i

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [Roger Chesser, (703) 347-8516

Elizabeth Fertich, (703) 347-8560]

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 

pesticide petition. Simply replace the instructions that appear in green, i.e., “[insert 

company name],” with the information specific to your action.

TEMPLATE:

[Diversey, Inc.]

[Petition Number 1E7843]

EPA has received a pesticide petition ([1E7843]) from [Diversey, Inc.], [8310 

16th Street, Sturtevant, WI, 53177] 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

to establish an exemption from the requirement of a tolerance for the residues of 

FD&C Red No. 40 (conforming to 21 CFR 21 CFR §74.340) if used as an inert 

ingredient (colorant) in no-rinse, food contact surface sanitizer (sanitizer) products. 

EPA has determined that the petition contains data or information regarding the elements 

set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the 

sufficiency of the submitted data at this time or whether the data supports granting of the 

petition. Additional data may be needed before EPA rules on the petition.

FD&C Red No. 40 is an azo dye with the structural formula listed below. 

The full chemical name of FD&C Red No. 40 is 2-NAPHTHALENESULFONIC 

ACID, 6-HYDROXY-5-[(2-METHOXY-5-METHYL-4-SULFOPHENYL)AZO]-, 

DISODIUM SALT, and it has the CAS Registry Number 25956-17-6. Commonly 

used synonyms are Food Red No. 40 and FD&C Red No. 40 in the United States and 

Allura Red AC in Europe. The physical/chemical properties of the molecule have 
2

been previously summarized (EPA, 2004).

A. Residue Chemistry

1. Plant metabolism. 

2. Analytical method. [NA-Remove]

3. Magnitude of residues. [Use of FD&C Red No. 40 in sanitizers will not 

result in any residues on plants. Residues of FD&C Red No. 40 are exempt from the 

requirements of a tolerance when used as an inert ingredient in pesticide 

formulations that are intended for application on growing crops or on raw 

agricultural commodities after harvest (40 CFR 180.910). The colorant cannot be 

used above 0.002% (20 ppm) by weight in the formulation and must meet the 

certification requirements specified in 21 CFR 74.340. FD&C Red No. 40 is 

similarly approved for use as a dye or coloring agent for seed treatment with a 

maximum concentration of 2% by weight in the pesticide formulation (40 CFR 

180.920).

The primary source of dietary exposure to FD&C Red No. 40 will most likely occur 

from its existing use as a food and drug additive. FDA estimates that 95-97% of the 

certified color additives produced in the United States are used domestically to 

manufacture food, drugs and cosmetics (FDA, 2010). An estimated 3%-5% of the 

domestic production is exported. Of these, approximately 73% is used in food, 10% 

in drugs and 3% in cosmetics. Pesticidal uses were not mentioned but would fall 

within the remaining 9-11% of use. Accordingly, use of colorant in sanitizers is 

expected to represent only a small percentage of the total population exposure to the 

colorant. 

Sanitizers are used in commercial eating establishments and food and dairy 

processing facilities to sanitize food contact surfaces after cleaning. The products 

are applied after the surface has been thoroughly cleaned. The sanitizer is not 

rinsed off and is allowed to air dry, resulting in a small amount of colorant residue 

on the food contact surface. Accumulation of FD&C Red No. 40 residues is not 

expected since the surfaces are extensively cleaned between sanitizer applications. 

In the tolerance assessment for the use of FD&C Red No. 40 in conventional 

pesticides, EPA noted that dyes are typically incorporated into pesticide products at 

less than 0.1% (1000 ppm) based on information in the PIRAT database (EPA, 

2004). Most sanitizer products are concentrates. The product is diluted with water 

to produce the use-solution, which is actually used to sanitize the surface. There are 

some ready-to-use food contact surface sanitizing products available in the 

consumer markets that do not require dilution, but these are relatively rare. 

