1 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES April 1, 2004 Memorandum SUBJECT: Zinc Pyrithione ( Zinc Omadine ® ) : Toxicology Science Chapter For the Reregistration Eligibility Decision Document, PC Code 088002, Case 3030, Barcode: D301369 FROM: Timothy F. McMahon, Ph. D. Senior Toxicologist Antimicrobials Division ( AD) ( 7510C)

THRU: Nader Elkassabany, Ph. D. Team Leader Team II Risk Assessment and Science Support Branch Antimicrobials Division ( AD) ( 7510C)

TO: Deborah Smegal, Risk Assessor Risk Assessment and Science Support Branch Antimicrobials Division ( AD) ( 7510C)

Attached please find the Toxicology science chapter for Zinc Pyrithione ( Zinc Omadine ® ) in support of the Reregistration Eligibility Decision document. 2 TABLE OF CONTENTS 1.0 Hazard Characterization................................................................................................... 3 2.0 Toxicology Data Requirements........................................................................................ 5 3.0 Data Gaps......................................................................................................................... 5 4.0 Hazard Assessment.......................................................................................................... 6 4.1 Acute Toxicity................................................................................................... 6 4.2 Subchronic Toxicity........................................................................................... 6 4.3 Developmental/ Reproductive Toxicity.............................................................. 7 4.4 Chronic Toxicity/ Carcinogenicity..................................................................... 10 4.5 Mutagenicity..................................................................................................... 11 4.6 Neurotoxicity.................................................................................................... 11 4.7 Metabolism....................................................................................................... 12 5.0 Hazard Endpoint Selection........................................................................................... 13 5.1 Acute Reference Dose...................................................................................... 14 5.2 Chronic Reference Dose................................................................................... 16 5.3 Occupational/ Residential Exposure.................................................................. 17 5.3.1 Dermal Absorption................................................................................ 17 5.3.2 Short Term Dermal ( 1 7 Days)............................................................. 18 5.3.3 Intermediate Term Dermal.................................................................... 18 5.3.4 Long Term Dermal................................................................................ 19 5.3.5 Inhalation Exposure............................................................................... 19 5.3.6 Margins of Exposure............................................................................. 20 5.4 Classification of Carcinogenic Potential........................................................... 20 6.0 FQPA Considerations.................................................................................................... 20 6.1 Special Sensitivity to Infants and Children....................................................... 20 6.2 Database Uncertainty........................................................................................ 22 7.0 References.................................................................................................................... 24 3 1.0 Hazard Characterization The toxicology database for zinc pyrithione has been reviewed by the Office of Pesticide Program's Health Effects Division and Antimicrobials Division. The hazard database supporting the uses to be reregistered is adequate for this purpose. A database uncertainty factor was applied to non occupational risk assessments for lack of studies characterizing the dose response relationship for neurotoxicity of zinc pyrithione and for lack of chronic studies to select a chronic dietary endpoint. Acute and subchronic neurotoxicity studies have been requested for zinc pyrithione.

The toxicology database for zinc pyrithione indicates that by the oral route, zinc pyrithione is moderately toxic ( LD50 is 267 mg/ kg; Toxicity Category II) but that acute toxicity by the dermal route is not as significant ( LD50 > 2000 mg/ kg; Toxicity Category III). Acute toxicity by the inhalation route is also relatively low (> 0.61 mg/ L; Toxicity Category III). Zinc pyrithione is a severe eye irritant ( Toxicity category I) but does not appear to demonstrate significant dermal irritation ( Toxicity category IV). Zinc pyrithione does not demonstrate dermal sensitization potential.

Repeated dose ( 13 weeks) toxicity studies indicate that by the dermal route, zinc pyrithione is relatively non toxic ( decreased food consumption, decreased body weight gain, decreased food efficiency at the limit dose of 1000 mg/ kg/ day), but by the oral route, toxicity is significantly greater ( increased relative organ weights, clinical toxicity, and hindlimb weakness at 3.75 mg/ kg/ day). In both oral developmental studies in rats and rabbits, there was no quantitative evidence of increased susceptibility [ i. e., maternal and developmental no observed adverse effect levels ( NOAELs) were the same]. There was however, qualitative evidence of increased susceptibility ( i. e., fetal effects were considered to be more severe in the presence of minimal maternal toxicity). Neurotoxicity in maternal animals is also manifest at these doses. Data on neurotoxicity in developing animals are lacking. Reproductive toxicity testing using sodium pyrithione showed no apparent increased susceptibility of offspring to the reproductive toxicity of sodium pyrithione. However, based on the available evidence, the HIARC concluded that there was qualitative evidence of increased susceptibility to developing fetuses/ pups.

Zinc Pyrithione has not been classified as to carcinogenicity due to the absence of carcinogenicity studies for this chemical. A dermal carcinogenicity study in mice and an oral carcinogenicity study in rats exist for sodium pyrithione which have been reviewed by the Office of Pesticide Programs. There was no evidence for carcinogenicity in the rat study or the mouse study, but the mouse study was considered inadequate for risk assessment purposes. Therefore, sodium pyrithione could not be classified as to carcinogenic potential without an adequate study in the mouse.

The available evidence for gene mutations using the Ames Salmonella test system suggests that zinc pyrithione is negative for mutations in this system. In a Chinese hamster ovary forward gene mutation assay, zinc pyrithione failed to induce a mutagenic response at doses which included 4 cytotoxicity. In an in vivo micronucleus assay in mice, there was no evidence of a positive effect. Therefore, the data indicate that zinc pyrithione is negative for mutagenic effects. Sodium pyrithione has also been shown to be negative for mutagenic effects in the same assays.

Disposition and metabolism of zinc pyrithione has been examined in older studies which provide incomplete data. Studies from the published literature were summarized, but not reviewed by the Agency. In Yorkshire pigs administered an intravenous 5 mg/ kg dose of zinc pyrithione, plasma elimination was described as biphasic, with a t ½ alpha of 2.0 2.9 hr, and a t ½ beta of 26.6 36.3 hr. There were apparent differences in urinary elimination of 14C derived radioactivity from administration of sodium pyrithione ( 95%) vs. Zinc pyrithione ( 45 65%). In rabbits administered a 40 mg/ kg oral dose of zinc pyrithione, 75% of the administered radioactivity ( 14C) was eliminated in urine by 6 hours post dose, but only 0.05% of zinc was eliminated in urine. Pharmacokinetic studies in rats showed 74 84% of administered oral doses of 0.5, 1.25, and 12.5 mg/ kg eliminated in urine by 96 hours post dose. There were apparent sex differences in pharmacokinetics. Klaasan ( 1976) utilized 14C zinc pyrithione and isotopic65 zinc pyrithione to study zinc pyrithione. The author's conclusion indicate that zinc and pyrithione go to different locations in the body and are eliminated at different rates and different routes. The data do suggest less in vivo dissociation of zinc pyrithione vs. sodium pyrithione and greater retention of zinc in tissues vs. the pyrithione moiety.

In making its determination of safety for human health risks, AD considered potential dietary exposure to zinc pyrithione residues in food and water through the indirect food contact uses of this chemical. In addition, several residential exposure scenarios were included in the safety assessment. Thus, for purposes of this reregistration eligibility decision, aggregate exposure and risk assessments were conducted for dietary and short term, intermediate term, and long term occupational/ residential risk for zinc pyrithione.

Uncertainties There is concern for the neurotoxic effects of zinc pyrithione that have not been completely characterized in the available toxicology data. This uncertainty was addressed through the use of a database uncertainty factor applied to non occupational risk assessments for zinc pyrithione until adequate data are obtained. 5 2.0 Toxicology Data TOXICOLOGY DATA FOR ZINC Pyrithione TABLE 1 TOXICOLOGY DATA SUMMARY Guideline Number Data Requirement MRID Number 870.1100 Acute Oral Toxicity 42827901 870.1200 Acute Dermal Toxicity 42146701 870.1300 Acute Inhalation Toxicity 42146703 870.2400 Primary Eye Irritation 42146702 870.2500 Primary Dermal Irritation 42146704 870.2600 Dermal Sensitization 43950201 870.3250 Subchronic Dermal Toxicity 42827902 870.3465 Subchronic Inhalation Toxicity 42827903 870.4100 Chronic Toxicity ( sodium pyrithione) 41178101 870.4200 Carcinogenicity in Mice ( sodium pyrithione) 42100801 870.4300 Combined Chronic Toxicity / Carcinogenicity in Rats ( sodium pyrithione) 42100901 870.3700 Developmental Toxicity in Rats 42827904 870.3700 Developmental Toxicity in Rabbits 42827905 870.3800 2 Generation Reproduction Toxicity in Rats ( sodium pyrithione) 41097201 870.5575 Salmonella Plate Incorporation Assay 41906502 870.5265 CHO/ HGPRT Assay 41906503 870.5395 Mouse Micronucleus Assay 41906501 870.6200 Neurotoxicity screening battery no study available 1 Y = Yes; N = No; N/ A = Not Applicable. 2required if a carcinogenicity risk assessment is needed. 3 studies conducted according to the OPPTS guideline were not available for these endpoints. The available literature data indicate the need for conduct of a Neurotoxicity Screening Battery.

3.0 Data Gaps The toxicological data base for Zinc Pyrithione is adequate to support reregistration of this chemical. However, the need for acute and subchronic neurotoxicity studies to properly characterize the dose response relationship for this effect have been previously noted. 6 4.0 Hazard Assessment 4.1 Acute Toxicity The following table summarizes the acute toxicity of Zinc Pyrithione.

Guideline No. Study Type MRID # Results Toxicity Category § 81 1 ( OPPTS 870.1100) Acute Oral Toxicity 42827901 LD50 = 267 mg/ kg II § 81 2 ( OPPTS 870.1200 Acute Dermal Toxicity 42146701 LD50 > 2000 mg/ kg III § 81 3 Acute Inhalation Toxicity 42146703 LC50 > 0.61 mg/ L III § 81 4 ( OPPTS 870.2400) Primary Eye Irritation 42146702 severe irritant I § 81 5 ( OPPTS 870.2500) Primary Dermal Irritation 42146704 slight erythema and edema IV § 81 6 ( OPPTS 870.2600 Dermal Sensitization 43950201 no sensitization observed using Buehler method N/ A § 81 8 ( OPPTS 870.6200) Neurotoxicity screening battery non guideline study available  progressive hindlimb weakness and muscle atrophy at 12.5 mg/ kg/ day 4.2 Subchronic Toxicity Acceptable studies are available to satisfy subchronic testing requirements for this chemical.

