[Federal Register Volume 88, Number 120 (Friday, June 23, 2023)]
[Notices]
[Pages 41099-41100]
[FR Doc No: 2023-13380]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. CP23-494-000]

ANR Pipeline Company; Notice of Request Under Blanket
Authorization and Establishing Intervention and Protest Deadline

    Take notice that on June 7, 2023, ANR Pipeline Company (ANR), 700
Louisiana Street, Suite 1300, Houston, Texas 77002-2700, filed in the
above referenced docket, a prior notice request pursuant to sections
157.205 and 157.213(b) of the Commission's regulations under the
Natural Gas Act (NGA), and ANR's blanket certificate issued in Docket
No. CP82-480-000, for authorization to construct and operate three new
injection/withdrawal storage wells, associated storage field pipelines,
and appurtenances, located in the Lincoln-Freeman Storage Field. The
above facilities are in Clare County, Michigan. The project will allow
ANR to maintain overall storage field performances; The proposed new
wells will restore deliverability lost due to the geologic degradation
overtime and deliverability lost from wells that have been previously
plugged and abandoned due to integrity concerns and poor deliverability
performance. The estimated cost for the project is approximately $7.7
million, all as more fully set forth in the request which is on file
with the Commission and open to public inspection.
    In addition to publishing the full text of this document in the
Federal Register, the Commission provides all interested persons an
opportunity to view and/or print the contents of this document via the
internet through the Commission's Home Page (www.ferc.gov) using the
``eLibrary'' link. Enter the docket number excluding the last three
digits in the docket number field to access the document. At this time,
the Commission has suspended access to the Commission's Public
Reference Room. For assistance, contact the Federal Energy Regulatory
Commission at [email protected] or call toll-free, (886) 208-
3676 or TTY<PHONE_NUMBER>.
    Any questions concerning this request should be directed to David
A. Alonzo, Manager, Project Determinations, ANR Pipeline Company, 700
Louisiana Street, Suite 1300, Houston, Texas 77002-2700, (832) 320
5477, [email protected].

Public Participation

    There are three ways to become involved in the Commission's review
of this project: you can file a protest to the project, you can file a
motion to intervene in the proceeding, and you can file comments on the
project. There is no fee or cost for filing protests, motions to
intervene, or comments. The deadline for filing protests, motions to
intervene, and comments is 5:00 p.m. Eastern Time on August 15, 2023.
How to file protests, motions to intervene, and comments is explained
below.
    The Commission's Office of Public Participation (OPP) supports
meaningful public engagement and participation in Commission
proceedings. OPP can help members of the public, including landowners,
environmental justice communities, Tribal members and others, access
publicly available

information and navigate Commission processes. For public inquiries and
assistance with making filings such as interventions, comments, or
requests for rehearing, the public is encouraged to contact OPP at
(202) 502-6595 or [email protected].

Protests

    Pursuant to section 157.205 of the Commission's regulations under
the NGA,\1\ any person \2\ or the Commission's staff may file a protest
to the request. If no protest is filed within the time allowed or if a
protest is filed and then withdrawn within 30 days after the allowed
time for filing a protest, the proposed activity shall be deemed to be
authorized effective the day after the time allowed for protest. If a
protest is filed and not withdrawn within 30 days after the time
allowed for filing a protest, the instant request for authorization
will be considered by the Commission.
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    \1\ 18 CFR 157.205.
    \2\ Persons include individuals, organizations, businesses,
municipalities, and other entities. 18 CFR 385.102(d).
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    Protests must comply with the requirements specified in section
157.205(e) of the Commission's regulations,\3\ and must be submitted by
the protest deadline, which is August 15, 2023. A protest may also
serve as a motion to intervene so long as the protestor states it also
seeks to be an intervenor.
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    \3\ 18 CFR 157.205(e).
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Interventions

    Any person has the option to file a motion to intervene in this
proceeding. Only intervenors have the right to request rehearing of
Commission orders issued in this proceeding and to subsequently
challenge the Commission's orders in the U.S. Circuit Courts of Appeal.
    To intervene, you must submit a motion to intervene to the
Commission in accordance with Rule 214 of the Commission's Rules of
Practice and Procedure \4\ and the regulations under the NGA \5\ by the
intervention deadline for the project, which is August 15, 2023. As
described further in Rule 214, your motion to intervene must state, to
the extent known, your position regarding the proceeding, as well as
your interest in the proceeding. For an individual, this could include
your status as a landowner, ratepayer, resident of an impacted
community, or recreationist. You do not need to have property directly
impacted by the project in order to intervene. For more information
about motions to intervene, refer to the FERC website at https://www.ferc.gov/resources/guides/how-to/intervene.asp.
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    \4\ 18 CFR 385.214.
    \5\ 18 CFR 157.10.
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    All timely, unopposed motions to intervene are automatically
granted by operation of Rule 214(c)(1). Motions to intervene that are
filed after the intervention deadline are untimely and may be denied.
Any late-filed motion to intervene must show good cause for being late
and must explain why the time limitation should be waived and provide
justification by reference to factors set forth in Rule 214(d) of the
Commission's Rules and Regulations. A person obtaining party status
will be placed on the service list maintained by the Secretary of the
Commission and will receive copies (paper or electronic) of all
documents filed by the applicant and by all other parties.

Comments

    Any person wishing to comment on the project may do so. The
Commission considers all comments received about the project in
determining the appropriate action to be taken. To ensure that your
comments are timely and properly recorded, please submit your comments
on or before August 15, 2023. The filing of a comment alone will not
serve to make the filer a party to the proceeding. To become a party,
you must intervene in the proceeding.

How To File Protests, Interventions, and Comments

    There are two ways to submit protests, motions to intervene, and
comments. In both instances, please reference the Project docket number
CP23-494-000 in your submission.
    (1) You may file your protest, motion to intervene, and comments by
using the Commission's eFiling feature, which is located on the
Commission's website (www.ferc.gov) under the link to Documents and
Filings. New eFiling users must first create an account by clicking on
``eRegister.'' You will be asked to select the type of filing you are
making; first select ``General'' and then select ``Protest'',
``Intervention'', or ``Comment on a Filing''; or \6\
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    \6\ Additionally, you may file your comments electronically by
using the eComment feature, which is located on the Commission's
website at www.ferc.gov under the link to Documents and Filings.
Using eComment is an easy method for interested persons to submit
brief, text-only comments on a project.
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    (2) You can file a paper copy of your submission by mailing it to
the address below. Your submission must reference the Project docket
number CP23-494-000.
    To file via USPS: Kimberly D. Bose, Secretary, Federal Energy
Regulatory Commission, 888 First Street NE, Washington, DC 20426.
    To file via any other method: Kimberly D. Bose, Secretary, Federal
Energy Regulatory Commission, 12225 Wilkins Avenue, Rockville, Maryland
20852.
    The Commission encourages electronic filing of submissions (option
1 above) and has eFiling staff available to assist you at (202) 502-
8258 or [email protected].
    Protests and motions to intervene must be served on the applicant
either by mail or email (with a link to the document) at: David A.
Alonzo, Manager, Project Determinations, ANR Pipeline Company, 700
Louisiana Street, Suite 1300, Houston, Texas 77002-2700, or by
[email protected]. Any subsequent submissions by an intervenor
must be served on the applicant and all other parties to the
proceeding. Contact information for parties can be downloaded from the
service list at the eService link on FERC Online.

Tracking the Proceeding

    Throughout the proceeding, additional information about the project
will be available from the Commission's Office of External Affairs, at
(866) 208-FERC, or on the FERC website at www.ferc.gov using the
``eLibrary'' link as described above. The eLibrary link also provides
access to the texts of all formal documents issued by the Commission,
such as orders, notices, and rulemakings.
    In addition, the Commission offers a free service called
eSubscription which allows you to keep track of all formal issuances
and submittals in specific dockets. This can reduce the amount of time
you spend researching proceedings by automatically providing you with
notification of these filings, document summaries, and direct links to
the documents. For more information and to register, go to
www.ferc.gov/docs-filing/esubscription.asp.

    Dated: June 16, 2023.
Kimberly D. Bose,
Secretary.
[FR Doc. 2023-13380 Filed 6-22-23; 8:45 am]
BILLING CODE 6717-01-P


Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 1 EPA/ OW/ OST/ HECD Final draft APPENDIX E. HYDROGEN CHLORIDE I. Health Effects in Animals A. Short Term Exposures Using the toxicity of HCl to evaluate the toxic potential of cyanogen chloride is somewhat problematic. As discussed in Chapter 3, essentially all pathways for cyanogen chloride metabolism result in the production of HCl. However, using the toxicity of ingested HCl to estimate the toxicity of HCl formed in the body from cyanogen chloride is problematic, in light of the acidic pH of the stomach and our lack of quantitative knowledge of the percentage of ingested HCl that is absorbed from the stomach. HCl could form in the blood from reaction of glutathione with cyanogen chloride, resulting in a toxic effect from the lowered pH, but quantitatively evaluating that toxic potential is difficult. This latter issue was addressed further in Chapter 7 of the main document and in Section 3 of this appendix.

Oral toxicity studies for HCl are summarized in Table E 1, and inhalation studies are summarized in Table E 2. HCl is highly irritating and corrosive. The primary target of inhalation exposure is the nasal tract, although high exposures can also damage the lungs. Sensory irritation and pulmonary irritation have also been observed. The only short term study of oral exposure to HCl was a study of HCl used in the water mixed with feed for 14 days ( Throssell et al., 1996). Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 2 EPA/ OW/ OST/ HECD Final draft No studies on the effects in animals of acute exposure to HCl via the oral or dermal routes were located, but sufficiently high concentrations would be expected to be corrosive at the site of contact ( e. g., the trachea for oral exposure and the skin for dermal exposure).

