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16
Propylene Glycol
Raghupathy Ramanathan, Ph.D.
Toxicology Group
Habitability and Environmental Factors Division
Johnson Space Center
National Aeronautics and Space Administration
Houston, Texas
BACKGROUND AND PURPOSE
On the Mir space station, several gallons of ethylene glycol were used as a coolant. In one incident, gallons of coolant leaked out and ethylene glycol vapors were detected in the air. A high concentration of ethylene glycol was also found in the humidity condensate that would be used as a source of water for recycling on the International Space Station. On the basis of extensive literature on the toxicity of ethylene glycol, its use was not recommended. Propylene glycol (PG) is generally believed to be less toxic than ethylene glycol (LaKind et al. 1999). NASA is planning to use PG-based coolant for the Orion crew exploration vehicle, which is part of the Constellation Program to send human explorers back to the moon and onward to Mars and other destinations in the solar system.
The purpose of this document is to review the existing inhalation toxicology literature on PG and develop maximum acceptable air concentrations for 1 h, 24 h, 7 d, 30 d, 180 d, and 1,000 d of potential exposure to vapors of PG.
STRUCTURE OF PROPYLENE GLYCOL
PG is a colorless, practically odorless and tasteless, and somewhat viscous liquid (see Table 6-1 for physical and chemical properties of propylene glycol).
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TABLE 16-1 Physical and Chemical Properties of Propylene Glycol
Chemical formula:
CH3CHOHCH2OH or C3H8O2
Chemical name:
Propylene glycol
Synonyms:
1,2-propanediol, 1,2-dihydroxypropane, methyl glycol
Molecular weight:
78
CAS number:
57-55-6
Boiling point:
187°C
Vapor pressure:
0.07 mm Hg at 20°C; 0.13 mm Hg at 25°C
Concentration in air at saturation:
170 ppma at 25°C
Conversion factor:
1 ppm = 3.2 mg/m3, 1 mg/m3 = 0.31 ppm, 1 mg/L = 313 Ppm
aCalculated from the vapor pressure at that temperature.
Source: Data from Rowe and Wolf 1982.
OCCURRENCE AND USE
PG is commonly used as an additive in cosmetics and in medicinal agents. It is thought to have low toxicity and is used as a vehicle for intravenous (IV) medications, topical medications, and cosmetics. The Food and Drug Administration considers it safe for use in medication and cosmetics. It is also antibacterial, which makes it useful as a preservative and disinfectant. PG is the principal component of aircraft deicing and anti-icing fluids and of motor vehicle antifreeze. As the general weight of evidence in the toxicology literature supports the conclusion that PG will be less toxic than ethylene glycol, PG-based coolant is strongly considered for use in NASA Constellation Program transport vehicles.
PHARMACOKINETICS AND METABOLISM
No data, human or animal, describing the toxicokinetics of PG exposure through inhalation are available. Because the solubility of PG in water is high, one might expect that any inhaled vapor reaching the lungs would be very well absorbed by the lung and metabolized by the liver in a fashion similar to its metabolism from an ingested dose, although one might expect some quantitative differences. Cavender and Sowinski (1994) described a work in which humans were exposed to 10% PG in a mist tent with labeled deionized water. Less than 5% of the mist entered the body and, of this amount, 90% lodged in the nasopharynx and disappeared in the stomach; very little was found in the lungs. It appears that most of the inhaled PG aerosol becomes trapped in the upper respiratory tract and does not reach the lungs.
For orally administered PG, the metabolites are lactic acid and pyruvic acid, which the body uses as an energy source (either through oxidation by the
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tricarboxylic acid cycle or through the generation of glycogen and glucose by the glycolytic pathway) (Ruddick 1972). One-third of absorbed PG is excreted via the kidneys (Browning 1965a,b).
