Table of Contents (continued) IX. APPENDIX I -Sampling Procedure for Collection of Tetrachloroethylene X. APPENDIX II -Analytical Procedure for Determination of Tetrachloroethylene XI.# REVIEW CONSULTANTS vil I. RECOMMENDATIONS FOR A TETRACHLOROETHTLENE STANDARD

# RESPIRATOR SELECTION GUIDE FOR PROTECTION AGAINST TETRACHLOROETHYLENE

# Concentrations of Tetrachloroethylene
Respirator Type 500 ppm or less (1) A chemical cartridge respirator with a full facepiece and organic vapor cartridge(s) (2) A gas mask with chln-style or a front or back-mounted organic vapor canister. (3) A supplled-alr respirator with a full facepiece, helmet or hood (4) A self-contained breathing apparatus with a full facepiece >500 ppm (1) Self-contained breathing apparatus or with a full facepiece operated in entry and escape pressure-demand or other positive from unknown pressure mode concentra tions
(2) A combination respirator which includes a Type C supplied-air respirator with a full facepiece operated in pressure-demand or other positive pressure or continuous-flow mode and an auxiliary self-contained breathing apparatus operated in pressuredemand or other positive pressure mode Firefighting Self-contained breathing apparatus with a full facepiece operated in pressure-demand or other positive pressure mode Escape (1) A gas mask providing protection against organic vapors (2) An escape self-contained breathing apparatus 6 (D)    Two cases of hepato-nephritis due to occupational exposure to tetrachloroethylene were reported in the French literature in 1955 and 1964.

# Respiratory protective devices described in
 In both cases, the subjects were using tetrachloroethylene for degreasing metal parts. The atmospheric concentrations of the solvent were not measured but contact with the solvent was direct in one case and within a few meters in the other.
Vallud et al  reported the post mortem examination of one man after his death but gave no clinical description. Post mortem showed an average size liver, with "localized degenerations" and enlarged, yellowish kidneys with congestion in the pyramidal zone.
Dumortier et al  concluded that the case of hepato-nephritis they had diagnosed was due to occupational exposure to tetrachloroethylene. The patient experienced vomiting, jaundice, and anuresls within 1 week after he started using tetrachloroethylene to clean metal. There was no evidence of previous infectious disease or medication that would have been predisposing. However, the 34-year-old man had a history of alconolism.
Two years prior to the occupational exposure, hepatomegaly had been diagnosed. On admission to the hospital, the liver was found to be He became unconscious and was found 30 minutes iater lying or. tht. floor.
Clinical examination revealed erythema and blistering over 30% of his body.
In 5 days, the erythema subsided and the blistering disappeared. Some dryness and irritation of the skin reportedly occurred thereafter.
Skin effects due to chronic tetrachloroethylene exposure have been reported in other studies.  Munzer and Heder  reported a case of eczema as a direct effect of exposure of a man in a drycleaning plant.
Gold  reported that a drycleaner had severe neurologic disturbances and had dry, scaly forearms and hands. 
The body burden of exposure to tetrachloroethylene was indicated by the distribution in expired air, blood and urine. Breath analyses showed that tetrachloroethylene is excreted in the breath for long periods after exposure. At 21 hours after a 3-hour exposure at 100 ppm, mean breath concentrations of tetrachloroethylene foT days 1 through 5 were 1.00, 2.63,  There also was a reduction of electrical conductivity by 24-40% after 5 months of exposure.

# Microscopic investigation revealed swollen and vacuollzed protoplasm
In some cells, but these occurred only sporadically, most cells being normal.
One to two months after exposure, the EEG and electric conductivity were only slightly or not at all different from controls. The 5-month exposure at 1.5 ppm resulted only In a slightly higher impedance of the cerebral tissue than was found with the controls.