870.3250 90 Day Dermal Toxicity in Rats In a subchronic dermal toxicity study ( MRID # 42827902), male and female CrlCD BR rats were treated with Zinc pyrithione ( Zinc Omadine ® ) FPS by dermal occlusion at doses of 0, 20, 100, 7 and 1000 mg/ kg/ day for 6 hours/ day, 5 days/ week for 13 weeks. Treatment related effects included decreased food consumption ( 91.6% of control), decreased body weight gain ( 48.9% of control), and decreased food efficiency ( 53.8% of control) over the entire treatment period for females in the 1000 mg/ kg/ day dose group. Group mean body weights for females ( 1000 mg/ kg/ day) were decreased 13% to 21% relative to controls for weeks 2 13. The systemic NOAEL = 100 mg/ kg/ day in females, and 1000 mg/ kg/ day in males. The systemic LOAEL = 1000 mg/ kg/ day in females ( decreased body weight gain, food consumption, and food efficiency), and > 1000 mg/ kg/ day in males .

This study is classified as acceptable and satisfies the guideline requirement ( § 82 3) for a subchronic dermal toxicity study in rats.

870.3465 Subchronic Inhalation Toxicity in Rats In a subchronic inhalation toxicity study ( MRID # 42827903), groups of 15 male and 15 female Sprague Dawley rats were dynamically exposed in whole body exposure chambers to zinc pyrithione ( 52.2% aqueous suspension) aerosols at concentrations of 0.0005, 0.0025, or 0.01 mg/ L/ day for 6 hours/ day, 5 days/ week for 13 weeks. One male and 1 female exposed to 0.0025 mg/ L/ day and 3 males and 4 females exposed to 0.01 mg/ L/ day died over the course of the study. Treatment related clinical signs of toxicity included rales, labored breathing, and gasping in animals that died on study. At 0.01 mg/ L/ day, body weights of females were depressed as much as 23%, compared to controls, total food consumption was decreased 10%, and food efficiency was decreased 53%. Hematologic, clinical chemistry, or urinalysis effects were not considered biologically significant for any of the exposure groups, and ophthalmologic examinations and gross necropsy findings were negative. Biologically significant increases in absolute and ( relative) lung weights of + 20% (+ 34%) and + 22% (+ 38%) in males, and + 13% (+ 18%) and + 25% (+ 68%) in females were seen at concentrations of 0.0025 and 0.01 mg/ L/ day, respectively. The increased lung weights corresponded to histopathologic findings of trace to mild subacute inflammation of the interstitial tissue of the lung and medial hypertrophy of pulmonary arteries which were biologically significant at 0.01 mg/ L/ day. Based on the results of this study, the systemic NOAEL = 0.0005 mg/ L/ day, and the systemic LOAEL= 0.0025 mg/ L/ day ( labored breathing, rales, increased salivation, decreased activity, dry red brown material around the nose, increased absolute and relative lung weights, and death of undetermined cause)

This study is classified acceptable and satisfies the guideline requirement ( § 82 4; OPPTS 870.3465) for a subchronic inhalation toxicity study in rats.

4.3 Developmental Toxicity Available developmental toxicity studies are adequate to satisfy guideline requirements.

870.3700 Developmental Toxicity in Rats 8 In a developmental study ( MRID 42827904), thirty pregnant Sprague Dawley rats per group were administered Zinc Pyrithione by oral gavage on days 6 15 of gestation at doses of 0, 0.75, 3, or 15 mg/ kg/ day. One dam in the 15 mg/ kg/ day dose group died on gestation day 16 of unspecified causes. No maternal or developmental toxicity was observed at 0.75 mg/ kg/ day.

The most sensitive indicator of maternal toxicity was increased salivation immediately after dosing which was observed in the 3 and 15 mg/ kg/ day groups ( 27% and 97% of dams, respectively). Other dose related signs seen at 15 mg/ kg/ day included biologically significant decreases in body weight gains ( 67%; p

0.01; absolutes of 4 12%) and food consumption ( 24% during dosing, 16% throughout gestation; p

0.01), and dilated pupils ( 57%). The maternal toxicity NOEL is 0.75 mg/ kg/ day, and the maternal toxicity LOAEL is 3.0 mg/ kg/ day, based upon excessive salivation during the dosing period.

Developmental toxicity was characterized by a dose related increase in postimplantation loss at the mid and high doses with the 15 mg/ kg/ day group being significantly different than controls ( p < 0.01). This correlated with an increase in early resorptions ( 3.6%/ dam) with whole litter resorption occurring in 3 high dose dams. There was also a significant reduction ( p

0.05) in the number of live fetuses per litter ( 12.5/ litter compared to 14.5/ litter in the controls), mean fetal weights ( 16%), and gravid uterine weights ( 16%; p

0.01) in the 15 mg/ kg/ day group as compared to controls.

A significantly greater number of litters in the 15 mg/ kg/ day group contained fetuses with external, visceral, or skeletal malformations/ variations. The most common were digit anomalies ( 5 of 24 treated litters vs. 0 of 27 control litters; p

0.05), dilated renal pelvis ( 7 of 24 treated litters vs. 1 of 27 control litters; p

0.05) which is considered indicative of hydronephrosis, and a vertebral/ rib anomaly ( 24 of 24 treated litters vs. 0 of 27 control litters; p

0.01). Others included sternal, rib, and limb ( radius or ulna absent) malformations. Dose related fused ribs were observed in the mid and high dose groups ( 3 fetuses/ 2 litters, and 5 fetuses/ 4 litters, respectively). Although pairwise comparisons, on the basis of litters, were not statistically significant ( p= 0.226 and p= 0.060 for the mid and high dose groups, respectively), a statistically significant linear trend was evident ( Cochran Armitage test; p= 0.009), and historical control values were exceeded. The developmental toxicity NOEL is 0.75 mg/ kg/ day, and the developmental toxicity LOAEL is 3.0 mg/ kg/ day, based upon increased incidences of fused ribs.

This study is classified Acceptable and satisfies the guideline requirement for a developmental study ( § 83 3; OPPTS 870.3700) in rats.

870.3700 Developmental Toxicity in Rabbits In a developmental toxicity study in rabbits ( MRID # 42827905), inseminated New Zealand White rabbits, randomly assigned to one control and three treatment groups of 20 animals each, were administered Zinc Pyrithione 48% Aqueous Dispersion by oral gavage at doses of 0, 9 0.5, 1.5, or 3.0 mg/ kg/ day on gestation days ( GD) 6  18. Cesarean section examinations were performed on all surviving does on GD 29, followed by an examination of all fetuses.

One mid dose doe died on GD 16, probably due to a gavage error. A decrease in body weight gain ( p

0.01) during the dosing period for the mid and high dose groups ( 41% and 99%, respectively) cannot be considered biologically significant since the absolute body weight changes were only  4% and  6%, respectively. There was no dose related effect on food consumption. The does' body weights rebounded after the dosing interval. There were no compound related gross lesions. One high dose doe aborted on GD 27, and five others had total resorptions. One mid dose doe had total litter resorption. Dose related early resorptions were seen in the mid and high dose does. These findings corresponded with a dose related increase in postimplantation loss ( early resorption) and a decrease in viable fetuses. It is not clear whether the resorptions were due to maternal or developmental toxicity. No statistically significant differences were seen in the incidence of external, visceral, or skeletal anomalies in the treated groups as compared to controls. Three fetuses from two high dose litters contained multiple cephalic and limb malformations. The Maternal/ Developmental NOAEL is 0.5 mg/ kg/ day. The LOAEL is 1.5 mg/ kg/ day, based on increased postimplantation loss and decreased number of viable fetuses ( it is not clear whether the resorptions were due to maternal or developmental toxicity).

This study is classified as acceptable and satisfies the guideline requirement ( § 83 3; OPPTS 870.3700) for a developmental toxicity study in rabbits.

870.3800 Reproductive Toxicity Data are available for sodium pyrithione that will satisfy the data requirement for zinc pyrithione.

In a two generation reproduction study ( MRID # 41097201) conducted with 40% sodium pyrithione, Crl: CD( SD) BR rats received the test chemical in distilled water by gavage at dose levels of 0, 0.5, 1.5, or 3.5 mg/ kg/ day at a dose volume of 10ml/ kg. The high dose of 3.5 mg/ kg/ day was originally 4.5 mg/ kg/ day, but was scaled back to 3.5 mg/ kg/ day based on excessive toxicity at the 4.5 mg/ kg/ day dose. At 3.5 mg/ kg/ day, one female parental rat in the F0 generation was sacrificed on day 87 after demonstrating hunched posture, impaired hindlimb mobility, rapid breathing, and peri orbital, peri nasal, and abdominal staining. In the F1 generation, two females at the 3.5 mg/ kg/ day dose were also sacrificed in days 225 and 235, based on similar clinical signs of toxicity as those observed in the F0 female. Excessive salivation was also observed in all male and female rats at the 1.5 and 3.5 mg/ kg/ day dose levels. Decreased body weight was observed in both parental generations of females and the F0 generation of males at the 3.5 mg/ kg/ day dose. Decreases were in the range of 88 96% of control values. There was no reported effect on food consumption of either sex or generation of parental rats. Wasting of hindlimb muscles was observed in those females at 3.5 mg/ kg/ day sacrificed during the study. Skeletal muscle atrophy was observed histologically in both sexes and generations of parental rats 10 at the 1.5 and 3.5 mg/ kg/ day dose levels. This was characterized as reduction and variation in the diameter of muscle fibers, increase in number of sarcolemmal nuclei, and fatty replacement of muscle fibers.

