a b s t r a c t

Objectives: This retrospective study aims to review California Poison Control System data to qualitatively describe reported methyl acetate (MA) exposures and determine if a metabolic acidosis develops.

Methods: We queried the Poison Control System data between January 1997 and December 1, 2010. Inclusion criteria were single MA ingestions.

Results: Eighty-three cases were analyzed. Females made up 52% of study subjects. Seventy-five cases (90%) were 5 years or younger. Most (93%) ingestions were unintentional. Sixty-two cases (75%) were referred to a health care facility (HCF). Of these, 75% of cases referred to an HCF had no effect, and 25% of cases had a minor effect. There were no major effects, including deaths reported. One case received single-dose activated charcoal, and 1 case received intravenous fluids as therapy. All other cases were observed only. Of all cases, including home-managed and HCF cases, 63 (76%) had no symptoms. Vomiting was observed in 12 cases (14%), drowsiness in 1 case, ataxia in 1 case, abdominal pain in 1 case, and throat/oral irritation in 5 cases. Fifty-three percent of cases referred to HCF had at least 1 chemistry panel done (27% had N 1 chemistry panel done). One patient had a mild metabolic acidosis without symptoms that resolved after a period of observation. There was no renal dysfunction.

Conclusion: These data suggest that minor ingestions of MA may be observed at home, but a prospective study is needed to exclude the risk of home observation.

(C) 2013

Introduction

In an effort to reduce volatile organic compound emissions, many manufacturers of nonacetone nail polish removers (NNPRs) have changed their formulations from ethyl acetate to methyl acetate (MA) [1]. Although more environmentally friendly, MA is readily hydro- lyzed in acidic environments to methanol and Acetic acid [2]. Given that, in 2010, more than 9000 exposures involving NNPRs were reported to Poison control centers in the United States, the potential risk of methanol poisoning is concerning. Because of this concern, patients who have ingested more than a lick or taste of an MA- containing NNPR are frequently referred to a health care facility (HCF) for evaluation. However, acute MA ingestions resulting in metabolic acidosis has not been previously reported.

This retrospective study aims to review poison center data to describe our experience with MA ingestions.

* Corresponding author. 200 West Arbor Drive, MC 8925, San Diego, CA 92103-8925, USA. Tel.: +1 858 692 5257; fax: +1 858 715 6361.

E-mail address: [email protected] (A.B. Minns).

Methods

Our institutional review board reviewed and approved this retrospective case series. A retrospective chart review of our poison control system electronic database (Visual Dotlab, Madera, CA) for cases between January 1997 and December 2010 was performed. Search codes included the terms “methyl acetate” and “nail polish remover”; to ensure that all cases were identified, the database was searched both according to substance coding and within free-text descriptions of the cases. Cases were assessed by the investigators only after removal of all patient identifiers. Inclusion criteria included patients of any age with reported single-substance exposure to an MA-containing nail polish remover. Exclusion criteria were history of any coingestants or incomplete poison center records. When triaging poison center calls regarding MA exposures, referral to an HCF is considered if any of these criteria are met: (1) the patient is symptomatic, (2) large ingestions, and (3) exposure is a self-harm gesture. Regarding the amount ingested, there are no defined threshold doses for these products given the paucity of existing data in humans. Therefore, any patient suspected to have ingested more than a taste or lick is typically referred to an HCF.

0735-6757/$ – see front matter (C) 2013 http://dx.doi.org/10.1016/j.ajem.2013.02.038

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Information collected included basic demographic data as well as clinical data. These include, where available, side effects of MA (symptoms after initial exposure), duration of effects, dose and route of exposure, laboratory results, length of stay for MA-exposed patients treated in an HCF, and severity of clinical effects/outcomes. A metabolic acidosis was defined as having a serum Bicarbonate concentration less than normal according to the reporting facility (typically b 22 mmol/L). These data were collected and tabulated using a standardized spreadsheet template. medical outcome categories were standards used by all American Association of Poison Control Centers (AAPCC)- certified poison centers in the United States and have been published in detail elsewhere [3]. The categories used were minor, moderate, major effects, and death. See Table 1 for a description of the categories.

Results

Between January 1997 and December 2010, 219 MA-related cases were reported to the California Poison Control System. As noted above, those cases with coingestions were excluded, resulting in a total of 83 cases that were analyzed.

Females made up 52% of study subjects. Thirty-two cases (39%) were younger than 2 years, 43 cases (52%) were between 2 and 5 years old, 2 cases were between 6 and 9 years old, 2 cases were between 10 and 18 years old, and 4 cases (5%) were older than 19 years. Most (93%) of the ingestions were unintentional. Amount ingested was difficult to discern with 11 cases (13%) estimated to be more than a mouthful. Sixty-two cases (75%) were referred to an HCF. Of these, 75% of cases referred to an HCF had no effect, and 25% of cases had a minor effect. There were no major effects, including deaths reported. One case received single-dose activated charcoal, and 1 case received intravenous fluids as therapy. All other cases were observed only. Of call cases, including home and HCF cases, 63 (76%) had no symptoms. Vomiting was observed in 12 cases (14%); drowsiness, in 1 case; ataxia, in 1 case; abdominal pain, in 1 case; and throat/oral irritation, in 5 cases (Table 2).

