All shipping and storage containers for lithium chromate, lithium bichromate, sodium chromate, sodium bichromate, potassium chromate, potassium bichromate, rubidium chromate, rubidium bichromate, cesium chromate, cesium bichromate, and ammonium chromate, the hydrates of these compounds, high purity aqueous solutions of these compounds, and dry mixtures containing only these materials shall bear the same label except that "Inhalation may cause cancer" shall be deleted and "Extreme Health Hazard" shall be replaced by "Moderate Health Hazard". (c) Because of the flammable characteristics of ammonium bichromate (dichromate), shipping and storage containers for dry forms of this compound shall bear the following label in addition to, or in combination with, labels required by other statutes, regulations, or ordinances: AMMONIUM BICHROMATE DANGER! HIGHLY FLAMMABLE MODERATE HEALTH HAZARD MAY CAUSE IRRITATION, RASH, OR EXTERNAL ULCERS. Keep away from heat, sparks, and open flame. Keep container closed. Avoid contact with skin and eyes. Avoid breathing dust or solution spray. In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Call a physician. Flush skin with water. Wash clothing before reuse.Combination supplied air respirator, pressure-demand type, with auxiliary self-contained air supply.# I. RECOMMENDATIONS FOR A CHROMIUM(VI) STANDARD
The National Institute for Occupational Safety and Health (NIOSH) recommends that worker exposure to chromium(VI), ie, hexavalent chromium or Cr(VI), 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 all sections of the standard should prevent all noncarcinogenic adverse effects of exposure to chromium(VI) In the workplace air and through skin exposure and should reduce materially the risk of lung cancer from occupational exposure to carcinogenic chromium(VI). The standard is measurable by techniques that are valid, reproducible, and available. Sufficient technology exists to permit compliance with the recommended standard. The standard will be subject to review and revision as necessary.
For the purpose of this standard, "chromium(VI)" is defined as the chromium In all materials in the +6 (hexavalent) state.
There are 2 recommended standards for chromium(VI). One addresses occupational exposure to a group of noncarcinogenic, but otherwise hazardous, materials, while the other pertains to occupations and workplaces where there is exposure to other chromium(VI) materials associated with an increased incidence of lung cancer.
On the basis of the chemical analysis of airborne chromium(VI) materials, there is no practical means of distinguishing between these 2 groups of chromium(VI) materials. Until the airborne chromium(VI) in a particular workplace is demonstrated by the employer to be of the type considered to be noncarcinogenic, all airborne chromium(VI) shall be considered to comprise carcinogenic materials.
Based . on current evidence, "noncarcinogenic chromium(VI)" is the chromium(VI) in monochromates and bichromates (dichromates) of hydrogen, lithium, sodium, potassium, rubidium, cesium, and ammonium, and chromium(VI) oxide (chromic acid anhydride). "Carcinogenic chromium(VI)" comprises any and all chromium(VI) materials not included in the noncarcinogenic group above. "Occupational exposure to carcinogenic chromium(VI)" is defined as exposure to airborne chromium(VI) at concentrations greater than one-half of the workplace environmental limit for carcinogenic chromium(VI). "Occupational exposure to noncarcinogenic chromium(VI)" is defined as exposure to airborne chromium(VI) at concentrations greater than one-half of the workplace environmental limit for noncarcinogenic chromium(VI). Exposure to chromium(VI) at concentrations less than one-half of the workplace environmental limit will not require adherence to the following sections, except for 3(a,b,c,d), 4a, 5, 6(b,c,e,f), and 7. Procedures for sampling and analysis of chromium(VI) in air shall be as provided in Appendices I and II, or by any method shown to be equivalent in precision, accuracy, and sensitivity to the methods specified.

# Section 2 -Medical
Medical surveillance shall be made available as outlined below for all workers with occupational exposure to carcinogenic or noncarcinogenic chromium(VI), including maintenance personnel periodically exposed during routine maintenance or emergency repair operations.
(a) Preplacement and annual medical examinations shall include:
(1) A comprehensive or interim work history.
A detailed medical history Including information on conditions Indicating the Inadvisability of further exposure to chromium(VI), eg, potential skin or pulmonary sensitization, a skin or mucous membrane condition that may be exacerbated by chromium(VI), smoking habits, and history of liver or kidney disease.
(3) Examination of the skin for evidence of dermatitis or chrome ulcers, and of the membranes of the upper respiratory tract for irritation, bleeding, ulcerations, or perforations.
(4) An evaluation of the worker's ability to use negative or positive pressure respirators.
(5) Urinalysis.
(b) For workers with occupational exposure to carcinogenic chromium(VI), preplacement and annual medical examinations shall include 14" X 17" chest X-rays. Other tests, including sputum cytology and liver function studies, shall be considered by the responsible physician.
(c) For workers with occupational exposure to noncarcinogenic chromium(VI) and not to carcinogenic chromium(VI), preplacement medical examinations shall include 14" x 17" chest X-rays. Thereafter, X-ray examinations shall be offered at 5-year intervals and annually after age 40.
Other tests, such as liver function studies, may be considered by the responsible physician.
(d) Medical examinations shall be made available to all workers with signs or symptoms of skin or upper respiratory tract irritation likely to have been the result of exposure to chromium(VI).
(e) If clinical evidence of adverse effects due to chromium(VI) is developed from these medical examinations, the worker shall be kept under a physician's care until the worker has completely recovered or maximal improvement has occurred.
(f) Initial annual examinations for presently employed workers shall be offered within 6 months of the promulgation of a standard incorporating these recommendations.
(g) The medical representatives of the Secretary of Health, Education, and Welfare, of the Secretary of Labor, and of the employer shall have access to all medical records.
Physicians designated and authorized by any employee or former employee shall have access to that worker's medical records.
(h) Medical records shall be maintained for all employees with occupational exposure to carcinogenic or noncarcinogenic chromium(VI) and for maintenance personnel with periodic exposure. Preplacement X-rays and X-rays for the 5 years preceding termination of employment and all medical records with pertinent supporting documents shall be retained at least 30 years after the individual's employment is terminated. All storage containers of chromic acid, or chromium(VI) oxide (chromic acid anhydride) shall bear the following label in addition to, or in combination with, labels required by other statutes, regulations, or ordinances.

# CHROMIUM TRIOXIDE (CHROMIC ACID) DANGER! POWERFUL OXIDIZER CONTACT WITH OTHER MATERIAL MAY CAUSE FIRE MAY CAUSE DELAYED BURNS OR EXTERNAL ULCERS
Keep container closed. Do not get in eyes, on skin, on clothing. Do not breathe dust or mist from solutions. In case of contact, immediately flush skin or eyes with plenty of water for at least 15 minutes. For eyes, get medical attention immediately. Wash clothing before reuse. Use fresh clothing daily. Take showers after work, using plenty of soap.

# (e)
In areas where there Is occupational exposure to carcinogenic chromium(VI), the following warning sign shall be posted in readily visible locations, particularly at the entrances to the area.

# WARNING CANCER-SUSPECT AGENT USED IN THIS AREA UNAUTHORIZED PERSONS KEEP OUT
The sign shall be printed both in English and in the predominant language of non-English-speaking workers, if any, unless they are otherwise trained and informed of the hazardous areas. All  The sign shall be posted in readily visible locations, particularly at the entrances to the area. The sign shall be printed both in English and in the predominant language of non-English-speaking workers, if any, unless they are otherwise trained and informed of the hazardous areas.
All illiterate workers shall receive such training. (1) Coveralls or other full-body protective clothing shall be worn in areas where there is occupational exposure to chromium(VI).
Protective clothing shall be changed at least daily at the end of the shift and more frequently if it should become grossly contaminated.
(2) Impervious gloves, aprons, and footwear shall be worn at operations where solutions of chromium(VI) may contact the skin.
Protective gloves shall be worn at operations where dry compounds of chromium(VI) are handled and may contact the skin.
(3) Eye protection shall be provided by the employer and used by the employees where eye contact with chromium(VI) is likely.
Selection, use, and maintenance of eye protective equipment shall be in accordance with the provisions of the American National Standard Practice for Occupational and Educational Eye and Face Protection, ANSI Z87. .
Unless eye protection is afforded by a respirator hood or facepiece, protective goggles or a face shield shall be worn at operations where there is danger of contact of the eye with dry or wet compounds of chromium(VI) because of spills, splashes, or excessive dust or mists in the air.
The employer shall ensure that all personal protective devices are inspected regularly and maintained in clean and satisfactory working condition.
(5) Work clothing shall not be taken home by employees.
The employer shall provide for maintenance and laundering of protective clothing.
The employer shall ensure that precautions necessary to protect laundry personnel are taken when soiled protective clothing is laundered.
(b) Respiratory Protection from Carcinogenic Chromium(VI)
Engineering controls shall be used wherever feasible to maintain airborne carcinogenic and noncarcinogenic chromium(VI) concentrations below those recommended in Section 1 above. Compliance with the permissible exposure limits by the use of respirators is only allowed when airborne chromium(VI) concentrations are in excess of the workplace environmental limit because required engineering controls are being installed or tested, when nonroutine maintenance or repair is being accomplished, or during emergencies. When a respirator is thus permitted, it shall be selected and used in accordance with the following requirements:
(1) For the purpose of determining the type of respirator to be used, the employer shall measure the airborne concentration of chromium(VI) in the workplace initially and thereafter whenever process, worksite, climate, or control changes occur which are likely to increase the airborne concentration of chromium(VI); this requirement does not apply when carcinogenic chromium(VI) is present.
The employer shall ensure that no worker is overexposed to chromium(VI) because of improper respirator selection, fit, use, or maintenance.
The employer shall provide respirators in accordance with Table 1-1, or Table 1-2 when appropriate, and shall ensure that the employee uses the respirator provided.
(5) Respirators described in Tables 1-1 and 1-2 shall be those approved under the provisions of 29 CFR 1910.134 and 30 CFR 11.
The employer shall ensure that respirators are adequately cleaned, and that employees are instructed on the use of respirators assigned to them and on how to test for leakage.
Where an emergency may develop which could result in employee injury from chromium(VI), the employer shall provide an escape device as listed in Table 1-1, or in Table 1-2 where appropriate. Instruction shall Include, as a minimum, all information in Appendix III which is applicable to the specific chromium(VI) product or material to which there is exposure. This information shall be posted in the work area and kept on file, readily accessible to the worker at all places of employment where chromium(VI) is involved in unit processes and operations. Evacuation or Escape (no concen tration limit)
Half-mask respirator with replaceable high efficiency filter(s) or Type C supplied-air respirator, demand type (negative pressure), with half-mask facepiece Full facepiece respirator with replaceable high efficiency filter(s) or Type C supplied-air respirator, demand type (negative pressure), with full facepiece or Self-contained breathing apparatus in demand mode (negative pressure), with full facepiece Powered air-purifying (positive pressure) respirator with high efficiency filter(s) Self-contained breathing apparatus with positive pressure in full facepiece or Combination supplied-air respirator, pressure-demand type, with auxiliary self-contained air supply Self-contained breathing apparatus with positive pressure in full facepiece or Combination supplied-air respirator, pressure-demand type, with auxiliary self-contained air supply Self-contained breathing apparatus in demand or pressure-demand mode (negative or positive pressure) or Gas mask, Type N, with high efficiency filter, and mouthpiece respirator with high efficiency filter(s) Note: A high efficiency filter is defined as a filter having an efficiency of at least 99.97% against 0.3 jum DOP(Dioctyl Phthalate) A continuing educational program shall be instituted to ensure that all workers have current knowledge of job hazards, proper maintenance procedures, and cleanup methods, and that they know how to use respiratory protective equipment and protective clothing correctly. (2) Clean protective clothing shall be put on before each work shift.
