UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION PESTICIDES AND TOXIC SUBSTANCES TXR Number: 0050338 MEMORANDUM DATE: January 21, 2002 SUBJECT: Pronamide (Propyzamide): Report of the Mechanism of Toxicity Assessment Review Committee (MTARC) Evaluation of the Available Mechanistic Information for the Active Ingredient, Pronamide. PC Code: 101701. DP Barcode: D279550. Submission Number: S597844.

FROM: Michelle M. Centra, Pharmacologist Reregistration Branch III Health Effects Division (7509C)

THRU: Pauline Wagner, Co Chair Karl Baetcke, Co Chair Mechanism of Toxicity Science Assessment Review Committee (MTARC) Health Effects Division (7509C)

TO: Jess Rowland, Co Chair Elizabeth Doyle, Co Chair Hazard Identification Assessment Review Committee (HIARC) Health Effects Division (7509C)

cc: Anna Lowit MTARC Secretary Health Effects Division (7509C) and Catherine Eiden, Branch Senior Scientist Jose Morales, Risk Assessor Reregistration Branch III Health Effects Division (7509C)

On October 23, 2001, the Mechanism of Toxicity Assessment Review Committee (MTARC) met to prescreen the available Pronamide toxicology data submitted in support of a proposed threshold mechanism for the induction of thyroid and testicular neoplasms and to determine whether a full MTARC review is required. The Committee's data evaluation and conclusions are presented in this report. 2 Committee Members in Attendance Members present were: Karl Baetke, Karen Hammernik, Anna Lowit Member( s) in absentia: Pauline Wagner Data evaluation prepared by: Michelle M. Centra, Reregistration Branch III (RRB III)

Also in attendance were: Steve Knizner (RRBIII), Jose Morales (RRBIII)

Data Evaluation / Report Presentation Michelle M. Centra Pharmacologist 3 Cl Cl O C CH 3 N H CH CH 3 I. MTARC DECISION Based on the absence of any additional information as well as the MTARC's evaluation of the existing pronamide toxicology data base and the Agency's previous hazard characterization of this active ingredient (Memorandum: N. Thoa, May 26, 1993), the Committee determined that the postulated threshold mechanism for the induction of thyroid and testicular neoplasms remains incomplete and is not supported by the available data. Therefore, a full Committee review for pronamide is not required.

II. BACKGROUND INFORMATION A. Introduction Pronamide [3, 5 dichloro N( 1, 1 dimethyl 2 propynyl) benzamide], trade name Kerb ® , is a selective, systemic, pre and post emergence herbicide which inhibits root and shoot growth from seedlings and is used to control a wide range of annual and perennial grasses as well as certain broadleaf weeds. It is produced and formulated for use as a 50 W wettable powder in water soluble pouches (EPA Reg. No. 707 159) by Rohm and Hass Co., Springhouse, Pennsylvania. It is registered for use in/ on several food and feed crops (alfalfa, apples, globe artichokes, birdsfoot trefoil, blackberries, blueberries, cherries, clover, crown vetch, endive, grapes, lettuce, nectarines, peaches, pears, plums, prunes, raspberries, and sainfoin). Pronamide is also registered for terrestrial non domestic, non food use on woody ornamentals (azalea, holly, juniper, pine, rhododendron, and yew), Christmas trees, nursery stocks (forsythia, holly, juniper, pine, rhododendron, and yew) and for domestic outdoor uses on lawns, turfs, and fallow land to control bermudagrass, centipedegrass, St. Augustinegrass, and zoysiagrass.

B. Chemical Identification Chemical Structure:

Empirical Formula: C12H11NOCl2 Common Synonyms: propyzamide; 3,5 dichloro N (1,1 dimethyl 2 propynyl) benzamide, Kerb ®

9CI Name: 23950 58 5 Physical Properties: Technical pronamide is a white crystalline solid. Molecular Weight: 256.13 Melting point: 155 156 0 C Specific gravity: 0. 48 g/ cc Water Solubility: The solubility of pronamide in water at 25 0 C is 15 ppm. 4 Pronamide is soluble in dimethyl sulfoxide and dimethyl formamide at 33 ppm; in mesityl oxide, isophorone, methyl ethyl ketone, and cyclohexanone at 20 ppm; in methanol, isopropanol, and chlorobenzene at 12 15 ppm; in butyl cellosolve, xylene, acetonitrile, and kerosene at 10 ppm; and in nitrobenzene and ethylene dichloride at 5 ppm. CAS No.: 23950 58 5 PC Code: 101701 C. Toxicity Summary Pronamide appears to be a liver toxicant. Adverse liver related effects (increases in liver weight and/ or liver related serum enzymes and/ or histopathology) were consistently observed in every animal species studied, including the rat (subchronic, chronic, and 2 generation reproduction studies), mouse (carcinogenicity studies), rabbit (developmental study), and dog (subchronic and chronic studies).

Other target organs included the thyroid in rats (increase in weight and/ or histopathology observed in the chronic toxicity/ carcinogenicity and the 2 generation reproduction studies as well as a subchronic, special 13 week thyroid function study), the testes in rats (histopathology in the chronic toxicity/ carcinogenicity study) and the kidneys, adrenal glands thymus, heart, testes, and brain in dogs (increase in organ weights in the chronic toxicity study), and the pituitary in rats (histopathology observed in the subchronic and 2 generation reproduction studies). Many chemicals belonging to the class of organochlorine chemicals are known to produce disruption of the endocrine system 1 . Pronamide belongs to this class of chemicals.

The Carcinogenicity Peer Review Committee (CPRC) classified Pronamide as a group B2  probable human carcinogen with inadequate evidence in humans (Memorandum: N. B. Thoa and E. Rinde, May 26, 1993). This decision was based on the finding of two types of tumors in the rat (benign testicular interstitial cell tumors and uncommon thyroid follicular cell adenomas), and one type of tumor in the mouse (hepatocellular carcinomas). A linear, low dose approach (Q1 *) was used for human risk characterization. The most potent unit risk Q1 *, based on male mouse liver adenoma and/ or carcinoma combined tumor rates, is 2. 59 x 10 2 (mg/ kg/ day) 1 in human equivalents [converted from animal to humans by use of the (mg/ kg body weight) 3/ 4 interspecies scaling factor] (Memorandum: L. Brunsman, October 26, 2001).

In addition to the required guideline toxicity studies, two special studies were conducted to evaluate pronamide's effect on hormonal balance in support of a threshold mechanism for the induction of thyroid and testicular neoplasms. The CPRC also considered this data in its weight of evidence deliberations and concluded the following:

° The data provided on thyroid mechanism were suggestive of a thyroid pituitary hormonal control mechanism but were not conclusive, based on the Agency's six criteria for a threshold model of thyroid neoplasia (See Appendix, Carcinogenicity Peer Review of Pronamide 3 rd ). For example, there were no dose related and/ or sustained increases in TSH levels, no dose related increases in incidence of thyroid hypertrophy/ hyperplasia, and no information on thyroid hormone synthesis. 5 ° The Agency has no policy which implements a threshold model for testicular neoplasia. Endocrine function of the testis may or may not be regulated through a feedback mechanism similar to that controlling thyroid function, e. g. through an involvement of the anterior pituitary. Even if a testis pituitary hormonal control mechanism existed, the evidence supporting pronamide induced testicular tumors in the rat via a disruption in the testis pituitary balance is very limited. There was no clear increase in interstitial cell hypertrophy/ hyperplasia, no alteration in testosterone level, no information on testicular hormone synthesis and no reversibility of testicular lesions.

Although several endocrine effects have been observed in pronamide toxicity studies, the data provided in special studies conducted to explore potential mechanisms of endocrine toxicity, are incomplete. Based on the CPRC's weight of evidence evaluation of this data base, it was determined that even if a hormonal mechanism could be demonstrated for tumors in the rat, the mouse liver tumors can not be discounted (the Q1 * is based on the incidence of liver tumors in mice). Therefore, a mechanistic approach to risk assessment for the active ingredient pronamide is not plausible.