Reproductive toxicity was observed at the 3.5 mg/ kg/ day dose level in the F0 parents and the F1 offspring. Mating index in males was reduced significantly as was fertility index. The number of estrous cycles per mating was increased in F0 females at 3.5 mg/ kg/ day. There were no effects on total live pups, mean number of live pups per litter, live birth index, viability index, or lactation index in F1 pups. Mean pup body weight was decreased slightly on post natal day 1 but this decrease was not significant. Developmental landmarks ( percentage of pups with ears open on lactation day 3 and percentage of pups with eyes open on lactation day 15) was decreased by 19% and 7% respectively, but was not statistically significant. Mean percentage of pups with startle response on lactation day 15 was decreased significantly by 10%. In the F1 parents and the F2 offspring, mating and fertility indices were reduced at all dose levels relative to control, but it is likely that atrophy of hindlimb muscles in males could impact mating success and therefore would explain the decrease in mating and fertility indices. Mean percentage of pups with startle response on lactation day 15 and mean percentage of pups with eyes open on lactation day 15 was decreased by 13% and 14% respectively, but this was not statistically significant.

Based on the results of this study, the Systemic NOAEL is determined to be 0.5 mg/ kg/ day, and the Systemic LOAEL is determined to be 1.5 mg/ kg/ day, based on increased incidence of histological alterations of the hindlimb skeletal muscle in F0 males and F1 males and females. The Reproductive toxicity NOAEL is determined to be 1.5 mg/ kg/ day, and the Reproductive toxicity LOAEL is determined to be 3.5 mg/ kg/ day, based on slightly decreased number of pups per litter in both generations, delayed development in pups from both generations, and decreased pup body weight in both generations. This study is classified as acceptable ( guideline) and satisfies the data requirement for a reproductive toxicity study in rats.

4.4 Chronic Toxicity and Carcinogenicity There were no submitted chronic toxicity or carcinogenicity studies on zinc pyrithione. A dermal carcinogenicity study in mice and an oral carcinogenicity study in rats exist for sodium pyrithione which have been reviewed by the Office of Pesticide Programs. There was no evidence for carcinogenicity in the rat study or the mouse study, but the mouse study was considered inadequate for risk assessment purposes. Therefore, sodium pyrithione could not be classified as to carcinogenic potential without an adequate study in the mouse.

4.5 Mutagenicity Mutagenicity data are available for zinc pyrithione which satisfy the data requirements for this 11 chemical.

Gene Mutation Salmonella typhimurium Assay In a mutagenicity study ( MRID # 41906502), doses of zinc pyrithione ( 48% aqueous dispersion) ranging from 0.03 5.0  g/ plate under non activated condition and 10 333  g/ plate under S 9 activated conditions were evaluated for the potential to induce reverse gene mutations in five tester strains of Salmonella typhimurium ( TA98, TA100, TA1535, TA1537, TA1538). Cytotoxicity was observed in this assay at 3.3  g/ plate and above under non activated conditions, and at 333  g./ plate and above under activated conditions. There was no reproducible evidence of a mutagenic effect in either the absence or presence of metabolic activation in this study.

Gene Mutation in Cultured Chinese Hamster Ovary Cells In a mutagenicity study using Chinese Hamster Ovary ( CHO) cells ( MRID # 41906503) assays were conducted in the absence of metabolic activation ( doses of 0.25 2.0  g/ ml) and the presence of metabolic activation ( 2.5 30  g/ ml). In this study, zinc pyrithione failed to induce a mutagenic response.

In vivo Micronucleus Assay in Mice In this study ( MRID # 41906501), intraperitoneal injection of single doses of 11, 22, or 44 mg/ kg zinc pyrithione ( 48% aqueous dispersion) to ICR mice did not cause a significant increase in the frequency of micronucleated polychromatic erythrocytes ( MPEs) in bone marrow cells harvested 24, 48, or 72 hours post dose. High dose mice exhibited signs of toxicity ( including mortality, lethargy, piloerection, and diarrhea) but there was no evidence of a cytotoxic effect on the target organ. Therefore, zinc pyrithione is concluded to be negative for mutagenicity in this test system..

4.6 Neurotoxicity No recent guideline studies have been submitted to the Agency with respect to the neurotoxicity of zinc pyrithione. In a non guideline toxicity study, CD male rats, 150 250g, were divided into 63 pairs. Technical grade zinc pyrithione ( 97.0%) was administered to one rat of each pair at a dose of 250 ppm for either 9 or 14 days. Gastrocnemius and soleus muscles were examined in five treated and five pair fed controls. Eighteen treated and 18 pair fed controls were used for ultrastructural evaluation of nervous tissue. Nerve conduction velocity of the sural nerve was determined in a total of 74 treated and pair fed controls. In vitro recording of nerve conduction velocity was also made using the sciatic nerve. Histologic morphology of all examined muscles was normal. Sciatic, sural, and spinal nerve roots were not altered after 14 days of treatment. Myelinated sural nerve axons in rats recovered for 2 weeks showed accumulation of dense 12 granular axoplasmic deposits. The most prominent changes were observed in intramuscular lumbrical fibers, where axons were enlarged and contained abundant mitochondria and electron dense granules. Sensory nerve conduction velocities measured in vivo showed no significant difference between treated and control rats. However, peak to peak sensory potential amplitudes were significantly different between treated and control rats. At 2 and 4 weeks after treatment, clinical signs were absent in treated rats, but sensory nerve evoked potential amplitudes remained significantly different after 2 weeks recovery. The results of this study suggest a primary toxic effect of zinc pyrithione on muscle fibers, and a toxic effect on nerve fibers consistent with random axonal loss by Wallerian degeneration or inactivation. i. e. approximately 5 mg/ kg and above.

Several studies published in the open scientific literature have also noted neurotoxic effects from exposure to zinc pyrithione. Ross and Lawhorn ( Neurotoxicol. Teratol 12( 2): 153 159, 1990) observed reduction in forelimb and hindlimb grip strength and electrophysiological changes after administration of zinc pyrithione in the diet at 50 ppm ( 2.5 mg/ kg/ day) indicative of neurotoxicity at the neuromuscular junction. Snyder et al. ( Food Cosmet. Toxicol. 17( 6), 651 660, 1979) observed progressive hind limb weakness, motor incoordination, and reduced sensory and mixed sensory/ motor nerve evoked potential amplitude ( but no reduction in conduction velocity) in male rats administered 250 ppm ( 12.5 mg/ kg/ day) zinc pyrithione in the diet for 9 or 14 days with a 4 week recovery period. Although clinical signs abated during the recovery period, decreases in nerve evoked potential amplitude remained decreased. Administration of zinc pyrithione to dogs has produced blindness and retinal detachment ( Grant, W. M. Toxicology of the Eye. 3rd ed. Springfield, IL. Charles C. Thomas, Pub.)

4.7 Metabolism Metabolism data for zinc pyrithione are incomplete. Available data consist Agency summaries of submitted data, performed in 1978, and a single report from the scientific literature, also dated 1978.

An Agency summary of a report published in Toxicology and Applied Pharmacology 36: 523 531, 1976, was obtained. In this study, a single dose of zinc pyrithione at 5 mg/ kg ( labeled in the 2,6 positions) was administered intravenously through the jugular vein to 2 female Yorkshire pigs. Plasma half life, urinary excretion rate, and metabolism was investigated. Cholinergic effects ( parasympathetic and somatomotor) were observed after test article administration, although the time of onset after test article administration was not observed. The duration of symptoms was stated as 30 60 minutes. Plasma decline was described as biphasic. Specific values for zinc pyrithione were not stated, as the sodium salt and magnesium adduct were also examined in this study. The alpha phase was stated as 2.0 2.9 hours, and the beta phase from 26.6 36.3 hours. Urine appears to have been the major route of excretion for the administered radioactivity. While 95% of the administered radioactivity from administration of sodium pyrithione was recovered in urine, the summary stated that only between 45 65% of zinc pyrithione radioactivity was recovered in urine. This observed difference could reflect the fact that zinc pyrithione would dissociate less in vivo than sodium pyrithione. This observation is also consistent with the finding 13 that a higher percentage of radioactivity was found in tissues ( liver, kidney, and pancreas) from zinc pyrithione treated pigs vs. other treated groups, although specific values were not stated. TLC analysis of urine indicated the presence of the metabolite 2( pyridyl N oxide) sulfonic acid after zinc pyrithione administration, while sodium pyrithione metabolites in urine consisted of pyrithione disulfide.

In a second study published in Toxicology and Applied Pharmacology ( 35: 581 587, Klaassen, 1976), rabbits ( three per group) were given either a 1 mg/ kg intravenous dose via the ear vein or a 40 mg/ kg oral dose by gavage of zinc pyrithione labeled either with 14 C ( position of label not stated) or 65 Zn. A dual label was not administered in this experiment. Rabbits were sacrificed at 6 hours post dose. Urinary excretion and plasma clearance were measured at timed intervals prior to sacrifice. Tissue levels were examined at sacrifice. After intravenous administration, 75% of administered 14 C was stated to be in urine, while the blood level of 65 Zn was stated to be relatively constant, with only 0.05% excreted in urine. Tissue concentrations of radiolabeled zinc at 6 hours post dose were stated to be approximately 10 times that of the radiolabeled pyridinethione. ( i. e. 5% 14 C vs. 55% 65 Zn per gram liver tissue). The author's conclusion indicate that zinc and pyrithione go to different locations in the body and are eliminated at different rates and different routes. It appears that, based on the starting material, zinc pyrithione does not dissociate to the extent that sodium pyrithione does.

In a third published report ( J. H. Wedig, et al., Fd. Cosmet. Toxicol. 16: 553 561), the pharmacokinetics of 2,6 [ C 14] labeled zinc pyrithione were examined in male and female Sprague Dawley rats. Concentration of radioactivity was determined in blood, urine, and feces as a function of time following oral doses of 0.5, 1.25, and 12.5 mg/ kg. Urine appeared as the major route of excretion at all dose levels ( 74 84% of administered radioactivity), with fecal excretion between 13 21% of the administered radioactivity. Sex differences were apparent with respect to plasma elimination, renal clearance, time required to maximum blood concentration, and rate of absorption. Male rats were observed with significantly lower blood concentrations of [ C 14], and were also observed with a higher rate for metabolism of zinc pyrithione.

