Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 1 EPA/ OW/ OST/ HECD Final draft APPENDIX C. CYANATE I. Health Effects in Animals A. Short Term Exposure Cyanate. Toxicity studies for cyanate are summarized in Table C 1. No specific shortterm studies of cyanate by the inhalation or dermal route of exposure were located. However,

cyanic acid ( HOCN) is described as highly irritating to the eyes, skin, and mucous membranes ( O'Neil et al., 2001). The LD 50 of sodium cyanate by gavage is 1,500 mg/ kg ( corresponding to 975 mg cyanate/ kg). This is five times greater than that administered intraperitoneally, 310 mg sodium cyanate/ kg ( 202 cyanate/ kg) ( Haut et al., 1975). Haut et al. ( 1975) also reported that guinea pigs appeared to be more sensitive than rats to sodium cyanate.

Haut et al. ( 1975) conducted a series of experiments investigating the effects in rats of exposures to cyanate for increasing durations, and comparing the effects in rats and guinea pigs.

Haut et al. ( 1975) evaluated the short term effects of sodium cyanate in male albino rats.

Rats ( Walter Reed Carworth Farm strain; 27 treated animals) received sodium cyanate by gavage at doses of 0 or 400 mg sodium cyanate/ kg day ( 260 mg cyanate/ kg day) for 3 to 5 days. After sacrifice, the livers were removed and evaluated histopathologically and biochemically. Sixteen of Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 2 EPA/ OW/ OST/ HECD Final draft the 27 rats treated died within three to five days. The rats that died developed convulsions 15 to 30 minutes after dosing. Livers of the remaining treated animals demonstrated increased glycogen deposits and significantly decreased glucose 6 phosphatase activity in the livers compared to controls. Based on increased mortality, the dose of 260 mg cyanate/ kg day is considered to be a frank effect level ( FEL).

Haut et al. ( 1975) evaluated the short term effects of sodium cyanate in guinea pigs ( strain and sex not specified). Guinea pigs received sodium cyanate by gavage at doses of 100 mg/

kgday ( 65 mg cyanate/ kg day) for 7 days or 200 mg/ kg day ( 130 mg cyanate/ kg day) for 3 days ( 9 and 5 animals/ group, respectively). After sacrifice, the livers were evaluated histopathologically and biochemically. Four of the nine animals in the 65 mg cyanate/ kg day group died following treatment. The livers of the animals receiving this dose demonstrated inflammatory infiltration and patchy necrosis. All animals receiving the higher dose showed signs of neurotoxicity characterized by paralysis and lethargy. Based on increased mortality, the dose of 100 mg/ kg day ( 65 mg cyanate/ kg day) is considered to be a FEL.

Haut et al. ( 1975) investigated the effects of administering 0 or 200 mg sodium cyanate/ kg day ( 130 mg cyanate/ kg day) by gavage for 10 days to male albino rats ( Walter Reed Carworth Farm strain; 3 treated groups of 10 15 animals, numbers of controls not specified).

Body weight gain, food consumption, and clinical signs were recorded. Blood was collected for analysis of serum chemistry. After sacrifice, livers were removed and evaluated Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 3 EPA/ OW/ OST/ HECD Final draft histopathologically and biochemically. Body weight gain and food consumption were decreased in treated animals compared with controls; however, no information was presented on the statistical significance of these findings. Treated rats showed signs of neurotoxicity: one half of the rats developed neuromuscular paralysis of their hind legs and nearly all showed marked lethargy compared to controls. Treated rats had statistically significantly decreased blood sugar and increased serum glutamic oxaloacetic transaminase ( SGOT) levels compared with controls.

Livers of treated rats were characterized by perinuclear vacuolization, glycogen deposits, and increased mitotic activity. In addition, the activities of glucose 6 phosphatase and glucose 6

phosphate dehydrogenase ( G6PD) in the livers were significantly decreased. Based on neurotoxicity and liver toxicity, a LOAEL of 200 mg/ kg day ( 130 mg cyanate/ kg day) was identified.

Haut et al. ( 1975) also administered sodium cyanate by gavage at doses of 0 and 50 mg/ kg day ( 32 mg cyanate/ kg day) to male albino rats ( Walter Reed Carworth Farm strain,

number not specified) for 8 weeks. Body weight gain, food consumption, and clinical signs were recorded. Blood was collected for analysis of serum chemistry. After sacrifice, livers were removed and evaluated histopathologically and biochemically. Administration of sodium cyanate had no effect on body weight gain or food consumption. No differences were observed between treated animals and controls in serum chemistry parameters. Treated animals displayed a mild lethargy. Livers of treated animals appeared normal under light microscopy, but showed a slight increase in glycogen deposits. The authors noted that this dose of cyanate was well tolerated. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 4 EPA/ OW/ OST/ HECD Final draft Based on this, 50 mg/ kg day ( 32 mg cyanate/ kg day) was identified as the NOAEL. It should be noted, however, that mild lethargy was observed, and more sensitive indicators of neurotoxicity were not evaluated.

Graziano et al. ( 1973) evaluated the effect on thyroid function of short term oral exposure to sodium cyanate. Female Sprague Dawley female rats ( 10/ group) were fed either stock diet or diet containing 0.33% sodium cyanate for one month ( assuming a body weight of 0.204 kg and a daily food consumption of 0.02 kg/ day [ U. S. EPA, 1988], this is equivalent to a dose of 209 mg cyanate/ kg day). The authors measured the distribution of 125I among thyroid hormones and the ability of the thyroid to concentrate 125I. Administration of sodium cyanate had no effect on thyroid function. Based on this, 209 mg cyanate/ kg day was identified as a NOAEL.

Teisseire et al. ( 1986) injected albino rats ( strain and sex not specified) intraperitoneally with 0 or 60 mg sodium cyanate/ kg day ( 39 mg cyanate/ kg day) 5 times a week for either 3 weeks ( 15/ group) or 6 weeks ( 10/ group). After the 3 week treatment, the animals were anesthetized and evaluated for oxygen transport and hemodynamic parameters. The animals were then sacrificed and the heart excised and weighed. The animals treated for 6 weeks were weighed weekly, had blood drawn at regular intervals, and were evaluated for hematological parameters.