Throssell et al. ( 1996) investigated the renal effects of metabolic acidosis on groups of 12 female Wistar rats. The animals were fed a powdered diet containing 20% casein as a paste mixed with water ( 1/ 1 w/ w) and 2% methylcellulose for a 2 week induction period prior to dosing. The control animals received plain water mixed with the feed for the rest of the study,

while the experimental group then received the same feed mixed with 0.8 M HCl for 14 days.

Twenty four hour urine samples were collected at 7 and 14 days. The study authors calculated that the rats received a mean daily HCl dose of 19.7 mmol. Using the reported body weight of 200 g, this corresponds to a dose of approximately 3600 mg/ kg day. There was a statistically significant, 5 fold increase in urine volume in the acidotic animals compared to baseline. Urine pH decreased slightly and nonsignificantly, while there was a marked, statistically significant increase in urinary protein excretion, as well as in daily excretion of lysozyme, N acetyl glucosaminidase ( NAG), and albumin, with a smaller rise in immunoglobulin G ( IgG) excretion.

Acidosis was confirmed by arterial blood gas measurements. Body weight of the acidotic rats was comparable to controls at baseline, but was significantly lower ( by 15%) after two weeks;

kidney weights were increased by 15%. There were, however, no structural lesions apparent on histopathologic examination of the kidney, although the density of tubular nuclei was significantly decreased. Among the acidotic rats, staining of tubular cells with antibody to the Tamm Horsfall Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 3 EPA/ OW/ OST/ HECD Final draft protein ( THP) was less prominent than in controls, but THP positive tubular casts were observed,

suggesting tubular injury. The study authors interpreted the decreased tubular nuclear density as suggesting that tubular cell hypertrophy was the predominant mechanism of the increased kidney size. Overall, the results indicated that the renal tubule was the primary target of acidosis in the kidney.

In an attempt to determine the HCl hazard at a missile test firing site, Darmer et al. ( 1974)

calculated 30 minute LC 50 values for Sprague Dawley derived CFE rats and ICR derived CF 1 mice of 4701 and 2644 ppm ( 7018 and 3947 mg/ m3), respectively. The LC 50 values for 5 minute exposures were 40,989 ( rat) and 13,745 ppm ( mice) ( corresponding to 61,190 and 20,519 mg/ m3). The animals were monitored for 7 days after the exposure. Thus, it appeared that mice are 2 to 3 times more sensitive than rats to the lethal effects of HCl exposure. Similar LC 50 values were calculated for rats and mice exposed to a fine aerosol of HCl ( 64% of droplets

1  m,

99.9% of droplets

5  m). Histopathological examination revealed lesions of the respiratory tract, including the lung and nose, but not other tissues.

In a short term study, lightly anesthetized baboons ( 3 males/ group) were exposed to nominal concentrations of 0, 500, 5000, or 10,000 ppm HCl ( 0, 746, 7460, or 14,900 mg/ m3) for 15 minutes and observed for 3 months ( Kaplan, 1987; Kaplan et al., 1988). A concentrationrelated increase in respiratory frequency and minute volume was observed during exposure, but the tidal volume was unaffected. Despite the increased minute volume, the two higher Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 4 EPA/ OW/ OST/ HECD Final draft concentrations caused decreased arterial PO 2 during exposure and for at least 10 minutes postexposure but follow up pulmonary function and blood gas measurements at 3 days or 3 months following exposure did not show any abnormalities. The study authors noted that no mortality was observed in this study, while much lower concentrations are lethal to mice. In light of the similarity of the structure and complexity of the upper airways of the baboon and the human child,

baboons would be expected to resemble humans more than mice would. ( The complexity of the upper airways is related to the degree of scrubbing of inhaled irritants, and increases with age in humans.) On the other hand, the study authors noted the contrast between the increased respiratory rate seen in baboons and the reflex inhibition of respiratory rate due to trigeminalnerve stimulation seen in rodents. In a separate experiment ( Kaplan, 1987), baboons ( 1 animal/ concentration) were exposed to one of eight concentrations of HCl ranging from 190 to 17,290 ppm ( 284 to 25,800 mg/ m3) for 5 minutes, and then tested for avoidance/ escape performance. No effect on this endpoint was observed in the baboons, or in rats exposed for 5 minutes at one of 12 concentrations ( 1 rat/ concentration) ranging from 11,800 ppm ( 17,600 mg/ m3) to a lethal concentration of 76,730 ppm ( 114,500 mg/ m3). The baboons exposed to the two highest concentrations died of bacterial pneumonia several weeks after exposure.

Several studies evaluated the concentrations at which HCl causes sensory irritation.

Sensory irritation is defined as the stimulation of the trigeminal nerve endings in the cornea and nasal mucosa, causing a stinging sensation. In laboratory animals, sensory irritation causes a short pause in breathing following each inspiration, resulting in decreased respiratory rate and a Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 5 EPA/ OW/ OST/ HECD Final draft lengthened expiratory phase. By contrast, pulmonary irritation includes an initial increase in respiratory rate followed by a decreased rate. The decreased respiratory rate with pulmonary irritation is due to a pause following each expiration, as a result of stimulation of irritant receptors within the lung. Sensory irritation is appropriate as an indication of a chemical's potential for respiratory tract irritation, but not for dose response assessment ( U. S. EPA, 1994).

Burleigh Flayer et al. ( 1985) exposed groups of 4 8 male English smooth haired guinea pigs to 0, 320, 680, 1040, or 1380 ppm HCl ( 0, 480, 1015, 1550, or 2060 mg/ m3) for 30 minutes,

and measured respiratory rate and induction of sensory or pulmonary irritation. Deaths were observed in 3/ 8 animals at the high concentration and in 2/ 8 animals ( after exposure termination)

at 1040 ppm. For sensory irritation, the concentration duration response relationship was not linear with time. Sensory irritation appeared at 6 minutes at 320 ppm ( 480 mg/ m3), but occurred almost immediately at all higher concentrations ( 680 1380 ppm). By contrast, time to pulmonary irritation decreased linearly with concentration. Guinea pigs exposed to 1040 ppm were sacrificed at 2 and 15 days post exposure. In contrast to the results of Buckley et al. ( 1984), lung injury was observed at this lethal concentration, including multifocal acute alveolitis, congestion, and squamous metaplasia with loss of cilia in the larger conducting airways at 2 days post exposure.

Mild bronchitis and lymphoid hyperplasia were observed at 15 days post exposure. Corneal opacities were also observed. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 6 EPA/ OW/ OST/ HECD Final draft Barrow et al. ( 1977) evaluated sensory irritation in a similar study, conducted in male Swiss Webster mice ( 4/ group). The concentration eliciting a 50% decrease in respiratory rate ( i. e., the RD 50) was 309 ppm ( 461 mg/ m3). Histopathological analysis was not conducted as part of this study.

Buckley et al. ( 1984) attempted to determine the potential for pathologic damage following exposure to sensory irritants at the RD 50. Based on the mouse RD 50 for HCl of 309 ppm, a group of 16 24 male Swiss Webster mice were exposed for 3 days, 6 hours/ day to a timeweighted average concentration of 304 ppm ( range 295 310 ppm) HCl ( 454 mg/ m3). ( The study reported the results for a number of different chemicals, and it was unclear how many animals were tested with HCl.) Half the group was sacrificed immediately after the termination of exposure, and half were necropsied 3 days post exposure; the respiratory tract was examined histopathologically in both groups. Only three exposures were conducted ( as opposed to five for other irritants), because of a high incidence of deaths; all of the mice died or were found moribund by the end of the study. The severity of lesions was highest in the anterior portion of the nasal cavity. Severe necrosis and exfoliation of the respiratory epithelium were observed along with minimal necrosis of the olfactory epithelium. No abnormalities were noted in the trachea or lungs.

Stavert et al. ( 1991) compared the acute toxicity of HCl in nose breathing male Fisher 344 rats and in rats breathing through an endotracheal tube (" mouth breathers"). After baseline ventilatory parameters were measured, the rats were exposed for 30 minutes to approximately Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 7 EPA/ OW/ OST/ HECD Final draft 1300 ppm HCl ( 1940 mg/ m3) or to clean air ( 8/ group). Mortality was ~ 6% among the nose breathers and 46% among the mouth breathers. As expected, the nose breathers had significant nasal histopathology, including necrosis, exudate, and inflammation, while nasal sections of the mouth breathers were generally normal. Mild epithelial necrosis of the trachea was observed in nose breathers exposed to HCl, and somewhat more severe tracheal necrosis was seen in mouthbreathing rats exposed to air ( compared to the normal nose breathing controls). The mouth breathers exposed to HCl had a severe diffuse ulcerative tracheitis with necrosis of the mucosa and submucosa and fibrin and neutrophilic exudate. These lesions were more severe than in the mouth breathing controls. Nose breathers exposed to HCl had no lung lesions, but similarlyexposed mouth breathers had increased neutrophils in the alveoli, and some necrosis of the larger bronchi with PMN infiltrations, but the latter lesion was not statistically increased over the mouthbreathing controls. Lung wet weight was slightly, but significantly, increased in the mouth breathers, but not in the nose breathers. A stronger degree of weight loss was seen in the nose breathers.