5.0 Hazard Endpoint Selection Toxicity end point selection is summarized below.

5.1 Acute Reference Dose ( RfD)

Subpopulation: Females 13+

Study Selected: Developmental Toxicity  Rabbit MRID No.: 42827905 Executive Summary: In a developmental toxicity study in rabbits ( MRID # 42827905), 14 inseminated New Zealand White rabbits, randomly assigned to one control and three treatment groups of 20 animals each, were administered zinc pyrithione 48% Aqueous Dispersion by oral gavage at doses of 0, 0.5, 1.5, or 3.0 mg/ kg/ day on gestation days ( GD) 6  18. Cesarean section examinations were performed on all surviving does on GD 29, followed by an examination of all fetuses. One mid dose doe died on GD 16, probably due to a gavage error. A decrease in body weight gain ( p 0.01) during the dosing period for the mid and high dose groups ( 41% and 99%, respectively) cannot be considered biologically significant since the absolute body weight changes were only  4% and  6%, respectively. There was no dose related effect on food consumption. The does' body weights rebounded after the dosing interval. There were no compound related gross lesions. One high dose doe aborted on GD 27, and five others had total resorptions. One mid dose doe had total litter resorption. Dose related early resorptions were seen in the mid and high dose does. These findings corresponded with a dose related increase in post implantation loss( early resorption) and a decrease in viable fetuses. It is not clear whether the resorptions were due to maternal or developmental toxicity. No statistically significant differences were seen in the incidence of external, visceral, or skeletal anomalies in the treated groups as compared to controls. Three fetuses from two high dose litters contained multiple cephalic and limb malformations. The Maternal/ Developmental NOAEL is 0.5 mg/ kg/ day. The LOAEL is 1.5 mg/ kg/ day, based on increased postimplantation loss and decreased number of viable fetuses ( it is not clear whether the resorptions were due to maternal or developmental toxicity).

Dose Selected for Risk Assessment: NOAEL= 0.5 mg/ kg/ day based on increased postimplantation loss and decreased viable fetuses at 1.5 mg/ kg/ day ( LOAEL).

Uncertainty Factor: 300 ( 10 x for inter species variation, 10x for intra species extrapolation, 3x database uncertainty)

Comments about Study/ Endpoint Uncertainty Factor: The endpoint of concern ( increased post implantation loss and decreased viable fetuses) is an in utero effect, and therefore is applicable only to this subpopulation ( Females 13+). Also, these developmental effects are presumed to occur after a single exposure ( dose), thus are applicable for this exposure period of concern.

Acute RfD ( Females 13+) = 0.5 mg/ kg/ day ( NOAEL) = 0.0016 mg/ kg 300 ( UF)

Acute RfD Subpopulation: General Population including Infants and children Study Selected : Developmental Toxicity  Rat 15 MRID No.: 42827905 Executive Summary: In a developmental study ( MRID 42827904), thirty pregnant Sprague Dawley rats per group were administered Zinc Pyrithione by oral gavage on days 6 15 of gestation at doses of 0, 0.75, 3, or 15 mg/ kg/ day. One dam in the 15 mg/ kg/ day dose group died on gestation day 16 of unspecified causes. No maternal or developmental toxicity was observed at 0.75 mg/ kg/ day. The most sensitive indicator of maternal toxicity was increased salivation immediately after dosing which was observed in the 3 and 15 mg/ kg/ day groups ( 27% and 97% of dams, respectively). Other dose related signs seen at 15 mg/ kg/ day included biologically significant decreases in body weight gains ( 67%; p 0.01; absolutes of 4 12%) and food consumption ( 24% during dosing, 16% throughout gestation; p 0.01), and dilated pupils ( 57%). The maternal toxicity NOEL is 0.75 mg/ kg/ day, and the maternal toxicity LOAEL is 3.0 mg/ kg/ day, based upon excessive salivation during the dosing period.

Developmental toxicity was characterized by a dose related increase in post implantation loss at the mid and high doses with the 15 mg/ kg/ day group being significantly different than controls ( p < 0.01). This correlated with an increase in early resorptions ( 3.6%/ dam) with whole litter resorption occurring in 3 high dose dams. There was also a significant reduction ( p < 0.05) in the number of live fetuses per litter ( 12.5/ litter compared to 14.5/ litter in the controls), mean fetal weights ( 16%), and gravid uterine weights ( 16%; p 0.01) in the 15 mg/ kg/ day group as compared to controls. A significantly greater number of litters in the 15 mg/ kg/ day group contained fetuses with external, visceral, or skeletal malformations/ variations. The most common were digit anomalies ( 5 of 24 treated litters vs. 0 of 27 control litters; p 0.05), dilated renal pelvis ( 7 of 24 treated litters vs. 1 of 27 control litters; p 0.05) which is considered indicative of hydronephrosis, and a vertebral/ rib anomaly ( 24 of 24 treated litters vs. 0 of 27 control litters; p < 0.01). Others included sternal, rib, and limb ( radius or ulna absent) malformations. Dose related fused ribs were observed in the mid and high dose groups ( 3 fetuses/ 2 litters, and 5 fetuses/ 4 litters, respectively). Although pairwise comparisons, on the basis of litters, were not statistically significant ( p= 0.226 and p= 0.060 for the mid and high dose groups, respectively), a statistically significant linear trend was evident ( Cochran Armitage test; p= 0.009), and historical control values were exceeded. The developmental toxicity NOEL is 0.75mg/ kg/ day, and the developmental toxicity LOAEL is 3.0 mg/ kg/ day, based upon increased incidences of fused ribs.

Dose Selected for Risk Assessment: NOAEL= 0.75 mg/ kg/ day based on salivation in dams at 3.0 mg/ kg/ day ( LOAEL).

Uncertainty Factor: 300 ( 10 x for inter species variation, 10x for intra species extrapolation, 3x database uncertainty)

Acute RfD = 0.75 mg/ kg/ day ( NOAEL) = 0.0025 mg/ kg 16 300 ( UF)

Comments about Study/ Endpoint Uncertainty Factor: The endpoint ( salivation) was seen in maternal animals during the dosing period, and thus are relevant for this subpopulation and exposure period of concern.

5.2 Chronic Reference Dose Study Selected: Developmental Toxicity  rat In a developmental study ( MRID 42827904), thirty pregnant Sprague Dawley rats per group were administered Zinc Pyrithione by oral gavage on days 6 15 of gestation at doses of 0, 0.75, 3, or 15 mg/ kg/ day. One dam in the 15 mg/ kg/ day dose group died on gestation day 16 of unspecified causes. No maternal or developmental toxicity was observed at 0.75 mg/ kg/ day.

The most sensitive indicator of maternal toxicity was increased salivation immediately after dosing which was observed in the 3 and 15 mg/ kg/ day groups ( 27% and 97% of dams, respectively). Other dose related signs seen at 15 mg/ kg/ day included biologically significant decreases in body weight gains ( 67%; p

0.01; absolutes of 4 12%) and food consumption ( 24% during dosing, 16% throughout gestation; p

0.01), and dilated pupils ( 57%). The maternal toxicity NOEL is 0.75 mg/ kg/ day, and the maternal toxicity LOEL is 3.0 mg/ kg/ day, based upon excessive salivation during the dosing period.

Developmental toxicity was characterized by a dose related increase in postimplantation loss at the mid and high doses with the 15 mg/ kg/ day group being significantly different than controls ( p < 0.01). This correlated with an increase in early resorptions ( 3.6%/ dam) with whole litter resorption occurring in 3 high dose dams. There was also a significant reduction ( p < 0.05) in the number of live fetuses per litter ( 12.5/ litter compared to 14.5/ litter in the controls), mean fetal weights ( 16%), and gravid uterine weights ( 16%; p < 0.01) in the 15 mg/ kg/ day group as compared to controls.

A significantly greater number of litters in the 15 mg/ kg/ day group contained fetuses with external, visceral, or skeletal malformations/ variations. The most common were digit anomalies ( 5 of 24 treated litters vs. 0 of 27 control litters; p < 0.05), dilated renal pelvis ( 7 of 24 treated litters vs. 1 of 27 control litters; p < 0.05) which is considered indicative of hydronephrosis, and a vertebral/ rib anomaly ( 24 of 24 treated litters vs. 0 of 27 control litters; p < 0.01). Others included sternal, rib, and limb ( radius or ulna absent) malformations. Dose related fused ribs were observed in the mid and high dose groups ( 3 fetuses/ 2 litters, and 5 fetuses/ 4 litters, respectively). Although pairwise comparisons, on the basis of litters, were not statistically significant ( p= 0.226 and p= 0.060 for the mid and high dose groups, respectively), a statistically significant linear trend was evident ( Cochran Armitage test; p= 0.009), and historical control values were exceeded. The 17 developmental toxicity NOEL is 0.75 mg/ kg/ day, and the developmental toxicity LOEL is 3.0 mg/ kg/ day, based upon increased incidences of fused ribs.

Dose and endpoint: NOAEL of 0.5 mg/ kg/ day, based on increased post implantation loss and decreased viable fetuses at 1.5 mg/ kg/ day.

Uncertainty Factor: 300 ( 10 x inter species variation, 10x intra species extrapolation, 3x database uncertainty).

Chronic RfD = 0.5 mg/ kg/ day ( NOAEL) = 0.0016 mg/ kg/ day 300 ( UF)

Comments about Study/ Endpoint Uncertainty Factor: Since no long term feeding studies are available, a developmental toxicity study in rats with the lowest NOAEL in the toxicology database was selected.

5.3 Occupational / Residential Exposure 5.3.1 Dermal Absorption Study Selected: Dermal Absorption  Domestic Swine MRID No.: HED document no. 003933 Executive Summary: Twenty six mature Yorkshire pigs were used in this study. Radiolabelled zinc pyrithione was applied for 8 hours either as a single dose ( 50, 100, and 400 mg/ kg) or as a 5 day repeated dose ( 100 mg/ kg). Serial samples of blood, urine, and feces were taken after dosing. Radioassay of necropsy material, urine, blood, and feces showed recovery of 86.8 98.2% of applied radioactivity. Greater than 90% of recovery was obtained from washings of the application site. Urinary excretion was 3% in animals with intact skin. Levels of radioactivity in blood, urine, and feces returned to background by 48 hours post application.

