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EPA BIOPESTICIDES AND POLLUTION PREVENTION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA Biopesticides and Pollution Prevention Division contact: Linda Hollis #17 (703 - 308 - 8367)
INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases where the outline element does not apply, please insert “NA - Remove” and maintain the outline. Please do not change the margins, font, or format in your pest icide petition. Simply replace the instructions that appear in green , i.e., “ [ insert company name ] ,” with the information specific to your action. SUBMISSION: E - mail the completed template to: hollis . linda @epa.gov. TEMPLATE: Arkion Life Sciences [Insert petition number]

EPA has received a pesticide petition ( [insert petition number] ) from Interregional Research Project Number 4(IR
- 4) 500 College Road East, Suite 201W Princeton, New Jersey on behalf of Arkion Life Sciences , 551 Mews Drive Suite J, New Castle DE 19720 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180. (Options (pick one) 1. by establishing a tolerance for residues of 2. to establish an exemption from the requirement of a tolerance for 3. to establish an amendment/expansion of an existing tolerance exemption for the (Options (pick one) 1. microbial pesticide [insert name of active ingredient] 2. biochemical pesticide 9, 10 anthraquinone2 3. plant

- pesticide [insert name of active ingredient] in or on [insert commodity]. Pursuant to section 408(d)(2)(A)(i) of FFDCA, as amended, Interregional Research Project Number 4(IR

- 4) on behalf of Arkion Life Sciences has sub mitted the following summary

of information, data, and arguments in support of their pesticide petition. This summary

was prepared b y Interregional Research Project Number 4(IR

- 4) on behalf of Arkion Life Sciences and EPA has not fully evaluated the merits of the pesticide petition. The summary may have been edited by

EPA if the terminology

used was unclear, the summary contained extraneous material, or the summary unintentionally made the reader conclude that the findings reflected EPA’s position and not the position of the petitioner. I. Arkion Life Sciences Petition Summary [Insert petition number] A. Product Name and Proposed Use Practices Avipel liquid corn seed treatment. Avipel will be used for the protection of planted field and sweet corn seed against consumption by blackbirds, cranes, grackles and pheasants. Application will be performed to corn seed either by commercial seed treatment businesses or on farm as a planter box seed treatment. B. Product Identity/Chemistry 1. Iden tity of the pesticide and corresponding residues. The active ingredient in Avipel is 9,10 anthraquinone (CAS 84

- 65

- 1). Residues of 9,10 anthraquinone, 1

- hydrox y anthraquinone and 2

- hydroxy anthraquinone have been quantitatively

and qualitatively

mea sured using a GL P Magnitude of Residue study conducted under the auspices of IR

- 4 and included in this filing. 2. Magnitude of residues at the time of harvest and method used to determine the residue

. Anthraquinone, the active ingredient in Avipel  liquid formulation and Avitec  dry powder formulation, is a pesticide used on field corn for control of sandhill crane. To provide the sponsor with residue chemistry data to support the establishment of a tolerance for anthraquinone in or on field corn, 15 field trials were conducted for this study during the 2006 and 2007 growing seasons, two each in Michigan (EPA Region 5) and New York (Region 1); three in North Dakota (one Region 5, two Region 7); one each in Ohio (Region 5), South Dakota (Region 5), and Texas (Region 6); and five in Wisconsin (Region 5). Six varieties of field corn seed were treated with Avipel  liquid formulation at targeted rates of approximately 0.005 lb ai/lb seed (1X), and at 0.025 lb ai/lb seed (5X) (2006 trials) , or 0.05 lb ai/lb seed (10X) (2007 trials) . In addition, at the3

Wisconsin 06

- WI 07 and North Dakota 06

- ND04 trials, seed was treated with Avitec  dry powder formulation at rates of approximately 0.005 lb ai/lb seed (1X) and 0.025 lb ai/lb seed (5X). The seed was planted and samples of kernels plus cob with husk s removed (K+CWHR) and samples of forage were collected at the milk stage. Samples of grain and stover were collected at crop maturity

. Sample anal ys is for residues of anthraquinone, 1

- hydroxy anthraquinone, and 2

- hydroxy anthraquinone was conducted by Cornell Analy

tical Laboratories, Geneva, NY. The procedure used was “Residue Anal ys is of Anthraquinone on Corn (field) including Kernels plus Cob with Husks Removed (K+CWHR), Forage, Grain, and Stover by L C/MS Detection”, Version #1 The results from the 15 trials show that no residues above the LLMV of 0.10 ppm of anthraquinone, 1