# (b) Effects on Liver and Kidneys
Carpenter  attempted to discover the highest concentration of tetrachloroethylene vapors that would not anesthetize rats exposed for 8 hours. Rats exposed at 31,000 ppm (3.1%) died after a few minutes of exposure and after 30 to 60 minutes when exposure was 19,000 ppm (1.9%).
Some rats survived exposure at 19,000 ppm but their livers showed congestion and granular swelling. Similar liver effects were found after exposure at 9,000 ppm. In addition, there was marked granular swelling of the kidneys. No deaths were reported after a single exposure at 9,000, 4,500, or 2,750 ppm (0.7, 0.45, 0.275%), Post mortem examinations of rats exposed to those concentrations showed a slight increase in the prominence of liver and kidney markings.
Carpenter  (1) Fatty degeneration involving a thin cell layer, up to two to three cells in width, usually at the periphery of the lobules;
(2) Same as in ( 1), but involving a layer of three to five cells in width;
( investigators reported that, starting from the fifth month of exposure, the mortality of male rats exposed at 600 ppm was significantly higher than that of control. The cause of death was not stated. There was no difference in mortality rates in male rats exposed at 300 ppm or female rats exposed at 300 or 600 ppm.
The investigators reported that spontaneous tumors appeared with comparable frequency in both exposed and nonexposed animals after 29 months.
The National Cancer Institute is currently conducting a study of the carcinogenic potential of tetrachloroethylene. The results of this study will be evaluated when they become available. Yllner  determined the urinary metabolites of C 14-labeled tetra chloroethylene in five female mice exposed for 2 hours to vapor in doses of 1.3 mg/g bodyweight. In 4 days, 90% of the absorbed tetrachloroethylene was excreted or metabolized, 70% in expired air, 20% in urine, and less than 0.5% In feces. Using chromatographic, radiographic. Isotope dilution methods and, In part, Jondorf's method, the following metabolites were identified In the urine according to the percentage of total urinary activity: trichloroacetic acid, 52%; oxalic acid, 11%; and traces of dlchloroacetlc acid.
Daniel  studied the partition of Cl 36-labeled tetrachloroethylene in urine, feces and expired air of rats. Wlstar rats were administered 1.75 ftcl or 13 /ucl of the labeled tetrachloroethylene by stomach tube. The half-life of expiration of tetrachloroethylene was found to be 8 hours, and 97.9% of the radioactivity was found In the expired air 48 hours after administration of the labeled tetrachloroethylene. After 18
days, 1.6-2.1% of the radioactivity was found In the urine. No radioactivity was found In the feces. Trichloroacetic acid and Inorganic chloride were the only metabolites detected in the urine. On the addition of sliver nitrate to the urine, 25% of the total urinary chlorine was precipitated as chloride.
The remaining urinary radioactivity was accounted for by trichloroacetic acid. Oxalic acid was not found.  The toxicity of trichloroacetic acid, a metabolite of tetrachloroethylene, has been the subject of some reports in the literature.  Woodard et al  reported the LD50 to be 3.32 g/kg for rats and 4.97 g/kg for mice. The consequences of chronic excretion of trichloroacetic acid were considered by Frant and Westendorp.  Trichloroacetic acid Is a strong organic acid which may be neutralized In the. body by sodium or potassium. Whether this constant elimination of fixed alkali will result in acidosis or diminution of the carbon dloxldecomblnlng power of the blood has not been studied. Daniel  also exposed seven male and seven female rats at 1,000 ppm tetrachloroethylene to determine the effect on liver lipid content.
The exposures were for three successive periods of 6 hours each. In the exposed female rats, 8.0 + 1.5 mg lipid/100 mg dry liver weight was found compared to 10.7 + 2.2 in controls, but this was not considered significant. In the exposed males, 11.3 mg lipid/100 mg dry liver weight was found compared with 11.2 for the controls.
Van Dyke and Wlneman  found that little chloride was liberated from tetrachloroethylene in vitro by their dechlorinatlng enzyme system.
The enzyme system was located in hepatic microsomes and required NADPH, oxygen, and a factor present in the 105,000 G supernatant.

# It was
Inducible by phenobarbital or benzpyrene, but not by methylcholanthrene.
Cornish and Adefuin  studied the effect of administering ethanol to rats 16-18 hours before exposing them to different chlorinated hydrocarbons. Two groups of rats, 6 each, were treated with chlorinated hydrocarbons and one of these groups was also pretreated with alcohol.
Tetrachloroethylene exposure concentrations of 4,000 ppm for 6 hours, 5,000 ppm for 4 hours, 10,000 ppm for 2 hours, and 15,000 ppm for 2 hours were     Behavioral tests revealed that subjects exposed at 150 ppm showed impaired coordination after 7.5 hours of exposure.
In an earlier experiment, Stewart et al  found that, in a group of 15 male subjects exposed for one 7-hour period at a mean concentration of 101 ppm, 60% complained of mild eye, nose and throat Irritation during the first 2 hours which subsided by the end of the experiment; 40% of the subjects felt slightly sleeply and 25% felt lightheadedness, developed mild frontal headaches or had some difficulty speaking.