As part of the 90 day study described under the section on longer term studies,

ToxiGenics, Inc. ( 1984) conducted an interim sacrifice after short term exposure. In this study,

groups of 31 males and 21 females for each strain/ species of B6C3F1 mice and Sprague Dawley and Fisher 344 rats were exposed to HCl at 0, 10, 20, or 50 ppm ( 0, 15, 30, or 75 mg/ m3,

respectively) for 6 hours/ day. Adjusting for the 6 hour/ day exposure results in adjusted daily exposure concentrations of 0, 3.7, 7.5, and 19 mg/ m3. Ten animals/ group were sacrificed on day Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 8 EPA/ OW/ OST/ HECD Final draft 5 ( after 4 exposures). The high concentration male and female mice lost weight as compared to their pre exposure levels; in comparison, the controls, low and mid concentration groups gained weight. The body weight increase in the high concentration male and female Fisher 344 rats and the high concentration male Sprague Dawley rats was statistically significantly lower than in the corresponding controls; there was no significant effect on body weight in the female Sprague

Dawley rats. Histological examination found that lesions were limited to the nose. In both Fisher 344 and Sprague Dawley rats, there was minimal to mild rhinitis of the anterior portion of the nasal cavity, with the males being more affected. Fisher 344 rats also had occasional hyperkeratosis. No treatment related histological lesions were seen in mice of either sex. ( See Tables E 3.)

In an evaluation of the potential for subtle neurological effects of HCl, Einhorn and Moore ( 1990) exposed Long Evans rats ( 4/ exposure, sex not reported) to 0, 75, 150, or 300 ppm ( 0,

112, 224, 448 mg/ m3) for 5 15 minutes, and conducted neurophysiology evaluations. They observed a decreased brainstem auditory evoked response ( BAER) at all exposure levels. In addition, the electroencephalogram ( EEG) was altered at 150 and 300 ppm. The biological significance of these subtle changes is unclear, and was not addressed by the authors.

Summary. In the only study of the effects in animals of short term oral exposure to HCl, metabolic acidosis, decreased body weight, and increased kidney weight were observed in rats provided feed mixed with acidified water ( Throssell et al., 1996). No other studies on the Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 9 EPA/ OW/ OST/ HECD Final draft short term effects of oral exposure, and no studies on the effects of dermal exposure of animals to HCl were located, but toxicity at the site of contact would be expected to result from exposure to sufficiently high concentrations. Several studies evaluated the effects of inhalation exposure to HCl. As expected, exposure to the acid resulted in sensory irritation, nasal inflammation and necrosis ( Burleigh Flayer et al., 1985; ToxiGenics, Inc., 1984).

B. Long Term Exposures Long term ingestion of relatively large quantities of HCl results in metabolic acidosis.

Due to the corrosive effect of concentrated HCl, these long term studies have administered the HCl in dilute solutions. The total doses of HCl needed to cause this condition are relatively large due to the natural secretion of HCl by the stomach, and are estimated at several times the amount of free HCl secreted by the stomach. Metabolic acidosis is a well characterized condition with a variety of causes ( reviewed in Chan, 1983; Robertson, 1989). The physiological response to metabolic acidosis includes a rapid increase in the respiratory rate. This is followed by stepwise increments of net acid excretion that occur over a period of 3 4 days until maximal renal acidification occurs. Studies in laboratory animals found that prolonged exposure to high levels of HCl resulted in decreased body weight and increased kidney weight ( Throssell et al., 1995,

1996). Urinary excretion of proteins increased and then returned to normal, indicating that compensatory changes occurred and the damage was transient ( Throssell et al., 1995). Weanling mice may be more sensitive than adult mice to the effects of acidified water, with water at pH 2 3 Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 10 EPA/ OW/ OST/ HECD Final draft causing decreased weight gains ( reported only in an abstract, as cited by Tober Meyer et al.,

1981), and severe intestinal irritation at pH 1.7 ( McDougall et al., 1987). Exposure to acidified drinking water for 2 years caused dentine erosion in rats ( Tober Meyer et al., 1981). However,

neither effects of HCl on the stomach nor on the teeth are likely to be relevant to HCl produced endogenously from the metabolism of cyanogen chloride, since they result from high acidity at the portal of entry. Several of the studies of acidified drinking water were published only as abstracts or only in German, and so were not reviewed.

Tober Meyer et al. ( 1981) administered normal or acidified drinking water ( pH 2.3 2.5) to groups of 10 male Han: Wistar rats for 7 months. The authors estimated the HCl concentration at 6.14 mmol HCl/ L, corresponding to a dose of 36 mg/ kg day for rats ( using a drinking water consumption of 0.16 L/ kg day for a subchronic study in female Wistar rats, U. S. EPA, 1988).

Parameters evaluated included red blood cell count, differential blood cell count, hemoglobin,

blood glucose and other typical serum biochemistry endpoints ( including the electrolytes sodium,

potassium, and calcium), blood gas analysis, serum protein, SGOT, serum glutamic pyruvic transaminase ( SGPT), body weight, liver and kidney weights, and histopathological analysis of major organs. Urinary proteins were not evaluated. Blood was drawn in weeks 5, 9, 13, 17, 21,

25, and 29. In a similar study, groups of 8 male New Zealand White rabbits were treated with normal or acidified water ( doses of 0 or approximately 25 mg/ kg day for rabbits, using a drinking water consumption of 0.11 L/ kg day); blood was sampled in weeks 4, 8, 12, 17, 21, and 26. The endpoints evaluated were the same as in the rat study. No significant effects were observed in Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 11 EPA/ OW/ OST/ HECD Final draft either rats or rabbits. The study authors calculated that the rats ingested approximately 1/ 4 of the free HCl secreted by the stomach.

Throssell et al. ( 1995) investigated the renal effects in female Wistar rats of prolonged metabolic acidosis. The rats were fed a powdered diet containing 20% casein as a paste mixed with water ( 1/ 1 w/ w) and 2% methylcellulose throughout the study, and for a 2 week induction period prior to dosing. A group of 21 pair fed controls received plain water mixed with the feed,

while the experimental group of 32 rats received the same feed mixed with 0.5 M HCl for 14 weeks. The study authors calculated that the rats received a mean daily HCl dose of 10.3 mmol.

Using the average of the initial and final body weights ( 225 g), this corresponds to a dose of approximately 1670 mg/ kg day. All of the rats had free access to tap water. Food consumption was measured daily, body weights were measured weekly, and 24 hour urine samples were collected every other week. The glomerular filtration rate ( GFR) was measured at 14 weeks, and then the rats were sacrificed, weighed, and the kidneys were weighed and fixed. Body weight in the acidotic rats was decreased throughout the study, with a final body weight at 80% of the control value, even though food consumption was slightly higher in the acidotic rats. Kidney weight was slightly, but not significantly increased, and relative kidney weight was significantly increased. Urine volume was significantly increased at 14 weeks, and urine pH was significantly decreased. Total urinary protein, lysozyme, and albumin peaked at week 8, and were at or near baseline levels by week 12 14. Only a slight increase in immunoglobulin G ( IgG) in urine was observed. Mean arterial pH at sacrifice was lower in the acid supplemented group, but there was Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 12 EPA/ OW/ OST/ HECD Final draft no effect on GFR or serum creatinine concentration. Microscopic examination found no histopathologic effects in the kidney, and specialized stains found no increase in macrophage infiltration. Based on the absence of histological effects or effects on GFR, and on the recovery in urinary protein levels, the study authors concluded that metabolic acidosis neither causes nor exacerbates chronic renal injury. The authors suggested that the resolution of the proteinuria was due to either transient tubular damage that resolved before sacrifice, or to a short term reduction of endocytosis or intralysosomal degradation of tubular proteins. Nonetheless, based on the transient kidney effects, 1670 mg/ kg day was a LOAEL in this study.

Clausing and Gottschalk ( 1989) provided male Ico/ Shoe: WIST rats ( 8 10/ group) with untreated drinking water ( controls), or drinking water acidified to pH 2 or pH 3 with HCl for 21 weeks. Based on the pH, HCl was in the drinking water at approximately 0, 0.01, or 0.001 M,

corresponding to doses of 0, 5.4, and 54 mg/ kg day, assuming a default water consumption of 0.147 L/ kg day. There were no effects on hematology, or on serum creatinine, blood urea nitrogen ( BUN), or alkaline phosphatase. The urine volume was decreased in a dose related fashion at 13 weeks, and the decrease was statistically significant at 21 weeks. The study authors attributed the decrease to altered kidney function. By contrast, drinking water intake in the pH 3 group was elevated over the control levels. ( Drinking water intake data were not reported for the pH 2 group.) The authors did not report whether the animals exhibited evidence of water retention, which would indicate a kidney effect. Alternatively, the rats may have been " playing"

with the drinking water dispenser due to poor palatability, so that the actual intake was lower Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 13 EPA/ OW/ OST/ HECD Final draft than reported. Decreased protein excretion ( statistically significant at 21 weeks), decreased protein concentration in urine, and decreased phenol red excretion after i. v. injection were also observed, although there was no dose response for the effects on protein at 21 weeks. This study is limited by internal inconsistencies and inconsistencies with similar studies, as well as limited reporting of results.

In an attempt to rid a mouse colony ( strain not reported) of Pseudomonas aeruginoasa,

McDougall et al. ( 1987) acidified the drinking water to 0.02 M or 0.005 M with HCl ( pH 1.7 and 2.3, respectively). They noted that " a large number of weanling mice kept on the higher level of acid developed severe intestinal irritation." This irritation was not observed at the lower HCl dose. The authors noted that a viral origin of the irritation could not be ruled out. However, the lack of irritation at the lower HCl concentration suggests a relationship to the HCl dosing. The duration of exposure and number exposed were not reported, and other endpoints of toxicity were apparently not evaluated. Since the effect observed was at the portal of entry, the concentration of the exposure at the LOAEL ( i. e., 0.02 M) may have been more important than the total daily dose ( 254 mg/ kg day, assuming a daily water intake of 0.3483 L/ kg, based on the average across strains and sexes [ U. S. EPA, 1988]). At the NOAEL of 0.005 M, the estimated dose is 64 mg/ kg day. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 14 EPA/ OW/ OST/ HECD Final draft Inhalation studies in animals include studies up to chronic duration, and found that the primary targets of long term inhalation exposure are the nasal epithelium, along with the larynx and trachea.

