinical 

parameters and testicular degeneration. These effects were at least partly attributed to 

stress and inflammation due to the severe irritation caused by the test substance. Minimal 

to mild skin irritation was seen in dose groups starting from 0.54 g/kg b.w./day, whereas 

no clinical, haematological, or organ changes were reported at this dose. At and below 

0.18 g/kg b.w./day, none of the described adverse effects was seen... 
A reproduction study summarized in the Handbook of Detergents, Part B is provided below. The 

full study is not available. (Willing, 2004) 

C10/16 alkyl polyglycosides were investigated in male and female rats following daily 

administration by oral gavage of 100-, 300-, and 1000-mg/kg/day doses. Each group 

contained 10 male and 10 female F0 rats. Dams were allowed to litter and rear their 

offspring to post partum day 4. No effects indicative of general toxicity were observed in 

parental animals. Relative and absolute weights of testes, epididymides, and seminal 

vesicles did not differ between test and control animals. A marginal reduction in absolute 

and relative prostate weights was seen in all treated males compared to the control group, 

being significant for the low-dose group only and not dose dependent. Therefore, this 

finding was not considered to be substance related. With regard to reproductive 

parameters, no test substance–related symptoms were observed. Mean litter weights, 

mean pup weights, sex ratios, and gestation periods were similar among groups. Some 

variations in prebirth loss were seen in the high-dose group without being dose dependent 

or significantly different to the controls. Pre-weaning clinical signs showed no treatmentrelated effects in pups, nor did necropsy reveal any effects in decedent or Fl pups. 

Macroscopic examination revealed no difference between treated and control animals. On 

the basis of the results obtained in this one-generation screening assay, a NOAEL of 1000 

mg/kg/day for reproductive effect can be deduced. 

In a rat developmental toxicity study, APGs (C12-C14) was administered by gavage at dose levels 

of 0, 100, 300, and 1,000 mg/kg/day on gestation days 6 to 15. (MRID 46090902) No treatment 

related maternal deaths, clinical signs, or decreases in mean body weight, weight gain, corrected 

weight gain or gross lesions were observed in this study. In addition, there were no treatmentrelated developmental effects (e.g., external abnormalities, visceral abnormalities or skeletal 

malformations/variations); therefore, the developmental and maternal NOAEL is 1,000 

mg/kg/day. A LOAEL was not determined. 

Table 2. Repeat Dose Studies 

Study/Species Test 

Substance 

Dose Results 

90-day oral 

toxicity/rat 

C12-C14 0, 250, 500, or 

1,000 

mg/kg/day 

NOAEL = 1,000 mg/kg/day (highest dose tested) 

LOAEL not established 

14-day 

dermal/rabbit 

C8-C10 60-3000 

mg/kg/day 

Systemic NOAEL not established 

Systemic LOAEL not established 

Developmental 

toxicity/rat 

C12-C14 0, 100, 300, or 

1,000 

mg/kg/day 

Maternal NOAEL = 1,000 mg/kg/day (highest dose tested) 

Maternal LOAEL not established 

Developmental NOAEL = 1,000 mg/kg/day (highest dose tested) 

Developmental LOAEL not established 

Reproductive 

screening 

toxicity/rat 

C10-C16 0, 100, 300, or 

1,000 

mg/kg/day 

Reproductive NOAEL = 1,000 mg/kg/day (highest dose tested) 

LOAEL not established 

An in vivo study is not available; however, an in vitro dermal penetration study using 

caprylyl/capryl glucoside on human skin showed that when the substance was diluted to 10% and 

tested the mean recovery was 0.52% of caprylyl/capryl glucoside from two tape strips and 0.30% 
of caprylyl/capryl glucoside in the remaining 18 tape strips, after 24 hours. The mean amount of 

caprylyl/capryl glucoside removed from the skin (by washing) ranged from 109-145% of the 

dose applied. The mean absorbed dose of caprylyl/capryl glucoside, as the sum of the amounts 

found in the viable epidermis, dermis, and receptor medium, was 0.01%. (Across Barriers 

GmbH, 2009). Full study report not available. 

Mutagenicity studies on various chain lengths of alkyl polyglucosides were negative indicating 

that APGs are not likely to be mutagenic. (Banduhn, 1994 and Banduhn, 1995) Table 3 was 

taken directly from the Final Rule for Alkyl (C10-C16) Polyglycosides published in the Federal 

Register on September 14, 2005 (70 FR 54281). No carcinogenicity studies are available on 

APGs; however, APGs are not expected to be carcinogenic based on lack of mutagenicity, lack 

of any systemic toxicity at high doses (up to and including 1,000 mg/kg/day) and rapid 

metabolism to sugars and alcohols in the body and excretion from the body. 

