December 13, 2001 MEMORANDUM SUBJECT: Lindane (009001) Reregistration Case No. 0315. Revised Anticipated Residues, Acute and Chronic Dietary Exposure and Risk Analyses for the HED Human Health Risk Assessment. DP Barcode D279260.

FROM: Thurston G. Morton, Chemist Reregistration Branch 4 Health Effects Division (7509C)

THROUGH: David Soderberg, Chemist Sheila Piper, Chemist Dietary Exposure Science Advisory Council and Susan V. Hummel, Branch Senior Scientist Reregistration Branch 4 Health Effects Division (7509C)

TO: Rebecca Daiss, Risk Assessor Reregistration Branch 4 Health Effects Division (7509C)

and Mark Howard/ Betty Shackleford Reregistration Branch 3 Special Review & Reregistration Division (7508C)

Action Requested Prepare the revised anticipated residues and acute, chronic, and cancer dietary exposure and risk analyses for lindane (009001) incorporating comments from the public and deleting seed treatment uses on broccoli, Brussels sprouts, cabbage, cauliflower, lettuce, radishes, and spinach which are no longer being supported for reregistration by Inquinosa. The OPP/ Cancer Assessment Review Committee (CARC) has completed the reviewof newlysubmitted carcinogenicitystudyinCD 1 mice 2 along with other data. In accordance with the EPADraft Guidelines for Carcinogen Risk Assessment (July, 1999), the CARC has classified lindane into the category "Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential" based on an increased incidence of benign lung tumors in female mice only. The Committee, therefore, recommended that the quantification of human cancer risk is not required.

Executive Summary ° Estimated acute dietary exposure is below HED's level of concern for all population subgroups at the 99.9 th percentile. The maximum dietary risk estimate is 17 % of the acute PAD (% aPAD) for the population subgroup All Infants (Table 18) and 7 % of the aPAD for the U. S. Population when the feeding studies were adjusted using the metabolism studies.

° Estimated chronic dietary risk is below HED's level of concern for all population subgroups. The resulting risk estimates are 3 % of the chronic PAD (% cPAD) for the U. S. Population and 11 % of the cPAD for Children 1 6 years of age (highest exposed population subgroup) and 6 % of the cPAD for Children 7 12 yrs. The remaining population subgroups were  5 %of the cPAD( Table 18) when the feeding studies were adjusted using the ratio of ppm TRR/ ppm lindane identified in the metabolism studies (Table 18).

Toxicological Information Memoranda providing details of relevant toxicological information include the HIARC report dated 7/ 27/ 00 and the FQPA Safety Factor Committee report dated 8/ 2/ 00.

The acute and chronic FQPA safety factors of 10X were reduced to 3X (see FQPA Safety Factor Document, 8/ 2/ 00). Areference dose (RfD) which includes the FQPA safety factor (10X, 3Xor 1X) is defined as the Population Adjusted Dose (PAD). Doses and endpoints for dietary risk assessment are presented in Table 1.

The OPP/ Cancer Assessment Review Committee (CARC) has completed the review of newly submitted carcinogenicity study in CD 1 mice along with other data. In accordance with the EPA Draft Guidelines for Carcinogen Risk Assessment (July, 1999), the CARC has classified lindane into the category "Suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential" based on an increased incidence of benign lung tumors in female mice only. The Committee, therefore, recommended that the quantification of human cancer risk is not required. 3 Table 1. Lindane: Toxicological Doses and Endpoints for Dietary Risk Assessment.

EXPOSURE SCENARIO DOSE (mg/ kg/ day) ENDPOINT STUDY TYPE/ MRID Acute Dietary general population NOAEL= 6 mg/ kg UF = 100 FQPA = 3X LOAELis20 mg/ kgbased on increasedgrip strength, increased Motor Activity Acute Neurotoxicity in Rats/ 44769201 Acute RfD (Gen. Pop.) = 0. 06 mg/ kg/ day Acute Population Adjusted Dose (aPAD) = 0. 02 mg/ kg/ day Chronic Dietary NOAEL= 10 ppm (0. 47 mg/ kg/ day)

UF = 100 FQPA = 3X LOAEL is 100 ppm (4. 81 mg/ kg/ day) periacinar hepatocyte hypertrophy, increased liver/ spleen weight, and increased platelets Chronic Feeding and Carcinogenicity in Rats 41094101 41853701 42891201 Chronic RfD = 0. 0047 mg/ kg/ day Chronic Population Adjusted Dose (cPAD) = 0. 0016 mg/ kg/ day Consumption Data HED conducts dietary risk assessments using the Dietary Exposure Evaluation Model (DEEM™), which incorporates consumption data generated in USDA's Continuing Surveys of Food Intakes by Individuals (CSFII), 1989 1992. For acute dietary risk assessments, the entire distribution of single day food consumption events is combined with either a single residue level (deterministic analysis, risk at 95th percentile of exposure reported) or a distribution of residues (probabilistic analysis, referred to as "Monte Carlo," with risk at 99. 9th percentile of exposure reported) to obtain a distribution of exposures in mg/ kg/ day. For chronic dietary risk assessments, the three day average of consumption for each sub population is combined with average residues in/ on commodities to determine an average exposure in mg/ kg/ day.

Residue Information Tolerances for residues of lindane in/ on food and feed commodities are currently established under 40 CFR §180.133 and are expressed in terms of lindane per se. The nature of the residue in plants and ruminants is not adequately understood. New nature of the residue studies fromseed treatment are required for a cereal grain, leafy vegetable, and radish. Additional data are required for the ruminant metabolismstudy. The nature ofthe residue in poultry is adequately understood. The HED MetabolismAssessment ReviewCommittee(T. Morton, 8/ 30/ 00, D267069) concluded that theTRRs should be used for risk assessment purposes and calculation of dietary burdens, pending receipt of additional metabolismdata. The anticipated residues (ARs) were presented to the HED ChemSAC on 9/ 6/ 00. Exposure to lindane was determined by using the ratio (ppm TRR/ ppm lindane parent) fromthelivestock metabolismstudies. TheBiologicaland EconomicAnalysisDivision (OPP/ BEAD) verified the registrant's percent market share estimate for lindane (I. Yusuf email, 7/ 17/ 00). The usage data are provided as Attachment 1; inclusion of the data in dietary exposure analyses is discussed below. Acanola processing studyfor lindane wasrecentlyreviewed (T. Morton, D269388, 5/ 10/ 01). Lindane was not detected in bleached/ deodorized canola oil (< 0.005 ppm). Therefore, ½ 4 LOQ (0.0025 ppm) will be used as the DEEM™ adjustment factor 1. DEEM™ default concentrations factors (adjustment factor 1) will be used for all other concentration factors. The wheat grain and forage TRRs were translated to barley, oats, and rye. The corn grain and forage TRRs were translated to sorghum.

The following metabolism and feeding studies were used to determine the appropriate residue values to be used in both the dietary burden calculation and the DEEM™ input files.

Seed Treatment Metabolism Study (N. Dodd, 3/ 24/ 88, RCB 3259, MRID 40431207)

Various seeds were treated with 14 C lindane. Spring wheat seeds were treated at 370 ppm (0. 3x), field corn seeds at 1800 ppm (0. 8x), and sweet corn seeds at 1400 ppm (0. 6x). Seeds were then planted outdoors. Samples were analyzed for radioactivity periodically by oxidative combustion and autoradiography. Samples were extracted and analyzed for 14 C by liquid scintillation counting (LSC) and for lindane by gas liquid chromatography (GLC) when significant residues were found by combustion. This study was deemed inadequate due to insufficient characterization/ identification of the radioactive residues. A new nature of the residue study from seed treatment is required for a cereal grain. The HED MARC (T. Morton, 8/ 30/ 00, D267069) concluded that the TRRs should be used for calculation of dietary burdens. The TRRs are summarized in the following table.

Table 2. Summary of TRR in various crops after seed treatment with 14 C labeled lindane.

Crop Matrix TRR (ppm)

Field corn root 0. 340 Field corn foliage 0.064 Field corn grain < 0. 01 Sweet corn foliage 0.051 Sweet corn grain < 0.01 Wheat foliage 2.925 Wheat grain 0.052 The TRR used for barley, canola, oats, rye, and wheat grain was 0.052 ppm. The TRR value used for corn grain and sorghum grain was 0.01 ppm.

Meat, Milk, Poultry, & Eggs 5 The following acute dietary burdens (Table 3) were calculated using the appropriate TRRs fromthe seed treatment metabolism study presented in the previous table (Table 2). The chronic dietary burdens (Table 4) have incorporated the percent market share of the feed item into the dietary contribution.

Table 3. Lindane Acute Dietary Burden. 6 Feed Commodity % Dry Matter % Diet Anticipated Residue (ppm) Dietary Contribution (ppm)

Beef Cattle Field corn grain 88 50 0.01 0.0057 Wheat forage 25 25 2. 925 2.925 Sorghum forage 35 15 0. 064 0.028 Wheat grain 89 10 0.052 0.006 Total 100 2.96 Dairy Cattle Field corn grain 88 40 0.01 0.0045 Wheat grain 89 10 0.052 0.006 Wheat forage 25 50 2. 925 5.85 Total 100 5.86 Poultry Field corn grain NA 20 0.01 0.002 Wheat grain NA 80 0.052 0.0416 Total 100 0.044 Swine Field corn grain NA 20 0.01 0.002 Wheat grain NA 80 0.052 0.0416 Total 100 0.044 Table 4. Lindane Chronic Dietary Burden. 7 Feed Commodity % Dry Matter % Diet Anticipated Residue (ppm) Percent Market Share Dietary Contribution (ppm)

Beef Cattle Field corn grain 88 50 0.01 0.15 0.0009 Wheat forage 25 25 2. 925 0.03 0.0878 Sorghum forage 35 15 0. 064 0.03 0.0008 Wheat grain 89 10 0.052 0.03 0.0002 Total 100 0.0897 Dairy Cattle Field corn grain 88 40 0.01 0.15 0.0007 Wheat grain 89 10 0.052 0.03 0.0002 Wheat forage 25 50 2. 925 0.03 0.1755 Total 100 0.1764 Poultry Field corn grain NA 20 0.01 0.15 0.0003 Wheat grain NA 80 0.052 0.03 0.0012 Total 100 0.0015 Swine Field corn grain NA 20 0.01 0.15 0.0003 Wheat grain NA 80 0.052 0.03 0.0012 Total 100 0.0015 Ruminant Metabolism Study (MRID 44867104) 8 Lactating goats were orally administered 14 C Lindane capsules (via balling gun) immediately after the morning milking once per day for 7 days. The actual dose rat e was 13 mg/ kg. This dose rate is equivalent to approximately a 2x exaggerated rate for dairy cattle and approximately 4.4x for beef cattle based on an acute dietary burden as calculated by HED. The acute anticipated residues using the TRR alone for cattle and swine are summarized in Table 6 and 7. The chronic anticipated residues usingthe TRRalone forcattle andswine aresummarizedinTable 8 and 9.

