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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [insert name and telephone number with area 

code]

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:

[Clariant Corporation, [4000 Monroe Road, Charlotte, NC 28205] 

EPA has received a pesticide petition (IN 10631) from [Clariant

Corporation (EPA Company Number 8340, 4000 Monroe Road, Charlotte, NC 28205] 

requesting, 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

[C.I. Pigment Red 112, (CAS RN 6535-46-2) also known as 3-hydroxy-N-(2-

methylphenyl)-4- [2-(2,4,5-trichlorophenyl) diazenyl]- naphthalene-2-carboxamide), as a

seed treatment pigment, not to exceed 10% wt/wt, under 40 CFR §180.920 pursuant to 

Section 408(d)(1) of the Federal Food, Drug, and Cosmetic Act (FFDCA). There are

currently no approved non-food uses or food use tolerance exemptions for C.I. Pigment 

Red 112 as a pesticide inert ingredient. 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.
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Proposed 40 CFR §180.920 Tolerance Exemption and Limitations

Inert Ingredient CAS Reg. No. Limits

C.I. Pigment Red 112 

6535-46-1

10% (wt/wt) seed 

treatment formulation

A. Residue Chemistry

1. Plant metabolism. [Not applicable/Not required for the establishment 

of a tolerance exemption for inert ingredients.]

2. Analytical method. [Not applicable/Not required for the establishment 

of a tolerance exemption for inert ingredients.]

3. Magnitude of residues. [Not applicable/Not required for the establishment 

of a tolerance exemption for inert ingredients.]

B. Toxicological Profile

1. Acute toxicity. [The following acute toxicity data are available: OECD 401 

(rat acute oral) LD 50 > 15,000 mg/kg/day.(EPA IV, practically non-toxic); OECD 402 

(rat acute dermal) LD50 > 5000 mg/kg, EPA Category III; OECD 404 (rabbit dermal 

irritation), non-irritating; OECD 405 (rabbit acute eye irritation) non-irritating; OECD

429 (mouse local lymph node assay) non-sensitizing; and OECD 406 (guinea pig

Buehler Assay) non-sensitizing.

2. Genotoxicty. [C.I. Pigment Red did not display mutagenic activity in the 

following assays: AMES bacterial (OECD 471) assay with and without metabolic 

activation; Chinese hamster lung fibroblast cell micronucleus test (OECD 487, version 

3) with and without metabolic activation and negative and the mammalian cell gene 

mutation assay (OECD 476) with and without metabolic activation.]

3. Reproductive and developmental toxicity. [In evaluating the potential for reproductive 

and developmental toxicity of C.I. Pigment Red 112 when used only as an inert ingredient 

in seed treatment formulations, Clariant requests that EPA should take into account both the 

relevant reproductive/developmental toxicity endpoints in the OECD 407 28-Day Rat Oral 

Toxicity Study in rats and its physicochemical properties, which make the possibility of 

foliar residues and dietary exposures to sensitive populations highly unlikely. 

Although there were no reproductive or developmental toxicity studies available for C.I. 

Pigment Red 112, the OECD 407 28-Day Rat Oral Toxicity Study in rats included relevant 

endpoints specific to reproductive toxicity including organ weights, gross pathology and 

histopathology. The study demonstrated that there were no treatment-related effects on the 

relative and absolute organ weight data for the testes or epididymides when compared to 
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the vehicle control group mean. Gross pathology of the reproductive organs did not reveal 

any treatment-related effects in reproductive organs. Furthermore, histopathology of 

epididymides, prostate gland, seminal vesicles, testes, ovaries, vagina, cervix, and uterus of 

the high dose and vehicle control group animals demonstrated no differences at doses up to 

1000 mg/kg/bw/day. Additionally, as noted below, the DEREK modeling did not indicate 

any structural alerts for reproductive toxicity or endocrine-related toxicity.

In evaluating reproductive and developmental toxicity, EPA should also take into account 

that the physicochemical proprieties for C.I. Pigment 112 prevent the likelihood of potential 

foliar residues that could result in dietary exposures to the sensitive populations. EPA has 

previously applied a policy based Pigment Red 1physicochemical based qualitative 

rationale in its FQPA evaluation of the potential reproductive and developmental toxicity 

for another azo-colorants when they are used only as inert ingredients in soil treatment 

pesticide formulations. that should be applicable in assessing the reproductive and 

developmental risk of C.I. Pigment Red 112 used an inert ingredient in seed treatment 

formulations.