- hydroxyanthraquinone, and 2

- hydr oxy anthraquinone were observed in any of the samples following seed treatment at rates of approximately 0.025 lb ai/lb seed (5X), or 0.05 lb ai/lb seed (10X) in an y grain sample. Residues of 0.12 ppm 1

- hydroxy anthraquinone were observed in one stover sampl e treated with Avipel  liquid formulation at the 10X rate from the Texas trial. The sample was reanal yz ed at a later date and no residues above the LLMV were observed.

3. A statement of why an analytical method of detecting and measuring the levels of the pesticide residue are not needed. An anal yt ical method is available. Sample anal ys is for residues of anthraquinone, 1

- hydroxy anthraquinone, and 2

- hydrox yanthraquinone was conducted b y Cornell Analy tical Laboratories, Geneva, NY. The procedure used was “Residue Analysis of Anthraquinone on Corn (field) including Kernels plus Cob with Husks Removed (K+CWHR), Forage, Grain, and Stover by L C/MS Detection”, Version #1. C. Mammalian Toxicological Profile The information submitted on this formulation as Flight Control for outdoor nonfood use was previously reviewed b y BPPD and states: Adequate mammalian toxicology

data are available and support registration of the active ingredient 9,10

– anthraquinone. The registrant, (Arkion Life Sciences) , submitted acceptable acute to xicity studies for both the Technical Grade Active Ingredient (TGAI) and the end

- use product. For the TGAI: (i) acute oral LD50 in rats was >5000 mg/kg (Tox categ ory I V); (ii) acute dermal LD50 in rabbits was >5000 mg/kg (Tox category I V); (iii) acute inhalation L C50 in rats was >2.11 mg/L (Tox category I V); and (iv) the EP caused mild ocular irritation sy mptoms in rabbit s which cleared in 72 hours post

- instillation (Tox category I II ). For the EP: (i) acute oral LD50 in rats was >5000 mg/kg (Tox category IV) ; (ii) acute dermal LD50 in rats was >5000 mg/kg (Tox category I V); (iii) acute inhalation LD50 in rats was > 2.04 mg/L (Tox category I V); (iv) the EP caused mild ocular irritat ion4

sy mptoms in rabbits which cleared b y 72 hours post instillation (Tox category III); (v) the EP caused slight dermal irritation sy mptoms in rabbits which cleared by 24 hours post dosing (Tox category

I II) ; and (vi) the EP was shown to be a contact sensi tizer in guinea pigs using the Buehler Method. The National Toxicology Program (NTP) has conducted a series of studies on anthraquinone . All these studies were conducted with anthraquinone samples produced from a process based on anthracene. The current process does not give rise to this impurity . The sample of anthraquinone used in the NTP studies were contaminated with up to 0.11% 9

- nitroanthracene (9

- NA) and 0.6% of mutagenic impurities. The sample was produced using an anthracene

- derived process. Th is process has not been used for decades and is not used in any of the Arkion Life Sciences material. The level of 9

- nitroanthracene in the studies were calculated at roughl y 4 ppm in the diet at 3750 ppm anthraquinone The high dose tested in the rat st udy was 7500 ppm anthraquinone. The contamination of the anthraquinone sample with the potent mutagen 9

- nitroanthracene was well documented in both the NTP report and the open literature. Estimates based on mutagenic potency indicate it is plausible that the 9

- NA and other contaminants could have been responsible for a portion, if not all, of the tumor induction observed in the NTP study

. In a subchronic oral toxicity study in rats conducted by

the NTP, groups of 10 male and 10 female F344/N rats were fed diets containing 0, 1,875, 3,750, 7,500, 15,000, or 30,000 ppm anthraquinone (equivalent to average dail y doses of approximately 135, 275, 555, 1,130, or 2,350 mg anthraquinone/kg bod y weight) for 14 weeks. All rats survived until the end of the stud y. Me an body weights of females were significantly less in the exposed groups than in the control group. Feed consumption by the exposed and control groups was similar at the end of the study . Liver and kidney weights of exposed groups were greater than those o f the controls, as were testis weights of males exposed to 7,500 ppm or greater. A minimal, responsive anemia was apparent in groups of male and female rats exposed to 3,750 ppm or greater by day 26 of the study . The anemia persisted and involved all expos ed groups of rats at the end of the study but the response was weak and the dose response curve was flat across all treated groups . Renal function was also affected b y anthraquinone exposure as demonstrated by increases in urine protein and glucose concentrations and aspartate aminotransferase and N