1 Hileman, B., March 19, 1993. Concerns broaden over chlorine and chlorinated hydrocarbons calls for gradual phaseout of classes of chlorinated organics are being made in response to evidence of adverse health effects on humans and wild life. C & E News, volume 71, No. 16, pp 11 20. 6 III. Data Presentation A. Listing and Presentation of Available Data Table 1. Endocrine/ Other Effects Observed in Pronamide Toxicity Studies Study Type (MRID Number) Dose and Exposure Duration Endocrine and Other Effects Study Citation and Study Classification Chronic Toxicity/ Car cinogenicity Study  Rats (MRID 41714001, 41714002) Pronamide was administered to Crl: CD( BR) VAF/ Plus Rats in the diet at either 0, 25, 100, or 400 ppm for the first 2 weeks, followed by 0, 35, 140, or 560 ppm for the next 3 weeks and thereafter, 0, 40, 200, or 1000 ppm (equal to 0, 1. 73, 8.46, and 42.59 mg/ kg/ day for males and 0, 2. 13, 10.69, and 55.09 mg/ kg/ day for females, respectively). Increased incidences of non neoplastic lesions were observed in the liver, thyroid, and ovaries of high dose (1000 ppm) rats.

In the liver, centrilobular hypertrophy was observed in males and females at 12 months (65% in males; 95% in females) and 24 months (20% in males; 48% in females). Hypertrophy was accompanied by eosinophilic cell alteration at 24months (positive trend in both sexes; pair wise comparison in high dose/ controls for males and females).

In the thyroid, follicular cell hypertrophy was observed (positive trend in males and in females) at 12 months but not at 24 months. The increased incidence observed at 1000 ppm was only significant (pair wise comparison in high dose/ controls) in females. At 24 months, follicular cell hyperplasia was observed in females (positive trend) but the increased incidence observed at 1000 ppm was not statistically significant.

In the ovaries, sertoliform tubular hyperplasia (positive trend) was observed in females at 24 months and the increase in incidence observed at 1000 ppm was significant by pair wise comparison. Bailey, D. E. (1990): Kerb ® Herbicide (Technical, no clay): 24 Month Dietary Chronic Toxicity/ Oncogenicity Study in Rats; Hazleton Laboratories America, Inc. for Rohm & Haas Co.; HLA 417 426S, HLA 417 426M; November 2, 1990 (Unpublished Study)

Acceptable Guideline Table 1. Endocrine/ Other Effects Observed in Pronamide Toxicity Studies Study Type (MRID Number) Dose and Exposure Duration Endocrine and Other Effects Study Citation and Study Classification 7 Non Guideline Endocrine Study  Male Rats (MRID 42093401) Pronamide was administered to male Crl: CD ® BR Rats in the diet at concentrations of 0, 40, 1000 or 4000 ppm Pronamide for either 4 or 15 weeks. Parameters of thyroid function, T4 hepatic metabolism, and exogenous 125 I biliary clearance were investigated, in support of Pronamide's thyroid tumorigenic mechanism of action involving disruption of the thyroid pituitary hormonal balance. At 1000 ppm, pronamide treatment resulted in decreased body weights and food consumption, increased absolute and/ or relative weights of the liver and thyroid (absolute after 4 weeks; absolute and relative after 15 weeks), increased serum TSH (at 4 weeks but not at 13 weeks), decreased serum T4, and an increased incidence of thyroid and pituitary hypertrophy/ hyperplasia. The highest dose tested (4000 ppm) produced more profound effects on the body weights, liver weights and serum T4 than was seen in the mid dose (1000 ppm). Pronamide exposure resulted in increased thyroid (relative) weight and increased incidences of thyroid and pituitary hypertrophy/ hyperplasia which were comparable to the mid dose, but did not statistically change serum TSH levels. Specific parameters were investigated only at the high dose: T4 hepatic metabolism and 125 I biliary clearance were both increased and all of the thyroid and liver related changes occurring after 4 weeks of dosing, were either reduced in severity or absent 11 weeks following discontinuation of the dosing.

Based on the six Agency criteria for thyroid effects, there is suggestive evidence that the thyroid tumors in the rat associated with pronamide administration may result from disruption of the thyroid pituitary hormonal balance. This evidence is weakened by the lack of a dose related and sustained increase in serum TSH, and the lack of a dose related increase in the incidence of thyroid follicular cell hypertrophy/ hyperplasia. There was also no investigation of T4 hepatic metabolism and biliary clearance at the high dose level (1000 ppm) which was also a test dose used in the rat chronic toxicity/ carcinogenicity study that demonstrated thyroid adenomas. Hazelton, G. A., Didonato, L. J., Donofrio, K. F, Kulwich, B. A. (1991): Pronamide (Kerb ® Herbicide): Thyroid Function and Hepatic Clearance of Thyroxine inMale Rats; Rohm & Haas Co., Toxicology Department for Rohm & Haas Co.; 90R 178; October 9, 1991 (Unpublished Study)

Acceptable Nonguideline Table 1. Endocrine/ Other Effects Observed in Pronamide Toxicity Studies Study Type (MRID Number) Dose and Exposure Duration Endocrine and Other Effects Study Citation and Study Classification 8 Non Guideline, Pilot Endocrine Study  Male Rats (MRID 42139601) Pronamide was administered to male Crl: CD ® BR Rats in the diet at concentrations of either 0, or 4000 ppm for 13 weeks. Clinical chemistry and histopathological parameters of testicular function, as well as hepatic metabolism of testosterone were investigated, to lend support to Pronamide's testicular tumorigenic mechanism of action involving disruption of the pituitary testis hormonal balance. Clinical chemistry parameters were also measured in male rats treated with 0, 40, 1000, or 4000 ppm pronamide for 4 weeks. In the 13 week study, pronamide (4000 ppm) produced decreased body weight (weeks 1 13) and food consumption (weeks 1 8), increased serum LH and FSH levels (respective increases at 4 and 13 weeks were 60% and 58% for FSH, and 100% and 77% for LH), increased liver weight (absolute and relative to body and brain weight), microsomal protein content, oxidation of testosterone, activity of cytochrome P450 , cytochrome B5, NADPH cytochrome C reductase, and gross pathology of the liver (enlarged/ dark), and increased testicular relative (to body) weight , and testicular interstitial cell hyperplasia.

In the 4 week study, alterations in clinical chemistry parameters (increases in serum LH and FSH) were noted only at 4000 ppm and were comparable to the increases observed after 13 weeks of dosing.

The most positive supporting evidence for the involvement of the pituitary in testicular neoplasia is the increase in serum LH and FSH levels after 4 and 15 weeks of treatment. There was, however, no concomitant decrease in serum testosterone. Futhermore, studies were not conducted which may have demonstrated that this lack of effect was produced by some additional effect of pronamide (e. g., an increase in testosterone clearance accompanying the moderate stimulatory effect [54% increase/ g liver] on testosterone metabolism). There also was no evidence of testicular lesion progression and/ or lesion reversibility. The CPRC concluded that this data is, at best, incomplete and additional studies should be conducted in order to support the Registrant's theory of a pronamide induced testicular neoplastic effect via disruption of the pituitary testis hormonal balance. Hazelton, G. A., Didonato, L. J., Donofrio, K. F., Kulwich, B. A. (1991): Pronamide (Kerb ® Herbicide): Effects on Endocrine Regulation of the testis in Rats  Pilot Study; Rohm & Haas Co., Toxicology Department for Rohm & Haas Co.; 90R 179; December 6, 1991 (Unpublished Study)

Acceptable Nonguideline Table 1. Endocrine/ Other Effects Observed in Pronamide Toxicity Studies Study Type (MRID Number) Dose and Exposure Duration Endocrine and Other Effects Study Citation and Study Classification 9 Two Generation Reproduction Study  Rats (MRID 41540301) Pronamide was administered to Crl: CD ® BR Rats in the diet at concentrations of 0, 40, 200 or 1500 ppm (equal to 3.1, 16.0 and 120.7 mg/ kg/ day for females and 3.6, 18.0 and 130.1 mg/ kg/ day for males for the 40, 200 and 1500 ppm dose groups, respectively) through 2 generations (one mating period per generation). Parental systemic effects were observed in rats treated with 1500 ppm pronamide: decreased body weight and feed consumption in both sexes and increased incidences of histopathology of the liver (centrilobular hepatocytes hypertrophy; both sexes), adrenal glands (zona glomerulosa cellular hypertrophy; both sexes), thyroid gland (follicular cell hypertrophy; females), and anterior pituitary gland (cellular hypertrophy; males) in both P1 and P2 generations, and increased incidences of uterine gross pathology (black foci/ serosal surface) in P2 females. Solomon, H. M., Brown, W. R. (1990): Pronamide: Two Generation Reproduction Study in Rats; Rohm andHaas Company, Toxicology Department for Rohm and Haas Company; Study Number: 88P 309; Report No. 88R 257; June 14, 1990 (Unpublished)

