# I. RECOMMENDATIONS FOR A STANDARD FOR THE OXIDES OF NITROGEN (NITROGEN DIOXIDE AND NITRIC OXIDE)
The National Institute for Occupational Safety and Health (NIOSH) recommends that employee exposure to the oxides of nitrogen (nitrogen dioxide and nitric oxide) in the workplace be controlled by adherence to the following sections. The standard is designed to protect the health and safety of workers for up to a 10-hour workday, 40-hour workweek over a working lifetime; compliance with the standard is measurable by techniques that are valid, reproducible, and available to industry and government agencies. Sufficient technology exists to permit compliance with the recommended standard. The criteria and standard will be subject to review and revision as necessary.
For the purpose of this standard, "oxides of nitrogen" refers to nitric oxide and nitrogen dioxide. Since nitrogen dioxide in the working environment results, at least in part, from oxidation of nitric oxide, occupational exposures are customarily to mixtures of these gases rather than to either gas alone. "Occupational exposure to the oxides of nitrogen" is defined as exposure to the oxides of nitrogen equal to or above one-half the recommended workroom limit. Adherence only to sections  7) is required when workplace environmental concentrations of oxides of nitrogen are not greater than one-half of the recommended workplace environmental limit.
Procedures for identification of exposure areas can be accomplished by determinations using sampling and analytical methods described in Appendices I and IX, or III or by any method shown to be equivalent in accuracy, precision, and sensitivity to the methods specified.

# Section 2 -Medical
Medical surveillance with particular emphasis on the respiratory system shall be made available as specified below for all workers subject to "exposure to the oxides of nitrogen."
(a) Preplacement and periodic medical examinations shall be made available to workers occupationally exposed to the oxides of nitrogen.
These periodic examinations shall be administered annually or as otherwise indicated by the responsible physician, and shall include as a minimum:
(1) Comprehensive or interim medical and work histories.
(2) Pulmonary function tests including auscultation of the chest, measurement of Forced Vital Capacity (FVC), and Forced Expiratory Volume in the first second (FEV 1).
(3) A judgment of the worker's physical ability to use negative or positive pressure respirators as defined in 29 CFR 1910.134.
In addition to the above, a 14" x 17" posterior-anterior chest X-ray shall be included in the preplacement medical examination.
Additional evaluations of pulmonary function, such as tests of pulmonary compliance and diffusion studies, may be found useful in the medical surveillance of workers exposed to nitrogen oxides.
(b) Initial examinations for presently employed workers shall be offered within 6 months of the promulgation of a standard incorporating these recommendations and annually thereafter. (2) When a respirator is permitted by paragraph (a) (1) of this Section, it shall be selected and used pursuant to the following requirements:
(A) For the purpose of selecting the respirator tc be used by employees, the employer shall measure the concentrations of nitrogen dioxide and nitric oxide in the workplace air initially and i thereafter whenever control, process, operation, worksite, or climate changes occur which may likely affect the concentrations of oxides of nitrogen. This does not apply during emergencies and during firefighting.

# (B)
The employer shall ensure that no employee is exposed at concentrations of oxides of nitrogen in excess of prescribed limits because of improper respirator selection, fit, use, or maintenance.
(C) A respiratory protection program meeting the requirements of 29 CFR 1910.134 and 30 CFR 11 shall be established and carried out by the employer.
(D) The employer shall provide employees with respirators in accordance with Table 1-1 and shall ensure that employees use the respirators provided in a proper manner.
(E) Respirators described in Table 1-1 shall be those approved under the provisions of 30 CFR 11 as amended.
(F) Respirators specified in Table 1-1 for use in atmospheres of higher concentrations of oxides of nitrogen may be permitted for use in atmospheres which contain lower concentrations.
(G) Wherever bulk nitrogen dioxide or nitric oxide is stored or is introduced into an operation or process from a source under pressure, the employer shall store emergency and escape-type respirators so that they are readily accessible to each employee.

# (H)
The employer shall assign an employee to a job which requires the wearing of a respirator for protection against oxides of nitrogen only with a medical evaluation of the employee's physical ability to safely perform his or her duties while wearing a respirator.

