The Acetone Toxicity Database contains data on acetone itself as well as on isopropanol. Since isopropanol can be easily metabolized to acetone in the body, the Agency concluded that isopropanol data in conjunction with acetone data can be used to characterize acetone toxicity. There are very few data on the direct effects of pyridine exposure during pregnancy. Therefore, it is not possible to draw firm conclusions. Effects on the unborn child are more likely to occur if exposure to acetone causes the mother to feel unwell. Children exposed to acetone have similar effects to adults. They are not expected to be more sensitive to the effects of acetone. Specific information on the studies obtained and the nature of the adverse reactions caused by acetone and the NOAEL and LOAEL values of the toxicity studies can be found under www.regulations.gov in the document “Acetones – Decision Document for pesticide petition 7E7239, Acetones, CAS No. 67-64-1; PC code 844101”, in the file identification number EPA-HQ-OPP-2008-0039. Acetone released into the environment usually degrades within a few days and does not accumulate. It is broken down by sunlight and bacteria in soil and water.
Therefore, acetone levels in the environment would be expected to be low. The EPA has not established that acetone shares a common mechanism of toxicity with other substances, and acetone does not appear to produce a toxic metabolite produced by other substances, however, isopropanol is easily metabolized to acetone in humans. For isopropanol and its metabolite, acetone, no endpoints of concern were identified for various dietary and non-dietary exposure scenarios. For the purposes of this tolerance measure, the EPA therefore assumed that acetone does not have a common mechanism of toxicity with other substances. Information on the EPA`s efforts to determine which chemicals have a common mechanism of toxicity and to assess the cumulative effects of those chemicals can be found on the EPA`s website under www.epa.gov/pesticides/cumulative. Acetone is currently approved for use as an inert ingredient in pesticide formulations used before and after harvest below 40 CFR 180,910. Acetone is found or found in a variety of foods and consumer products. Acetone has been approved by the FDA as a secondary direct food additive (21 CFR 173,210).
Available toxicity studies suggest that acetone has very low toxicity. NOAEL concentrations were 900 mg/kg/day and above, with the exception of a 90-day gavage toxicity study in rats in which the NOAEL of 100 mg/kg/day was based on the renal toxicity observed at the 500 mg/kg/day DLL. The observed differences in efficacy between the Drinking Water and Nutrition Study and the Gavage Study may be related to acetone metabolism. The EPA`s Integrated Risk Information System (IRIS) concluded that the drinking water pathway more accurately mimics potential long-term human exposure scenarios. For this reason, the EPA concluded that the results of the Gavage study for acetone may not be appropriate for long-term risk assessments. As indicated in this unit, the lowest NOAEL determined in the database is 900 mg/kg/bw/day. For all intents and purposes, this is the dose limit set by the Agency. For substances that show no signs of toxicity equal to or greater than the limit dose, a quantitative risk assessment is not required.
As no of worrying endpoints have been identified for the assessment of acute and chronic dietary exposure and for short and intermediate exposure to patients by skin and inhalation, a quantitative risk assessment for acetone is not necessary. This Regulation provides for a derogation from the requirement of a tolerance for residues of acetone (67-64-1) when used as an inert ingredient as a solvent or co-solvent, 40 CFR 180.930, in pesticide products used in animals. Whitmire Micro-Gen (now affiliated with BASF Corp.; 3568 Tree Court Industrial Blvd., St. Louis, MO 63112) has filed a petition with the EPA under the Federal Food, Drug and Cosmetic Act (FFDCA) requesting the introduction of an exemption from the tolerance requirement. This Regulation removes the need to set a maximum permitted level for residues of acetone. Low exposure after appropriate use of household products containing acetone is not expected to have adverse health effects. The toxicity of acetone has been evaluated in several subchronic toxicity studies in mice and rats by drinking water, gavage and inhalation. The most notable results in subchronic studies were an increase in liver and kidney weight and a decrease in spleen weight. Adverse reactions (hepatic and renal toxicity) were observed in mice given acetone via drinking water at doses ≥1,600 milligrams/kilogram/bw/day (mg/kg/bw/day). Rats treated with acetone during the 90-day period showed a decrease in body weight and an increase in the relative weight of the kidneys and liver, hemosiderosis of the spleen, and an increased incidence and severity of nephropathy at 1,700 mg/kg/day.
The NOAEL in rats was 900 mg/kg/day. In a subchronic toxicity study in rats using gavage, acetone resulted in changes in renal weight and lesions at 500 mg/kg/day. The NOAEL in this study was 100 mg/kg/day. Male Sprague-Dawley rats were exposed to acetone by inhalation at a concentration of 19,000 ppm (45,106 mg/m3) for 3 hours/day, 5 days/week, for 8 weeks. The groups were sacrificed after 2, 4 and 8 weeks and 2 weeks after exposure. No treatment-related effects were observed in this study at exposure concentrations of 19,000 ppm (equivalent to 11,703 mg/kg/day). There were no dermal toxicity studies. In accordance with Section 408(c)(2)(A) of the FFDCA and the factors referred to in Section 408(c)(2)(B) of the FFDCA, the EPA has reviewed the available scientific data and other relevant information in support of this measure. The EPA has sufficient data to assess and determine the hazards of exposure to acetone, including the exposure resulting from the exemption established by this measure.