Of the 4 adults (>=19 years), the reportED volumes ingested ranged from “a mouthful” to 150 mL. Of these 4 cases, 3 were Intentional ingestions. A 19-year-old woman who drank a half-bottle (size of bottle unknown) complained of a sore throat only. The largest ingestion reported, the 71-year-old woman who drank 150 mL, was asymptom- atic. There were 2 additional intentional ingestions, a 16-year-old adolescent girl who ingested 80 mL and had vomiting. In addition, a 17- year-old adolescent girl, who took “a sip,” was asymptomatic.

Fifty-three percent of cases referred to HCF had at least 1 blood chemistry panel done with 27% having more than 1 chemistry panel performed. One patient (a 2-year-old male) ingested an estimated

12 mL of Fung-Off No Lift fungal liquid for nails. The amount

Table 1

AAPCC medical outcomes

Category Description

Minor Development of some signs or symptoms as a result of the exposure, but they were minimally bothersome and generally resolved rapidly with no residual disability or disfigurement.

Moderate Development of signs or symptoms as a result of the exposure that were more pronounced, more prolonged, or more systemic in nature than minor symptoms. Usually, some form of treatment is indicated. Symptoms were not life threatening, and the patient had no residual disability or disfigurement.

Major Development of signs or symptoms as a result of the exposure that were life threatening or resulted in significant residual disability or disfigurement.

Death The patient died as a result of the exposure or as a direct complication of the exposure.

Medical outcome categories used by AAPCC-certified poison centers in the United States.

Table 2

Symptoms reported

ingested was determined based on the volume missing from the bottle. The percentage of MA in the product was not known. He had an initial serum bicarbonate of 17 mmol/L and an anion gap of 16 approximately 3 hours after the ingestion. No intravenous fluids were administered before the initial Blood draw. The laboratory abnormalities resolved after a period of observation alone, and the patient was discharged from the emergency department. There was no renal dysfunction.

Discussion

Nail polish removers consist primarily of organic solvents including acetone, ethanol, methanol, or Isopropyl alcohol. Acetone- free products often contain ethyl acetate, MA, or butyl acetate.

Methyl acetate has been demonstrated to be stoichiometrically hydrolyzed to methanol in vitro and that the reaction is rapid. A study by Mizunuma et al [2] demonstrated that almost 60% of MA added to blood was converted to methanol in 2 hours, and MA disappeared in 8 hours [4]. To our knowledge, there are no data on Interindividual variation in in vivo hydrolysis of MA in humans. Methanol is slowly converted hepatically, first to formaldehyde via alcohol dehydroge- nase, then to formic acid via acetaldehyde dehydrogenase. These 2 metabolites, formaldehyde and formic acid (formate), cause the toxicity associated with methanol poisoning. Formic acid inhibits cytochrome oxidase activity and cellular respiration resulting in tissue hypoxia and lactic acid formation. Accumulation of both formate and lactate contributes to an anion gap acidosis. Formate is also responsible for ocular toxicity including Visual disturbances and blindness [5,6].

Despite the frequency of poison center reports, there is a paucity of reports of toxicity in the literature regarding MA. Optic neuropathy from sniffing MA-containing paint thinner has been reported, however these products contain other organic solvents such as methanol and toluene, therefore toxicity from MA alone cannot be determined [7].

This study has several limitations. Methodological limitations of retrospective analyses from poison center data include possible insufficiencies and inaccuracies. Data collection may not have been recorded in a consistent manner given the variability among personnel at different poison centers. Adverse effect symptoms may not have been completely recorded, due to lack of information. Furthermore, when recording doses, overestimation is common to ensure conservative treatment of worst-case scenarios [8]. Self- reported information is not the most reliable source, and medication histories are often ambiguous. Many patients do not keep count of the remaining fluid in a bottle, which limits our ability to access an objective dose.

Most of our cases involve children. Significant bias may have been introduced especially among this group due to unproven ingestion [8]. laboratory confirmation that MA was actually ingested was not performed because plasma MA concentrations are not routinely available. In addition, methanol concentrations were not performed. The availability and turnaround time of this test vary from institution to institution and, in general, are not obtainable in time to change the acute management of a patient.

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Conclusion

To our knowledge, this is the first retrospective review summa- rizing cases of MA ingestion. Methyl acetate ingestions were not associated with the development of a clinically significant metabolic acidosis, and observation at home may be considered for minor unintentional ingestions. However, a prospective study is needed to exclude the risk of home observation.

References

1. Regulation For Reducing Volatile Organic Compound Emissions From Consumer Products, Subchapter 8.5 Consumer Products, 94509; http://www.arb.ca.gov/ regact/midterm2/isor.pdf.
2. Mizunuma K, Kawai T, Yasugi T, Horiguchi S, Iwami O, Ikeda M. In vitro hydrolysis of methyl acetate, a limitation in application of head-space gas chromatography in biological monitoring of exposure. Toxicol Lett 1992;62:247-53.
3. Bronstein AC, Spyker DA, Cantilena LR, Green JL, Rumack BH, Dart RC. 2010 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS). Clin Toxicol 2011;49:910-41.
4. Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE). Opinion on the results of the Risk Assessment of: Methyl acetate. http://ec. europa.eu/health/archive/ph_risk/committees/sct/documents/out142_en.pdf.
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6. Seme MT, Summerfelt P, Henry MM, Neitz J, Eells JT. Formate-induced inhibition of photoreceptor function in methanol intoxication. J Pharmacol Exp Ther 1999;289: 361-70.
7. Ogawa Y, Takatsuki R, Uema T, Seki Y, Hiramutsu K, Okayama A, et al. Acute optic neuropathy induced by thinner sniffing: inhalation of mixed organic solvent containing methyl alcohol. Ind Health 1988;26:239-44.
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