For example, the Pigment Red 48 is also a synthetic azo-naphthalene di-sodium salt 

derivative that has been granted a tolerance exemption for use as an inert dye ingredient is 

seed treatment formulation. Refer to the Inerts Tolerance Reassessment Petition 

(Attachment III; EPA, 2009). Specifically, as a result of the Pigment Red 48 EPISuite 

physicochemical properties analysis, the Agency could determine that the Pigment Red 48 

in seed treatments would not result in foliar residues. As such, the Agency rendered the 

following FQPA policy decision:

As stated on Page 8 of the February 10, 2008 Action Memorandum “Inerts Reassessment 

Pigment Red, CAS Reg No. 3564-21-4) that, despite of no relevant reproductive toxicity 

and developmental toxicology data the following conclusions was reached:

“No significant health concerns were identified and so Pigment Red 48 was given a 

low concern for human health effects. ...There is little or no probability of 

exposure to Pigment Red 48 expected from its use as an inert ingredient in pesticide 

formulations, and therefore, risk concerns are not expected by the Agency. 

Taking into consideration all available information on Pigment Red 48, it has been 

determined that there is reasonable certainty that no harm to any population 

subgroup will result from aggregate exposure to Pigment Red when considering 

dietary exposure and all other non-occupational sources of pesticide exposure for 

which there is reliable information. Therefore, it is recommended that the 

exemption from the requirement of a tolerance established for residues of Pigment 

Red when used as a dye for seed treatment only can be considered reassessed as 

safe under section 408(q) of the FFDCA”
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In rendering this FQPA decision, EPA made note of the physicochemical properties of 

Pigment Red 48 and that there was little likelihood of foliar residues resulting from the use 

of Pigment Red 48 as a seed treatment only. 

As specified on page 5/8 in the EPA (2009) Tolerance Reassessment:

“Therefore, this estimated is based solely on estimated properties. Red Dye 48 is not 

expected to rapidly degrade in the environment; primary degradation is expected to 

occur in the order of weeks and ultimate degradation (mineralization) on the order 

of months. The compound is classified as not readily biodegradable. Red Dye 48 

has a low octanol-water co-efficient (Kow of -1.25), this not likely to bioaccumulate 

in the environment. Red Dye 48 is soluble, non-volatile and likely to be mobile. 

Leaching into ground water is expected because of low estimated soil partition 

coefficient. Potential to volatize from surface water is very low and atmospheric 

degradation is expected to be fairly rapid”

Clariant is not bridging the physicochemical properties for C.I. Pigment Red 112 to 

Pigment Red 48, but rather is requesting that the Agency consider (along with the OECD 

407 28-Day Rat Oral Toxicity Study data)the physicochemical properties of C.I. Pigment 

Red 112, the likelihood of foliar residues and how the potential of foliar residues may result 

in the evaluation of C.I. Pigment Red 112 reproductive and developmental effects. Clariant 

emphasizes that the use of C.I. Pigment Red 112 as an inert ingredient in seed treatments 

should result in less environmental risk than Pigment Red 48. Specifically, there is less 

likelihood of foliar residues because, unlike a dye, as a solid pigment the C.I. Pigment 112 

pigment particles are less likely to diffuse into the soil from the seed treatment formulation. 

Additionally, EPA should take into account that in comparison to Pigment Red 48, C.I. 

Pigment Red 112, has a more extensive acute and repeat dose toxicology database. 

While EPISuite physicochemical properties indicate that both Pigment Red 48 and C.I. 

Pigment Red 112 may degrade slowly in the environment, and would not bioaccummulate 

and quickly degrade in air, C.I. Pigment Red 112, unlike Pigment Red 48, is not readily 

soluble in water and Koc calculations confirm that C.I. Pigment Red will, unlike Pigment 

Red 48, bind tightly to soil and sediment. Therefore, there is less likelihood that C.I. 

Pigment Red 112 may leach into ground or drinking water than Pigment Red 48. 