GENERAL TOXICITY INFORMATION ON PG
No reports of human toxicity from environmental or occupational exposure to PG vapors have been published. However, there are several clinical case reports of PG-associated toxicities, such as hyperlactatemia, metabolic acidosis, hyperosmolality, and renal toxicity occurring when patients received certain sedatives such as benzodiazepines (diazepam or lorazepam, etomidate) by continuous IV infusion for several hours (LaKind et al. 1999, Zar et al. 2007). Surprisingly, almost all reports of PG-associated toxicity come from cases treated with lorazepam by IV infusion, although a long list of medications contain PG as a suspension medium. In all these medications, the solvent contained several milligrams to grams of PG (see Yaucher et al. 2003, Wilson et al. 2005, Zar et al. 2007), which amounted to moderate to high doses of PG, the concentrations one is least likely to receive via inhalation. These studies may not be directly relevant to an inhalation route of exposure; however, the observations indicate the toxicity potential of PG.
ACUTE EXPOSURE
Human case studies reporting death caused by exposure to PG (including exposure through industrial use) were not found in the scientific literature (Cavender and Sowinski 1994).
Wieslander et al. (2001) studied the acute ocular and respiratory effects of experimental exposure to PG in an aviation emergency training simulator. Nonasthmatic volunteers (22 men and 5 women) were exposed in an aircraft simulator to PG mist over 1 min to concentrations ranging from 176 to 851 milligrams per cubic meter (mg/m3) (geometric mean concentration of PG was 309 mg/m3). Tests conducted within 15 min after the exposures included an estimate of tear-film stability breakup time, nasal patency by acoustic rhinometry, dynamic spirometry, and a symptom questionnaire with 23 yes-or-no questions for ocular and respiratory symptoms (nasal and throat irritation, difficulty in breathing); smell; dermal symptoms; and symptoms of headache, nausea, fatigue, dizziness, and intoxication. After exposure to PG mist for 1 min, tear-film stability decreased, ocular and throat symptoms increased, forced expiratory volume in 1 s per forced vital capacity was slightly reduced, and self-rated severity of dyspnea was slightly increased. Subjects exposed to the higher concentrations had a more pronounced increase in throat symptoms and a more pronounced decrease in tear-film stability. The four subjects who reported developing an irritative cough during exposure to PG also had an increased perception of mild dyspnea (shortness of breath, difficult or labored breathing).
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In an animal study, Konradova et al. (1978) exposed rabbits to 10% PG by aerosol inhalation for 20 and 120 min to examine its effect on tracheal epithelium. After 20 min of exposure, no noteworthy alterations in the epithelia were observed. After prolonged exposure, pathologic alteration of the cilial cells was noted. In addition, both exposure durations produced alterations in goblet cells (increased number of degenerated mucus-discharging goblet cells in the rabbits’ tracheal lining).
Short-Term and Subchronic Inhalation Exposure Studies
No human data on the effects of short-term or subchronic duration exposure to PG vapors were found in the literature.
In a 90-d nose-only inhalation exposure animal study, the frequency of certain clinical signs was measured every week, so the results are used here as short-term study observations. Suber et al. (1989) conducted a subchronic nose-only inhalation exposure study of PG in male and female Sprague-Dawley rats. They exposed rats to PG aerosol for 6 h/d, 5 d/wk for 90 d at concentrations of 0.16, 1.01, and 2.18 mg per liter (L) (160, 1,000, and 2,200 mg/m3 or 50, 313, and 688 parts per million [ppm]). These levels were measured and were not target concentrations. The mass median aerodynamic diameters of the diluted aerosols were less than 2.22 and 1.96 micrometers for the medium- and high-concentration groups, with geometric standard deviations of 1.44 and 1.57, respectively. Statistically significant nasal hemorrhaging and ocular discharge were observed beginning the second week of exposure. The reported incidence of nasal hemorrhaging and ocular discharge in the second week of exposure to the lowest test concentration, 50 ppm, was only 3%. The authors attributed the observed nasal hemorrhaging and ocular discharge to dehydration of the nasal passages and eyes. In males the incidence of these symptoms remained essentially constant throughout the exposure (69.9% at 2 wk versus 65.8% at 13 wk), but in females the incidence dropped dramatically from 65.1% at 2 wk to 0.0% at 13 wk.
Respiratory rates and tidal volumes were also measured in four rats per group per sex on day 7; measurements were repeated on days 42 and 84. The measured respiratory parameters were found to be unaltered. The authors also measured hematology and clinical chemistry before the experiment and before necropsy, but not during the weeks of exposure.