In an unpublished 90 day inhalation study using B6C3F1 mice and Sprague Dawley and Fisher 344 rats ( ToxiGenics, Inc., 1984), groups of 31 males and 21 females of each strain/ species were exposed to HCl at 10, 20, or 50 ppm ( 0, 15, 30, or 75 mg/ m3, respectively) for 6 hours/ day,

5 days/ week for 90 days. The duration adjusted concentrations were 0, 2.7, 5.3, and 13 mg/ m3.

Several animals died during the study; however, the deaths did not appear to be exposure related.

Ten males and ten females per group were sacrificed after four exposures, as described above in the section on short term exposures, and 10 animals/ sex/ group were sacrificed and evaluated after 90 days. Body weights in male and female mice at the high exposure were decreased compared to the control by ~ 10% ( statistically significant). High concentration male Fisher 344 rats also had sporadic instances of significantly lower body weight. There was no effect on hematology,

clinical chemistry, or urinalysis. The histopathology examination included an extensive list of organs, including the nasal turbinates ( four sections), trachea, larynx, and lung. All tissues were examined from the control and high concentration groups, and only the nasal turbinates, trachea,

lungs, and any gross lesions from the low and mid concentration groups. Histologic examination showed minimum to mild rhinitis in both strains of rats ( Table E 4). Lesions occurred in the anterior portion of the nasal cavity and were concentration and time related. In mice exposed to 50 ppm, there was cheilitis and accumulation of macrophages in the perioral tissues after 90 days. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 15 EPA/ OW/ OST/ HECD Final draft " Eosinophilic globules" in the epithelial lining of the nasal tissues were also observed in female mice at all concentrations and high exposure male mice. Congestion was also observed in the mice, but was not concentration related; there was no nasal or other respiratory tract inflammation in mice. The low concentration was the LOAEL in all three species/ strains. Based on the more sensitive sex, the LOAEL( HEC) was 0.24 mg/ m3 in male Fisher 344 rats, 0.34 mg/ m3 in male Sprague Dawley rats, and 0.25 mg/ m3 in female mice.

In a chronic inhalation study in rats, male Sprague Dawley rats ( 100/ group) were exposed to 0 or 10 ppm ( 0 or 15 mg/ m3) HCl for 6 hours/ day, 5 days/ week ( duration adjusted concentration, 2.5 mg/ m3) for their lifetimes. Because the animals were not exposed on holidays,

in addition to other days of no exposure, exposures were for 4.7 days/ week on average. Interim results were reported by Albert et al. ( 1982), and the full study was reported by Sellakumar et al.

( 1985). All animals were observed daily, weighed monthly, and allowed to die naturally or killed when moribund, with the study ending at week 128. Complete necropsies were performed on all animals, with particular attention given to the respiratory tract. Histologic sections were prepared from the head ( four sections), lung ( one section from each lobe), trachea, larynx, liver, kidneys,

testes, and other organs where gross pathological signs were present. However, neither study discussed histopathological events in organs other than the respiratory tract. HCl exposed animals showed no differences in body weights or survival when compared with air controls. No nasal tumors were observed. Epithelial or squamous hyperplasia was observed in the nasal mucosa ( location not specified) of 62/ 99 exposed animals, compared to 51/ 99 in the concurrent Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 16 EPA/ OW/ OST/ HECD Final draft control group ( Table E 5). The incidence of squamous metaplasia of the nasal mucosa was 9/ 99 and 5/ 99 in the exposed and control rats, respectively. Rhinitis was observed in > 70% of the exposed and control animals. In the laryngeal tracheal segments, hyperplasia was observed in the larynx in 22/ 99 exposed rats, and in the trachea in 26/ 99 exposed rats, compared with 2/ 99 and 6/ 99 controls, respectively. Squamous metaplasia was not reported in the larynx or trachea. The authors did not report any grading of the severity of any of these changes, although they stated that no " serious irritating effects" in the nasal epithelium were observed. Based on these results,

the 10 ppm ( 15 mg/ m3) concentration can be considered a LOAEL ( LOAEL( HEC) = 6.1 mg/ m3).

This study is limited for the purpose of evaluating carcinogenic potential due to the testing of only one exposure level.

No studies on the effects of long term dermal exposure to HCl were located.

Summary. Several studies have evaluated the longer term effects of ingested HCl,

primarily as part of investigations of the effect of metabolic acidosis ( Throssell et al., 1995;

Clausing and Gottschalk, 1989). Other studies evaluated the effects of drinking water that was acidified as part of a disinfection effort ( Tober Meyer et al., 1981; McDougall et al., 1987). The studies of acidosis found that the kidney was the primary target, although one study ( Throssell et al., 1995) found that the effects on the kidneys had reversed by the end of the study, due to the kidney adapting to the acidosis. In the only study of HCl ingestion that examined the liver ( Tober Meyer et al., 1981), no effect was seen on liver weight or serum enzymes indicating liver Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 17 EPA/ OW/ OST/ HECD Final draft injury ( SGOT, SGPT), at drinking water doses of 36 mg/ kg day in rats and 25 mg/ kg day in rabbits. The studies on the effects of acidified water indicate that pH 1.7 water can cause stomach irritation in weanling rats, but pH 2 water results in minimal or no effects ( Tober Meyer et al., 1981; McDougall et al., 1987; Clausing and Gottschalk, 1989). The data are insufficient to determine whether weanlings are more sensitive, or whether the difference between these two concentrations identifies a NOAEL/ LOAEL boundary. Either way, the effects of HCl on the stomach are of questionable relevance to the effects of cyanogen chloride and its metabolites,

since the stomach would not be expected to be the primary site of cyanogen chloride metabolism and HCl production. The potential for metabolic acidosis resulting from HCl production from cyanogen chloride is probably of greater relevance.

Longer term inhalation studies of HCl found hyperplasia of the nasal mucosa, and in the trachea and larynx, and nasal rhinitis ( Sellakumar et al., 1985; Albert et al., 1982; ToxiGenics,

Inc., 1984). Rats were more sensitive than mice to the same exposure concentration, or when the concentration was normalized by the HEC. The studies are limited by the testing of only a single concentration ( Sellakumar et al., 1985; Albert et al., 1982) or by incomplete reporting and histopathology; no NOAEL has been identified. No longer term studies of dermal effects of HCl were identified. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 18 EPA/ OW/ OST/ HECD Final draft C. Reproductive/ Developmental Toxicity Les ( 1968) investigated the effect on mouse reproduction of disinfecting water with sodium hypochlorite and HCl. As part of preparing new matings in the Jackson Laboratory production colony, mice from the inbred strains C3H/ HeJ and C57BL/ 6J ( 168 cages/ strain/ condition) were provided either tap water ( pH 9.2 9.8) or water to which sodium hypochlorite and HCl had been added to achieve 10 13 ppm residual chloride and pH 2.5.

Matings were either in pairs or trios ( 1 male and 2 females). Matings were continued for 6 months. For the C3H/ HeJ strain, the numbers of mice born, mice weaned, and the number born/ dam and weaned/ dam were statistically significantly higher in the treated group than the control group. Similar results were obtained with the C57BL/ 6J strain, although a much stronger improvement was observed in the trios than in the pair mated cages. Thus, the groups drinking disinfected water had better reproductive performance. Although the mice were exposed to a mixture, the data suggest that drinking water of pH 2.5 alone would have no adverse effect on reproductive performance in these strains.

The only developmental toxicity data for HCl are two low quality studies conducted via the inhalation route. Pavlova ( 1976) exposed groups of 8 15 female Wistar rats to 0 or 302 ppm ( 450 mg/ m3) HCl via inhalation for 1 hour. One group was exposed 12 days prior to mating, and the other group on day 9 of gestation. One third of the exposed rats died, with signs of severe dyspnea and cyanosis. Survivors had decreased oxygen saturation, hyperchloruria, and Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 19 EPA/ OW/ OST/ HECD Final draft hyperproteinuria. Fetal mortality was significantly higher in rats exposed during pregnancy. Fetal body weight at age 4 weeks was significantly decreased compared to controls in the rats exposed prior to mating. When the progeny were subjected to an additional exposure of 35 ppm HCl ( 52 mg/ m3) at the age of 2 3 months, functional abnormalities in the organs of the progeny were similar to those found in the mothers ( i. e., in the lungs and kidney). No general conclusion regarding the developmental toxicity of HCl is possible from this study, because it did not use standard developmental toxicity exposure methods or methods for evaluation of effects, and tested a very high exposure concentration.

In another study from the same laboratory ( GEOMET Technologies, Inc., 1981), female rats were exposed to 302 ppm ( 450 mg/ m3) HCl for 1 hour prior to mating. Exposure killed 20

30% of the rats. In rats surviving 6 days after exposure, a decrease in blood oxygen saturation was noted, as was kidney, liver, and spleen damage. In addition, treatment altered the estrus cycles. In rats mated 12 16 days postexposure and killed on day 21 of pregnancy, fewer live fetuses, a decrease in fetal weight, and an increase in relative lung weights of the fetuses were observed. ( It is not clear if this is really a separate study, or just a separate reporting of the same data as reported by Pavlova [ 1976]).

Summary. Studies of reproductive and developmental toxicity of HCl are limited to a single study investigating the effect on reproductive performance of disinfecting drinking water with sodium hypochlorite and HCl ( Les, 1968), and two low quality inhalation studies Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 20 EPA/ OW/ OST/ HECD Final draft investigating the effects of exposure for one hour to a concentration that produced some deaths in rats, either prior to mating or on gestation day 9 ( Pavlova, 1976; GEOMET Technologies, Inc.,

1981). There was no adverse effect on reproductive performance in the drinking water study.

Increased fetal mortality and altered organ function of the progeny were observed in the inhalation study, but these effects may have been secondary to the high maternal toxicity.