Additionally, as noted in Section VII, Potential Foliar Residues, we also ask EPA to take 

into account that the proposed amounts of C.I. Pigment 112 for seed treatment, not to 

exceed 10% wt/wt in the formulation, is low compared to the weight of the seeds that 

should be expected to be applied per acre. Following seed germination, it is also unlikely 

that any of the pigment would be taken up by the plant because C.I. Red Pigment 112 is 

expected to be tightly bound to soil. 
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This is comparable to the same rationale for Pigment Red 48 that was stated on Page 8 of 

the February 10, 2008 Action Memorandum “Inerts Reassessment Pigment Red, CAS Reg 

No. 3564-21-4”:

“The amount applied to seeds is small compared to the weight of the seeds. 

By the time seeds germinate most of the dye will be absorbed by the soil and 

eventually degraded with little of the dye available for potential plant 

uptake.” 

To summarize, Clariant requests that in consideration of the OECD 407 28-Day Rat Oral 

Toxicity Study and the physicochemical properties for C.I. Pigment Red 112 that EPA can 

conclude that the use of Pigment Red 112 only as an inert ingredient in seed treatment 

formulations does not pose undue reproductive or developmental risk to sensitive 

populations.]

5. Subchronic toxicity. [The general systemic toxicity NOAEL from the OECD 407 

28-Day Rat Oral Toxicity Study in rats was 1000 mg/kg body weight/day. 

6. Chronic toxicity. [Toxicological studies of chronic duration are not available for 

C.I. Pigment Red 112. Based on the available repeated dose testing in which the highest 

dose tested, 1000 mg/kg bw/day produced no treatment-related effects, a chronic 

Reference Dose (RfD) of 10 mg/kg bw/day can be derived based on the application of 

uncertainty factors for interspecies (10X) and intra-species (10X) differences. A Derived 

No Effect Level (DNEL) can also be calculated. The DNEL quantifies the no effect 

concentration for human exposure based on the application of uncertainty factors for 

interspecies differences (5X), intra-species differences (4X), and a factor for time 

extrapolation (2X). A factor of 1 was applied for remaining interspecies differences, 

because C.I. Pigment Red 112 is not likely to become systemically available in relevant

amounts based on ECETOC . The resulting overall assessment factor is 40 (5 x 4 x 2) for

a DNEL of 25 mg/kg bw/day.]

7. Animal metabolism. [There are no publically available mammalian metabolism 

data reported for C.I. Pigment Red 112, but it is unlikely that metabolism would result

in the production of toxic or carcinogenic metabolites.] Clariant has proposed the 

following rationale to address the potential animal metabolism in humans.

“The toxicokinetic profile of a substance comprises its absorption into the 

body, its distribution in the body, its metabolism in the body and its 

excretion from the body. Taking into account the physicochemical 

properties and the toxicological test results, qualitative estimates for these 

aspects may be deduced for Pigment Red 112.
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Absorption: A prerequisite for a relevant absorption is that the substance 

can be dissolved in either aqueous (e. g., gastrointestinal fluid, blood 

plasma, sweat) or lipophilic (e. g., lipoproteins, lipid membranes, 

triglycerides) media or in both. Pigment Red 112 can be considered 

insoluble because it has an extremely low solubility in water and noctanol. Therefore, it is unlikely that Pigment Red 112 becomes 

systemically bioavailable after oral, dermal or inhalation exposure. The 

results of acute oral toxicity, acute dermal toxicity and repeated oral 

toxicity studies also give valuable indications with regard to absorption

of the test substance. Based on the acute oral toxicity and the 28-day oral 

toxicity studies, which did not reveal any systemic effects that would 

indicate that the pigment had entered the body, no indications of 

significant absorption via the gastrointestinal tract has to be assumed.

Pigment Red 112 does not have particular skin or eye irritating or skin 

sensitizing properties that would imply a dermal absorptive potential. In 

the unlikely event of exposure to aerosolized pigment in respirable form, 

the substance is considered likely to behave like an inert dust. Therefore, 

the deposited pigment particles will mostly be cleared from the lung via 

the mucocilliary transport. As the pigment will not dissolve in the lung 

surfactant, the only way the pigment can enter the body is via 

phagocytosis of pigment particles by lung macrophages followed by 

migration of the macrophages into the interstitium and into the draining 

lymph nodes. However, the internal dose delivered via this mechanism 

can be considered negligible.

