Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 3 (2008) / Chapter Skim
Currently Skimming:
6 Propylene Glycol
6 Propylene Glycol
Pages 165-188
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 165... ...
Hence, PG is the choice to replace EG, as it is generally believed to be less toxic. The purpose of this document is to review the existing toxicology literature on PG and develop spacecraft water exposure guidelines (SWEGs)
|
From page 166... ...
As the general weight of evidence in the toxicology literature supports the conclusion that PG-based fluids are preferable to EGbased fluids, the ISS program prefers to use PG rather than EG as a coolant. TABLE 6-1 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 Water solubility 100 g/100 g of H2O at 25ºC Specific gravity 1.04 Melting point –60°C Boiling point 187°C Vapor pressure 0.07 mm Hg at 20°C; 0.13 mm Hg at 25°C Concentration in air at 170 ppm at 25°C (calculated from vapor pressure at saturation that temperature)
|
From page 167... ...
About 55% of PG is metabolized in the liver to lactic acid by alcohol dehydrogenase. The lactic acid is then converted through the gluconeogenic pathway to yield acetate and pyruvate, which is converted to glucose (Ruddick 1972, Morshed et al.
|
From page 168... ...
contained at least 828 mg of PG. Although the clinical significance of elevated PG concentrations and associated toxicity has not been well described or well documented in these cases, they all present metabolic evidence of PG toxicity (increased lactic acid, metabolic acidosis, hyperosmolality)
|
From page 169... ...
slight increase in serum bilirubin noted; hemoglobin, 1971 packed cell volume, and RBC count were lower; no effects on organ weights, urine biochemical parameters, liver function tests, hepatotoxicity marker enzymes, water consumption, body weight, or histopathology in low–dose group; increased urine output in 5 g/kg/d PG-treated female groups; NOAEL = 2 g/kg/d. (Continued)
|
From page 170... ...
NOAEL = 1,600 mg/kg/d. 16, 74.3, 345, and 1,600 Gestation Oral Mouse; 25/group No noticeable effect on nidation or maternal or fetal FDRL 1973 mg/kg days 6 to intubation survival; extent of skeletal tissue abnormalities was 15 the same as in untreated controls.
|
From page 171... ...
In almost all of them, Heinz body formation due to PG administration and subsequent RBC lysis were reported. Heinz body formation seems to be unique to cats and they are not suitable models for human risk assessment.
|
From page 172... ...
Serum lactic acid, arterial pH, and other clinical parameters such as osmolality and anion gap were not measured. • In a short-term infusion pharmacokinetic Phase I study of a cytostatic agent containing PG, nine cancer patients were infused 4 h daily for 5 d at doses of 120 and 180 mg/m2, amounting to a PG dose of 5.1 or 7.5 g/d (Speth et al.
|
From page 173... ...
Four patients who received IV lorazepam or diazepam did not show signs of clinical deterioration, but had metabolic evidence of PG toxicity (elevated anion gap, decreased serum bicarbonate, elevated serum osmolality)
|
From page 174... ...
. This individual was infused with high doses of lorazepam and on the eighth day developed severe metabolic acidosis, a significant increase in serum creatinine (indication of acute kidney toxicity)
|
From page 175... ...
, which exhibited Heinz body formation (aggregates of denatured hemoglobin protein globin chains precipitated within the RBCs) followed by increased hemosiderin pigment in liver Kupffer cells and spleen endothelial cells.
|
From page 176... ...
No human studies describing exposure to PG for this duration are available in the toxicology literature. Rats given 10% PG in drinking water for 100 d showed no change in body weight after an initial loss during the first 10 d (Weatherby and Haag 1938)
|
From page 177... ...
One group of male and female dogs was given 5% PG in water two times a day and another group of only males was allowed to drink 600 mL of water containing 10% PG per day. Kidney function was assessed by phenosulfonaphthalein excretion and liver function was studied by measuring rose bengal (rose bengal test for liver function)
|
From page 178... ...
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY No human reproductive toxicity data on PG could be located. The NTP conducted a reproduction and fertility assessment in CD-1 mice administered PG in their drinking water (Gulati et al.
|
From page 179... ...
RATIONALE The following paragraphs provide a rationale for proposing 1-, 10-, 100-, and 1,000-d SWEGs for PG in NASA's spacecraft water. The values for SWEGs were based on ACs for each respective duration derived according to Methods for Developing Spacecraft Water Exposure Guidelines (NRC 2000)
|
From page 180... ...
As the data are from humans, no species factor will be applied. Using this value as a NOAEL, a 1-d AC for abnormal serum parameters (hyperosmolality, osmolal gap, hyperlactatemia, and metabolic acidosis)
|
From page 181... ...
L-Lactate concentrations increased to 2.5-fold higher than those of controls and D-lactate increased to 30fold higher than the controls. TABLE 6-4 SWEGs for PG Duration, d SWEG, g/L Toxicity End Point Principal Study 1 25 Hyperosmolality, osmolal gap, Clinical case studies hyperlactatemia, and metabolic (see Zar et al.
|
From page 182... ...
All these data are from IV studies. Persistent high levels of blood lactate can lead to an increased osmolal gap.
|
From page 183... ...
The first study considered was by van Winkle and Newman (1941) , who investigated the effect of 5% and 10% PG in the drinking water of male and female dogs after 9 mo of treatment.
|
From page 184... ...
Since there are no chronic drinking water studies available, the 2-y chronic exposure studies reviewed above were considered for deriving the 1,000-d AC. A comprehensive look at these studies seems to indicate that the kidney is not a target organ for PG toxicity in animals.
|
From page 185... ...
=2 1971 SWEG 25 8 8 1.7 a 3 = spaceflight safety factor for abnormal hematology. Abbreviation: -- , none derived.
|
From page 186... ...
1980. Propylene glycol intoxication and lactic acidosis.
|
From page 187... ...
2000. Methods for Developing Spacecraft Water Ex posure Guidelines.
|
From page 188... ...
1997. Propylene glycol-induced proximal renal tubular cell injury.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.