Methyl Ethyl Ketone Safety Characterization for Infants and Children: Assessment in the USEPA Voluntary Children's Chemical Evaluation Program

ABSTRACT

A safety characterization specific to children was performed for methyl ethyl ketone (MEK) according to the guidelines of the Voluntary Children's Chemical Evaluation Program (VCCEP). The characterization indicates that MEK exposures are not expected to pose an acute or chronic risk to children. Hazard information, summarized as per the VCCEP Tier structure, indicated no need for additional studies. All exposure pathways potentially relevant to children were considered, including child contact with environmental media, food, drinking water, parental transfer to child (human milk or dermal contact), direct consumer product use, and presence during product use. The assessment found that exposures from anthropogenic sources that children may encounter on a daily basis are very low, and in particular well below the chronic inhalation and oral health benchmarks (RfC and RfD) derived by the U.S. Environmental Protection Agency (USEPA). Indoor uses of consumer products can result in higher acute exposures, but these are short-lived and also fall below chronic benchmarks adjusted to an acute timeframe. In addition, MEK is rapidly metabolized and excreted, thus acute exposures do not lead to an increase in body burden over time. The USEPA concluded the VCCEP submission sufficiently characterized potential risks to children, and that no additional toxicity tests were needed for MEK.

Key Words:

• methyl ethyl ketone
• MEK
• VCCEP
• hazard assessment
• exposure assessment
• risk characterization
• children's exposure

ACKNOWLEDGMENTS

The VCCEP Data Submission and this manuscript were supported by the American Chemistry Council Ketones Panel. Sponsors were Celanese, E.I. DuPont deNemours & Company, ExxonMobil Chemical Company, and Shell Chemical LP.

Notes

^a Extensive neuropathology was performed on the 90-day and 6-month repeated-dose animals that were also clinically asymptomatic.

^b Tissue examination of fetuses in multiple guideline developmental toxicity studies showed no indication of a primary effect on the nervous system. Clinical/behavioral observations in long-term rodent studies and human exposure studies showed no concern for neurotoxicity.

¹Tissue examination of fetuses in multiple guideline developmental toxicity studies showed no indication of a primary effect on the nervous system. Clinical/behavioral observations in long-term rodent studies and human exposure studies showed no concern for neurotoxicity.

¹For consumer products, results are presented for active product use for ages 16–19 for all scenarios and ages 12–15 for hobby scenarios, and passive presence in the house for other age groups.

²For consumer products, ranges represent exposure estimates for median and maximum use scenarios. Acute consumer product exposures were adjusted to a chronic basis for comparison to the RfD. Margins of Safety were calculated based upon median exposures when both median and maximum estimates were provided, as median exposures were considered more representative of chronic, repeated exposures; MOS can similarly be calculated based upon the maximum values provided in the table. When only a maximum exposure was estimated, the MOS was calculated based upon this value. Scenario details are in complete VCCEP submissions at: http://www.tera.org/peer/vccep/MEK/MEKwelcome.html

¹For consumer products, results are presented for active product use for ages 16–19 for all scenarios and ages 12–15 for hobby scenarios, and passive presence in the house for other age groups.

²For consumer products, ranges represent exposure estimates for median and maximum use scenarios. Scenario details are in complete VCCEP submissions at: http://www.tera.org/peer/vccep/MEK/MEKwelcome.html

¹Margin of exposure (MOE) is determined by dividing the NOAEL for sensory irritation by the estimated 4-hour TWA exposure for each use scenario. The NOAEL for sensory irritation is 200 ppm (590 mg/m³), based on 4-hour exposures to human volunteers, as reported by Dick et al. (1992).

²As described in text, an alternate acute benchmark based on an adjustment of the RfC was calculated for comparison to acute exposures.