Treated rats had statistically significantly decreased body weight, decreased relative heart weight,

and decreased right ventricle weight compared to control rats. By 21 days of treatment, the treated rats had significantly increased hematological parameters compared with controls, Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 5 EPA/ OW/ OST/ HECD Final draft including hematocrit, hemoglobin concentration, number of red blood cells, and mean cell volume.

The study authors concluded that chronic sodium cyanate treatment produced hypoxia like effects ( i. e., induced polycythemia, pulmonary hypertension, right ventricular hypertrophy, and blunted pulmonary pressor response to acute hypoxia). Based on the decreased body weight and decreased relative heart weight, a LOAEL of 39 mg/ kg day was identified. However, this study was conducted using intraperitoneal injection, a route of exposure that is not relevant to environmental exposure. Therefore, this study provides an understanding of the potential hazard posed by cyanate, but is not suitable for dose response assessment.

Summary. The short term toxicity of cyanate has been evaluated in rats ( Haut et al.,

1975; Graziano et al., 1973; Teisseire et al., 1986) and guinea pigs ( Haut et al., 1975). Guinea pigs appear to be more sensitive to cyanate than rats. A dose of 260 mg cyanate/ kg day for 3 to 5 days resulted in increased mortality in rats, while a dose of only 65 mg cyanate/ kg day for 7 days resulted in increased mortality in guinea pigs ( Haut et al., 1975). Short term exposure to cyanate resulted in severe weight loss and signs of neurotoxicity ( convulsions, lethargy, and limb paralysis) and liver toxicity ( vacuolization and glycogen deposits). An oral dose of 130 mg cyanate/ kg day for 10 days was a LOAEL in rats, based on neurotoxicity and liver toxicity. An oral gavage dose of 32 mg cyanate/ kg day for 8 weeks was a NOAEL in rats ( Haut et al., 1975),

but mild lethargy was observed at this dose and no sensitive evaluation of neurotoxicity was conducted. Oral exposure to cyanate at a dose of 209 mg cyanate/ kg day had no effect on thyroid function ( Graziano et al., 1973). Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 6 EPA/ OW/ OST/ HECD Final draft B. Long Term Exposure Cyanate. In an 18 month study, Tellez Nagel et al. ( 1977) fed 15 Sprague Dawley rats a diet containing 0.3% sodium cyanate by weight ( based on an average food factor of 0.075 kg/ day for male and female Sprague Dawley rats in a chronic study [ U. S. EPA, 1988], equivalent to a dose of 145 mg cyanate/ kg day). The rats were examined and weighed bi weekly and half of the controls and treated rats were sacrificed at 18 months. The rats were sacrificed by perfusionfixation and the fixed brain, spinal cord, dorsal and ventral spinal roots, sciatic, peroneal, tibial and plantar nerves were examined by light and electron microscopy. All treated rats failed to gain as much weight as the controls and showed marked weakness of the hind limbs, which progressed to involve the upper extremities as well. A peripheral neuropathy involving mostly the lumbar roots and sciatic nerves was found along with vacuolization of myelin. The myelin sheaths were distended. Macrophages were actively splitting the myelin and phagocytizing the myelin remnants. Axoplasmic changes were subtle and consisted of accumulation of glycogen within vacuoles and occasional adaxonal invaginations of Schwann cell cytoplasm. Based on the demyelination of the peripheral axons, a LOAEL of 145 mg/ kg day was identified.

Kern et al. ( 1977) fed a total of 15 beagle dogs ( 11 females, 4 males) doses of 30 to 170 mg sodium cyanate/ kg day ( 20 to 111 mg cyanate/ kg day) 5 days/ week for 12 to 39 months. The administered dose varied depending on whether the dogs exhibited toxic effects. The dogs were examined and weighed monthly. Blood was obtained for a complete analysis; carbamylation was Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 7 EPA/ OW/ OST/ HECD Final draft evaluated based on levels of hydantoin residues. Ocular examinations were performed and at sacrifice the eyes were measured for cation concentration, reduced glutathione, and lens water.

Extracellular space was calculated and expressed as a percentage of total water in the lens.

Fourteen dogs developed cataracts. Five animals developed corneal lesions. Nearly all animals that developed cataracts showed signs of weight loss and nervous system ( tremors, seizure) or gastrointestinal ( vomiting, diarrhea) involvement. Younger animals appeared more susceptible to cataractogenic effect than older animals. Biochemical changes in the involved lens included an increase in intracellular sodium with a decrease in potassium, which the authors believed indicated increased leakiness of plasma membranes. Lens instability was also evidenced by a 61% increase in extracellular space. There was similarly a 34% decrease in intracellular lens glutathione, cation leakage, and a 12% increase in lactate leakage. Carbamylation was greater in dogs with corneal lesions than the cataractous group as a whole. A single dog received only the lowest dose of 20 mg cyanate/ kg day. The only effect seen at this dose was tremors; no lens effects were observed.

At the next higher dose of 58 mg cyanage/ kg day, weight loss, tremors, diarrhea, and lens effects were seen. Since animals that did not exhibit signs of toxicity at lower doses were given higher doses, it is reasonable to conclude that most of the dogs did not exhibit signs of toxicity at 20 mg cyanate/ kg day, and the single animal receiving the lowest dose can be considered a sensitive subject for clinical signs. Similarly, since this " sensitive" animal did not have weight loss or lens effects, it appears reasonable to suggest that the lens effects occurs at higher levels than tremors do in the sensitive population. Therefore, based on the tremors in this dog, supported by weight loss and cataracts at higher doses, a LOAEL of 20 mg cyanate/ kg day was identified in a sensitive Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 8 EPA/ OW/ OST/ HECD Final draft population.