# Out of 10 cases of tetrachloroethylene intoxication reported by Lob
 in 1957, there was one case of liver involvement.
Liver cell necrosis was part of the pathologic diagnosis from an autopsy of a 33-year-old man who died from exposure to tetrachloroethylene.
 The man had been working in a drycleaning establishment for 4 months.
The investigators made two measurements of tetrachloroethylene and reported the concentrations of 50 and 250 ppm. The acute exposures occurred when tetrachloroethylene periodically spilled out of the drycleaning machine and fell on hot pipes, when it vaporized. Exposure also occurred when machines were being filled with tetrachloroethylene.
Bilirubin and thymol turbidity determinations were significantly affected in the 113 exposed workers studied by Pranke and Eggellng [721 when compared with A3 unexposed workers.
Elevated SGOT was found In eight of nine firemen 12 days after a 3mlnute exposure at an unknown concentration of tetrachloroethylene.
An enlarged liver and spleen were found In one man upon examination. At the time of exposure, all nine men became "woozy" for a few minutes. Rowe et al  found no effects in the livers of monkeys, rabbits and rats after repeated 7-hour exposures at concentrations up to 400 ppm.
However, effects on the liver were evident in guinea pigs. After 132 7hour exposures at 100 ppm, liver weights of female guinea pigs were increased; slight to moderate fatty infiltration of the liver was noted after exposure at 200 ppm and was more pronounced after exposure at 400 ppm; and slight cirrhosis was observed In guinea pigs exposed 7 hours/day for 169 days at 400 ppm.

# (c) Carcinogenicity, Mutagenicity, Teratogenicity
The potential of tetrachloroethylene to produce carcinogenic, mutagenic or teratogenic effects has not been studied conclusively.
The effects of tetrachloroethylene in pregnant animals anc! their offspring were reported in two studies.  Carpenter  reported that fertility of rats increased slightly after exposure at 230 or 470 ppm for up to 7 months. Schwetz et al  found that mice and rats exposed at 300 ppm tetrachloroethylene for 7 hours/day on days 6 through 15 of gestation showed an Increase In the relative maternal liver weights of mice, decrease in maternal body weights of rats, and increase in incidence of fetal resorptions In rats. In fetal mice, there were decreased body weights and Increased incidences of subcutaneous edema, delayed ossification of skull bones, and split sternebrae.
Most of the effects found in the study by Schwetz et al  represent fetal and maternal toxicity. Only the delayed ossification of skull bones and split sternebrae could be considered as possible teratogenic effects. These occurred in mice but not in rats.
The number of animals used in this study was too few to establish the significance of these findings, since the Incidences of the abnomalltles in large samples of these strains of rata and mice are not known. Whether these effects would occur In other species Including humans has not been determined.
This Is an Important requirement of further research.

# (d) Metabolism
The metabolic pathways of tetrachloroethylene are still questions for Investigation. Trichloroacetic acid and trlchloroethanol have been found
In the urine of humans and animals. to XII-11. Peak concentrations near 1,000 ppm were found in some plants.
Kerr  reported that the greatest single factor to influence tetrachloroethylene vapor concentrations in the drycleaning operations studied was ventilation. In one of the drycleaning plants he found that a mean concentration of 100 ppm was accompanied by an air movement of 125 to 205 feet/minute while a 270 ppm mean concentration was observed when no air movement was recorded.
In   Depending on the type of detector tube, the air can be drawn directly through the tube and compared with a calibration chart, or the air may be drawn into a pyrolyzer accessory prior to the detection tube.
 In either case, the analysis is not specific for tetrachloroethylene since liberated halogen ions produce the stain and any halogen or halogenated The ACGIH Committee on Threshold Limits recommended, and the ACGIH adopted, a threshold limit value (TLV) of 100 ppm for tetrachloroethylene in 19A7.  No basis for this change was given. The 19A7 TLV for tetrachloroethylene was restored to 200 ppm in 1953.
 The basis given for the change was information received from conference members that was not elaborated upon.
A preface to future tables of threshold limits proposed by the TLV Committee and adopted by the ACGIH in 1953 defined the values as "maximum average atmospheric concentration of contaminants to which workers may be exposed for an 8-hour working day without injury to health."  The preface was modified in 1958, and included the statement that "They  tetrachloroethylene was used, severe neurological disorders were observed.
In the case of one man working for 4 years In a poorly ventilated environment, loss of memory, blindness in the left eye, pronounced dermographism and vestibular dysfunction were observed upon examination.
These disorders persisted even after the exposure had been discontinued.
Mild central nervous disorders were found in another man 2 months after he began using tetrachloroethylene in his work. However, 6 months prior to his work with tetrachloroethylene, he had degreased metal parts with trichloroethylene. He worked with tetrachloroethylene for 9 months, enduring the symptoms until they progressed to include numbness of the fingers, difficulty walking, trembling, exaggerated dermographism, and general weakness. Slight but positive reactions for urinary urobilinogen were also found.
Gold  reported that a man who worked for 3 years in a drycleaning operation presented symptoms of increasing fatigue, dizziness, muscle cramps, memory difficulties, and restlessness. Neurological examination revealed an absence of olfactory sensitivity, deviation of the septum, and conjunctivitis, all on the right side. Most signs and symptoms persisted during the follow up year after exposure had ceased.
Peripheral neuropathies have also been reported resulting from tetrachloroethylene exposures (E Baginsky, written communication, March 1975).
The failure to find irreversible neurologic changes in the two studies of German drycleaning plants where concentrations ranged to 400 ppm was consistent with studies by Rowe et al  of four animal species.
Rats, rabbits, monkeys and guinea pigs were exposed at up to 400 ppm for 7 hours/day, 5 days/week for up to 6 months. No neurologic changes were observed.
There is little information on the effects of chronic exposures to tetrachloroethylene at 0-200 ppm. Studies of acute exposures show effects consistent with the action of a central nervous system depressant. EEG tracings of subcllnlcal central nervous system response to repeated 7.5-hour daily exposures of humans at 100 ppm.