# Cl)
The employer shall instruct the employee in how to don the respirator and how to check its fit and operation.

# (J)
The employer shall provide the employee with instructions in the proper wearing of the respirator.

# CK)
The employer shall instruct the employee to use the respirator provided in accordance with instructions and training received, to test the fit of the respirator before entering an atmosphere contaminated with oxides of nitrogen, to guard against damage to the respirator, and to report any malfunction of the respirator to his or her supervisor.

# (L)
The employer shall instruct the employee in how to recognize and handle emergency situations.

# (M)
The employer shall establish and carry out a program of cleaning, sanitizing, inspecting, maintaining, repairing, and storing of respirators to ensure that employees are provided with respirators that are in good operating condition, and shall instruct employees in day-to-day maintenance of respirators.
(N)
The employer shall periodically monitor the use of respirators to ensure that the proper type of respirator is being worn in a satisfactory manner.
The employer shall periodically evaluate t effectiveness of the respiratory protection program and eliminate any deficiencies. (2) A gas mask with a front-or backmounted N02 canister
(3) Any supplied-air respirator with a full facepiece, helmet, or hood (4) Any self-contained breathing apparatus with a full facepiece (1) Type C supplied-air respirator oper ated in demand mode (negative pressure) with full facepiece
(2) Self-contained breathing apparatus operated in demand mode (negative pressure) with full facepiece   (1) Self-contained breathing apparatus operated in pressuredemand mode (positive pressure) with full facepiece Firefighting (1) Self-contained breathing apparatus operated in pressure-demand mode (positive pressure) with full facepiece *Respirators equipped with a quarter-mask or half-mask facepiece are not recommended because eye irritation may become significant at low concentrations of nitrogen dioxide in air.