- acet yl

- β

- D
- glucosaminidase activities. Estrous cy cles were longer in 15,000 and 30,000 ppm females than in the controls. Groups of exposed rats had liver h yp ertrophy ; eosinophilic hy aline droplets in the kidney ; congestion, hematopoietic cell proliferation, and pigmentation of the spleen; and bone marrow h yperplasia. The incidences of nephropath y in 15,000 and 30,000 ppm females were significantly greater than that in the controls, and the severities of nephropathy

were increased in exposed groups of males and in 30,000 ppm females. The concentrations of α

- 2u

- gl obulin in the kidney s were significantly greater in all exposed groups of males. Th yroid gland follicular cell hypertroph y was present in all males and females exposed to 3,750 ppm or greater. Incidences of inflammation and transitional cell hy perplasia in the urinary

bladder of 30,000 ppm females were greater than those in the controls. This study

was performed with samples of anthraquinone containing the5

impurity 9

- aminoanthracene, a known toxicant. The U S EPA Guideline sets the limit dose for 90

- day

studies at 1000 mg/kg. The high dose in this study exceeded the limit dose. The NTP has conducted a subchronic oral toxicity study in mice. Groups of 10 male and 10 female B6C3F1 mice were fed diets containi ng 0, 1,875, 3,750, 7,500, 15,000, or 30,000 ppm anthraquinone (equivalent to average daily doses of approximately 250, 500, 1,050, 2,150, or 4,300 mg/kg to males and 300, 640, 1,260, 2,600, or 5,300 mg/kg to females) for 14 weeks. All mice survived until the end of the stud y. Mean body weights and feed consumption were similar among exposed and control groups. A responsive anemia occurred in exposed mice at week 14 but a clear dose response was not evident and the response was weak . L iver weights of expose d groups of mice were significantly greater than those of the control groups. The incidences of centrilobular h ypertroph y in the liver of mice exposed to 3,750 ppm or greater were significantly greater than those in the controls, and the severities increas ed with increasing exposure concentration. Cy toplasmic alteration of the urinary bladder was observed in all exposed mice, and the severities increased with increasing exposure concentration. The incidences of hematopoietic cell proliferation were increase d in all exposed groups of males and females, and pigmentation was observed in the spleen of all exposed mice (except one male and one female in the 30,000 ppm groups). This study was performed with samples of anthraquinone containing the impurity 9

- aminoanthracene, a known toxicant. The US EPA Guideline sets the limit dose for 90

- day studies at 1000 mg/kg. The high dose in this study exceeded the limit dose. In an NTP study

for oncogenicity

in rats, groups of 50 male and 50 female F344/N rats were fed di ets containing 469, 938, or 1,875 ppm anthraquinone for 105 weeks. Groups of 60 male and 60 female F344/N rats received 0 or 3,750 ppm anthraquinone for the same period. Five males and five females receiving 0 or 3,750 ppm were evaluated for histopathology and α2u

- globulin concentrations at 3 months and for organ weights and histopathology

at 12 months. These dietary anthraquinone concentrations resulted in average dail y doses of approximately 20, 45, 90, and180 mg/kg to males and 25, 50, 100, and 200 mg/kg to females. Additional groups of 18 males given 469, 938, 1,875, or 3,750 ppm for 8 day s and 10 males and 10 females given 469, 938, or 1,875 ppm for 3, 6, 12, or 18 months were designated for toxicokinetic studies. Survival of all groups of males was sim ilar, and survival of exposed groups of females was greater than that of the controls. Mean bod y weights of exposed groups of males during the latter part of the study and mean bod y weights of exposed females throughout most of the study were less than tho se of the controls. Feed consumption by exposed groups was similar to that by the controls. The incidences of renal tubule adenoma and renal tubule adenoma or carcinoma (combined) occurred with positive trends and were increased in all exposed groups of f emale rats. The incidences of renal tubule adenoma in all exposed groups of male rats exceeded the historical control range, but the incidence was significantl y increased in the 938 ppm group onl y . Increased incidences of nonneoplastic lesions of the kidne y associated with anthraquinone exposure included hy aline droplet accumulation, pigmentation, and mineralization in the renal medulla and transitional epithelial6

hy perplasia in males and females and renal tubule hy perplasia in females. Incidences of nephro path y were increased in females, and severities of nephropath y were increased in males. At 3 months, the concentration of α2u