# Rowe
 There is also evidence that these changes were maintained for at least 3 days after four 5-day weeks of 7.5-hours/day exposures at average concentrations of 20-150 ppm.
 Data were not presented nor discussed for the results of EEG tracings during the week of exposure at 20 ppm of tetrachloroethylene.
 The EEG tracings obtained with 100 ppm exposures indicated that the preliminary signs of narcosis were present in most subjects exposed at 100 ppm for 7.5
hours/day. 
The alteration of EEG tracings (increased delta wave activity), and subjective responses such as headaches, reported by Stewart et al,  after exposures at 100 ppm for 7.5 hours/day, were the only effects found at this concentration. While these alterations may be a preliminary subcllnlcal response to tetrachloroethylene exposure, their appearance can result from various other factors unrelated to exposure.

# Stewart et al
 reported no EEG alterations for subjects exposed at 20 ppm.
The data on human exposures at less than 100 ppm is sparse. Tuttle This limit should prevent neurologic effects as well as eye and respiratory tract irritation. No evidence of liver damage at or near the recommended limit has been reported.
Human exposures at concentrations between 100 and 300 ppm have resulted in neurologic effects such as difficulty maintaining a normal Romberg test and impaired motor coordination on the Flanagan test. To protect against temporary neurologic dysfunction, it is recommended that ceiling exposures be limited to 100 ppm as determined by sampling periods of 15 minutes.
It is recognized that many workers handle small amounts of tetrachloroethylene or work in situations where, regardless of the amounts used, there is only negligible contact with the substance. Under these conditions, it should not be necessary to comply with all of the provisions of this recommended standard. However, concern for worker health requires that protective measures be instituted below the enforceable limit to ensure that exposures stay below that limit. Therefore, environmental monitoring and recordkeeping is recommended for those work situations which involve exposure above one-half the recommended limit, to delineate work areas that do not require the expenditure of health resources for control of inhalation hazards. One-half the environmental limit has been chosen on the basis of professional judgment rather than on quantitative data that delineate nonhazardous areas from those in which a hazard definitely exists.
Tetrachloroethylene has caused abnormalities in fetal animals.  These Included an Increased incidence of subcutaneous edema, delayed ossification of skull bones, and split sternebrae in fetal mice. There was also an increased incidence of fetal resorptions in rats. In both species, exposures occurred on days 6 through 15 of gestation for 7 hours a day at 300 ppm. The significance of these findings and their applicability to human workers is still in question. However, since the effects observed in the animals studied reflect in part maternal effects that the recommended environmental limits are expected to prevent, it is not recommended that additional considerations for exposure be given to females of child bearing age.
Further Investigations are warranted and discussed in Chapter VII.
Additional considerations for protecting women of child bearing age will be recommended if Indicated by results of additional research.
Other information which may affect the recommended environmental limit are the results of the National Cancer Institute study of carcinogenesis which is currently in progress. When this information is made available It will be evaluated and the recommended standard will be revised If necessary.