# (b)
Eye and Face Protection
(1) Eye and face protection shall be achieved by adherence to the requirements of 29 CFR 1910.133.
(2) Chemical safety goggles -cup-type or rubber-framed goggles, equipped with approved impact-resistant glass or plastic lenses, shall be worn whenever there is danger of eye contact, such as working with pipelines, valves, etc, which might leak and spurt liquid nitrogen dioxide or nitric oxide.
(3) Spectacle-type safety goggles -metal-or plastic-rim safety spectacles with unperforated side shields, or suitable all-plastic safety goggles may be used where continuous eye protection is desirable.
(4) Face shield -plastic shields with forehead protection should be worn in addition to goggles. (2)
A closed process for handling the oxides of nitrogen is the preferred engineering control and shall be used wherever possible to prevent contamination of the work area.
(3) An enclosed process with exhaust ventilation is the next preferred means of engineering control of oxides of nitrogen and shall be used wherever possible if a closed process is not feasible. These systems shall be designed and constructed to prevent the escape of oxides of nitrogen into workplaces. Also, appropriate measures are to be taken to ensure that the discharge of oxides of nitrogen to the outdoor atmosphere is in accordance with applicable federal, state, and local environmental pollution control laws and regulations. (1) Persons who must enter enclosed spaces not known to be safe, such as tanks, reaction vessels, and small rooms which contain oxides of nitrogen or wherein oxides of nitrogen may be liberated, shall wear either a combination type C supplied-air respirator operated in the continous-flow mode (positive pressure) or pressure-demand mode (positive pressure) and auxiliary self-contained breathing air supply operated in the pressure-demand mode (positive pressure) equipped with a full facepiece, or a self-contained breathing apparatus operated in the pressure-demand mode (2)
The employer shall ensure that employees are familiar with procedures covering emergencies.
(3) Self-contained breathing apparatus operated in the pressure-demand mode (positive pressure) and equipped with a full facepiece shall be stored so that they are immediately available to persons who need them to escape from an area where an emergency may occur.
(4) Persons who must enter an area where an emergency has occurred to carry out cleanup operations, maintenance, or repair, shall be equipped with respirators and safety harnesses as prescribed in paragraph (b) (1) of this Section. Also, at least one standby person as described in paragraph (b) (1) of this Section shall be present in a safe place near the area where the emergency has occurred for possible rescue of persons inside the hazardous area. Communications as described in paragraph (b) (1) of this Section shall be maintained between persons inside the hazardous area and the standby person.
(5) Only a self-contained breathing apparatus operated in the pressure-demand mode (positive pressure) and equipped with a full facepiece shall be used by a person engaged in firefighting.
(6) Eyewash fountains and drench-type safety showers shall be readily available in areas where liquid forms of the oxides of nitrogen are being handled. This equipment shall be inspected and tested at least every 30 days to insure proper operation.
(e) Preventive Maintenance (1) The employer shall carry out a preventive maintenance program which shall include regular and periodic inspection of equipment for leakage of oxides of nitrogen into work areas and immediate repair of leaking equipment.
The employer shall ensure that containers of oxides of nitrogen are stored properly to minimize the escape of oxides of nitrogen into work areas.
( The records shall be retained for at least 20 years after termination of an individual worker's employment.
(3) An industrial hygiene survey of the work area shall be made when equipment changes, process modifications, or worksite changes may reasonably be expected to increase the concentrations of the oxides of nitrogen above the levels defining occupational exposure.
(b) Occupational Exposure to Oxides of Nitrogen (1) If, from the results of an industrial hygiene survey or the judgment of a compliance officer, there is "occupational exposure" to oxides of nitrogen, the employer shall monitor the environmental concentrations of the oxides of nitrogen by the procedures described in Appendix I at least semianually, except as indicated by a professional industrial hygienist, with procedures described in Appendix I.
The first environmental monitoring of the worksite shall be completed within 6 months of the promulgation of a standard incorporating these recommendations.
(3) Environmental monitoring of the workplace shall be carried out by the employer within 30 days after installation of a new process or within 30 days after equipment changes, process modifications, or worksite changes.  Oxides of nitrogen are important and fairly common hazards of the workplace and are also among the most important and frequently encountered contaminants in the general atmosphere. Produced by processes involving high temperatures, they are important constituents of vehicular exhaust gases, electric power generating plant emissions, agricultural silos, and other operations involving combustion. Recognition of the potential sources of nitrogen oxides is important and is a prerequisite to the design of measures for control of occupational exposures.