Dermal Absorption Factor: 3%

Comments about Dermal Absorption Factor: A dermal absorption factor is not required since a dermal NOAEL was selected for dermal risk assessments. However, it is noted that the 3% dermal absorption factor demonstrated in the swine study is supported by a literature study in mice ( 1975; HED Doc. No. 003933) which also showed a dermal absorption of 3%. Additionally, low dermal absorption is indicated by the lack of systemic toxicity in male rats following repeated dermal applications at the Limit Dose ( 1000 mg/ kg/ day) for 90 days in a dermal toxicity study. 18 5.3.2 Short Term Dermal ( 1 day 1 month)

Study Selected: 90 Day Dermal Toxicity  rats MRID No.: 42827902 Executive Summary: In a subchronic dermal toxicity study ( MRID # 42827902), male and female CrlCD BR rats were treated with Zinc Pyrithione FPS by dermal occlusion at doses of 0, 20, 100, and 1000 mg/ kg/ day for 6 hours/ day, 5 days/ week for 13 weeks. Treatment related effects included decreased food consumption ( 91.6% of control), decreased body weight gain ( 48.9% of control), and decreased food efficiency ( 53.8% of control) over the entire treatment period for females in the 1000 mg/ kg/ day dose group. Group mean body weights for females ( 1000 mg/ kg/ day) were decreased 13% to 21% relative to controls for weeks 2 13. The systemic NOAEL = 100 mg/ kg/ day in females, and 1000 mg/ kg/ day in males. The systemic LOAEL = 1000 mg/ kg/ day in females ( decreased body weight gain, food consumption, and food efficiency), and > 1000 mg/ kg/ day in males .

Dose and Endpoint : NOAEL of 100 mg/ kg/ day, based on body weight decrements in female rats at the limit dose of 1000 mg/ kg/ day. An uncertainty factor of 100 was recommended for this risk assessment.

Comments about Study/ Endpoint: This study is appropriate for the route ( dermal) and exposure period ( 1 7 days) of concerns since the route of treatment ( dermal) in animals simulates real life occupational exposure ( dermal) scenarios.

5.3.3 Intermediate Term Dermal ( 1 6 months )

Study Selected: 90 Day Dermal Toxicity  rats MRID No.: 42827902 Executive Summary: See executive summary above for short term dermal.

Dose and Endpoint Proposed for Consideration: NOAEL of 100 mg/ kg/ day, based on body weight decrements in female rats at the limit dose of 1000 mg/ kg/ day. An uncertainty factor of 100 was recommended for this risk assessment.

Comments about Study/ Endpoint: none 19 5.3.4 Long Term Dermal (> 6 months)

Study Selected: 90 Day Dermal Toxicity  rats MRID No.: 42827902 Executive Summary: see above for short term dermal Dose and Endpoint : see above for short term dermal.

Comments about Study/ Endpoint: The 90 day dermal study was deemed to be appropriate since following repeated dermal dosing, there was no systemic toxicity in males at the Limit Dose and in females toxicity at this dose was limited decreased body weight gain and food consumption.

5.3.5 Inhalation Exposure Study Selected: 90 day Inhalation Toxicity Study in Rats MRID No.: 42827903 Executive Summary: Groups of 15 male and 15 female Sprague Dawley rats were exposed in whole body exposure chambers to zinc pyrithione aerosols at concentrations of 0.0005, 0.0025, or 0.01 mg/ L/ day for 6 hours/ day, 5 days/ week for 13 weeks. One male and 1 female exposed to 0.0025 mg/ L/ day and 3 males and 4 females exposed to 0.01 mg/ L/ day died over the course of the study. Treatment related clinical signs of toxicity included rales, labored breathing, and gasping in animals that died on study. At 0.01 mg/ L/ day, body weights of females were depressed as much as 23%, compared to controls, total food consumption was decreased 10%, and food efficiency was decreased 53%. Hematologic, clinical chemistry, or urinalysis effects were not considered biologically significant for any of the exposure groups, and ophthalmologic examinations and gross necropsy findings were negative.

Biologically significant increases in absolute and ( relative) lung weights of + 20% (+ 34%) and + 22% (+ 38%) in males, and + 13% (+ 18%) and + 25% (+ 68%) in females were seen at concentrations of 0.0025 and 0.01 mg/ L/ day, respectively. The increased lung weights corresponded to histopathologic findings of trace to mild subacute inflammation of the interstitial tissue of the lung and medial hypertrophy of pulmonary arteries which were biologically significant at 0.01 mg/ L/ day. NOAEL = 0.0005 mg/ L/ day. LOAEL = 0.0025 mg/ L/ day ( labored breathing, rales, increased salivation, decreased activity, dry red brown material around the nose, increased absolute and relative lung weights, and death of undetermined cause) 20 Dose and Endpoint: NOAEL of 0.0005 mg/ L/ day, based on clinical signs, increased lung weights, and mortality at 0.0025 mg/ L/ day.

Comments about Study/ Endpoint: The selected dose will be used for short, intermediate and long term exposure risk assessments.

5.3.6 Margin of Exposure for Occupational/ Residential Exposures:

An MOE of 100 is adequate for occupational dermal exposure risk assessments. For residential incidental oral, dermal, and inhalation risk assessments, an MOE of 300 is adequate.

For acute aggregate exposure risk assessment, combine the high end exposure values from food + water and compare it to the acute RfD for Females 13+ and the acute RfD for the General Population including Infants and Children.

For Short, intermediate and long term aggregate exposure risk assessment, the oral, dermal and inhalation MOEs cannot be combined due to different toxicological endpoints for oral ( developmental), dermal ( decreased body weight gain and food consumption) and inhalation ( clinical signs) routes.

5.4 Classification of Carcinogenic Potential No chronic toxicity or carcinogenicity studies are available to assess the carcinogenic potential of zinc pyrithione . Data on sodium pyrithione suggest no carcinogenic potential but data are inadequate to make a final determination.

6.0 FQPA Considerations The following evaluation of zinc pyrithione is provided to address FQPA considerations on the sensitivity of infants and children.

6.1 Special sensitivity for infants and children:

Under the Food Quality Protection Act ( FQPA), P. L. 104 170, which was promulgated in 1996 as an amendment to the Federal Insecticide, Fungicide, and Rodenticide Act ( FIFRA) and the Federal Food, Drug and Cosmetic Act ( FFDCA), the Agency was directed to " ensure that there is a reasonable certainty that no harm will result to infants and children" from aggregate exposure to a pesticide chemical residue. The law further states that in the case of threshold effects, for purposes of providing this reasonable certainty of no harm, " an additional tenfold margin of safety for the pesticide chemical residue and other sources of exposure shall be applied for infants and children to take into account potential pre and post natal toxicity and completeness of the data 21 with respect to exposure and toxicity to infants and children. Notwithstanding such requirement for an additional margin of safety, the Administrator may use a different margin of safety for the pesticide residue only if, on the basis of reliable data, such margin will be safe for infants and children."

The HIARC in 1999 recommended retention of the 10x safety factor for the protection of infants and children based on qualitative evidence of increased susceptibility in the rat and rabbit prenatal developmental toxicity studies. Since that time, updated guidance on interpretation of the FQPA safety factor ( http:// www. epa. gov/ oppfead1/ trac/ science/ determ. pdf ) has been published. Based on this updated guidance, the special hazard based FQPA safety factor for zinc pyrithione was reduced to 1x. This reduction was based on the following: For zinc pyrithione, the developmental toxicity database shows effects in offspring at similar dose levels as effects in adults, while the reproductive toxicity database for sodium pyrithione ( a structurally related chemical) shows effects in offspring at doses above those occurring in parental animals. Effects observed in offspring from developmental toxicity studies have been selected for use in dietary risk assessments, thus being protective of infants and children. Therefore the hazard based FQPA safety factor can be reduced to 1x since the degree of concern is low ( i. e. a complete developmental and reproductive database is available with clear NOAELs/ LOAELs for parental and offspring toxicity) and there are no residual uncertainties for prenatal toxicity.

The doses and toxicological endpoints selected for various exposure scenarios are summarized below. 22 Exposure Scenario Dose Used in Risk Assessment, UF LOC for Risk Assessment Study and Toxicological Endpoints Acute Dietary ( Females 13  50) NOAEL = 0.5 mg/ kg/ day UF = 300 Acute RfD = 0.0016 mg/ kg/ day FQPA SF = 1x aPAD = acute RfD FQPA SF aPADa ( females 13+) = 0.0016 mg/ kg/ day Developmental Toxicity Study in Rabbits LOAEL = 1.5 mg/ kg/ day, based on increased post implantation loss and decreased viable fetuses Acute Dietary ( General population, including infants/ children) NOAEL = 0.75 mg/ kg/ day UF = 300 Acute RfD = 0.0025 mg/ kg/ day FQPA SF = 1x aPAD = acute RfD FQPA SF aPAD = 0.0025 mg/ kg/ day Developmental Toxicity Study in Rats LOAEL = 3.0 mg/ kg/ day based on increased salivation in maternal rats.

Chronic Dietary ( all populations) NOAEL = 0.5 mg/ kg/ day UF = 300 Chronic RfD = 0.0016 mg/ kg/ day FQPA SF = 1x cPAD = acute RfD FQPA SF cPAD = 0.0016 mg/ kg/ day Developmental Toxicity Study in Rabbits LOAEL = 1.5 mg/ kg/ day, based on increased post implantation loss and decreased viable fetuses Incidental Oral, Short and Intermediate Term Maternal NOAEL= 0.75 mg/ kg/ day MOE = 300 ( residential) Developmental Toxicity Study in Rat LOAEL = 3.0 mg/ kg/ day, Based on increased salivation in maternal rats.

Short, Intermediate, and Long Term Dermal Dermal NOAEL = 100 mg/ kg/ day MOE = 300 ( residential) MOE = 100 ( occupational) Subchronic Dermal Toxicity in Rats LOAEL = 1000 mg/ kg/ day, based on decreased body weight gain, food consumption, and food efficiency in female rats.