Acceptable Guideline Table 1. Endocrine/ Other Effects Observed in Pronamide Toxicity Studies Study Type (MRID Number) Dose and Exposure Duration Endocrine and Other Effects Study Citation and Study Classification 10 Subchronic Toxicity Study  Rats (MRID 42669403) Pronamide was administed to Crl: CD ® BR Rats in the diet at concentrations of 0, 40, 200, 1000, or 4000 ppm (equal to 0, 2.5, 12.3, 60.0, and 254.0 mg/ kg/ day for males and 0, 3.1, 15.0,74.6, and 289.2 mg/ kg/ day for females, respectively) for 3 months At 1000 ppm, pronamide treatment resulted in increases in liver relative (to body) weight, and incidence of liver centrilobular hypertrophy in both sexes, decreases in body weight/ weight gain and feed consumption in females, and increases in blood cholesterol levels in males.

Additional toxicities observed at 4000 ppm included an increase in clinical signs (brown and/ or yellow staining of the anogenital area) in males, decreases in body weight/ weight gain and feed consumption in males and further exacerbation of the later in females. In addition, more pronounced effects were observed in the liver, thyroid and pituitary at the highest dose tested: increases in cholesterol (both sexes), SGOT and alkaline phosphatase (males), triglycerides (females), liver absolute/ relative weights (both sexes), incidence/ severity of liver centrilobular hypertrophy (both sexes), incidence of thyroid follicular hypertrophy (both sexes) and anterior pituitary cellular hypertrophy (males). The liver, thyroid and pituitary appear to be target organs.

After 4 weeks of recovery, most of the adverse effects observed at the high dose were partially or totally reversed but the increase in the incidence of pituitary cellular hypertrophy in males was not diminished. Anderson, D. M., Kulwich, B. A., Hazelton, G. A. (1989): Pronamide Technical (no clay): Three Month Dietary Toxicity Study in Rats; Rohm & Haas Co. Tox Dept for Rohm & Haas Co.; Report No. 88R 053; September 15, 1989 (Unpublished Study)

Acceptable Guideline Table 1. Endocrine/ Other Effects Observed in Pronamide Toxicity Studies Study Type (MRID Number) Dose and Exposure Duration Endocrine and Other Effects Study Citation and Study Classification 11 Chronic Toxicity Study  Dogs (MRID 41807601, 41807602) Pronamide was administered to Beagle Dogs in the diet at concentrations of 0, 300, 875, or 1750 ppm (equal to 0, 11.9, 33.1, 67.7 mg/ kg/ day for males and 0, 11.9, 36.1, 69.0 mg/ kg/ day for females, respectively) for 52 weeks. At 875 ppm, pronamide treatment produced toxicity in several organs.

In the liver, systemic toxicity included increases in serum alkaline phosphatase activity (males), increases in absolute and relative (to body) liver weight (males and females), increases in the incidence of hepatocytic hypertrophy/ hyperplasia and granular brown pigmentation and mononuclear infiltration of Kupffer cells (males and females).

At 1750 ppm, further increases in serum alkaline phosphatase activity were observed in both sexes, along with increases in serum gamma glutamyl transferase (males and females) and alanine amino transferase activities (females). The incidence/ severity of the histopathologic alterations in the liver were also exacerbated.

Other organs affected at 1750 ppm dose included the kidneys (increase in relative weight in females and occurrence of brown pigmentation in proximal tubules in both sexes), thyroid gland (increase in relative weight in females), adrenal glands (increase in relative weight in males and absolute/ relative weights in females), thymus (increase in relative weight in females), and heart and testes (increases in relative weights in males). Briffaux, J. P. (1991): Pronamide (Kerb ®

Technical Herbicide): 52 week oral (dietary) toxicity study in the Beagle Dog; Hazleton France (HF) for Rohm & Haas Co.; HF Project ID No. 616/ 503, Report No. HF 505069, Rohm & Haas Report No.: 89RC 110; February 20, 1991 (Unpublished Study)

Acceptable Guideline 12 B. Data Evaluation The following data is excerpted from the CPRC document (Memorandum: N. Thoa, May 26, 1993):

Study Citation Bailey, D. E. (1990): Kerb ® Herbicide (Technical, no clay): 24 Month Dietary Chronic Toxicity/ Oncogenicity Study in Rats; Hazleton Laboratories America, Inc. for Rohm & Haas Co.; HLA 417 426S, HLA 417 426M; November 2, 1990 (Unpublished Study); MRID Number 41714001 and 41714002.

Increased incidences of non neoplastic lesions were observed in the liver, thyroid, and ovaries of highdose rats.

In the liver, a positive trend (p < 0.01) in the incidence of centrilobular hypertrophy was observed in males and females in both phases (12 and 24 month); the increases observed at 1000 ppm were significant by pair wise comparison (p < 0.01, both sexes) and appeared more pronounced in the 12 month phase (rate = 65% in males and 95% in females) than in the 24 month phase (rate = 20% in males and 48% in females). Hypertrophy was accompanied by eosinophilic cell alteration in the 24month phase( p< 0. 01forpositivetrendin both sexes; pair wisecomparison in high dose/ controls, p < 0. 05 in males and p < 0. 01 in females).

In the thyroid, a positive trend (p < 0. 05 in males and p < 0. 01 in females) in the incidence of follicular hypertrophy was observed in the 12 month phase but not the 24 month phase. The increased incidence observed at 1000 ppm was only significant (p < 0.01, high dose/ controls) in females, but the increased incidence observed at 1000 ppm was not statistically significant.

In the ovaries, a positive trend (p < 0.01) in the incidence of sertoliform tubular hyperplasia was observed in females in the 24 month phase, and the increase in incidence observed at 1000 ppm was significant (p < 0.01) by pair wise comparison.

Discussion of Tumor Data At 1000 ppm, in the 24 month phase, both male and female rats had increased rates of thyroid follicular cell adenomas, and male rats had an increased incidence of benign testicular interstitial cell tumors. Thyroid tumors were not observed until weeks 53 and 82 for males and females, respectively, and testicular tumors were not observed until week 67. The increase in thyroid tumor rate was statistically significant by pair wise comparison (p < 0. 01) only in males, but there was a positive trend (p < 0. 01) for both sexes. Both high dose male and female tumor rates (21% and 10%, respectively) exceeded the historical control range which was 0 14.8% (a mean value of 5% for males) and 0 9. 5% (a mean value of 2% for females). Historical control data for SD rats was obtained from 13 studies conducted between 1985 and 1990 at Hazleton Laboratories, Vienna, VA. There were no significant differences in thyroid follicular cell carcinoma rates between groups. There were increasing trends and/ or rates in combined incidences of thyroid follicular cell adenomas and carcinomas (trend p < 0. 01 in males, p < 0. 05 in females; pair wise comparison of high dose males/ controls, p < 0. 05) which were a reflection of the treatment related changes in thyroid follicular cell adenoma rates. The increase in testicular interstitial cell benign tumor rate was statistically significant by pair wise comparison (p < 0.05) and there was a positive trend (p < 0.01). In high dose males, the tumor rate (27%) exceeded the historical range of 4. 8 18.2% with a mean value of 5. 6% (Hazleton Laboratories, Vienna, VA: historical control data for SD rats obtained from 11 studies conducted between 1985 and 1990). In 13 the 12 month phase, thyroid follicular cell and testicular interstitial cell neoplasia were not observed in any group.

Benign pituitary adenomas of the pars distalis were observed in every dose group during both the 12 and 24 month phases, but the tumor rates were statistically comparable among all groups. The respective tumor rates for the 0, 40, 200, and 1000 ppm dose groups were 1/ 19, 0/ 19, 0/ 20, and 3/ 20 in males and 0/ 20, 2/ 20, 1/ 19, and 3/ 20 in females for the 12 month phase and 31/ 60, 33/ 60, 35/ 60, and 34/ 60 in males and 49/ 60, 49/ 60, 49/ 60, and 54/ 60 in females for the 24 month phase.