Table 5. Summary of TRR characterized/ identified in tissues of lactating goats orally dosed with 14 C Lindane at 13 ppm.

Tissue Total Radioactive Residue (TRR) ppm Fat 3. 46 ppm Liver 2. 25 ppm Kidney 0. 48 ppm Muscle 0.20 ppm Milk Fat 0. 136 ppm Table 6. Cattle Acute Anticipated Residues From Nature of the residue study (M. Kovacs Jr., 9/ 20/ 88, RCB 4037).

Tissue 13 ppm Feeding Level (4. 4X) a Cattle AR Fat 3. 46/ 4.4= 0.786 0.786 ppm Muscle 0.2/ 4.4= 0.045 0.045 ppm Milk Fat 0. 136/ 2= 0.068 0.068 ppm Liver 2. 25/ 4.4= 0.511 0.511 ppm b Kidney 0.48/ 4.4= 0.109 0.109 ppm a The 13 ppm feeding level represented 2x the dairy dietary burden. b Use for liver, meat byproducts, and other organ meats for beef, goat, horses, sheep, and veal.

Table 7. Swine Acute Anticipated Residues based on metabolism data from the ruminant metabolism study.

Tissue 13 ppm Feeding Level (295X) Swine AR Fat 3. 46/ 295= 0.012 0.012 ppm Muscle 0.2/ 295= 0.001 0.001 ppm Liver 2. 25/ 295= 0.008 0.008 ppm a Kidney 0.48/ 295= 0.002 0.002 ppm a Use for liver, meat byproducts, and other organ meats for pork.

Table 8. Cattle Chronic Anticipated Residues From Nature of the residue study (M. Kovacs Jr., 9/ 20/ 88, RCB 4037). 9 Tissue 13 ppm Feeding Level (145X) a Cattle AR Fat 3. 46/ 145= 0.02 0.02 ppm Muscle 0.2/ 145= 0.001 0.001 ppm Milk Fat 0. 136/ 74= 0.002 0.002 ppm Liver 2. 25/ 145= 0.02 0.02 ppm b Kidney 0.48/ 145= 0.003 0.003 ppm a The 13 ppm feeding level represented 74x the chronic dairy dietary burden. b Use for liver, meat byproducts, and other organ meats for beef, goat, horses, sheep, and veal.

Table 9. Swine Chronic Anticipated Residues based on metabolism data from the ruminant metabolism study.

Tissue 13 ppm Feeding Level (8700X) Swine AR Fat 3. 46/ 8700= 0.0004 0.0004 ppm Muscle 0.2/ 8700= 0.00002 0.00002 ppm Liver 2. 25/ 8700= 0.0003 0.0003 ppm a Kidney 0.48/ 8700= 0.00006 0.00006 ppm a Use for liver, meat byproducts, and other organ meats for pork.

Poultry Metabolism Study (MRID 40271301)

Following 4 days of dosing with [ 14 C] lindane at levels equivalent to 120 (2700x) ppm in the acute diet, 14 C residues accumulated to the greatest extent in fatty tissues. In the high dose hens, TRRs were highest in fat (96.98 ppm) followed by skin (49.93 ppm), thigh muscle (11.81 ppm), liver (11.65 ppm), and breast muscle (1.44 ppm).

14 C Residues were readily extracted (80 141% TRR) fromyolks, thigh muscle, liver, skin, and fat of high dose hens using organic solvents, and 66.4 121.3% of the TRR was subsequently identified. Lindane was the principal 14 C residue identified in eggs and tissues, accounting for 94.5% of the TRR in egg yolks, 70.8 86.0% of the TRR in muscle, skin, and fat, and 51.5% of the TRR in liver. 1, 2, 4Trichlorobenzene was identified as accounting for 19.4% of the TRR in liver, and 0.6 3.5% of the TRR in egg yolks and other tissues. 1, 3, 5 Trichlorobenzene and dichlorobenzene( s) were also detected in liver at 6.4 and 9.5% of the TRR, respectively. Tetrachlorobenzene (either 1,2,4,5 or 1,2,3,4) was detected in thigh muscle at 17.7% of the TRR and in other tissues at 2.2 3.1% of the TRR. Pentachlorocyclohexene was identified as accounting for 3. 8 6. 1% of the TRR in yolks and tissues. The remaining metabolites (1, 2, 3, 4 tetrachlorobenzene/ tetrachlorocyclohexene; 1,2,3,4,5 pentachlorobenzene; and hexachlorocyclohexene) detected intissues and/ or yolks each accounted for  4.4% of the TRR. The acute anticipated residues using the TRR alone for poultry are summarized in Table 10. The chronic anticipated residues using the TRR alone for poultry are summarized in Table 11. 10 Table 10. Summary of TRR characterized/ identified in tissues of laying hens orally dosed with 14 C Lindane at 120 ppm (2700x acute dietary burden) normalized to 1x the acute dietary burden.

Tissue Total Radioactive Residue (TRR) ppm Acute Anticipated Residue (ppm)

Fat 97.0 ppm/ 2700= 0.04 0.04 Liver 11.7 ppm/ 2700= 0.004 0.004 Skin 49.9 ppm/ 2700= 0.02 0.02*

Thigh 11.8 ppm/ 2700= 0.004 0.004 Egg White 0.21/ 2700= 0.00008 0.00008 Egg Yolk 10.8 ppm/ 2700= 0.004 0.004 Whole Egg 0.7( 0.00008)+ 0. 3( 0. 004)= 0. 001 *Use for poultry meat byproducts Table 11. Summary of TRR characterized/ identified in tissues of laying hens orally dosed with 14 C Lindane at 120 ppm (80000x acute dietary burden) normalized to 1x the chronic dietary burden.

Tissue Total Radioactive Residue (TRR) ppm Chronic Anticipated Residue (ppm)

Fat 97.0 ppm/ 80000= 0.001 0.001 Liver 11.7 ppm/ 80000= 0.0001 0.0001 Skin 49.9 ppm/ 80000= 0.0006 0.0006*

Thigh 11.8 ppm/ 80000= 0.0001 0.0001 Egg White 0.21/ 80000= 0.000003 0.000003 Egg Yolk 10.8 ppm/ 80000 0.0001 Whole Egg 0.7( 0.000003)+ 0. 3( 0. 0001)= 0. 00003 *Use for poultry meat byproducts Ruminant Feeding Study (M. Kovacs Jr., 9/ 20/ 88, RCB 4037)

Dairy cattle were fed at three feeding levels of 20 ppm( 6. 7x acute beef cattle dietary burden), 60 ppm (20x acute beef cattle dietary burden), and 200 ppm (67x acute beef cattle dietary burden). The exaggerated feeding rates correspond to 3. 4x, 10x, and 34x for the acute dairy cattle dietary burden, respectively. The exaggerated feeding rates correspond to 450x, 1400x, and 4500x for the acute swine dietary burden, respectively. The acute anticipated residues for cattle and swine using the feeding studies along with information fromthe metabolismstudies are summarized in Tables 12 and 13. The chronic anticipated residues for cattle and swine using the feeding studies along with information from the metabolism studies are summarized in Tables 14 and 15.

Table 12. Summary of lindane residues in cattle fed at 20, 60, and 200 ppm normalized to a 1x acute feeding level. 11 Sample 20 ppm (6.7x) a 60 ppm (20x) a 200 ppm (67x) a Average (ppm) * (ppm TRR/ ppm lindane) b Milk (Day 7) 0.41/ 3.4 = 0.120 1.64/ 10 = 0. 164 3.95/ 34 = 0. 116 0.133 * 1. 22 = 0.163 Liver 0. 10/ 6.7 = 0.015 0.19/ 20 = 0. 009 0.72/ 67 = 0. 011 0.012 * 6. 25 = 0.073 Kidney 0.34/ 6.7 = 0.051 1.07/ 20 = 0. 053 4.57/ 67 = 0. 068 0.057 * 2. 82 = 0.162 Muscle 0.97/ 6.7 = 0.145 1.80/ 20 = 0. 090 8.75/ 67 = 0. 130 0.122 * 1. 25 = 0.152 Fat 11.9/ 6.7 = 1.78 20.2/ 20 = 1. 01 58.1/ 67 = 0. 87 1. 22 * 1. 18 = 1.44 a First number in column is residue value from feeding study which is then divided by the exaggerated feeding rate. b Average residue value from three feeding levels multiplied by the ratio of (ppm TRR/ ppm lindane) in metabolism study.

Table 13. Summary of lindane residues in swine translated from the cattle feeding study and normalized to 1x acute feeding level.

Sample 20 ppm (450x) a 60 ppm (1400x) a 200 ppm (4500x) a Average (ppm) * (ppm TRR/ ppm lindane) b Liver 0. 10/ 450= 0.0002 0.19/ 1400= 0.0001 0.72/ 4500= 0.0002 0.0002 * 6. 25 = 0.001 Kidney 0.34/ 450= 0.0007 1.07/ 1400= 0.0008 4.57/ 4500= 0.001 0.0008 * 2. 82 = 0.002 Muscle 0.97/ 450= 0.002 1.80/ 1400= 0.001 8.75/ 4500= 0.002 0.002 * 1. 25 = 0.002 Fat 11.9/ 450= 0.026 20.2/ 1400= 0.014 58.1/ 4500= 0.013 0.018 * 1. 18 = 0.021 a First number in column is residue value from feeding study which is then divided by the exaggerated feeding rate. b Average residue value from three feeding levels multiplied by the ratio of (ppm TRR/ ppm lindane) in metabolism study.