Tellez et al. ( 1979) administered 0, 15, 25, or 35 mg sodium cyanate ( 0, 10, 16, or 23 mg cyanate/ kg day) to 11 adult pigtailed monkeys ( sex not reported) by subcutaneous injection for 2,

4, or 6 months. Following sacrifice, the fixed tissues of the cerebrum, brain stem, cerebellum, and spinal cord were examined by light and electron microscopy. The animals receiving 16 or 23 mg/ kg day developed a predominantly demyelinating lesion in the pyramidal tracts of the spinal cord. This was characterized by distension of the myelin sheaths and the presence of large intramyelinic spaces formed by myelin breakdown. No neuronal changes were observed in the motor cortex, basal ganglia, midbrain, medulla or anterior horn cells of the spinal cord. There was no peripheral neuropathy, and, except for an occasional distended fiber with dense bodies and whorls of neurofilaments, there was no axoplasmic damage. The controls and the monkeys maintained at 10 mg/ kg day displayed no clinical or anatomical abnormality associated with cyanate exposure. The authors concluded that cyanate produces myelin damage similar to that observed in the peripheral nervous system of the rat. However, in the monkey, this damage is located in the pyramidal tracts of the spinal cord. Based on the demyelinating lesions of the spinal cord, a NOAEL of 10 mg cyanate/ kg day and a LOAEL of 16 mg cyanate/ kg day were identified.

However, this study was conducted using subcutaneous injection, a route of exposure that is not relevant to environmental exposure. Therefore, this study provides an understanding of the potential hazard posed by cyanate, but is not suitable for dose response assessment. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 9 EPA/ OW/ OST/ HECD Final draft Summary. Long term studies of cyanate by the oral route of exposure are available in monkeys ( Tellez et al., 1979), rats ( Tellez Nagel et al., 1977), and dogs ( Kern et al., 1977). No data on the long term effects of cyanate by inhalation or dermal exposure are available. These studies are all limited for risk assessment purposes because they all only evaluated limited endpoints ( either neurotoxicity or cataracts). In addition, the monkeys were dosed by subcutaneous injection, which is not an environmentally relevant route of exposure. Nonetheless,

these studies confirm results observed in human case studies that long term exposure to cyanate results in severe weight loss, demyelination of either spinal cord ( monkeys) or peripheral nerves ( rats), and cataracts ( dogs). However, no data are available to rule out toxicity in other organ systems. The lowest LOAEL observed was 20 mg cyanate/ kg day in dogs ( Kern et al., 1977).

C. Reproductive/ Developmental Toxicity Graziano et al. ( 1973) examined the effects of cyanate on the reproductive capacity of mice. C57BL/ 6J mice ( 6 male/ female pairs/ group) were fed 1% sodium cyanate by weight ( assuming an average food factor of 0.19 for males and 0.20 for females [ U. S. EPA, 1988], this is equivalent to a dose of approximately 1235 and 1312 mg cyanate/ kg day for males and females,

respectively). The doses were administered beginning on the day of cohabitation, the day of cervical plug ( gestation day 0), or 7 or 14 days after the cervical plug. The authors observed the number of: successful matings, young born in each litter, young weaned; and the length of the estrus cycle. The birth weights of the litter were recorded and, at the conclusion of the study, a Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 10 EPA/ OW/ OST/ HECD Final draft histological examination was performed. There were no significant effects on the number of:

successful matings, young born and weaned, or the birth weight of the pups. In addition, there were no gross abnormalities in the pups. However, the cyanate fed females did not have any further pregnancies while maintained on the cyanate treatment. These mice had a prolonged anestrus cycle and came into estrus only occasionally and sporadically. The authors concluded that this block in reproductive capacity was reversible, since normal pregnancies and litters were observed following resumption of a regular diet. Histological examination revealed no lesions in the ovaries or testes. No other endpoints were evaluated. Based on a reduced reproductive capacity, a LOAEL of 1235 mg cyanate/ kg day was identified.

Summary. No standard multigeneration or developmental toxicity studies of cyanate are available. In the only study of reproductive effects, Graziano et al. ( 1973) found that a dose of approximately 1200  1300 mg cyanate/ kg day in the diet of male and female mice had no effect on the number of successful matings, the number of live pups born, or the birth weight of pups.

However, females maintained on this diet following the first pregnancy had a prolonged anestrus cycle and did not have any further pregnancies while exposed to cyanate. This effect was reversible; females were able to conceive after exposure to cyanate stopped.

D. Mutagenicity and Genotoxicity Only one study regarding the mutagenicity of cyanate was located. Melzer et al. ( 1983) Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 11 EPA/ OW/ OST/ HECD Final draft determined that although potassium cyanate was cytotoxic at concentrations

0.3 mM, it does not induce ouabain resistant mutants in Chinese Hamster V79 cells at any concentration.

E. Carcinogenicity No studies on the carcinogenicity of cyanate by any route of exposure were located.

II. Health Effects in Humans A. Case Reports and Clinical Studies A number of human clinical studies on orally administered cyanate are available, because cyanate underwent clinical trials in the 1970' s as a therapeutic agent to treat sickle cell anemia.

These studies are summarized in Table C 1. No studies on the dermal or inhalation effects of cyanate were located.

Peterson et al. ( 1974) and Ohnishi et al. ( 1975) examined the effects of sodium cyanate administered to patients with sickle cell anemia. Peterson et al. ( 1974) evaluated nerve conduction in 27 patients who were treated with cyanate to treat sickle cell anemia for periods ranging from 47 days to 749 days. The authors measured the maximum motor conduction velocities of the median, ulnar, common peroneal, and posterior tibial nerves; sensory latency Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 12 EPA/ OW/ OST/ HECD Final draft time; and cutaneous sensation ( measured in two cases prior to sural nerve biopsy). In 16 of the 27 patients, the results of the nerve conduction study were consistent with polyneuropathy.

These patients exhibited marked weakness of the upper and lower extremities, with distal weakness greater than proximal and right sided effects more prominent than the left. There was a decrease in touch pressure, joint position, and vibration sensations in the hands and feet. Patients had a broad based gait characteristic of foot drop. The proximal and distal muscles showed spontaneous fibrillations and a moderate to marked reduction of voluntary recruited motor unit potentials, some of which were irregular and slightly larger in amplitude. Twelve of the 16 patients showing nerve conduction abnormalities showed a severe weight loss. Children appeared to have a higher incidence of subnormal conduction velocities. The effects were reversible upon cessation of treatment. The authors concluded that the adverse effects were related to both the peak dose and total exposure time. In the 16 patients with nerve conduction abnormalities, the sodium cyanate dose ranged from 32 49 mg/ kg day, with a mean of 38 mg/ kg day ( 25 mg cyanate/ kg day). In the 11 patients without nerve conduction abnormalities, the sodium cyanate dose ranged from 28 to 45 mg/ kg day, with a mean of 33 mg/ kg day ( 21 mg cyanate/ kg day).

