# I. RECOMMENDATIONS FOR A CHLOROFORM STANDARD
The National Institute for Occupational Safety and Health (NIOSH) recommends that worker exposure to chloroform (CHC13) 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 day, 40-hour week over a working lifetime; compliance with the standard should therefore prevent adverse effects of chloroform on the health and safety of workers.
The standard is measurable by techniques that are valid, reproducible, and available to industry and governmental agencies.
Sufficient technology exists to permit compliance with the recommended standard. The standard will be subject to review and revision as necessary.
"Exposure to chloroform" is defined as exposure above half the timeweighted average (TWA) environmental limit. Exposures at lower environmental concentrations will not require adherence to the following sections, except for Sections 4 (b) and (c) and Section 6 (d).

# Section 1 -Environmental (Workplace Air) (a) Concentration
Occupational exposure shall be controlled so that no worker will be exposed to chloroform in excess of 10 ppm (48.9 mg/cu m) determined as a time-weighted average exposure for up to a 10-hour workday, 40-hour workweek, or for any 10-minute period to more than 50 ppm (244 mg/cu m ) .

# (b)
Sampling and Analysis
The procedure for sampling and analysis of workroom air for compli ance with the standard shall be as provided in Appendix I, or by any method shown to be equivalent or better in precision, sensitivity, accuracy, and specificity.
Section 2 -Medical (a) Comprehensive preplacement medical examinations shall be made available to all workers subject to "exposure to chloroform" and yearly thereafter, unless a different frequency is indicated by professional medical judgment.
(b) These examinations shall include, but shall not be limited to:
(1) A comprehensive or interim medical and work history giving special attention to gastrointestinal symptoms and mental status.
The worker's alcohol consumption should be reviewed.
(2) A comprehensive medical examination, giving particular attention to cardiac rhythm, liver and kidney function. Liver function tests and urinalysis shall be performed.
(3) An evaluation of the advisability of the worker's using negative-or positive-pressure respirators. Avoid breathing vapor.
Avoid contact with skin.
May generate toxic phosgene gas on contact with flame or very hot metal surface.
This warning sign shall be printed both in English and in the pre dominant language of non-English-speaking workers, if any, unless they are otherwise trained and informed of the hazardous conditions. All illiterate workers shall receive such training.
If exposures to chloroform in the workroom exceed the recommended standard, and a variance permitting the use of respiratory controls has been granted, the following shall be added to the sign: No worker allowed to enter area without proper respiratory protection.

# Section 4 -Personal Protective Equipment and Clothing
When the limit of exposure to chloroform prescribed in subsection (a) of Section 1 cannot be met through application of available engineering controls in the design of equipment, systems, or operating procedures, an employer must utilize, as provided in subsection (a) of this Section, a program of respiratory protection to effect the required protection of every worker exposed.

# (a) Respiratory Protection
Appropriate respirators shall be provided and used when a variance has been granted to allow respirators as a means of control of exposure to routine operations and while the application is pending. Administrative controls can be used to reduce exposure. Respirators shall also be provided and used for nonroutine operations (occasional brief exposures above the standard and for emergencies); however, for these instances a variance is not required but the requirements set forth below continue to apply. Appropriate respirators as described in Table 1-1 shall only be used pursuant to the following requirements:
(1) For the purpose of determining the type of r tor to be used, the employer shall measure the atmospheric concentration of chloroform in the workplace when the initial application for variance is made and thereafter whenever process, worksite, climate, or control changes occur which are likely to increase the chloroform concentration. This requirement shall not apply when only atmosphere-supplying positive pressure respirators are used.
The respirator and cartridge or canister used shall be of the appropriate class, as determined on the basis of exposure to chloroform.
The employer shall ensure that no worker is being exposed to chloroform in excess of the standard because of improper respirator selection, fit, use, or maintenance.
The employer shall provide respirators in accordance with Table 1-1 and shall ensure that the employee uses the respirator provided.
(5) Respiratory protective devices described in Table I-1 shall be those approved under provisions of 30 CFR 11.
(6) Respirators specified for use in higher concentra tions of chloroform are permitted in atmospheres of lower concentrations.
(7) Chemical cartridges and canisters shall not be used for periods of time in excess of those indicated in Table 1-1.
Employees shall be given instruction on the use of respirators assigned to them, cleaning of the respirators, and how to test for leakage.
(9) Wherever bulk chloroform is handled, emergency and escape-type respirators shall be made readily available for each worker.
Continuous contact must be maintained with employees working in enclosed spaces where chloroform concentration may become excessive.

# (b) Protective Clothing
In any operation where the worker may come into direct contact with liquid chloroform, protective clothing shall be worn. The clothing must be both impervious and resistant (such as neoprene or polyvinyl chloride) to chloroform. Bib-type aprons should be at least knee length, gloves should be lined to absorb perspiration, and boots or overshoes shall be provided when necessary. Impervious supplied air hoods or suits should be worn when entering areas with limited egress such as pits or tanks. All protective clothing should be well aired and inspected for physical defects prior to reuse. 1) Full face gas mask, chest or back mounted type, with industrial size organic vapor canister. Maximum service life of 2 hours. 2) Type C supplied air respirator, demand type (negative pressure), with full facepiece.
1) Type C supplied air respirator, con tinuous flow or pressure-demand type (positive pressure) with full face piece, hood or helmet.
1) Self-contained breathing apparatus with positive pressure in full facepiece. 2) Combination supplied air respirator pressure-demand type, with auxiliary self-contained air supply.
1) Self-contained breathing apparatus with positive pressure in facepiece. 2) Combination supplied air respirator, pressure-demand type, with auxiliary self-contained air supply.
1) Self-contained breathing apparatus in demand or pressure-demand mode (negative or positive pressure). 2) Full-face gas mask, front or back mount type with industrial size organic vapor canister. 3) Mouthpiece respirator with escape type organic vapor canister (escape type gas mask).
(c)
Eye Protection
Eye protection shall be provided for any employee engaged in an operation where chloroform liquid or mist may enter the eye. Chemical-type goggles, safety glasses with splash shields, or plastic face shields made completely of chloroform resistant materials shall be used.
Suitable eye protection shall be provided in accordance with 29 CFR 1910.133.

# Section 5 -Informing Employees of Hazards from Chloroform
At the beginning of employment in a chloroform area, each employee shall be informed of the hazards, relevant symptoms, effects of overexposure to and the proper conditions and precautions concerning safe use and handling of chloroform.
The information explaining the hazards of working with chloroform shall be kept on file and readily accessible to the worker at all places of employment where chloroform is manufactured, used, stored, or transported.
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 correctly use respiratory protective equipment and protective clothing.
Information on file and readily accessible to workers shall include that specified in Appendix II, on US Department of Labor Form 0SHA-2Q "Material Safety Data Sheet", or a similar form approved by the Occupa tional Safety and Health Administration, US Department of Labor. Where employees are required to enter confined areas where containers of chloroform are stored, such as a delivery van, entry shall not be made until the space has been ventilated or checked for concentrations of chloroform.
(2) Storage containers, piping, and valves shall be periodically checked for leakage.
(3) Storage facilities shall be designed to contain spills and prevent contamination of workroom air.
(b) Contaminant Controls Suitable engineering controls designed to limit exposure to chloroform to that prescribed in subsection (a) of Section 1 shall be utilized where appropriate and feasible. Where ventilation systems are used to achieve such control, they shall be designed to prevent the accumulation or recirculation of chloroform in the workroom and to effectively remove chloroform from the breathing zones of workers.
Ventilation systems shall be subjected to regular preventive maintenance and cleaning to ensure maximum effectiveness, which shall be verified by periodic airflow measurements.
In addition, necessary measures shall be taken to ensure that discharge outdoors will be in conformance with all appropriate environmental regulations.

