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<br /> Chemical Summary Methyl-Tert-Butyl Ether - Microsoft Internet Explorer Page 7 of 13
<br /> 2 Animals - The subchronic oral toxicity of MTBE was evaluated in
<br /> a 90-day bioassay in which Sprague-Dawley rats were dosed by
<br /> gavage with 0, 100, 300, 900 or 1200 mg MTBE/kg/day Animals
<br /> in all treatment groups exhibited diarrhea. A dose level of
<br /> 1200 mg/kg/day resulted in an increase in hyaline droplets and
<br /> blockage of renal tubules with granular cysts, increased kidney
<br /> and liver weights, increases in hemoglobin, hematocrit, and
<br /> erythrocytes, decreases in blood glucose, blood urea nitrogen
<br /> (BUN) , and calcium, and elevations in cholesterol and aspartate
<br /> aminotransferase (AST) (U.S. EPA 1993x) Pathological changes
<br /> ' in the kidney were not seen at the lower dose levels, however,
<br /> males and females treated with 900 mg/kg MTBE and females
<br /> treated with 300 mg/kg/day exhibited increases in relative
<br /> kidney weight as well as several changes in blood chemistry such
<br /> as a decrease in BUN The oral reference dose (RfD) for MTBE
<br /> is currently under review by EPA (U S EPA 1994)
<br /> In tests in which rats were exposed to MTBE concentrations of 797,
<br /> 3920, or 8043 Ppm (6 h/day, 5 days/wk for 13 wk) , the two highest
<br /> concentrations resulted in increased liver, kidney and adrenal
<br /> weights, changes in hematologic parameters (increased hemoglobin,
<br /> decreased erythrocyte counts and increased reticulocyte counts) ,
<br /> ' altered serum chemistry (increases in calcium and protein, and
<br /> decreases in blood glucose, and AST and alanine aminotransferase
<br /> (ALT) activities) , lymphoidal hyperplasia, splenic hemosiderosis,
<br /> and an increase in the size of hyaline droplets in the renal
<br /> ' proximal tubular epithelial cells (U.S. EPA 1993a) No adverse
<br /> effects were seen at 797 ppm The concentration of 8043 ppm is
<br /> roughly equivalent to 4, 639 mg/kg/day (see end note 2) .
<br /> Exposure of mice and rats to concentrations of 0, 403, 3023,
<br /> or 7977 ppm MTBE for 6 h/day, 5 days/week, for up to 18 months
<br /> (mice) or 24 months (rats) resulted in clinical signs of toxicity
<br /> at the two highest exposure levels (U.S. EPA 1993a) Effects
<br /> seen in rats included increased incidences of swollen periocular
<br /> tissue, decreases in absolute body weight and body weight gain;
<br /> increases in absolute and relative liver weight in females; an
<br /> increase in kidney weight, and an increase in the incidence of
<br /> I chronic nephropathy (glomerulosclerosis, tubular proteinosis,
<br /> interstitial nephritis, and interstitial fibrosis) Effects seen
<br /> in mice included increases in absolute and relative liver and
<br /> kidney weights, increases in absolute and relative adrenal
<br /> weights in males, increases in hepatocellular hypertrophy and
<br /> ' liver masses, and a slightly increased frequency of urinary
<br /> bladder dilation/distension in males. The 403 ppm exposure level
<br /> was considered a NOAEL Based on the results of the rat study,
<br /> the U S EPA (1994) calculated a chronic RfC (reference concen-
<br /> tration) of 3 mg/m3 For MTBE
<br /> D Carcinogenicity
<br /> Information on the potential carcinogenicity of MTBE in humans is
<br /> lacking and the results of animal studies are still under review
<br /> within EPA, however, the current unfinished assessment supports a
<br /> hazard classification of "possible" human carcinogen based upon
<br /> 1 "limited" animal evidence (U.S. EPA 1993c, Anderson 1994) .
<br /> 1 Humans - No studies were found in the available secondary
<br /> sources evaluating the potential carcinogenicity of MTBE to
<br /> humans
<br /> 2. Animals - The Carcinogenicity of MTBE has been evaluated in
<br /> inhalation exposure studies using CD-1 mice and F344 rats
<br /> (U S. EPA 1993a) In female mice, the incidence of liver
<br /> adenomas was significantly increased over control values
<br /> Friday, August 16, 1996 4 25 PM
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