D. Mutagenicity and Genotoxicity No effect on mutation rate was observed in S. typhimurium strains TA97, TA98, TA100,

TA102, or TA1535 using the standard plate incorporation assay and buffered solutions down to pH 5.5 in the presence and absence of S9 ( Cipollaro et al., 1986). Although HCl itself was not tested, this study evaluated the effects of increased hydrogen ion concentrations. Decreased viability was observed at pH 5, and complete lethality at lower pH values.

Morita et al. ( 1989) evaluated the potential of HCl to produce chromosome aberrations in Chinese hamster ovary ( CHO K1) cells at concentrations up to 16 mM ( S9) or 12 mM (+ S9).

The highest concentration tested in the absence or presence of S9 was cytotoxic. Chromosome aberrations were increased at 14 mM HCl  S9 ( measured pH of 5.5 initially, and pH 6.7 after 24 hours) and 10 mM HCl + S9 ( pH 5.8 immediately and 6.3 after 6 hours). The aberrations were primarily chromatid breaks and chromatid exchanges. The observed effects were primarily due to the low pH, rather than the HCl per se, since similar effects were seen with organic buffers at Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 21 EPA/ OW/ OST/ HECD Final draft acidic pHs. Cell survival at the clastogenic concentrations was not reported. Levis and Majone ( 1981) found that HCl at 0.01 or 0.025 N had no effect on the production of chromosome aberrations in CHO cells, apparently in the absence of S9.

In a report on EPA's Gene Tox Program, Heidelberger et al. ( 1991) reported that HCl at concentrations of 31 500  g/ mL was negative for cell transformation in SA7/ SHE cells. The basis for the choice of concentrations tested was not provided, but testing sufficiently high doses was included in the criteria for an acceptable assay. This assay measures the ability of chemicals to enhance adenovirus induced transformation.

HCl was negative in a microsuspension adaptation of the Bacillus subtilis " rec" assay that used E. coli DNA repair deficient strains ( McCarroll et al., 1981a). The strains tested were WP2,

WP2 uvrA, WP67 uvrA polA, CM611 uvrA recA, W3110polA+, and p3478 polA. The endpoint in this assay is whether the chemical causes preferential kill of repair deficient strains, and thus the assay measures primary DNA damage. Similarly, HCl was negative in a microsuspension adaptation of the " rec" assay that used B. subtilis strains M45 rec and H17 rec+ ( McCarroll et al.,

1981b).

In a test of a number of leather tannins and the materials used to dissolve them, Venier et al. ( 1985) found no effect on the induction of sister chromatid exchanges ( SCEs) in CHO cells by Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 22 EPA/ OW/ OST/ HECD Final draft HCl concentrations up to 0.01 N. Levis and Majone ( 1981) also found that HCl at 0.01 or 0.025 N ( apparently in the absence of S9) had no effect on the production of SCEs in CHO cells.

Summary. Genotoxicity studies of HCl include gene mutation assays in S. typhimurium ( Cipollaro et al., 1986), chromosome aberration assays in CHO cells ( Morita et al., 1989; Levis and Majone, 1981), an assay for cell transformation in SA7/ SHE cells ( Heidelberger et al., 1991),

and several assays for DNA damage ( McCarroll et al., 1981a, 1981b; Venier et al., 1985; Levis and Majone, 1981). These studies found that HCl was not genotoxic. The one positive study found an increase in chromosome aberrations in CHO cells, a finding that was attributed to the low pH and resulting cell stress, rather than genotoxicity of HCl per se ( Morita et al., 1989).

E. Carcinogenicity As discussed in the section on longer term toxicity, Sellakumar et al. ( 1985) and Albert et al. ( 1982) reported on a chronic inhalation study conducted in male Sprague Dawley rats ( 100/ group) exposed to 0 or 10 ppm ( 0 or 15 mg/ m3) HCl for 6 hours/ day, 5 days/ week ( duration adjusted concentration, 2.5 mg/ m3) for their lifetimes. Complete necropsies were performed on all animals, with particular attention given to the respiratory tract.

Histopathological effects were reported only for the respiratory tract. HCl exposed animals showed no differences in body weights or survival when compared with air controls. No treatment related tumors were observed, although the treated group had an elevated incidence of Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 23 EPA/ OW/ OST/ HECD Final draft epithelial or squamous hyperplasia of the nasal mucosa and hyperplasia of the larynx and trachea.

This study is limited for the purpose of evaluating carcinogenic potential, due to the testing of only one exposure level.

Summary. The only available study on HCl carcinogenicity study in animals is an inhalation assay ( Sellakumar et al., 1985; Albert et al., 1982). The one concentration tested produced respiratory tract hyperplasia but no tumors. This study is limited for the purpose of evaluating carcinogenic potential, due to the testing of only one exposure level.

II. Health Effects in Humans A. Case Reports and Clinical Studies Case reports of dermal or oral exposure to HCl were not identified, but irritation and necrosis at the sites of contact would be expected, based on the caustic effect of HCl. The relevance of such effects to cyanogen chloride is questionable. Oral toxicity studies for HCl are summarized in Table E 1, and inhalation studies are summarized in Table E 2.

Deschamps et al. ( 1994) reported on a case of a woman with no preexisting respiratory complaints, who developed asthma after she accidentally inhaled a mixture of sodium hypochlorite and hydrogen chloride. The subject was atopic at initial evaluation a few days after the accident, Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 24 EPA/ OW/ OST/ HECD Final draft with a positive reaction to aeroallergens and increased IgE. Her first asthma attack was 44 days after the accident, and then attacks occurred periodically for at least 2 years after the accident.

Bronchial histologic examination showed partial to total epithelial destruction and a slight inflammatory response. The authors suggested that the asthma resulted from epithelial destruction impeding the release of bronchodialator neuropeptides.

Adults ( age 18 25) with mild asthma ( 5/ sex) were exposed to 0, 0.8 and 1.8 ppm HCl ( 0,

1.2, and 2.7 mg/ m3) for 45 minutes, and pulmonary function tests performed immediately after exposure were compared to baseline levels ( Stevens et al., 1992). Each subject was exposed to each concentration in a double blind fashion, with exposures separated by at least a week. The exposure periods consisted of 15 minutes treadmill walking, 15 minutes rest, and 15 minutes walking. A half face mask was used to allow nose and mouth breathing, but to eliminate ocular exposure. No exposure related effects were observed in subjective symptoms or in pulmonaryfunction tests, including forced expiratory volume in 1 second ( FEV 1), forced vital capacity ( FVC), maximal flow at 50% and 75% of vital capacity ( V max50 and V max75), respiratory resistance,

and peak flow. This is the only available controlled human exposure study of HCl.

B. Epidemiological Studies Data on the long term effects of acute, high level exposure to HCl are limited, and no studies evaluated the noncancer effects of long term human exposure to HCl via the oral, Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 25 EPA/ OW/ OST/ HECD Final draft inhalation, or dermal routes. However, Kilburn ( 1996) reported on a 20 month follow up of a population accidentally exposed to unspecified levels of HCl fumes in an accident. The study was initiated because the officer initially responding to the spill developed impaired balance, decreased memory, headaches, and respiratory illnesses. No study was conducted immediately after the spill, although the investigating officer and exposed residents reported tearing eyes, burning throats, headache, chest pain, shortness of breath, and flu like symptoms. The subjects completed questionnaires on respiratory symptoms, neurologic disorders, other symptoms, and exposure;

completed a profile of mood states ( POMS), and underwent physiologic and psychologic testing and spirometry. The exposed group consisted of 45 adults and 24 children who occupied the mobile home park where the accident occurred. A referent population of 56 adults and 39 children were recruited from a nearby mobile home park, and an attempt was made to match referents to the exposed group for age and educational characteristics, although the education level was still significantly lower in the exposed group. Statistically significant effects were seen among the adults for a number of endpoints, with the strongest effects on reaction time, digit symbol ( a measure of cognitive function), and POMS scores. Significant effects were also seen on scores of balance and perceptual motor speed, and the frequency for a number of subjective symptoms. The effect was stronger when only women ( who were more likely to be home at the time of the initial exposure) were analyzed, and effects on balance, pulmonary midflow, and reaction time were more abnormal among the subjects who lived closest to the spill. Covariance analysis with adjustments for potential confounders ( including education level) found that effects on reaction time, balance, and digit symbol were statistically significantly associated with Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 26 EPA/ OW/ OST/ HECD Final draft exposure. Statistically significant effects were also seen for reaction time and balance in the children ( ages 8 17). Spirometry measurements were reduced compared to predicted in both the exposed and referent groups. Significant decreases compared to the referents were seen in 1

second forced expiratory volume ( FEV 1) and forced expiratory midflow rate at 25 75% of vital capacity ( FEF 25 75), but it is unclear whether these decreases occurred in adults or children, due to inconsistencies between the text and table. The study author noted that the exposed group had a higher occupational exposure to chemical refining and to solvents, but that these exposures did not contribute to the observed variation. No further details on the analysis were, however,

reported. The study author also noted that he had found evidence of chlorine neurotoxicity in a separate study.

There are several epidemiology studies evaluating the potential carcinogenicity of inhaled HCl. Bond et al. ( 1991) conducted a case control study of lung cancer, nested in a cohort of 19,608 male chemical manufacturing employees employed by Dow Chemical Company in Texas.

The case group consisted of all 308 subjects who died from cancer of the trachea, bronchus, or lungs in the period 1940 1980. The controls were individually matched based on race, year of birth, and year of hire. Two control groups were chosen  one a decedent control and the other a " living series," chosen from all of the other members of the cohort without lung cancer. HCl exposure was estimated from knowledge of the chemical processes and limited monitoring data.