# (c) Equipment Maintenance and Emergency Procedures
Air saturated with chloroform is immediately dangerous to life and if a limited egress situation exists, emergency procedures must be established and followed.

# Chloroform hazard areas
Exits shall be plainly marked. Emergency exit doors shall be conveniently located and shall open to areas which will remain free of contamination in an emergency.
(2) Confined spaces (A) Entry into confined spaces or in other situations of limited egress shall be controlled by a permit system.
Permits shall be signed by an authorized representative of the employer certifying that preparation of the confined space, precautionary measures, personal protective equipment, and procedures to be used are all adequate.
(B) Tanks, pits, tank cars, process vessels, tunnels, sewers, etc, which have contained chloroform, shall be thoroughly ventilated, tested for chloroform, and inspected prior to entry.
(C) Inadvertent entry of chloroform into the confined space while work is in process inside shall be prevented by disconnecting and blanking off chloroform supply lines.
(D) Confined spaces shall be ventilated or otherwise maintained to keep the chloroform concentration below the limit and to prevent oxygen deficiency.
(E) Personnel entering confined spaces shall be equipped with a lifeline tended by another worker outside the space who shall be equipped with approved respiratory, eye, and skin protection.
(F) Written operating instructions and emergency medical procedures shall be formulated and posted in conspicuous locations where accidental exposure to anesthetic concentrations of chloroform may occur. These instructions and procedures 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.

# (d) Showers and Eye Wash Fountains
Showers and eye wash fountains shall be provided and so located as to be readily accessible in all areas where skin or eye splash with chloroform is likely. If chloroform is splashed on the skin, contaminated clothing shall be promptly removed and the skin washed with soap and water.
If liquid chloroform contacts the eyes, they shall be thoroughly irrigated with clean water. Medical assistance shall be promptly provided in cases of eye splash. Such incidents shall be reported to the immediate supervisor by the affected employee or by a fellow worker. Chloroform was originally made from acetone and bleaching powder and can also be made by reduction of carbon tetrachloride. The principal method of manufacture is now chlorination of methane.  Prior to World War II, chloroform was used primarily as an anesthetic and a pharmaceutical. The annual production of chloroform in the United States at that time was between 2,000,000 and 3,000,000 lbs. It is now seldom used as an anesthetic,  but it is used by many manufacturers for pharmaceutical purposes.  The production of chloroform for the manufacture of chlorodifluoromethane has grown over the years from 40,396,000 lbs in 1955 to 230,766,000 lbs in 1971, the latest year for which data are available. NIOSH estimates that 80,000 people are potentially exposed to chloroform in their working environment.

# Historical Reports
Simpson,  a surgeon and obstetrician in Edinburgh, reported in an 1847 issue of Lancet on the merits of chloroform as an anesthetic agent.
He advocated its use because it was pleasant to inhale, its action was more rapid and complete than that of ether, only a small amount was needed to produce narcosis, and it did not require the use of a special inhaler or instrument for its administration. He especially recommended it for use in obstetric practice because it alleviated maternal pain and recovery from anesthesia was rapid.
In 1874, Witte  observed that it required less chloroform to anesthetize frogs by absorption through the skin of the abdomen or thigh than by inhalation. He reported that rabbits also could be anesthetized by application of chloroform to the shaved abdomen, and he recommended that humans be anesthetized by absorption through the skin rather than by inhalation.
One of the first detailed descriptions of death from liver damage following chloroform anesthesia published in the English literature appeared in the January 26, 1894 issue of Lancet.
 A 4-year old boy seemed to be well after an operation which lasted about 1 hour, but early the next morning he began to vomit, his pulse became weak, breathing was shallow and irregular, and he lapsed into unconsciousness. Vomiting continued (the vomitus being dark brown in color), little urine was passed, consciousness was never regained, and death occurred 30 hours after the operation. At autopsy, the liver was found to be small (14 1/2 oz), pale buff color, studded with minute purple dots, and greasy to the touch.
Microscopy revealed intense fatty infiltration with no apparent fatty degeneration.
In 1898, Desgrez and Nicloux  reported that carbon monoxide was formed in dogs during chloroform anesthesia. They considered that the amount of carbon monoxide in the blood after 3-5 hours of anesthesia was equivalent to that present after exposure for 30 minutes to 100 ppm of carbon monoxide in air. Carbon monoxide was measured by a "grisoumeter" and chloroform did not interfere with the analytical method.
In 1904 Schwenkenbecher  reported that immersion of white mice up to their necks in aqueous solutions of chloroform was lethal. The solutions ranged from 0.3%-0.7% and the immersion time from 45-165 minutes.
A special collar was used to preclude inhalation, and the genital and anal openings were closed.
Moore and Roaf  in 1906 reported that chloroform added to hemoglobin solutions at body temperature caused a change in color and a precipitation of the hemoglobin.
In 1909, Whipple and Sperry  published studies of liver necrosis in dogs following anesthesia with chloroform. They compared the liver damage observed in dogs to that seen in a 19-year old woman who died 3 days after anesthesia with chloroform for 35 minutes. They concluded that in dogs chloroform anesthesia for 1-2 hours would invariably cause central liver necrosis, and that the anatomic changes in the human autopsy were identical to those observed in the experimental dogs.
Lehmann  was the first to mention the industrial hygiene aspects of chloroform. He stated that in Germany more than 100 tons of chloroform was produced annually and that its manufacture in well designed factories did not create any danger to workers.
Lewin  in 1920 reported that the use of chloroform as a solvent for fats and resins was associated with a feeling of being "stoned", head ache, dizziness, breaking of the voice, sometimes an increase in saliva flow, bronchial catarrh, pounding of the heart, and with continued exposures, disturbances of metabolism, leading to a "real change in substance in the kidney and even to albumin in the urine."