Therefore, based on the incidence of polyneuropathy and weight loss, the dose of 38 mg/ kg day ( 25 mg cyanate/ kg day) can be considered a LOAEL.

Ohnishi et al. ( 1975) conducted fascicular biopsies in two patients with sickle cell anemia who had been treated with sodium cyanate at doses of 41 and 44 mg/ kg day ( 26 and 28 mg cyanate/ kg day) for 440 and 600 days, respectively. The biopsies revealed a slight decrease in Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 13 EPA/ OW/ OST/ HECD Final draft density of large and small myelinated fibers. One of the two patients had an occasional fiber with axonal enlargement and thin myelin sheath. The most common abnormality in the patient who had an abnormally elevated touch pressure sensation threshold was segmental demyelination. The most common abnormality in the patient with normal touch pressure sensation threshold was the presence of linear rows of myelin ovoids. Ohnishi et al. ( 1975) concluded that axonal degeneration is the main pathological change in the sural nerves of patients with polyneuropathy resulting from cyanate ingestion.

In a drug trial, Charache et al. ( 1975) treated six sickle cell anemia patients with oral doses of 20 30 mg sodium cyanate/ kg day ( 13 19 mg cyanate/ kg day) for approximately 3 to 7 months. Hematologic and chemical determinations were conducted, irreversibly sickled cells were counted, and measurements of valine hydantoin were made. Four of the six patients exhibited signs of definite or suspected toxicity. One patient developed a worsening of an underlying psychiatric disorder. Another exhibited severe weight loss and a peculiar taste in her mouth. Two patients had decreased nerve conduction velocity after 6 and 7 months of treatment.

However, no baseline was established prior to initiation of the treatment. Of the two patients with decreased nerve conduction velocity, one was profoundly disabled by motor neuropathy that primarily affected his legs. In this patient, the neuropathy was reversible, since he regained the use of his legs after cyanate treatment was stopped. Based on peripheral neuropathy, a LOAEL of 13 mg cyanate/ kg day was identified. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 14 EPA/ OW/ OST/ HECD Final draft Nicholson et al. ( 1976) evaluated two patients who had been treated with orallyadministered sodium cyanate at 30 or 35 mg/ kg day ( 19 or 23 mg cyanate/ kg day) for six months.

Both patients developed bilateral posterior subcapsular cataracts. In one of the patients, the opacity of the lens regressed spontaneously 3 month after treatment was discontinued. By experimental design, one patient was crossed over to placebo therapy for 6 months, followed by another 6 month treatment course. Following the first treatment, no subjective change in visual function and acuity was noted, although small axial posterior subcapsular cataracts were noted.

In addition, the patient experienced a 7% weight loss. During the second course of treatment, the patient developed cataracts, but maintained his body weight. The authors also noted that the patient's nerve conduction was normal throughout treatment. No other toxicity endpoints were discussed. Based on the development of cataracts, a LOAEL of 19 mg cyanate/ kg day was identified.

B. Epidemiological Studies No epidemiological studies of cyanate were located.

C. Summary of Human Studies There are several clinical studies of oral exposure to cyanate, because sodium cyanate has been used to treat sickle cell anemia. The primary target of cyanate exposure is the peripheral Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 15 EPA/ OW/ OST/ HECD Final draft nervous system, resulting in peripheral neuropathy ( Peterson et al., 1974; Ohnishi et al., 1975;

Charache et al., 1975). This effect was characterized by decreased nerve conduction velocity,

altered gait, weakness, and decreased sensation in the hands and feet. Severe weight loss was also reported. All of the published studies tested only one dose and reported an effect at that dose. Exposures were to 13 29 mg cyanate/ kg day, for 47 749 days. Cataract formation has also been associated with ingestion of cyanate, at 20 mg cyanate/ kg day for 6 months ( Nicholson et al., 1976). No data on the effects of dermal or inhalation exposure to cyanate were located.

No epidemiological studies of cyanate were located.

III. Quantification of Toxicological Effects Methods for the quantification of toxicological effects are described in Section VIII. A of the main document. Health Advisories for cyanate are summarized in Table C 2.

A. Noncarcinogenic Effects A. 1. One day Health Advisory Cyanate. No suitable studies were located. The available studies are not appropriate as the basis for the One day HA, because only frank effect levels ( causing paralysis and death) were identified ( Haut et al., 1975). In the absence of adequate data, the Ten day HA value is Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 16 EPA/ OW/ OST/ HECD Final draft recommended as a conservative estimate of an appropriate one day HA value.

A. 2. Ten day Health Advisory Haut et al. ( 1975) observed mild lethargy and a slight increase in liver glycogen deposits in rats exposed by gavage for 8 weeks to 32 mg cyanate/ kg day. In light of the minimal and nonadverse nature of these effects, this dose can be considered a NOAEL. Graziano et al. ( 1973)

found no effect on thyroid function in rats administered 209 mg/ kg day for 1 month in diet.

Although the single dose tested was a NOAEL, the likely target organ ( nervous system) was not evaluated, limiting the reliability of the NOAEL. There are several human studies in which a single dose level of cyanate was tested for periods ranging from 3 months to 1 year as a treatment in people with sickle cell anemia ( Peterson et al., 1974; Ohnishi et al., 1975; Charache et al.,

1975; Nicholson et al., 1976). These studies identified LOAELs of 13 25 mg/ kg day, based on severe weight loss and peripheral neuropathy. None of these studies indicated the minimum duration of exposure at which these symptoms began to appear. It is unclear whether weight loss and neuropathy began to appear as early as after 10 days to a month of exposure, which is the appropriate study duration for developing the 10 day HA. However, human data are preferred over animal data as the basis for the ten day Health Advisory, therefore the Charache et al. ( 1975)

is judged as the most appropriate option for the derivation of the 10 day HA. Furthermore, the same Health Advisory would be developed if it were decided to default to the Longer term Health Advisory for the ten day value. Thus, the Ten day Health Advisory is based on a LOAEL of 13 Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 17 EPA/ OW/ OST/ HECD Final draft mg cyanate/ kg day reported by Charache et al. ( 1975) in a case study of three sickle cell anemia patients administered sodium cyanate for 3 7 months. Although there were only a few subjects in this study, the identified LOAEL is supported by a LOAEL of 25 mg cyanate/ kg day in a study of 27 people exposed for a year ( Peterson et al., 1974; Ohnishi et al., 1975); no corresponding NOAELs were identified. An uncertainty factor of 10 is used to account for the use of a LOAEL,

and a factor of 10 is used to protect sensitive populations. Neither the metabolism of cyanate nor the mechanism of action of cyanate appear to be related to hemoglobin, and so there is no reason to expect sickle cell anemia patients to constitute a sensitive population.