Distribution: The 28-day oral repeated dose toxicity study did not indicate any 

relevant histopathological changes in any of the investigated organs. This may 

indicate that either the pigment does not affect special organs as targets, i.e., is nontoxic, or is not distributed within the body in significant amounts. As indicted 

above, the physico-chemical parameters of the pigment support the conclusion that 

the pigment is not absorbed into the body and thus does not become systemically 

available. There were also no other signs of deposition of the pigment in any organ 

including excretory organs, like the kidney, indicating that even exposure to high 

doses of the pigment does not lead to bioaccumulation in special compartments of 

the body.

Metabolism: Since the dissolution of the substance in cellular fluid or 

cellular membranes is a prerequisite for its metabolism, it is unlikely

that the insoluble pigment becomes accessible for metabolizing systems in 

relevant amounts. The results of the mutagenicity tests provide useful 

indications for qualitative consideration of the metabolic fate of Pigment 

Red 112. In the mutagenicity tests, the pigment proved to be non-toxic

and nonmutagenic in the absence as well as in the presence of an 

exogenous metabolizing system, indicating that the pigment is not 
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converted into toxic or genotoxic metabolites. This conclusion is also 

supported by the lack of any morphological and histopathological changes 

of organs involved in xenobiotic metabolism, such as the liver, in the 

repeated dose toxicity study.

Excretion: The available data indicate that Pigment Red 112 is not 

absorbed into the body. In line with this conclusion, the 28-day oral 

repeated dose toxicity study did not indicate morphological or 

histopathological effects of the pigment on organs involved in excretion 

of chemicals from the body, such as the kidney. There was no indication 

that the substance was present in the urine. Moreover, from the repeated 

oral toxicity studies, it can be concluded that, after oral exposure, the 

pigment is excreted unchanged via the faeces.

7. Metabolite toxicology. [No Data]

8. Endocrine disruption. [C.I. Pigment Red 112 does not belong to a class of 

chemicals known or suspected of having adverse effects on the estrogen receptor or 

endocrine system.]

C. Aggregate Exposure

1. Dietary exposure. [While no specific residue information is available for C.I.

Pigment Red 112, on the basis of the proposed tolerance exemption and the physical 

chemical properties analysis, it is not likely that dietary exposures could result from the

use of C.I. Pigment Red 112 as pesticide inert ingredients only in seed treatment

formulations under 40 CFR §180.920 at concentrations not to exceed 10%. The seed

treatment formulations containing C.I. Pigment Red 112 will be applied directly to the

seeds and if released into the environment, the pigment will bind tightly to soil and

sediment and not be soluble in water. Under these conditions, C.I. Pigment 112 

would not be taken up by the germinated seedlings and translocated within the plant 

vascular system to result in crop residues and dietary exposures.

A dietary risk assessment sundertaken to confirm that potentially, if foliar residues should 

result from seed treatment use, that C.I. Pigment Red 112 does not pose undue dietary risk 

to US general and sensitive populations. 

EPA assesses potential dietary exposures to inert ingredients used in agricultural pesticide 

formulations using a screening-level model referred to as “I-DEEM,” in which the “I” 

stands for inerts and “DEEM” is the dietary exposure evaluation model that is used by EPA 

to assess dietary exposures to active ingredients in pesticide products. EPA’s Inert 

Ingredients Assessment Branch and residue chemists in the Health Effects Division of the 

Office of Pesticide Programs jointly developed I-DEEM. The model, as developed by 

EPA, uses crop-specific residue data (i.e., maximum tolerances) for 57 active ingredients as 

surrogates for potential inert ingredient residue levels. I-DEEM estimates that inert 

ingredients are used on all crops, and that 100 percent of all crops are assumed to be 
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“treated” with the inert ingredient(s). I-DEEM also assumes that the inert is present at a 

concentration of 50% in all the pesticide formulations. In addition, EPA includes potential 

residues of 100 ppb in water for potential drinking water exposures. Using these 

assumptions, and including the 10% cap for use in seed treatments, the chronic dietary 

exposure is estimated to be 0.040 mg/kg/d for the general U.S. population and 0.144 

mg/kg/d for children 1-2 years of age (i.e., the most highly exposed subpopulation]. 

Calculation of Chronic Reference Dose

[The no-observable-adverse-effect-level (NOAEL) for C.I. Pigment Red 112 may be 

assigned as 1000 mg/kg/day. 