Short, Intermediate, and Long Term Inhalation Inhalation NOAEL = 0.0005 mg/ L MOE = 300 ( residential) MOE = 100 ( occupational) Subchronic Inhalation Toxicity Study in Rats LOAEL = 0.0025 mg/ L Based on clinical signs of toxicity, decreased activity, and increased lung weights..

6.2 Database Uncertainty Based on the need for acute and subchronic neurotoxicity testing, a database uncertainty factor of 3x is applied to non occupational risk assessments for zinc pyrithione, due to the lack of 23 characterization of neurotoxic dose response relationships for zinc pyrithione. A 3x factor for lack of neurotoxicity data ( as opposed to a higher factor of 10x) is adequate because neurotoxicity observed in the available data occurs at similar effect levels as other adverse responses, the doses and endpoints selected for dietary and non dietary assessments encompass the doses at which neurotoxicity is observed, there is no quantitative evidence of susceptibility to the toxic effects of zinc pyrithione, and traditional uncertainty factors afford a degree of protection that is considered conservative. 24 REFERENCES 1) Moreno O. M., Cerven D. R., Altenbach, E, J. ( 1986): Single Dose Oral Toxicity in Rats/ LD 50 in Rats. Study performed by M B Research Laboratories, Inc, Spinnerstown, Pennsylvania for Olin Corporation. MRID # 42827901. Unpublished.

2) Cerven, D. R. ( 1991): Acute Dermal Toxicity in Rabbits/ LD50 in Rabbits. Study performed by M B Research Laboratories, Inc, Spinnerstown, Pennsylvania for Olin Corporation. MRID # 42146701. Unpublished.

3) Ulrich, C. E. ( 1991): Acute Inhalation Toxicity Evaluation on Zinc Omadine in Rats. Study performed by International Research and Development Corporation for Olin Corporation. MRID # 42146703. Unpublished.

4) Cerven, D. R. ( 1991): Primary Eye Irritation/ Corrosion in Rabbits. Study performed by M B Research Laboratories, Inc, Spinnerstown, Pennsylvania for Olin Corporation. MRID # 42146702. Unpublished.

5) Cerven, D. R. ( 1991): Primary Dermal Irritation in Albino Rabbits. Study performed by M B Research Laboratories, Inc, Spinnerstown, Pennsylvania for Olin Corporation. MRID # 42146704. Unpublished.

6) Newconb, T ( 1996): Delayed Contact Dermal Sensitization Test ( Buehler Method). Study performed by M B Research Laboratories, Inc, Spinnerstown, Pennsylvania for Olin Corporation. MRID # 43950201. Unpublished.

7) Ulrich, C. E. ( 1993): 90 Day Subchronic Dermal Toxicity Study on Zinc Omadine in Rats. Study performed by International Research and Development Corporation for Olin Corporation. MRID # 42827902. Unpublished.

8) Schardein, J. L. ( 1993): Developmental Toxicity Study in Rats with Zinc Omadine. Study performed by International Research and Development Corporation for Olin Corporation. MRID # 42827904. Unpublished.

9) Schardein, J. L. ( 1993): Developmental Toxicity Study in New Zealand White Rabbits with Zinc Omadine. Study performed by International Research and Development Corporation for Olin Corporation. MRID # 42827905 and 42827906. Unpublished.

10) Ridgway, P. and Wood, C. M. ( 1989): Sodium Omadine Rat Two Generation Reproduction Toxicity Study. Study performed by Toxicol Laboratories for Olin Corporation. MRID # 41097201. Unpublished.

11) Ulrich, C. E. ( 1993): Thirteen Week Subchronic Inhalation Toxicity Study on Zinc Omadine in Rats. Study performed by International Research and Development Corporation for Olin Corporation. MRID # 42827903 and 42827907. Unpublished.

12) San, R. H. C. and Shelton, J. B. ( 1990): Salmonella/ Mammalian  Microsome Plate Incorporation Mutagenicity Assay ( Ames Test) with a Confirmatory Assay. Study performed by Microbiological Associates, Inc., Rockville, MD for Olin Corporation. MRID # 41906502. Unpublished.

13) Jacobson Kram, D. and Sigler, C. I. ( 1990): CHO/ HGPRT Mutation Assay with Confirmation. Study performed by Microbiological Associates, Inc., Rockville, MD for Olin Corporation. MRID # 41906503. Unpublished.

14) Putman, D. L. and Morris, M. J. ( 1990): Micronucleus Cytogenetic Assay in Mice. Study performed by Microbiological Associates, Inc., Rockville, MD for Olin Corporation. MRID # 41906501. Unpublished. 25 15) Preliminary Neurological Evaluation of Generalized Weakness in Zinc Pyrithione treated rats. Study performed by Olin Corporation ( no date given). Unpublished. HED document number 003933.

16) Klaassen, C ( 1976): Absorption, Distribution, and Excretion of Zinc Pyridinethione in Rabbits. Toxicol. Appl. Pharmacol. 35: 581 587.

17) Wedig, J. H., et al. ( 1978): Disposition of Zinc Pyrithione in the Rat. Fd. Cosmet. Toxicol. 16: 553 561.

18) Adams, M., Jordan, R., and Borzelleca, J. ( no date): Acute Toxicity and Disposition of Sodium Omadine, Zinc Omadine, and Omadine MDS following Intravenous Administration to Swine. Study performed by the Medical College of Virginia.

19) Husband, R. F., Newman, A. J., Lee, P. N. ( 1991): 104 Week Oral ( Gavage) Combined Carcinogenicity and Toxicity Study in the Rat. Study conducted by Toxicol Laboratories Ltd., Ledbury, England and submitted to the EPA under MRID 42100901. Unpublished.

20) Husband, R. F., Newman, A. J., Lee, P. N. ( 1991): 80 Week Dermal Carcinogenicity Study in the Mouse. Study conducted by Toxicol Laboratories Ltd., Ledbury, England and submitted to the EPA under MRID 42100801. Unpublished.

21) Johnson D. E. ( 1989): One Year Oral Toxicity Study in Cynomolgus Monkeys. Study conducted by International Research and Development Corporation, Mattawan, MI and submitted to the EPA under MRID 41178101. Unpublished.

22) Ross, J. F. and Lawhorn, G. T. ( 1990): ZPT related Distal Axonopathy: behavioral and electrophysiologic correlates in rats. Neurotoxicol. Teratol 12( 2): 153 159, 1990 23) Snyder, D. R., deJesus, C. P. V., Towfighi, J., Jacoby, R. O., Wedig, J. H. ( 1979): Neurological, Microscopic, and Enzyme Histochemical Assessment of Zinc Pyrithione Toxicity. Food Cosmet. Toxicol. 17( 6), 651 660, 1979.

24) Grant, W. M. Toxicology of the Eye, 3rd edition. Charles C. Thomas, pub. ( 1993)


[Federal Register Volume 83, Number 206 (Wednesday, October 24, 2018)]
[Notices]
[Pages 53646-53650]
[FR Doc No: 2018-23160]

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DEPARTMENT OF HOMELAND SECURITY

Federal Emergency Management Agency

[Docket ID: FEMA-2018-0008]

Assistance to Firefighters Grant Program

AGENCY: Federal Emergency Management Agency (FEMA), Department of
Homeland Security (DHS).

ACTION: Notice of availability of grant application and application
deadline.

-----------------------------------------------------------------------

SUMMARY: Pursuant to the Federal Fire Prevention and Control Act of
1974, as amended, the Administrator of FEMA is publishing this notice
describing the Fiscal Year (FY) 2018 Assistance to Firefighters Grant
(AFG) Program application process, deadlines, and award selection
criteria. This notice explains the differences, if any, between these
guidelines and those recommended by representatives of the national
fire service leadership during the annual meeting of the Criteria
Development Panel, which was held January 17, 2018. The application
period for the FY 2018 AFG Program began September 24, 2018 and closes
October 26, 2018, and was announced on the AFG website at: https://www.fema.gov/welcome-assistance-firefighters-grant-program, as well as
at www.grants.gov.

DATES: Grant applications for the Assistance to Firefighters Grant
Program are accepted electronically at https://portal.fema.gov, from
September 24, 2018 through October 26, 2018 at 5:00 p.m. Eastern
Standard Time.

ADDRESSES: Assistance to Firefighters Grant Branch, DHS/FEMA, 400 C
Street SW, 3N, Washington, DC 20472-3635.

FOR FURTHER INFORMATION CONTACT: Catherine Patterson, Branch Chief,
Assistance to Firefighters Grant Branch, 1-866-274-0960.

SUPPLEMENTARY INFORMATION: The AFG Program awards grants directly to
fire departments, non-affiliated emergency medical services (EMS)
organizations, and State Fire Training Academies (SFTAs) for the
purpose of enhancing the health and safety of first responders and
improving their abilities to protect the public from fire and fire-
related hazards.
    Applications for the FY 2018 AFG Program will be submitted and
processed online at https://portal.fema.gov. Before the application
period started, the FY 2018 AFG Notice of Funding Opportunity (NOFO)
was published on the AFG website. The AFG website provides additional
information and materials useful to applicants including Frequently
Asked Questions, a Get Ready Guide, and a Quick Reference Guide. Based
on past AFG application periods, FEMA anticipates the receipt of 10,000
to 15,000 applications for the FY 2018 AFG Program, and the ability to
award approximately 2,500 grants.