Adequacy of the Dose Levels Tested The dosing was considered to be adequate for assessing the carcinogenic potential of Pronamide, based on body weight gain depressions (p < 0.05) of  10% observed at 1000 ppm (weeks 0 26 in males; weeks 0 52 in females). Feed consumption was also depressed (p < 0.05) at 1000 ppm in males during weeks 1 13 (7%), 1 26 (7%), and 1 52 (5%). Survival rate was comparable between groups. The statistical evaluation of mortality indicates no significant incremental changes with increasing doses of Pronamide in either male or female rats.

Survival rate was comparable between groups. The statistical evaluation of mortality indicates no significant incremental changes with increasing doses of pronamide in either male or female rats.

Study Citation Hazelton, G. A., Didonato, L. J., Donofrio, K. F., Kulwich, B. A. (1991): Pronamide (Kerb ® Herbicide): Thyroid Function and Hepatic Clearance of Thyroxine in Male Rats; Rohm & Haas Co., Toxicology Department for Rohm & Haas Co.; 90R 178; October 9, 1991 (Unpublished Study); MRID Number 42093401.

Histopathology of the Thyroid Treatment with 1000 and 4000 ppm pronamide for 4 or 15 weeks was associated with similar increases (p < 0. 05) in incidence of diffuse hypertrophy/ hyperplasia of the thyroid follicular cells. There was a positive trend after both 4 and 15 weeks. The lesions were observed throughout the thyroid and were characterized by follicular cells with increased height, and by follicles reduced in size and in colloid content. The increase in incidences observed after 4 weeks of treatment with the highdose (10/ 10) was reduced (5/ 9) after the recovery period. The severity of the lesions was greater at 4000 ppm than at 1000 ppm.

Thyroid Hormone and TSH (4 and 15 week observations at 1000 and 4000 ppm in male rats)

Treatment with 40 4000 ppm pronamide for 4 or 15 weeks was not associated with any reduction in T3 or rT3 .T4 was moderately reduced (decreased at 1000 ppm: 61% after 4 weeks and 48% after 15 weeks; decreased at 4000 ppm: 87% after 4 weeks and 84% after 15 weeks). Except for a moderate increase (72%) observed after 4 weeks of treatment with 1000 ppm pronamide, TSH remained unaffected. The decrease in T4 which observed after 4 weeks of treatment with 4000 ppm pronamide was absent after 11 weeks of recovery. 14 T4 Hepatic Uridine Diphosphate Glucuronosyl Transferase (UDPGT) Activity Treatment with 4000 ppm pronamide for 4 or 15 weeks was associated with a 2 2. 5 fold increase in UDP GT activity (enzyme activity was expressed as nmol T4 glucuronide formed/ min/ mg liver microsomal protein). The increased activity observed after 4 weeks of treatment with 4000 ppm pronamide was absent after 11 weeks of recovery.

Bile flow and Biliary Clearance of 125 I T4 Treatment with 4000 ppm pronamide for 4 or 15 weeks was associated with significant (p < 0.05) increases in bile flow (  65%), biliary clearance of 125 I T4 (7 10 fold) and 125 I T4 glucuronide (1 2 fold), and 125 I bile/ plasma ratio after 4 weeks of treatment. The alterations in bile flow and biliary clearance were completely reversed after 11 weeks of recovery.

Adequacy of Dosing for Assessment of Thyroid Effects The dosing was considered to be adequate for assessing the thyroid effects of pronamide, based on significant (p < 0.05) depressions of body weight (2 5% at 1000 ppm, weeks 1 4; 17 24% at 4000 ppm, weeks 1 15) and feed consumption (4 10% at 1000 ppm, weeks 1 4; 11 38% at 4000 ppm, weeks 1 15). Absolute (abs) and/ or relative (rel) liver weight was significantly increased (p < 0. 05) at  1000 ppm, in a dose related manner (4 week increases: 29% abs and 36% rel at 1000 ppm, 50% abs and 91% rel at 4000 ppm; 15 week increases: 32% rel at 1000 ppm; 42% abs and 86% rel at 4000 ppm). Thyroid weight was significantly increased (p < 0. 05) at  1000 ppm in a non dose related manner (4 week increases: 29% abs and 36% rel at 1000 ppm, 32% rel at 4000 ppm. 15 week increases: 21% rel at 1000 ppm, 33% rel at 4000 ppm).

Study Citation Hazelton, G. A., Didonato, L. J., Donofrio, K. F., Kulwich, B. A. (1991): Pronamide (Kerb ® Herbicide): Effects on Endocrine Regulation of the testis in Rats  Pilot Study; Rohm & Haas Co., Toxicology Department for Rohm & Haas Co.; 90R 179; December 6, 1991 (Unpublished Study). MRID 42139601.

Histopathology of the Testes Treatment with 4000 ppm pronamide for 13 weeks was associated with an increase in the number of testicular interstitial cells. The incidences were 1/ 20 for the control group and 7/ 20 for the treated group. Interstitial cells are located between the seminiferous tubules, normally in 2 3 cell focal clusters instead of layers. In this study, the observed increase was determined to be equivocal because of "the small degree of change being evaluated and the possibility of producing this appearance through fortuitous tangential sectioning of seminiferous tubules." The CPRC determined that this type of sectioning could be seen in all dose groups.

Clinical Chemistry Changes Treatment with 4000 ppm pronamide for 4 or 13 weeks was associated with increases in serum LH and FSH. The increases were moderate and were slightly higher at 4 weeks than at 13 weeks (respective increases at 4 and 13 weeks were 60% and 58% for FSH, and 100% and 77% for LH). Serum LH and FSH levels were not affected by the mid level dose (1000 ppm). Serum testosterone levels were not affected by treatment with pronamide. 15 Liver Microsomal Enzymes Activity Treatment with 4000 ppm pronamide for 13 weeks increased the activity of the liver microsomal enzymes (cytochrome P450, cytochrome B5, and NADPH cytochrome C reductase) and the rate of oxidation of testosterone, expressed as  mol product/ whole liver. Concomitant increases in liver weight (50%) and liver microsomal protein content (34%) were observed, which suggests that oral administration of relatively high doses of pronamide (4000 ppm) for a certain period of time (13 weeks) may result in induction of the liver enzymes responsible for its metabolism.

Adequacy of Dosing for Assessment of Testicular Effects The dosing (4000 ppm) was considered to be adequate for assessing the testicular effects of pronamide, based on significant (p < 0.05) depressions of body weight (14 17%, weeks 1 13) and feed consumption (37%, week 1; 9 12%, weeks 2 8). Testicular relative (to body) weights were slightly increased (26%; p < 0. 05) and liver absolute and relative (to body) weights were moderately increased (59% absolute; 92% relative; p < 0. 05). The liver related enzymes, SGPT and SGOT, were not affected by treatment with pronamide.

IV. Conclusions Based on an evaluation of the pronamide toxicology data presented in this report , the MTARC reaffirmed the following conclusions of the CPRC (Memorandum: N. Thoa, May 26, 1993):

° The postulated mechanism of action is at best incomplete; the Registrant's postulated threshold mechanism for the induction of thyroid and testicular neoplasms is not supported by the available data.

° Even if a hormonal mechanism could be demonstrated for tumors in the rat, the mouse liver tumors can not be discounted (the Q1 * is based on the incidence of liver tumors in mice) Therefore, a mechanistic approach to risk assessment for the active ingredient pronamide is not plausible.

° Additional studies should be conducted to evaluate the potential for a pronamideinduced thyroid and testicular neoplastic effect via disruption of the pituitary thyroid and pituitary testis hormonal balance, respectively.

In the absence of any additional data, the MTARC prescreening committee determined that a full MTARC review of the toxicology data base for the active ingredient pronamide is not required.

V. Attachment (not available electronically)

Carcinogenicity Peer Review of Pronamide (3rd; Memorandum: N. Thoa, May 26, 1993) 16 ATTACHMENT Carcinogenicity Peer Review of Pronamide (3rd; Memorandum: N. Thoa, May 26, 1993)

An electronic version of this document is not available. See the hard copy file.