Table 14. Summary of lindane residues in cattle fed at 20, 60, and 200 ppm normalized to a 1x chronic feeding level.

Sample 20 ppm (223x) a 60 ppm (669x) a 200ppm( 2230x) a Average (ppm) * (ppm TRR/ ppm lindane) b Milk (Day 7) 0.41/ 113= 0.004 1.64/ 340= 0.005 3.95/ 1134= 0.003 0.004 * 1. 22 = 0.005 Liver 0. 10/ 223= 0.0004 0.19/ 669= 0.0003 0.72/ 2230= 0.0003 0.0003 * 6. 25 = 0.002 Kidney 0. 34/ 223= 0.002 1.07/ 669= 0.002 4.57/ 2230= 0.002 0.002 * 2. 82 = 0.006 Muscle 0.97/ 223= 0.004 1.80/ 669= 0.003 8.75/ 2230= 0.004 0.004 * 1. 25 = 0.005 Fat 11.9/ 223= 0.05 20.2/ 669= 0.03 58.1/ 2230= 0.03 0.04 * 1. 18 = 0.05 a First number in column is residue value from feeding study which is then divided by the exaggerated feeding rate. b Average residue value from three feeding levels multiplied by the ratio of (ppm TRR/ ppm lindane) in metabolism study.

Table 15. Summary of lindane residues in swine translated fromthe cattle feeding study and normalized to 1x chronic 12 feeding level.

Sample 20 ppm (13300x) a 60 ppm (40000x) a 200 ppm (133000x) a Average (ppm) * (ppm TRR/ ppm lindane) b Liver 0. 10/ 13300= 0.000 008 0.19/ 40000= 0.0000 05 0.72/ 133000= 0.000005 0.000006 * 6. 25 = 0.00004 Kidney 0.34/ 13300= 0.000 03 1.07/ 40000= 0.0000 3 4.57/ 133000= 0.00003 0.00003 * 2. 82 = 0.00008 Muscle 0.97/ 13300= 0.000 07 1.80/ 40000= 0.0000 5 8.75/ 133000= 0.00007 0.00006 * 1. 25 = 0.00008 Fat 11.9/ 13300= 0.000 9 20.2/ 40000= 0.0005 58.1/ 133000= 0.0004 0.0006 * 1. 18 = 0.0007 a First number in column is residue value from feeding study which is then divided by the exaggerated feeding rate. b Average residue value from three feeding levels multiplied by the ratio of (ppm TRR/ ppm lindane) in metabolism study.

Poultry Feeding Study (G. Otakie, 8/ 31/ 88, RCB 4034)

Poultry were fed lindane at 1.5 (34x the acute dietary burden), 4. 5 (102x the acute dietary burden), and 15 (340x the acute dietary burden) ppmfeeding levels. The acute anticipated residues for poultry using the feeding study along with information from the metabolism study are summarized in Table 16. The chronic anticipated residues for poultry using the feeding study along with information from the metabolism study are summarized in Table 17.

Table 16. Summary of lindane residues in poultry fed at 1.5, 4.5, and 15 ppm normalized to a 1x acute feeding level.

Sample 1.5 ppm (34x) a 4.5 ppm (102x) a 15 ppm (340x) a Average (ppm) * (ppm TRR/ ppm lindane) b Eggs 0.216/ 34 = 0. 006 0.672/ 102 = 0. 006 2.357/ 340 = 0. 007 0.006 * 1. 06 = 0.006 Liver 0. 12/ 34 = 0. 003 0.51/ 102 = 0. 005 0.78/ 340 = 0. 002 0.003 * 1. 95 = 0.006 Heart 0. 33/ 34= 0. 010 0. 89/ 102= 0. 009 2. 26/ 340= 0. 007 0. 009 *1 =0. 009 c Thigh 0. 19/ 34 = 0. 005 0.36/ 102 = 0. 003 1.35/ 340 = 0. 004 0.004 * 1. 40 = 0.006 Fat 2. 54/ 34 = 0. 075 7.8/ 102 = 0. 076 27.7/ 340 = 0. 081 0.077 * 1. 17 = 0.090 a First number in column is residue value from feeding study which is then divided by the exaggerated feeding rate. b Average residue value from three feeding levels multiplied by the ratio of (ppm TRR/ ppm lindane) in metabolism study. c 100% of the TRR in the chicken heart was identified as lindane. This residue was used for chicken byproducts, chicken giblets (excl. liver), turkey byproducts, turkey other organ meats, and turkey giblets (excl. liver).

Table 17. Summaryof lindane residues in poultry fed at 1.5, 4.5, and 15 ppm normalized to a 1x chronic feeding level. 13 Sample 1.5 ppm (1000x) a 4.5 ppm (3000x) a 15 ppm (10000x) a Average (ppm) * (ppm TRR/ ppm lindane) b Eggs 0.216/ 1000= 0.0002 0.672/ 3000= 0.0002 2.357/ 10000= 0.0002 0.002 * 1. 06 = 0.0002 Liver 0. 12/ 1000= 0.0001 0.51/ 3000= 0.0002 0.78/ 10000= 0.00008 0.0001 * 1. 95 = 0.0002 Heart 0. 33/ 1000= 0.0003 0.89/ 3000= 0.0003 2.26/ 10000= 0.0002 0.0003 *1 =0. 0003 c Thigh 0. 19/ 1000= 0.0002 0.36/ 3000= 0.0001 1.35/ 10000= 0.0001 0.0001 * 1. 40 = 0.0002 Fat 2. 54/ 1000= 0.003 7.8/ 3000= 0.003 27.7/ 10000= 0.003 0.003 * 1. 17 = 0.004 a First number in column is residue value from feeding study which is then divided by the exaggerated feeding rate. b Average residue value from three feeding levels multiplied by the ratio of (ppm TRR/ ppm lindane) in metabolism study. c 100% of the TRR in the chicken heart was identified as lindane. This residue was used for chicken byproducts, chicken giblets (excl. liver), turkey byproducts, turkey other organ meats, and turkey giblets (excl. liver).

Uncertainties There are no adequate nature of the residue studies for plants fromseed treatment application. Anew metabolism study is required for a grain crop; however, a seed treatment metabolism study (which was classified as inadequate) was reviewed by HED and used in the determination of the TRR for use in this dietary exposure analysis. The wheat grain and forage TRRs were translated to barley, oats, and rye. The corn grain and forage TRRs were translated to sorghum. The nature of the residue in poultry is understood. The nature of the residue in livestock is adequately understood. The magnitude of the residue studies in poultry and cattle only analyzed for lindane. The lindane residue values were derived using a ratio of total radioactive residue divided by the amount of lindane present in the livestock metabolism studies. This would be worst case estimate since we are assuming that all of the TRR would be residues of concern and adjusting the lindane residues in the livestock magnitude of the residue studies accordingly to account for the TRR.

The dietaryexposure analyses using the total radioactive residues is a Tier 3 assessment since percent crop treated was used in the analyses. The dietary exposure analyses that were based on the adjustment of the lindane residues in the feeding studies is a Tier 3 assessment. Percent market share was available for all crops included in the analyses. Since lindane is being supported for reregistration for seed treatments only, there is no difference in the percent crop treated values between crops grown for the fresh market and those grown for processing. A processing study was available for canola only; the default DEEM™ processing factors were used for all other foods.

Results/ Discussion 14 Estimated acute dietary exposure is below HED's level of concern for all population subgroups at the 99.9 th percentile. The maximum dietary risk estimate is 17 % of the aPAD for All Infants when the feeding studies were adjusted using the metabolism studies (Table 18).

Estimated chronic dietary risk is below HED's level of concern for all population subgroups. The resulting risk estimates are 3 % of the chronic PAD (% cPAD) for the U. S. Population and 11 % of the cPADfor Children 1 6 years of age (highest exposed population subgroup) and 6 %of the cPAD for Children 7 12 yrs. The remaining population subgroups were  5% ofthe cPAD (Table 18) when the feeding studies were adjusted using the ratio of ppm TRR/ ppm lindane identified in the metabolism studies (Table 18).

Table 18. Estimated Acute and Chronic Dietary Exposure and Risk using the feeding studies and adjusting lindane residues using the metabolism studies.

Population Subgroup Acute (99.9th % ile) Chronic Exposure (mg/ kg/ day) %aPAD Exposure (mg/ kg/ day) % cPAD U. S. Population 0. 001305 7 0. 000054 3 All infants (< 1 yr) 0.003320 17 0.000072 5 Children (1 6 yrs) 0. 001973 10 0.000173 11 Children (7 12 yrs) 0.001088 5 0. 000096 6 Females (13 50 yrs) 0.000467 2 0. 000034 2 Males (13 19 yrs) 0.000670 3 0. 000061 4 Males (20+ yrs) 0.000458 2 0. 000034 2 Seniors (55+ yrs) 0.000409 2 0. 000030 2 cc : Chem F, Chron F. Morton , L. Richardson RDI: Chemistry SAC (9/ 6/ 00); DE SAC (9/ 25/ 00) (S. Piper, 12/ 13/ 01 & D. Soderberg, 12/ 13/ 01); SVH: 12/ 13/ 01 TM, Thurston Morton, Rm. 816D CM2, 305 6691, mail code 7509C List of Attachments: Attachment 1: Quantitative Usage Analysis, 7/ 17/ 00 (I. Yusuf, BEAD/ OPP). Attachment 2: Residue Distribution Files. Attachment 3: Residue Information. Attachment 4: Acute Analysis. Attachment 5: Chronic Analysis.

Attachment 1: Quantitative Usage Analysis, 7/ 17/ 00 (I. Yusuf, BEAD/ OPP).

(Registrant submission approved by BEAD) 15 From the Small Grains petition, Page 79.

B. Market share representing maximum percent of crop treated is 15% for field corn, 10% for canola, 1% for sweet corn, and 3% each for wheat, oats, barley, and grain sorghum.