# Effects on Humans (a) Central Nervous System Effects
The most outstanding effect of chloroform on the central nervous system is narcosis. Because of this property, chloroform was extensively used as an anesthetic. Featherstone  concluded from a review of the literature that 20,000 ppm of chloroform was usually used to produce anesthesia and that 40,000 ppm, if continued for several minutes, could be an overdose. He suggested, for induction of anesthesia, gradually increasing the concentration of chloroform during the first 2 or 3 minutes to attain and maintain a concentration of 25,000 or 30,000 ppm until full anesthesia developed. The concentration used to produce anesthesia is usually not maintained for the duration of the operation but is replaced by a lower maintenance concentration such that the integrated exposure was actually much lower than 20,000 ppm.
In the experiments reported by Lehmann and Hasegawa   Fokina  reported effects of chronic exposure in the work environment to mixtures of chlorinated methanes, including chloroform.
Although the concentrations were not given, it was stated that the maximum permissible concentrations of individual components were exceeded at times.
(There was no MAC for chloroform in Russia in 1965.  ) The majority of workers showed signs of autonomic dysfunction, including diminution or disappearance of the corneal reflexes, dissociation between the deep (exaggerated) and superficial (sluggish) reflexes, marked persistent dermographism, general hyperhydrosis, acrohyperhydrosis, blotchiness of the skin of the hand and forearms, tenderness when pressure was applied to specific cervical points, and arterial hypotension. Autonomic dysfunction was mainly found in workers employed for less than 3 years. Workers employed for more than 5 years showed diencephalic disturbances and autonomic polyneuritis.  In the case of delayed chloroform poisoning reported by Whipple and Sperry,  urine specimens contained a trace of albumin, a few hyaline casts, and considerable quantities of leucine and tyrosine. At autopsy, the convoluted tubules of the kidneys showed a definite fatty degeneration with some of the epithelial cells having undergone necrosis. The capillaries were also found to be congested.
In the studies by Gibberd  and Lunt  laboratory findings indicated renal dysfunction; there were albumin, red blood cells, and pus in the urine, congestion of cortical vessels, fatty deposits, and necrosis.

# (d) Cardiovascular Effects
Cardiac irregularities were found frequently by Kurtz et al  in 1936 during electrocardiographic (ECG) surveillance of 113 surgical procedures.
Arrhythmias were reported in all 6 cases in which chloroform was used for anesthesia and in 83 of 107 operations in which other anes thetics were used, including ethyl ether, cyclopropane, nitrous oxide, tribromoethanol, procaine, vinyl ether, and ethylene. The authors  did not report the durations of anesthesia.
In 1951, Orth et al   stated that "this is a higher incidence of irregularities than is observed clinically with any other anesthetic agent except trichloroethylene". The irregularities were attributed to both reflex effects on cardiac automaticity and a direct depressant effect on the myocardium. In view of the high incidence of ECG abnormalities with all studied anesthetics,  the possibility of all other factors in the etiology of the abnormalities needs to be considered in drawing conclusions from this study. For example Orth et al  did not report the durations of anesthesia while Whitaker and Jones  considered this to be important.
Whitaker and Jones  in 1965 found less frequent cardiovascular effects among 1,502 cases where chloroform was administered by a precision vaporizer in concentrations not exceeding 22,500 ppm. There were 9 cases of arrhythmia in the 1,164 operations in which anesthesia lasted 30 minutes or less and there were 10 cases of arrhythmia in 338 operations in which the duration of anesthesia was greater than 30 minutes.

# (e) Hemolysis
Belfiore and Zimmerman  found that chloroform could affect the fragility of the red blood cell membrane without first being metabolized in the liver. Erythrocytes from 12 healthy adults were suspended in saline solution with chloroform ranging from 0.0125-0.10 mole/liter. The control was erythrocytes in a saline solution. At concentrations of 0.0125, 0.02, and 0.025 mole/liter there was no demonstrable effect. In concentrations of 0.05 mole/liter, erythrocyte leakage of hemoglobin, lactic dehydrogenase (LDH), and malic dehydrogenase began at 7 minutes and reached a maximum at 20 minutes for hemoglobin and at 10 minutes for the enzymes.
Belfiore and Zimmerman  found that incubation of cells with reduced glutathione (GSH) and oxidized glutathione (GSSG) inhibited hemolysis as measured by a loss of hemoglobin. They found that inhibition increased as the concentration of GSSG increased, but did not increase as the concentration of GSH increased. It has been suggested more recently, however, that it is only the GSSG that enters the intact red blood cell;
the effect of GSH is due to its oxidation to GSSG.  (f) Effects on the Skin Malten et al  measured injury and regeneration of forearm skin exposed to liquid industrial solvents, including chloroform. The solvents were contained in glass cylinders 2 cm in diameter which were fixed to the skin by agar-agar for 15 minutes a day for 6 consecutive days. An unspeci fied number of sites served as controls. The rate of water evaporation from these sites was determined daily to evaluate the degree of skin damage and regeneration. Exposure to chloroform was reported to be similar in effect to ethanol and to cause an increase in the rate of water evaporation with repeated exposures. Recovery of normal water retention, indicative of the formation of a new horny layer, occurred slowly during the 30 days after the last exposure.
Hoffman  suggested that chloroform could be used on skin to combat mosquitoes and other biting insects.
It seems doubtful that present-day dermatologists would recommend this use of such an irritating substance. Hoffman cautioned against getting chloroform into eyes and mucous membranes because of irritating effects.
Oettel  carried out systematic experiments with chloroform administered to the skin by way of a small glass vessel, 1 cm in diameter, one end of which was open, with glass hooks fused into it. Vessels were filled with chloroform and tied onto the arms of 5 subjects. Pure chloroform was used for various exposure times. Three minutes after application of chloroform, there was a sensation of burning and stinging.
When exposure time was increased to 6 minutes, the pain became more intense and then subsided quickly. When the chloroform was removed, the pain increased again, only to be replaced by a loss of feeling. Erythema was noted and the hyperemia which also occurred after 3 minutes of exposure was somewhat stronger, more cherry red with a light yellow undertone. In a 30minute period after removal of the chloroform, there was a fading away of the erythema and hyperemia, and 5 hours later, little blisters formed at the edge of the area of application. Erythema and pigmentation disappeared 7 days after the exposure.
From these studies,  it can be concluded that exposure of the skin to liquid chloroform will cause irritation, erythema, hyperemia, and destruction of the epithelium. Much of this information on skin irritation from chloroform is based on prolonged contact. However, it should be noted that repeated, brief contact can cause skin defatting. Thereafter, the rate of elimination decreased, and "small amounts" were reported to have been detected in the blood 8 hours after exposure.
Concentrations of chloroform in the blood were also measured by Cullen et al   Breath concentrations of chloroform in a worker after an industrial exposure to a mixture of solvents including chloroform, carbon tetrachloride, trichloroethylene, and perchlorethylene were measured by Stewart et al  in 1965. The exposure was defined as a "few minutes" without a gas mask followed by an unspecified time with a general purpose chemical respirator, to unknown concentrations with "strong" odors. The exposed worker experienced dizziness, weakness, nausea, and finally unconsciousness. The duration of unconsciousness is not known, but "10 minutes later" he was coherent, though uncoordinated and nauseated. Thirty minutes after his collapse, infrared analysis of his expired breath contained: perchlorethylene, 11 ppm; carbon tetrachloride, 9.5 ppm; chloroform, 7 ppm; and trichloroethylene, 11 ppm. Three days later, 0.1 ppm chloroform was found in the exhaled breath; 12 days after exposure, there was no chloroform found in the exhaled breath.
Several authors have reported on the concentration of chloroform in tissues following suicide, homicide, or death during or after an operation.
Gettler 