[Federal Register: October 21, 2009 (Volume 74, Number 202)]
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Resolution 601.
Intended Effective Date: December 1, 2009.

    Docket Number: DOT-OST-2009-0234.
    Date Filed: September 29, 2009.
    Parties: Members of the International Air Transport Association.
    Subject:

TC123 South Atlantic.
Expedited Resolution 002bh (Memo 0454).
Intended Effective Date: November 1, 2009.

    Docket Number: DOT-OST-2009-0235.

    Date Filed: September 28, 2009.
    Parties: Members of the International Air Transport Association.
    Subject:

TC31 North & Central Pacific.
TC3--Central America, South America.
Expedited Resolution 002bj.
(Memo 0495).
Intended Effective Date: November 1, 2009.

    Docket Number: DOT-OST-2009-0236.
    Date Filed: September 29, 2009.
    Parties: Members of the International Air Transport Association.
    Subject:

TC123 Mid Atlantic.
Expedited Resolution 002bk (Memo 0453).
Intended Effective Date: November 1, 2009.

    Docket Number: DOT-OST-2009-0237.
    Date Filed: September 29, 2009.
    Parties: Members of the International Air Transport Association.
    Subject:

TC123 North Atlantic (except between USA and Korea, Rep. of, Malaysia).
Expedited Resolution 002bg.
(Memo 0452).
Intended Effective Date: November 1, 2009.

    Docket Number: DOT-OST-2009-0238.
    Date Filed: September 29, 2009.
    Parties: Members of the International Air Transport Association.
    Subject:

TC123 North Atlantic between USA and Korea, Rep. of Malaysia.
Expedited Resolution 002bg.
(Memo 0451).
Intended Effective Date: November 1, 2009.

Barbara J. Hairston,
 Supervisory Dockets Officer, Docket Operations, Alternate Federal
Register Liaison.
[FR Doc. E9-25317 Filed 10-20-09; 8:45 am]

BILLING CODE 4910-62-P


[Federal Register Volume 81, Number 223 (Friday, November 18, 2016)]
[Notices]
[Page 81755]
[FR Doc No: 2016-27816]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. ER17-245-000]

Waterford Power, LLC; Supplemental Notice That Initial Market-
Based Rate Filing Includes Request for Blanket Section 204
Authorization

    This is a supplemental notice in the above-referenced proceeding
Waterford Power, LLC`s application for market-based rate authority,
with an accompanying rate tariff, noting that such application includes
a request for blanket authorization, under 18 CFR part 34, of future
issuances of securities and assumptions of liability.
    Any person desiring to intervene or to protest should file with the
Federal Energy Regulatory Commission, 888 First Street NE., Washington,
DC 20426, in accordance with Rules 211 and 214 of the Commission's
Rules of Practice and Procedure (18 CFR 385.211 and 385.214). Anyone
filing a motion to intervene or protest must serve a copy of that
document on the Applicant.
    Notice is hereby given that the deadline for filing protests with
regard to the applicant's request for blanket authorization, under 18
CFR part 34, of future issuances of securities and assumptions of
liability, is November 30, 2016.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper, using the FERC Online links at http://www.ferc.gov. To facilitate electronic service, persons with Internet
access who will eFile a document and/or be listed as a contact for an
intervenor must create and validate an eRegistration account using the
eRegistration link. Select the eFiling link to log on and submit the
intervention or protests.
    Persons unable to file electronically should submit an original and
5 copies of the intervention or protest to the Federal Energy
Regulatory Commission, 888 First Street NE., Washington, DC 20426.
    The filings in the above-referenced proceeding are accessible in
the Commission's eLibrary system by clicking on the appropriate link in
the above list. They are also available for electronic review in the
Commission's Public Reference Room in Washington, DC. There is an
eSubscription link on the Web site that enables subscribers to receive
email notification when a document is added to a subscribed docket(s).
For assistance with any FERC Online service, please email
<EMAIL_ADDRESS>or call<PHONE_NUMBER> (toll free). For
TTY, call<PHONE_NUMBER>.

    Dated: November 10, 2016.
Kimberly D. Bose,
Secretary.
[FR Doc. 2016-27816 Filed 11-17-16; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register: August 25, 2006 (Volume 71, Number 165)]
[Notices]
[Page 50407]
[DOCID:fr25au06-59]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings 1

Friday, August 18, 2006.
    Take notice that the Commission received the following electric
rate filings.
    Docket Numbers: ER02-783-005, ER02-852-005, ER02-855-005, ER01-
2262-007, ER03-438-005 and ER05-723-004.
    Applicants: EPCOR Merchant and Capital (US) Inc., EPCOR Power
Development, Inc., EPDC, Inc., Frederickson Power L.P., Manchief Power
Company, LLC and EPCOR Power (Castleton) LLC.
    Description: EPCOR Merchant and Capital (US) Inc et al submits a
notice of change in status.
    Filed Date: 08/14/2006.
    Accession Number: 20060816-0060.
    Comment Date: 5 p.m. Eastern Time on Tuesday, September 5, 2006.

    Docket Numbers: ER06-1362-000.
    Applicants: Southwest Power Pool, Inc.
    Description: Southwest Power Pool Inc proposes to revise its
regional Open Access Transmission Tariff.
    Filed Date: 08/14/2006.
    Accession Number: 20060816-0062.
    Comment Date: 5 pm Eastern Time on Tuesday, September 5, 2006.

    Docket Numbers: ER06-1363-000.
    Applicants: NorthWestern Corporation.
    Description: NorthWestern Corp submits a notice of cancellation of
Service Agreement 325 under its FERC Electric Tariff, Sixth Revised
Volume 6 with Montana Megawatts I, LLC.
    Filed Date: 08/14/2006.
    Accession Number: 20060816-0087.
    Comment Date: 5 p.m. Eastern Time on Tuesday, September 5, 2006.

    Docket Numbers: ER06-13h64-000.
    Applicants: International Paper Company.
    Description: International Paper Co submits a petition for an order
authorizing IPC to sell electric power and related services at market-
based rates and granting IPC certain waivers and blanket approvals.
    Filed Date: 08/14/2006.
    Accession Number: 20060816-0061.
    Comment Date: 5 p.m. Eastern Time on Tuesday, September 5, 2006.

    Docket Numbers: ER06-1365-000.
    Applicants: ISO New England Inc.
    Description: ISO New England Inc submits its Capital Project Report
for the quarter ending 6/30/06 and the schedule of the unamortized
costs of the ISO funded capital expenditures.
    Filed Date: 08/14/2006.
    Accession Number: 20060816-0084.
    Comment Date: 5 p.m. Eastern Time on Tuesday, September 5, 2006.

    Docket Numbers: ER06-783-002.
    Applicants: New York Independent System Oper., Inc.
    Description: New York Independent System Operator Inc requests
leave to file its Compliance Filing one day out-of-time and submits
revisions to its Open Access Transmission Tariff etc.
    Filed Date: 08/14/2006.
    Accession Number: 20060816-0059.
    Comment Date: 5 p.m. Eastern Time on Tuesday, September 5, 2006.

    Docket Numbers: ER06-826-003.
    Applicants: PJM Interconnection, LLC.
    Description: PJM Interconnection, LLC submits Substitute Third
Revised Sheet 448 et al to FERC Electric Tariff, Sixth Revised Volume 1
in compliance with FERC's order of 7/14/06.
    Filed Date: 08/14/2006.
    Accession Number: 20060816-0085.
    Comment Date: 5 p.m. Eastern Time on Tuesday, September 5, 2006.