From the Small Grains petition, Page 35 MARKET SHARE Reasonable estimates for the percentage of seeds of wheat, barley, oats, rye, and sorghum treated with lindane i. e., the market share, are 1% to 3%. The market share on corn may be as high as 15%. Market share information was used in calculations of Maximum Theoretical Dietary Burdens for livestock, and was considered in some estimations of human dietary exposure.

From the vegetables petition, Page 22.

MARKET SHARE:

Reasonable estimates for the percentage of acres employing lindane treated seeds are: corn 15%, brassica < 1%, leafy vegetables < 1%, and radishes < 1%. (Personal Communication: T. McArtle, Trace Chemical and Seed Treatment Coalition representative, December 1998).

Attachment 2: RDFs Documentation: doc beef fat lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 16 TOTALFREQ= 1 15,1.44 Documentation: doc beef meat lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.152 Documentation: doc beef meat by products lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.162 Documentation: doc beef liver lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.073 Documentation: doc milk lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.163 Documentation: doc poultry eggs lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.006 Documentation: doc poultry meat byproducts lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.009 Documentation: doc poultry liver lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.006 17 Documentation: doc poultry giblets lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.009 Documentation: doc poultry fat lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.09 Documentation: doc poultry meat lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.006 Documentation: doc swine fat lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.021 Documentation: doc swine meat byproducts lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.002 Documentation: doc swine liver lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.001 Documentation: doc swine meat lindane DOC ASSUMING 15% crop treated for highest feed item TOTALZ= 85 TOTALFREQ= 1 15,0.002 Attachment 3: Residue Information Acute Analysis using feeding study 18 F i l e n a m e :  C :\d e e m \ 9 1\R e v i s e d Analysis\ 12 11 1\ 12 11 1RevacuteTRR. RS7 Chemical:  Lindane R D( Chronic): . 16  mg/ kg  bw/ day   NOEL( Chronic): . 47  mg/ kg  bw/ day R D( Acute): . 2  mg/ kg  bw/ day   NOEL( Acute):   6  mg/ kg  bw/ day  Q*=  1. 1 Date  created/ last  modi ied:  12 3 2 1/ 5: 14: 17/ 8           Program ver.  7. 75 Comment:  Re erence  doses  have  3X  FQPA  actored  in.    This  is  a dietary  analysis  using  the  total  radioactive  residues  rom  the plant  and  animal  metabolism  studies.

RDL  indices  and  parameters  or  Monte  Carlo  Analysis:

Index  Dist  Parameter # 1         Param # 2   Param # 3   #    Code

   1     6    bee meat. rd    2     6    bee at. rd    3     6    bee liver. rd    4     6    bee mbyp. rd    5     6    poultryegg. rd    6     6    poultry at. rd    7     6    poultrygiblets. rd    8     6    poultryliver. rd    9     6    poultrymbyp. rd    1     6    poultrymeat. rd    11    6    swine at. rd    12    6    swineliver. rd    13    6    swinembyp. rd    14    6    swinemeat. rd    15    6    milk. rd Food  Crop  Food  Name                          De  Res      Adj. Factors RDL Code   Grp                                    ( ppm)       # 1     # 2  Pntr

 265  15    Barley                              . 52     1.

. 3

 323  M     Bee dried                          . 45     1. 92 .15     1 19  324  M     Bee  at  w/ o  bones                  .786     1.

.15     2  325  M     Bee kidney                         .1 9     1.

.15     4  327  M     Bee lean ( at/ ree)  w/ o  bones      . 45     1.

.15     1  326  M     Bee liver                          .511     1.

.15     3  321  M     Bee meat  byproducts                .511     1.

.15     4  322  M     Bee other  organ  meats              .511     1.

.15     4  3 1  O     Canola  oil ( rape  seed  oil)          . 25     1.

.1

 366  P     Chicken byproducts                  . 4     1.

.15     9  368  P     Chicken at  w/ o  bones               . 4     1.

.15     6  367  P     Chicken giblets( liver)              . 4     1.

.15     8  385  P     Chicken giblets ( excl.  liver)       . 4     1.

.15     7  369  P     Chicken lean/ at  ree  w/ o  bones     . 4     1.

.15    1  267  15    Corn  grain bran                     . 1     1.

.15

 266  15    Corn  grain endosperm                . 1     1.

.15

 289  15    Corn  grain oil                      . 1     1.

.15

 268  15    Corn  grain/ sugar/ h cs               . 1     1. 5 .15

 388  15    Corn  grain/ sugar molasses           . 1     1. 5 .15

 237  15    Corn/ pop                            . 1     1.

.15

 238  15    Corn/ sweet                          . 1     1.

. 1

 364  P     Eggs white  only                     . 8     1.

.15     5  363  P     Eggs whole                          . 1     1.

.15     5 20  365  P     Eggs yolk  only                      . 4     1.

.15     5  33  M     Goat at  w/ o  bone                   .786     1.

.15     2  331  M     Goat kidney                         .1 9     1.

.15     4  333  M     Goat lean ( at/ ree)  w/ o  bone       . 45     1.

.15     1  332  M     Goat liver                          .511     1.

.15     3  328  M     Goat meat  byproducts                .511     1.

.15     4  329  M     Goat other  organ  meats              .511     1.

.15     4  334  M     Horsemeat                           . 45     1.

.15     1  398  D     Milk based  water                    . 68     1.

.15    15  319  D     Milk at  solids                     . 68     1.

.15    15  318  D     Milk non at  solids                  . 68     1.

.15    15  32  D     Milk  sugar ( lactose)                . 68     1.

.15    15  399  15    Oats bran                           . 52     1.

. 3

 269  15    Oats                                . 52     1.

. 3

 344  M     Pork at  w/ o  bone                   . 12     1.

.15    11  345  M     Pork kidney                         . 2     1.

.15    13  347  M     Pork lean ( at  ree)  w/ o  bone       . 1     1.

.15    14  346  M     Pork liver                          . 8     1.

.15    12  342  M     Pork meat  byproducts                . 8     1.

.15    13  343  M     Pork other  organ  meats              . 8     1.

.15    13  362  P     Poultry other at  w/ o  bones         . 4     1.

.15     6 21  361  P     Poultry other giblets( liver)        . 4     1.

.15     8   36   P     Poultry other lean  ( at  ree)  w/      . 4       1.

.15    1  274  15    Rye lour                           . 52     1.

. 3

 273  15    Rye germ                            . 52     1.

. 3

 272  15    Rye rough                           . 52     1.

. 3

 338  M     Sheep at  w/ o  bone                  .786     1.

.15     2  339  M     Sheep kidney                        .1 9     1.

.15     4  341  M     Sheep lean ( at  ree)  w/ o  bone      . 45     1.

.15     1  34  M     Sheep liver                         .511     1.

.15     3  336  M     Sheep meat  byproducts               .511     1.

.15     4  337  M     Sheep other  organ  meats             .511     1.

.15     4  275  15    Sorghum ( including  milo)            . 1     1.

. 3

 355  P     Turkey byproducts                   . 4     1.

.15     9  357  P     Turkey at  w/ o  bones               . 4     1.

.15     6  356  P     Turkey giblets ( liver)              . 4     1.

.15     8  358  P     Turkey  lean/ at  ree  w/ o  bones     . 4     1.

.15    1  449  P     Turkey other  organ  meats            . 4     1.

.15     9  429  M     Veal dried                          . 45     1. 92 .15     1  424  M     Veal at  w/ o  bones                  .786     1.

.15     2  426  M     Veal kidney                         .1 9     1.

.15     4  425  M     Veal lean ( at  ree)  w/ o  bones      . 45     1.

.15     1 22  427  M     Veal liver                          .511     1.

.15     3  43  M     Veal meat  byproducts                .511     1.

.15     4  428  M     Veal other  organ  meats              .511     1.

.15     4  278  15    Wheat bran                          . 52     1.

. 3

 279  15    Wheat lour                         . 52     1.

. 3

 277  15    Wheat germ                          . 52     1.

. 3

 437  15    Wheat germ  oil                      . 52     1.

. 3

 276  15    Wheat rough                         . 52     1.

. 3

Chronic Analysis using feeding study F i l e n am e :  C :\d e e m \ 9 1 \R e v i s e d Analysis\ 12 11 1\ 12 11 1RevchronicTRR. RS7 Chemical:  Lindane R D( Chronic): . 16  mg/ kg  bw/ day   NOEL( Chronic): . 47  mg/ kg  bw/ day R D( Acute): . 2  mg/ kg  bw/ day   NOEL( Acute):   6  mg/ kg  bw/ day  Q*=  1. 1 Date  created/ last  modi ied:  12 3 2 1/ 5: 15: 47/ 8           Program ver.  7. 75 Comment:  Fe erence  doses  have  3X  FQPA  actored  in.   This  is  the dietary  analysis  using  the  metabolism  and  eeding  studies.

Food  Crop                                    De  Res      Adj. Factors Code   Grp   Food  Name                         ( ppm)       # 1    # 2

 265   15   Barley                              . 52     1.

. 3  323   M    Bee dried                          . 5     1. 92 1.

 324   M    Bee  at  w/ o  bones                  . 5     1.

1.

 325   M    Bee kidney                         . 6     1. 23 1.

 327   M    Bee lean ( at/ ree)  w/ o  bones      . 5     1.

1.

 326   M    Bee liver                          . 2     1.

1.

 321   M    Bee meat  byproducts                . 6     1.

1.

 322   M    Bee other  organ  meats              . 6     1.

1.

 3 1   O    Canola  oil ( rape  seed  oil)          . 25     1.

.1  366   P    Chicken byproducts                  . 3     1.

1.

 368   P    Chicken at  w/ o  bones               . 4     1.

1.

 367   P    Chicken giblets( liver)              . 2     1.

1.

 385   P    Chicken giblets ( excl.  liver)       . 3     1.

1.

 369   P    Chicken lean/ at  ree  w/ o  bones     . 2     1.

1.

 267   15   Corn  grain bran                     . 1     1.

.15  266   15   Corn  grain endosperm                . 1     1.

.15  289   15   Corn  grain oil                      . 1     1.