# Epidemiologic Studies
There are very few reports of industrial workers exposed to chloroform. The studies of Challen et al  and Bomski et al  are the only studies that contain exposure concentration measurements, descriptions of symptoms and diagnoses, and comparisons with control groups.
In 1958, Challen et al  reported a study of a confectionery firm in England that manufactured medicinal lozenges. In 1950, the operators began to complain of the chloroform vapor given off during the production of the lozenges. A system of part-time work was initiated to alleviate complaints of lassitude, flatulence, water brash (British term indicative of symptoms of dyspepsia), dry mouth, thirst, depression, irritability, and frequent and "scalding" micturition, but this was not successful, and fi nally the operators refused to work on that particular process. In 1954, a new team of operators was engaged and in 1955 a system of exhaust ven tilation was installed, after which the work proceeded without interrup tion.
In order to confirm the effectiveness of the ventilation system, Challen and his associates  were asked to ascertain the concentrations of chloroform. Additionally, clinical investigations were performed and an attempt was made to simulate the original conditions in order to compare the chloroform concentrations before and after remedial measures were introduced. The original conditions were simulated by closing the doors and windows and shutting off the ventilation system.
A single air sample was taken continously in the breathing zone of the operator of the ingredient mixing process during a period of 20 minutes coinciding with the duration of the process. Sampling at the rate of 2 liters/min was done by drawing air through 2 U tubes containing dried silica gel. Additionally, at a point in the operation where a peak concentration was expected, a 6-liter "grab" sample was taken. Air samples of 30-minute durations each were also taken in the breathing zones of cutting room operators. The samples were taken during 2 periods of production for 3 different operations on the same day (under current conditions) and during 3 periods on another day (during the simulated conditions Clinical investigations of 3 different groups of workers were per formed by Challen et al.  One group of 8 employees was termed the "long service operators". These were people who refused to continue in the lozenge department after they experienced the previously described symptoms. This group of workers, when exposed to chloroform vapor in probable concentrations ranging from 77 to 237 ppm, had been observed staggering about the work area. After terminating work in the lozenge department the "long service operators" reported experiencing nausea and stomach upset after even short exposures to the smell of chloroform.
A second group of 9 employees in this study,  termed the "short service operators", were the replacements of the "long service operators".
Two of these 9 employees did not report unpleasant experiences from chloroform exposure. Among the other 7, 5 reported dryness of the mouth and throat at work; 2 were subject to lassitude in the evening; 1 complained of lassitude and flatulence at work, and the experiences of 2 others were similar to those of the "long service operators". The "short service operators" worked in locations where the chloroform concentrations ranged from 23-71 ppm.
A third group of 5 employees in this study  who worked in other departments of the firm served as controls and exhibited no symptoms.
Neither tests of liver function (thymol turbidity, thymol flocculation, direct van den Bergh, and serum bilirubin), clinical examinations, nor urinary urobilinogen showed significant differences among the 3 groups of workers.
In 1967, Bomski et al  reported on liver injury from chloroform among workers in a pharmaceutical factory in Poland.
The study included the entire group of 294 workers who used chloroform in the course of production; of these, 68 were exposed to chloroform for 1-4 years and still had contact with chloroform, 39 had chloroform contact at one time, 23 had viral hepatitis with icterus 2-3 years earlier and were designated as posticterus controls and were working in a germ-free area, and 165 worked in a germ-free area with no history of viral hepatitis. Blood pressure, blood morphology, urinalysis, blood albumin, serum protein, thymol turbidity, zinc sulfate turbidity, the "Takata-Ara" sulfate (colorimetric) test, urobilinogen, SGOT, and SGPT were measured in all. A complete medical history was taken. Sixty of the people were hospitalized for determination of BSP clearance and urinary urobilinogen.
The air in the production room was sampled and chloroform concentra tions were determined using the Grabowicz  method. The concentration of chloroform ranged from 2-205 ppm. No other concentration measurements were reported nor was there any mention of the frequency of sampling.
The authors  compared the frequency of viral hepatitis and jaundice among a group of inhabitants of the city, 18 years and older, with that of the same 68 pharmaceutical workers who used chloroform. The results showed that in 1960, 0.35% of city inhabitants had viral hepatitis, while 16.67% of the chloroform exposed workers had viral hepatitis. In 1961, the frequency for city inhabitants was 0.22% and the frequency among the chloroform workers was 7.50%. In 1962 the frequency of viral hepatitis was 0.38% for city inhabitants and 4.4% for workers using chloroform. The authors suspected that the toxic liver changes occurring as a result of exposure to chloroform promoted a viral infection in such cases, but they did not give information on the incidence of viral hepatitis among other plant workers, which might have helped resolve questions about sanitary practices and facilities in the plant.
The majority of the workers who were in contact with chloroform during the investigation period covered in this study complained of headache, nausea, belching, and loss of appetite.
Among the 68 workers using chloroform, 10 cases of splenomegaly were found compared to none in the controls. They did not explain the splenomegaly but point out it was not present in controls.
The frequency of enlarged livers (17 out of 68) among workers exposed to chloroform exceeded the frequency of enlarged livers in the other groups (5 out of 39, and 2 out of 23). Livers were judged to be enlarged if they extended at least 1 cm beyond the rib arch in the midclavicular line. The upper margin was apparently not measured. In 3 of the 17 chloroform workers with enlargement of the liver, toxic hepatitis was diagnosed on the basis of elevated serum enzyme activities and elevated serum gamma globulin. The measured amounts of these serum constituents in these 3 workers were not reported. In the remaining 14 cases of liver enlargement, fatty liver was diagnosed. It was claimed that the latter diagnoses were substantiated by a 79% reduction in the incidence of hepatomegaly in the people studied during a 12-month period when hygienic work conditions were improved as a consequence of the studies.  In a continuing study  by the Department of Labor and Industries, Commonwealth of Massachusetts, worker exposure to chloroform, methylene chloride, and toluene in a plant manufacturing plastic film was investigated. The workers were exposed to levels of chloroform from 7-170 ppm, with a mean of 47 ppm.
Physical examinations and the following laboratory tests were performed regularly on all employees connected with the process: SGOT, LDH, alkaline phosphatase, blood bilirubin, BUN, creatinine, cholesterol, serum protein, urobilin, urobilinogen, urine bilirubin.
The blood tests were performed yearly and urine tests quarterly.
The liver function tests have been done for more than 2 years, the kidney function tests for only 1 year. Some of the employees at times experienced what was termed "dry heaves". Laboratory findings have been normal so far, but there appeared to be a significant number of findings in the upper normal range, particularly for the blood bilirubin and BUN. There was no evidence, though, that there was a progressive increase in the values found. However, the evaluations of the laboratory findings were based on the normal range for the general population rather than a specific control group for this particular investigation.
It is not apparent from this study what the time-weighted average exposures were.