- globulin in the kidney of 3,750 ppm males was greater than that in the control group. The incidence of urinary

bladder transitio nal epithelial papilloma was significantly greater in 1,875 ppm males than in the control group, and the incidences in groups of males exposed to 938 ppm or greater exceeded the historical control range. There were positive trends in the incidences of tran sitional epithelial hy perplasia and papilloma or carcinoma (combined) of the urinary bladder in females. The incidences of hepatocellular adenoma or carcinoma (combined) were slightl y increased in exposed males and females; the incidences in groups of fema les exposed to 938 ppm or greater exceeded the historical control range

. T he incidences of several nonneoplastic liver lesions of minimal severit y were also increased. The incidences of congestion, pigmentation, and hematopoietic cell proliferation of the spleen were greater in exposed males and females than in the controls. The incidences of bone marrow h yperplasia were increased in most groups of exposed rats, and the incidences of bone marrow atroph y were increased in exposed females. The incidences of m ononuclear cell leukemia were significantly less in all exposed groups than in the controls at 2 years, and the incidences were less than the historical control ranges. The NOEL was 469 ppm (20 mg/kg males, 25 mg/kg females) based on pathological findings in the liver, kidney and bladder at 938 ppm (45 and 50 mg/kg males and females, respectivel y). In an NTP study

for oncogenicity

in mice, g roups of 50 male and 50 female B6C3F1 mice were fed diets containing 0, 833, 2,500, or 7,500 ppm anthraquinone (equiv alent to average dail y doses of approximately 90, 265, or 825 mg/kg to males and 80, 235, or 745 mg/kg to females) for 105 weeks. Additional groups of 36 males given 833, 2,500, or 7,500 ppm for 8 day s and 10 males and 10 females given 833, 2,500, or 7,50 0 ppm for 12 months were designated for toxicokinetic studies. Survival was decreased for 7,500 ppm males than for the control group. Mean bod y weights of 7,500 ppm males during the last 6 months of the study

and mean body

weights of 7,500 ppm females at the end of the study were less than those of the control groups. Feed consumption was similar in all groups of males and females. In cidences of hepatocellular neoplasms (including multiple neoplasms) increased with a positive trend in male and female mice, and the incidences were increased in all exposed groups. Incidences of hepatoblastoma were significantly increased in males exposed to 2,500 or 7,500 ppm. The incidences of several nonneoplastic lesions of the liver were increased in exposed mice. There w as a marginal increase in the incidences of neoplasms of thy roid gland follicular cells in males and females. Incidences of intracytoplasmic inclusion body

of the urinary

bladder and hematopoietic cell proliferation of the spleen in males and females and thy roid gland follicular cell hy perplasia and kidney

pigmentation in males were greater in exposed groups than in the controls. The NOEL was 833ppm (90 mg/kg and 80 mg/kg males and females, respectively) based on pathological findings in the liver, kidney , thy roid and spleen at 2500 ppm (265 and7

235 mg/kg males and females, respectively). For developmental and reproductive toxicity , no studies have been conducted for anthraquinone. However, a structural analog, emodin (1, 3, 8

- trihydroxy

- 6

- methyl

anthraqui none), has been tested for developmental toxicity by the NTP in rats and mice. Emodin is a naturally

occurring and pharmacologically active anthraquinone found in the roots and bark of certain plant species. T ime mated Sprague Dawley (CD®) rats (25/group ) were exposed to emodin at nominal concentrations of 0, 425, 850, and 1700 ppm in NIH