Although statistically significant differences were reported between the control groups and the highest-dose group (2.18 mg/L or 688 ppm) for certain hematologic parameters, such as white blood cell count and lymphocyte count, and for the activity of serum enzymes such as serum sorbitol dehydrogenase (all decreases), no dose-dependent relationship was observed. The observed trend of decreases in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase were hard to interpret.
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Chronic Inhalation Exposure Studies
No published toxicity data exist on humans exposed chronically to PG vapors either occupationally or from environmental exposures. Data were available from only one rodent study. Robertson et al. (1947) exposed rats (for 18 months) and monkeys (for 12 months) to PG vapor (at various percentages of atmospheric saturation in the case of monkeys). They used the following concentrations: rats, 0.17 to 0.35 mg/L (53 to 110 ppm); monkeys, 0.23 to 0.35 mg/L (72 to 110 ppm).
In rats, general behavior and appearance; body weight (growth rate) of males; and gross and microscopic examination of lungs, kidneys, liver, and spleen were determined. Kidney function was also evaluated. No significant PG-related adverse effects could be found in the rats. There was no sign of eye irritation in any of the exposed animals.
Monkeys were exposed to 60% saturated or supersaturated PG concentrations for 12 months (Robertson et al. 1947). General behavior and appearance, eye irritation, appetite, blood counts and hemoglobin, gross and microscopic organ lesions, and kidney function were assessed. PG-related increases in numbers of red blood cells and hemoglobin content of blood were the only changes reported. Kidney function was not affected. It was noted that monkeys (both treated and untreated) had infections, to a variable extent, with parasites (roundworms) and lung mites. Many had anemia and were sick or dying during the experiment. Because of these adverse health conditions, only limited confidence can be placed in these data (see Table 16-2).
CARCINOGENICITY
There is no reported incidence of cancer from occupational exposures to PG. Neither the International Agency for Research on Cancer nor the National Toxicology Program has reported that this chemical is a potential carcinogen (NTP 2004). No chronic inhalation exposure study exists in which the carcinogenic potential of PG was evaluated. In several chronic oral ingestion studies (2-y feed studies; see Gaunt et al. 1972), no evidence of tumor induction was found in any of the tissues.
GENOTOXICITY
No in vivo genotoxicity studies have been conducted in humans or animals exposed to PG by inhalation. In vitro tests using various strains of Salmo-
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TABLE 16-2 Toxicity Studies of Propylene Glycol (Inhalation Exposures)
Exposure Concentration
Form of Administration
Species
General Effects
References
Range, 176 ppm to 851 mg/m3; geometric mean, 309 mg/m3; 1- min exposure at several different times
Aerosol spray
Human volunteers
Data on tear-film stability, rhinometry, lung function tests (dynamic spirometry), symptom assessments were collected; reported significant ocular irritation and throat irritation; some breathing difficulty.
Wieslander et al. 2001
0.16 mg/L (50 ppm), 1.0 mg/L (313 ppm), 2.18 mg/L (688 ppm); exposures were for 6 h/d, 5 d/wk for 90 d.
Inhalation (nose only) (aerosol)
Rat
Observations: a high incidence of nasal hemorrhaging and ocular discharge; significantly reduced body weights in medium- and high-dose females; reduced red blood cells in high-dose females. No changes in respiratory rates, tidal volume, or minute volume; unremarkable gross pathology of tissues (at necropsy); thickening of respiratory epithelium with increased number of goblet cells in medium- and high-dose groups.
Suber et al. 1989
230 mg/m3 (72 ppm) for 12 to 18 months, continuous exposure
Inhalation (vapor)
Monkey
No effects on any of the parameters measured for systemic effects; high mortality in control and treated groups due to various infections.
Robertson et al. 1947
170 mg/m3 (53 ppm) for 12 to 18 months, continuous exposure
Inhalation (vapor)
Rat
No effects on any of the parameters measured for systemic effects.
Robertson et al. 1947
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nella typhimurium with and without metabolic activation were negative (Clark et al. 1979, Pfeiffer and Dunkelberg 1980). In vitro studies using mammalian cells (human fibroblasts, Chinese hamster ovary cells, and Chinese hamster lung cells) that measured chromosome aberrations and DNA damage in cells exposed to PG were negative (Swenberg et al. 1976, Sasaki et al. 1980 as cited in Abe and Sasaki 1982).