Dilutions rates for sanitizer concentrates typically vary from 1:64 (1.54%) to 1:1028 

(0.01%). Assuming the maximum concentration of FD&C Red No. 40 in the 

concentrated product is 0.1% based on the information in the PIRAT database, the 
3

expected amount of FD&C Red No. 40 in the use-solutions will range from 15 ppm 

(0.0015%) to 0.1 ppm (0.00001%). 

The primary dietary exposure to FD&C Red No. 40 will occur from the transfer of 

the chemical residues from the food contact surface into food during processing. 

Both FDA and EPA assume, in the absence of the other data, that the amount of 

residue left behind after sanitizing and draining is 1 mg of use-solution per cm2 of 

food contact surface. Assuming 20 ppm of FD&C Red No. 40 in the use-solution, 

this corresponds to a maximum residue concentration of 2 g FD&C Red No. 40 per 

cm2of food contact surface. The estimated dietary exposures to FD&C Red No. 40 

are discussed in section C.

EPA reviewed the environmental impact from use of FD&C Red No. 40 in 

agricultural pesticides. In agricultural use, the products are discharged directly 

into the environment without treatment. Based on their review, EPA concluded that 

“modeling results indicate that expected potential risks to aquatic organisms and 

soil and sediment dwelling organisms resulting from the use of FD&C Blue No. 1, 

FD&C Red No. 40, and FD&C Yellow No. 5 as inert ingredients in pesticide 

formulations are low.” (EPA, 2004)

No-rinse food contact sanitizing solutions are typically indoor use products. These 

products are used at commercial facilities where there is no direct discharge to the 

environment during recommended use. The used solutions are drained into the 

sanitary sewer of the facility, where they are treated in accordance with permits 

issued under the Clean Water Act. After leaving the food processing facility, the 

concentration of FD&C Red No. 40 in the waste-water will be reduced further by 

dilution with other waste streams and by processing at the waste water treatment 

facility. Therefore, we would the ultimate concentration of FD&C Red No. 40 

discharged by a waste-water treatment facility should be less than the concentration 

directly discharged to the environment from agricultural uses.]

B. Toxicological Profile

1. Acute toxicity. [The European Food Safety Authority (EFSA) has 

conducted the most recent (2009) full review of the toxicology of FD&C Red No. 40. 

This document relied heavily on the earlier reviews conducted by the Joint 

FAO/WHO Expert Committee on Food Additives (JECFA) which set the current, 

permanent Acceptable Daily Intake (ADI) 0-7 mg/kg-bw/day.(JECFA, 1981). For 

purposes of this petition, Diversey, Inc. will summarize the key studies reported in 

these documents as the basis for the toxicity discussion on FD&C Red No. 40. The 

references cited here correspond to the references in the EFSA, 2009 review. No 

compound related effects were observed when FD&C Red No. 40 (Allura Red AC) was 

given to rats by gavage at doses varying from 215 to 10000 mg/kg. Based on these studies, 

JECFA set the LD50 for rats at 10000 mg/kg-bw. Other studies in rabbits, dogs and mice 

produced LD50 values of 10,000, 5000 and >2000 mg/kg, respectively. Overall, the EFSA 

concluded that “the acute oral toxicity of Allura Red AC (FD&C Red No. 40) is low.” ]
4

2. Genotoxicity. [EFSA cited reviews by the European Scientific Committee 

for Food (SCA), the JECFA and by TemaNord, to conclude that FD&C Red No. 40 

was determined to be non-mutagenic in a variety of in vitro and in vivo based 

mutagenicity studies. This determination is consistent with EPA’s conclusion in the 

2004 Tolerance Reassessment for FD&C Red No. 40 (EPA, 2004).

In their 2009 review, EFSA cited a study from 2001 conducted on FD&C Red No. 40 

using the Comet assay. The study showed an increase in migration of nuclear DNA 

in the glandular stomach and the colon of male mice exposed to doses of FD&C Red 

No. 40 of 100 mg/kg-bw and 10 mg/kg-bw respectively. Since histopathology of the 

effected organs appeared negative, the study authors concluded that observed effect 

was not likely to be related to cytotoxicity. In light of the negative in vivo

carcinogenicity studies conducted on FD&C Red No. 40 (see below), EFSA 

concluded that the significance of the Comet assay results was uncertain.]