The development of the recommended standard for occupational exposure to oxides of nitrogen has revealed deficiencies in data in the following areas:
(1) Carefully controlled cross-sectional epidemiologic studies concerned with chronic pulmonary changes and hematologic changes as well as studies on the incidence of chronic obstructive pulmonary diseases in workers exposed to low concentrations of oxides of nitrogen.
(2) Chronic effects in experimental animals exposed to oxides of nitrogen according to schedules and concentrations of exposure which simulate the occupational environment.
(3) The role of oxides of nitrogen in the production of teratogenic, mutagenic, and carcinogenic changes in animals.
( Ultraviolet energy or sufficiently high temperatures to accomplish this in the occupational environment are encountered in electric or gas welding, in the combustion of fuels, eg, in furnaces or internal combustion engines, and in the detonation of explosives.  Nitric oxide is also produced when nitrogen dioxide is dissolved in warm water. The net reaction is:
3N02 + H20 = 2HN03 + NO 
Nitrogen dioxide is formed by the spontaneous oxidation of nitric oxide in air at ordinary temperatures, the equation for this reaction is given by:
2N0 + 02 = 2N02 
Both nitric oxide and nitrogen dioxide are formed when nitric acid reacts with reducing agents. For dilute nitric acid, the resultant mixture contains 'predominantly NO, while for concentrated nitric acid more N02 is produced.  Nitric oxide and nitrogen dioxide rarely exist independently in the occupational environment. The rate at which nitric oxide in air is oxidized to nitrogen dioxide is expressed as:
d(N02)/dt = K(02)(NO)2
where (N02) and (02) represent the concentrations of nitrogen dioxide and oxygen, (NO)2 represents the square of the nitric oxide concentration, t is time, and K is a constant for any temperature (K = 14.8 x 109 at 20C).  Since the rate of oxidation is dependent upon the square of the nitric oxide concentration, oxidation is much more rapid at high concen-trations.  From Wade et al  (b) Sources of Exposure Although nitric oxide is the oxide of nitrogen initially produced in the welding arc or flame,  its concentration in such operations is only rarely reported.
In many field studies   It is difficult to estimate how many people are exposed to oxides of nitrogen since hazardous occupations also involve all workers located in the vicinity of operations or processes having conditions conducive to the generations of nitrogen oxidation, ie, furnaces, boilers, welding, internal combustion engines, and nitrogen oxides produced from numerous chemical processes. The difficulty in delineating the incidence of exposure has been shown by Storlazzi  in a study of welding and burning operations in US naval shipyards. Although only 6,000 workers were directly engaged in such activities, approximately 60,000 workers were indirectly exposed to the byproducts of these operations. NIOSH estimates that 1,500,000 workers are potentially exposed to the oxides of nitrogen. In view of the factors mentioned, this figure is low. The nitrous gases were produced by one of two methods. In the first method, gases produced by the reaction of nitric acid and copper were collected in a gasometer over water, transferred in a tenfold dilution with hydrogen into a paraffin oil gasometer, and then mixed with a stream of fresh air. In the second method, a small amount of air was aspirated by smoking nitric acid and then mixed with a current of fresh air. Airborne concentrations, expressed as concentrations of nitrous acid, were determined by oxidation of samples by hydrogen peroxide or by chemical reduction using potassium iodide. Cats exposed at concentrations of 41, 64, and 57 ppm for 3, 6, and 7 hours, respectively, did not show any signs during exposure or macroscopic lung changes after the animals were killed.
Cats exposed at 117 ppm and above for periods from approximately 1 to 8 hours showed definite changes in respiration, and most animals died during exposure. At necropsy, pulmonary edema and methemoglobinemia were observed. Rabbits exposed at identical concentrations did not show the same signs as the cats.
In this study,   bronchiolitis fibrosa obliterans were, in the opinion of many authors,  largely attributable to the action of the high concentration of nitrogen dioxide.
An experimental study on human subjects on the retention of nitrogen dioxide was reported in 1970 by Wagner.  Seven subjects were exposed to nitric oxide at several different concentrations (5, 1, 0.5 and 0.33 ppm) under conditions of normal and of maximal oral respiration. By comparative analyses of inhaled and exhaled gases, the percentage absorption of the nitric oxide was measured. The retention was uniformly high (from 85 to 93%), seemingly independent of concentration within the range tested, and somewhat higher with maximal as opposed to normal respiration.
A parallel series of studies was conducted with nitrogen dioxide. Absorption rates were similar to those reported for nitric oxide.