.15  268   15   Corn  grain/ sugar/ h cs               . 1     1. 5 .15  388   15   Corn  grain/ sugar molasses           . 1     1. 5 .15  237   15   Corn/ pop                            . 1     1.

.15  238   15   Corn/ sweet                          . 1     1.

. 1  364   P    Eggs white  only                     . 2     1.

1.

 363   P    Eggs whole                          . 2     1.

1.

 365   P    Eggs yolk  only                      . 2     1.

1.

 33    M    Goat at  w/ o  bone                   . 5     1. 24 1.

 331   M    Goat kidney                         . 6     1.

1.

 333   M    Goat lean ( at/ ree)  w/ o  bone       . 5     1.

1.

 332   M    Goat liver                          . 2     1.

1.

 328   M    Goat meat  byproducts                . 6     1.

1.

 329   M    Goat other  organ  meats              . 6     1.

1.

 334   M    Horsemeat                           . 5     1.

1.

 398   D    Milk based  water                    . 5     1.

1.

 319   D    Milk at  solids                     . 5     1.

1.

 318   D    Milk non at  solids                  . 5     1.

1.

 32    D    Milk  sugar ( lactose)                . 5     1.

1.

 399   15   Oats bran                           . 52     1.

. 3  269   15   Oats                                . 52     1.

. 3  344   M    Pork at  w/ o  bone                   . 7     1.

1.

 345   M    Pork kidney                         . 8     1.

1.

 347   M    Pork lean ( at  ree)  w/ o  bone       . 8     1.

1.

 346   M    Pork liver                          . 4     1.

1.

 342   M    Pork meat  byproducts                . 8     1.

1.

 343   M    Pork other  organ  meats              . 8     1.

1.

 362   P    Poultry other at  w/ o  bones         . 4     1.

1.

 361   P    Poultry other giblets( liver)        . 2     1.

1.

  36     P      Poultry other lean  ( at  ree)  w/      . 2       1. 25 1.

 274   15   Rye lour                           . 52     1.

. 3  273   15   Rye germ                            . 52     1.

. 3  272   15   Rye rough                           . 52     1.

. 3  338   M    Sheep at  w/ o  bone                  . 5     1.

1.

 339   M    Sheep kidney                        . 6     1.

1.

 341   M    Sheep lean ( at  ree)  w/ o  bone      . 5     1.

1.

 34    M    Sheep liver                         . 2     1.

1.

 336   M    Sheep meat  byproducts               . 6     1.

1.

 337   M    Sheep other  organ  meats             . 6     1.

1.

 275   15   Sorghum ( including  milo)            . 1     1.

. 3  355   P    Turkey byproducts                   . 3     1.

1.

 357   P    Turkey at  w/ o  bones               . 4     1.

1.

 356   P    Turkey giblets ( liver)              . 2     1.

1.

 358   P    Turkey  lean/ at  ree  w/ o  bones     . 2     1.

1.

 449   P    Turkey other  organ  meats            . 3     1.

1.

 429   M    Veal dried                          . 5     1. 92 1.

 424   M    Veal at  w/ o  bones                  . 5     1.

1.

 426   M    Veal kidney                         . 6     1.

1.

 425   M    Veal lean ( at  ree)  w/ o  bones      . 5     1.

1.

 427   M    Veal liver                          . 2     1.

1.

 43    M    Veal meat  byproducts                . 6     1. 26 1.

 428   M    Veal other  organ  meats              . 6     1.

1.

 278   15   Wheat bran                          . 52     1.

. 3  279   15   Wheat lour                         . 52     1.

. 3  277   15   Wheat germ                          . 52     1.

. 3  437   15   Wheat germ  oil                      . 52     1.

. 3  276   15   Wheat rough                         . 52     1.

. 3 Attachment 4: Acute Analysis Acute Analysis Using Feeding Studies U. S.  Environmental  Protection  Agency

    Ver.  7. 74 DEEM  ACUTE  Analysis  or  LINDANE

(1989 92  data)

Residue  ile:  12 11 1RevacuteTRR. RS7                  Adjustment actor # 2  used.

Analysis  Date:  12 11 2 1/ 16: 9:      Residue  ile  dated:

12 3 2 1/ 5: 14: 17/ 8 NOEL ( Acute) =    6.  mg/ kg  body wt/ day Daily  totals  or  ood  and  ood orm  consumption  used.

MC  iterations =  5        MC  list  in  residue  ile      MC  seed =

1 281 Run  Comment: " Re erence  doses  have  3X  FQPA  actored  in.   This  is  a dietary  ana lysis  using  the  total  radioactive  residues  rom  the  plant  and animal  metabolism  studies."

=================================================================

==============

Summary  calculations ( per  capita): 27        95th  Percentile              99th  Percentile

99. 9th  Percentile  Exposure  %  aR D      MOE     Exposure  %  aR D      MOE     Exposure %  aR D      MOE

U. S.  Population:

   . 16      .8     37614     . 516     2. 58    11627     . 13 5    6. 52     4598

U. S.  Population ( spring  season):

   . 16      .8     3739      . 5 3     2. 51    11934     . 129    6. 45     465

U. S.  Population ( summer  season):

   . 152     .76    39455     . 521     2. 6     11525     . 1434    7. 17     4185

U. S.  Population ( autumn  season):

   . 166     .83    36 52     . 563     2. 82    1 648     . 1294    6. 47     4636

U. S.  Population ( winter  season):

   . 161     .8     37353     . 478     2. 39    12541     . 1221    6. 1      4914

Northeast  region:

   . 152     .76    39479     . 521     2. 61    1151      . 1414    7. 7     4243

Midwest  region:

   . 181     .91    331 1     . 574     2. 87    1 452     . 1383    6. 92     4337

Southern  region:

   . 151     .76    39732     . 457     2. 29    13125     . 11 6    5.53     5424

Western  region:

   . 158     .79    37994     . 523     2. 62    11466     . 1376    6. 88     436

Hispanics:

   . 179     .89    336 4     . 616     3. 8     9745     . 1456    7. 28     4122

Non hispanic  whites:

   . 159     .79    37742     . 5 9     2. 54    11795     . 1281    6. 41     4682

Non hispanic  blacks:

   . 15      .75    4 4      . 474     2. 37    12662     . 13 7    6. 54     459    28 Non hisp/ non white/ non black:

   . 158     .79    38 1      . 591     2. 96    1 149     . 1593    7. 97     3765

All  in ants:

   . 2 4     1. 2    29448     . 837     4. 19     7167     . 332  16. 6      18 7

Nursing  in ants (< 1  yr  old):

   . 64     .32    941      . 288     1. 44    2 823     . 698    3. 49     8599

Non nursing  in ants (< 1  yr  old):

   . 234     1. 17    25658     . 1521     7. 6      3945     . 3626  18. 13     1654

Children  1 6   yrs:

   . 668     3.34     8987     . 1264     6. 32     4748     . 1973    9. 86     3 41

Children  7 12  yrs:

   . 353     1. 76    17 17     . 642     3. 21     9342     . 1 88    5. 44     5513

Females  13+ ( preg/ not  nursing):

   . 191     .95    31424     . 342     1. 71    17528     . 5 9    2. 54    11797

Females  13+ ( nursing):

   . 148     .74    4 598     . 352     1. 76    17 23     . 623    3. 11     9632

Females  13 19 ( not  preg  or  nursing):

   . 16      .8     374 5     . 311     1. 55    19293     . 676    3.38     8874

Females  2 + ( not  preg  or  nursing):

   . 99     .5     6 5 3     . 2 7     1. 4    28962     . 4 5    2. 2    14816

Females  13 5  yrs:

   . 111     .55    54255     . 245     1. 23    24444     . 467    2. 34    12844

Males  13 19  yrs:

   . 2 1     1.     29852     . 413     2. 6    14542     . 67    3.35     896

Males  2 +  yrs:

   . 1 6     .53    56425     . 225     1. 13    26647     . 458    2. 29    131 4

Seniors  55+:

   . 99     .5     6 477     . 2 3     1. 1    29619     . 4 9    2. 4    14676   29 Paci ic:

   . 156     .78    38498     . 531     2. 66    11297     . 1344    6. 72     4462

       30 Attachment 5: Chronic Analysis Chronic Analysis Using Feeding Study U. S.  Environmental  Protection  Agency

   Ver.  7. 73 DEEM  Chronic  analysis  or  LINDANE

(1989 92  data)

Res i d u e   i l e   n a m e :  C :\d e e m \ 9 1 \R e v i s e d Analysis\ 12 11 1\ 12 11 1RevchronicTRR. RS7                                                       Adjustment actor # 2  used.

Analysis  Date  12 12 2 1/ 13: 26: 48      Residue  ile  dated:

12 3 2 1/ 5: 15: 47/ 8 Re erence  dose ( R D,  Chronic) = . 16  mg/ kg  bw/ day COMMENT  1:  Re erence  doses  have  3X  FQPA  actored  in.   This  is  the dietary  analysis  using  the  metabolism  and  eeding  studies.