- 07 ground rodent diet from gestational day

(gd) 6 to 20. Average dail y intake was 0, 31, and 57 mg emodin/kg of body weight/day

for the control, low

- and mid

- dose groups . Average daily intake for the 1700 ppm group was 80

- 144 mg emodin/kg of body weight/day

. There were no differences among groups for the number of corpora lutea/dam, number of implantation sites/litter, or percent preimplantation loss/litter. Postimplantat ion loss (resorptions or late fetal deaths), live litter size, percent male fetuses/litter, and average fetal body weight/litter (males, females or both) were likewise unaffected. Emodin did not affect the incidence of fetal malformations or variations. T h e maternal LOAEL was considered to be 1700 ppm (80

- 144 mg/kg/day) based on maternal body weight and weight gain, and the NOAEL was 850 ppm (57 mg/kg/day). The developmental toxicity NOAEL was greater than or equal to 1700 ppm (80

- 144 mg/kg/day). A LOAEL fo r developmental toxicity was not established in this study

. In an NTP study , time

- mated Swiss albino (CD

- 1®) mice (25/group) were exposed to emodin at concentrations of 0, 600, 2500 or 6000 ppm in NI H
- 07 rodent diet from gestational day

(gd) 6 to 17. Avera ge dail y intake was 0, 94, 391, and 1005 mg emodin/kg/day . Nominal concentrations of emodin (ppm in feed) and calculated intake of emodin (mg/kg/day) are expressed as the bulk test article (96.2% purity) unless otherwise noted

. There were no differences am ong groups for the number of corpora lutea/dam, number of implantation sites/litter, or percent preimplantation loss/litter. Postimplantation loss (resorptions or late fetal deaths), live litter size, and percent male fetuses/litter were likewise unaffecte d. At 6000 ppm, average fetal body weight/litter (males, females or both) was reduced b y 10

- 11%, and this effect was statistically significant. In gested emodin failed to significantl y affect the incidences of fetal malformations or variations. At 2500 ppm, external malformations included exencephaly (3 fetuses in 3 litters) and cleft palate (2 fetuses in 2 litters). However, this increase in external malformations was not considered to be treatment related due to the clear absence of a dose

- response relatio nship. At 6000 ppm, no external malformations were found among 302 fetuses (24 litters), nor had an y been observed among 161 fetuses (13 litters) at 6000 ppm in the screening study (NTP, 2000). T he maternal toxicity

L OAELwas considered to be 6000 ppm (100 5 mg/kg/day) based on reduction of maternal body weight and weight gain, and the NOAEL was 2500 ppm (391 mg/kg/day). The developmental toxicity L OAELwas 6000 ppm (1005 mg/kg/day) based on reduction of fetal body weight, and the NOAEL was 2500 ppm (391 mg/kg/day).8

Emodin was not a developmental toxin. It is not anticipated that anthraquinone will be a developmental toxin. Several mutagenicit y studies were conducted b y NTP on anthraquinone using S. typhimurium , and mouse peripherial blood micronuclei S t atistically s ignificant i ncreases in the frequencies of micronucleated normochromatic ery throcy tes were observed in peripheral blood samples from male and female mice exposed to anthraquinone (99.8% pure) in feed for 14 weeks but the frequency was low . How ever, results of an acute exposure mouse bone marrow micronucleus test, with anthraquinone administered b y intraperitoneal injection, was negative . The NTP concluded that there was evidence of increased ery

thropoiesis in the 14

- week treated mice and concl uded that the increased rate of ery

thropoiesis may

have contributed to the micronucleus responses seen in the high exposure concentration groups. (Increased cell proliferation can produce increased levels of mitotic errors.) Overall, NTP concluded that anthraquinone was negative for genotoxicity

. In EPA Guideline studies, anthraquinone was negative in bacterial mutation tests using Salmonella and E. coli with and without activation

. Anthraquinone was also negative in a mouse ly mphoma gene mutation test with and without metabolic activation. Anthraquinone did not induce chromosomal aberrations in Chinese hamster ovary (CHO) cells in the presence or absence of activation. Additionally , another mouse micronucleus bone marrow stud y was also negative follo wing an acute exposure. In studies conducted as part of the NTP studies, the metabolism and disposition of anthraquinone in male F344/N rats were examined. Animals were administered uniformly labeled 14C