Despite the fact that nitrogen dioxide is an irritant gas, there are few primary references in the literature as to its effects upon the eyes or mucosae other than that on the lower respiratory tract. In 1970, Morley
and Silk  reported conjunctivitis and pharyngitis occurring in five men welding zinc-plated steel in a confined space. These effects had subsided 18 hours later when the men were reexamined. Representative atmospheric measurements showed total oxides of nitrogen, expressed as nitrogen dioxide, in the 4-20 ppm range with an average of 7.4 ppm (19 measurements). Rodin and Boyenko  in 1970 reported a prevalence of 64%
-f "chronic catarrhal processes in the upper respiratory tract" in 334 arc welders who had up to 10 years of work history. In the workers who had more than 10 years service in welding, 22% had subatrophic rhino pharyngitis.  to the point of mixing manifested strikingly different toxic effects than those exposed in the same apparatus, but in a more distal section. In the first instance, where the content of unoxidized nitric oxide in the mixture was still relatively high, cyanosis occurred after a few minutes, the red eyegrounds (probably conjunctival or red reflux) became gray-blue, and then breathlessness appeared with paralysis and convulsions. If the mice were promptly removed and exposed to fresh air, they recovered rapidly and completely without apparent sequelae. Mice exposed in the distal part of the apparatus where, according to the author, nitrogen dioxide was predominant showed immediate signs of irritation but no cyanosis and no paralysis. Death resulted from pulmonary edema.
The following year, in their book on toxic gases, Flury and Zemik
 gave some quantitative data on exposure of mice to nitric oxide, probably from the same experiments. Mice exposed at a concentration of 5,000 ppm died after 6-8 minutes. With inhalation at a concentration of 2,500 ppm, the animals were observed to be on their sides after 6-7 minutes of exposure and died after 12 minutes. Removal of the mice after 4-6 minutes of exposure resulted in full recovery within 24 hours.  Both studies indicated that the relationship between concentration and time was best represented by an exponential function.
The thresholds for nitrogen dioxide toxicity were approximately 25% of the rat LC50 values.
 At these concentrations, dogs showed no gross or microscopic changes which were different from controls. Rats showed no gross pathologic lesions; however, microscopic studies indicated that some animals had pulmonary edema.
In In 50% of the guinea pigs exposed for 15-18 months, changes judged to be equivalent to human microbullous emphysema were seen. Such changes were not, however, observed in rats or rabbits.  The authors speculated that nitrogen dioxide exposure might destroy opsinogenic factors and surfactant, or in some way affect the motility of macrophages. Evans et al  continously exposed rats at 15-17 ppm for 48 hours. The results showed that there was a large increase in the number of dividing macrophages and an increase in the total number. tachypnea and all animals died of nonpulmonary diseases (predominantly of nephrosclerosis). Airflow resistance and dynamic compliance were not affected. Some microscopic changes were seen in the terminal and respiratory bronchiolar epithelium, ie, loss of exfoliative activity, reduced blebbing of cytoplasm into the airways, reduction or loss of cilia, and the appearance of rod-shaped intracytoplasmic crystalloid inclusions.
In 1972, Stephens et al  reported results of a study in which rats were exposed continuously at 2 ppm for periods ranging from a few hours to 21 days. They showed loss of cilia, hypertrophy, and focal hyperplasia in the epithelium of the terminal bronchioles. Animals allowed to survive returned to normal after 21 days of continuous exposure. Evans et al  exposed rats continuously at 2 ppm for up to 360 days. An increase in type 2 pneumocytes, ie, cuboidal rather than flattened and ultra-thin, was observed in peripheral alveoli after two days of exposure.
However, the number of cells declined to control levels by the fifth day.
There was no increase in cells in other alveoli or in the bronchioles.   Animals exposed daily for 6 months showed no microscopic reaction attributable to the inhaled gas. After 1 year, dogs showed a general pattern of moderately dilated alveolar ducts and sacs which contained some edema fluid and an occasional macrophage. Necropsy of dogs at 18 months showed, in addition to the above findings, an occasional area of mild to moderately thickened alveolar septa with chronic inflammatory cells.
Daily exposure of guinea pigs to nitrogen dioxide at 1 ppm for 3 months revealed an essentially normal lung parenchyma, a mild hyperplasia of bronchial epithelium, and a prominence of lymph follicles. At 3 and 6 months, the reaction in rabbits exposed daily at 1 ppm was that of an increased incidence of congestion with no visible lesions or other tissue alterations. The findings in the other 2 species exposed to nitrogen dioxide at 1 ppm were not described separately, but the authors implied that they were essentially negative.  After 14 months of exposure, the incidence of tumors was essentially the same for controls and exposed animals. Experimentally exposed animals killed after 16 months of exposure showed the same number of pulmonary tumors as controls. Comments were generated as a result of these findings, criticizing the small sample size.