The chronic reference dose (cRfD) is therefore 10 mg/kg/day. 

 cRfD = 1000 mg/kg body weight/day / 100 

 cRfD/cPAD = 10 mg/kg/day

The data and use pattern of low level soil application as a seed treatment support that the 

FQPA safety factor for C.I. Pigment Red 112 should be reduced from 10X to 1X. 

Therefore, only the 10X factors for intra- and inter- species variability should be included 

in calculating the chronic reference dose (cRfD) and the chronic population adjusted dose 

(cPAD). 

The dietary (food plus drinking water) exposures for C.I. Red Pigment 112 are expressed as 

a percentage of the proposed cPAD are summarized in Table 3. Chronic Safety Assessment, 

% cPAD for the general U.S. population and children 1-2 years old, the subpopulation with 

the highest potential exposures. Based on I-DEEM screening level calculations for , the 

chronic dietary exposures are estimated to be 0.40% of the cPAD for the general U.S. 

population and 1.44% of the cPAD for children 1-2 years old. These data demonstrate that 

the I-DEEM screening-level chronic dietary (food and drinking water) exposures are below 

the cPAD and are therefore below EPA’s established level of concern for all U.S. 

subpopulations.

On the basis of the proposed chronic NOEL (1000 mg/kg/day derived from the OECD 407 

compliant 28-day oral repeated dose toxicity study) and comparison of I-DEEM exposure 

estimates, Clariant contends that there is sufficient basis for EPA to grant a tolerance 

exemption for the 180.920 seed treatment uses at the maximum level of 10% in formulated 

products.]

i. Food. [The chronic dietary exposures estimated using the conservative IDEEM screening level model (food and drinking water) are well below 100% of the

cPAD, and are therefore below the level of concern for all U.S. subpopulations.]
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ii. Drinking water. [Drinking water is included in the I-DEEM 

exposure assessment and based on anticipated concentrations expected to be

negligible.]

2. Non-dietary exposure.None

D. Cumulative Effects

[It has not been determined that C.I. Pigment Red 112 has a common 

mechanism of toxicity with other substances.]

E. Safety Determination

1. U.S. population. [Based on the conservative exposure estimates, there is a 

reasonable certainty that no harm will result to the U.S. population from the

aggregate exposure to C.I. Pigment Red 112 used at 10% concentration in seed 

treatment only formulations with chronic dietary exposure estimated to be 0.04 

mg/kg/day (0.40%. PAD) for the general US population. 

There are no proposed uses for Pigment Red 112 that would result in 

residential exposures to the US Population. ]

2. Infants and children. [The FFDCA Section 408 requires an additional 

tenfold margin of safety for the protection of infants and children in case of threshold 

effects to account for prenatal and postnatal toxicity, and an inadequate toxicity

database. Where an adequate and reliable database is available and there is a lack of 

evidence for increased susceptibility, the FQPA safety factor may be reduced or 

removed. Based on available information discussed herein, Claraint, Inc. believes the 

FQPA safety factor should be reduced to 1X .for the reasons described below . The 

cRfD is therefore equivalent to the chronic population adjusted dose (cPAD).]

 An evaluation of susceptibility and uncertainty issues associated with the use to 

C.I. Pigment Red 112 used at 10% concentration in seed treatment formulations 

resulted in I-DEEM estimated chronic dietary exposures to children 1-2 years of 

age (the potentially most exposed population of 0.144 mg/kg/day (1.44% PAD).

 C.I. Pigment 112 has a scientifically sound mammalian toxicology database that 

includes acute, subchronic, and genotoxicity data. These test data, did not 

indicate developmental, reproductive, neurological endpoints or genotoxic 

effects.

 DEREK modeling also did not provide structural alerts for reproductive or 

developmental toxicity. 

 Physicochemical/environmental properties analysis indicates that crop residues,

that may result in dietary exposures to sensitive populations, are unlikely when 

C.I. Pigment Red 112 is used only as an inert ingredient in seed treatment 

formulation at concentrations not to exceed 10% wt/wt. 
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 C.I. Pigment Red 112 does not belong to a class of chemicals known or suspected 

of having adverse effects on the estrogen receptor or endocrine system.]

F. International Tolerances

[There are no known international tolerances for C.I. Pigment Red 112.]