=================================================================

==============

                     Total  exposure  by  population  subgroup

                                                     Total  Exposure

           Population                          mg/ kg

Percent  o

            Subgroup                        body  wt/ day

R d

U. S.  Population ( total)                      . 54

   3. 4%

U. S.  Population ( spring  season)              . 54

   3.3%

U. S.  Population ( summer  season)              . 53              31    3.3%

U. S.  Population ( autumn  season)              . 56

   3.5%

U. S.  Population ( winter  season)              . 53

   3.3%

Northeast  region                             . 53

   3.3%

Midwest  region                               . 6

   3. 7%

Southern  region                              . 51

   3. 2%

Western  region                               . 53

   3.3%

Hispanics                                    . 59

   3. 7%

Non hispanic  whites                          . 54

   3. 4%

Non hispanic  blacks                          . 49

   3. 1%

Non hisp/ non white/ non black                 . 56

   3.5%

All  in ants (<  1  year)                       . 72

   4. 5%

Nursing  in ants                              . 19

   1. 2%

Non nursing  in ants                          . 94

   5. 9%

Children  1 6   yrs                            . 173

 1 .8%

Children  7 12  yrs                            . 96

   6. %

Females  13 19 ( not  preg  or  nursing)          . 46

   2. 9%

Females  2 + ( not  preg  or  nursing)            . 29

   1. 8%

Females  13 5  yrs                            . 34

   2. 1%

Females  13+ ( preg/ not  nursing)               . 49              32    3. %

Females  13+ ( nursing)                        . 43

   2. 7%

Males  13 19  yrs                              . 61

   3.8%

Males  2 +  yrs                                . 34

   2. 1%

Seniors  55+                                  . 3

   1. 9%

Paci ic  Region                               . 53

   3.3%


[Federal Register Volume 86, Number 3 (Wednesday, January 6, 2021)]
[Notices]
[Pages 538-539]
[FR Doc No: 2020-29249]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. EL21-37-000]

Michigan Public Power Agency; Notice of Filing

    Take notice that on December 23, 2020, Michigan Public Power Agency
submitted the annual revenue requirement for the provision of Reactive
Supply and Voltage Control from Generation or Other Sources from the
reactive power production capability of the Belle River generating
station, Units 1 and 2, in the above captioned proceeding.
    Any person desiring to intervene or to protest this filing must
file in accordance with Rules 211 and 214 of the Commission's Rules of
Practice and Procedure (18 CFR 385.211, 385.214). Protests will be
considered by the Commission in determining the appropriate action to
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proceeding. Any person wishing to become a party must file a notice of
intervention or motion to intervene, as appropriate. Such notices,
motions, or protests must be filed on or before the comment date. On or
before the comment date, it is not necessary to serve motions to
intervene or protests on persons other than the Applicant.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper using the eFiling link at http://www.ferc.gov. Persons unable to file electronically should submit an
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last three digits in the docket number field to access the document. At
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    Comment Date: 5:00 p.m. Eastern Time on January 13, 2021.

    Dated: December 30, 2020.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2020-29249 Filed 1-5-21; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 82, Number 144 (Friday, July 28, 2017)]
[Notices]
[Pages 35198-35200]
[FR Doc No: 2017-15968]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OW-2017-0260; FRL-9965-39-OW]

Request for Scientific Views: Draft Updated Aquatic Life Ambient
Water Quality Criteria for Aluminum in Freshwater

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of Availability.

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

SUMMARY: The Environmental Protection Agency (EPA) is announcing the
availability of Draft Updated Aquatic Life Ambient Water Quality
Criteria for Aluminum in Freshwater for public comment. EPA first
released freshwater criteria for aluminum in 1988 to protect aquatic
life from harmful effects of aluminum toxicity. EPA is updating its
recommended aluminum criteria to reflect the latest science and to
provide users the flexibility to develop site-specific criteria based
on site-specific water chemistry. The draft document provides a
scientific assessment of ecological effects and is not a regulation.
Following closure of this 60-day public comment period, EPA will
consider the comments, revise the draft document, as appropriate, and
then publish a final document that will provide recommendations for
states and authorized tribes to establish water quality standards. The
recommendations found in this draft document do not replace or
supersede EPA's 1988 national recommended criteria for aluminum in
ambient water.

DATES: Comments must be received on or before September 26, 2017.

ADDRESSES: Submit your comments, identified by Docket ID No. EPA-HQ-OW-
2017-0260 to the Federal eRulemaking Portal: http://www.regulations.gov. Follow the online instructions for submitting
comments. Once submitted, comments cannot be edited or withdrawn. EPA
may publish any comment received to its public docket. Do not submit
electronically any information you consider to be Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. Multimedia submissions (audio, video, etc.) must be
accompanied by a written comment. The written comment is considered the

official comment and should include discussion of all points you wish
to make. EPA will generally not consider comments or comment contents
located outside of the primary submission (i.e., on the web, cloud, or
other file sharing system). For additional submission methods, the full
EPA public comment policy, information about CBI or multimedia
submissions, and general guidance on making effective comments, please
visit http://www2.epa.gov/dockets/commenting-epa-dockets.

FOR FURTHER INFORMATION CONTACT: Diana Eignor, Health and Ecological
Criteria Division, Office of Water (Mail Code 4304T), Environmental
Protection Agency, 1200 Pennsylvania Avenue NW., Washington, DC 20460;
telephone:<PHONE_NUMBER>; or email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. How can I get copies of this document and other related information?

    1. Docket. EPA has established a docket for this action under
Docket ID No. EPA-HQ-OW-2017-0260. Publicly available docket materials
are available either electronically through www.regulations.gov or in
hard copy at the Water Docket in the EPA Docket Center, (EPA/DC) EPA
West, Room 3334, 1301 Constitution Ave. NW., Washington, DC. The EPA
Docket Center Public Reading Room is open from 8:30 a.m. to 4:30 p.m.,
Monday through Friday, excluding legal holidays. The telephone number
for the Public Reading Room is<PHONE_NUMBER>, and the telephone number
for the Water Docket is<PHONE_NUMBER>.
    2. Electronic Access. You may access this Federal Register document
electronically from the Government Printing Office under the ``Federal
Register'' listings FDSys (http://www.gpo.gov/fdsys/browse/collection.action?collectionCode=FR).

II. What is Aluminum and how does it affect aquatic life?

    Aluminum is found in most soils and rocks and is the third most
abundant element and the most common metal in the earth's crust.
Aluminum can enter the water via natural processes, like weathering of
rocks. Aluminum is also released to water by mining, industrial
processes using aluminum, and waste water treated with alum, an
aluminum compound. Aluminum is considered a non-essential metal because
fish and other aquatic life do not need it to function. Elevated levels
of aluminum can affect some species ability to regulate ions and
inhibit respiratory functions. Aquatic plants are generally less
sensitive to aluminum than fish and other aquatic life.

III. What are EPA's updated recommended levels of aluminum in
freshwater?

    The recommended level of aluminum in freshwater depends on a site's
water quality parameters. Studies have shown that three water chemistry
parameters, pH, dissolved organic carbon (DOC), and hardness, can
affect the toxicity of aluminum by affecting the bioavailability of
aluminum in the water to aquatic species. Unlike the fixed criteria
values in EPA's 1988 criteria document, these updated draft criteria
use a Multiple Linear Regression (MLR) model to normalize the data, and
the resulting criteria are based on site pH, DOC, and hardness. This
allows users to develop site-specific aluminum criteria for fresh
waters that appropriately reflect water quality parameters. See Table 1
for a comparison of EPA's currently recommended and updated draft
criteria values.
[GRAPHIC] [TIFF OMITTED] TN28JY17.011

IV. What are section 304(a) water quality criteria?

    Section 304(a) water quality criteria are recommendations developed
by EPA under authority of section 304(a) of the Clean Water Act based
on the latest scientific information which examines the effect of a
particular constituent concentration on an aquatic species and/or human
health.
    Section 304(a)(1) of the Clean Water Act directs the EPA to develop
and publish and, from time to time, revise criteria for water quality
accurately reflecting the latest scientific knowledge. Water quality
criteria developed under section 304(a) are based solely on data and
scientific judgments on the relationship between pollutant
concentrations and environmental and human health effects. Section
304(a) criteria do not reflect consideration of economic impacts or the
technological feasibility of meeting pollutant concentrations in
ambient water.
    Section 304(a) criteria provide guidance to states and authorized
tribes in adopting water quality standards that ultimately provide a
basis for controlling discharges of pollutants. The criteria also
provide guidance that EPA considers when promulgating federal
regulations under section 303(c) when such action is necessary. Under
the Clean Water Act and its implementing regulations, states and
authorized tribes are to adopt water quality criteria to protect
designated uses (e.g., aquatic life, recreational use). EPA's water
quality criteria recommendations are not regulations. Thus, EPA's
recommended criteria do not constitute legally binding requirements.
States and authorized tribes may adopt other scientifically defensible
water quality criteria that differ from these recommendations. As part
of the WQS

triennial review process defined in section 303(c)(1) of the CWA, the
states and authorized tribes are responsible for maintaining and
revising WQS. Standards consist of designated uses, water quality
criteria to protect those uses, a policy for antidegradation, and may
include general policies for application and implementation. Section
303(c)(1) requires states and authorized tribes to review and modify,
if appropriate, their WQS at least once every three years. States and
authorized tribes must adopt water quality criteria that protect
designated uses. Consistent with EPA's regulations at 40 CFR 131.11(a),
protective criteria must be based on a sound scientific rationale and
contain sufficient parameters or constituents to protect the designated
uses. Criteria may be expressed in either narrative or numeric form.
States and authorized tribes have four options when adopting water
quality criteria for which EPA has published section 304(a) criteria.
They may: (1) Establish numerical values based on recommended section
304(a) criteria; (2) Adopt section 304(a) criteria modified to reflect
site-specific conditions; (3) Adopt criteria derived using other
scientifically defensible methods; or (4) Establish narrative criteria
where numeric criteria cannot be established or to supplement numeric
criteria (40 CFR 131.11(b)).

V. Solicitation of Scientific Views

    EPA is soliciting additional scientific views, data, and
information regarding the science and technical approach used in the
derivation of the draft criteria.

    Dated: July 17, 2017.
Michael H. Shapiro,
Acting Assistant Administrator.
[FR Doc. 2017-15968 Filed 7-27-17; 8:45 am]
 BILLING CODE 6560-50-P


[Federal Register Volume 81, Number 23 (Thursday, February 4, 2016)]
[Notices]
[Page 6103]
[FR Doc No: 2016-02096]

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DEPARTMENT OF TRANSPORTATION

National Highway Traffic Safety Administration

[Docket No. DOT-NHTSA-2014-0050]

Notice and Request for Comments

AGENCY: National Highway Traffic Safety Administration (NHTSA),
Department of Transportation.

ACTION: Notice and request for comments.

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

SUMMARY: In compliance with the Paperwork Reduction Act of 1995 (44
U.S.C. 3501 et seq.), this notice announces that the Information
Collection Request (ICR) abstracted below is being forwarded to the
Office of Management and Budget (OMB) for review and comments. A
Federal Register Notice with a 60-day comment period soliciting
comments on the following information collection was published on May
9, 2014 FR NHTSA-2014-0050). No comments were received.

DATES: Comments must be submitted on or before March 7, 2016.