    Docket Numbers: ER99-2948-009, ER00-2918-008, ER00-2917-008, ER05-
261-005, ER01-558-007, ER01-559-007, ER01-557-007, ER01-560-007, ER01-
556-007, ER01-1654-010, ER01-2641-008, ER02-2567-008, ER05-728-005,
ER01-1949-008, ER04-485.005.
    Applicants: Baltimore Gas & Electric Company, Constellation Power
Source Generation, Inc., Calvert Cliffs Nuclear Power Plant, Inc.;
Constellation Energy Commodities Group, Inc.; Holland Energy, LLC; Wolf
Hills Energy, LLC; University Park Energy, LLC; Big Sand Peaker Plant,
LLC; Handsome Lake Energy, LLC; Nine Mile Point Nuclear Station, LLC;
High Desert Power Project, LLC; Constellation NewEnergy, Inc.;
Constellation Energy Commodities Group Maine, LLC; Power Provider LLC;
R.E. Ginna Nuclear Power Plant, LLC.
    Description: Constellation MBR Entities submit their joint
triennial market power update.
    Filed Date: 08/14/2006.
    Accession Number: 20060818-0078.
    Comment Date: 5 p.m. Eastern Time on Tuesday, September 5, 2006.
    Any person desiring to intervene or to protest in any of the above
proceedings must file in accordance with Rules 211 and 214 of the
Commission's Rules of Practice and Procedure (18 CFR 385.211 and Sec.
385.214) on or before 5 p.m. Eastern time on the specified comment
date. It is not necessary to separately intervene again in a subdocket
related to a compliance filing if you have previously intervened in the
same docket. Protests will be considered by the Commission in
determining the appropriate action to be taken, but will not serve to
make protestants parties to the proceeding. Anyone filing a motion to
intervene or protest must serve a copy of that document on the
Applicant. In reference to filings initiating a new proceeding,
interventions or protests submitted on or before the comment deadline
need not be served on persons other than the Applicant.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper, using the FERC Online links at http://www.ferc.gov.
 To facilitate electronic service, persons with Internet

access who will eFile a document and/or be listed as a contact for an
intervenor must create and validate an eRegistration account using the
eRegistration link. Select the eFiling link to log on and submit the
intervention or protests.
    Persons unable to file electronically should submit an original and
14 copies of the intervention or protest to the Federal Energy
Regulatory Commission, 888 First St. NE., Washington, DC 20426.
    The filings in the above proceedings are accessible in the
Commission's eLibrary system by clicking on the appropriate link in the
above list. They are also available for review in the Commission's
Public Reference Room in Washington, DC. There is an eSubscription link
on the Web site that enables subscribers to receive e-mail notification
when a document is added to a subscribed dockets(s). For assistance
with any FERC Online service, please e-mail<EMAIL_ADDRESS>
or call<PHONE_NUMBER> (toll free). For TTY, call<PHONE_NUMBER>.

Magalie R. Salas,
Secretary.
[FR Doc. E6-14131 Filed 8-24-06; 8:45 am]

BILLING CODE 6717-01-P


[Federal Register Volume 82, Number 183 (Friday, September 22, 2017)]
[Rules and Regulations]
[Pages 44301-44304]
[FR Doc No: 2017-19767]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2016-9185; Product Identifier 2016-NM-077-AD; Amendment
39-19040; AD 2017-19-10]
RIN 2120-AA64

Airworthiness Directives; The Boeing Company Airplanes

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Final rule.

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

SUMMARY: We are adopting a new airworthiness directive (AD) for certain
The Boeing Company Model 757-200, -200PF, and -200CB series airplanes.
This AD was prompted by an analysis of the cam support assemblies of
the main cargo door (MCD) that indicated that the existing maintenance
program for the cam support assemblies is not adequate to reliably
detect cracks before two adjacent cam support assemblies could fail.
This AD requires an inspection to determine part numbers, repetitive
inspections to detect cracking of affected cam support assemblies of
the MCD, and replacement if necessary. We are issuing this AD to
address the unsafe condition on these products.

DATES: This AD is effective October 27, 2017.
    The Director of the Federal Register approved the incorporation by
reference of a certain publication listed in this AD as of October 27,
2017.

ADDRESSES: For service information identified in this final rule,
contact Boeing Commercial Airplanes, Attention: Contractual & Data
Services (C&DS), 2600 Westminster Blvd., MC 110-SK57, Seal Beach, CA
90740-5600; telephone<PHONE_NUMBER>; Internet https://www.myboeingfleet.com. You may view this service information at the
FAA, Transport Standards Branch, 1601 Lind Avenue SW., Renton, WA. For
information on the availability of this material at the FAA, call 425-
227-1221. It is also available on the Internet at http://www.regulations.gov by searching for and locating Docket No. FAA-2016-
9185.

Examining the AD Docket

    You may examine the AD docket on the Internet at http://www.regulations.gov by searching for and locating Docket No. FAA-2016-
9185; or in person at the Docket Management Facility between 9 a.m. and
5 p.m., Monday through Friday, except Federal holidays. The AD docket
contains this final rule, the regulatory evaluation, any comments
received, and other information. The address for the Docket Office
(phone:<PHONE_NUMBER>) is Docket Management Facility, U.S. Department of
Transportation, Docket Operations, M-30, West Building Ground Floor,
Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590.

FOR FURTHER INFORMATION CONTACT: Chandra Ramdoss, Aerospace Engineer,
Airframe Section, FAA, Los Angeles ACO Branch, 3960 Paramount
Boulevard, Lakewood, CA 90712-4137; phone:<PHONE_NUMBER>; fax: 562-627-
5210; email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

Discussion

    We issued a notice of proposed rulemaking (NPRM) to amend 14 CFR
part 39 by adding an AD that would apply to all The Boeing Company
Model 757-200, -200PF, and -200CB series airplanes. The NPRM published
in the Federal Register on October 4, 2016 (81 FR 68371) (``the
NPRM''). The NPRM was prompted by an analysis of the cam support
assemblies of the MCD that indicated that the existing maintenance
program for the cam support assemblies is not adequate to reliably
detect cracks before two adjacent cam support assemblies could fail.
The NPRM proposed to require an inspection to determine part numbers,
repetitive inspections to detect cracking of affected cam support
assemblies of the MCD, and replacement if necessary. We are issuing
this AD to detect and correct cracking of the cam support assemblies of
the MCD, which could result in reduced structural integrity of the MCD
and consequent rapid decompression of the airplane.

Comments

    We gave the public the opportunity to participate in developing
this final rule. The following presents the comments received on the
NPRM and the FAA's response to each comment.

Requests To Revise Applicability

    Boeing, Delta Air Lines (DAL), European Air Transport Leipzig GmbH
(EAT), DHL Express (DHL), FedEx Express (FedEx), and United Airlines
(UAL) requested that we revise the proposed AD applicability. DAL and
UAL requested that airplanes that do not have a MCD be excluded from
the AD applicability.
    Three of these commenters requested that the actions of the service
information be applicable only to