(3) If, during the shift, the clothing becomes wetted with a solution, slurry, or paste of a chromium(VI) material, or grossly contaminated with a dry form of such material, it shall be removed promptly and placed in a special container for garments for decontamination or disposal.
The employee shall wash the contaminated skin area thoroughly with soap and a copious amount of water. A complete shower is preferred after anything but limited, minor contact. Then, clean protective clothing shall be put on before resuming work. When working directly with chromium(VI) oxide, with unsealed containers of chromium(VI) oxide, or with chromium(VI) oxide in other than fully enclosed operations, protective devices and clothing shall be removed and the arms, hands, and face thoroughly washed after working with chromium(VI) oxide, and at 30-minute intervals when working with chromium(VI) oxide for extended periods of time.
(4) Minor areas of skin (principally the hands) contaminated by contact with chromium(VI) shall be washed immediately and thoroughly with an abundance of water. Water shall be easily accessible in the work areas from low-pressure, free-running hose lines or showers.
(5) If chromium(VI) comes into contact with the eyes, the eyes should be flushed with a large volume of low-pressure flowing water for at least 15 minutes. Medical attention shall be obtained without delay but not at the expense of thoroughly flushing the eyes.
(c) Procedures for emergencies, including firefighting, shall be established to meet foreseeable events. Necessary emergency equipment, including appropriate respiratory protective devices, shall be kept in readily accessible locations. Only self-contained breathing apparatus with positive pressure in the faceplece shall be used in firefighting.
Appropriate respirators shall be available for use during evacuation.
(d) Special supervision and care shall be exercised to ensure that  the exposures of repair and maintenance personnel to chromium(VI) shall be within the limits prescribed by this standard.
(e) Prompt cleaning of spills of chromium(VI)
No dry sweeping shall be performed. Wet methods or dry vacuuming shall be used as appropriate.
(2) Wet spills and flushing of wet or dry spills shall be channeled for appropriate treatment or collection for disposal. They shall not be channeled directly into the sanitary sewer system.
(f) General requirements
(1) Good practices of housekeeping shall be observed to prevent or minimize contamination of areas and equipment and to prevent build-up of such contamination.
(2) Good personal hygiene practices shall be encouraged.
(3) Equipment shall be kept in good repair and free of leaks.
(4) Containers of dry chromium(VI) shall be kept covered insofar as is practical.
Section 7 -Sanitation (a) Washing Facilities
Emergency showers and eye-flushing fountains with adequate pressure of cool water shall be provided and be quickly accessible in areas where there is potential of skin or eye contact with chromium(VI). This equipment shall be frequently inspected and maintained in good working condition.
Showers and washbasins shall be provided in the employees' locker areas. Employees exposed to chromium(VI) shall wash before eating or smoking during the work shift.
(b) Food Facilities Food storage, preparation, and eating shall be prohibited in areas where chromium(VI) is handled, processed, or stored.
Eating facilities provided for employees shall be located in nonexposure areas. Washing facilities should be accessible nearby.
(c) Employees shall not smoke in areas where chromium(VI) is handled, processed, or stored. Appendix II; if samples can be demonstrated to contain only noncarcinogenic chromium(VI), other methods of chemical analysis equivalent to the method in Appendix II may be used. Records of these surveys, including the basis for concluding that there is no occupational exposure to chromium(VI) shall be maintained until a new survey is conducted.
In workplaces where chromium(VI) is handled or processed, surveys shall be repeated annually and when any process change indicates a need for reevaluation.
Requirements set forth below apply to areas in which there is occupational exposure to chromium(VI).
Employers shall maintain records of workplace environmental exposures to chromium(VI) based upon the following sampling, analytical, and recording schedules:
(a) In all monitoring, samples representative of the exposure in the breathing zone of employees shall be collected by personal samplers.
(b) An adequate number of samples shall be taken in order to permit construction of TWA exposures for every operation or process.
Except as otherwise determined by a professional industrial hygienist, the minimum number of representative TWA determinations for an operation or process shall be based on the number of workers exposed as provided in (c) The first determination of the workers' exposures to airborne chromium(VI) shall be completed within 6 months after the promulgation of a standard incorporating these recommendations.
(d)
A reevaluation of the exposures of workers to airborne chropium(VI) shall be made within 30 days after installation of a new process or process changes.
(e) Samples of airborne chromium(VI) shall be collected and analyzed at least every 2 months for those work areas with occupational exposure to carcinogenic chromium(VI) and at least every 3 months if the airborne chromium(VI) is noncarcinogenic.
(f) A reevaluation of the worker's exposures to airborne chromium(VI) shall be repeated at 1-week intervals when the airborne concentration has been found to exceed the recommended workplace environmental limit. In such cases, suitable controls shall be instituted and monitoring shall continue at 1-week intervals until 3 consecutive surveys indicate the adequacy of controls.
(g) Records of all sampling and analysis of airborne chromium(VI)
and of medical examinations shall be maintained for at least 30  Silica is also found in the ore in varying amounts.  According to Bourne and Yee  the approximate analysis of chromite ores from Rhodesia and Transvaal is 48% chromium(III) oxide, 18% iron(III) oxide, 15% aluminum oxide, 3% silicon dioxide, and 12% magnesium oxide.
In the United States, the 3 most common methods of producing chromium(VI) compounds are the high-lime, the low-lime, and the lime-free processes.  Each of these processes involves the roasting of chromite ore with soda ash and various amounts of lime with subsequent treatment to form sodium chromate.
Other chromium(VI) compounds may be formed by a change of pH and the addition of other compounds. Solutions of chromium(VI) compounds thus formed may then be crystallized, purified, packaged, and sold.  Chromium(VI) has been found in glue,  cement,  detergents,  and other materials, including chromite ore. [ the fingers and on the glans penis. The finger lesion was in an area where there had been either a wound or an abrasion of the cuticle. Cumin described the effects of habitual application of bichromate solution to the skin as an eruption of papulae which become pustular and, upon prolonged exposure, develop deep sloughs under the pustules. The sloughs were described as peculiarly penetrating to the extent of producing in one instance a complete perforation of the muscular substance of the hand.
Ducatel  in 1753 noted that ulceration of the skin could occur from the action of potassium bichromate. He also described a worker who accidentally drank some of it and vomited violently until his death 5 hours later.
Delpech and Hillairet in 1869  described the manufacture of potassium chromate and bichromate in Argenteuil, France, and the effects on workers which resulted from exposure to those chromium(VI) materials. In the process described, chromite ore was either roasted with potassium nitrate, thus producing potassium chromate, or with potassium sulfate and calcium carbonate, followed by treatment with sulfuric acid, to produce potassium bichromate. Seven cases were described in which all workers had perforated nasal septa and 3 also had skin ulcers. Their exposures were to both acidic and alkaline chromiun(VI) salts but not to chromic acid anhydride.
In 1884 Mackenzie described  the toxic effects of potassium bichromate. He was told by a workman, who had been engaged in the factory for 15 years, that destruction of the nasal septum sometimes took place after 24^-48 hours of exposure to bichromate. It is likely that exposures were massive in the plant for at that time hand-rabbled reverberatory furnaces were used  with little or no forced ventilation or good work practices.
DaCosta et al  in 1916 described in detail 19 of 44 cases of chrome ulcers in tanners and dyers. The most common sites of ulcers were the folds of the dorsal surface of the fingers over the knuckles, with other cases on palms, forearms, backs of hands, interdigital folds, sides of fingers, edges of finger nails, wrists, knees, and on other parts of the body, notably 1 near the groin and another on the foreskin of the penis.
It was noted that the ulcerated area had been kept wet with chromate solution in practically all cases. Aside from describing the etiology of the ulcerations, the authors suggested preventive measures including various impervious coverings for the hands and wrists and a preventive ointment of lanolin and petrolatum; therapy consisted of soaking in hot lead water (diluted lead subacetate) and carbonate of soda.
In 1925, Parkhurst  reported 3 cases of chrome dermatitis in workers in contact with blueprints that were fixed in a solution of potassium dichromate.
One case was a 19-year-old woman who had been engaged in the production of blueprints for 6 weeks. The appearance of the lesion was that of crowded vesicles of pinpoint size on a diffusely erythematous and edematous background on the hands, wrists, and forearms.
She showed a positive patch test with a 0.5% solution of potassium dichromate. The eruption subsided a few days after discontinuation of exposure.
Frequent rinsing of hands with a solution of sodium bisulfite and then with water was suggested as a preventive measure to reduce hexavalent chromium to trivalent chromium. The other 2 cases treated by another physician were apparently similar. He prescribed treatment with a 1% solution of aluminum acetate, Lassar's paste, and calamine lotion.
Bloomfield and Blum  in 1928 published a study of workers engaged in a chromium plating operation. Workers were exposed primarily to an acidic mist of chromium(VI), which the authors called chromic acid, emanating from plating tanks. Of the 23 workers examined in the operation, 20 had perforated or ulcerated nasal septa, inflamed mucosa, nosebleed, and cutaneous ulcers ("chrome holes").
In the same year, 12 cases of ulceration and signs of irritation of the respiratory tract from solutions of "chromic acid" were reported by
Blair.  The workers suffered from coryza, sneezing, watery discharge from the eyes and nose, itching and burning of the nose, ulceration of the nasal mucosa, perforation of the nasal septum (chrome holes), and ulcerative lesions of the hands and fingers (chrome ulcers).
In 1930 the Inspectorate of Factories in London issued a report  which dealt with the examination of 223 persons engaged in chromium-plating and an unspecified number of people engaged in anodic oxidation. Of the 223 chromium-plating workers, 95 (42.6%) had dermatitis, skin ulcers, or scars from old skin ulcers; 116 (52%) had perforated or ulcerated nasal septa or "devitalization of the mucous membrane." Times from onset of exposure to appearance of symptoms were as short as 2 weeks for ulceration of the nasal mucous membrane and 6-48 months for perforation of the nasal septum.
Smith  in 1931 described a man who, upon admission to hospital, had ulceration of the skin of both hands, difficulty in breathing, and tenderness of muscles of extremities. Prior to hospitalization he was engaged in washing zinc plates with a solution of ammonium bichromate.
Smith observed erythema of the forearms and hands, desquamation on areas of fingers and palms, vesicular lesions, and shallow ulcers on both hands and forearms.
In addition, she noted 2 similar lesions on the abdomen. The diagnosis was chronic chrome poisoning with dermatitis venenata, acute nephritis, asthma, and acute myositis of the upper and lower extremities.
The patient was patch-and intradermally-tested with solutions of ammonium bichromate followed by evidence of sensitization.