ADDRESSES: Send comments regarding the burden estimate, including
suggestions for reducing the burden, to the Office of Management and
Budget, Attention: Desk Officer for the Office of the Secretary of
Transportation, 725 17th Street NW., Washington, DC 20503.

FOR FURTHER INFORMATION CONTACT: Glaceria Mason, National Highway
Traffic Safety Administration, Room W52-211 Department of
Transportation, 1200 New Jersey Avenue SE., Washington, DC 20590. Ms.
Mason's telephone number is<PHONE_NUMBER>. Please identify the
relevant collection of information by referring to its OMB Control
Number.

SUPPLEMENTARY INFORMATION:
    Title: NHTSA: Drunk Driver Segmentation Research Survey.
    OMB Control Number: 2127-XXXX.
    Type of Request: Web-based Segmentation Research Survey.
    Abstract: The purpose of NHTSA's Web-based At-Risk Drunk Drivers/
Riders Segmentation Research Survey is to obtain information about the
characteristics of drivers and motorcycle riders who are at most risk
for driving/riding drunk. NHTSA will conduct segmentation analysis to
classify ``at-risk'' drivers/riders based on common demographics,
drinking behaviors, attitudes, lifestyle characteristics and media
habits to better target and reach the intended audiences with
communications methods and techniques to reduce the number of deaths,
injuries and economic losses resulting from drunk driving crashes on
our Nation's roadways.
    Affected Public: At-Risk Drunk Drinkers/Riders ages 21-54 years
old.
    Estimated Number of Respondents: The number of respondents is
estimated to be 10% of the 22,000 respondents; thereby determining
2,200 respondents being eligible to take the full survey.
    Estimated Total Annual Burden Hours: 5,868.
    Public Comments Invited: You are asked to comment on any aspects of
this information collection, including (a) whether the proposed
collection of information is necessary for the proper performance of
the functions of the Department, including whether the information will
have practical utility; (b) the accuracy of the Department's estimate
of the burden of the proposed information collection; (c) ways to
enhance the quality, utility and clarity of the information to be
collected; and (d) ways to minimize the burden of the collection of
information on respondents, including the use of automated collection
techniques or other forms of information technology.

    Authority:  The Paperwork Reduction Act of 1995; 44 U.S.C.
Chapter 35, as amended; and 49 CFR 1:48.

Susan McMeen,
Office Director, Office of Consumer Information.
[FR Doc. 2016-02096 Filed 2-3-16; 8:45 am]
 BILLING CODE 4910-59-P


MEMORANDUM DATE: April 29, 2004 TO: Effluent Guidelines Planning Record FROM: M. Ahmar Siddiqui RE: Telephone discussion regarding PBSTs with Jim Ball and Eric Beck, Rhode Island Department of the Environment, Providence, RI As part of its study of the Petroleum Bulk Stations and Terminals ( PBST, SIC 5171) industry, EPA contacted permit writers and compliance officials to discuss permitting and other issues unique to PBSTs. On March 31, 2004, Mr. M. Ahmar Siddiqui contacted Messrs. Jim Ball and Eric Beck of the Rhode Island Department of the Environment to discuss these facilities. The telephone script, which served as a guide to the conversations, is part of another memorandum to the Effluent Guidelines Planning Record ( Summary of discussions with permit writers about PBST facilities, April 29, 2004).

When asked about wastewater sources at PBSTs, Mr. Ball stated that stormwater was the largest source. Among process water sources, Mr. Ball identified tank bottoms water, hydrostatic test water, and truck wash water ( though this volume is very small). Mr. Ball also identified spills and leachate as another source. He said that this was due in large part to the fact that many tanks in Rhode Island are now rather old and becoming less structurally sound with age. Mr. Beck added that many facilities discharge PAHs and that the discharge of individual PAHs was generally tied to the products handled by the PBST.

Mr. Beck could not enumerate the number of facilities that sent their wastewaters to refineries for reuse. This question arose from an assertion by the American Petroleum Institute that more than 50 percent of PBSTs associated with refineries sent their tank bottoms waters to refineries for recycle/ oil recovery purposes. Mr. Beck did say, however, that the Exxon East Providence, RI PBST ( ranked number one in the 2000 PCS database for toxic discharges) sent its wastes tank bottoms water to a co located Exxon refinery's groundwater treatment system.

Mr. Ball stated that treatment in place at most PBSTs is limited to oil/ water separation, with a discharge standard of 15 mg/ L of oil and grease. For those facilities that had groundwater contamination issues, Mr. Beck said that treatment systems might be more elaborate, though he could not say how. However, he did note that, in Rhode Island, new permits are now being issued using activated carbon as a technology basis, with the expectation that performance would continue to improve.

As to the question of pollution prevention, Mr. Beck noted that it was largely limited to the use of dikes and improved emergency controls. The use of pollution prevention, he said, was driven by EPA SPCC and stormwater rules. He could not, however, quantify the impact of these practices on pollutant discharges from PBSTs. Mr. Beck said that Rhode Island does not face any particular difficulties with permitting PBSTs, largely because the state has only seven permitted facilities and, even then, two are in the process of shutting down.


[Federal Register Volume 81, Number 138 (Tuesday, July 19, 2016)]
[Notices]
[Pages 46938-46940]
[FR Doc No: 2016-17009]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0315]

E2C(R2) Periodic Benefit-Risk Evaluation Report and E2C(R2)
Periodic Benefit-Risk Evaluation Report--Questions and Answers;
International Council for Harmonisation; Guidances for Industry;
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of guidances for industry entitled ``E2C(R2) Periodic
Benefit-Risk Evaluation'' (E2C(R2) guidance) and ``E2C(R2) Periodic
Benefit-Risk Evaluation Report--Questions and Answers'' (E2C(R2) Q&A
guidance). These guidances were prepared under the auspices of the
International Council for Harmonisation (ICH), formerly the
International Conference on Harmonisation. The E2C(R2) draft guidance,
issued April 11, 2012, updated and combined two ICH guidances, ``E2C
Clinical Safety Data Management: Periodic Safety Update Reports for
Marketed Drugs'' (E2C guidance) and ``Addendum to E2C Clinical Safety
Data Management: Periodic Safety Update Reports for Marketed Drugs''
(addendum to the E2C guidance). The E2C(R2) guidance is intended to
describe the format, content, and timing of a Periodic Benefit-Risk
Evaluation Report (PBRER) for an approved drug or biologic, and it
finalizes the draft guidance. The E2C(R2) Q&A guidance is a
supplementary guidance that is intended to clarify key issues in the
E2C(R2) guidance.

DATES: Submit either electronic or written comments on Agency guidances
at any time.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked, and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2012-D-0315 for ``E2C(R2) Periodic Benefit-Risk Evaluation Report
and E2C(R2) Periodic Benefit-Risk Evaluation Report--Questions and
Answers; International Council for Harmonisation; Guidances for
Industry; Availability.'' Received comments will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at http://www.regulations.gov or at the Division of
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. If you do not
wish your name and contact information to be made publicly available,
you can provide this information on the cover sheet and not in the body
of your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of these guidances to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002, or the Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. The guidances may also be obtained by mail by calling
CBER at 1-800-835-4709 or<PHONE_NUMBER>. See the SUPPLEMENTARY
INFORMATION section for electronic access to the guidance documents.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Maureen
Melvin, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4480, Silver
Spring, MD 20993-0002,<PHONE_NUMBER>; or Stephen Ripley, Center for
Biologics Evaluation and Research, Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002,
240-402-7911.
    Regarding the ICH: Amanda Roache, Center for Biologics Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 51, Rm. 1128, Silver Spring, MD 20993-0002,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, many important initiatives have been undertaken by
regulatory authorities and industry associations to promote
international harmonization of regulatory requirements. FDA has
participated in many meetings designed to enhance harmonization and is
committed to seeking scientifically based harmonized technical
procedures for pharmaceutical development. One of the goals of
harmonization is to identify and then reduce differences in technical
requirements for drug development among regulatory agencies.
    ICH was organized to provide an opportunity for harmonization
initiatives to be developed with input from both regulatory and
industry representatives. FDA also seeks input from consumer
representatives and others. ICH is concerned with harmonization of
technical requirements for the registration of pharmaceutical products
for human use among regulators around the world. The six founding
members of the ICH are the European Commission; the European Federation
of Pharmaceutical Industries Associations; the Japanese Ministry of
Health, Labour, and Welfare; the Japanese Pharmaceutical Manufacturers
Association; CDER and CBER, FDA; and the Pharmaceutical Research and
Manufacturers of America. The Standing Members of the ICH Association
include Health Canada and Swissmedic. Any party eligible as a Member in
accordance with the ICH Articles of Association can apply for
membership in writing to the ICH Secretariat. The ICH Secretariat,
which coordinates the preparation of documentation, operates as an
international nonprofit organization and is funded by the Members of
the ICH Association.
    The ICH Assembly is the overarching body of the Association and
includes representatives from each of the ICH members and observers.
    In the Federal Register of April 11, 2012 (77 FR 21782), FDA
published a notice announcing the availability of a draft guidance
entitled ``E2C(R2) Periodic Benefit-Risk Evaluation Report.'' The draft
E2C(R2) guidance updated and combined the E2C guidance and the addendum
to the E2C guidance. The notice gave interested persons an opportunity
to submit comments by May 11, 2012.
    After consideration of the comments received and revisions to the
guidance, a final draft of the guidance was submitted to the ICH
Steering Committee and endorsed by the regulatory agencies in November
2012.
    The E2C(R2) guidance provides guidance on the format, content, and
timing of a PBRER for an approved drug or biologic, and it finalizes
the draft guidance. The PBRER will serve as a common standard for
periodic reporting on approved drugs or biologics among the ICH
regions. The harmonized PBRER is intended to promote a consistent
approach to periodic postmarket safety reporting among the ICH regions
and to enhance efficiency by reducing the number of reports

generated for submission to the regulatory authorities.
    Since the E2C(R2) draft guidance was made available in 2012, ICH
has identified questions linked to the interpretation and application
of the E2C(R2) guidance. The E2C(R2) Q&A guidance is intended to
clarify questions relating to implementation of the E2C(R2) guidance.
    These guidances are being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The guidances represent
the current thinking of FDA on the E2C(R2) PBRER. They do not establish
any rights for any person and are not binding on FDA or the public. You
can use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations.