 Although the incidence of tumors was greater in the exposed mice than in the controls following 12 months of exposure, subsequent statistical analysis shows this difference was not significant. In view of this statistical insignificance as well as the evident similarity in the incidence of tumors between controls and exposed animals after 14 and 16 months of exposure, the supposition that nitrogen dioxide has a tumorpromoting effect must be questioned. Further studies, with larger numbers of animals, should be performed before making inferences concerning the tumor-promoting capacity of nitrogen dioxide.
In a brief note with few supporting data, Henschler and Ross  reported that mice intermittently exposed to nitrogen dioxide at 40 ppm over a period of 18 months had no evidence of malignant tumors on serial section of lungs. They also found an increasing incidence of lung adenomas with a decreasing frequency of exposure, thus a decreasing dose. They added that there was not an increasing incidence of lung cancer in nitrogen dioxide-exposed workers, but gave no data in support of this conclusion.  Kosmider et al  in 1972 reported an epidemiologic study on 70 chemical plant workers exposed 6-8 hours daily, for 4-6 years, to nitrogen oxides concentrations ranging from 0.4 to 2.7 ppm. There was evidence of chronic bronchitis in an unstated number of these workers. No abnormality was seen in the chest roentgenograms, and there were no significant changes in spirometric measurements or blood gases compared with controls.
However, the total proteins in the blood serum were significantly lower than in controls. The exposed workers showed a reduction in albumin and gammaglobulins and an increase in the alpha-1, alpha-2, and betaglobulins.
There were also significant increases in the urinary hydroxyproline and acid mucopolysaccharides in the exposed men. The authors concluded that these abnormalities were indicative of protein synthesis inhibition and decomposition of collagen, consistent with the emphysema process.   Kosmider et al,  in a study of men from a chemical works, reported that these workers were exposed daily at nitrogen oxides con centrations fluctuating between 0.4 and 2.7 ppm as nitrogen dioxide over 6- Collectively, the work of Bretschneider and Matz  and Fine et al  suggests that N-nitroso compounds may be formed in the workplace air or in the sampling train.
However, extensive research will be required to Although the LC50 for beagle dogs was not determined, the dogs appeared to succumb at lower concentrations than did the rats and mice. Effects noted included polydypsia, loss of appetite, ascites, hyperacute liver necrosis, leukopenia, disruption of normal blood coagulation, and hemorrhage into the wall of the gastrointestinal tract, the abdominal cavity, and other tissues. Analogous effects have been noted in humans accidentally exposed The solid-type adsorber is simpler to use and avoids other disadvantages encountered in trying to perform personal sampling with a liquid-type collector.
In addition, Blacker reported that samples collected on the solid adsorber have a high degree of stability for at least 2 weeks. This is important in the event that analyses cannot be performed promptly.
If a second solid-type adsorber is substituted for the bubbler in the sampling train described by the Intersociety Committee, a personal sampling device for measuring both nitrogen dioxide and nitric oxide is produced. Such a device, described in Appendix I, represents the recommended method for sampling the oxides of nitrogen. The method is recommended because of its simplicity, suitability for personal sampling, and because samples remain stable during shipment to the laboratory.
The samples may then be analyzed by the procedure described by  
The American National Standards Institute (ANSI) recommended a 5-ppm ceiling as acceptable for repeated daily exposures to nitrogen dioxide.
 A concentration of 15 ppm was defined as the maximum "peak" for an 8-hour workday. The total exposure period at this "peak" was not to exceed 5 minutes and it was assumed that such excursions above the ceiling would be infrequent (not daily). In 1937, Vigdortschik et al  reported an epidemiologic study of 127 workers exposed to "oxides of nitrogen" and to "no other injurious gases" at levels "mostly below 2.8 ppm," in sulfuric acid plants and in print-etching shops- An increased prevalence of emphysema was reported in these workers, as compared with a control group matched in all respects but unexposed to "toxic substances." In addition, many other blood, biochemical, and urinary abnormalities were reported, but the actual prevalence of the abnormalities was not given for either the exposed workers or the control group. Moreover, the assertion that the workers were exposed to nitrogen oxides alone and to "no other injurious gases" is questionable, especially with respect to workers in sulfuric acid plants.    in animals exposed to nitrogen dioxide at and below the current federal standard. In view of these results, it is concluded that the federal standard of 5 ppm should be reduced.