Pfeil  in 1935 reported 2 cases of pulmonary carcinoma in men who worked in the chrome x industry in Germany. In 1911, a foreman in a large chromium manufacturing plant in Germany complaining about coughing and expectoration was examined by Pfeil.  The man's sputum had a reddish tinge. Costal pleurisy set in accompanied by a bloody exudate. The patient also suffered fractured ribs and was diagnosed as having a lung tumor. Post mortem examination confirmed his diagnosis of primary pulmonary carcinoma with metastases. In the next year, Pfeil treated a second patient for exudative costal pleurisy. This patient, who worked in the same chrome plant as the first, was found to have pulmonary carcinoma upon his death. The foreman was involved in a secondary process where he was apparently exposed to residues from quinone production which probably contained a complex mixture of chromium(III) and chromium(VI). The second man was said to work in the chrome industry but no further description was given. Five more men died from lung cancer in this same chrome plant before 1935. Of the cases of lung cancer and gastrointestinal cancer studied by Teleky,  some occurred among chrome workers. Teleky concluded from this that chromium is a lung carcinogen and might be a gastrointestinal carcinogen, but the data he presented do not support more than a suggestion of the relationships.
In later years, many additional deaths from lung cancer occurred in the German chromate industry,  but it was not until 1948  that an excessive incidence of lung cancer was reported among workers in the United States chromate industry.

# Effects on Humans
In a review, Mertz  summarized the occurrence of chromium in nature and its function in biologic systems. Later, Glinsmann and Mertz  studied the relationship between chromium(III) and glucose tolerance in humans by the oral administration of aqueous solutions of chromium(III) chloride.
Six subjects with maturity onset diabetes (where the impairment in glucose tolerance did not appear to be related to a simple insulin deficiency but rather insulin effectiveness appeared to be reduced) were given 0.06-1 mg chromium(III) 3 times/day with meals for periods of 15-120 days. During this time, oral glucose tolerances were determined. Three of the 6 had improved tolerances while on chromium(III), compared to control periods.
In 10 nondiabetic subjects with normal oral glucose tolerance, administration of 0.15-1 mg chromium(III)/day for 21 days resulted in no detectable alterations. The authors interpreted these results to suggest that chromium is required for optimum glucose use in man.
Several studies have reported and reviewed concentrations of chromium in various biologic tissues and fluids.
 However, any interpretation of the amounts of chromium found in biologic samples should be accompanied by a close scrutiny of the analytical chemical methods employed.
As new, more sensitive, and precise methods have been developed
and used, authors have reported lower estimates of the quantities of chromium in certain biologic materials.  The National Academy of

# Sciences-National Research Council Committee on Biologic Effects of
Atmospheric Pollutants  reported a wide range of concentrations of chromium occurring in biologic samples from both unexposed and occupationally exposed populations.
For this reason, it would be very difficult to interpret biologic concentrations of chromium as a measure of the absorption of chromium.
Mancuso  reported that men exposed to airborne water-soluble chromium compounds excreted more chromium in the urine than those exposed to water-insoluble ones. He also noted elevated concentrations of chromium in the blood and urine for several years after exposure to chromiumcontaining materials. However, because of the wide disparity of "normal"
and "exposed" blood and urine concentrations reported in the literature, any such correlations between exposure and biologic concentrations of chromium must be Interpreted with caution. were observed in half the workers in the brilliant-chrome industries.
Duration of exposure was unstated, but it was mentioned that the harmful effects were noted in less than a year, and that few workers remained many years in the industry. Individual safety equipment was lacking in 26.6% of the plants; this may have been responsible for the high incidence of cutaneous ulcers.
Zvaifler  and Gresh  published separate reports of an anodizing plant study. Zvaifler  noted that there was a distinct difference in the physiologic effects of chromium(VI) mists from plating tanks and the mists from anodizing tanks but he presented no data to support his conclusion. He mentioned that the chromium(VI) poisonings which resulted from exposure to mists emanated from anodizing tanks containing "5% chromic acid" generally involved ulceration of the nasal mucosa and skin rashes but rarely perforation of the septum. Gresh [ The investigation revealed that personal protective equipment was not worn and employees frequently wiped their faces and picked their noses with unwashed fingers or while wearing gloves.
The authors thus concluded, probably correctly, that poor work practices were responsible to some degree for the nasal involvement.
Determinations of pulmonary involvement were not reported in the study.
In another study by NIOSH  of a different chromium plating plant, a maximum airborne chromium(VI) concentration of 3 Mg/cu m was found. In this operation, the plating solution contained approximately 210 g chromium(VI) oxide/liter. No ulcerated nasal mucosae or perforated nasal septa were found, although half of the 32 employees had varying degrees of mucosal irritation. This incidence of mucosal irritation was not thought to be significant by the investigators because the survey was carried out at the peak of the 1972-73 influenza epidemic. Fifteen workers had been employed 8 years or more, 7 between 4 and 8 years, 4 between 1 and 4 years, and 6 less than 1 year.
Although he did not report airborne concentrations of chromium(VI),
Meyers  in 1950 observed 2 patients who had inhaled chromic acid mists, for only a few hours one day. One man developed a cough, severe frontal headaches, pulmonary congestion and edema, dyspnea, and persisting sub8temal pain. The other developed hoarseness and a cough productive of green mucoid sputum. Five months after exposure, the X-ray examination showed some emphysematous changes and a small pleural effusion.
Pascale et al  in 1952 reported 5 persons with hepatic injury apparently due to exposure to chromic acid mist from plating baths. One who had been employed 5 years at a chromium plating factory was hospitalized with jaundice and was found to be excreting significant amounts of chromium. Her lungs and cardiovascular system were normal. A liver biopsy showed microscopic changes resembling those found in toxic hepatitis.
To Investigate the possibility that the liver damage was of occupational origin, 8 fellow workers were screened for urinary chromium excretion.
Four of these were found to be excreting significant amounts and were examined in more detail. In 3 workers who had been exposed to chromic acid mists for 1 to A years, liver biopsies and a series of 12 hepatic tests showed mild to moderate abnormalities. No liver biopsy was taken from the fifth worker, who had been removed from further exposure because of nasal ulceration after 6 months at the plating bath. Only 1 of his liver function tests indicated a borderline abnormality. The urinary excretion of chromium (2.8 and 2.9 mg/24 hours) by the 2 workers employed 4 years was greater than the excretion (1.48 mg/24 hours) by the worker employed 5 years who suffered the greatest liver damage. The lowest urinary chromium excretion (0.184 mg/24 hours) was measured in the fifth worker, the individual with least exposure. All 5 exhibited some signs of damage to the nasal mucosa. This plus the concentrations of urinary chromium suggests that exposures to chromium(VI) were significant, but no environmental data were reported.
Several authors  have dealt with exposures to chromium(VI) materials, exclusive of chromic acid anhydride and aqueous solutions thereof (known as "chromic acid").
In the chromate-producing industry in the United States, only a small part of which produced chromic acid anhydride, the principal exposures to chromium(VI) were probably to sodium chromate and bichromate. To a lesser degree, exposure to potassium chromate and bichromate was also present. In 1884 Mackenzie  described the toxic effects of potassium bichromate.
He related having been told by a workman, who had been engaged in the factory for 15 years, that destruction of the nasal septum sometimes took place after 24-48 hours of exposure. From his own experience, Mackenzie observed that this destruction was preceded by general congestion of the mucous membrane, nosebleed, and coryza. The turbinates, nasal pharynx, and lower pharynx were also ulcerated. What he described as the lower respiratory tract (probably the lower part of the upper respiratory tract)
was generally found to be highly inflamed and swollen. Accompanying the catarrhal symptoms, there were sometimes intense headache, inflammation and perforation of the tympanic membranes and subsequent otorrhea. At that time hand-rabbled reverberatory furnaces were used  and since there was little or no forced ventilation or good work practices, it is probable that exposure levels were high.
Much later, in 1948, Machle and Gregorius  described the incidence of nasal irritation and septal perforation in a chromateproducing plant that manufactured sodium chromate and bichromate. The incidence of nasal septal perforation was 43.5% in 354 employees. Airborne chromate concentrations were determined to range from 10 to 2,800 jug/cu m at the time of the study, but the plant has been in operation for at least 17 years. Some employees had probably worked in the plant when reverberatory furnaces were used, a notorious source of high exposure.
In the early fifties, an epidemiologic study as reported by Bourne
and Yee  and by Mancuso   The incidence of these signs, as was the incidence of ear disorders such as discharge, impaired hearing, and tinnitus, was more than twice that found in nonchromate-worker control groups. Liver enlargement was noted in 14 chromate workers. Those with enlarged livers were at least 15 years older and had worked an average of 4 years longer in the chromate industry than those without enlarged livers, but the number in the group was too small to allow a statistical comparison with a group not exposed to chromate. Those with cutaneous ulcers or scars of ulcers numbered 451. Most of the active ulcers had occurred within the 6 months prior to the study. Lung cancers were also found in this group and will be discussed later.
Urinalysis revealed white and red blood cells and casts with greater frequency than is usually observed in the average industrial population.
Casts in urine were found in a greater percentage of workers who had worked 10 years or more than in those who had worked less than 10 years.
Frequency of white blood cells in urine of chromate workers showed an increase with years of exposure. The number of red blood cells in urine did not change appreciably with years of chromate exposure.
As a result of dental examinations of 561 workers, incidences of keratosis of the lips, gingiva, and palate; yellow-stained teeth and tongue; and periodontitis were greater than twice the incidences in a control population of 124.
The observed signs of excessive exposure to chromium(VI)-nasal mucosal irritation and ulceration and to a lesser extent nasal septal perforation-were likely, in the acute or subacute nature of the lesions, to be closely related to airborne chromium(VI) at the average concentration measured at the time of the study-68 ng/cu m. There is reason to suspect that liver and kidney damage occurred, based on observations of enlarged livers and casts in urine, as a result of long-term exposure to chromium(VI) , but the results were not conclusive.
Numerous cases of allergic dermatitis with varying degrees of eczema have been reported. 21,25,61,62, Parkhurst  in 1925 reported the case of a woman employed in blueprint production using a process where a 1% potassium dichromate solution was used as a fixative.
He rubbed a 0.5% potassium dichromate solution on the right thigh of the woman and soon there was a local sensation of itching and burning. Twelve hdurs later, the patient developed a follicular erythematopapular dermatitis where the solution had been applied. A similar application was made to the left thigh with resulting itching and burning. However, the application of an aqueous saturated solution of bisulfite prevented the development of a dermatitis in this area.
In 1931, Smith  observed a case of chrome poisoning with manifes tations of sensitization in a man employed in a photographic printing firm, where his duties involved handling and washing sheets of zinc treated with a solution of ammonium dichromate, and occasionally preparing the solution.
The man developed a mild erythema 24 hours following a patch test with 1% ammonium dichromate solution on a 1-sq cm area of normal skin on his forearm. After 3 days the erythematous area had doubled in size and had developed vesicles.
Eight days later, an intradermal injection of 0.1 cc of a 0.5% aqueous solution of ammonium bichromate was given in the right forearm.
Within an hour the patient developed a generalized pruritus with soreness at the site of the injection. Within 6 hours he had (1) a slight erythema at the site of a previously negative patch test, (2) an erythematous area 5 cm x 3 cm with tenderness at the injection site, (3) a localized patch of maculopapules on the area in which the patch test had been 9 days earlier, (4) a vesicular erythematous dermatitis covering the entire hands and lower parts of the forearms, (5) generalized mild erythema with a few urticarial wheals on the buttocks, and (6) a recurrence of the diaphoresis and sibilant rales he had had some 15 days earlier, upon admission to the hospital. The man recovered after his exposure to chromium(VI) ceased. Three control subjects were similarly injected and showed no reaction.
Hall  in 1944 reported 132 dermatitis cases in aircraft workers who had contact with a primer consisting of a suspension of zinc chromate powder and magnesium silicate in a xylene solution of certain resins, including a phenol-formaldehyde resin. Apparently, the mean duration of employment was 7 months (range: 1 week-9 years) for those who had dermatitis from the primer and who were allergic to zinc chromate pigment.