# Animal Toxicity
The majority of animal studies of chloroform toxicity have been con
ducted to provide supplementary information relevant to the clinical use of chloroform as an anesthetic.
Consequently these animal studies include concentrations of chloroform many times greater than would be experienced in daily occupational situations except in the case of accidents. The following subsection contains a summation of some of these studies. Jones et al  in 1958 studied the relative hepatotoxicity of inhalation anesthetic drugs using chloroform as a standard of reference.
Chloroform was given orally to 350 white mice, each weighing approximately 20 g. The mice were killed 72 hours after exposure and livers were fixed in formalin. The authors  were able to estimate the following effects of acute injury from esophageal instillation of chloroform: Rats and guinea pigs given the 0.4 mg/kg dose of chloroform showed no changes in conditioned reflexes or in autonomic or cardiac activity, blood protein ratios, catalase concentrations, or phagocytic capacity.
There was an increase in ascorbic acid in the adrenals of the guinea pigs.
 Some guinea pigs given doses of 35 mg/kg died during the course of the experiment. Five of the guinea pigs lived longer than 2 months, but only 2 of these lived longer than 3 months. The ratio of blood protein fractions in the guinea pigs given 35 mg/kg was altered by the end of the first month. These changes consisted of an increase in the globulin content (from 32.91.09 to 40.92.22%) involving the alpha and gamma fractions and a decrease in the albumin content, so that the albumin-globulin ratio decreased from 2.1-0.4. The change in this ratio was even more pronounced at the end of the second month. The guinea pigs in the 35 mg/kg groups also showed a decrease in blood catalase activity from 2.00.13-1.20.11 (no units given) in the second month of the experiment.
The guinea pigs which had died from a dose of 35 mg/kg of chloroform had structural lesions of the liver, heart muscle, and stomach wall upon The effect of chloroform on rats exposed to 300 ppm was confused by changes in dietary intake.
It was not possible to determine whether decreased food consumption was the result of loss of appetite or the inability to eat due to narcosis.
Exposure of pregnant rats to 100 ppm on days 6 through 15 of gestation revealed a significant incidence of fetal abnormalities as compared to controls. There were significant increased incidences of acaudia, imperforate anus, subcutaneous edema, missing ribs, and delayed skull ossification.
Rats exposed to 30 ppm showed significant incidences of delayed skull ossification and wavy ribs, but no other effects.
The teratogenicity of oral doses of chloroform was studied in rats and rabbits.
 There was no evidence of teratogenicity in either species at any dosage level tested. However, in both species reduced birth weights (7.5% in rats and 1.1% in rabbits) were observed with the highest dosages, 126 and 50 mg/kg, respectively. tried to determine whether structural damage affecting protein synthesis occurs when chloroform acts on the liver of a rat. Twenty Sprague-Dawley rats were fasted for 10 hours and 4 were exposed to 1 vol % chloroform Preliminary examinations of all animals anesthetized showed a slight increase in respiratory acidosis but no signs of arterial hypoxemia or metabolic acidosis. After 4 1/2 hours of chloroform anesthesia, the livers of most exposed rats showed gross enlargement of the centrilobular hepatic cells.
The cells also showed a striking paleness, and upon staining of frozen sections, fatty degeneration was also observed. On electron microscopy it was found that chloroform produced an early dilation of the granular endoplasmic reticulum with detachment of the ribosomes producing a marked reduction of centrilobular protein synthesis. Additionally, after anesthesia with chloroform, extensive necrosis of portions of the renal tubular epithelium was found, while the lung revealed severe leucocytic infiltrations in the alveolar septa. In light of this latter finding, it should be noted that in 1966 Wattenberg  stated that kidney and lung tissue also contain hydroxylating enzyme systems. This enzymatic activity is less intense than in the liver, but can be increased by some lipid- All experiments showed reduced liver function as indicated by prolonged pentobarbital sleeping times and elevated BSP retention. The liver succinic dehydrogenase activity was depressed when chloroform was administered 12 or 24 hours after ethanol, but not when it was administered 48 hours after ethanol. Ethanol alone or chloroform alone did not significantly depress succinic dehydrogenase activity.
In mice pretreated with ethanol 15 hours, or 1, 2, or 4 days before the administration of chloroform, microscopic examination revealed livers with cytoplasmic vacuolization in pericentral cells. The pericentral cells were also enlarged and almost completely devoid of eosinophilic material.
In a similar study, Sipes et al  pretreated rats with isopro panol and reported enhanced ability to covalently bind radioactive carbon labeled chloroform to microsomal protein.
Dingell and Heimberg  studied the hepatic metabolism of aminopyrine and hexobarbital in rat liver microsomes after the administration of chloroform or carbon tetrachloride or methylene chloride. The chlorinated hydrocarbons were administered in equimolar doses by gastric intubations and killed 24 hours later. Liver microsomes were prepared from rat livers weighing from 250-375 mg. Either 5 jumoles of aminopyrine or 1.9 /imoles of hexobarbital was added to a mixture of enzyme substrates.
The rate of metabolism of hexobarbital was measured by estimation of the disappearance of substrate. The rate of demethylation of aminopyrine was measured by estimation of the amount of formaldehyde formed. For both the aminopyrine and hexobarbital pretreatment before carbon tetrachloride decreased the rate of metabolism significantly to 14 and 29%, respectively, of control values.
Chloroform, however, only decreased metabolism of aminopyrine to 61% and hexobarbital to 95% of control values.
McLean  fed male mice either stock diet or protein free diets for 1 week before intragastric administration of chloroform. Some of the mice of each group were also given sodium phenobarbital in the drinking water (1 mg/ml) for 1 week before chloroform administration; others were given a single subcutaneous injection of DDT (100 mg/kg) 1 week before chloroform. The purpose of DDT and the phenobarbital administration was to stimulate liver hydroxylating enzyme activity. The purpose of the protein deficient diet was to reduce the liver hydroxylating enzyme activity, but in this experiment this was not realized. Phenobarbital and DDT increased the liver hydroxylating enzyme activity and the toxicity of chloroform was more than doubled by the phenobarbital and DDT pretreatment as measured by the LD50.