The subjects were grouped by estimated 8 hour TWA HCl exposure into workers exposed to 0,

0.2 0.3 ppm, 0.9 2.0 ppm, and 2.2 5.1 ppm ( 0.3 0.4, 1.3 3, and 3.3 7.6 mg/ m3). Cumulative Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 27 EPA/ OW/ OST/ HECD Final draft exposure scores were also calculated for each subject using the midpoint of the TWA range for each job, and were grouped into four categories ( 0, 0.1 3.9, 4.0 12.4, and  12.5 ppm years).

Smoking histories were available for 70.8 of the cases and 75.5% of the controls from telephone interviews. Other exposures at the plant included asbestos, benzene, beryllium, carbon tetrachloride, sulfur dioxide, and wood dust. Similar results were obtained with both control groups, so the results were pooled to increase statistical power. HCl exposure had no effect on the lung cancer risk based on a comparison of the cases and controls ( relative risk [ RR] of 1.0,

95% confidence interval [ CI] of 0.8 1.3). Allowing for a 15 year latency from first exposure to HCl resulted in a slightly lower RR of 0.9 ( 95% CI, 0.7 1.2). There was no association between increasing cancer risk and several measures of HCl exposure, including the exposure duration,

cumulative exposure to HCl, and the highest average exposure. However, in light of other exposures of the cohort to lung cancer inducing agents, a smaller effect of HCl might have been missed. IARC ( 1992) stated that the use of Mantel Haenszel adjusted relative risks in this study " may not have been optimal." Further details were not provided.

Siemiatycki ( 1991, as cited by IARC, 1992) conducted a case control study of histologically confirmed cases of lung cancer among male residents of Montreal, Canada. The study included 3,730 cancer patients and 533 population controls from an age stratified sample of the general population. An additional control group consisted of cases of cancer at other sites ( cancer control). Detailed lifetime job histories and data on potential confounders were obtained,

and this information was converted into occupational exposures. The 293 most common Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 28 EPA/ OW/ OST/ HECD Final draft occupational exposures were evaluated as potential risk factors for cancer. Cumulative exposure indices were estimated, based on duration, concentration, frequency, and degree of certainty in the exposure assessment. Those exposed were classified as " any" or " substantial," a subset of " any." The analysis was repeated for the French Canadian subset of the population ( about 60%

of the total sample). There was no association between all cancers of the lung and HCl exposure.

The odds ratio for oat cell carcinoma of the lung was 1.6 compared to the cancer controls ( 19 cases, 90% CI, 1.0 2.6); for workers exposed at the " substantial" level, the odds ratio was 2.1 ( 8 cases, 90% CI 1.0 4.5). In an analysis restricted to the French Canadian subset and population controls, the odds ratio for non Hodgkins lymphoma was 1.6 ( 18 cases, 90% CI 1.0 2.5), and the odds ratio for rectal cancer was 1.9 ( 18 cases, 90% CI 1.1 3.4).

A cohort study of 1,165 male steel pickling workers exposed for at least 6 months during the period 1940 1964 ( Beaumont et al., 1987) included a subset of workers exposed to mists of acids other than sulfuric acid. [ Exclusion of sulfuric acid exposure is particularly important,

because sulfuric acid is a human carcinogen ( IARC, 1992).] The primary acid to which these workers were exposed was HCl. This study found an excess risk for lung cancer, with a standardized mortality ratio of 2.24 ( 9 deaths, 95% CI, 1.20 4.25). The excess persisted when workers who had been employed in 1950 1954 were evaluated, using other steelworkers as a control for socioeconomic and lifestyle factors such as smoking ( SMR, 2.00, 95% CI, 1.06 3.78). Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 29 EPA/ OW/ OST/ HECD Final draft C. Summary of Human Studies HCl is a strong acid, so acute high level exposures cause corrosion at the portal of entry via the oral, inhalation, or dermal routes. Human studies and reports of accidental exposures have generally been limited to acute ( e. g., 1 hour) inhalation exposures, and have found that the observed effects include nasal edema, throat irritation, coughing, and, at increasing concentrations, bronchitis, pulmonary edema and death. A clinical study of asthmatic adults exposed to a maximum concentration of 1.8 mg/ m3 HCl for 45 minutes found no effects on pulmonary function ( Stevens et al., 1992). There have been some reports of long term sequalae to acute exposures of humans, including a case report of asthma ( Deschamps et al., 1994) and an epidemiology study that found decrements in pulmonary function and in neurological function ( decreased balance and reaction time) one year after an accident resulting in exposure of a community ( Kilburn, 1996). Adjustments were made for other exposures, but insufficient details were provided for an independent evaluation.

Human data regarding the carcinogenicity of HCl are mixed, and include one US cohort study showing excess lung cancer risk ( Beaumont et al., 1987) and one Canadian case control study finding a borderline increased risk for oat cell carcinoma, but no effect on other histological types of lung cancer ( Siemiatycki, 1991). A large American case control study found no excess risk of lung, brain, or kidney cancer ( Bond et al., 1991). Since the positive findings were at the point of contact, the relevance to cyanogen chloride carcinogenicity is questionable. Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 30 EPA/ OW/ OST/ HECD Final draft III. Quantification of Toxicological Effects Methods for the quantification of toxicological effects are described in Section VIII. A.

A. Noncarcinogenic Effects A. 1. One day Health Advisory No studies of suitable duration were located. In the absence of adequate data, the health advisory for the next longer duration is usually recommended as a conservative estimate of an appropriate one day HA value. However, as described in the following sections, no health advisories are derived for HCl.

A. 2. Ten day Health Advisory The only study of a duration and route appropriate for a 10 day HA is a 14 day study in which liquid hydrochloric acid was mixed with the feed of rats ( Throssell et al., 1996). This study identified a LOAEL in rats of 3600 mg/ kg day based on metabolic acidosis that resulted in decreased body weight, increased kidney weight, and kidney histopathology detectable only using special stains. Although the acidosis is a systemic effect, these data cannot, however, be directly extrapolated to cyanogen chloride, due to differences in the toxicokinetics of ingested HCl and Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 31 EPA/ OW/ OST/ HECD Final draft HCl formed from cyanogen chloride metabolism. For example, ingested HCl is added to the HCl in the stomach, and must be absorbed systemically to cause acidosis, while cyanogen chloride ingestion results primarily in the production of HCl in the blood and liver. Therefore, a Ten day HA is not derived.

A. 3 Longer term Health Advisory Only limited data appropriate for derivation of a longer term HA are available, and these studies consist of two types. The NOAELs and LOAELs identified in the studies in which drinking water was acidified appeared to be lower on a body weight basis than those in studies in which acidified water was used to moisten feed and produce metabolic acidosis. This conclusion is limited, however, by the paucity of studies that identified both a NOAEL and a LOAEL. Thus,

free standing NOAELs of 25 36 mg/ kg day were identified in rats and rabbits provided drinking water at pH 2.3 2.5 for 7 months ( Tober Meyer et al., 1981), compared with a free standing LOAEL of 1670 mg/ kg day for decreased body weight and metabolic acidosis when acidified water was used to moisten feed in a rat study ( Throssell et al., 1995). The endpoints evaluated by Tober Meyer et al. ( 1981) included both kidney and liver effects. Improved reproductive performance was observed in a continuous mating reproduction study in mice exposed for 6 months to drinking water containing HCl at pH 2.5 and sodium chlorite ( approximately 29 mg/

kgday ( Les, 1968), making this dose a NOAEL. The only drinking water study in which an effect was seen was a study of unspecified duration, in which weanling rats were provided acidified Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 32 EPA/ OW/ OST/ HECD Final draft water of pH 2.3 or 1.7; severe stomach irritation was seen at the lower pH ( McDougall et al.,

1987). The corresponding estimated daily doses were 64 mg/ kg day ( NOAEL) and 254 mg/

kgday ( LOAEL). However, the relevance of these drinking water studies to cyanogen chloride is questionable, since ingested HCl is delivered directly to the stomach, while cyanogen chloride ingestion results primarily in the production of HCl in the blood and liver. Similarly, although acidosis is a systemic effect, information on HCl doses in feed that result in acidosis cannot be directly extrapolated to cyanogen chloride, due to uncertainties regarding the relative rate and amount of HCl and cyanogen chloride absorption from the stomach and intestines. Therefore, a Longer term HA is not derived.

A. 4 Reference Dose, Drinking Water Equivalent Level, and Lifetime Health Advisory As discussed above, differences in the toxicokinetics of HCl and cyanogen chloride make it inappropriate to extrapolate from HCl toxicity to cyanogen chloride. For example, ingested HCl is added to the HCl in the stomach, and must be absorbed systemically to cause acidosis,

while cyanogen chloride ingestion results in the production of HCl in the blood and liver.

Therefore, a Lifetime Health Advisory is not derived for HCl.

B. Carcinogenic Effects Drinking Water Criteria Document for Cyanogen Chloride and Potential Metabolites E 33 EPA/ OW/ OST/ HECD Final draft The only available study on HCl carcinogenicity study in animals is an inhalation assay ( Sellakumar et al., 1985; reported also as Albert et al., 1982). The one concentration tested produced respiratory tract hyperplasia but no tumors. This study is limited for the purpose of evaluating carcinogenic potential, due to the testing of only one exposure level. Human data regarding the carcinogenicity of HCl are mixed, and include one US cohort study showing excess lung cancer risk ( Beaumont et al., 1987) and one Canadian case control study finding a borderline increased risk for oat cell carcinoma, but no effect on other histological types of lung cancer ( Siemiatycki, 1991). A large American case control study found no excess risk of lung, brain, or kidney cancer ( Bond et al., 1991). Since the positive findings were at the point of contact, the relevance to cyanogen chloride carcinogenicity is questionable. Therefore, no carcinogenicity assessment of HCl was conducted as part of the cyanogen chloride assessment. Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites EPA/ OW/ OST/ HECD Final draft E 34 Table E 1. Summary of Oral Toxicity Studies for HCl.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg/

kgday LOAEL mg/

kgday Comments One Day HA: None Ten Day HA Wistar Rat ( 12 females/

group) Throssell et al., 1996 0, feed mixed with 0.8 M HCl intake: 19.7 mmol HCl/ day 0, 3600 mg/ kg day Water used to moisten feed 14 days Metabolic acidosis,

including inc urine volume, dec body weight, inc kidney weight, but kidney histopathology limited to tubular casts None 3600 Study was conducted to investigate the renal effects of metabolic acidosis; rats had free access to tap water for drinking.