A series of patch tests showed 90 of the workers (68%) were sensitive to the zinc chromate pigment only. (The zinc chromate pigment was apparently a mixture of zinc chromate and calcium carbonate.)
In 1949, Pirila and Kilpio  reported 45 cases of allergic contact dermatitis observed in the Helsinki area from 1945-48.
Forty-one reacted positively to patch-testing with a 0.5% aqueous solution of potassium dichromate (pH 4.15). The breakdown of cases by occupation was as follows: bookworkers, 11; cement and lime workers, 10; radio factory workers using a photostatic procedure, 7; metal factory workers, 4; painters and polishers, 4; fur workers, 3; others, 6.
In 1952, Gngebrigtsen  reported 8 cases of cement eczema among 300-400 Norwegian workers exposed "more or less directly" to cement dust that contained 0.002-0.020% water-soluble chromium(VI) described only as He did not react to distilled water. The control subjects did not react to any of these 3 chromium(VI) solutions.
In 1960, Calnan  showed that British cement contained from nondetectable amounts to 12 ppm chromium(VI), expressed as potassium bichromate. He concluded that cement dermatitis was primary irritant dermatitis complicated by a secondary contact sensitivity to "hexavalent chromate"
Winston and Walsh  reported that 6 out of 200 employees were incapacitated by chromate dermatitis in a diesel locomotive repair shop.
One of the 6 cases was described; the dermatitis consisted of patchy, pruritic, erythematous, slightly scaly lesions extending from the dorsum of the hands over both forearms to the elbows. All were exposed to an alkaline diesel locomotive radiator fluid which was prepared from sodium dichromate, soda ash, disodium phosphate, and sodium silicate. One and one-half pounds of this powdered mixture, which contained 66% sodium dichromate, was dissolved in 2 gallons of water in an open pail. This solution (approximately 6% sodium dichromate) was poured into the radiator and diluted with about 210 gallons of water, giving a solution of about 0.08% sodium dichromate. All of the men gave positive reactions to 0.25% sodium dichromate (pH 4.25) patch tests and to samples of the radiator fluid (pH 10).
Walsh  in a summary report on chromate hazards in industry described results of some patch tests: 2% "chromic acid" applied for 24 hours on superficial skin abrasions produced a crusted lesion in 3 weeks; 0.5% sodium dichromate, reapplied daily for 3 days, produced a crusted lesion in 3 weeks; 0.5% potassium chromate, applied for 8 hours/day for 3 days, produced lesions in 3 days; 0.05% sodium dichromate, 0.005% sodium dichromate, and pure zinc chromate also produced lesions in 3 days after being in contact with the skin for 8 hours/day for 3 days. Lead chromate did not produce a reaction after the same exposure period. A 10% solution of chromium(III) nitrate produced redness after the solution was reapplied daily for 3 days.
Edmundson  patch-tested 56 men who had chrome ulcers with 0.5% potassium bichromate for 24 hours. Only 2 yielded positive reactions and they were said to have a history of chrome dermatitis. He interpreted his results to indicate that when chrome produces ulcers it does not sensitize workers.
Morris  in 1955 reported 2 cases of sensitization to chrome glue prepared at least in part from scraps of chrome tanned leather. Both patients gave positive reactions to the otherwise undescribed chromebearing parent material to which they were exposed, and both were allergic to chrome-dyed leather shoes. From the nature of the tanning process it seems probable that the substance causing the sensitivity was chromium(III). One of these patients reacted positively to a 0.1% solution of sodium bichromate.
McCord et al  described in detail the lithography process, as it existed in 1930, which used an extremely acidic solution of chromium(VI).
Twenty-five lithographers and 12 tanning workers who had been exposed to chromium, but showed no signs of dermatitis, were selected for study. Each reactions. This report was apparently the first to note that injury from chromium(VI) could occur without previous skin trauma or disease.
Levin et al,  from similar studies conducted in the late 1950's, confirmed that chromium(VI) was the primary causative agent in lithographer's dermatitis. However, they found that trauma and the use of various other chemicals associated with lithography such as fat solvents and primary irritants made workers' skin more prone to irritation by the chromium(VI)-bearing materials.
In 1961, Fregert  described the manufacture of matches and demonstrated that match heads which contained chromium(VI) could partially dissolve when held in moist fingers and could cause an allergic eczematous contact dermatitis. The source of chromlum(VI) was probably an ingredient of the manufacture since potassium dichromate is usually added both to the igniting composition and to the striking composition. The author was, however, unable to find chromium(VI) in the striking composition, probably because it had been reduced to chromium(III). Although this study was done in Sweden, he attalyzed matches from 21 countries and found concentrations as high as 1.7% water-leachable chromium(VI) expressed as potassium dichromate in unburnt matches and 1-10% of the original chromium(VI) concentration in the burnt matches.
He stated that every patient in a group of 33 who had chromate eczema reacted positively to either unburnt or burnt match heads.
In 1963 2 separate studies  of dermatitis resulting from chromium(VI) used in the automobile industry were published. Engel and Calnan  investigated an outbreak of dermatitis in the British automobile industry among workers who were engaged in the wet sanding of primer paint containing zinc chromate. Almost all (91%) of them had positive reactions to a 0.5% solution of potassium dichromate (pH 4.15); however, a few did not react until the solution was made alkaline (pH 10.3)
Newhouse  found dermatitis in automobile assemblers from handling a chromate dip used as an antirust agent on bolts, nuts, screws, and washers. About one-quarter of these responded positively to potassium dichromate patch-testing.
Fregert and Ovrum  in 1963 reported a case of a welder who contracted a facial dermatitis after inhalation of and contact with welding fumes from either arc welding or oxygas welding. Subsequent investigation demonstrated that the chromium in certain welding rods could be oxidized to chromium(VI) and that chromium(VI) was dispersed into the air in the vicinity of the weld. The authors patch-tested 5 people who were hypersensitive to chromate with an aqueous solution of collected welding fumes calculated to be 0.1% chromium(VI) (as potassium dichromate). All gave positive reactions. The authors elicited no response from 10 subjects not hypersensitive to chromate.
Their analyses of various commercial welding rods showed chromium contents up to 18%.
A year later, Shelley  reported a similar case. A crane operator provided a history of chronic eczematous eruptions of both hands. Twentyeight compounds were patch-tested and the only positive reaction was to an aqueous 0.25% solution of potassium dichromate (pH 4.28). Two and one-half months later, the man walked by an acetylene-welding operation where the fumes were strong and experienced appreciable inhalation of the fumes. On the next day he reported a rapidly developing vesicular flare on his hands.
The dermatitis subsided after he avoided further contact with chromiumcontaining objects and welding fumes.
Jaeger and Pelloni  in France demonstrated that workers with Goldman and Karotkin  in 1935 reported a case of acute exposure involving a 25-year-old woman who had swallowed an aqueous solution containing a heaping teaspoonful of potassium dichromate crystals. Shortly thereafter she had a paroxysm of vomiting. Two days later she was hospitalized.
At this time she had severe nephritis and severe hepatitis, an erythematous skin eruption, and a "positive" chromium test in urine.
The skin rash began to fade 13 days after the initial reaction and disappeared after 5 more days; she recovered from hepatitis and nephritis in 3 months.
Major  reported the development of severe nephritis in a patient the day after chromium(VI) oxide was applied to a wound as a cauterant; the man died 19 days later.
Vigliani and Zurlo  studied over a 3-year period approximately 150 workers in a plant producing alkali chromates; during this time the airborne chromium(VI) concentration range was 57-78 ng/cu m. Ulceration of the nasal septum, inflammation of the conjunctiva and laryngeal mucosa, and chronic asthmatic bronchitis were the most commonly seen disturbances, but their frequency was not mentioned. One case of nasal septal cancer and 1 of lung cancer were also observed. No data regarding sampling locations, sampling techniques, or analytical methods were presented.
Unequivocal evidence relating a specific chromium(VI) compound to the development of lung cancer in humans has not been developed. There is, however, epidemiologic evidence in workers and experimental evidence in animals that suggests carcinogenic properties of some chromium(VI)-containing materials.
This evidence is discussed in the following 2 sections.

# Epidemiologic Studies
The first extensive epidemiologic studies involving exposure to chromium(VI)-containing materials and the risk of lung cancer were performed in Germany by Lehmann.  He found only 2 cancer cases and dismissed them as nonoccupatlonal in nature but the reasons for this conclusion seem to be faulty in view of current knowledge. Lehmann gave no information on the extent of exposure to chromium(VI).
Later German reports, reviewed by Baetjer   One of the studies referred to by Baetjer is of particular interest.  Because the authors apparently determined that the pancreas was the primary site adenocarcinoma, and as there have been no other reports of chromium(VI) causing cancer of the pancreas, it seems improbable that chromium(VI) was the causative agent.
In addition to the cancer cases in the cohort, 1 man developed an adenocarcinoma of the prostate after an unmentioned exposure period and another, a 33-year-old man, was diagnosed as having an adenoid cystic carcinoma of the inferior nasal turbinate after working in the plant for 3 months. The plants in which these men worked were not designated.
In light of the short, less than 3-year, period of employment of the worker who developed prostate cancer and the lack of any other report linking exposure to chromium(VI) and prostate cancer, it is unlikely that chromium(VI) was responsible. Because the worker who developed a carcinoma of the nasal turbinate was exposed for only 3 months, an extremely potent carcinogen must have been present. Other reports  do not suggest that chromium(VI) is capable of producing cancer in such a short time.
The authors calculated the risk of getting lung cancer for each worker separately for each calendar year of the observation period. This was accomplished by using the age-specific incidence rates of cancer supplied to them by the Cancer Registry of Norway. The total risk for the population of workers was then obtained by adding the risks for each worker for each year of the observation period. The expected number of cases of cancer obtained by this method was then compared to the observed number in the group. The expected number of lung cancer cases in the cohort was calculated to be 0.079 for the total period of observation. Since 3 cases were found, the observed/expected ratio was 38. The total number of manyears at risk of the cohort was 244. There were several shortcomings in the Machle and Gregorius study.  The authors differentiated exposure to 2 categories of chromium compounds, ie, soluble and insoluble, but did not differentiate between chromium(III) and chromium(VI).
Chromium(III) and chromium(VI) materials leachable by water were classified as the soluble group.  The insoluble group of compounds included all those not leached by the repeated treatment with water. This group probably included primarily chromite ore, based on the degrees of water-solubillty of the compounds which were probably present. Thus, although the authors did not determine chromium (III) and chromium(VI) directly, it appears that "insoluble" compounds were predominately chromium(III) and "soluble" compounds were predominately chromium(VI).
Chromium(VI) of only slight water solubility was not determined in this study, but based on the analytical procedure used  part of it was likely found in the soluble group and part in the insoluble group. The pH's of airborne samples were 6.7-9.4, indicating that most samples included both chromates and dichromates.
All samples germane to the chromate-plant study were apparently taken by air filtration using the apparatus mentioned by Bourne and Streett.  Collection efficiencies for chromium(VI) oxide as a mist using this apparatus were determined at 0.07 mg/cu m, 0.14 mg/cu m, and 0.22 mg/cu m to be 93.6%, 98.3%, and 92.5%, respectively, for 15-minute samples at a flow rate of 28.3 liters/min. Collection efficiencies for dust were determined at 4.62 mg/cu m and 25 mg/cu m to be 99.0% and 99.9%, respectively. Mists used in the collection efficiency test were generated using an apparatus, described by Silverman and Ege,  which nebulized into the air stream an aqueous solution of chromium(VI) oxide (25%) and sulfuric acid (0.125%).