II. The Paperwork Reduction Act of 1995

    These guidances refer to previously approved collections of
information found in FDA regulations. These collections of information
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3520).
The collection of information in the ``Guidance on Reporting in
Accordance with International Council for Harmonisation--Periodic
Benefit-Risk Evaluation Report (E2C(R2)) and Providing Waiver-Related
Materials'' has been approved under OMB control number 0910-0771. The
guidances also reference other collections of information. The
collection of information in 21 CFR 314.80 has been approved under OMB
control number 0910-0230, and the collection of information in 21 CFR
600.80 has been approved under OMB control number 0910-0308.

III. Electronic Access

    Persons with access to the Internet may obtain the document at
http://www.regulations.gov, http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

    Dated: July 13, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-17009 Filed 7-18-16; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register: April 25, 2007 (Volume 72, Number 79)]
[Rules and Regulations]
[Page 20428-20430]
[DOCID:fr25ap07-5]

=======================================================================
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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 70

[EPA-R03-OAR-2007-0254; FRL-8304-8]

State Operating Permit Programs; Maryland; Revisions to the Acid
Rain Regulations

AGENCY: Environmental Protection Agency (EPA).

ACTION: Direct final rule.

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

SUMMARY: EPA is taking direct final action to approve revisions to the
Maryland operating permit program. The revisions amend the Code of
Maryland Administrative Regulations' (COMAR) incorporation by reference
citations to ensure that future changes to the Federal Acid Rain
program will continue to be incorporated into Maryland's regulations.
EPA is approving these revisions in accordance with the requirements of
the Clean Air Act.

DATES: This rule is effective on June 25, 2007 without further notice,
unless EPA receives adverse written comment by May 25, 2007. If EPA
receives such comments, it will publish a timely withdrawal of the
direct final rule in the Federal Register and inform the public that
the rule will not take effect.

ADDRESSES: Submit your comments, identified by Docket ID Number EPA-
R03-OAR-2007-0254 by one of the following methods:
    A. http://www.regulations.gov. Follow the on-line instructions for

submitting comments.
    B. E-mail<EMAIL_ADDRESS>    C. Mail: EPA-R03-OAR-2007-0254, David Campbell, Chief, Permits and
Technical Assessment Branch, Mailcode 3AP11, U.S. Environmental
Protection Agency, Region III, 1650 Arch Street, Philadelphia,
Pennsylvania 19103.
    D. Hand Delivery: At the previously-listed EPA Region III address.
Such deliveries are only accepted during the Docket's normal hours of
operation, and special arrangements should be made for deliveries of
boxed information.
    Instructions: Direct your comments to Docket ID No. EPA-R03-OAR-
2007-0254. EPA's policy is that all comments received will be included
in the public docket without change, and may be made available online
at http://www.regulations.gov, including any personal information provided,

unless the comment includes information claimed to be Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Do not submit information that you consider to
be CBI or otherwise protected through http://www.regulations.gov or e-mail.

The http://www.regulations.gov Web site is an ``anonymous access'' system,

which means EPA will not know your identity or contact information
unless you provide it in the body of your comment. If you send an e-
mail comment directly to EPA without going through http://www.regulations.gov,

your e-mail address will be automatically captured and included as part
of the comment that is placed in the public docket and made available
on the Internet. If you submit an electronic comment, EPA recommends
that you include your name and other contact information in the body of
your comment and with any disk or CD-ROM you submit. If EPA cannot read
your comment due to technical difficulties and cannot contact you for
clarification, EPA may not be able to consider your comment. Electronic
files should avoid the use of special characters, any form of
encryption, and be free of any defects or viruses.
    Docket. All documents in the electronic docket are listed in the
http://www.regulations.gov index. Although listed in the index, some

information is not publicly available, i.e., CBI or other information
whose disclosure is restricted by statute. Certain other material, such
as copyrighted material, is not placed on the Internet and will be
publicly available only in hard copy form. Publicly available docket
materials are available either electronically in http://www.regulations.gov or

in hard copy during normal business hours at the Air Protection
Division, U.S. Environmental Protection Agency, Region III, 1650 Arch
Street, Philadelphia, Pennsylvania 19103. Copies of the State submittal
are available at the Maryland Department of the Environment, 1800
Washington Boulevard, Suite 705, Baltimore, Maryland 21230.

FOR FURTHER INFORMATION CONTACT: Paul Arnold,<PHONE_NUMBER>, or by e-
mail at<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. Background

    On February 13, 2007, Maryland submitted a formal revision to its
Title V operating permit program. The revisions amend The Code of
Maryland Administrative Regulations' (COMAR) incorporation by reference
citations to ensure that future changes to the Federal Acid Rain
program will continue to be incorporated into Maryland's regulations.

II. Summary of Title V Program Revision

    Both COMAR <IP_ADDRESS> and <IP_ADDRESS> currently incorporate by
reference the Federal Acid Rain Program. These revisions will update
COMAR <IP_ADDRESS> and COMAR <IP_ADDRESS> to ensure that future changes
to the Federal program will continue to be incorporated by reference
into Maryland's regulations.

III. Final Action

    EPA is approving this revision to the Maryland operating permit
program. EPA is publishing this rule without prior proposal because the
Agency views this as a noncontroversial amendment and anticipates no
adverse comment. However, in the ``Proposed Rules'' section of today's
Federal Register, EPA is publishing a separate document that will serve
as the proposal to approve the SIP revision if adverse comments are
filed. This rule will be effective on June 25, 2007 without further
notice unless EPA receives adverse comment by May 25, 2007. If EPA
receives adverse comment, EPA will publish a timely withdrawal in the
Federal Register informing the public that the rule will not take
effect. EPA will address all public comments in a subsequent final rule
based on the proposed rule. EPA will not institute a second comment
period on this action. Any parties interested in commenting must do so
at this time.

IV. Statutory and Executive Order Reviews

A. General Requirements

    Under Executive Order 12866 (58 FR 51735, October 4, 1993), this
action is not a ``significant regulatory action'' and therefore is not
subject to review by the Office of Management and Budget. For this
reason, this action is also not subject to Executive Order 13211,
``Actions Concerning Regulations That Significantly Affect Energy
Supply, Distribution, or Use'' (66 FR 28355, May 22, 2001). This action
merely approves state law as meeting Federal requirements and imposes
no additional requirements beyond those imposed by state law.
Accordingly, the Administrator certifies that this rule will not have a
significant economic impact on a substantial number of small entities
under the Regulatory Flexibility Act (5 U.S.C. 601 et seq.). Because
this rule approves pre-existing requirements under state law and does
not impose any additional enforceable duty beyond that required by
state law, it does not contain any unfunded mandate or significantly or
uniquely affect small governments, as described in the Unfunded
Mandates Reform Act of 1995 (Public Law 104-4). This rule also does not
have tribal implications because it will not have a substantial direct
effect on one or more Indian tribes, on the relationship between the
Federal Government and Indian tribes, or on the distribution of power
and responsibilities between the Federal Government and Indian tribes,
as specified by Executive Order 13175 (65 FR 67249, November 9, 2000).
This action also does not have Federalism implications because it does
not have substantial direct effects on the States, on the relationship
between the national government and the States, or on the distribution
of power and responsibilities among the various levels of government,
as specified in Executive Order 13132 (64 FR 43255, August 10, 1999).
This action merely approves a state rule implementing a Federal
requirement, and does not alter the relationship or the distribution of
power and responsibilities established in the Clean Air Act. This rule
also is not subject to Executive Order 13045 ``Protection of Children
from Environmental Health Risks and Safety Risks'' (62 FR 19885, April
23, 1997), because it approves a state rule implementing a Federal
standard.
    In reviewing SIP submissions, EPA's role is to approve state
choices, provided that they meet the criteria of the Clean Air Act. In
this context, in the absence of a prior existing requirement for the
State to use voluntary consensus standards (VCS), EPA has no authority
to disapprove a SIP submission for failure to use VCS. It would thus be
inconsistent with applicable law for EPA, when it reviews a SIP
submission, to use VCS in place of a SIP submission that otherwise
satisfies the provisions of the Clean Air Act. Thus, the requirements
of section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (15 U.S.C. 272 note) do not apply. This rule does not
impose an information collection burden under the provisions of the
Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.).

B. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. This rule is not a
``major rule'' as defined by 5 U.S.C. 804(2).

C. Petitions for Judicial Review

    Under section 307(b)(1) of the Clean Air Act, petitions for
judicial review of this action must be filed in the United States Court
of Appeals for the appropriate circuit by June 25, 2007. Filing a
petition for reconsideration by the Administrator of this final rule
does not affect the finality of this rule for the purposes of judicial
review nor does it extend the time within which a petition for judicial
review may be filed, and shall not postpone the effectiveness of such
rule or action. This action approves changes to Maryland's Title V
operating permit program and may not be challenged later in proceedings
to enforce its requirements. (See section 307(b)(2).)

List of Subjects in 40 CFR Part 70

    Environmental protection, Administrative practice and procedure,
Air pollution control, Reporting and recordkeeping requirements.

    Dated: April 17, 2007.
Donald S. Welsh,
Regional Administrator, Region III.

0
40 CFR part 70 is amended as follows:

PART 70--[AMENDED]

0
1. The authority citation for part 70 continues to read as follows:

     Authority: 42 U.S.C. 7401 et seq.

0
2. Appendix A to part 70 is amended by revising paragraph (c) in the
entry for Maryland to read as follows:

Appendix A to Part 70--Approval Status of State and Local Operating
Permits Programs

* * * * *

Maryland

* * * * *
    (c) The Maryland Department of the Environment submitted an
operating permit program amendment on February 13, 2007. The program
amendment contained in the February 13, 2007 submittal will update
Maryland's existing incorporation by reference citations to the
Federal Acid Rain Program. The state is hereby granted approval
effective on June 25, 2007.
* * * * *
[FR Doc. E7-7919 Filed 4-24-07; 8:45 am]

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