# The presence of dental erosion was
A reduction in effective lung compliance with a corresponding increase in inspiratory and expiratory maximum viscous resistance as well as significant decreases in arterial oxygen tension and single-breath carbon monoxide diffusing capacity have been noted in normal adult males exposed to nitrogen dioxide for 10-15 minutes at 4-5 ppm.  The Although the specific concentration at which these changes begin to occur in normal human subjects is unknown, it is likely to be at about the same or perhaps a slightly higher concentration than the one inducing pulmonary changes in humans with existing chronic bronchitis. Therefore, the environmental limit should be reduced to a ceiling value of 1 ppm to prevent acute irritant effects in the lungs of workers exposed to nitrogen dioxide.
In addition, the prevention of repeated acute episodes of irritancy should lessen the risk of developing chronic obstructive lung disease.
Concerning nitric oxide, there is no direct quantitative basis for an environmental limit. No environmental data are available on exposures to nitric oxide alone. Furthermore, it is improbable that exposures to nitric oxide alone, as opposed to a mixture of nitric oxide and nitrogen dioxide, would occur In an occupational situation. Even under experimental circumstances, it would be difficult to achieve human exposures to nitric oxide in the absence of higher oxides of nitrogen, particularly nitrogen dioxide, at concentrations above about 100 ppm because of the rapid rate of oxidation to nitrogen dioxide.
 At concentrations below 100 ppm, it might be feasible to achieve experimental exposures to nitric oxide virtually free of nitrogen dioxide because of the much slower rate of oxidation,  but such experiments addressed to toxicity have not been reported.
One experiment on seven human volunteers exposed at 5, 1, 0.5, and 0.33 ppm by inhalation through the mouth has been reported.  However, this study presented only the proportion of the inhaled gas which was absorbed, and no subjective or objective effects or durations of exposure were mentioned. The proportionate absorption of the inhaled gas containing nitric oxide or nitrogen dioxide was found to be virtually the same.
In 1941, McCord et al  reported a study of 4 arc-welders who were exposed, for an unstated period of time, to "nitrous gas" expressed as nitrogen dioxide at levels ranging from 2.0 to 10.3 ppm. Independent experiments have demonstrated  that, in the presence of an electric arc, the initial proportion of nitric oxide present in the "nitrous gas" may be above 90%. At nitric oxide concentrations around 10 ppm, the rate of oxidation is very slow (by calculation, it would take 2-3 hours for a 25% conversion to nitrogen dioxide at 20 C).
 Therefore, it is inferred that the four welders observed by McCord et al  were exposed predominantly to nitric oxide rather than to nitrogen dioxide. The welders all had methemoglobin present in their blood to the extent of 2.3, 2.3,  administration was discontinued, and 100% oxygen was given. The patient showed signs of some respiratory distress but made a complete recovery. It must be stressed that the levels of exposure to nitric oxide and nitrogen dioxide suggested in these two cases are speculated approximations only.
The actual gas mixture which was administered to the two patients was never analyzed; however, contamination of the nitrous oxide with nitric oxide in excess of 1.5% was determined from analyses performed by the manufacturer on other cylinders from the same production batch.
In addition, if fractional distillation had occurred,  the first gas released from the cylinder would probably have been primarily nitric oxide; thus, the first patient might have been exposed to nitric oxide in excess of 1.5%. methemoglobinemia and cyanosis in both humans and experimental animals, so an environmental limit is obviously needed. In the absence of data showing toxic effects for humans and animals exposed at and below 25 ppm, it is believed that the current federal standard of 25 ppm should be continued as a TWA for up to 10 hours/day and 40 hours/week to protect workers from exposure to nitric oxide. Future research should be conducted to determine concentrations of nitric oxide that result in impairment of respiratory or other biologic functions so that a soundly based standard may be promulgated.
It is recognized that many workers are exposed to the oxides of nitrogen at ambient air concentrations or at concentrations considerably below the recommended occupational limits.
Under these conditions, it should not be necessary to comply with many of the provisions of this recommended standard. However, concern for worker health requires that protective measures be instituted below the enforceable limits to ensure that exposures do not exceed the standard. For this reason, "occupational exposure to the oxides of nitrogen" has been defined as exposure above half the environmental limits, thereby delineating those work situations which do not require the installation of unnecessary controls and the expenditure of health resources for provisions such as environmental and medical monitoring, and associated recordkeeping.