# Correlation of Exposure and Effect
The use of chloroform as an anesthetic agent has provided information about the effects to be expected from acute exposure.
Exposures during anesthesia have usually been to concentrations of around 20,000 ppm,  and exposure times have been from 30-240 minutes.
 One or 2 days after chloroform anesthesia, nausea, jaundice, and vomiting may develop, often followed by elevated temperature and pulse, epigastric pain, muscle twitching, delirium, and coma. In some cases, death has occurred 3-10 days after anesthesia. Habitual inhalation of 1 oz daily of chloroform for 7 years followed by 2 oz/day for 5 more years was associated with delusions, restlessness, depression, convulsions, ataxia, dysarthria, tremor of the tongue and fin gers, and insomnia; at autopsy, the brain showed slightly thickened menin ges in the frontal lobe, many fibroblasts and dilated blood vessels.  In other cases of habitual chloroform inhalation for periods of time ranging up to 30 years, hallucinations, delirium, and tremors were common manifestations.  The exposures ( The data presented by Challen et al  provide some quantitative information about exposure and effect, even though some of the information about exposure was obtained after the fact. Employees in a confectionery The incidence of enlarged livers among these 68 workers was sig nificantly higher than in the controls. It was noted that there was a reduction in hepatomegaly in 79% of the people studied during the 6-12 month period when hygienic conditions at work were improved.  Schwetz et al  studied the effects of 30, 100, and 300 ppm of chloroform on pregnant rats for 7 hours/day on days 6 through 15 of gestation. There were significant incidence of delayed skull ossification and "wavy ribs" in litters from dams exposed to 30 ppm of chloroform.
The authors  found that in litters from dams exposed to 100 ppm there were significant incidences of acaudia, imperforate anus, subcutaneous edema, missing ribs, and delayed sternebrae ossification.
Rats exposed to chloroform at 300 ppm ate so little food (1 g/day) that it would be impossible to consider any of the other effects as characteristic of chloroform.
 Kylin et al  found that mice exposed to 100 ppm chloroform for 4 hours showed moderate fatty infiltration and degeneration at the periphery of the liver lobules, one day after exposure. These effects were found less frequently 3 days after exposure, indicating a certain amount of regeneration. A direct dose-response relationship, evidenced by increasing liver alterations and necrosis, was observed at concentrations ranging from 100 to 800 ppm. Further indication of a dose-response relationship was the increase of the serum ornithine carbamoyl transferase with increasing concentrations of chloroform.
Animal studies   there are no studies on workroom concentrations of chloroform used in their production.
Challen et al   Air samples should be collected and transported to a laboratory, then desorbed or chemically treated, and finally analyzed quantitatively.
Silica gel has been used extensively in the past as a collection medium.
 Silica gel is a polar adsorbent and shows pronounced selectivity in adsorbing polar molecules, particularly water. Hence, when sampling large volumes, the atmospheric moisture may compete for the adsorptions sites and displace the chloroform being sought. When sampling large volumes (more than 3 liters), the silica gel adsorption tube may become saturated with water thus impairing the retentive properties of the collec tion medium.  Activated charcoal as a collection method has been used in conjunc tion with gas chromatography.  Activated carbon is nonpolar and will consequently adsorb organic vapors in preference to water vapor so that sampling of volumes higher than 3 liters can be accomplished without noticeable moisture interferences.  Williams and Umstead  have developed a collection method in which atmospheric samples are concentrated on porous polymer beads. The same column utilized for sample collection is subsequently used for GC analysis. The advantage of this method is that it integrates collection and analysis into one operation. However, it has not yet been developed for field use. The dechlorination method (alkali hydrolysis) requires collection of the chloroform contaminated atmosphere over a suitable collection medium followed by hydrolysis in isopropyl alcohol. Solid KOH is added and the mixture is allowed to sit overnight (about 20 hours). After neutralization the liberated chloride ion is titrated with silver nitrate.  The percentage of chlorine hydrolyzed is determined by comparison between samples and known controls. This method has the disadvantage of a long and elaborate procedure in which the amount of chloride ion liberated depends on the duration of the process of alkali dechlorination. When a mixture of chlorinated hydrocarbon vapors is analyzed, there is the additional problem of specificity; it is necessary then to differentiate the contribution of each chlorinated compound to the total amount of chloride ion liberated.
 The gas chromatographic method of analysis provides a specific when enveloped by an atmosphere contaminated with halogenated hydrocarbons.
 The instrument is sensitive to all halogens and halogenated compounds and consequently is nonspecific for chloroform. The Halide meter seems suitable for continuous monitoring if there is only chloroform present as the air contaminant.

# (d) Conclusions and Recommendations (1) Compliance Method
On the basis of the review of the analytical methods it is recommended that gas chromatography be chosen as the compliance method.
The method is recommended in conjunction with activated charcoal tubes as a collection method and the use of carbon disulfide as a desorbent. However, a disadvantage of the method is the indirect system of measurement requiring collection and desorption prior to analysis.

# 2) Monitoring Methods
It is also recommended that direct reading colorimetric tubes (gas detection tubes) be used as an inexpensive way to determine whether exposure, as defined in Chapter I, exists. The tubes must be used with manufacturer's instructions and for monitoring purposes only. Chloroform concentrations in the blood have been measured during and following anesthesia.  These data show that chloroform in the blood is eliminated rapidly at first but that some remains for at least 8 hours after exposure to anesthetic concentrations. These data are inadequate for evaluating industrial exposure.

# V. DEVELOPMENT OF A STANDARD

# Basis for Previous Standards
In 1946, the Sub-Committee on Threshold Limits of the ACGIH published a list entitled "Maximum Allowable Concentrations of Air Contaminants for 1946", with the understanding that the list would be revised each year.
 The list of values was compiled from 3 sources:
(a)
The list reported by the Sub-Committee on Threshold Limits at the 5th Annual Meeting of the ACGIH in 1942.

# (b)
The then comprehensive list published by Cook in Industrial
Medicine.  (c) Published values of the Z-37 Committee of the American Stan dards Institute.
The value proposed for chloroform by the ACGIH  was 100 ppm.
In 1959, the Threshold Limit Value (TLV) for chloroform was reduced to a time-weighted average of 50 ppm for a normal working day by the ACGIH  in their annual review of the TLV values.
In 1962, the ACGIH  published its Documentation of Threshold Limit Values (TLV's) in which it cited the recommendations of Cook  that exposures to chloroform be kept below 50 ppm, and the study of Challen et al.  The 1968 TLV, which was unchanged from the 1962 recommendation, was promulgated $s a regulation by OSHA. This was published, apparently in error, as a ceiling value of 50 ppm, in the Federal Register, volume 39, page 23541, dated June 27, 1974.
In 1969, the ACGIH changed the time-weighted average limit to a ceiling and documented this in 1971.  This ceiling limit of 50 ppm was considered adequate to prevent any serious short-term effects on the liver, but it was recommended that chloroform be used with close medical surveillance, particularly with those workers who consume alcohol. The recommendation was based in part on the studies of Challen et al,  Bomski et al,  and unpublished data from the Massachusetts Division of Occupational Hygiene. A notice of intended change for chloroform from 50
(ceiling) to 25 ppm (time-weighted average) was made by the ACGIH in 1972
 and 1973.
The AIHA Hygienic Guide Series of 1965 for Chloroform  suggested that a time-weighted average (TWA) of 10 ppm be used with a ceiling of 25 ppm. This recommendation was based on unpublished experimental animal data.
In 1970, the International Labour Office in Geneva published tables of Permissible Levels of Toxic Substances in the Working Environment . for many countries.  The chloroform standards for 8 different countries are listed below; it is not clear from the reference whether these are time-weighted averages or ceiling concentrations. The major exposure to chloroform has been as an anesthetic  and most experiments have been related to this use. Cardiac arrhythmias have occurred, especially when chloroform anesthesia has been prolonged beyond 30 minutes.  Liver and kidney injuries have also been found, sometimes resulting in death several days after anesthetic exposure.  It is difficult to evaluate the total exposure to chloroform during anesthesia since concentrations frequently were not reported. However, it should be noted that the concentrations in anesthesia are extremely high and are not constant throughout the exposure period.