( 13 mg/ kg day) ( 10 kg) Ten day HA ( for a child) = = 1.3 mg/ L, rounded to 1 mg/ L ( 100)( 1 L/ day)

where:

13 mg/ kg day = LOAEL, based on the finding of severe weight loss and peripheral neuropathy in case studies of sickle cell anemia patients administered sodium cyanate for 3 7 months ( Charache et al., 1975).

10 kg = assumed body weight of a child.

100 = composite uncertainty factor, chosen to account for extrapolation from a LOAEL in humans and to protect sensitive subpopulations.

1 L/ day = assumed daily water consumption by a 10 kg child.

A. 3 Longer term Health Advisory No studies of suitable duration via an appropriate route of exposure that identified a Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 18 EPA/ OW/ OST/ HECD Final draft NOAEL were located in either humans or animals. However, there is a series of case studies in people with sickle cell anemia treated with cyanate at oral doses ranging from 13 to 25 mg cyanate/ kg day for 3 months to one year ( Peterson et al., 1974; Ohnishi et al., 1975; Charache et al., 1975; Nicholson et al., 1976). The adverse effects included peripheral neuropathy characterized by demyelination and cataracts. In all cases, these symptoms were preceded by severe weight loss. These findings are supported by a 6 month study in monkeys treated by subcutaneous injection which identified a NOAEL of 10 mg/ kg day and a LOAEL of 16 mg/

kgday based on demyelination of the spinal cord ( Tellez et al., 1979). No subchronic animal studies of cyanate conducted via the oral, inhalation, or dermal routes were identified. Therefore, these human studies can be used to develop a Longer term Health Advisory, based on a the lowest human LOAEL of 13 mg cyanate/ kg day ( Charache et al., 1975). An uncertainty factor of 10 is used to extrapolate from the LOAEL to a NOAEL, and a factor of 10 is used to protect sensitive individuals, in light of the absence of available data on human variability in toxicokinetics and toxicodynamics. In addition to the human data, the database for animal toxicity studies with cyanate via environmentally relevant routes includes chronic oral studies in rats ( Tellez Nagel et al., 1977) and dogs ( Kern et al., 1977). There is also a subchronic monkey study conducted by injection ( Tellez et al., 1979). There are, however, no reproductive or developmental toxicity studies of cyanate. Based on these considerations, an uncertainty factor of 3 is included for database deficiencies. The resulting composite uncertainty factor is 300.

( 13 mg/ kg day) ( 10 kg) Longer Term HA ( for a child) = = 0.43 mg/ L ( rounded to 0.4 mg/ L) ( 300)( 1 L/ day) Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 19 EPA/ OW/ OST/ HECD Final draft where:

13 mg/ kg day = LOAEL, based on finding of severe weight loss and peripheral neuropathy in case studies of sickle cell anemia patients administered sodium cyanate for 3 7 months ( Charache et al., 1975).

10 kg = assumed body weight of a child.

300 = composite uncertainty factor, chosen to account for extrapolation from a LOAEL, for protect sensitive subpopulations, and insufficiencies in the database ( lack of reproductive and developmental toxicity studies).

1 L/ day = assumed daily water consumption by a 10 kg child.

The Longer term HA for a 70 kg adult consuming 2 L/ day of water is calculated as follows:

( 13 mg/ kg day) ( 70 kg) Longer Term HA ( for an adult) = = 1.5 mg/ L ( rounded to 2 mg/ L) ( 300)( 2 L/ day)

where:

13 mg/ kg day = LOAEL, based on finding of severe weight loss and peripheral neuropathy in case studies of sickle cell anemia patients administered sodium cyanate for 3 7 months ( Charache et al., 1975).

70 kg = assumed body weight of an adult.

300 = composite uncertainty factor, chosen to account for extrapolation from a LOAEL, for protection of sensitive subpopulations, and insufficiencies in the database ( lack of reproductive and developmental toxicity studies).

2 L/ day = assumed daily water consumption by a 70 kg adult.

A. 4 Reference Dose, Drinking Water Equivalent Level, and Lifetime Health Advisory Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 20 EPA/ OW/ OST/ HECD Final draft No adequate studies of suitable duration conducted via an appropriate route of exposure that identified a NOAEL were located in either humans or animals. However, there is a series of case studies in people with sickle cell anemia treated with cyanate at oral doses ranging from 13 to 25 mg cyanate/ kg day for 3 months to one year ( Peterson et al., 1974; Ohnishi et al., 1975;

Charache et al., 1975; Nicholson et al., 1976). The adverse effects included peripheral neuropathy characterized by demyelination and cataracts. In all cases, these symptoms were preceded by severe weight loss. An 18 month rat study ( Tellez Nagel et al., 1977) confirmed the effects of severe weight loss and peripheral neuropathy, but the only dose tested, 145 mg cyanate/ kg day, was an order of magnitude greater than the doses causing similar effects in humans. A chronic oral study of dogs administered cyanate in capsules 5 times/ week for 12 38 months ( Kern et al., 1977) also demonstrated tremors in a single dog at 20 mg cyanate/ kg day.

Other dogs apparently tolerated this dose, and so were given higher doses of 58 mg cyanate/

kgday and higher, and exhibited weight loss, tremors, diarrhea, and cataracts. The RfD is based on the Charache et al. ( 1975) study, in light of the variability of doses administered to the dogs, and because it is more appropriate to base the RfD on human studies, when possible. Therefore, the cyanate RfD is based on the lowest human LOAEL of 13 mg cyanate/ kg day ( Charache et al.,

1975). A total of four uncertainty factors was used with this LOAEL. A factor of 10 each was used to account for human variability and use of a LOAEL. A factor of 3 was used to account for the fact that people in the studies had a less than lifetime exposure. This partial uncertainty factor was determined to be sufficient for subchronic to chronic extrapolation, given the support of the chronic dog study, which identified a LOAEL in an apparent sensitive population that is Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 21 EPA/ OW/ OST/ HECD Final draft comparable to the LOAELs seen in the human studies. An additional factor of 3 was used to account for deficiencies in the database ( the lack of reproductive and developmental toxicity studies of cyanate). A factor of 3 is appropriate to account for the absence of reproductive and developmental studies, in the presence of systemic toxicity studies in multiple species. A composite uncertainty factor of 1000 results.