3. Reproductive and developmental toxicity. [Relevant reproductive and 

developmental toxicity studies cited in the EFSA document are summarized in 

Table 1. Blackmore, 1969, observed slight growth suppression in F1 and F2 pups 

exposed to 5.19% of FD&C Red No. 40 in the diet during a multi-generation type 

reproduction study in rats. This dose was calculated to be equivalent to 2595 

mg/kg/day. The fetal No Adverse Effect Level (NOAEL) was 1.39% in the diet; 

equivalent to 695 mg/kg/day. The maternal NOEAL was 5.19% in the diet, which 

was equivalent to 2595 mg/kg/day. No other significant anomalies were detected in 

growth, litter size, pup weight, gross pathology, implantation sites, resorption sites, 

live fetuses indices, appearance, anatomy and structure were observed. The ADI of 

7 mg/kg-bw/day for FD&C Red No. 40 was partially based on this study. 

Teratology studies in rats and rabbits showed no evidence of adverse effects at 200 

mg/kg-bw/day (gestation day (g.d.) 0-19) and 700 mg/kg/day (g.d. 6-18), respectively.

Reproductive toxicity endpoints were also monitored in three long-term studies. 

In a lifetime study in mice, the animals were fed up to 5.19% of FD&C Red No. 40 

in the diet. Animals were also exposed throughout gestation and lactation. At the 

highest dose level, lower body weights and effects on organ weight and organ/body 

weight ratios were noted but considered to be “inconsequential.” (Serota et al., 

1977a). 

In a nearly identical lifetime study with larger group numbers (100/sex/group versus 

50/sex/group in the original study), no compound related adverse effects were 

observed. The NOAEL’s in both studies were determined to be 5.19% FD&C Red 

No. 40 in the diet, which was calculated to be equivalent to 7300 and 8300 mg/kgbw/day in male and female mice, respectively. (Reno et al., 1978)
5

Dietary administration of 5.19% FD&C Red No. 40 in rats was also studied (Serota 

et al., 1977b). Administration started throughout parental breeding, gestation and 

lactation and continued for 118 and 121 weeks in male and female rats, respectively. 

For the female rats in the study, mean body weights and growth rates were 

significantly lower in the high dose group relative to controls. No other significant 

adverse effects were reported. The NOAEL was 5.19% (2821 mg/kg-bw/day) in 

male rats and 1.3% (901 mg/kg-bw/day) in female rats.

A review conducted by TemaNord, 2002, discussed four additional 

reproductive/developmental toxicity studies. 

Rats (group number not reported) were exposed to up to 10% of FD&C Red No. 40 

in the diet (calculated doses of 0, 1250, 2500 and 5000 mg/kg-bw/day). Litter 

mortality was increased between 22-24 days of age at a concentration of 10% in the 

diet. Significantly decreased running wheel activity was observed in all exposed 

groups. Increased open-field rearing was observed in the two highest dose groups. 

The Low Adverse Effect Level (LOAEL) was determined to be 1250 mg/kg-bw/day; 

a NOAEL could not be determined from this study (Voorhees, et al., 1983). 

In a mouse study, animals (10/sex/group) were exposed to up to 1.68% FD&C Red 

No. 40 in the diet over two generations (equivalent to 2400 mg/kg-bw/day). The 

study showed no significant, dose-related adverse effects on reproduction or 

neurobehavioral endpoints following exposure to FD&C Red No. 40 (Tanaka, 1994). 

In rats (group number not reported) dosed with FD&C Red No. 40 up to 0.7% in 

drinking water (equivalent to 939 mg/kg-bw/day) on g.d. 0-20, a significant increase 

in the incidence of fetuses with reduced ossification of the hyoid was observed at the 

highest dose level. No other fetal malformations were observed. The NOAEL from 

this study was determined to be 546 mg/kg-bw/day (Collins et al., 1989a). 