# (b) Medical Monitoring
It is recommended that all workers be given preplacement and annual medical examinations. The preplacement examinations may Identify workers that might be susceptible, due to predisposing conditions, to exposure to tetrachloroethylene below the recommended environmental limit.
Examinations given prior to employment will provide data for evaluating workers after various lengths of exposure. The annual medical examination has been recommended to supplement the environmental monitoring which is not continuous. These examinations should provide additional evaluation of the effectiveness of the recommended environmental limit. The medical examinations should be general with emphasis on the hepatic and nervous systems, which have been reported to be the most effected systems.
 Since information on the effects of tetrachloroethylene on pregnant women and offspring is inconclusive it Is recommended that physicians report any spontaneous abortions or fetal abnormalities that ftlght result from exposure to tetrachloroethylene. The annual schedule for the examinations will provide the opportunity for early detection of effects on the health of the workers.

# VI. WORK PRACTICES
The manufacture of tetrachloroethylene requires large amounts of chlorine.  Information on safe handling of chlorine is available.
 Other chlorohydrocarbons may be used as starting materials or may be formed as coproducts. Caution must be taken to avoid exposure to these substances as well as any hydrocarbons which may be used as starting materials.
Further information concerning specific work practices for tetra chloroethylene can be found in the Manufacturing Chemists Association Safety Data Sheet SD-24, and in various other publications.  Tetrachloroethylene has been found to cause effects on the skin.
Prolonged or repeated exposure of skin to tetrachloroethylene should be avoided to prevent cutaneous effects.
Due to the toxicity of tetrachloroethylene, processes in which it is used in large quantities should be carried out In closed systems. Veil designed hoods and ventilation systems should be used to maintain exposures at or below concentrations specified by this standard. Further protective measures Include the use of personal protective equipment and clothing and purging of equipment prior to and during servicing and maintenance.
Tetrachloroethylene Is a component of some insecticidal fumigants and conventional work practice guidelines are Inappropriate to protect agricultural workers from the hazards of exposure. For these uses, fumi gants containing tetrachloroethylene must be used in a manner consistent with their labeling requirements. These usually specify allowable time limits before a fumigated area or space may be reentered, and safe practices for the application of the particular pesticide. Consideration must be given to the wearing of personal protective equipment including a long-sleeved shirt, long-legged pants (or suitable coveralls), a hat, shoes, socks, and solvent-resistant gloves. Specific requirements of worker protection standards for agricultural pesticides may be found in 40 CFR 170.
Where a funlgant Is applied to a crop in confined storage, hazardous One factor that affects the overall performance of demand-type (negative pressure) respirators is the variability of the face seal.
Facepiece leakage is the major limitation of half-mask and quarter-masV facepieces operated with a negative pressure.
For purposes of uniform regulations covering the many face sizes and shapes of the US population, NIOSH recommends that the half-mask or quarter-mask facepieces operated with a negative pressure not be used for protection above 10 times the TWA limit, although the majority of wearers can obtain protection in atmospheres of higher tetrachloroethylene concentrations.
On the same basis, NIOSH recommends that the full facepiece, operated with negative pressure, may be used up to 50 times the TWA limit.

# VII. RESEARCH NEEDS
There is a need for data concerning the long-range effects of chronic exposures to tetrachloroethylene at or below the recommended environmental Unit.
Of particular concern is the area of behavioral and neurological effects.
A preliminary study showed that certain behavioral and neurological tests will reflect tetrachloroethylene exposure.
While the results of the study are inconclusive due to small numbers of subjects and differences between exposed and unexposed groups, the approach Is valid and should be studied further. Additional research could be conclusive if the number of subjects is Increased and the experiment is ore rigorously designed.    (1)
The date and time of sample collection.
(2) Sampling duration.
(3) Total sample volume.  (2)
The smaller section of charcoal Is used as a reserve and should be positioned nearest the sampling pump.
The charcoal tube should be placed In a vertical posi tion during sampling.
(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 sample can be taken at flowrates of 25-1,000  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, le, "10-40% vol" or "10% max wt" to avoid disclosure of trade secrets.
Toxic hazard data shall be stated In terms of concentration, mode of exposure or test, and animal used, le, "100 ppm LC50 rat," "25 mg/kg LD50-
(1) 40 ml/min (70 psig) helium carrier gas flow.
(2) 65 ml/min (24 psig) hydrogen gas flow to detector.
(3) 500 ml/min (50 psig) airflow to detector.

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Human Data