airplanes in the service information effectivity. These commenters
explained that the service information effectivity includes only
airplanes that have a MCD installed by Boeing, either as a Boeing
factory-delivered freighter or as a Boeing Supplemental Type
Certificate (STC)-converted freighter, and not airplanes that have been
converted to a freighter by a non-Boeing STC.
    EAT and DHL requested that we revise the applicability of the
proposed AD to exclude Model 757 airplanes with passenger to freighter
modification STC ST01529SE by Precision Conversions.
    FedEx requested that we either withdraw the NPRM and issue a new
one, to include a separate section for airplanes modified under VT
Mobile Aerospace Engineering STC ST03562AT, or exempt the airplanes
modified by that STC from the NPRM and issue a new NPRM for airplanes
modified by that STC. FedEx also requested that we revise the NPRM to
mandate, for Model 757-200 airplanes modified in accordance with STC
ST03562AT, VT Mobile Aerospace Engineering Service Bulletin MAE757SF-
SB-52-l 601, Revision 0, dated April 15, 2016, or a subsequent
revision, instead of Boeing Alert Service Bulletin 757-52A0094, dated
December 23, 2015. FedEx explained that the MCD that is installed by
the Precision Conversion STC is different than that installed by Boeing
or VT Mobile Aerospace Engineering and does not have the affected cam
support fittings installed. FedEx stated that it prefers the VT Mobile
Aerospace Engineering service information for modifying airplanes
instead of the Boeing service information, since Boeing does not
provide support for the VT Mobile Aerospace STC, and any discrepancies
or questions on the Boeing service information would be addressed by
Boeing based on goodwill, rather than by contractual agreement.
    We partially agree with the commenters' requests. We agree that the
unsafe condition does not apply to Model 757-200 airplanes that do not
have a MCD and to airplanes modified from passenger to freighter in
accordance with Precision Conversions STC ST01529SE. The unsafe
condition applies only to MCD cam support assemblies with the specified
part numbers.
    We disagree that the AD should apply only to Boeing converted
freighters. We also disagree that a separate AD should be issued to
address Model 757-200 freighters modified by STC ST03562AT or any of
the other passenger-to-freighter modification STCs because these
support assemblies having affected part numbers could be installed
during original aircraft manufacture, or during passenger-to-freighter
modification. The unsafe condition applies only to airplanes with
certain part number cam support assemblies installed, and it does not
apply to Model 757-200 airplanes that do not have a MCD.
    Paragraphs (g) and (h) of this AD list the part numbers of the cam
support assemblies that have the unsafe condition. We have confirmed
that the cam support assemblies having affected part numbers are not
installed on Model 757 airplanes as part of the Precision Conversions
STC ST01529SE passenger-to-freighter conversion. We have revised the
SUMMARY section, Discussion section, and paragraph (c) of this AD to
state that the AD applies to all Model 757-200, -200PF, and -200CB
series airplanes equipped with a MCD, except those airplanes that have
been converted from a passenger to freighter configuration in
accordance with STC ST01529SE.
    We expect that the actions specified in Boeing Alert Service
Bulletin 757-52A0094, Revision 2, dated May 2, 2017 (``ASB 757-52A0094,
R2''), can be accomplished on airplanes that are not identified in that
service information. In addition, we do not consider it appropriate to
include various provisions in an AD applicable only to an operator's
unique configuration of affected airplanes. However, if an operator
with a Model 757-200 freighter cannot accomplish the required actions
specified in the service information, or prefers to use different
service information that is specific to their design (such as FedEx's
request to use VT Mobile Aerospace Engineering Service Bulletin
MAE757SF-SB-52-l 601, Revision 0, dated April 15, 2016), an alternative
method of compliance (AMOC) can be requested in accordance with
paragraph (j) of this AD.

Requests To Revise the Compliance Time

    Boeing and FedEx requested that we revise the compliance time in
paragraph (g)(l) of the proposed AD from ``18,000 total flight cycles''
to ``18,000 door flight cycles.'' The commenters explained that some of
the affected airplanes have been converted from passenger to freighter
airplanes, and for these converted airplanes, the cam support
assemblies were installed at the time of the aircraft conversion, not
when the airplanes were produced. The commenters stated that, for these
converted airplanes, the initial compliance time for inspection should
be based on the number of flight cycles since the part has been
installed. In addition, Boeing stated that ASB 757-52A0094, R2, was
revised to change the inspection threshold for Boeing converted
freighter airplanes to total flight cycles after freighter conversion
redelivery.
    We agree with the commenters' request. For airplanes that have been
converted to freighters, the compliance time for the initial inspection
should be based on the number of cycles the cam support assembly has
been in service. We have revised paragraph (g)(1) of this AD
accordingly.

Request To Withdraw the NPRM and Reference Revised Service Information

    FedEx requested that we withdraw the NPRM and issue a new NPRM to
require compliance with ASB 757-52A0094, R2, instead of Boeing Alert
Service Bulletin 757-52A0094, dated December 23, 2015.
    We partially agree with the commenter's request. We agree with the
commenter's request to reference ASB 757-52A0094, R2, as the
appropriate source of service information. Revision 1 of Boeing Alert
Service Bulletin 757-52A0094, dated April 21, 2016 (``ASB 757-52A0094,
R1''), removed one airplane from the effectivity and updated some
references and publications affected. ASB 757-52A0094, R2, removed non-
Boeing-STC-converted freighter airplanes from the effectivity and
changed the initial compliance time for the converted freighter
airplanes to flight cycles after freighter conversion redelivery.
    We disagree with withdrawing the NPRM and reissuing a new NPRM
requiring compliance with ASB 757-52A0094, R2, because doing so would
unnecessarily delay issuance of the final rule. Additionally, the
compliance time can be corrected in the final rule without the need for
a supplemental NPRM since the corrected compliance time will provide
additional time for the converted freighter airplanes and will not
reduce the initial compliance time for any airplane. We have revised
this AD to refer to ASB 757-52A0094, R2, as the appropriate source of
service information. We have also added paragraph (i) to this AD to
provide credit for actions required by paragraph (h) of this AD, if
those actions were performed before the effective date of this AD using
Boeing Alert Service Bulletin 757-52A0094, dated December 23, 2015; or
ASB 757-52A0094, R1. We have redesignated subsequent paragraphs
accordingly.

Request To Correct Manual Reference in the Service Information

    United Parcel Service (UPS) requested that we revise paragraph (h)
of the

proposed AD to specify use of Airplane Maintenance Manual (AMM) 52-32-
11 in lieu of Component Maintenance Manual (CMM) 52-32-03 for the cam
and bell-crank assembly installation. UPS explained that Boeing Alert
Service Bulletin 757-52A0094, dated December 23, 2015, included an
incorrect manual reference.
    We partially agree with the commenter's request. We agree that the
manual reference is incorrect in Boeing Alert Service Bulletin 757-
52A0094, dated December 23, 2015. The incorrect reference was changed
in ASB 757-52A0094, R2, and, as explained previously, ASB 757-52A0094,
R2, is referenced as the appropriate source of service information in
this AD. No further change is necessary in this regard.

Conclusion

    We reviewed the relevant data, considered the comments received,
and determined that air safety and the public interest require adopting
this final rule with the changes described previously and minor
editorial changes. We have determined that these minor changes:
     Are consistent with the intent that was proposed in the
NPRM for correcting the unsafe condition; and
     Do not add any additional burden upon the public than was
already proposed in the NPRM.
    We also determined that these changes will not increase the
economic burden on any operator or increase the scope of this final
rule.

Related Service Information Under 1 CFR Part 51

    We reviewed Boeing Alert Service Bulletin 757-52A0094, Revision 2,
dated May 2, 2017. This service information describes procedures for an
ultrasonic inspection of the cam support assemblies of the main cargo
door, and replacement of the cam support assemblies. This service
information is reasonably available because the interested parties have
access to it through their normal course of business or by the means
identified in the ADDRESSES section.

Costs of Compliance

    We estimate that this AD will affect 212 airplanes of U.S.
registry.
    We estimate the following costs to comply with this AD:

                                                                     Estimated Costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
         Action                Labor cost         Parts cost                  Cost per product                          Cost on U.S. operators
--------------------------------------------------------------------------------------------------------------------------------------------------------
Inspection..............  6 work-hours x $85                $0  $510 per inspection cycle..................  $108,120 per inspection cycle.
                           per hour = $510 per
                           inspection cycle.
--------------------------------------------------------------------------------------------------------------------------------------------------------

    We estimate the following costs to do any necessary replacements
that would be required based on the results of the inspection. We have
no way of determining the number of aircraft that might need these
replacements:

                                               On-Condition Costs
----------------------------------------------------------------------------------------------------------------
                                                                                Cost per
                    Action                                 Labor cost               Parts cost        product
----------------------------------------------------------------------------------------------------------------
Replacement (per pair of cam support            60 work-hours x $85 per hour =           $15,298         $20,398
 assemblies).                                    $5,100.
----------------------------------------------------------------------------------------------------------------

Authority for This Rulemaking

    Title 49 of the United States Code specifies the FAA's authority to
issue rules on aviation safety. Subtitle I, section 106, describes the
authority of the FAA Administrator. Subtitle VII: Aviation Programs,
describes in more detail the scope of the Agency's authority.
    We are issuing this rulemaking under the authority described in
Subtitle VII, Part A, Subpart III, Section 44701: ``General
requirements.'' Under that section, Congress charges the FAA with
promoting safe flight of civil aircraft in air commerce by prescribing
regulations for practices, methods, and procedures the Administrator
finds necessary for safety in air commerce. This regulation is within
the scope of that authority because it addresses an unsafe condition
that is likely to exist or develop on products identified in this
rulemaking action.
    This AD is issued in accordance with authority delegated by the
Executive Director, Aircraft Certification Service, as authorized by
FAA Order 8000.51C. In accordance with that order, issuance of ADs is
normally a function of the Compliance and Airworthiness Division, but
during this transition period, the Executive Director has delegated the
authority to issue ADs applicable to transport category airplanes to
the Director of the System Oversight Division.

