ABSTRACT

This white paper quantifies an opinion regarding the relative consumer risk to exposure to metofluthrin in Nutone HAVEN_TM by evaluating relative acute and subchronic toxicity levels with the recommended amount and usage times for the product.

 The EPA lists toxicology as the best method by which to assess a potential hazard. While there are several toxicology categories listed on the MSDS sheet, the two most applicable are acute and subchronic inhalation, as HAVEN_TM is delivered as an airborne mist to envelop an outdoor patio space. The relevant conclusions of this study are as follows with regard to metofluthrin:

 Acute inhalation exposure

Target: LC50 should be below 1.08 mg metofluthrin / L air

HAVEN_TM: 0.0675 mg metofluthrin / L air

Subchronic inhalation

Target: NOAEL should not exceed 16 mg metofluthrin / kg body weight / day

HAVEN_TM: 5 mg metofluthrin / kg body weight / day

  After review of the toxicology data, the opinion of this report is that the quantity of metofluthrin present in Nutone HAVEN_TM is not expected to pose a risk to consumers based on the published toxicology limits and classifications.

On a warm summer night, a group of friends and family gathers at dusk around a patio table. Torches are lit, food and drinks are served, and music is playing. As the group settles in to enjoy their evening, one of the guests smacks the back of his neck. A look of unrest on the faces of the hosts eventually melts away, as they see no further signs of an attack. To their horror, another guest starts swatting; then another. Soon, all the guests start moving around, distracted from the conversation by an invisible intrusion. The hosts dejectedly suggest moving the party into the kitchen, succumbing to the realization that their peaceful outdoor evening has been thwarted.

 Repelling insects is a critical part of maximizing the enjoyment of an outdoor living space. They are prevalent all over the world, easily capable of destroying any outdoor event. Worse, they carry diseases such as Zika, West Nile, and Lyme. Though the problem has existed for as long as people have owned backyards, it has not yet been solved due to the complexity of the repellency mechanism coupled with concern over the effects of the products on humans. Researchers have developed natural repellents, but Consumer Reports confirmed that they are largely ineffective. While chemists have not agreed on a universal solution, several formulas have emerged as the best options to address mosquitos.

 Among the popular synthetic options, metofluthrin has exhibited very high levels of efficacy. This study from Journal of Insect Science found metofluthrin to repel an average of 73% of the test-subject mosquitos. The delivery method plays a small factor, but generally, the more metofluthrin released per volume of test space, the more effective the product. The EPA ascribes toxicology as the best method to identify a potential hazard. The study states that the dose of substance to which a person is exposed is just as important as how toxic the substance is.

 This white paper will review the relevant toxicology categories and exposure levels associated with repellency products for consumer use, list metofluthrin’s toxicology levels compared with other similar products by reviewing EPA and FDA publications, and render an opinion about the relative risk of metofluthrin for patio insect repellency.

 The objective of the paper is to provide consumer confidence in Nutone HAVEN_TM by comparing its toxicology levels to other known compounds toxicologically viewed as low-risk by the EPA.

 Per the EPA study mentioned above, toxicology will be used to evaluate metofluthrin and to compare it with other similar technologies. It is important to note that a given substance is “toxic” only beyond the concentration (or level) at which it becomes poisonous. It does NOT a specific group of substances. Stated differently, the overall toxicity of a given substance depends on its dosage. Over-exposure to toxic levels is even possible with water, as about 6 liters (1.6 gallons) of water consumed at once would reach the level of the median lethal dose for a 165lb adult.

 The International Union of Pure and Applied Chemistry (IUPAC) defines two applicable kinds of toxicity that can be used to evaluate metofluthrin. They are defined below.

Acute toxicity – adverse effects occurring following oral or dermal administration of either a single dose or multiple doses of a substance given within 24 hours, or an inhalation exposure of 4 hours. Adverse effects need to occur within 14 days.

Chronic toxicity – development of adverse effects resulting from long-term exposure. It can manifest as either direct lethality or (more often) as symptoms such as stunted growth, reduced reproduction or behavioral changes.

            Sub-chronic inhalation toxicity – adverse effects occurring as a result of the repeated daily exposure of experimental animals by inhalation for part (approximately 10%) of a lifespan.