Step 1: Determination of a RfD for Cyanate RfD = 13 mg/ kg day = 0.013 mg/ kg day, rounded to 0.01 mg/ kg day 1000 where:

13 mg/ kg day = LOAEL, based on finding of severe weight loss and peripheral neuropathy in case studies of sickle cell anemia patients administered sodium cyanate for 3 7 months ( Charache et al., 1975).

1000 = composite uncertainty factor for use of a LOAEL, for protection of sensitive individuals, use of a less than lifetime study and incomplete database ( lack of reproductive and developmental toxicity studies).

Step 2: Determination of a Drinking Water Equivalent Level ( DWEL) for Cyanate DWEL = ( 0.013 mg/ kg day) ( 70kg) = 0.46 mg/ L ( rounded to 0.5 mg/ L) ( 2 L/ day)

where:

0.013 mg/ kg day = RfD ( before rounding) 70 kg = assumed body weight of an adult 2 L/ day = assumed drinking water consumption of a 70 kg adult Step 3: Determination of Lifetime HA for Cyanate Lifetime HA = ( 0.46 mg/ L) ( 20%) = 0.092 mg/ L ( rounded to 90  g/ L) Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites C 22 EPA/ OW/ OST/ HECD Final draft where: 0.46 mg/ L = DWEL ( before rounding) 20% = assumed relative source contribution from water B. Carcinogenic Effects There are no cancer bioassays of cyanate. Cyanate was negative in the only genotoxicity study located, a mammalian gene mutation assay ( Melzer et al., 1983). Due to this lack of data,

cyanate is classified as Group D, Not Classifiable as to Human Carcinogenicity, using the U. S.

EPA ( 1986) guidelines. Using the U. S. EPA ( 1999) Draft Guidelines for Carcinogen Risk Assessment, the data are inadequate for an assessment of the human carcinogenic potential of cyanate. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites EPA/ OW/ OST/ HECD Final draft C 23 Table C 1. Summary of Oral Toxicity Studies for Cyanate.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg cyanate/

kg day LOAEL mg cyanate/

kg day Comments One Day HA Rat, Carworth Farm ( 27 males/ group) Haut et al.,

1975 0, 400 mg Na cyanate/ kg day ( 260 mg cyanate/ kg day) Gavage 3 5 days Inc mortality,

convulsions,

inc liver glycogen and dec liver G6P activity None 260 (

FEL) None Guinea Pig ( strain and sex not specified,

5/ group) Haut et al.,

1975 0, 200 mg Na cyanate/ kg day ( 130 mg cyanate/ kg day) Gavage 3 days Paralysis and lethargy None 200 mg/ kg day ( 130 mg cyanate/

kg day,

FEL) None Ten Day HA Rat ( 15/ group;

strain and sex not specified) Teisseire et al., 1986 0, 60 mg Na cyanate/ kg day ( 39 mg cyanate/ kg day) i. p. injection 5x/ week for 3 or 6 weeks Dec body weight, dec relative heart weight None 60 mg/

kgday ( 39 mg cyanate/

kg day) Route of exposure not relevant to environmental exposure, but provides information on hazard characterization Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites Table C 1. Summary of Oral Toxicity Studies for Cyanate.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg cyanate/

kg day LOAEL mg cyanate/

kg day Comments EPA/ OW/ OST/ HECD Final draft C 24 Guinea Pig ( strain and sex not specified,

9/ group) Haut et al.,

1975 0, 100 mg Na cyanate/ kg day ( 65 mg cyanate/ kg day) Gavage 7 days Death in 4/ 9;

liver inflammatory infiltration and necrosis None 100 mg/ kg day ( 65 mg cyanate/

kg day) None Rat, Carworth Farm ( males,

30 45) Haut et al.,

1975 0, 200 mg Na cyanate/ kg day ( 130 mg cyanate/ kg day) Gavage 10 days Dec body weight gain and food consumption.

lethargy and hindlimb paralysis.

liver vacuolation and glycogen deposits None 200 mg/ kg day ( 130 mg cyanate/

kg day) None Rat, Carworth Farm ( males,

numbers not specified) Haut et al.,

1975 0, 50 mg Na cyanate/ kg day ( 32 mg cyanate/ kg day) Gavage 8 weeks Mild lethargy,

slight inc in liver glycogen deposits 50 mg/

kgday ( 32 mg cyanate/

kg day) None None Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites Table C 1. Summary of Oral Toxicity Studies for Cyanate.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg cyanate/

kg day LOAEL mg cyanate/

kg day Comments EPA/ OW/ OST/ HECD Final draft C 25 Rat, Sprague

Dawley ( 10 females/

group) Graziano et al., 1973 0, 0.33% Na cyanate ( 209 mg cyanate/

kgday a Diet 1 month No effect on thyroid function ( iodine uptake or distribution of hormones) 209 mg/ kg day None No other endpoints evaluated in these animals; no information on possible neurological effects Dose calculated assuming a body weight of 0.204 kg and a daily food consumption of 0.02 kg/ day [ U. S. EPA,

1988]

Subchronic Human ( 27 patients) Peterson et al., 1974;

Ohnishi et al,

1975 28 49 mg sodium cyanate/ kg day,

( 18 32 mg cyanate/ kg day)

dose range for affected and unaffected subjects Oral Approximatel y 1 year Peripheral neuropathy characterized by demyelination and axonal degeneration None 38 mg/

kgday ( 25 mg cyanate/

kg day),

based on mean max. dose of affected group Case studies of people being treated with cyanate for sickle cell anemia. 16 of 27 people included in study developed neuropathy. Symptoms preceded by severe weight loss. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites Table C 1. Summary of Oral Toxicity Studies for Cyanate.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg cyanate/

kg day LOAEL mg cyanate/

kg day Comments EPA/ OW/ OST/ HECD Final draft C 26 Human ( 3 males, 3 females) Charache et al., 1975 20 30 mg sodium cyanate/ kg day ( 13 19 mg cyanate/ kg day) Oral Approximatel y 3 7 months Peripheral neuropathy None 20 mg/

kgday ( 13 mg cyanate / kg day) Case studies of 3 patients treated for sickle cell anemia with cyanate. Symptoms preceded by severe weight loss. Basis of 10 day HA,

longerterm HA and RfD in this Criteria Document.