Table 3. Mutagenicity Studies 

Type of Study Test Substance Results 

Salmonella/Escherichia reverse gene 

mutation assay ) Ames Test 

C12-C14 Negative. No evidence of induced 

mutant colonies over background. 

Salmonella typhimurium reverse (Ames 

Test) 

Not specified Did not induce reverse mutations in 

tested strains of Salmonella 

typhimurium either with our without 

metabolic activation 

In vitro cytogenetic test in Chinese 

hamster V79 lung fibroblast 

Not specified Considered to be non-mutagenic. 

In vitro mammalian cytogenetics assay C12-C14 Negative with and without activation. 

When evaluating inert ingredients for food use the agency is responsible for addressing the Food 

Quality and Protection Act (FQPA) safety factor to protect infants and children. Testicular 

atrophy was observed in the 14-day dermal study at 1,500 mg/kg/day; however, these effects are 

likely attributable to stress and inflammation due to the severe skin irritation caused by the test 

substance and therefore a NOAEL for systemic effects was not established. In addition, oral 

reproductive and developmental studies did not show any effects at does as high as 1,000 

mg/kg/day. Based on the low acute and subchronic toxicity of the chemical and the lack of 

endpoint of concern (including reproductive and developmental) in repeat dose studies at doses 

as high as 1,000 mg/kg/day, the agency feels a safety factor analysis is not necessary. 

APGs are currently approved under 40 CFR 180.910 and 180.930 without limitation which 

allows the inert ingredient to be used on food both pre- and postharvest and use on animals. 

Subsequently, unrestricted nonfood use as an inert ingredient in pesticide products is permitted. 

Non-occupational exposure is possible via the oral route resulting from eating foods treated with 

the inert ingredient, consuming animal products from animals exposed to the inert ingredient, or 

by ingesting residues left on utensils and dishes treated with antimicrobial food sanitizing 

solutions containing the inert ingredient. In addition, there is a potential for residue transfers to 

food that comes in contact with these treated areas (e.g., food-contact surfaces in public eating 

places, dairy-processing equipment, or food-processing equipment). Dermal and inhalation 

exposure is also possible when applying the pesticide formulation containing the inert ingredient 

in residential settings. Occupational exposure via the dermal and inhalation route is possible. 
While oral, dermal, and inhalation exposures are possible there was no endpoint of concern 

identified in toxicity studies up to 1,000 mg/kg/day. In addition, metabolism studies on 

structurally-related chemicals indicate that the body can effectively metabolize D-glucopyranose, 

oligomeric, C10-C16-alkyl glycosides to water-soluble substances (predominantly sugar and 

various alcohols) that are readily excreted from the body. (MRID 46059205) Based on the low 

acute toxicity, the body’s ability to rapidly metabolize the inert ingredient, and the lack of an 

endpoint of concern for repeat dose studies at the limit dose (1,000 mg/kg/day) a qualitative risk 

assessment was conducted. 

Predictive modeling (Federal Register, September 14, 2005 (70 FR 54281)) and various 

screening test for biodegradation (Willing, 2004; MRID 46059207) indicate that APGs are 

expected to undergo rapid degradation (estimated to be hours to days for primary degradation) 

and ultimate degradation to water and carbon dioxide in days to weeks. Therefore, it is unlikely 

that APGs will reach either ground or surface water or bioaccumulate in the environment. EPA 

previously assessed ecotoxicity for APGs using predictive models and SAR analysis which led to 

the conclusion that these chemicals were moderately to highly toxic to aquatic species. However, 

experimental studies for APGS have shown that alkyl (C8-C10) polyglycosides are only slightly 

toxic to aquatic species (Table 4). (Willing, 2004) 

Table 4. Acute Ecotoxicological Data of APG-Freshwater Organisms 

Test Substance 

Endpoint OECD Method Duration C8-C10 C12-C14 C16-C18

Fish 203 96-hr, LC50 101 mg/L 3.0 mg/L 2.6 mg/L 

(48 hr) 

Daphnia 202/I 48-hr, EC50 20 mg/L 7.0 mg/L n.d. 

Algae 201 72-hr, EC50 47 mg/L 10 mg/L n.d. 

Based on the low acute toxicity, the lack of a toxic endpoint in available studies at doses up to 

and including 1,000 mg/kg/day, the body’s ability to metabolize the inert ingredient, coupled 

with the low ecotoxicity; the agency believes there is reasonable certainty of no harm to human 

health and the environment by expanding the current approval under 40 CFR 180.910 and 

180.930 to include an exemption under 40 CFR 180.940(a). Therefore an exemption from the 

requirement of tolerance under 40 CFR 180.940(a) for D-Glucopyranose, oligomeric, decyl octyl 

glycosides has been established. 
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