In rats dosed with FD&C Red No. 40 on g.d. 0-19 (group number not reported), no 

significant, dose-related effects were observed at doses up to 1000 mg/kg/day 

(Collins et al., 1989b).]

 

4. Subchronic toxicity. [FD&C Red No. 40 was studied in rats, dogs and pigs 

in the following short-term studies.

In rats, groups of 20 animals (10 males and 10 females per group) were fed diets 

containing 0-2595 mg/kg-bw/day) for six weeks. The NOAEL was determined to be 

at least 2595 mg/kg-bw/day. 

Both of the dog studies were determined to be too limited to derive a NOAEL. 

The pig study appeared to be a non-standard design. Groups of 4 animals (2 males 

and 2 females per group) were dosed with 1000 mg/kg-bw/day of FD&C Red No. 40 
6

for 21 days. The dose was increased to 1500 mg/kg-bw/day for an additional 54 

days. No compound related effects were reported.

5. Chronic toxicity. [The chronic toxicity/carcinogenicity of FD&C Red No. 40 

was studied in 5 key studies. These are summarized in Table 2. 

In general, exposure to FD&C Red No. 40 did not result in significant adverse 

effects. In one mouse study, higher rates of early onset lymphoma were observed in 

animals exposed to FD&C Red No. 40 (Serota et al., 1977a). However, this 

observation was not statistically significant in this study and could not be replicated 

in a subsequent study that used a higher number of animals per group (100 versus 

50) and an additional control group. In general, the only significant effects reported 

in these studies appeared to be growth suppression or body weight reductions at 

high dietary doses used in these studies.]

6. Animal metabolism. [The applicable studies were summarized in JECFA, 

1980. In rats fed 5.19% FD&C Red No. 40 in the diet, only 0.1% and 29% of the 

unmetabolized dye was found to be excreted in the urine and feces, respectively. 

Using 35S labeled FD&C Red No. 40, in dogs, 92-95% of the recovered radioactivity 

appeared in the feces and between 2.7 and 3.6% in the urine within 72 hours of 

administration. In rats, 76-92% of the radioactivity was recovered in the feces and 

5.7-19.8% in the urine within the same timeframe. Significant retention of the dye 

was noted in the intestinal contents and in the washed intestines of both species. 

The total carcass and viscera of both species retained only 0.4% of the total 

administered dose. 

FD&C Red No. 40 is absorbed to a limited extent and that the major route of the 

excretion is through metabolic by-products eliminated through the feces. Urinary 

excretion is negligible.]

7. Metabolite toxicology. [Cresidine-4-sulfonic acid was identified as the major 

metabolite in the urine and feces of both rats and dogs along with the parent 

compound and two unknown metabolites. In the dog, an additional unknown 

metabolite was observed in the feces and possibly the urine. Metabolism in the GI 

tract may occur though the reduction of the azo group in the parent compound.]

8. Endocrine disruption. [In the 2004 tolerance reassessment, EPA did not 

make a formal determination as to whether FD&C Red No. 40 impacts the 

endocrine system pending the outcome of assays under the Endocrine Disrupter 

Screening Program. Overt effects on the endocrine system were not reported in the 

toxicological studies conducted on the FD&C Red No. 40. 

EFSA, 2009, reported that FD&C Red No. 40 was able to inhibit aromatase activity 

in an in vitro rat ovarian microsome system with an IC50 of 24 M. Aromatase 

catalyzes the conversion of androgens to estrogens and presents a possible target for 

endocrine disrupting chemicals. EFSA concluded; however, that these data did not 
7

trigger a concern for FD&C Red No. 40 since the chemical has limited systemic 

bioavailability and that there was no evidence of related adverse effects in the 

various reproduction studies conducted on the chemical.]