Human ( 2 males) Nicholson et al., 1976 30, 35 mg sodium cyanate/ kg day ( 19, 23 mg cyanate/ kg day) Oral 6 months Cataracts None 30 mg/

kgday ( 19 mg cyanate/

kg day) Case studies of 2 patients treated for sickle cell anemia with cyanate. Symptoms preceded by severe weight loss.

Monkey, pigtailed Tellez et al,

1979 0, 15, 25, 35 mg Na cyanate/ kg day ( 0, 10, 16, 23 mg cyanate/

kgday Subcutaneous injection 2, 4, or 6 months Demyelination in spinal cord.

Lesions appeared earlier at higher doses. 15 mg/

kgday ( 10 mg cyanate/

kg day) 25 mg/

kgday ( 16 mg cyanate/

kg day) Route of exposure not relevant to environmental exposure, but provides infomation on hazard characterization Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites Table C 1. Summary of Oral Toxicity Studies for Cyanate.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg cyanate/

kg day LOAEL mg cyanate/

kg day Comments EPA/ OW/ OST/ HECD Final draft C 27 Chronic Rat, Sprague

Dawley ( 15/ group, sex not specified) Tellez Nagel et al., 1977 0.3% sodium cyanate ( 167 mg cyanate/

kgday Diet 18 months Dec body weight gain,

weakness and motor deficit of limbs,

100% incidence of peripheral neuropathy characterized by demyelination None 167 mg/ kg day Dose calculated based on an average food factor of 0.075 kg/ day for male and female Sprague Dawley rats in a chronic study [ U. S. EPA, 1988]

Dog, beagle ( 11 females, 4 males) Kern et al.,

1977 30 170 mg Na cyanate/ kg day ( 20 111 mg cyanate/ kg day) Capsules 5x/ week, 12

39 months Weight loss,

vomiting and diarrhea,

seizures and tremors, cataracts ( in all but the 1 dog on 30 mg/ kg day) None 30 mg/

kgday ( 20 mg cyanate/

kg day) Methods also describe rats exposed to 0.3%

diet for 12 months and monkeys exposed orally to 50 100 mg/ kg/ day for 36 months. Report indicates no effects in these other species,

but no data presented. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites Table C 1. Summary of Oral Toxicity Studies for Cyanate.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg cyanate/

kg day LOAEL mg cyanate/

kg day Comments EPA/ OW/ OST/ HECD Final draft C 28 Reproductive and Developmental Mouse, C57BL/ 6J ( 6 mated pairs/

group) Graziano et al., 1973 0, 1% Na cyanate ( 1235 mg cyanate/

kgday for males and 1312 mg cyanate/ kg day for females) Diet Animals started on test diet either on the day of cohabitation,

GD 0, GD 7,

or GD 14 and continued throughout pregnancy No effect on #

of successful matings, #

pups/ litter,

litter weight,

or pup gross abnormalities.

Prolonged anestrus and no subsequent litters. None 1235 mg cyanate/

kg day No other endpoints evaluated in this group; no information on signs of neurotoxicity. Dose calculated assuming an average food factor of 0.19 for males and 0.20 for females ( U. S.

EPA, 1988)

a assuming a body weight of 0.35 kg and food consumption of 0.03 kg/ day; ratio of cyanate to sodium cyanate is 0.65 Dec = decrease; FEL = frank effect level; GD = gestation day; Inc = Increase. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites EPA/ OW/ OST/ HECD Final draft C 29 Table C 2. Summary of Development of the Health Advisories for Cyanate Principal Study Critical Effect NOAEL/

BMDL LOAEL Uncertainty Factorsa RfD ( mg/ kg/ day) Health Advisory ( mg/ L)

Ten day Charache et al.,

1975 Severe weight loss, peripheral neuropathy, cataracts None 13 100 ( 10H, 10L) a N/ A 1 Longer term Charache et al.,

1975 Severe weight loss, peripheral neuropathy None 13 300 ( 10H, 3D, 10L) N/ A Child: 0.4 Adult: 2 Lifetime Charache et al.,

1975 Severe weight loss, peripheral neuropathy, cataracts None 13 1000 ( 10H, 3D, 10L,

3S) 0.01 0.09


[Federal Register Volume 83, Number 84 (Tuesday, May 1, 2018)]
[Notices]
[Pages 19136-19137]
[FR Doc No: 2018-09121]

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DEPARTMENT OF TRANSPORTATION

Federal Railroad Administration

[Docket Number FRA-2018-0034]