# Country

# Whipple and Sperry
 demonstrated in experiments with dogs that chloroform anesthesia for a period of 1-2 hours caused central liver necrosis. At autopsy of a woman who had died from delayed chloroform poisoning, they found liver changes that resembled changes found in dogs. The only other experimental study of liver changes after inhalation of chloroform was that by Kylin et al  in 1963 who exposed 20 mice to 100, 200, 400, and 800 ppm for 4 hours. In this study, the mice exposed to 100 ppm did not develop demonstrable liver necrosis, however, moderate fatty infiltration of the liver was noted. In mice exposed to 200 ppm, some necrotic areas appeared in the liver and there was an increase in serum ornithine-carbamoyl transferase. Exposures to 400 and 800 ppm resulted in increasing necrosis and serum enzyme activity.
Although Schwetz et al  did not report detailed studies of liver changes in female rats exposed to chloroform 7 hours/day for 10 days, they did report that liver weights, both absolute and relative, increased as a result of exposure to 100 and 300 ppm but not to 30 ppm. However, embryo and fetal anomalies, including delayed skull ossification and the formation of wavy ribs, were found in the offspring of the rats exposed to 30 ppm.
The only account of liver abnormalities among industrial workers exposed to chloroform is a report by Bomski et al.  These investi gators found 17 cases of hepatomegaly in a group of 68 workers exposed to chloroform in concentrations ranging from 2-205 ppm for 1-4 years in a pharmaceutical firm. Three of the 17 workers with hepatomegaly were judged by the authors to have toxic hepatitis on the basis of elevated serum enzymes, and elevated serum gamma globulin. This group of workers was also considered to be much more susceptible to viral hepatitis than the inhabitants of the city in which the plant was located, but the basis for this inference is tenuous, since no information was given on possible contributions to the problem by poor sanitation, for example the incidence of viral hepatitis in other plant workers was not mentioned.
In the study by Challen et al  no liver abnormalities were found among 17 workers exposed to chloroform. Nine workers were exposed to chloroform at TWA concentrations ranging from 23-71 ppm, but for only 4 hours/day. These workers had been working under these conditions for 10-24 months.
Another group of workers who had previously been exposed to chloroform in concentrations estimated to have ranged from 77-237 ppm for up to 8 hours/day, also had no abnormal liver findings. However, it had been many months since this latter group had been exposed to chloroform.
These studies indicate that liver damage may occur in workers from exposure to chloroform in varying concentrations up to 205 ppm.  The studies with mice showed some liver cell necrosis from 4 hours' exposure to 200 ppm and fatty infiltration of the liver from 100 ppm for 4 hours.
The studies with rats showed increased liver weights from 10 consecutive 7hour daily exposures to 100 ppm, but not to 30 ppm exposures.
 The studies by Challen et al  indicated no liver injury from 4 hours per day exposure of workers to 23-71 ppm chloroform.
While the exposure conditions studied by Challen et al  (23-71 ppm chloroform for 4 hours/day) seem below the threshold for liver injury, they are not adequate to protect workers from other undesirable responses such as dryness of the mouth and throat at work, and lassitude in the evening, which occurred among the workers exposed to 23-35 ppm chloroform for 4 hours a day. It seems reasonable to infer from these observations
that the lassitude reflects central nervous system depression and that dry mouth and throat and the digestive tract symptoms reflect a local irritant action in those areas.
It can be interpreted from the study of Challen and co-workers  that a safe level to exposure for workers lies somewhere between 23 and 35 ppm for 4-hour workdays, or about 10 to about 18 ppm for 8-hour workdays.
The appropriate limit within this range is not clear, but because of mild effects in this group (mouth and throat dryness and evening fatigue) and because of the fetal abnormalities found in rats exposed to 30 ppm,  it is concluded that the environmental limit to be recommended should be the lowest in this range, namely 10 ppm, as a time-weighted average.
The absorption of chloroform resulting from exposure to a given time-weighted average concentration for 8 hours a day, 5 days a week, would be about the same as that absorbed for 10 hours a day, 4 days a week.
Thus, the same time-weighted average limit is applicable whether the 40hour workweek is applied over 5 8-hour days or 4 10-hour days.
It is likely that a central nervous system depressant, such as chloroform, might at briefly high concentrations affect attention, judgment or perception sufficiently so that if an emergency were to occur the worker might not take appropriate action. This suggests the need for a ceiling concentration to be observed, as a limitation on excursions above the timeweighted average and as a limit applicable to occasional and brief use of chloroform. However, after detailed consideration of the data applicable to derivation of such a ceiling, no basis from the scientific data appears.
The ceiling proposed by American Industrial Hygiene Association  in its Hygienic Guide Series is based on animal data that seem more applicable to development of a time-weighted average limit. Thus, a ceiling limit of 50 ppm based on a 10-minute sampling period is proposed on the basis of good practice.
It is recognized that many workers handle small amounts of chloroform or are working in situations where, regardless of amounts used, there is only negligible contact with the substance.
Under these conditions, it should not be necessary to comply with all provisions of this recommended standard, which has been prepared primarily to protect worker health under hazardous circumstances. On the other hand, concern for worker health requires that protective measures be instituted below the enforceable limit to ensure that exposures stay below that limit. For these reasons, "exposure to chloroform" has been defined as exposure above half the environmental limit, thereby delineating those work situations which do not require the expenditure of health resources for environmental and medical monitoring and associated recordkeeping.
Half the environmental limit has been chosen on the basis of professional judgment rather than on quantitative data that delineate nonhazardous areas from areas in which a hazard may exist. However, it is recommended that appropriate work practices and protective measures to prevent skin and eye contact and to prevent exposure to pyrolysis products be required, regardless of air concentrations of chloroform.