Regulatory Findings

    This AD will not have federalism implications under Executive Order
13132. This AD will not have a substantial direct effect 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.
    For the reasons discussed above, I certify that this AD:
    (1) Is not a ``significant regulatory action'' under Executive
Order 12866,
    (2) Is not a ``significant rule'' under DOT Regulatory Policies and
Procedures (44 FR 11034, February 26, 1979),
    (3) Will not affect intrastate aviation in Alaska, and
    (4) Will not have a significant economic impact, positive or
negative, on a substantial number of small entities under the criteria
of the Regulatory Flexibility Act.

List of Subjects in 14 CFR Part 39

    Air transportation, Aircraft, Aviation safety, Incorporation by
reference, Safety.

Adoption of the Amendment

    Accordingly, under the authority delegated to me by the
Administrator, the FAA amends 14 CFR part 39 as follows:

PART 39--AIRWORTHINESS DIRECTIVES

0
1. The authority citation for part 39 continues to read as follows:

    Authority:  49 U.S.C. 106(g), 40113, 44701.

Sec.  39.13  [Amended]

0
2. The FAA amends Sec.  39.13 by adding the following new airworthiness
directive (AD):

2017-19-10 The Boeing Company: Amendment 39-19040; Docket No. FAA-
2016-9185; Product Identifier 2016-NM-077-AD.

(a) Effective Date

    This AD is effective October 27, 2017.

(b) Affected ADs

    None.

(c) Applicability

    This AD applies to The Boeing Company Model 757-200, -200PF, and
-200CB series airplanes, certificated in any category, equipped with
a main cargo door (MCD), except those airplanes that have been
converted from a passenger to freighter configuration in accordance
with Supplemental Type Certificate ST01529SE (http://rgl.faa.gov/
Regulatory_and_Guidance_Library/rgstc.nsf/0/
9c0283b6ce0b9ff18625806b007340b9/$FILE/ST01529SE.pdf).

(d) Subject

    Air Transport Association (ATA) of America Code 52, Doors.

(e) Unsafe Condition

    This AD was prompted by an analysis of the cam support
assemblies of the MCD that indicated that the existing maintenance
program for the cam support assemblies is not adequate to reliably
detect cracks before two adjacent cam support assemblies could fail.
We are issuing this AD to detect and correct cracking of the cam
support assemblies of the MCD, which could result in reduced
structural integrity of the MCD and consequent rapid decompression
of the airplane.

(f) Compliance

    Comply with this AD within the compliance times specified,
unless already done.

(g) Inspection To Determine Part Numbers

    At the later of the times specified in paragraphs (g)(1) and
(g)(2) of this AD: Inspect the cam support assemblies of the MCD to
determine whether part number (P/N) 69-23588-5, 69-23588-6, 69-
23588-7, 69-23588-8, 69-23588-9, or 69-23588-10 is installed. A
review of airplane maintenance records is acceptable in lieu of this
inspection if the part number(s) of the cam support assemblies of
the MCD can be conclusively determined from that review.
    (1) Before the accumulation of 18,000 total flight cycles since
installation of the MCD. If the flight cycles since installation of
the MCD are not known, use total airplane flight cycles.
    (2) Within 2,743 flight cycles or 27 months after the effective
date of this AD, whichever occurs later.

(h) Inspections and Corrective Actions

    If, during the inspection required by paragraph (g) of this AD,
any cam support assembly of the MCD having P/N 69-23588-5, 69-23588-
6, 69-23588-7, 69-23588-8, 69-23588-9, or 69-23588-10 is determined
to be installed: At the later of the times specified in paragraphs
(g)(1) and (g)(2) of this AD, do an ultrasonic inspection to detect
cracking of the affected cam support assemblies of the MCD; and do
all applicable replacements; in accordance with the Accomplishment
Instructions of Boeing Alert Service Bulletin 757-52A0094, Revision
2, dated May 2, 2017. Do all applicable replacements before further
flight. Repeat the inspection thereafter at intervals not to exceed
6,000 flight cycles. Replacement of a cam support assembly of the
MCD does not terminate the repetitive inspections required by this
paragraph.

(i) Credit for Previous Actions

    This paragraph provides credit for actions required by paragraph
(h) of this AD, if those actions were performed before the effective
date of this AD using Boeing Alert Service Bulletin 757-52A0094,
dated December 23, 2015; or Boeing Alert Service Bulletin 757-
52A0094, Revision 1, dated April 21, 2016.

(j) Alternative Methods of Compliance (AMOCs)

    (1) The Manager, Los Angeles ACO Branch, FAA, has the authority
to approve AMOCs for this AD, if requested using the procedures
found in 14 CFR 39.19. In accordance with 14 CFR 39.19, send your
request to your principal inspector or local Flight Standards
District Office, as appropriate. If sending information directly to
the manager of the certification office, send it to the attention of
the person identified in paragraph (k)(1) of this AD. Information
may be emailed to<EMAIL_ADDRESS>    (2) Before using any approved AMOC, notify your appropriate
principal inspector, or lacking a principal inspector, the manager
of the local flight standards district office/certificate holding
district office.
    (3) An AMOC that provides an acceptable level of safety may be
used for any repair, modification, or alteration required by this AD
if it is approved by the Boeing Commercial Airplanes Organization
Designation Authorization (ODA) that has been authorized by the
Manager, Los Angeles ACO Branch, to make those findings. To be
approved, the repair method, modification deviation, or alteration
deviation must meet the certification basis of the airplane, and the
approval must specifically refer to this AD.
    (4) For service information that contains steps that are labeled
as Required for Compliance (RC), the provisions of paragraphs
(j)(4)(i) and (j)(4)(ii) of this AD apply.
    (i) The steps labeled as RC, including substeps under an RC step
and any figures identified in an RC step, must be done to comply
with the AD. If a step or substep is labeled ``RC Exempt,'' then the
RC requirement is removed from that step or substep. An AMOC is
required for any deviations to RC steps, including substeps and
identified figures.
    (ii) Steps not labeled as RC may be deviated from using accepted
methods in accordance with the operator's maintenance or inspection
program without obtaining approval of an AMOC, provided the RC
steps, including substeps and identified figures, can still be done
as specified, and the airplane can be put back in an airworthy
condition.

(k) Related Information

    (1) For more information about this AD, contact Chandra Ramdoss,
Aerospace Engineer, Airframe Section, FAA, Los Angeles ACO Branch,
3960 Paramount Boulevard, Lakewood, CA 90712-4137; phone: 562-627-
5239; fax:<PHONE_NUMBER>; email<EMAIL_ADDRESS>    (2) Service information identified in this AD that is not
incorporated by reference is available at the addresses specified in
paragraphs (l)(3) and (l)(4) of this AD.

(l) Material Incorporated by Reference

    (1) The Director of the Federal Register approved the
incorporation by reference (IBR) of the service information listed
in this paragraph under 5 U.S.C. 552(a) and 1 CFR part 51.
    (2) You must use this service information as applicable to do
the actions required by this AD, unless the AD specifies otherwise.
    (i) Boeing Alert Service Bulletin 757-52A0094, Revision 2, dated
May 2, 2017.
    (ii) Reserved.
    (3) For service information identified in this AD, contact
Boeing Commercial Airplanes, Attention: Contractual & Data Services
(C&DS), 2600 Westminster Blvd., MC 110-SK57, Seal Beach, CA 90740-
5600; telephone<PHONE_NUMBER>; Internet https://www.myboeingfleet.com.
    (4) You may view this service information at the FAA, Transport
Standards Branch, 1601 Lind Avenue SW., Renton, WA. For information
on the availability of this material at the FAA, call<PHONE_NUMBER>.
    (5) You may view this service information that is incorporated
by reference at the National Archives and Records Administration
(NARA). For information on the availability of this material at
NARA, call<PHONE_NUMBER>, or go to: http://www.archives.gov/federal-register/cfr/ibr-locations.html.

    Issued in Renton, Washington, on September 7, 2017.
Jeffrey E. Duven,
Director, System Oversight Division, Aircraft Certification Service.
[FR Doc. 2017-19767 Filed 9-21-17; 8:45 am]
 BILLING CODE 4910-13-P