# VII. RESEARCH NEEDS

# Epidemiologic Studies
Three epidemologic studies (56,70,71) indicated that chronic effects on the pulmonary system as well as hematologic changes may be observed in workers exposed to oxides of nitrogen at and below the current federal limits. However, each of these studies contained errors or omissions in at least one of the following categories:     "safety solvent," or "aliphatic hydrocarbon" when the specific name is known.
The "%" may be the approximate percentage by weight or volume (indicate basis) which each hazardous ingredient of the mixture bears to the whole mixture. This may be indicated as a range or maximum amount, ie, "10-40% vol" or "10% max wt" to avoid disclosure of trade secrets.

# P R E C A U T IO N A R Y ST A T E M E N T S IX SP E C IA L PRECAUTIO N S O T H E R H A N D L IN G A N D S T O R A G E R E Q U IR E M E N T S P R E P A R E D BY
A DDRESS:           From Adley 
DATE
Riddick

# PRO DUCT IDENTIFICATION M A N U F A C T U R E R 'S N A M E R E G U L A R T E L E P H O N E NO E M E R G E N C Y T E L E P H O N E NO A D D R E S S TRADE NAM E SYN O N Y M S M HAZARDOUS IN G RED IEN T S M A T E R IA L O R C O M P O N E N T % H A Z A R D D A T A III PH Y SIC A L DATA B O IL IN G PO IN T . 760 M M HG M E L T IN G PO INT S P E C IF IC G R A V IT Y ( H j O -U V A P O R P R E S S U R E V A PO H D E N S IT Y (A IR = 1) S O L U B IL IT Y IN H 20. % B Y WT % V O L A T IL E S 8 Y VO L E V A P O R A T IO N R A T E (BUTYL. A C E T A T E = 1) A P P E A R A N C E A N D O D O R 6 6

# IV FIRE AND EXPLO SIO N DATA F LA SH PO INT (TEST M ETH O D ) A U T O IG N IT IO N T E M P E R A T U R E F L A M M A B L E L IM IT S IN A IR , % BY VOL. LO W ER UPPER E X T IN G U IS H IN G M E D IA SP E C IA L F IR E F IG H T IN G P R O C E D U R E S U N U SU A L FIR E A N D E X P L O S IO N H A Z A R D V HEALTH HAZARD INFORMATION H E A L T H H A Z A R D D A T A R O U T E S OF E X P O SU R E IN H A L A T IO N S K IN C O N TA C T S K IN A B S O R P T IO N EYE C O N T A C T IN G E S T IO N E F F E C T S OF O V E R E X P O S U R E A C U T E O V E R E X P O S U R E C H RO N fC O V E R E X P O S U R E E M E R G E N C Y A N D FIR ST A ID P R O C E D U R E S EY ES S K IN IN H A L A T IO N IN G EST IO N NO T ES TO P H Y S IC IA N

# XIII. TABLES AND FIGURES

# I n t e r m i t tent: 21-23 h r s / d a y A n t i g e n s e n s i t i z a t i o n M i c r o s c o p i c c h a n g e s in l u n g tissue T h r e s h o l d of to xicity a p p r o x i m a t e l y 2 5 % of L C 5 0 l e v e l s for rats. A t these levels, dogs s h o w e d n o gross or m i c r o s c o p i c changes ra t s sh o w e d some p u l m o n a r y edema. E x p o s u r e at 100 p p m r e s u l t e d in de a th w i t h i n 24 hrs.

# Rats e x p o s e d at 12.5 p p m h a d m o d e r a t e h y p e r t r o p h y an d h y p e r p l a s i a of b r o n c h i a l a n d b r o n c h l o l a r e p i t h e l i u m as well i r r e g u l a r a l v e o lar ducts a n d al v e o li a f t e r 4 0 da y s of exposure. E x p o s u r e at 70 p p m e n h a n c e d s e n s i t i z a tion 40 p p m and less d i d not. 1/3 o f a n i m a l s died w i t h i n fi r s t 3 days. E p i t h e l i a l h y p e r p l a s i a an d h y p e r t r o p h y of b r o n c h i a l and a l v e o l i n o t e d in a n i m a l s k i l l e d im m e d i a t e l y af t e r e x p o s u r e . R e g r e s s i o n of i n f l a m m a t o r y and e p i t h e l i a l h y p e r p l a s t i c ch