C. Aggregate Exposure

1. Dietary exposure. [See below]

i. Food. [Historically, FDA regulated sanitizer chemicals as indirect food 

additives under the Federal Food, Drug and Cosmetic Act (codified in 21 CFR 

§178.1010). In 1993, FDA published guidance for assessing dietary exposure to 

chemicals from sanitizing FDA described a tiered assessment process for evaluating 

the safety of sanitizer solutions based on where they are intended for use. Solutions 

were approved for use on food-contact surfaces in public eating places, dairyprocessing equipment and on food-processing equipment and utensils. 

The model developed for public eating facilities was considered sufficiently 

conservative to assure the safe use of sanitizers on food processing equipment in 

dairy and other industries [40 CFR §180.940 (b) and (c)]. FDA considered this a 

worst-case assessment and if a chemical was approved for use in public eating 

facilities, it could also be used at similar concentrations on dairy processing 

equipment and food processing equipment and utensils.

Upon passage of the Food Quality Protection Act in 1996, EPA assumed 

responsibility for the regulation of sanitizers. The regulations governing the use of 

sanitizers are currently codified under 40 CFR §180.940 and follow the basic FDA 

outline from 21 CFR §178.1010.

 180.940 (a)- regulates chemicals used as ingredients in 

antimicrobial pesticide formulation that are applied to foodcontact surfaces in public eating places, dairy-processing 

equipment, and food processing equipment and utensils.

 180.940 (b)-regulates chemicals used as ingredients in 

antimicrobial pesticide formulations that are applied to dairyprocessing equipment and food processing equipment and utensils.

 180.940 (c)-regulates chemicals used as ingredients in 

antimicrobial pesticide formulations that are applied to food 

processing equipment and utensils.

The exposure model published by FDA in 1993 was adopted by EPA in modified 

form for dietary risk assessments conducted on antimicrobials as part of 

Reregistration. For purposes of this assessment, we relied on the dietary exposure 

models used by EPA in their review of Alkyl Dimethyl Benzyl Ammonium Chloride 

(ADBAC) under Reregistration (Shamim, 2006). 

Public Eating Facilities
8

The EPA public eating facility model from the ADBAC Reregistration Eligibility 

Decision (RED) is listed below. 

EDI (mg/p/day) = AR x RS x SA x F x 10-6

DDD (mg/kg/day) = AR x RS x SA x F x 10-6/BW 

EDI= Estimated Daily Intake 

DDD= Daily Dietary Dose

AR = Application rate (ppm)

RS = Residual solution (mg/cm2) = 1 mg/cm 2

SA = Surface area of the treated surface which comes into contact with food (cm2)= 

4000 cm2

F = Fraction of the pesticide transferred or migrated to food (unitless) = 1

BW = Body weight (kg)

Consistent with FDA’s 1993 guidance, the model assumes that all of the food 

consumed by a single individual in a day contacts 4000 cm2of food contact surface 

area. This figure represents a total surface area of dishes, eating utensils and 

drinking glasses used by a person eating 3 meals a day in an institutional or other 

public eating facility. The worst-case amount of sanitizer residue (use-solution) is 

presumed to be 1 mg/cm2. 

In the ADBAC RED, EPA slightly modified FDA’s original model to fit their risk 

assessment requirements. EPA converted the EDI to a “Daily Dietary Dose” (DDD) 

by dividing the EDI by body weight. The DDDs for adult males (70kg), adult 

females (60 kg) and children (15 kg) were determined. EPA also incorporated a 

transfer factor (F), which is the fraction of the chemical transferred or migrated to 

food. For ADBAC, the Agency assumed that “F” equalled 10%. 

Countertops

In the ADBAC RED, EPA also includes a model for countertop exposures from the 

use of these products as disinfectants at a higher concentration of active ingredient. 

This model is identical to the one developed for public eating facilities except that it 

assumes that food will come into contact with 2000 cm2 of countertop area per day. 

Diversey, Inc. incorporated this model into our assessment, assuming that our 

products could be used to sanitize countertops that may intentionally or 

inadvertently come into contact with food.