IMMUNOTOXICITY
There are no reports of immunotoxicity from inhalation of PG by humans. The published animal inhalation studies have not specifically looked at changes in immune system parameters.
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY
There are no published reports of reproductive or developmental toxicity in humans from inhalation of PG vapors in either an occupational setting or by environmental exposure. There are also no published animal data on this subject.
RATIONALE
Acceptable concentrations (ACs) were determined following the guidelines of the National Research Council (NRC 1992) Subcommittee on Guidelines for Developing Spacecraft Maximum Allowable Concentrations (SMACs) for Space Station Contaminants 1992. In the following paragraphs, derivation of ACs for durations of 1 h, 24 h, 7 d, 30 d, 180 d, and 1,000 d are shown for various effects as available and the SMAC for each duration will be determined based on the lowest AC for that duration.
As a part of this process, NASA will also review the existing proposed guidelines, advisories, and regulatory values from various organizations, both regulat ory and nonregulatory.
There are no standards or health values for PG. The U.S. Environmental Protection Agency reference dose/reference concentration work group did not derive an inhalation reference concentration for PG. The airborne exposure limits set by the American Industrial Hygiene Association (AIHA) workplace environmental exposure level (WEEL) (8-h time-weighted average workplace environmental exposure level) for PG are 50 ppm for vapor and aerosol, 10 mg/m3 for aerosol only, and 400 ppm for PG mist and PG vapors (AIHA 1985).
The Agency for Toxic Substances and Disease Registry (ATSDR) did not derive an acute-duration inhalation minimal risk level (MRL) for PG because no adequate studies were found. ATSDR derived an intermediate-duration inhalation MRL of 0.009 ppm for nasal hemorrhaging (ATSDR 1997) based on observations in rats in the Suber et al. (1989) study. Because details were lacking, the ATSDR did not derive a chronic-duration inhalation MRL for PG after review-
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ing the only data available from one animal study of chronic-duration exposure in monkeys and rats (Robertson et al. 1947).
Table 16-3 summarizes SMACs for various durations. The principal studies selected, the adverse end point chosen, the rationale, and detailed calculations have been presented in the preceding paragraphs.
Derivation of 1- and 24-h ACs for Inhalation of PG
For deriving the 1-h AC, the human subject experiment by Wieslander et al. (2001) was considered. Nonasthmatic volunteers were exposed to PG mist during aviation emergency training and several measurements were collected after 1-min exposures to PG mist at a mean concentration of 309 mg/m3 (about 96 ppm). Data collected on symptoms (average ratings on 10 questions, data collected on visual analog scale of 1 to 100) indicated that ocular irritation and throat irritation were significantly higher than preexposure responses. Dyspnea was higher but only of marginal significance (P = 0.048). The ocular irritation was not from redness of the eye or swollen eyes. On the basis of this study, it was considered that the concentration of 309 mg/m3 is a minimal lowest-observed-adverse-effect level (LOAEL) (mild adverse effect). As such sensory effects are based on concentration, and the symptoms were minor, it was decided to use this value for 1 h. Because exposures were just for 1 min, it was decided to use an uncertainty factor of 3 (or LOAEL to NOAEL factor) to derive a 1-h AC as follows:
TABLE 16-3 Spacecraft Maximum Allowable Concentrations for PG
Duration
SMAC, ppm
Target Toxicity
Principal Study
1 h
32.0
Eye, throat, and respiratory system irritation
Wieslander et al. 2001
24 h
17.0
Nasal hemorrhage and ocular discharge
Suber et al. 1989
7 d
9.0
Nasal hemorrhage and ocular discharge
Suber et al. 1989
30 d
3.0
Nasal hemorrhage and ocular discharge
Suber et al. 1989
180 d
1.5
Thickening of respiratory epithelium with increased goblet cells and increased mucin
Suber et al. 1989
1,000 d
1.5
Thickening of respiratory epithelium with increased goblet cells and increased mucin
Suber et al. 1989
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For deriving the 24-h AC, the preceding study could not be used, primarily because of the very brief duration of exposure (1 min). Although the discomfort of ocular irritation and throat dryness at 32 ppm may be acceptable for 1 h, these symptoms may not be appropriate for extending the 1-min exposure data to 24 h. Therefore, on the recommendation of the NRC Spacecraft Exposure Guidelines (SEG) committee, the ten Berge method (ten Berge et al. 1986) of extrapolation from the 7-d AC (168 h) to 24 h was used as follows (see below for details of the 7-d AC derivation):
8.93 × 168 h = C3 × 24 h, where 8.9 ppm is the 7-d AC, 3 is a default factor for the chemical-specific exponent, and C is the concentration to be determined for 24 h, which can be calculated as 17 ppm.