The dusts were generated in the same equipment except that the nebulizer was replaced with a vibrating vessel into which dust was introduced.
The size distribution of the particles in the mist in the chromate plant was: 15.87% less than 1.5 pm, 50% less than 3.8 jum, and 84.13% less than 9.8 /an. In the dust the distribution was 15.87% less than 0.8 fm, 50% less than 1.7 /xm, and 84.13% less than 3.7 im.
Mancuso and Hueper  investigated the incidence of cancer in this chromate plant. Using the results of analyses of air samples for soluble and insoluble chromium, they calculated the possible exposures of 7 men who died from lung cancer between 1938 and 1950. Although none of the 7 were working in the plant when the sampling and analysis were performed, the calculated TWA exposures could have had some relationship to their actual exposures.
The years of first exposure in the chrome plant for the 7 were 1931-41. Changes in the concentrations of chromium in airborne dusts and mists could have occurred during the years of exposure of these men to decrease the relevance of determinations of TWA exposures made at the time of this study. The scope of such changes is very difficult to evaluate.
The airborne concentrations of chromium leachable by water determined by Mancuso and Hueper  to which the 7 were exposed were 0.01-0.15 mg/cu m (Table XI-5). These concentrations were apparently calculated timeweighted average concentrations taking into account the various jobs the men accomplished during the average day. The men were also exposed to chromium not leachable by water, in addition, at airborne concentrations of 0.1-0,58 mg/cu m. Because of the lack of specificity in the analytical method used , the airborne concentration of the only slightly watersoluble chromium(VI) is inestimable.
In another paper, Mancuso  reported the incidences of other effects found in the epidemiologic study. Although the various groups were defined by total chrome exposure and ratio of insoluble to soluble chrome, the actual maximum ranges of concentrations of chromium, either leachable or not leachable by water, have been calculated from their data and appear in In 1959 Baetjer et al  reported the determination of chromium in the lungs of 16 decedents who had been employed in old chromate plants.
Eleven of the men who had been employed for 2-42 years had lung cancer; 5 of the men employed 1.5-19 years did not. The results of analyses by the method presented in an appendix to their report  were both highly variable and inconclusive, that is, there was no significant correlation between the presence of lung cancer and chromium in lung tissue.
The US Public Health Service published in 1953 a report  of an extensive study of the health of 897 workers in the chromate-producing industry.
Morbidity and mortality data were based upon paid death claims and cases of sickness and nonindustrial injuries disabling for 8 calendar days or longer among the members of the sick benefit plans of the plants.
From 1940 to 1948, there were 28.9 times as many deaths from respiratory cancer among males in the study as would have been expected on the basis of the average death rate for the United States for the period 1940-48 inclusive, excluding violent, accidental deaths.
Medical examinations were performed on about 96% (897 males) of the total work force of the 6 study plants. Ten workers were considered to have bronchogenic carcinoma, a rate for chromate workers of more than 50 times the rate for the general population. Three of these men were known to have had lung cancer prior to the survey. These 10 men, who averaged 54.5 years of age, had a mean duration of exposure of 22.8 years (Table XI- 7). This represents a very high lung cancer incidence. Five hundred nine (56.7%) had perforation of the nasal septum. The incidence of perforation of the nasal septum was stated to have no relation to either years of exposure or to the incidence of lung cancer. Studies relating exposure to chromium compounds and incidence of dental caries indicated a low degree of correlation, but there was an increased incidence of gingivitis and periodontitis. X-ray examinations showed no significant fibrosis, but bilateral hilar enlargements were noted.
There was no significant correlation between duration of exposure and heart disease. Other positive correlations mentioned were an increased frequency of white blood cells and casts in the urine and a decreased sedimentation rate of erythrocytes, all of which were related to years of exposure. Blacks appeared to be more severely affected, in general, than whites, perhaps due to a greater exposure among blacks.
This study also involved an extensive sampling program in which over 1,800 samples of air contaminants, settled dust, and process material were collected and analyzed. The report stated that the dry-end processes, ie, milling, roasting, and leaching, generated dusts containing principally lime, chromite ore, soda ash, roast residue, and sodium chromate. Sodium dichromate and sodium sulfate were usually associated with the wet-end operations of neutralizing, treating, and concentrating.
In 1952, Brinton et al  published a study of the morbidity and mortality in the chromate workers of another study.
 They demonstrated a greater rate of sickness and nonindustrial injury in chromate workers as compared to a large industrial group. This difference was due to the 10fold increase in the incidence of cancer in chromate workers, largely because of respiratory cancer, which was increased 14-fold for whites and 80-fold for nonwhites.
In 1966 Taylor reported a study   Chromium(VI) concentrations were less than 1 up to 25 mg/cu m. The author observed either diffuse thickening or rupture of alveolar walls and proliferation of cellular elements along the blood vessels and bronchi.
Desquamation of the bronchial epithelium was also found. No tumors were found, but the maximum exposure was only 8 months.
In 1930, Hunter and Roberts  injected subcutaneously Macacus rhesus monkeys with various amounts of an aqueous 2% solution of potassium bichromate.
One monkey given 36.3 cc of the solution (0.02 g/kg) and another given 10 cc were dead 12 hours later. Evidence of acute lesionswas present in the kidneys of both animals. Four other monkeys were given repeated, 1-5 cc doses of the solution at 3-to 7-week intervals. In 2 of these, acute lesions were also found in the kidneys. The other 2 animals lived longer, for about 160 days, and sustained chronic renal damage; in 1, practically all the original epithelium of both proximal and distal convoluted tubules was destroyed. The authors further remarked that the regeneration of tubular epithelium was of distinctly atypical morphology and that the tissue was apparently resistant to further injury by bichromate.
In 1940 Shimkin and Leiter  reported the intravenous injection of various materials into tumor-susceptible strain A mice. Single, 5-mg injections of chromite ore did not result in an increased incidence of   In another series, 12.5 mg of calcium chromate in gelatin capsules was implanted intramuscularly and intrapleurally in rats.
After 7 months, of the 6 rats with intramuscular implants, 2 developed tumors; of the 6 rats with intrapleural implants, 3 developed tumors. The latter experiment, despite its lack of a control group, appears to verify that the chromium(VI) compounds and not the sheep fat were the causative agents for the tumors observed.
Payne  fractionated and analyzed the residue from the first leaching of roasted chromite ore, and tested the material in animals. This In a further study, Hueper and Payne  gave rats monthly intrapleural and intramuscular injections of sodium dichromate in gelatin.
Each injection consisted of 2 mg of sodium dichromate dissolved in 0.05 ml of a 10% gelatin solution. A total of 16 injections were given. Survivors were sacrificed at the end of a 24-month observation period. Various tumors were seen. Of the 20 male and 19 female rats in each series receiving intrapleural injections, 3 developed malignant tumors, 1 of which was at the site of injection. Rats receiving intramuscular injections developed 4 benign and 2 malignant tumors, none at the site of injection.
The 4 tumors which were not at the injection sites were of a type found in a similar incidence in control animals. Four benign and 12 malignant tumors, none at the site of injection, were observed in the control group.
Because of the greater incidence of malignant tumors in control animals, it is impossible to conclude that sodium dichromate was responsible for any malignancies.
In another experiment,   In 1968 and 1969 Laskin et al  reported a study of selected chromium compounds in a cholesterol carrier using a new intrabronchial implantation technique. The pellets used were in the form of a cylindrical matrix of stainless steel mesh and about 1 mm in diameter and 5 mm in length. They were implanted in the bronchus and held in place by a trochar fitted with spring-wire hooks and introduced through a tracheotomy. One of 100 rats implanted with process residue developed a squamous cell carcinoma at the site after 594 days. No other compounds produced tumors at the site of implantation, although among the 100 rats in each group hepatocell carcinomas were observed in 1 rat given process residue, in 1 rat given chromium(III) chromate, and in 2 rats given chromium(VI) oxide.
Five of 24 control rats developed squamous metaplasia and, in addition, 1 developed a sarcoma. Of the tumors seen, all were invasive and some had metastasized.
In all experimental groups except the 1 exposed to chromium(VI) oxide, there was evidence of atypical squamous metaplasia of the bronchus.
Since these studies implicated calcium chromate as a lung carcinogen, inhalation studies using this compound were begun.  Early rangefinding studies  with calcium chromate resulted in rapid and significant mortality at both 10 and 20 mg/cu m (2.7 and 5.4 mg chromium(VI)/cu m, respectively) in both rats and hamsters. Results  reported in 1972 suggested a carcinogenic action in rats and possibly in hamsters after chronic exposure to calcium chromate aerosols at 2.0 mg/cu tn (0.67 mg chromium(VI)/cu m ) .
After 589 exposures over 891 days, 4 carcinomas were observed.
Of the original 100 rats, 1 keratinizing squamous cell carcinoma of the lung, 1 laryngeal squamous cell carcinoma with invasion of perineural spaces and adjoining cartilaginous rings, and 1 malignant peritruncal tumor of undetermined type and origin were observed.
One squamous cell carcinoma of the larynx was found among the original 100 hamsters. In addition, a number of mucosal changes were noted.  In rats, 2 animals showed laryngeal hyperplasia and 3 showed laryngeal squamous metaplasia. Effects in hamsters were more marked with 8 animals showing laryngeal hyperplasia. Eight additional animals showed squamous metaplasia of which 5 were atypical with downgrowth. Another hamster, dying at 611 days, showed a squamous papilloma in the larynx with hyperplasia and hyperkeratosis.  Nettesheim et al  exposed 136 female mice and 136 male mice, all germ-free derived and specific-pathogen-free C57BL/6, to 1 jun diameter calcium chromate aerosol at a concentration of 13 mg/cu m. He also exposed 545 mice of the same type to PR8 influenza virus prior to the calcium chromate exposure. Two control groups of the same size and composition breathing filtered air were used and only 1 was infected with the virus.
In all, 21 pulmonary adenomas were obaerved in the 2 exposed groups and only 5 in the uninfected controls. No tumors were found in the infected controls.
No bronchogenic tumors were found. The authors determined that there was a significantly larger (P<0.0077) incidence of lung tumors in mice exposed to calcium chromate, compared to controls. Prior exposure to 100 roentgens of whole-body X-radiation in another series of mice did not affect tumor incidence, but prior PR8 influenza infection appeared to reduce the incidence of tumors from calcium chromate.
The authors  also gave 15 weekly intratracheal injections of calcium chromate to 2 groups of hamsters. Hamsters in 1 group received 0.5 mg/week, the hamsters in the other group received 0.1 mg/week. The lesions produced were similar to those observed in the mice, but scarring of the lung parenchyma was more widespread and adenomatosis was regularly observed. Hamsters also had frank bullous emphysema and extensive goblet cell hyperplasia in all parts of the tracheobronchial tree.
In a study by Zekeev et al  in 1973, the blastomogenic and toxic effects of chromium(III) oxide, ammonium bichromate, sodium bichromate, chromium ores, and dolomite were observed in rats. Some rats were preliminarily treated with "non-carcinogenic" doses of 3,4-benzpyrene. Positive control groups received 3-methylcholanthrene. Lungs of all rats either dying during the study or killed at its termination were examined both macroscopically and microscopically. Apart from those in the lung, tumors were similar both in type and number in all groups. The bronchial tumors found and microscopically confirmed are given in Table III  and discoloration of the teeth.