Petition for Waiver of Compliance

    Under part 211 of Title 49 Code of Federal Regulations (CFR), this
document provides the public notice that on March 14, 2018, BNSF
Logistics (BNSF-L) petitioned the Federal Railroad Administration (FRA)
for a waiver of compliance from certain provisions of the Federal
railroad safety regulations contained at 49 CFR part 231, Railroad
Safety Appliance Standards, and Association of American Railroads (AAR)
Standard S-2044, Appendix D1, which governs the Safety Appliances for
Flatcars with Full Decks. FRA assigned the petition Docket Number FRA-
2018-0034.
    BNSF-L seeks relief to allow the transport of wind towers and wind
turbine blades by removing tall hand grabs at the corners of flatcars
that can foul the loaded cars with the towers and blades. Specifically,
BNSF-L proposes to:
     Remove any tall handgrabs that could be damaged by lading
during the initial loading.
     Provide formal, engineered storage on each car for the
removed tall handgrabs.
     Add a handgrab to the side sill that extends at least 6''
above the deck and is between 27'' to 34'' above the sill step.
     Apply decals stating that ``This location not suitable for
riding'' to mark these locations.
     Disable the coupler on both cars where the overhang is
located to prevent uncoupling. Note that in many cases this location is
equipped with a drawbar instead of couplers.
     Reapply standard safety appliances and remove the decals
only when car is released from unit wind service.
    BNSF-L believes this proposal will avoid damage to safety
appliances and cargo.
    A copy of the petition, as well as any written communications
concerning the petition, is available for review online at
www.regulations.gov and in person at the U.S. Department of
Transportation's (DOT) Docket Operations Facility, 1200 New Jersey
Avenue SE, W12-140, Washington, DC 20590. The Docket Operations
Facility is open from 9 a.m. to 5 p.m., Monday through Friday, except
Federal Holidays.
    Interested parties are invited to participate in these proceedings
by submitting written views, data, or comments. FRA does not anticipate
scheduling a public hearing about these proceedings since the facts do
not appear to warrant a hearing. If any interested parties desire an
opportunity for oral comment and a public hearing, they should notify
FRA, in writing, before the end of the comment period and specify the
basis for their request.
    All communications concerning these proceedings should identify the
appropriate docket number and may be submitted by any of the following
methods:
     Website: http://www.regulations.gov. Follow the online
instructions for submitting comments.
     Fax:<PHONE_NUMBER>.
     Mail: Docket Operations Facility, U.S. Department of
Transportation, 1200 New Jersey Avenue SE, W12-140, Washington, DC
20590.

     Hand Delivery: 1200 New Jersey Avenue SE, Room W12-140,
Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday,
except Federal Holidays.
    Communications received by June 15, 2018, will be considered by FRA
before final action is taken. Comments received after that date will be
considered if practicable.
    Anyone can search the electronic form of any written communications
and comments received into any of our dockets by the name of the
individual submitting the comment (or signing the document, if
submitted on behalf of an association, business, labor union, etc.).
Under 5 U.S.C. 553(c), DOT solicits comments from the public to better
inform its processes. DOT posts these comments, without edit, including
any personal information the commenter provides, to
www.regulations.gov, as described in the system of records notice (DOT/
ALL-14 FDMS), which can be reviewed at https://www.transportation.gov/privacy. See also https://www.regulations.gov/privacyNotice for the
privacy notice of regulations.gov.

    Issued in Washington, DC.
Robert C. Lauby,
Associate Administrator for Railroad Safety, Chief Safety Officer.
[FR Doc. 2018-09121 Filed 4-30-18; 8:45 am]
BILLING CODE 4910-06-P


[Federal Register Volume 88, Number 64 (Tuesday, April 4, 2023)]
[Rules and Regulations]
[Page 19857]
[FR Doc No: 2023-06836]

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DEPARTMENT OF HOMELAND SECURITY

Coast Guard

33 CFR Part 100

[Docket No. USCG-2023-0224]

Special Local Regulations Northern California and Lake Tahoe Area
Annual Marine Events; Opening Day on San Francisco Bay, San Francisco,
CA

AGENCY: Coast Guard, DHS.

ACTION: Notification of enforcement of regulation.

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SUMMARY: The Coast Guard will enforce the special local regulations for
the annual Opening Day on the San Francisco Bay Boat Parade on April
30, 2023 to provide for the safety of life on navigable waterways in
the San Francisco Bay during this event. Our regulation for marine
events in Northern California identifies the regulated area for this
event in San Francisco, CA. During the enforcement period, unauthorized
persons or vessels are prohibited from entering into, transiting
through, or loitering or anchoring in the regulated area, unless
authorized by the designated Patrol Commander (PATCOM) or other
Federal, State, or local law enforcement agencies on scene to assist
the Coast Guard in enforcing the regulated area.

DATES: The regulations in 33 CFR 100.1103 will be enforced for the
location in Table 1 to Sec.  100.1103, Item number 2 from noon to 3
p.m. on April 30, 2023.

FOR FURTHER INFORMATION CONTACT: If you have questions about this
notification of enforcement, call, or email MST1 Shannon Curtaz-Milian,
Sector San Francisco Waterways Management, U.S. Coast Guard; telephone
(415) 399-7440, email [email protected].

SUPPLEMENTARY INFORMATION: The Coast Guard will enforce the special
local regulations in 33 CFR 100.1103, Table 1 to Sec.  100.1103, Item
number 2 for the Opening Day on San Francisco Bay regulated area from
noon to 3 p.m. on April 30, 2023. This action is being taken to provide
for the safety of life on navigable waterways during this event. Our
regulation for marine events within Northern California, Sec.
100.1103, specifies the location of the regulated area for the Opening
Day on San Francisco Bay Boat Parade which encompasses portions of the
San Francisco Bay. During the enforcement period, the regulated area
will be in effect in the navigable waters, from surface to bottom,
defined by a line drawn from Fort Point; thence easterly approximately
5,000 yards; thence easterly to the Blossom Rock Bell Buoy; thence
westerly to the Northeast corner of Pier 39; thence returning along the
shoreline to the point of origin.
    During the enforcement period, under the provisions of 33 CFR
100.1103(b), if you are the operator of a vessel in the regulated area
you must comply with directions from the Patrol Commander (PATCOM) or
any other Official Patrol, defined as a Federal, State, or local law
enforcement agency on scene to assist the Coast Guard in enforcing the
regulated area. During the enforcement period, if you are the operator
of a vessel that participates in the marine event within the regulated
area, you must follow the parade route established by the marine event
sponsor, be capable of maintaining an approximate speed of 6 knots, and
comply with directions from the Patrol Commander or other Official
Patrol. The PATCOM or Official Patrol may, upon request, allow the
transit of commercial vessels through regulated areas when it is safe
to do so.
    In addition to this notification of enforcement in the Federal
Register, the Coast Guard plans to provide notification of this
enforcement period via the Local Notice to Mariners. If the Captain of
the Port determines that the regulated area need not be enforced for
the full duration stated in this notice, a Broadcast Notice to Mariners
or other marine broadcast may be used to grant general permission to
enter the regulated area.

    Dated: March 22, 2023.
Taylor Q. Lam,
Captain, U.S. Coast Guard, Captain of the Port San Francisco.
[FR Doc. 2023-06836 Filed 4-3-23; 8:45 am]
BILLING CODE 9110-04-P