Thus, the 24-h AC = 17 ppm
Derivation of 7-d AC for Inhalation of PG
Suber et al. (1989) conducted a 90-d subchronic nose-only inhalation exposure study of PG in male and female Sprague-Dawley rats (19 males and 19 females each). In this study, the rats were exposed 6 h/d, 5 d/wk for 90 d to PG as an aerosol at concentrations of 0.16, 1.01, and 2.18 mg/L (160, 1,000, and 2,200 mg/m3 equivalent to 50, 313, and 688 ppm, respectively). During this study, the frequency of certain clinical signs was measured every week. Statistically significant nasal hemorrhaging (all exposed groups) and ocular discharge were seen beginning with the second week of exposure. By the end of the first week of exposure to the lowest test concentration, 50 ppm, the incidence of these effects was only 3% (males). The authors attributed the observed nasal hemorrhaging and ocular discharge to dehydration by PG of the nasal passages and eyes. Regardless of the mechanism of action, ACs have been calculated on the basis of such end points. Based of these data, a no-observed-adverse-effect level (NOAEL) of 50 ppm for up to 1 wk can be identified.
The review of the effects clearly shows that by the second week, 69% of the animals had nasal hemorrhaging and ocular discharge, even in the 50-ppm group. Thus, it appears that with longer exposure times, the incidence rate will increase for at least up to 2 wk (as the percent incidence did not change from 2 wk to 13 wk). Therefore, the exposure concentration has to be adjusted with a factor for discontinuous-to-continuous exposure. As far as the use of a species factor is concerned, it was considered that these effects may be due to the dehydrating effect of PG aerosol (physicochemical effect). Known differences between rats and humans in the structure of the nasal region may be important when considering effects on the respiratory tract and lung or when the metabolite of a compound affects the nasal mucosa. As this (dehydration) is a localized effect, the severity of the effect for a particular exposure concentration can be
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expected to be similar for rodents and humans. Therefore, a species factor is not needed. Thus, the 7-d AC can be calculated as follows:
Thus, the 7-d AC for effects on the nasal region is 9 ppm.
Derivation of 30-d AC for Inhalation of PG
The same adverse end points of nasal hemorrhaging and ocular discharge from the Suber et al. study were used to derive a 30-d AC, as no other data were presented in this study that could be used. From weeks 2 to 14, the average incidence of these effects in males, as stated in the body of the text of the authors’ document, was <1% in controls and 65%, 74%, and 75% in low-, medium-, and high-concentration exposure groups. As significant effects were noted at 2 wk, 50 ppm is the LOAEL for 2 wk. Because the data reflect the increased frequency of occurrence and not the severity of the effects, a factor of 3 from LOAEL to NOAEL for these sensory effects would be justifiable. As these effects are primarily due to the dehydrating effect of the chemical rather than to progressive tissue injury, a factor of 10 from LOAEL to NOAEL is not needed. In addition, it must be pointed out that, in a study by Robertson et al. (1947), described earlier under “Chronic Inhalation Exposure Studies,” no nasal hemorrhaging, ocular discharge, or systemic toxicity was reported in rats or monkeys during a 12-to 18-month continuous whole-body exposure to at least 53 and 72 ppm of PG vapor, respectively (note that this study was not used to derive the AC for subchronic and chronic durations). The concentrations of PG in the Robertson et al. study (described earlier in this document) are comparable to that used in the Suber et al. study, but the exposure methods used in these studies were different. No species factor is used, as explained earlier. The 30-d AC is calculated as shown below.
