Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 3 (2008) / Chapter Skim
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3 Ethylene Glycol
3 Ethylene Glycol
Pages 86-125
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From page 86... ...
space capsules and was present in heat-exchange loops in the Russian Mir space station. Leakage of EG from coolant loops in Mir was a persistent problem during the past few years because the space station was used beyond its intended service life.
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From page 87... ...
Absorption Fasted rats given gavage doses of EG at 6 or 9 milliliters per kilogram (mL/kg) of body weight rapidly absorbed it into the body, where it reached peak blood concentrations in 1 to 4 h (Winek et al.
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From page 88... ...
Lactate dehydrogenase appears to be involved in converting glyoxal to glycolic acid, glycolic acid to glyoxylic acid, and glyoxylic acid to oxalic acid, which is further oxidized to formic acid and carbon dioxide by a process involving coenzyme A and flavin mononucleotides. Glyoxylic acid is metabolized to a number of other products, which have no apparent bearing on the toxicity of EG.
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From page 89... ...
Because blocking the major pathway also reduces the toxicity of EG, the authors suggested that the free radicals do not contribute significantly to the acute toxicity of EG. There is an alternative interpretation of the above 4-methylpyrazole data that Kadiiska and Mason (2000)
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From page 90... ...
Oxalate produced a concentration- and time-dependent entry of the red fluorescent dye into the cells with damaged membranes. Glycolic acid and glyoxylic acids failed to produce similar effects on the HPT cells at concentrations associated with renal effects in humans poisoned with EG.
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From page 91... ...
The long-term effects of EG ingestion in animals include adverse effects on the kidney, blood cells, and possibly the liver. There is some evidence that EG can cause reproductive and developmental toxicity in animals.
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The renal injury may be reflected in a urinalysis by the presence of protein, red and white blood cells (RBC and WBC) , casts, and calcium oxalate crystals.
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Walton 1978 1.6 g/kg Oral Human Minimum lethal estimate.a Gessner et al. 1961 1.1 g/kg Oral Human, n=7 Minimum lethal estimate.
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From page 94... ...
indices and WBC count in 4% group NOAEL was 2%.a 1990 0.5%-4.0% 10 d DW SD rat, M, n =10 Increased incidence or severity of renal lesions at 2% and 4%; Robinson et al. NOAEL was 0.5%.a 1990 1.0% 21 d DW Porton rat, M Oxalate deposits in kidney.
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0.04-1.0 g/kg/d 2 y feed F344 rat, M, NOAEL 0.2 g/kg/da renal injury (creatinine, BUN, lesions)
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. Abbreviations: DW, drinking water; F, female; LD50, 50% lethal dose; M, male; SD, Sprague-Dawley.
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From page 97... ...
and most were seriously ill but survived. If one assumes a body weight of 50 kg and that the EG was ingested at a rate of 50 mL/d for 3 d, then the daily dose was 1.1 g/kg.
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From page 98... ...
given drinking water containing 0.25% EG and fed a synthetic diet supplemented with large or small amounts of vitamin B6 or magnesium. There were no renal effects in rats given the high magnesium supplement, and in those given the high vitamin B6 supplement renal lesions were reduced in severity compared with rats given reduced supplements.
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From page 99... ...
Liver Injury Although EG is considered primarily a renal toxicant, there is evidence that liver damage can occur at subchronic dosages comparable to those that induce renal injury. Although death in rats given EG in their drinking water was believed to be due to renal failure, Hanzlik et al.
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From page 100... ...
; chronic studies using drinking water as the source of EG exposure were not found. The negative findings in the chronic monkey feeding study may seem to conflict with the positive findings reported for subchronic exposure of macaques by drinking water (Roberts and Seibold 1969)
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The National Research Council committee advised that the report of lung arterial medial hyperplasia is an unusual outcome related to the nature of the study rather than an adverse effect of EG ingestion. Hematotoxicity At the 12-month sacrifice of male rats DePass et al.
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EG was given to male and female CD-1 mice in their drinking water at concentrations of 0%, 0.25%, 0.5%, or 1.0% for about 15 wk beginning at 11 wk of age. One week into the study, the mice were paired for breeding and the offspring of the matings were evaluated to assess reproductive performance (Lamb et al.
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From page 103... ...
. Fetal abnormalities were also observed in offspring from the high-dose group of CD-1 mice given drinking water with 0%, 0.25%, 0.5%, or 1.0% EG for 15 wk before mating and during gestation (Lamb et al.
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From page 104... ...
The authors suggest that this is evidence that glycolic acid plays a major role in EG's developmental toxicity, that oxalic acid does not, and that EG doses must be quite high before sufficient glycolic acid is produced to elicit developmental toxicity (Pottenger et al.
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From page 105... ...
Ingestion of 2.8 L of water with an EG concentration of 20 mg/L, the 100-d spacecraft water exposure guideline (SWEG) , and a conversion efficiency for EG to oxalate of 0.023 (Reif 1950)
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From page 106... ...