Dose calculated using reported body weight of 200 g Subchronic Mouse Weanlings ( Number and strain NS) McDougall et al., 1987 0.02 M or 0.005 M HCl ( pH 1.7 or pH 2.3 64 or 254 mg/ kg/ day Drinking water NS  but evaluated as weanlings Severe stomach irritation 0.005 M 0.02 M NOAEL reported as concentration, since the effect at the site of contact suggests a concentrationrelated ( rather than total dose related) effect Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 1. Summary of Oral Toxicity Studies for HCl.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg/

kgday LOAEL mg/

kgday Comments EPA/ OW/ OST/ HECD Final draft E 35 Wistar Rat ( 32 females exposed,

21 pair fed female controls) Throssell et al., 1995 0, feed mixed with 0.5 M HCl intake: 10.3 mmol HCl/ day 0, 1670 mg/ kg day Water used to moisten feed 14 weeks Inc food consumption but dec body weight,

inc kidney weight,

urine volume. Urinary protein, lysozyme,

albumin peaked at week 8, but returned to baseline by end of study. None 1670 Rats had free access to tap water for drinking. No effect on GFR or kidney histopathology. Authors suggested that there was transient tubular damage, but the kidney adapts to the metabolic acidosis.

Dose calculated using average of initial and final body weights, 225 g Ico/ Shoe:

WIST Rat ( 8 10 males/ group) Clausing and Gottschalk,

1989 0, drinking water acidified to pH 2 or pH 3 with HCl Approximately 0.01M or 0.001 M HCl 0, 5.4, 54 Drinking water 21 weeks Dec urine volume,

protein excretion,

protein concentration in urine N/ A N/ A Study limited by internal inconsistencies and inconsistencies with similar studies, as well as limited reporting of results. Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 1. Summary of Oral Toxicity Studies for HCl.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg/

kgday LOAEL mg/

kgday Comments EPA/ OW/ OST/ HECD Final draft E 36 Han: Wistar Rat ( 10 males/ group) Tober

Meyer et al.,

1981 0, drinking water acidified to pH 2.3 2.5 with HCl Estimated at 6.14 mmol HCl/ L max 0, 36 mg/ kg day Drinking water 7 months No effect on the liver,

kidney, or hematological parameters 36 None Authors estimated that the rats ingested almost 1/ 4 of the free HCl secreted by their stomachs. Doses calculated using a drinking water factor of 0.16 for male Wistar rats in a subchronic study ( U. S. EPA, 1988)

New Zealand White Rabbit ( 8 M/ group) Tober

Meyer et al.,

1981 0, drinking water acidified to pH 2.3 2.5 with HCl Estimated at 6.14 mmol HCl/ L max 0, 25 mg/ kg day Drinking water 7 months No effect 25 None None. Doses calculated using a drinking water factor of 0.11L/ kg for New Zealand rabbits in a subchronic study ( U. S. EPA, 1988)

Reproductive and Developmental Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 1. Summary of Oral Toxicity Studies for HCl.

Strain, Species,

Sex Reference Dose Route Duration Response at LOAEL NOAEL mg/

kgday LOAEL mg/

kgday Comments EPA/ OW/ OST/ HECD Final draft E 37 C3H/ HeJ or C57BL/ 6J mouse ( 168 cages/

strain/ condition) Les, 1968 Tap water ( pH 9.2 9.8) or drinking water to which Na hypochlorite and HCl added to 10

13 ppm residual chloride and pH 2.5 Approximately 29 mg/ kg day Drinking water 6 months continuous matings Improved reproductive performance ( in number born/ dam and number weaned/ dam) 29 None Mice mated in pairs or 1 M and 2 Fs Improved performance considered due to disinfectant activity of hypochlorite and HCl.

Doses calculated using the average water consumption across mouse strains and sexes of 0.2649 L/ kg day ( U. S. EPA, 1988)

Dec = decreased; Inc = increased; NS = Not Specified; GFR = glomerular filtration rate; M = male; F = female Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites E 38 EPA/ OW/ OST/ HECD Final draft Table E 2. Summary of Inhalation Toxicity Studies for HCl.

Strain Species,

Sex Reference Exposure mg/ m3 Duration Duration

Adjusted mg/ m3 Response NOAEL/

LOAEL mg/ m3 NOAEL/

LOAEL ( HEC)

mg/ m3 Comments One Day HA Human ( 45 adults and 24 children exposed; 56 adult and 39 children controls) Kilburn,

1996 Accidental exposure,

not estimated Few hours

1 day N/ A Dec pulmonary function and neurological scores ( balance and reaction time were particularly affected)

20 months postexposure N/ A N/ A Although no exposure level available, this study is useful for hazard identification.

Effects were stronger among those expected to have higher exposure.

Effects apparent after adjustment for occupational solvent exposure, but details not provided.

Asthmatic adults ( 5/ sex) Stevens et al., 1992 0, 1.2, 2.7 ( 0, 0.8, 1.8 ppm) 45 min.

( 15' walking,

15' rest, 15'

walking) N/ A No effects on subjective symptoms or pulmonary function tests 2.7/ None 2.7/ None Study done doubleblind with each subject exposed to each concentration, separated by at least a week. Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 2. Summary of Inhalation Toxicity Studies for HCl.

Strain Species,

Sex Reference Exposure mg/ m3 Duration Duration

Adjusted mg/ m3 Response NOAEL/

LOAEL mg/ m3 NOAEL/

LOAEL ( HEC)

mg/ m3 Comments EPA/ OW/ OS/ HECD Final draft E 39 Baboon ( 3 males/

group) Kaplan,

1987; Kaplan et al., 1988 0, 746,

7460, 14,900 ( 0, 500,

5000, 10,000 ppm) 15 minutes N/ A Inc respiratory frequency and minute volume during exposure; no effect on pulmonary function at 3 days or 3 months None/

746 N/ A None English Guinea pig ( 4 8 males/ group) Burleigh

Flayer et al.,

1985 0, 480,

1015, 1550,

2060 ( 0, 320, 680,

1040, 1380 ppm) 30 minutes N/ A Sensory irritation resulting in decreased respiratory rate at all concentrations.

1040 ppm and higher caused mortality

histopath included acute alveolitis and lung congestion None/ 480 N/ A Concentration duration response not linear.

Irritation at 6 min at 320 ppm, but almost immediately at higher concentrations Fisher 344 Rats ( 8 males/ group) Stavert et al.,

1991 0, 1940 ( 0, 1300 ppm) 30 minutes N/ A Nasal necrosis,

exudate, inflammation 6% mortality N/ A N/ A The study also exposed rats via an endotracheal tube " mouth breathers". Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 2. Summary of Inhalation Toxicity Studies for HCl.

Strain Species,

Sex Reference Exposure mg/ m3 Duration Duration

Adjusted mg/ m3 Response NOAEL/

LOAEL mg/ m3 NOAEL/

LOAEL ( HEC)

mg/ m3 Comments EPA/ OW/ OS/ HECD Final draft E 40 Long Evans Rat ( 4/ exposure,

sex NS) Einhorn and Moore, 1990 0, 112, 224,

448 ( 0, 75, 150,

300 ppm) 5 15 minutes N/ A Dec brainstem auditory evoked response ( BAER) at all levels; EEG affected at 150 and 300 ppm N/ A N/ A Adversity of changes unclear Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 2. Summary of Inhalation Toxicity Studies for HCl.

Strain Species,

Sex Reference Exposure mg/ m3 Duration Duration

Adjusted mg/ m3 Response NOAEL/

LOAEL mg/ m3 NOAEL/

LOAEL ( HEC)

mg/ m3 Comments EPA/ OW/ OS/ HECD Final draft E 41 Wistar Rat ( 8 15) Pavlova,

1976 0, 450 ( 0, 302 ppm) 1 hour GD 9 N/ A One third of the animals died, with signs of severe dyspnea and cyanosis. Survivors had dec oxygen saturation, hyperchloruria, and hyperproteinuria.

Fetal mortality was significantly elevated. When the progeny were subjected to an additional exposure of 35 ppm ( 52 mg/ cu. m) at the age of 2 3 months,

functional abnormalities in the organs of the progeny were similar to those found in the mothers. None 450 No effect on hypoxic challenge of progeny at age 2 3 months. Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 2. Summary of Inhalation Toxicity Studies for HCl.

Strain Species,

Sex Reference Exposure mg/ m3 Duration Duration

Adjusted mg/ m3 Response NOAEL/

LOAEL mg/ m3 NOAEL/

LOAEL ( HEC)

mg/ m3 Comments EPA/ OW/ OS/ HECD Final draft E 42 Wistar Rat ( 8 15) Pavlova,

1976 0, 450 ( 0, 302 ppm) 1 hour Once,

12 days before mating N/ A One third of the animals died, with signs of severe dyspnea and cyanosis. Survivors had dec oxygen saturation, hyperchloruria, and hyperproteinuria.

When the progeny were subjected to an additional exposure of 35 ppm ( 52 mg/ m3) at the age of 2 3 months,

functional abnormalities in the organs of the progeny were similar to those found in the mothers. None 450 No effect on hypoxic challenge of progeny at age 2 3 months. Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 2. Summary of Inhalation Toxicity Studies for HCl.