Thus, the 30-d AC for nasal hemorrhaging is 3 ppm.
Derivation of 180-d AC for Inhalation of PG
For derivation of the 180-d AC, the same 90-d nose-only subchronic study by Suber et al. (1989) was used. At the end of the 90-d exposure, body weight changes, food consumption, organ weight changes (especially of the kidneys), and other variables were also determined. According to NRC guidelines (NRC 1992, 2000), in general, changes in such variables are not to be considered in the
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AC derivations. The important measurements that will reflect the systemic effects of PG are the changes in hematologic and clinical biochemistry variables. Hemoglobin concentration, white blood cell count and lymphocyte numbers, serum sorbitol dehydrogenase and gamma-glutamyl transferase activity, and total serum protein were measured in the study. However, these changes did not follow a definite dose-dependent pattern. There were no histopathologic changes. However, light microscopy of the respiratory epithelium showed thickening reflected in an increased number of goblet cells and an increase in their mucin content in both female and male animals with medium- and high-dose treatment groups. Because the authors reported that there were no histologic changes in the trachea, lungs, or larynx and minute volume, tidal volume, and respiratory rate were not significantly altered, the epithelial changes are considered mild adverse effects, and thus one could identify 50 ppm as the NOAEL for these effects.
For deriving the AC for 180 d, a factor for adjusting the exposure duration will be used. Although a species factor was not used for the nasal hemorrhaging end point earlier, a species factor of 3 will be used in this case. The factor is for the uncertainty in the severity of effects due to the differences between humans and rats in the nasal passage respiratory epithelium and the nature of the goblet cells. Because the AC is calculated for 180 d with data from a 90-d study, a time extrapolation factor of 180 d/90 d is used; 50 ppm is a NOAEL for this effect.
Thus, the 180-d AC for histologic changes in the nasal passages is 1.5 ppm.
The chronic whole-body exposure study of Robertson et al. (1947), described in detail earlier in this document, was also evaluated. Briefly, in the Robertson et al. study, monkeys and rats were continuously exposed to PG supersaturated vapor in chambers for 12 to 18 months at the following concentrations: rats, 0.17 to 0.35 mg/L (53 to 110 ppm) for 18 months; monkeys, 0.23 to 0.35 mg/L (72 to 110 ppm) for 12 months. During the exposure period, there were no differences between the unexposed and the exposed groups in the general condition of the animals or in their general activity or behavior. There was no sign of eye irritation in any of the exposed animals. There was also no impairment of kidney function. The red blood cell counts and hematocrit values were greater than those of untreated controls. Several of the exposed female rats bore normal-sized litters; all the offspring appeared to be normal. However, in the study, the author reported that the overall health of the monkeys was undesirable, and they had a high mortality rate. In the rats, although PG had caused no generalized or localized inflammation of the bronchi or lungs, microscopic examination of the lungs revealed a localized infectious process. This was also noted in 25% of the control rats. Even though this effect was seen only in rats
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kept 8 months or longer (18 months), the NRC SEG committee recommended that this study not be used for AC derivation because of the high incidence of infection in control rats, as evidenced by the microscopic changes in the lungs.
Derivation of 1,000-d AC for Inhalation of PG
Although in the Robertson et al. (1947) study an 18-month chronic exposure to PG vapors did not lead to any overt systemic effects after rats were exposed to 53 to 100 ppm of PG, the study could not be considered for 1,000-d AC derivation because of reported infectious activity (small to large areas of intraalveolar accumulation of polymorphonuclear leukocytes) in the lungs of 25% of the controls and in exposed rats.
To arrive at a 1,000-d AC, it was decided to use the 180-d AC derived from the Suber et al. (1989) study. As the nature of the effects (epithelial changes in the nasal passages) seemed to be adaptive, the NRC SEG committee recommended using the 180-d AC without any time extrapolation factors from 180 to 1,000 d.
Thus, the 1,000-d AC for nasal morphology change is 1.5 ppm
Table 16-4 summarizes the ACs derived for various end points for various durations from 1 h to 1,000 d and the SMACs for each of these durations.