2 mg/kg/d (70 mg/L) a ASTDR 1997 State Drinking Water Guidelines Five states 5.5-10 mg/L EPA 1993 Connecticut 0.1 mg/L New Jersey 0.29 mg/L Massachusetts ORSGL 14 mg/L a Assumes a water consumption of 2 L/d by a 70-kg person.
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From page 107... ...
. The relative source contribution is the fraction of EG present in drinking water as a portion of EG coming from all sources.
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From page 108... ...
In particular, TABLE 3-4 Spacecraft Water Exposure Guidelines for Ethylene Glycol Duration of Consumption, d Guideline, mg/L Toxicity Target for Protection 1 270 Kidney, central nervous system 10 140 Kidney, tubular degeneration 100 20 Kidney, tubular degeneration 1,000 4 Kidney, tubular degeneration
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From page 109... ...
In addition, any concomitant inhalation exposure to EG must be considered when one is assessing the health risk from EG in drinking water. Guideline for 1 d The 1-d guideline was based on an estimate of the minimum lethal concentration of 1.6 g/kg provided by Gessner et al.
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From page 110... ...
In the same 10-d study, the NOAEL for effects on blood cells in female rats was 2.0% or an average consumption of 2,950 mg/kg/d in drinking water. Because about a 10% loss of RBC mass occurs in astronauts within a few days of exposure to microgravity, they have been considered a susceptible population for hematotoxicants; a factor of 3 was applied to address this putative susceptibility.
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From page 111... ...
= 2.3 g/L. The NOAEL for decreased WBC count in female rats ingesting EGcontaminated drinking water for 90 d was 1.0% (1,150 mg/kg/d)
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(1990) were renal tubular degeneration, intratubular crystals, and subacute inflammation (90 d only)
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Conversion from mg/kg/d back to the percent of EG in the water was done using a divisor of 1,320, which was derived from average ratios in Table 3-5 for concentrations of 0.5% to 2.0%. TABLE 3-5 Kidney Lesions in Male Rats Exposed for 10 d to EG in Their Drinking Water Number of Renal Tubular Intratubular Dose, % Dose, mg/kg/d Rats Degeneration Crystals 0 0 10 2 0 0.5 650 10 2 0 1.0 1,340 10 2 1 2.0 2,620 10 6 5 4.0 5,280 10 9 7 TABLE 3-6 Log-Logistic Model of Kidney Lesions Found in Rats Drinking EG-Contaminated Water for 10 d Parameter/End Point Renal Tubular Degeneration Intratubular Crystals BMD10 1,410 mg/kg/d (1.07%)
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. Database and BMD Analysis for 90 d For consistency, a similar approach was applied to the kidney lesions found in rats ingesting EG-contaminated water for 90 d.
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Abbreviations: AIC, Akaike Information Criterion; BMD10, the maximum-likelihood dose expected to give a 10% response; BMD01, the maximum-likelihood dose expected to give a 1% response; BMDL10, the 95% lower confidence limit of the BMD10; BMDL01, the 95% lower confidence limit of the BMD01; IC, intratubular crystal; RTD, renal tubular degeneration; SI, subacute inflammation. response reversal between the control and low-dose groups.
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, we divide the 100-d AC of 20 mg/L by 5 as follows: 1,000-d AC(renal injury)
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1961 10-d NOAEL renal lesions, M/SD 1 10 3 3 1 -- 180 -- -- Robinson et 0.5% in drinking water rats al. 1990 10-d BMDL10 = 520 mg/kg/d M/SD 1 10 3 3 1 -- 140 -- -- Robinson et (IC)
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From page 118... ...
rats et al. 1990 drinking water 90-d NOAEL on WBC count, F/SD 1 10 3 3 1.1 -- 290 -- Robinson 1.0% (11 g/L)
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1999. Ethylene glycol developmental toxicity: Unraveling the roles of glycolic acid and metabolic acido sis.
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1993. Summary of Federal and State Drinking Water Standards and Guidelines.
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1985. Reproductive and developmental toxicity of ethylene glycol in the mouse.
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2000. Methods for Developing Spacecraft Water Exposure Guidelines.
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1995c. Assessment of the developmental toxicity of ethylene glycol applied cutaneously to CD-1 mice.
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P-value = 1.0000 Specified effect = 0.1 Risk Type = Extra risk BMD = 779 BMDL = 391
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From page 125... ...
Ethylene Glycol 125 Log-Logistic Model with 0.95 Confidence Level Log-Logistic 1 0.8 Fraction Affected 0.6 0.4 0.2 0 0 500 1000 1500 2000 2500 3000 BMDL BMD Dose 12:04 04/19 2007 FIGURE 3-4 Curve for 90-d subacute inflammation. p value = 0.248 Specified effect = 0.1 Risk Type = Extra risk BMD = 317 BMDL = 46.5
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