Dietary Exposure to FD&C Red No. 40 from Diversey, Inc. Products

Using EPA’s models as described in the ADBAC RED, we estimated the dietary 

exposure to FD&C Red No. 40 from Diversey, Inc. sanitizer products. For purposes 

of this assessment, we assumed a concentration of FD&C Red No. 40 of 20 ppm in 

the use-solution of the sanitizer product. For Diversey, Inc. products, the 

concentration of FD&C Red No. 40 in sanitizing use-solutions typically ranges from 

0.1-0.4 ppm. At disinfecting concentrations (which require a potable water rinse), 
9

the concentration range for FD&C Red No. 40 is from 0.2-3.1 ppm.

The use of 20 ppm is a worst-case scenario since it equals the maximum amount 

present in the undiluted sanitizer product and is significantly greater than the 

concentration of FD&C Red No. 40 in the actual sanitizer use-solutions.

As our reference value, we relied on the ADI established by the EFSA/FAO/WHO of 

7 mg/kg-bw/day. Since data were not available, we also assumed that all of the 

FD&C Red No. 40 in the use-solution transferred or migrated to food (F=1).]

ii. Drinking water. [Sanitizer products are not intended to be added to 

drinking water. Therefore, direct exposure to FD&C Red No. 40 from drinking 

water was not evaluated. In the tolerance reassessment for FD&C Red No. 40 

published in 2004, EPA estimated that the amount of FD&C Red No. 40 in the 

drinking water supply would be no greater than 1 ppb from use of the colorant in 

conventional pesticides. EPA concluded that at this concentration in water, 

exposure to FD&C Red No. 40 would be several orders of magnitude below current 

ADI’s.]

2. Non-dietary exposure. [None expected.]

D. Cumulative Effects

[When considering an exemption from the requirement of tolerance, the 

Federal Food, Drug and Cosmetic Act requires consideration of the cumulative 

effects of a particular pesticide residue under consideration and in combination with 

other chemicals that share a common mechanism of action. EPA did not assume 

that FD&C Red No. 40 shared a common mechanism of toxicity with any other 

substance in 2004, when the tolerance for FD&C Red No. 40 in agricultural 

pesticides was reassessed. Currently, EPA has not made a common mechanism of 

toxicity finding for FD&C Red No. 40 with any similar substances 

(http://www.epa.gov/pesticides/cumulative/).]

E. Safety Determination

1. U.S. population. [Our analysis indicates that dietary exposure to FD&C 

Red No. 40 at 20 ppm from use-solutions of sanitizers is only a small fraction of the 

current ADI as established by FDA, the World Health Organization and the 

European Food Safety Authority, for all relevant age groups. Our assessment is 

based on the FDA process, modified by EPA, which has historically been used to 

assess dietary exposure to sanitizer chemicals used in public eating establishments. 

The public eating establishment model is considered the worst-case assessment of 

dietary exposure to sanitizer chemicals. Therefore, these results are also applicable 

to sanitizers containing FD&C Red No. 40, when used on dairy-processing 

equipment and food processing equipment and utensils.]
10

2. Infants and children. [In the 2004 tolerance reassessment for FD&C Red 

No. 40, EPA concluded that there was “no concern for potential sensitivity to infants 

and children resulting from exposures to... FD&C Red No. 40.” (EPA, 2004)

In 2007, a paper was published studying the effect on children of dietary exposure to 

FD&C Red No. 40 in combination with three other artificial food colors and the 

preservative, sodium benzoate, on children. (McCann et al., 2007). The authors 

reported increased hyperactivity in the 8/9 year old children exposed to the food 

dye/sodium benzoate mixture. 

In response, the Center for Science in the Public Interest (CSPI) petitioned FDA in 

2008 to ban eight of the nine approved food colorants currently in use in the United 

States. The CPSI alleged that exposure to food colorants causes hyperactivity and 

behavioral issues in some children (CSPI, 2008). 

FDA initiated a review of the issue in response to the CSPI petition, which 

culminated in a meeting of the Food Advisory Committee in March, 2011. FDA 

prepared a comprehensive review of the available literature on the possible effects 

of food colorants on children (FDA, 2010). The McCann study was also reviewed in 

detail (Sobotka, et al., 2010). 