 Although it is apparent that any chromium(VI) materials may cause the less severe effects if they are present in aqueous solution in sufficient concentrations, the specific materials which were responsible for lung cancer have not been identified.
To some extent the toxicities of chromium(VI) materials vary with their solubilities, but denotation of compounds on the basis of solubility alone has not been sufficiently precise to suggest a dichotomy of toxic effects, where high incidences of ulceration and perforation occurred, there were 37 employees. Twelve of the 21 workers employed 1 year or less and 15 of the 16 workers employed more than 1 year had ulceration and crusting of septal mucosa, avascular scarified areas of septal mucosa without erosion or ulceration, or perforation of the nasal septum. In the plant in Finland,
 the incidence of signs and symptoms of chromium(VI) poisoning is impossible to establish because insufficient information was provided.
However, it is apparent that most persons with signs and symptoms had been employed for 1-5 years, during which time the working conditions were less hygienic than those in effect at the time of the study. The third plant  with 32 employees provided great contrast with the other 2.  In this plant  no ulceration or perforation occurred, despite the fact that the workers had been employed for a much longer period of time-15 were employed 8 years or more; 7, between 4 and 8 years; 4, between 1 and 4 years; and only 6, less than 1 year. to "chromic acid" and resulting skin ulceration, the lack of skin ulceration in the third contrasting study  suggests that good work practices were used in this plant.
The criteria document  on exposure to chromic acid concluded that, in the presence of good work practices, an environmental limit of 50 In 1884, Mackenzie  reported that ulceration of the nasal mucosal membrane followed by nasal septal perforation usually occurred after an exposure to bichromate of only a few days. Corrosion of both the nose and throat was also common and was occasionally accompanied by inflammation and perforation of the ear drums.
No estimates of the degree of exposure required to produce these disorders were presented, but at that time the manufacturing processes were undoubtedly accompanied by an extremely dusty environment.
In a survey of the chromate-producing industry in 1948, Machle and Gregorius   Fregert  found positive reactions to water-soluble hexavalent chromium in patients with chromate eczema. Morris  reported positive reactions to chrome-containing glue and chrome-dyed leather shoes. Calnan  concluded that cement dermatitis was primary irritant dermatitis complicated by a secondary contact sensitivity to "hexavalent chromate"
. Engebrigtsen  confirmed that workers with cement eczema reacted positively to patch tests with aqueous 0.5% solutions of potassium bichromate. Jaeger and Pelloni  found that 94% of those with cement eczema gave positive patch test results with aqueous 0.5% solutions of potassium bichromate. McCord et al   found that few workers who developed chrome ulcers were sensitized to an aqueous solution of 0.5% potassium bichromate.
Pirila and Kilpio  reported that some workers who had been exposed to materials likely to contain chromium compounds-bookworkers, cement and lime workers, persons working with fish glue, metal factory workers, painters and polishers, and fur workers-were allergic to aqueous 0.5% solutions of potassium dichromate. Denton et al  reported on a man who reacted strongly to an aqueous 0.005% solution of potassium dichromate.
Winston and Walsh  reported on a man who had a patchy, pruritic, erythematous dermatitis from working with a chromate-silicate-phosphate mixture (pH 10); the man had positive reactions to 0.25% sodium dichromate and to the above mixture. Levin et al  reported that lithographers developed an allergy to chromium(VI) which was elucidated by patch tests with various chromium(VI) materials including an aqueous 1% solution of potassium dichromate and other nondescript solutions. Engel and Calnan  found a group of workers who wet-sanded zinc chromate primer paint and who reacted positively to aqueous 0.5% solutions of potassium dichromate, and a group who did not react to an aqueous 0.5% solution of potassium dichromate until it was made alkaline (pH 10.3). Newhouse  found that 24% of the automobile assemblers studied yielded positive reactions to aqueous 0.5% solutions of potassium dichromate. The chromate dip used on bolts, nuts, and washers as an antirust agent was ascertained to have been responsible for the dermatitis. Fregert and Ovrum  found that welders exposed to aerosols of chromium(VI) developed hypersensitivity which was confirmed by patch testing with aqueous 0.1% solutions of chromium(VI) as potassium dichromate derived from welding fumes. Shelley  reported a similar sensitivity to welding fumes; a man with chronic, eczematous eruptions had positive reactions to aqueous 0.25% solutions of potassium dichromate.
Loewenthal  observed a green-tattooed bricklayer with eczema who yielded positive reactions to aqueous 0.1% and 2% solutions of potassium dichromate. Cairns and Calnan  described a green-tattooed cement worker with eczema who reacted to aqueous 0.1% and 0.5% solutions of potassium dichromate and to an aqueous 2% solution of cobalt chloride.
Walsh  ascertained that aqueous 0.5% sodium dichromate, 0.5% potassium chromate, 0.05% sodium dichromate, and 0.005% sodium dichromate solutions produced lesions on abraded skin. Perone et al  found that among 95 construction workers who worked regularly with cement, 1 reacted to an aqueous 0.25% solution of potassium dichromate and 1 other man reacted to an aqueous extract of cement containing 450 ppb (450 ng/g) hexavalent chromium but not to the 0.25% solution of potassium dichromate. Improvements were also made in other plants.  At the time of the study in 1949  the range of exposures for the 7 who died from lung cancer was estimated from employment histories, job classifications, and 1949-50 environmental chromium concentrations.
The range of exposures was calculated to be 10-150 fxg/cn m and the mean was 50 jig/cu m , (  Eight cancers were found in a group of 100 rats when pellets of calcium chromate in a cholesterol carrier were implanted intrabronchially.
Six of these were squamous cell carcinomas and were found in animals dying after 386-671 days. One animal dying after 474 days had metastases to the kidney. Two adenocarcinomas produced by calcium chromate were observed at 366 and 609 days. Both of these demonstrated mucus production. These rats showed atypical squamous metaplasia of the bronchus.  Calcium chromate produced cancers in 10 of 35 rats at the sites of intramuscular injections.  In addition, it produced cancers in 28 of 35 rats at the sites of intrapleural administration.  Inhalation of calcium chromate produced in rats 1 keratinizing squamous cell carcinoma, 1 laryngeal squamous cell carcinoma with invasion of perineural spaces and adjoining cartilagenous rings, and 1 malignant peritruncal tumor of undetermined type and origin.
At the same concentration of airborne calcium chromate, 1 hamster developed a squamous cell carcinoma of the larynx which was invading and destroying the cartilage.
In terms of chromium(VI), this calcium chromate concentration was 670 ig/cu m. Animals received 589 exposures at this concentration over 891 days. In view of these findings, the investigators examined the larynges. Two rats showed laryngeal hyperplasia and 3 showed laryngeal squamous metaplasia. Effects in hamsters were more marked with 8 animals showing laryngeal hyperplasia. An additional 8 animals showed squamous metaplasia of which 5 were "atypical with downgrowth." Another hamster, dying after 611 days, showed a squamous papilloma in the larynx with hyperplasia and hyperkeratosis.  One study  used calcium chromate with a solubility in water of 1,200-1,400 ppm ground in a ball mill after the solubility was determined.
Approximately 136 C57BL/6 mice of each sex were exposed to 13 mg calcium chromate/cu m for 5 hours/day, 5 days/week for their lifetimes. Six males in the exposed group developed lung tumors; 3 of the unexposed had lung tumors. Eight females in the exposed group had lung tumors; 2 in the control group had lung tumors. The lung tumors in the calcium chromate-exposed animals were generally not different from those in the control.
All tumors were pulmonary adenomas or adenocarcinomas.  This material has been referred to as chromic chromate in some instances.  In a study by Payne,  sintered calcium chromate was mixed with sheep fat and implanted into muscle tissue of the thighs of 52 mice. At the end of 14 months, a total of 9 implantation-site sarcomas were found. While the animal data leave much to be desired, there is sufficient information to support the conclusion that c h r o m i u m ( V I ) compounds are implicated in the production of cancer, regardless of the mode of administration.
From the information available, it appears that a chromium(VI) mate rial generated by the alkaline roasting of chromite ore, has carcinogenic characteristics when inhaled.      IV. ENVIRONMENTAL DATA Sampling and Chemical Analysis Air sampling for chromium compounds has been performed by a variety of methods suitable for particulate sampling and poses no significant prob lems.
Samples have been collected using electrostatic precipitators, It Is probable that chromium in other oxidation states will accompany chromium(VI) In the air; hence, analytical methods are required which differentiate between chromium(VI) and the other forms. Most published methods relying on Instrumental analysis are in reality total chromium methods, and will differentiate chromium(VI) from chromium(III) only if certain separation steps are included in the procedure. One separation procedure, the method for determining chromium(VI) recommended in the NIOSH criteria document for occupational exposure to chromic acid,  relies on the complexation of chromium(VI) with ammonium pyrrolidine dithiocarbamate (APDC), followed by extraction with methylisobutyl ketone polarography,  spark source mass spectrometry,  and X-ray fluorescence.
 It is also feasible, after forming chromium acetylacetonates or trifluoroacetylacetonates, to determine chromium by means of the very sensitive and selective gas chromatographic procedures.
 Beyerman  published a comprehensive review of the analytical methods for minute amounts of chromium. He critically compared the many methods with regard to their sensitivities, specificities, accuracies, and precisions. In addition he examined certain processes which are common to many methods such as the digestion of biologic samples in various strong acids. He specifically noted that consistently low results occurred when digestions were performed with perchloric acid due to the formation of chromyl chloride which was emitted as a gas. He further studied many common analytical reagents and showed that some of them were significantly contaminated with chromium, which could lead to erroneous results and high blank values. Errors due to the adsorption by the walls of glassware used were also appreciable, and other errors inherent in common analytical procedures were described. A particularly thorough study of extraction of chromium compounds with organic solvents was made, and various means of separating chromium(VI) by extraction were described.
The analytical methods considered by Beyerman Included those based on colorimetric measurements, emission spectrography, flame photometry, X-ray emission spectrography, activation analysis, and 2 electrometric methodspolarography and biamperometry.
Most Instrumental procedures are generally not specific for chromium(VI) and are not suitable for such analyses unless, as stated above, prior separations are made. In the NIOSH method recommended in the criteria document for occupational exposure to chromic acid  for example, atomic absorption spectrophotometrlc analysis is performed after extraction of chromium(VI) from the chromium(III).
There are means of performing an analysis in such a manner that only chromium(VI) is determined, and several such methods are based on the fact that chromlum(VI) reacts with iodide to form iodine that may thereafter be determined by a variety of standard iodometrlc procedures.  Such methods are not truly specific for chromium(VI) for they may be subject to interference by other oxidants or reductants. The reagents hematoxylin  and s-dlphenylcarbazlde 131,133, have been used for chromium(VI) analyses, and the latter reagent in particular is widely favored for analysis of chromium(VI) in air. s-Diphenylcarbazide forms a colored complex with chromium(VI), but not with other chromium compounds, and the stability of the color formed contributes to the sensitivity of the method. Several materials, notably iron, copper, nickel, and vanadium, may interfere with the analysis , but relatively large amounts are tolerated without significant effect. In addition, certain other compounds such as cyanides, organic matter, and reducing agents may also interfere. The effect of reducing substances, if present, must be taken into account in any method for determining chromium(VI), since they tend to decrease the actual airborne concentration of chromium(VI). In many sampling situations, however, the presence of significant quantities of such interferences may be ruled out and it is probable that in all but exceptional circumstances the method may be considered specific for chromium(VI) and subject to a minimum of interferences.