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TABLE 16-4 Summary of Acceptable Concentrations and SMACs for Various Durations
Adverse End Point
Exposure Data
Species and Reference
LOAEL/NOAEL
Acceptable Concentrations, ppm
1h
24 h
7 d
30 d
180 d
1,000 d
Ocular and throat irritation and slight dyspnea
Inhalation of PG; 1 min; mean concentration = 309 mg/m3 (~ 96 ppm)
Human, Wieslander et al. 2001
LOAEL = 96 pp
32
—
—
—
—
—
Nasal hemorrhage and ocular discharge
Inhalation of PG; 6 h/d, 5 d/wk; 0.16, 1.01, 2.18 mg/L (160, 1,000, 2,200 mg/m3 or 50, 313, 688 ppm)
Sprague-Dawley rat, Suber et al. 1989
NOAEL for 1 wk = 50 ppm; ten Berge method used
—
17
—
—
—
—
Nasal hemorrhage and ocular discharge
Inhalation of PG; 6 h/d, 5 d/wk; 0.16, 1.01, 2.18 mg/L (160, 1,000, 2,200 mg/m3 or 50, 313, 688 ppm)
Sprague-Dawley rat, Suber et al. 1989
NOAEL for 1 wk = 50 ppm
—
—
9
—
—
—
Nasal hemorrhage and ocular discharge
Inhalation of PG; 6 h/d, 5 d/wk; 0.16, 1.01, 2.18 mg/L (160, 1,000, 2,200 mg/m3 or 50, 313, 688 ppm)
Sprague-Dawley rat, Suber et al. 1989
LOAEL for 2 wk = 50 ppm
—
—
—
3
—
—
Thickening of respiratory epithelium with increased goblet cells and their mucin
Inhalation of PG; 6 h/d, 5 d/wk; 0.16, 1.01, 2.18 mg/L (160, 1,000, 2,200 mg/m3 or 50, 313, 688 ppm)
Sprague-Dawley rat, Suber et al. 1989
NOAEL = 50 ppm
—
—
—
—
1.5
1.5
SMACs
32
17
9
3
1.5
1.5
Abbreviations: LOAEL, lowest-observed-adverse-effect level; NOAEL, no-observed-adverse-effect level; —, not calculated.
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REFERENCES
AIHA (American Industrial Hygiene Association). 1985. Workplace Environmental Exposure Level (WEEL) Guide for Propylene Glycol. Fairfax (VA): American Industrial Hygiene Association.
ATSDR (Agency for Toxic Substances and Disease Registry). 1997. Toxicological Profile for Ethylene Glycol and Propylene Glycol. U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA. September 1997.
Abe, S., and M. Sasaki. 1982. SCE as an index of mutagenesis and/or carcinogenesis. Pp. 461-514 in Sister Chromatid Exchange. Progress and Topics in Cytogenetics Vol. 2, A.A. Sandberg, ed. New York: A.R. Liss.
Browning, E. 1965a. Ethylene glycol. Pp. 594-600 in Toxicity and Metabolism of Industrial Solvents. New York: Elsevier.
Browning, E. 1965b. Propylene glycol. Pp. 642-644 in Toxicity and Metabolism of Industrial Solvents. New York: Elsevier.
Cavender, F.L., and E.J. Sowinski. 1994. Glycols. Pp. 4645-4719 in Patty’s Industrial Hygiene and Toxicology, Vol. 2F. Toxicology, 4th Ed., G.D. Clayton, and F.E. Clayton, eds. New York: Wiley.
Clark, C.R., T.C. Marshall, B.S. Merickel, A. Sanchez, D.G. Brownstein, and C.H. Hobbs. 1979. Toxicological assessment of heat transfer fluids proposed for use in solar energy applications. Toxicol. Appl. Pharmacol. 51(3):529-535.
Gaunt, I.F., F.M. Carpanini, P. Grasso, and A.B. Landsdown. 1972. Long-term toxicity of propylene glycol in rats. Food Cosmet. Toxicol. 10(2):151-162.
Konradova, V., V. Vavrova, and J. Janota. 1978. Effect of the inhalation of a surface tension-reducing substance (propylene glycol) on the ultrastructure of epithelium of the respiratory passages in rabbits. Folia Morphol. (Praha) 26(1):28-34.
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