Strain Species,

Sex Reference Exposure mg/ m3 Duration Duration

Adjusted mg/ m3 Response NOAEL/

LOAEL mg/ m3 NOAEL/

LOAEL ( HEC)

mg/ m3 Comments EPA/ OW/ OS/ HECD Final draft E 43 Swiss Webster mouse ( 16 24 males, #

unclear) Buckley et al., 1984 454 TWA ( 304 ppm) 6 hours/ day 3 days 113 Severe necrosis and exfoliation of the respiratory epithelium were observed, along with minimal necrosis of the olfactory epithelium. None/ 454 N/ A All of the mice died or were found moribund by the end of the study.

Fisher 344 Rat ( 31 males, 21 females/ grou p) Toxigenics,

Inc., 1984 0, 15, 30, 75 ( 0, 10, 20,

50 ppm) 6 hr/ day 4 days 0, 3.7, 7.5,

19 ( exposure only 4 d, so no days/ wk adjustment Minimal to mild rhinitis, and occasional hyperkeratosis, of anterior portion of nasal cavity ( Males more affected) 3.7/ 7.5 N/ A 10 animals/ sex/ group killed on day 5,

10/ sex/ group killed and evaluated at 90 days

see subchronic section Sprague

Dawley Rat ( 31 males, 21 females/ grou p) Toxigenics,

Inc., 1984 0, 15, 30, 75 ( 0, 10, 20,

50 ppm) 6 hr/ day 4 days 0, 3.7, 7.5,

19 ( exposure only 4 d, so no days/ wk adjustment Minimal to mild rhinitis of anterior portion of nasal cavity ( Males more affected.) 3.7/ 7.5 N/ A 10 animals/ sex/ group killed on day 5,

10/ sex/ group killed and evaluated at 90 days

see subchronic section Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 2. Summary of Inhalation Toxicity Studies for HCl.

Strain Species,

Sex Reference Exposure mg/ m3 Duration Duration

Adjusted mg/ m3 Response NOAEL/

LOAEL mg/ m3 NOAEL/

LOAEL ( HEC)

mg/ m3 Comments EPA/ OW/ OS/ HECD Final draft E 44 B6C3F1 Mouse ( 31 males, 21 females/ grou p) Toxigenics,

Inc., 1984 0, 15, 30, 75 ( 0, 10, 20,

50 ppm) 6 hr/ day 4 days 0, 3.7, 7.5,

19 ( exposure only 4 d, so no days/ wk adjustment Body weight dec compared to preexposure at high concentration 7.5/ 19 N/ A 10 animals/ sex/ group killed on day 5,

10/ sex/ group killed and evaluated at 90 days

see subchronic section Ten Day HA: None Subchronic Fisher 344 Rat ( 31 males, 21 females/ grou p) Toxigenics,

Inc., 1984 0, 15, 30, 75 ( 0, 10, 20,

50 ppm) 6 hr/ day 5 d/ week 90 days 0, 2.7, 5.3,

13 Minimal to mild rhinitis, and occasional hyperkeratosis, of anterior portion of nasal cavity ( Males more affected) None/ 2.7 None/ 0.24 10 animals/ sex/ group killed on day 5,

10/ sex/ group killed and evaluated at 90 days Sprague

Dawley Rat ( 31 males, 21 females/ grou p) Toxigenics,

Inc., 1984 0, 15, 30, 75 ( 0, 10, 20,

50 ppm) 6 hr/ day 5 d/ week 90 days 0, 2.7, 5.3,

13 Minimal to mild rhinitis of anterior portion of nasal cavity ( Males more affected.) None/ 2.7 None/ 0.34 10 animals/ sex/ group killed on day 5,

10/ sex/ group killed and evaluated at 90 days Drinking Water Criteria Document for Cyanogen Chloride and Potential metabolites Table E 2. Summary of Inhalation Toxicity Studies for HCl.

Strain Species,

Sex Reference Exposure mg/ m3 Duration Duration

Adjusted mg/ m3 Response NOAEL/

LOAEL mg/ m3 NOAEL/

LOAEL ( HEC)

mg/ m3 Comments EPA/ OW/ OS/ HECD Final draft E 45 B6C3F1 Mouse ( 31 males, 21 females/ grou p) Toxigenics,

Inc., 1984 0, 15, 30, 75 ( 0, 10, 20,

50 ppm) 6 hr/ day 5 d/ week 90 days 0, 2.7, 5.3,

13 Eosinophilic globules in nasal turbinates, congestion ( females more affected) None/ 2.7 ( F) None/ 0.25 10 animals/ sex/ group killed on day 5,

10/ sex/ group killed and evaluated at 90 days.

No nasal or respiratory tract inflammation.

Chronic Sprague

Dawley Rat ( 100 males) Sellakumar et al., 1985;

Albert et al.,

1982 0, 15 ( 10 ppm) 6 hr/ d 5 d/ week for lifetime 0, 2.5 Hyperplasia of nasal mucosa, and in trachea and larynx None/ 2.5 None/ 6.51 Only one concentration tested; no severity grading, no reporting on extrarespiratory histopathology. Basis for EPA's current RfC 1The HEC presented on IRIS was used.

Dec = Decreased; Inc = Increased; N/ A = Not applicable; NS = not specified; GD = gestation day; TWA = time weighted average; d = days DrinkingWater Criteria Document for Cyanogen Chloride and Potential Metabolites EPA/ OW/ OS/ HECD Final draft E 46 Table E 3. Histopathology Results Following Acute Inhalation Exposure to HCl.

Lesion Exposure Concentration ( ppm)

Males Females 0 10 20 50 0 10 20 50 Fisher 344 Rats Acute Rhinitis ( Level A nasal turbinate) 0/ 10 0/ 10 1/ 10 4/ 10 0/ 10 0/ 10 0/ 10 4/ 10 Hyperkeratosis ( Level A nasal turbinate) 0/ 10 0/ 10 2/ 10 2/ 10 0/ 10 0/ 10 2/ 10 2/ 10 Subacute Rhinitis ( Level A nasal turbinate) 0/ 10 0/ 10 3/ 10 2/ 10 0/ 10 0/ 10 2/ 10 3/ 10 Levels B, C, D No lesions reported Sprague Dawley Rats Acute Rhinitis ( Level A nasal turbinate) 0/ 10 0/ 10 3/ 10 5/ 10 0/ 10 0/ 10 1/ 10 4/ 10 Levels B, C, D No lesions reported Mice No treatmentrelated lesions reported Adapted from ToxiGenics, Inc. ( 1984) EPA/ OW/ OS/ HECD Final draft E 47 Table E 4. Histopathology Results Following Subchronic Inhalation Exposure to HCl.

Lesion Exposure Concentration ( ppm)

Males Females 0 10 20 50 0 10 20 50 Fisher 344 Rats Hyperkeratosis ( Level A nasal turbinate) 0/ 10 0/ 10 0/ 10 2/ 10 0/ 10 0/ 10 1/ 10 1/ 10 Acute rhinitis ( Level A nasal turbinate) 0/ 10 3/ 10 7/ 10 9/ 10 0/ 10 3/ 10 5/ 10 6/ 10 Levels B, C, D: No lesions reported Sprague Dawley Rats Congestion ( Level A nasal turbinate) 1/ 10 0/ 10 0/ 10 1/ 10 0/ 10 0/ 10 0/ 10 0/ 10 Subacute rhinitis ( Level A nasal turbinate) 3/ 10 4/ 10 7/ 10 7/ 10 2/ 10 4/ 10 6/ 10 6/ 10 Congestion, Level B 1/ 10 0/ 10 0/ 10 1/ 10 0/ 10 0/ 10 0/ 10 0/ 10 Congestion, Level C 1/ 10 0/ 10 1/ 10 1/ 10 0/ 10 0/ 10 0/ 10 0/ 10 Congestion, Level D 1/ 10 0/ 10 0/ 10 2/ 10 0/ 10 0/ 10 0/ 10 0/ 10 Mice Nasal turbinate congestion, Level A 0/ 10 4/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 11 Eosinophilic globules in nasal turbinate, Level A 0/ 10 0/ 10 0/ 10 2/ 10 0/ 10 1/ 10 0/ 10 5/ 11 Congestion, Level B 0/ 10 4/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 11 Eosinophilic globules in nasal turbinate, Level B 0/ 10 0/ 10 0/ 10 2/ 10 0/ 10 3/ 10 6/ 10 6/ 11 Eosinophilic globules in nasal turbinate, Level C 0/ 10 0/ 10 0/ 10 1/ 10 0/ 10 0/ 10 0/ 10 1/ 11 Congestion, Level C 0/ 10 4/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 11 Focal Hemorrhage, Level D 1/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 11 Congestion, Level D 0/ 10 4/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 10 0/ 11 EPA/ OW/ OS/ HECD Final draft E 48 Adapted from ToxiGenics, Inc. ( 1984) EPA/ OW/ OS/ HECD Final draft E 49 Table E 5. Respiratory Tract Histopathology in Rats Chronically Exposed to HCl.

Observation HCl Air Control Colony Control Number of animals examined 99 99 99 Larynx Hyperplasia 22 2 2 Trachea Hyperplasia 26 6 2 Nasal Rhinitis 81 72 70 Epithelial or squamous hyperplasia 62 51 45 Squamous metaplasia 9 5 6 Adapted from Sellakumar et al. ( 1985)


[Federal Register Volume 81, Number 207 (Wednesday, October 26, 2016)]
[Notices]
[Pages 74427-74428]
[FR Doc No: 2016-25877]

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

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. ER17-94-000]

ESS Snook Project, 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 of
ESS Snook Project, 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 7, 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
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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
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    Dated: October 18, 2016.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2016-25877 Filed 10-25-16; 8:45 am]
 BILLING CODE 6717-01-P