As noted previously, Abell and Carlberg  have demonstrated that reduction of chromium(VI) by the organic matter of the filter does not occur if polyvinyl chloride filters are used, and it is likely, though not proved, that certain other types of filtration media would also be suitable.
Subsequent experience with, and the development of, refinements to the s-diphenylcarbazide method by NIOSH demonstrates the superiority of this method. NIOSH now recommends this as well for chromic acid instead of the method in the chromic acid criteria document  because the sdiphenylcarbazide method has shown at least indirectly the ability of many hygienists to obtain excellent results with it. In addition, the sdiphenylcarbazide method is simpler to use than the method in the chromic acid criteria document  and requires the purchase and use of less expensive, more commonplace analytical instrumentation.
For many years, test papers have been commercially available which rely on the reaction of chromium(VI) with a paper impregnated with sdiphenylcarbazide reagent.  Such papers, at best, give only an approximate indication of the concentration of chromium(VI) if present in a mist and cannot be expected to reliably indicate the presence of dry particulate matter containing chromium(VI).
There has been great interest in the determination of chromium in biologic materials, both for nutrition studies and in relation to occupa tional exposure to chromium compounds.  Dif ferential analysis for chromium(VI) in biologic samples is not easy, and most analyses reflect the total chromium intake. Many of the analytical difficulties encountered in chromium analyses are particularly troublesome in biologic samples where the extremely low concentrations of the element and the difficulties of ensuring complete oxidation of the chromium may cause substantial analytical errors. It is perhaps for these reasons that biologic monitoring of chromium, as discussed in Chapter III, is of relatively little value in assessing exposure to chromium(VI) in the occupational environment.

# Control of Exposure
In many operations in the production and use of chromium(VI), exposures can be eliminated or kept within safe limits by use of closed system operations for reactors, conveyors, and holding or storage containers.  In such systems care must be exercised to ensure tight and reliable seals and joints, access ports, covers, and other such places. Failure of such seals can result in dust or spray emission into the atmosphere of the workroom.  When possible, such closed systems should be maintained under negative gage pressure. Even with closed systems, there will be unloading, charging, transferring, discharging, packaging, and transporting operations which afford various opportunities for contact with chromium(VI) and for the emission of dust and mist containing chromium(VI).
Emission of airborne chromium(VI) can be controlled at the source by suitably designed exhaust ventilation. In employing exhaust ventilation for such control, certain recommended practices,  and design and operating fundamentals  should be followed. Sources of emission should be as fully enclosed by hoods as possible. The exhaust air should be passed through air cleaners of suitable efficiency to reduce the chromium(VI) concentration to acceptable levels before discharge into the community air.
Atmospheric exposure to and other contact with chromium(VI) can and should be reduced or controlled by isolating the process or emission source from employees.
Location of an operation in an isolated area can also limit the number of employees who will be exposed in that operation. Such operations must be amenable to remote or automated control or to only intermittent attention by an operator.
In effect, the worker can be Isolated from the process by providing a clean area (clean room) in which the atmosphere is maintained essentially free of chromium(VI) and other significant contaminants. This may be accomplished by supplying air from an uncontaminated area or by filtering ambient air through high-efficiency filters.
A clean area may be established as the control room for remote control operations or as an area to which operators may retreat for such periods as their presence may not be required at the process equipment.
Ventilation and Isolation of the processes will reduce the probability of excessive contact with chromium(VI). For protection of eyes and skin, however, these measures may not be adequate for some operations.
For those operations where contact of the chemicals with the eyes or skin may occur, whether by the nature of the work or by accidental splashes, sprays or spills, proper protective equipment, work clothing, and good work practices are required to control the exposure (see Chapter VI).
The operations for which it is most difficult to control exposures are those of the maintenance and repair workers. The duties of these employees require that they enter or otherwise come into close contact with equipment or areas which may be grossly contaminated with chromium(VI). The TLV documentation stated "A review of the present status of the suitability of the TLV between TLV subcommittee members and industrial-hygiene representatives of the chromate industry 10 years after improved controls had been in operation revealed that (1) the TLV for chromic acid mist was satisfactory; (2) it contained a safety factor of 3 or 4; and (3) the limit was probably satisfactory for the pre vention of lung cancer, as no new cases had appeared during the 10-year period; but (4) that the 10-year period was probably too short to be certain of its validity in this respect."  Data in support of these points were not presented and discussed.
In the 1973 edition of the Threshold Limit Values  a change was proposed in the chromium TLV's. The TLV for chromic acid and chromates remained 0.1 mg/cu m as chromic acid anhydride. The TLV for "Chromium, sol. chromic, chromous salts as Cr" remained 0.5 mg/cu m, but the category "chromium... metal and insoluble salts", which had been 1.0 mg/cu m,  was marked for intended changes in order to be included as a group of substances in industrial use that have proved carcinogenic in man, or have induced cancer in animals under appropriate experimental conditions. The group was labeled "Chromates, certain insoluble forms" with a TLV of 100
Mg/cu m. This group of certain insoluble chromates probably included calcium and zinc chromates and sintered chromium(VI) oxide (called chromic chromate) and others.
The group was discussed in the 1971 TLV documentation  under "Chromic Acid and Chromates" for which the TLV was 0.1 mg/cu m, but in 1973 these materials were apparently removed from that group and placed under "chromium...metal and insoluble salts." It was not mentioned, however whether this intended TLV, 100 ng/cu m, was in terms of chromium, chromium(VI) oxide, or as chromates. Thus, the intended change to 100 jug/cu m may have been an increase, no change, or a decrease in the TLV for these materials. Nonetheless, the intent was apparently to denote "Chromates, certain insoluble forms" as "Human carcinogens."

# I
In 1974 the situation was clarified,  in that the TLV for "chromic acid and chromates" was 0.1 mg/cu m as chromium(VI) oxide and that the TLV's of "Chromates, certain insoluble forms, (Pb, Zn, and chromatechromite ore...)" were 0.1 mg/cu m as chromium and these materials were noted as human carcinogens. It should be noted that the 1974 TLV for these compounds represented an increase in the TLV over the 1972 TLV.
The present (1975) federal standard for chromic acid and chromates is a ceiling concentration of 1 mg/10 cu m, ie, 100 ng/cu m, (29 CFR 1910.1000) based on the American National Standard Z37. 7-1971.  In 1963  the Threshold Limits Committee recommended a limit of 0.1 mg chromium(VI) oxide/cu m for tertiary butyl chromate, an ester of tertiary butyl alcohol and chromic acid, which was unchanged in the 1974 TLV's.  As support for this recommendation, they cited the study by Roubal and Krivucova  in the 1971 documentation.
 Roubal and Krivucova  68,83] pulmonary congestion and edema,  epigastric pain,  erosion and discoloration of the teeth,  and perforated eardrums  have been reported on occasions, but again it seems reasonable that sufficient contact with any chromium(VI) material could cause these effects.
In addition to causing these effects, some chromium(VI) compounds have been found to be associated with an increased incidence of lung cancer. 95,180]  Delpech and Hillalret in 1869  described the effects of potassium chromate and bichromate on workers in the French chromate industry.
Workers suffered respiratory ailments from the first day of their employment. One assigned the task of washing "simple chromates", began to suffer from nasal membrane injury, headache, and shortness of breath several days after he started this job. Another worker, involved in calcining and bichromate extraction also had shortness of breath. No environmental data were reported but exposures were probably high because of the then prevailing poor hygiene around reverberatory furnaces.
In the chromate-producing Industry in the United States, only a small part of which produced chromic acid anhydride, the principal exposures to chromium(VI) were evidently to sodium chromate and bichromate because these were and are the principal intermediate and product of the alkaline roasting operation.
To a lesser degree, there was also exposure to potassium chromate and bichromate. In 1884 Mackenzie  related having been told by a workman that destruction of the nasal septum sometimes took place after 24-48 hours of exposure. This destruction was associated with general congestion of the mucous membrane, nosebleed, coryza, ulceration of the turbinates, nasal pharynx, and lower pharynx, and inflammation of the lower respiratory tract. Intense headache, Inflammation and perforation of the tympanic membranes, and subsequent otorrhea also occurred. Exposures in this plant were probably very high, based on remarks about the history of the operation.  In 1948, Machle and Gregorius  reported the incidence of nasal septal perforation in a sodium chromate-sodlum bichromate-producing plant to be 43.5% in 354 employees. Airborne chromate concentrations were 10-2,800 Mg/cu m at the time of the study. The plant had been In operation for at least 17 years; thus, some employees had probably worked in the plant when reverberatory furnaces were used, a notorious source of exposure.
This study provided evidence that exposure to sodium bichromate and chromic acid anhydride does not produce lung cancer.
During the 17year period plant D2 had been in operation, no deaths from lung cancer occurred. By contrast, In plant Dl, which used alkaline roasting of chromite ore to manufacture sodium chromate, there were 5 deaths from lung cancer in the same period. As discussed in the section on Epidemiologic Studies, exposure to the intermediate in alkaline roasting has been associated with an Increased incidence of lung cancer.
In the early 1950's, an epidemiologic study  was carried out in a single chrome plant in Ohio which produced sodium chromate and bichromate but no chromium(VI) oxide. In this study, the overall incidences of nasal septum perforations, chronic chemical rhinitis, and chronic chemical pharyngitis were significantly greater than those of the control group.
The chromium(VI) concentration was as great as 0.5 mg/cu m. However, the incidences of these disorders in the groups of workers exposed at less than Results of analysis of airborne chromium showed cross-contamination of work areas in that airborne chromite ore and water-soluble chromium(VI) as well as acid-soluble, water-insoluble chromium, were found in nearly all areas of the plants; the acid-soluble, water-insoluble chromium was analyzed by direct colorimetry. Of the 897 workers examined, 57% had perforation of the nasal septum, 11% had a severely red throat, 8% had edema of the uvula and 50% had cutaneous ulcers or scars. The Incidence of severely reddened throat and edema of the uvula was greater than twice that of control groups. Data on cutaneous effects in the control group were not given.
There was also an Increased incidence of lung cancer in these chromate workers. A more recent study  has Indicated poor work practices (eg, nose-picking) to be the likely causes of nasal ulcers and perforations. It seems evident that ulcers on the skin and hands (and other exposed skin areas) are also from local contact, thus the result of poor work practices. Although Mancuso  and the US Public Health
Service report  did not make observations on this point, it seems likely that the high incidence of nasal and cutaneous ulcers and sequelae in their studies was also largely, conceivably entirely, due to such work habits.
However, a contributory role of airborne chromlum(VI) in the development of nasal ulcers and septal perforations and the major role in the development of primary nasal irritation must be considered.
Liver enlargement was noted In about 2% of the chromate workers.
Those with enlarged livers were at least 15 years older and had worked an average of 4 years longer in the chromate industry than those without enlarged livers. The frequency with which white and red blood cells and casts were found in the urine was usually greater than that in the average industrial population, suggesting kidney damage.
The nonneoplastlc signs of exposure to chromium(VI)-nasal mucosal irritation and ulceration and, to a lesser extent, nasal septal perforation-were likely to be closely related to airborne chromium(VI) at the average concentration measured at the time of the study, ie, 68 jug/cu m.