Based on the information available, FDA concluded that a causal relationship 

between exposure to color additives and hyperactivity in children in the general 

population had not been established. For certain susceptible children with ADHD 

and other problem behaviors, the FDA felt that the data suggested “these conditions 

may be exacerbated by exposure to a number of substances in food, including, but 

not limited to, artificial food colors.” FDA also concluded that the results of the 

cited studies indicate that the effects on behavior appear to be due to “a unique 

intolerance to these substances and not to any inherent neurotoxic properties.” The 

Food Advisory committee recommended that additional research be conducted on 

this subject. 

FDA’s decision is summarized in the background document prepared for the 

March, 2011 meeting (FDA, 2011). EFSA also reviewed the overall science (EFSA, 

2010) on this topic and also conducted a detailed review of the McCann study 

(EFSA, 2008). Their conclusions were similar to FDA. In their 2008 review of the 

McCann study, EFSA drew the following conclusions. 

 The study provides limited evidence that the two different mixtures of 

synthetic colors and sodium benzoate tested had a small and 

statistically significant effect on activity and attention on some 

children selected from the general population.

 The effects were not observed for all children in all age groups and 

were not consistent for the two mixtures. 

 The clinical significance of the effects was unclear and it is not known 

whether the small alterations in attention and activity would interfere 
11

with schoolwork or other intellectual functioning.

 Since only mixtures were studied, it is not possible to ascribe any of 

the observed effects to any one of components of the mixture. 

 The study was not sufficient to provide a basis to revise the existing 

ADI (7 mg/kg-bw/day) based on the overall weight of evidence and the 

relative weakness of the effects, and on the absence of information on 

the clinical significance of the observed behavioral changes.

These conclusions were affirmed by EFSA in their overall reevaluation of FD&C 

Red No. 40 as a food additive (EFSA, 2009).]

F. International Tolerances

[United States Food and Drug Administration

FD&C Red No. 40 is permanently listed as a color additive for use in food, drugs 

and cosmetics in the United States (21 CFR §74.340, Listing of Color Additives 

Subject to Certification). Certified versions of this colorant are commercially 

available that meet FDA requirements as specified under 21 CFR §70.25 (labelling), 

21 CFR §80 (certification), and 21 CFR §82.51 (specifications and labelling).

FDA does not specify an upper limit for the use of FD&C Red No. 40 in food, only 

that it be used “generally in amounts consistent with good manufacturing practices 

except that it may not be used to color foods for which standards of identity have 

been promulgated under section 401 of the Act unless added color is authorized by 

such standards.” 

Consistent with other reviewing authorities (see below), FDA has determined an 

ADI for FD&C Red No. 40 of 7 mg/kg-bw/day (FDA, 2011).

European Union (EU)

In the European Union, FD&C Red No. 40 is listed as Allura Red AC (E 129) on 

Annex 1 of Directive 94/36/EC, List of Permitted Food Colours. It is also approved 

for a number of specific food types under Annex III of the Directive; “Foodstuffs to 

Which Only Certain Permitted Colours may be Added.”(EU, 1994) 

Codex Alimentarius

The Codex Alimentarius is a joint program of the United Nations Food and 

Agricultural Organization and World Health Organization. The primary goals of 

the Code are “protecting health of the consumers and ensuring fair trade practices 

in the food trade, and promoting coordination of all food standards work 

undertaken by international governmental and non-governmental organizations.” 

The current approved food uses of FD&C Red No. 40 as listed in the code are 

included in the attached reference (Codex, 2010). 

European Food Safety Authority
12

1. EFSA. Scientific Opinion on the re-evaluation of Allura Red AC (E 129) as a 

food additive. EFSA Journal. 7(11): 1327. Accessed 1-24-2011 at 

http://www.efsa.europa.eu/en/efsajournal/pub/1327.htm .