- anthraquinone by intravenous injection at 0.35 mg/k g bod y weight or b y gavage at doses ranging from 0.35 to 350 mg/kg. Following oral administration, anthraquinone was absorbed from the gastrointestinal tract and distributed to tissues. N o indication of bioaccumulation was apparent in any tissue. The majo rity

of the radiolabel was eliminated in the feces and the urine by 24 hours after dosing at all four concentrations. At 96 hours after dosing, less than 5% of the administered dose remained in major tissues. Elimination of over 50% of the administered r adioactivity in the feces and there was substantial excretion of parent and/or metabolites in the bile. Anal ys is of the bile samples indicated that less than 3% of the radioactivity collected was present as the parent compound, suggesting extensive hepatic metabolism. Analy sis of urine from dosed rats reveale d the presence of as many as 11 metabolites. Two of the metabolites identified were 1

- hydrox yanthraquinone and 2

- hydrox yanthraquinone. The plasma half

- life in mice was determined to be 4 hours , and in rats it was between 10

- 12 hours.9

D. Aggregate Exposure 1. Dietary exposure. No exposure is expected based on the lack of measurable residues in the crop. A theoretical estimation of dietary risk was conducted using LifeLine TM version 5.0 with very conservative assumptions. Values of 0.1 ppm were used based on the LODs of the anal yt ical method for the parent and three presumptive metabolites. No residues at a 10x use rate were detected which represents a 10

- fold higher residue. A 100% crop treatment was also assumed. All LifeL ine default processing values were used. The NOEL for the chronic stud y was assumed to be 7 mg/kg, based on a 3X reduction in the NOEL of the NTP study . A 10X FQPA safet y factor was assumed as a conservative default. Us ing exaggerated assumptions of residue and hazard , chronic dietary risks did not exceed 5% of the Reference Dose (RfD) with the most sensitive subpopulation, children ages 3

- 5 with an estimate of 4.5% of the RfD. Taking the 95 th percentile of the chronic assessment for the acute dietary risk, the highest subpopulation was 7.9% of the chronic RfD. Neither acute or chronic exposures are of dietary concern. i. Food. No exposure is expected based on the lack of measurable residues in the crop. ii. Drinking water
. No exposure is expected in drinking water. 2. Non

- dietary exposure

. Based on its low toxicity

and use practice (repellent of a vertebrate pest), anthraquinone is not subject to the Worker Protection Standards (WPS). Moreover, the possibility

for dermal, eye and inhalation exposure is mitigated as long as the product is used according to label directions which recommends use of gloves, long sleeved shirts, long sleeved pants and NIOSH filters to prevent inhalation. It is anticipated that a majority of the treated corn seed will occur within a commercial seed treatment facility

.

E. Cumulative Effects Anthraquinone is not toxic and therefore there would be no expected cumulative effects from common mechanisms of toxicity

. F . Safety Determination10
1. U.S. population. Aggregate exposure would primarily occur in the mixer/loader/applicator subpopulations via dermal and inhalation routes. Risks associated with dermal and inhalation aggregate exposure s are measured via the a cute toxicity studies previously reviewed b y the EPA as part of the Flight Control (66969

- 1) registration process. Because the inhalation toxicity studies for anthraquinone showed no toxicity (Toxicity Category I V), the risks anticipated for this route of exposure are considered minimal. Results of the acute dermal study indicated low toxicity

(Toxicity Category IV), and no significant dermal irritation (Toxicity Category I V). Based on these results, the anticipated risks from dermal and inhalation exposures are also considered minimal. Therefore, the risks from aggregate exposure via dermal and inhalation exposure are a compilation of two low risk exposure scenarios and are considered negligible. Exposure is further mitigated b y use of worker protection equipment on the label. 2. Infants and children

. There is no anticipated residue associated with the proposed use of the anthraquinone. Therefore, the acute dietary risks should be negligible based on the lack of exposure. G. Effects on the Immun e and Endocrine Systems There are no anticipated residues, therefore there is no exposure to the population to trigger concern for immune and endocrine effects in the general population or in the high risk population of infants and children. H. Exis ting Tolerances There is no established direct food tolerance in food for anthraquinone. There is an indirect food tolerance issued by FDA for anthraquinone in paper products used in contact with food. The established tolerance in this case for paper products is 2 ppm. I . International Tolerances There is no established direct food tolerance in food for anthraquinone. There is an indirect food tolerance issued by FDA for anthraquinone in paper products used in contact with food. The establishe d tolerance in this case for paper products is 2 ppm.