There was some evidence that liver and kidney damage occurred as a result of long-term exposure to chromium(VI). Results were more conclusive relative to kidney damage in controlled experiments with monkeys, which sustained  kidney damage after subcutaneous Injections of sodium bichromate. Absorption of large amounts of chromium(VI) has, on a few occasions,  resulted in hepatic injury; it has also produced severe nephritis.  Because there have been several instances  in which kidney damage has apparently been the result of chromium(VI) absorption, routine urinalysis should be performed where there is occupational exposure to chromium(VI). Hepatic injury  has also been reported  as the result of chromium(VI) absorption; for this reason, it is recommended that in routine medical examinations the responsible physician should consider appropriate liver studies.
From these studies of the effects of exposure to sodium or potassium chromate or bichromate, two  contain information useful in deriving an exposure-effect relationship. The work of Mancuso   be modified and expanded to include these salts in addition to "chromic acid anhydride and aqueous solutions thereof" would be addressing a group of compounds of uniform toxicity.
In the light of the study by Machle and Gregorius  which showed an elevated incidence of lung cancer only in that part of the operation involving lime roasting, it seems clear that the lung cancer found in the US Public Health Service study  occurred in that part of the population involved in lime roasting. This is supported by some observations of the authors,  in that, of those workers with lung cancer whose work history was sufficiently described, most had worked at or near the lime mills or kilns. It is also supported by Laskln et al  and written information supplied by Levy in 1975 which indicated that the highest incidence of lung cancer was found in animals treated with calcium chromate. The information from Levy indicated no lung cancers were produced in animals treated with sodium chromate or bichromate.
When the toxicities of chromium(VI) compounds are examined, it becomes apparent that several have demonstrated carcinogenic activity.
95,107,117,118,120,161,180] Nearly all the implications of carcinogenicity have arisen from studies of the worker population of the chromate-bichromate producing industry and from animal studies using the intermediates produced in that industry. Some Implications have arisen from the pigment-producing industry  and from animal studies  using pigments and chemically analogous chromium(VI) compounds.
Other Industries and processes are suspect despite the absence of appropriate studies because they use or produce materials chemically similar to the Intermediates in the chromatebichromate industry or chromium(VI) pigments.  The only industry which has been extensively studied 95,161,180] has been the chromate-bichromate producing industry in the United States. However, even studies of this industry have provided only small amounts of information. Thus, the relationship between airborne concentrations of certain chromium(VI) compounds and the incidence of cancer is uncertain. Machle and Gregorius  published the first report of a high incidence of lung cancer among workers in the US chromate Plant , studied by Machle and Gregorius,  was later examined extensively by another team of investigators. 95,161,180] This plant produced sodium chromate and sodium bichromate through alkaline roasting of chromite ore, but no chromium(VI) oxide.
In 1 study, Mancuso and Hueper   the time between their periods of employment and the analysis of airborne chromium(VI), it is unlikely that the calculated TWA exposures adequately reflected the actual exposure to chromium(VI) the men had while working.
In addition, airborne chromium(III) and chromium(VI) were present in all areas of this plant making it impossible to associate the high incidence of lung cancer with exposure to a particular chromium compound.
In As in the above study  the large number of variables in this study  precludes the derivation of a dose-response relationship.
In 1975, Watanabe and Fukuchl reported preliminary results  of a recent survey of a Japanese chromate-produclng plant. The survey showed that in 136 workers who had been employed for at least 9 years there were 10 cases of lung cancer. The number of deaths from lung cancer was 21.2 times as high as the expected number of deaths. In the plants studied by Gross and Kolsch  which produced lead chromate pigments and zinc chromate pigments from chromium(VI), a high incidence of lung cancer was also reported. Unfortunately, no information was provided on airborne concentrations of chromlum(VI) materials in these plants.
Langard and Norseth  found the incidence of lung cancer in a plant producing both lead chromate and zinc chromate pigments to be 38 times the expected Incidence. In a cohort of 24 workers, the 3 who developed lung cancer were exposed for 6, 7. In animal studies, inhalation of calcium chromate was found  to produce 1 keratinizing squamous cell carcinoma, 1 laryngeal squamous cell

# VI. WORK PRACTICES
In the production and use of chromium(VI) materials, work practices must be designed to minimize or to prevent the inhalation of such materials and their contact with skin and eyes. Good work practices are a primary means of controlling certain exposures and will often supplement other control measures.
Enclosure of materials, processes, and operations is completely effective as a control only when the integrity of the system is maintained.
Such systems should be inspected frequently for leaks and any leaks found should be promptly repaired. Special attention should be given to the condition of seals and joints, access ports, and other such places.  Similarly, points of wear or damage should be inspected regularly. Gloves, aprons, goggles, face shields, and other personal protective devices must be maintained in good hygienic and uncontaminated condition.
They should be cleaned or replaced frequently and on a regular schedule.
Employees should keep such equipment In suitable, designated containers or places when the equipment is not in use.
Workers may reduce the potential exposures significantly by retiring to clean areas when their presence at the operation point is not necessary.
A clean area may simply be a room or a space where sustained environmental levels are such that it can be considered as being without occupational exposure to chromium(VI). A clean area can be deliberately established by means of ventilation which provides either filtered air or air from an uncontaminated source in a manner and amount which maintains the environ mental level of chromium(VI) at a nonexposure level.
In areas and at operation sites where the use of respiratory protection is required, the employee shall wear the designated type of respirator and observe the practices of the respiratory protective devices program. The necessity of cleanliness and maintenance of respirators should be emphasized. Practices which lead to the contamination of the interior of the facepiece should be prohibited.

# Precision and Accuracy
Ten filters spiked with 1.0 ng of chromium(VI) (a 0.01-ml droplet of 100 ppm chromium(VI) standard solution was placed on each filter and allowed to dry) gave recoveries of 93% with a relative standard deviation of 3.2% when analyzed within 1 hour of deposition; after 1 week, the average recovery dropped to 50%. Twenty-two filters, each loaded with about 5 n g of chromium(VI) in a chromic acid mist generator, gave results with a relative standard deviation of 4.3%. No corroborative tests have been performed on this method.
Apparatus 22-mm round, matched cuvettes.
Filtering apparatus.
Spectrophotometer set to operate at 540 nm.

# Reagents
Water: Unless otherwise designated, all water used is double distilled or deionized.
Half-normal sulfuric acid solution: Add 13.9 ml of concentrated sulfuric acid to some water in a 1-liter volumetric flask and dilute to mark. The exact concentration is not critical but it is suggested that the same solution be used for a complete test-samples, blanks, and standards.
After thorough mixing, it is convenient to transfer part of the solution to a small plastic wash bottle. (3) With each batch of samples, 1 filter labeled as a blank should be submitted. This filter should be subjected to exactly the same handling as the samples except that no air is drawn through it.
The samples should be shipped in a suitable container, designed to prevent damage in transit.
(c) Analysis of samples (1) Pipet 15 ml of water into each cuvette to be used. Put a piece of tape on the cuvette so that its bottom edge matches the meniscus. Rinse the cuvetteB.
(2) Blank filters are folded and placed directly into cuvettes. Sample filters are folded and placed in large test tubes.
(3) Six or 7 ml of 0.5 K sulfuric acid is added to each tube and the tube is shaken to assure that all surfaces of the filter are washed.
The filters are removed from the tubes with small forceps with careful washing of all surfaces with an additional 1 or 2 ml of 0.5 N sulfuric acid. The washed filters are discarded. The method is extremely simple, very selective for chromium(VI), and sensitive. The samples, when collected on PVC filters, are very stable.
The recovery after 2 weeks is essentially the same as for the first day.
Filters kept for 9 weeks gave an average recovery that was 79% of the first day's results. However, samples made by spiking PVC filters are not very stable and give poor recoveries. Spiked filters are therefore not recommended for standards.

# X. APPENDIX III -MATERIAL SAFETY DATA SHEET
The following items of Information which are applicable to a specific product or material shall be provided in the appropriate block of the Material Safety Data Sheet (MSDS).
The product designation is Inserted in the block in the upper left Chemical substances should be listed according to their complete name derived from a recognized system of nomenclature.
Where possible, avoid using common names and general class names such as "aromatic amine,"
"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.  The "Health Hazard Data" should be a combined estimate of the hazard of the total product. This can be expressed as a TWA concentration, as a permissible exposure, or by some other indication of an acceptable standard. Other data are acceptable, such as lowest LD50 if multiple components are involved.
Under "Routes of Exposure," comments in each category should reflect the potential hazard from absorption by the route in question. Comments should indicate the severity of the effect and the basis for the statement if possible. The basis might be animal studies, analogy with similar products, or human experiences. Comments such as "yes" or "possible" are not helpful. Typical comments might be:
Skin Contact-single short contact, no adverse effects likely; prolonged or repeated contact, mild irritation and possibly some blistering.
Eye Contact-some pain and mild transient irritation; no corneal scarring.
"Emergency and First Aid Procedures" should be written in lay language and should primarily represent first aid treatment that could be provided by paramedical personnel or individuals trained in first aid.
Information in the "Notes to Physician" section should include any special medical information which would be of assistance to an attending physician including required or recommended preplacement and periodic medical examinations, diagnostic procedures, and medical management of overexposed workers. Respirators shall be specified as to type and NIOSH or US Bureau of Mines approval class, ie, "Supplied air," "Organic vapor canister," "Suitable for dusts not more toxic than lead," etc. Protective equipment must be specified as to type and materials of construction.

# reliability,
itaalyses by the method recommended in the chromic acid criteria document, which uses atomic absorption spectrophotometry, have been subsequently found by NIOSH to be much more time consuming than those using the s-diphenylcarbazide colorimetric method; thus, it appears that routine analysis would be simplified by a recommendation that the sdiphenylcarbazide colorimetric method be used for the determination of all chromium(VI) compounds, whether or not carcinogenic.
Therefore, the recommended analytical chemical method is that described in Appendix II and it uses the spectrophotometric determination of a colored complex of chromium(VI) and s-diphenylcarbazide.
Because of the carcinogenicity of some chromium(VI) materials and the lack of evidence suggesting a safe workplace environmental limit, it seems appropriate to recommend that no detectable amounts of these substances be allowed in workplace air with a specified method of sampling and chemical analysis.
The recommended analytical method (v.s.) will reliably detect 0.5 jug chromium(VI). The lower detection limit is approximately 0.05 jig chromium(VI) by this method but detection and determination are not reliable at this limit because of (1) variations in the background concentrations of airborne and reagent substances that interfere with the determination of chromium(VI) at this trace level and (2) the Inherent unreliability of the calibration curve generated by determinations of known amounts of chromium below, at, and slightly above the detection limit.
Because of this unreliability at this limit of detection and the resultant questions about the validity of compliance actions at airborne chromium(VI) Some part of the total, usually between 10,000 and 20,000 tons was added directly to steel. The balance was used to make ferroalloys and Cr metal.  A small quantity, usually between 5,000 and 10,000 tons, was used in direct furnace repairs; the balance was used in making brick and other refractory products. Derived from reference 185 The projection includes allowance for losses during use of the ferroalloys in metallurgical processing and an additional 10% loss for processing chromite into ferroalloys. The average assay of ore for metallurgical uses is 50% Cr203; the average assay of ore for refractory use is 35% Cr203 and no processing loss is assumed; average assay of ore for chemicals and facing sand uses is 45% Cr203. Derived from reference 185