Acute exposure is quantified by five categories in which it can occur:

1)      Oral LD50 – the single dose of an ingested substance that kills 50% of a test sample, in mg substance/kg body weight

2)      Inhalation LC50 – the concentration of a chemical in air or water that kills 50% of a test sample from a single exposure, in mg substance / L air or water

3)      Dermal LD50 – the single dose of a contacted substance that kills 50% of a test sample, in mg substance/kg body weight

4)      Eye effects – level and/or timeframe of reversibility of corneal opacity

5)      Skin effects – severity of irritation at 72 hours after contact with substance

The Globally Harmonized System of Classification and Labeling (GHS) classifies the above 5 types of acute toxicity into four classes:

1)      Class I: highly toxic and severely irritating

2)      Class II: moderately toxic and moderately irritating

3)      Class III: slightly toxic and slightly irritating

4)      Class IV: practically non-toxic and not an irritant

Finally, [sub]chronic toxicity is evaluated by a No Observed Adverse Effect Limit (NOAEL) and Lowest Observed Adverse Effect Limit (LOAEL). Though there is no consistent, standard definition for NOAEL and LOAEL, it is defined based on expert opinion upon review of long-term exposure of test samples to a test substance. The difference in the two designations is that LOAEL is used in place of NOAEL when adverse effects are observed at all dosage levels.

 These exposure mechanisms and severities provide the basis for the opinion of this paper as to the suitability of metofluthrin for consumer use. Comparing the GHS-defined short and long-term exposure levels of metofluthrin against other known substances provides the basis for confidence in its use in outdoor spaces.

With the above definitions of acute and chronic toxicity, the table below describes the respective toxicity levels of metofluthrin, DEET, citronella oil, and neem (a natural pesticide included for reference).

Table 1: Acute and chronic toxicology in comparison of metofluthrin with other similar category products

As the product is dispensed into the outdoor space as a vapor, the primary concern is inhalation, both acute and subchronic. Acute oral, dermal, eye and skin effects of metofluthrin all fall in similar ranges to the other compounds included in the chart.

NuTone HAVEN_TM contains 4% metofluthrin by mass. Four fixtures protect 400 ft², so a patio of that area has an air volume of 1600 ft³, assuming a 4 ft protection height (top of a human sitting down). Assuming the patio’s air volume is entirely protected by HAVEN_TM, the acute exposure value is 0.0675 mg metofluthrin /L patio air, well below the lowest acute inhalation limit of pure metofluthrin of 1.08 mg/L (HAVEN_TM’s limit is 2.08 mg/L per MSDS). A protection height of 1 ft (simulating the height of a crawling infant) would still only provide an acute inhalation exposure of 0.270 mg/L. These values confirm that the acute inhalation exposure limit is not approached.

 The other toxicity concern is subchronic inhalation, which is repeated exposure over time. Pure metofluthrin has a NOAEL of 16 mg substance/kg subject/day, according to Table 1. It is nearly impossible to determine the amount of the repellent vapor actually inhaled by a human over a period of time due to absorption rate, exposure conditions, respiratory rate, and unit. A study by Dartmouth provides a method to compute chronic daily intake (shown in Figure 1), which can be used to calculate NOAEL as defined above. The primary difference is the substitution of the subchronic 10% lifetime exposure duration for the “ED” term below, which the study defines as 30 years in chronic cases. With those definitions and assumptions, the subchronic inhalation level for metofluthrin in HAVEN_TM is 5 mg/kg/day, assuming 100% of the metofluthrin is inhaled by a 15 kg child, 2.5 hours per day, 90 days a year for 7 years.

Figure 1: Intake Equation, from which NOAEL can be derived

 Repelling insects is critical in order to maximize the enjoyment of an outdoor patio space. In order to achieve the best environment possible, product development teams are challenged to balance the efficacy of the repellant with ensuring the consumers remain entirely safe while using it. This study uses published toxicology data to assess the relative level of risk of metofluthrin as present in Nutone HAVEN_TM for consumer use on outdoor patios.

 Natural pesticides have very low-risk toxicology profiles but are largely ineffective. Among the common, EPA-registered pesticide options, metofluthrin exhibits acute oral and dermal exposures, and skin and eye effects similar to those of DEET, Citronella Oil and Neem. While those toxicology levels are important, the most applicable and likely consumer exposure scenarios are acute and subchronic inhalation.

 Acute inhalation, at its lowest level, for metofluthrin is 1.08 mg/L. HAVEN_TM exhibits an exposure of 0.0675 mg/L. Subchronic inhalation NOAEL is 16 mg/kg/day; HAVEN_TM has a NOAEL of 5 mg/kg/day. Both these values confirm that the relative risk of HAVEN_TM for consumer use is extremely low, and its toxicology profile is well below published targets.

 It is smart and responsible for consumers to ensure they are not putting their families and friends into a potentially harmful situation by exposing them to excessive quantities of pesticides. To that end, the EPA and toxicologists have evaluated hundreds (if not thousands) of repellants to identify and define exposure levels and dosage mechanisms to protect consumers. The above summary of metofluthrin’s toxicology profile confirms that the levels contained in Nutone HAVEN_TM fall well below the published exposure limits.