Congressional Appropriations

    For the FY 2018 AFG Program, Congress appropriated $350,000,000
(Department of Homeland Security Appropriations Act, 2018 Pub. L. 115-
141). From this amount, $315,000,000 will be made available for AFG
awards. In addition, Section 33 of the Federal Fire Prevention and
Control Act of 1974, as amended (15 U.S.C. 2229), requires that a
minimum of 10 percent of available funds be expended for Fire
Prevention and Safety Grants (FP&S). FP&S awards will be made directly
to local fire departments and to local, regional, State, or national
entities recognized for their expertise in the fields of fire
prevention and firefighter safety research and development. Funds
appropriated for FY 2018 will be available for obligation and award
until September 30, 2019.
    The Federal Fire Prevention and Control Act of 1974 further directs
FEMA to administer these appropriations according to the following
requirements:
     Career fire department: Not less than 25 percent of
available grant funds.
     Volunteer fire department: Not less than 25 percent of
available grant funds.
     Combination fire department and departments using paid-on-
call firefighting personnel: Not less than 25 percent of available
grant funds.
     Open Competition (career, volunteer, and/or combination
fire departments and departments using paid-on-call firefighting
personnel): Not less than 10 percent of available grant funds awarded.
     Emergency Medical Services Providers including fire
departments and nonaffiliated EMS organizations: Not less than 3.5
percent of available grants funds awarded, with nonaffiliated EMS
providers receiving no more than 2 percent of the total available grant
funds.
     State Fire Training Academies: Not more than 3 percent of
available grant funds shall be collectively awarded to State Fire
Training Academy applicants, with a maximum of $500,000 per applicant.
     Vehicles: Not more than 25 percent of available grant
funds may be used for

the purchase of vehicles; 10 percent of those vehicle funds will be
dedicated to the funding of ambulances. Vehicle funds will be
distributed as equally as possible among urban, suburban, and rural
community applicants.
     Micro Grants: This is a voluntary funding limitation
choice made by the applicant for requests submitted within the
Operations and Safety activity; it is not an additional funding
opportunity. Micro Grants are awards that have a federal participation
(share) that does not exceed $50,000. Only fire departments and
nonaffiliated EMS organizations are eligible to choose Micro Grants,
and the only eligible Micro Grants requests are for Training,
Equipment, Personal Protective Equipment (PPE), and Wellness and
Fitness activities. Applicants that select Micro Grants as a funding
opportunity may receive additional consideration for award. If an
applicant selects Micro Grants in their application, they will be
limited in the total amount of funding their organization can be
awarded; if they are requesting funding in excess of $50,000 federal
participation, they should not select Micro Grants.

Background of the AFG Program

    Since 2001, AFG has helped firefighters and other first responders
to obtain critically needed equipment, protective gear, emergency
vehicles, training, and other resources needed to protect the public
and emergency personnel from fire and related hazards. FEMA awards
grants on a competitive basis to the applicants that best address the
AFG Program's priorities and provide the most compelling justification.
Applications that best address AFG priorities, as identified in the
Application Evaluation Criteria, will be reviewed by a panel composed
of fire service personnel.
    AFG has three program activities:

 Operations and Safety
 Vehicle Acquisition
 Regional Projects

    The priorities for each activity are fully outlined in the NOFO.

Application Evaluation Criteria

    Prior to making a grant award, FEMA is required by 31 U.S.C. 3321
note, 41 U.S.C. 2313, and 2 CFR 200.205 to review information available
through any Office of Management and Budget (OMB) designated
repositories of government-wide eligibility qualification or financial
integrity information. Therefore, application evaluation criteria may
include the following risk based considerations of the applicant: (1)
Financial stability; (2) quality of management systems and ability to
meet management standards; (3) history of performance in managing
federal awards; (4) reports and findings from audits; and (5) ability
to effectively implement statutory, regulatory, or other requirements.
    FEMA will rank all complete and submitted applications based on how
well they match program priorities for the type of jurisdiction(s)
served. Answers to activity specific questions provide information used
to determine each application's ranking relative to the stated program
priorities.
    Funding priorities and criteria for evaluating AFG applications are
established by FEMA based on the recommendations from the Criteria
Development Panel (CDP). CDP is comprised of fire service professionals
that make recommendations to FEMA regarding the creation of new, or the
modification of, previously established funding priorities, as well as
developing criteria for awarding grants. The content of the NOFO
reflects implementation of CDP's recommendations with respect to the
priorities and evaluation criteria for awards.
    The nine major fire service organizations represented on the CDP
are:

 International Association of Fire Chiefs
 International Association of Fire Fighters
 National Volunteer Fire Council
 National Fire Protection Association
 National Association of State Fire Marshals
 International Association of Arson Investigators
 International Society of Fire Service Instructors
 North American Fire Training Directors
 Congressional Fire Service Institute

Review and Selection Process

    AFG applications are reviewed through a multi-phase process. All
applications are electronically pre-scored and ranked based on how well
they align with the funding priorities outlined in this notice.
Applications with the highest pre-score rankings are then scored
competitively by (no less than three) members of the Peer Panel Review
process. Applications will also be evaluated through a series of
internal FEMA review processes for completeness, adherence to
programmatic guidelines, technical feasibility, and anticipated
effectiveness of the proposed project(s). Below is the process by which
applications will be reviewed:

1. Pre-Scoring Process

    The application undergoes an electronic pre-scoring process based
on established program priorities listed within the NOFO and answers to
activity specific questions within the online application. Application
narratives are not reviewed during pre-scoring. Request details and
budget information should comply with program guidance and statutory
funding limitations. The pre-score is 50 percent of the total
application score.

2. Peer Review Panel Process

    Applications with the highest pre-score will undergo peer review.
The peer review is comprised of fire service representatives
recommended by CDP national organizations. The panelists assess the
merits of each application based on the narrative section of the
application, including the evaluation elements listed in the Narrative
Evaluation Criteria below. Panelists will independently score each
project within the application, discuss the merits and/or shortcomings
of the application with his or her peers, and document the findings. A
consensus is not required. The panel score is 50 percent of the total
application score.

3. Technical Evaluation Process

    The highest ranked applications are considered within the fundable
range. Applications that are in the fundable range undergo both a
technical review by a subject matter expert, as well as a FEMA AFG
Branch review prior to being recommended for an award. The FEMA AFG
Branch will assess the request with respect to costs, quantities,
feasibility, eligibility, and recipient responsibility prior to
recommending an application for award. Once the technical evaluation
process is complete, the cumulative score for each application will be
determined and FEMA will generate a final ranking of applications. FEMA
will award grants based on this final ranking and the statutorily
required funding limitations listed in this notice and the NOFO.

Narrative Evaluation Criteria

1. Financial Need (25 Percent)

    Applicants should describe their financial need and how consistent
it is with the intent of the AFG Program. This statement should include
details describing the applicant's financial distress, summarized
budget constraints, unsuccessful attempts to secure other funding, and
proof that their financial distress is out of their control.

2. Project Description and Budget (25 Percent)

    This statement should clearly explain the applicant's project
objectives and the relationship between those objectives and the
applicant's budget and risk analysis. The applicant should describe the
activities, including program priorities or facility modifications,
ensuring consistency with project objectives, the applicant's mission,
and any national, State, and/or local requirements. Applicants should
link the proposed expenses to operations and safety, as well as the
completion of the project goals.

3. Operations and Safety/Cost Benefit (25 Percent)

    Applicants should describe how they plan to address the operations
and personal safety needs of their organization, including cost
effectiveness and sharing assets. This statement should also include
details about gaining the maximum benefits from grant funding by citing
reasonable or required costs, such as specific overhead and
administrative costs. The applicant's request should also be consistent
with their mission and identify how funding will benefit their
organization and personnel.

4. Statement of Effect/Impact on Daily Operations (25 Percent)

    This statement should explain how these funds will enhance the
organization's overall effectiveness. It should address how an award
will improve daily operations and reduce the organization's risks.
Applicants should include how frequently the requested items will be
used, and in what capacity. Applicants should also indicate how the
requested items will help the community and increase the organization's
ability to save additional lives or property.

Eligible Applicants

    Fire Departments: Fire departments operating in any of the 50
States, as well as fire departments in the District of Columbia, the
Commonwealth of the Northern Mariana Islands, the U.S. Virgin Islands,
Guam, American Samoa, the Commonwealth of Puerto Rico, or any federally
recognized Indian tribe or tribal organization.
    A fire department is an agency or organization having a formally
recognized arrangement with a State, territory, local, or tribal
authority (city, county, parish, fire district, township, town, or
other governing body) to provide fire suppression to a population
within a geographically fixed primary first due response area.
    Nonaffiliated EMS organizations: Nonaffiliated EMS organizations
operating in any of the 50 States, as well as the District of Columbia,
the Commonwealth of the Northern Mariana Islands, the U.S. Virgin
Islands, Guam, American Samoa, the Commonwealth of Puerto Rico, or any
federally recognized Indian tribe or tribal organization.
    A nonaffiliated EMS organization is an agency or organization that
is a public or private nonprofit emergency medical services entity
providing medical transport that is not affiliated with a hospital and
does not serve a geographic area in which emergency medical services
are adequately provided by a fire department.
    FEMA considers the following as hospitals under the AFG Program:

 Clinics
 Medical centers
 Medical colleges or universities
 Infirmaries
 Surgery centers
 Any other institutions, associations, or foundations providing
medical, surgical, or psychiatric care and/or treatment for the sick or
injured.

    State Fire Training Academies: A State Fire Training Academy (SFTA)
operates in any of the 50 States, as well as the District of Columbia,
the Commonwealth of the Northern Mariana Islands, the U.S. Virgin
Islands, Guam, American Samoa, and the Commonwealth of Puerto Rico.
Applicants must be designated either by legislation or by a Governor's
declaration as the sole fire service training agency within a state,
territory, or the District of Columbia. The designated SFTA shall be
the only agency/bureau/division, or entity within that state,
territory, or the District of Columbia.

Ineligibility

     To avoid a duplication of benefits, FEMA reserves the
right to review all program activities or grant applications where two
or more organizations share a single facility. To be eligible as a
separate organization, two or more fire departments or nonaffiliated
EMS organizations will have different funding streams, personnel
rosters, or Employee Identification Numbers (EINs). If two or more
organizations share facilities and each submits an application in the
same program area (i.e., Equipment, Modify Facilities, Personal
Protective Equipment, Training, and Wellness and Fitness Programs) FEMA
will carefully review each program for eligibility.
     Fire-based EMS organizations are not eligible to apply as
nonaffiliated EMS organizations. Fire-based EMS training and equipment
must be requested by a fire department under the AFG component program
Operations and Safety.
     Eligible applicants may submit only one application for
each activity (e.g., Operations and Safety or Regional), but may submit
for multiple projects within each activity. Under the Vehicle Activity,
applicants may submit one application for vehicles for their department
and one separate application to host a Regional vehicle. Duplicate
applications (more than one application in the same activity) may be
disqualified.
     An Operations and Safety applicant may submit one
application for an eligible project (i.e., turn out gear); it may not
submit a Regional application for the same project.