The EFSA, 2009 review on FD&C Red No. 40 is the most recent full analysis of the 

safety of FD&C Red No. 40. In their review, EFSA reaffirmed the FAO/WHO 

acceptable daily intake of 0-7 mg/kg-bw/day.

2. 2010- European Food Safety Authority (EFSA)- Scientific Opinion on the 

appropriateness of the food azo-colours Tartrazine (E 102), Sunset Yellow 

FCF (E 110), Carmoisine (E 122), Amaranth (E 123), Ponceau 4R (E 124), 

Allura Red AC (E129), Brilliant Black BN (E151), Brown FK (E 154), Brown 

HT (E 155) and Litholrubine BK (E 180) for inclusion in the list of food 

ingredients set up in Annex IIIa of Directive 2000/13/EC. Accessed 2-4-2011 

at http://www.efsa.europa.eu/en/efsajournal/pub/1778.htm.

Upon the request of the European Commission, the EFSA was asked to provide a 

scientific opinion on the potential of food azo-colors to cause intolerance and/or 

allergic reactions in humans following oral exposure. The Panel concluded that “it 

is unlikely that oral consumption of the food colours under consideration, either 

individually or in combination would trigger severe adverse reaction in human 

subjects at current levels of use.” Based on their review of the literature, they found 

no data linking FD&C Red No. 40 to any sensitivity or intolerance reactions while 

acknowledging that lack of clinical awareness may result in an unknown degree of 

under-reporting.

European Scientific Committee for Food (SCF)

1. Scientific Committee for Food. Reports of the Scientific Committee for 

Food. Fourteenth Series. EUR 8752 EN. 1983. pp. 52-53. Accessed 1-24-

2011 at http://ec.europa.eu/food/fs/sc/scf/reports/scf_reports_14.pdf .

The SCF established an ADI of 0-7 mg/kg-bw/day based on the review conducted by 

the Joint FAO/WHO Expert Committee on Food Additives at their 25th meeting (see 

below).

2. Scientific Committee for Food. Reports of the Scientific Committee for 

Food. Twenty-First Series. EUR 11617 EN. 1989. p. 4. Accessed 1-24-2011 

at http://ec.europa.eu/food/fs/sc/scf/reports/scf_reports_21.pdf .

The SCF maintained the ADI of 0-7 mg/kg-bw/day established in 1983.

Joint FAO/WHO Expert Committee on Food Additives (JECFA)

1. Joint FAO/WHO Expert Committee on Food Additives. (WHO Food 

Additive Series 6). Toxicological Evaluation of Some Food Colours, Enzymes, 
13

Flavour Enhancers, Thickening Agents, and Certain Food Additives. WHO 

Food Additives Series 6. 1975. Accessed 1-24-2011 at 

http://www.inchem.org/documents/jecfa/jecmono/v06je07.htm

In 1974, the JECFA conducted a review on FD&C No. 40 (Allura Red AC) but was 

unable to determine an ADI because of gaps in the toxicology data package.

2. Joint FAO/WHO Expert Committee on Food Additives (JECFA). (WHO 

Food Additive Series 15). Allura Red AC. Accessed 1-24-2011 at 

http://www.inchem.org/documents/jecfa/jeceval/jec_55.htm

http://www.inchem.org/documents/jecfa/jecmono/v15je02.htm

Upon receipt of the data requested in their 1974 review, the JECFA established a

temporary ADI of 0-7 mg/kg-bw/day for FD&C Red No. 40 (Allura Red AC). 

3. Joint FAO/WHO Expert Committee on Food Additives (JECFA). Evaluation 

of certain food additives. Twenty-Fifth Report of the Joint FAO/WHO 

Expert Committee on Food Additives. WHO Technical Report Series 669. 

1981. p. 18. Accessed 1-24-2011 at 

http://whqlibdoc.who.int/trs/WHO_TRS_669.pdf .

In this document, the JECFA made permanent the recommended ADI of 0-7 mg/kgbw/day from WHO Food Additive Series 15.]