# VI. WORK PRACTICES
The principal method for the manufacture of chloroform is chlorination of methane,  and suitable controls for safe use of methane Consideration should be given to pumping the diked spill to another tank.
In addition, it is advisable to have facilities for transfer of the contents of a leaking tank to another suitable tank. Respirators generally fall into the following classification according to their mode of operation: leakage is the major limitation of these devices. From the test results, it has been demonstrated that the half mask or quarter mask facepiece may be Used for protection up to 10X the TWA. The full facepiece, operated with a negative pressure, may be used up to 100X the TWA. The majority of the wearers can obtain a higher degree of protection. However, for purposes of uniform regulations, covering the many face sizes and shapes of the US working population, it is necessary to use these guides. These maximum use concentration guides do not take into account additional leakage from filters or canisters.
When providing respiratory protection against chloroform, the concentration immediately dangerous to life must be considered.
In this document, it is assumed that any concentration of chloroform greater than 2,500 ppm is immediately dangerous to life.
In selecting and using gas masks and chemical cartridge respirators, the service life must be considered.  An approved, calibrated, battery-operated personal sampling pump plus an activated charcoal tube shall be used to collect the sample.
The activated charcoal tube shall be attached to the clothing of the worker; the shirt collar is convenient for this purpose.
(4) Breathing zone samples shall be collected to permit determination of TWA workday exposures for every job involving exposure to chloroform in sufficient numbers to express the variability of the work situation.
The minimum number of TWA's to be determined is listed in Section 7 of this standard, according to the number of employees involved.  (2)
The smaller section of charcoal is used as a backup and should be positioned nearest the sampling pump.
The charcoal tube should be placed in a vertical position during sampling with the inlet facing down.
(4) Tubing may be used to connect the back of the tube to the pump, but air being sampled should not be passed through any hose or tubing before entering the charcoal tube.
The flowrates, sampling time involved and/or the total volume of air sampled must be measured accurately. The sample can be taken at flow rates of 50-1000 ml/min. Total sample volumes of 1-30 liters are recommended. It is also recommended that the sampling be less than 4 hours.
(6) Measure and record the temperature and pressure of the atmosphere being sampled.
The charcoal tubes should be capped with the supplied plastic caps immediately after sampling. Under no circumstances should rubber caps be used.
(8) One charcoal tube should be handled in the same man ner as the sample tube (break, seal, and transport) except that no air is sampled through this tube. This tube should be labeled as a blank.
(9) Capped tubes should be packed tightly after sampling to minimize tube breakage during transport.
(10) Charcoal tubes should be shipped separately from bulk samples.

# Sample Analysis (a)
Principle of the Method (1) A known volume of air is drawn through a charcoal tube to trap the chloroform vapor.
The charcoal in the tube is transferred to a small test tube and desorbed with carbon disulfide.
(3) An aliquot of the desorbed sample is injected into a gas chromatograph.
The area of the resulting peak is determined and compared with areas obtained from the injection of standards.
(b) Range and Sensitivity (1)
The lower limit for detection of chloroform at a 16
x 1 attenuation on a gas chromatograph with a 10:1 splitter is 0.10 mg/sample. This value can be lowered by reducing the attenuation or by eliminating the 10:1 splitter.
The upper limit value for chloroform is 2.0 mg/sample. This is the estimated amount of chloroform which the front section will hold before this compound is found on the backup section. If a particular atmosphere is suspected of containing a large amount of chloroform, it is recommended that a smaller sample volume be taken.

# (c) Interferences
(1) When the amount of water in the air is so great that condensation actually occurs in the tube, chloroform will not be trapped.
(2) Any compound which has the same retention time as chloroform at the operating conditions described in this method could be an interference.

# (d) Advantages of the Method
(1) This method is advantageous in that it provides one basic method for determining many different organic compounds.
The sampling device is small, portable, and involves no liquids.
(3) Interferences are minimal, and most of those which do occur can be eliminated by altering chromatographic conditions.
(4) The analysis of the tubes is accomplished by using a quick instrumental method.
(e) Disadvantages of the Method (1)
The amount of sample which can be taken is limited by the weight of chloroform which the tube will hold before overloading.
(2) When the sample value obtained for the backup section of charcoal exceeds 25% of that found on the front section, the possibility of appreciable sample loss exists. The area of the sample peak is measured by an electronic integrator or some other suitable form of area measurement, and preliminary sample results are read from a standard curve prepared as discussed below.
(A)

# Preparation of Standards
It is convenient to prepare standards in terms of mg chloroform per 0.5 ml of carbon disulfide because samples are desorbed in this amount of carbon disulfide. To minimize error due to the volatility of carbon disulfide, 20 times the weight can be injected into 10 ml of carbon disulfide. For example, to prepare a 0.3 mg/0.5 ml standard, 6.0 mg is injected into exactly 10 ml of carbon disulfide in a glass stoppered flask.
The density for chloroform is used to convert 6.0 mg into micro liters for easy measurement with a microliter syringe. (1)
The name, address, and telephone number of the manufacturer or supplier of the product. (1) Chemical or widely recognized common name of all hazardous ingredients.
( Detailed procedures to be followed with emphasis on precautions to be taken in cleaning up and safe disposal of materials leaked or spilled.
This includes proper labeling and disposal of containers holding residues, contaminated absorbents, etc.
(h) Section VIII. Special Protection Information.
Requirements for personal protective equipment, such as respirators, eye protection, clothing, and ventilation, such as local exhaust (at site of product use or application), general, or other special types.
Any other general precautionary information.
(i) Section IX. Special Precautions.

# U.S. DEPARTMENT OF LABOR

# D E P A R T M E N T O F H E A L T H . E D U C A T IO N . A N D W E L F A R E P U B L IC H E A L T H S E R V IC E C E N T E R F O R D IS E A S E C O N T R O L N A T IO N A L IN S T IT U T E F O R O C C U P A T IO N A L S A F E T Y A N D H E
Atmosphere-Supplying Respirators (A) Self-contained.
(B) Hose mask.
(C) Airline.
(D) Combination self-contained and airline.
(2) Air-Purifying Respirators (A) Gas and vapor (gas mask and chemical cartridge).
(B) Particulate (dust, fog, fume, mist, smoke, and sprays).
(C) Combination gas, vapor, and particulate.
(3) Combination Atmosphere-Supplying and Air-Purifying

# Respirators
The factors that affect the overall performance of an airpurifying respirator are the reliability of the face seal, the efficiency of the filters and/or absorbent canisters and other variables, such as leakage from exhalation valves. The performance of filters, canisters, and exhalation valves is predictable and controllable when test data are available. However, the current state of knowledge of the wearer's face size and shape and the respirator size and shape is such that the face seal is unpredictable and variable.
During the past several years, NIOSH has funded research and development projects to make quantitative respirators-man tests on all types of respirators to measure their performance and/or efficiency. The results of these tests made on half mask and quarter mask facepieces, operated with a negative pressure in the facepiece, show that the facepiece 102.  (3) A recorder and some method for determining peak area.
(4) Glass stoppered microtubes. The 2.5-ml graduated microcentrifuge tubes are recommended.
(5) Microsyringe of 10-jul capacity, and convenient sizes for making standards.
(6) Pipets. 0.5-ml delivery pipets or 1.0-ml graduated pipets in 0.1-ml increments.
(7) Volumetric flasks of 10-ml capacity or convenient sizes for making standard solutions.

# (g) Reagents
(1) Spectroquality carbon disulfide At least 5 tubes are prepared in this manner and allowed to stand at least overnight to assure complete adsorption of chloroform onto the charcoal. These 5 tubes will be referred to as the "desorption samples".
A parallel blank tube should be treated in the same manner except that no chloroform is added to it. The desorption sample and blank tubes are desorbed and analyzed in exactly the same manner as previously described.
Two or 3 desorption standards are prepared for analysis by injecting the same volume of compound into 0.