Statutory Limits to Funding

    Congress has enacted statutory limits to the amount of funding that
a grant recipient may receive from the AFG Program in any single fiscal
year (15 U.S.C. 2229(c)(2)) based on the population served. Awards will
be limited based on the size of the population protected by the
applicant, as indicated below. Notwithstanding the annual limits stated
below, the FEMA Administrator may not award a grant in an amount that
exceeds one percent of the available grants funds in such fiscal year,
except where it is determined that such recipient has an extraordinary
need for a grant in an amount that exceeds the one percent aggregate
limit.
     In the case of a recipient that serves a jurisdiction with
100,000 people or fewer, the amount of available grant funds awarded to
such recipient shall not exceed $1 million in any fiscal year.
     In the case of a recipient that serves a jurisdiction with
more than 100,000 people, but not more than 500,000 people, the amount
of available grant funds awarded to such recipient shall not exceed $2
million in any fiscal year.
     In the case of a recipient that serves a jurisdiction with
more than 500,000, but not more than 1 million people, the amount of
available grant funds awarded to such recipient shall not exceed $3
million in any fiscal year.
     In the case of a recipient that serves a jurisdiction with
more than 1 million people but not more than 2,500,000 people, the
amount of available grant funds awarded to such recipient is subject to
the one percent aggregate cap of $3,500,000 for FY 2018, but FEMA may
waive this aggregate cap in individual cases where FEMA determines that
a recipient has an extraordinary need for a grant that

exceeds the aggregate cap; if FEMA waives the aggregate cap, the amount
of grant funds awarded to such recipient shall not exceed $6 million
for any fiscal year.
     In the case of a recipient that serves a jurisdiction with
more than 2,500,000 people, the amount of available grant funds awarded
to such recipient is subject to the one percent aggregate cap of
$3,500,000 for FY 2018, but FEMA may waive this aggregate cap in
individual cases where FEMA determines that a recipient has an
extraordinary need for a grant that exceeds the aggregate cap; if FEMA
waives the aggregate cap, the amount of grant funds awarded to such
recipient shall not exceed $9 million for any fiscal year.
     FEMA may not waive the population-based limits on the
amount of grant funds awarded as set by 15 U.S.C. 2229(c)(2)(A).
    The cumulative total of the federal share of awards in Operations
and Safety, Regional, and Vehicle Acquisition activities will be
considered when assessing award amounts and any limitations thereto.
Applicants may request funding up to the statutory limit on each of
their applications.
    For example, an applicant that serves a jurisdiction with more than
100,000 people, but not more than 500,000 people, may request up to $2
million on their Operations and Safety Application, and up to $2
million on their Vehicle Acquisition request. However, should both
grants be awarded, the applicant would have to choose which award to
accept if the cumulative value of both applications exceeds the
statutory limits.

Cost Sharing and Maintenance of Effort

    Grant recipients must share in the costs of the projects funded
under this grant program as required by 15 U.S.C. 2229(k)(1) and in
accordance with applicable federal regulations at 2 CFR part 200, but
they are not required to have the cost-share at the time of application
nor at the time of award. However, before a grant is awarded, FEMA will
contact potential awardees to determine whether the grant recipient has
the funding in hand or if the grant recipient has a viable plan to
obtain the funding necessary to fulfill the cost-sharing requirement.
    In general, an eligible applicant seeking a grant shall agree to
make available non-federal funds equal to not less than 15 percent of
the grant awarded. However, the cost share will vary as follows based
on the size of the population served by the organization, with
exceptions to this general requirement for entities serving smaller
communities:
     Applicants that serve populations of 20,000 or less shall
agree to make available non-federal funds in an amount equal to not
less than 5 percent of the grant awarded.
     Applicants serving areas with populations above 20,000,
but not more than 1 million, shall agree to make available non-federal
funds in an amount equal to not less than 10 percent of the grant
awarded.
     Applicants serving areas with populations above 1 million
shall agree to make available non-federal funds in an amount equal to
not less than 15 percent of the grant awarded.
    The cost share for SFTAs will apply the requirements above based on
the total population of the State.
    The cost share for a regional application will apply the
requirements above based on the aggregate population of the primary
first due response areas of the Host and participating partner
organizations that execute a Memorandum of Understanding as described
in Appendix B, Section J, Regional projects, of the FY18 AFG Notice of
Funding Opportunity.
    On a case-by-case basis, FEMA may allow a grant recipient that may
already own assets (equipment or vehicles), acquired with non-federal
cash, to use the trade-in allowance/credit value of those assets as
``cash'' for the purpose of meeting the cost-share obligation of their
AFG award. In-kind, cost-share matches are not allowed.
    Grant recipients under this grant program must also agree to a
maintenance of effort requirement as required by 15 U.S.C. 2229(k)(3)
(referred to as a ``maintenance of expenditure'' requirement in that
statute). A grant recipient shall agree to maintain during the term of
the grant the applicant's aggregate expenditures relating to the
activities allowable under the NOFO at not less than 80 percent of the
average amount of such expenditures in the two fiscal years preceding
the fiscal year in which the grant amounts are received.
    In cases of demonstrated economic hardship, and at the request of
the grant recipient, the Administrator of FEMA may waive or reduce a
grant recipient's cost share requirement or maintenance of expenditure
requirement. AFG applicants for FY 2018 must indicate at the time of
application whether they are requesting a waiver and whether the waiver
is for the cost share requirement, for the maintenance of effort
requirement, or both. As required by statute, the Administrator of FEMA
is required to establish guidelines for determining what constitutes
economic hardship. FEMA has published these guidelines at FEMA's
website: https://www.fema.gov/media-library-data/1518026897046-483d76a37022b8a581ffb7d42fa9b17e/Eco_Hardship_Waiver_FPS_SAFER_AFG_IB_FINAL.pdf.
    Prior to the start of the FY 2018 AFG application period, FEMA
conducted applicant workshops and/or internet webinars to inform
potential applicants about the AFG Program. In addition, FEMA provided
applicants with information at the AFG website: https://www.fema.gov/welcome-assistance-firefighters-grant-program to help them prepare
quality grant applications. The AFG Help Desk is staffed throughout the
application period to assist applicants with the automated application
process as well as assistance with any questions.
    Applicants can reach the AFG Help Desk through a toll-free
telephone number during normal business hours (1-866-274-0960) or
electronic mail [email protected].

Application Process

    Organizations may submit one application per application period in
each of the three AFG program activities (e.g., one application for
Operations and Safety, one for Vehicle Acquisition, and/or a separate
application to be a Joint/Regional Project host). If an organization
submits more than one application for any single AFG program activity
(e.g., two applications for Operations and Safety, two for Vehicles,
etc.), either intentionally or unintentionally, both applications may
be disqualified.
    Applicants can access the grant application electronically at
https://portal.fema.gov. The application is accessible from the U.S.
Fire Administration's website http://www.usfa.fema.gov and http://www.grants.gov. New applicants must register and establish a user name
and password for secure access to the grant application. Previous AFG
grant applicants must use their previously established user name and
passwords.
    Applicants can answer questions about their grant request that
reflect the AFG funding priorities, described below. In addition, each
applicant must complete four separate narratives for each project or
grant activity requested. Grant applicants will also provide relevant
information about their organization's characteristics, call volume,
and existing organizational capabilities.

System for Award Management (SAM)

    Per 2 CFR 25.200, all federal grant applicants and recipients must
register in https://SAM.gov. SAM is the Federal Government's System for
Awards Management, and registration is free of charge. Applicants must
maintain current information in SAM that is consistent with the data
provided in their AFG grant application and in the Dun & Bradstreet
(DUNS) database. FEMA may not accept any application, process any
awards, and consider any payment or amendment requests, unless the
applicant or grant recipient has complied with the requirements to
provide a valid DUNS number and an active SAM registration. The grant
applicant's banking information, EIN, organization/entity name,
address, and DUNS number must match the same information provided in
SAM.

Criteria Development Panel (CDP) Recommendations

    If there are any differences between the published AFG guidelines
and the recommendations made by the CDP, FEMA must explain them and
publish the information in the Federal Register prior to awarding any
grant under the AFG Program. For FY 2018, FEMA accepted, and will
implement, all of the CDP's recommendations for the prioritization of
eligible activities.

Adopted Recommendations for FY 2018

    The FY 2018 AFG NOFO contains some changes to definitions,
descriptions, and priority categories. Changes to the FY 2018 AFG NOFO
include:
     Under the Equipment category, FEMA has updated the reasons
for equipment purchases. The new descriptions are:

 High priority--Obtain equipment to achieve minimum operational
and deployment standards for existing missions
 High priority--Replace unusable/unrepairable equipment to meet
current standard
 High priority--Replace non-compliant equipment to current
standard
 Medium priority--Obtain equipment for new mission
 Low priority--Upgrade technology to current standard

     Under the PPE category, FEMA has updated the purchase
reason for PPE/SCBA. The new descriptions are:

 High priority--Replace unusable/unrepairable PPE to meet
current standard
 High priority--Increase supply for new hires and/or existing
firefighters that do not have one set of turnout gear (PPE) or
allocated seated positions (SCBA)
 Medium priority--Replace non-compliant PPE equipment to
current standard

     Priority categories for Wellness and Fitness requests have
been updated
     Mass Casualty and HazMat Technician training have been
updated from a Medium to High funding priority for fire department and
regional training under the Training Activity.
     Cancer Screening Programs that meet NFPA 1582 were added
as a Priority 1 activity required for a Wellness and Fitness program.
     Specialized training has been added as a medium priority,
and includes training such as Crisis Intervention Training, to provide
specialized training to firefighters, paramedics, emergency medical
service workers, and other first responders to recognize individuals
who have mental illness and how to properly intervene with individuals
with mental illness, including strategies for verbal de-escalation of
crises.

    Authority: 15 U.S.C. 2229.

    Dated: October 18, 2018.
Brock Long,
Administrator, Federal Emergency Management Agency.
[FR Doc. 2018-23160 Filed 10-23-18; 8:45 am]
 BILLING CODE 9111-64-P