Frequently Asked Questions
©2004 RKD Peterson
Answers to FAQ:
Q1. What do you mean by reasonable worst-case exposure?
A1. As the name indicates, it is the scenario in which a person is expected to be exposed the most. It does not consider every parameter to be in its most unfavorable state (= worst case), but it presents a reasonable scenario in which a person is most exposed to, in this case, the insecticides. For example, in our acute dermal exposure assessment, we assumed that all subgroups (infants, toddlers, youth, adult female and adult male) are outside for 6 hours from when the spray passes, and that they are minimally clothed (e.g., the baby is in diapers only), so most of the skin is exposed to receive deposition from the spray. When you look at it this way, it may seem silly to think that a baby will be outside wearing only a diaper for 6 hours at night (mosquito adulticides are sprayed in the evening), from 9pm to 3am. In the case of acute inhalation exposure we assumed that they are outside for 6 hours breathing at a moderate rate as if they are exercising the entire time.
Q2. What do you mean by a tier-1 risk assessment?
A2. A tier-1 risk assessment is the initial screening and may be considered a worst-case assessment. It uses very conservative assumptions, such as the ones mentioned above, and all parameters are overestimated. If the risk estimates from these very conservative assumptions are below levels of concern, i.e., are considered acceptable, no refinements of the risk assessment are necessary. If the risk estimates are not acceptable at tier-1 level, then we need to incorporate more detailed and realistic data for key parameters. Higher tier assessments result in more realistic estimates of exposure and risk, but in tier-1 assessments we always start with very conservative assumptions that always err on the side of environmental and human-health safety.
Q3. What do you mean by “reference dose (RfD)”?
A3. A reference dose (RfD) is a chemical-specific dose, derived from a NOAEL (no-observed-adverse-effect-level) or a LOAEL (lowest-observed-adverse-effect-level) with uncertainty factors applied. A NOAEL is the dose at which no adverse effects were observed, and to that dose, uncertainty factor are added. In other words, it is the dose to which the people (including potentially sensitive subgroups) can be exposed on a daily basis without experiencing deleterious effects. Usually the RfD refers to an exposure per day over an entire human lifetime. For example, the acute dermal NOAEL for permethrin is 500 mg/kg/day from a study in rats. It means that at the dose of 500 mg/kg body weight/day no adverse effects were observed in rats. We divide that dose by 10, to account for interspecies differences, since the study that determined the NOAEL was done in rats, not humans. Then we divide it again by 10 to account for intraspecies differences (humans are not all the same, so that accounts for people who may be more sensitive to the chemical). That gives us a RfD of 5 mg/kg/day.
For pyrethrins (insecticidal chemicals extracted from chrysanthemum flowers), the RfD is 0.044 mg/kg/day. This RfD is based on the most sensitive LOAEL (42.9 mg/kg/day), which is the dose from a chronic toxicity study in rats. At that dose, there was an increased incidence of thyroid follicular cell hyperplasia. All other LOAEL from a battery of other toxicity studies with pyrethrins were greater (meaning less toxic) than the chronic toxicity LOAEL. The NOAEL from this study was 4.37 mg/kg/day. An additional 100-fold safety factor is applied to this value, so the RfD is 0.044 mg/kg/day. Therefore, EPA has determined that we can be exposed to as much as 0.044 mg/kg/day each day over a lifetime without experiencing adverse effects.For certain chemicals, additional safety factors may be applied to account for increased sensitivities for infants, children, and pregnant women.
Q4. What is a “risk quotient (RQ)”?
A4. A risk quotient (RQ) is the ratio of the potential exposure to effect. It integrates toxicity and exposure and is calculated by dividing the calculated potential exposure by the RfD for that chemical. When the resulting number is less than 1, then it is typically below levels of concern.
Q5. Does your assessment account for extra sensitivities in people (e.g., asthmatic children, pregnant women, senior citizens)?
A5. Yes. As explained in question 2, when calculating the reference dose (RfD), we incorporate uncertainty factors, and we incorporate a 10X intraspecies uncertainty, which accounts for different sensitivities among people. In other words, we divide the dose in which no adverse effects were observed by 10 to account for that.
Q6. What do you mean by subchronic risk?
A6. Subchronic exposure to chemicals typically means that the person is exposed each day for a duration of several days to 6 months. In our study, we determined exposures per day for three months instead of 6 months because this resulted in greater exposures per day and therefore was a more conservative risk assessment, and we also believe that 90 days reflect better a mosquito adulticide spraying program.
Q7. Why didn’t you assess chronic risks?
A7. For subchronic risks, we considered a time frame of 90 days and 10 spray events, which is a reasonable worst-case scenario applicable to one season of mosquito adulticide spraying during a human outbreak of West Nile virus. Chronic exposures can be anywhere from 6 months in duration to a lifetime. We did not think it was appropriate to conduct a chronic risk assessment because that would not compatible with how mosquito adulticides are used. Our scenarios were defined as an outbreak situation when the adulticides are warranted.
Even if we were to analyze chronic risks, due to the chemical properties of the compounds, we do not anticipate that the chronic exposure will be greater than the subchronic exposure. Since the values of potential exposure are expressed in a per- day basis, we have to average time when calculating chronic risks. For example, if you take the highest subchronic risk quotient from our study, i.e., infants exposure to malathion, and calculate their chronic potential exposure assuming 30 years of exposure over a 75-year lifetime, we expect their exposure to be at least 1 to 2 orders of magnitude less than their subchronic potential exposure and risk.
Q8. How did you evaluate whether someone who is exposed to the insecticide will not get sick years later?
A8. We compared our reasonable worst-case estimated exposures to toxicological and EPA regulatory endpoints. These endpoints are based on numerous toxicity studies, some of which address the toxicity associated with short- and long-term and eventual development of adverse effects (i.e., do they get sick later?). For example, for pyrethrins, the following animal studies have been conducted: acute oral toxicity, acute dermal toxicity, acute eye irritation, acute dermal irritation, dermal sensitization, acute neurotoxicity, 90-day oral toxicity, 28-day dermal toxicity, 90-day dermal toxicity, 90-day inhalation toxicity, prenatal developmental toxicity, reproduction and fertility effects, chronic toxicity, carcinogenicity, gene mutation assay, chromosomal aberration study, subchronic neurotoxicity, developmental neurotoxicity, metabolism and pharmokinetics study, and dermal penetration.
We cannot state whether someone who is exposed to the insecticide will not get sick years later. However, we can state that our risk assessment and the current weight of scientific evidence suggest that this is unlikely to occur.
Q9. Why didn’t you conduct a cancer risk assessment for these insecticides?
A9. Of the active insecticidal ingredients (malathion, naled, permethrin, phenothrin, pyrethrins, resmethrin) and the synergist (piperonyl butoxide), only permethrin and resmethrin are considered to be potential human carcinogens of concern by the EPA at this time. Permethrin and resmethrin currently are undergoing re-registration by the EPA. As of this writing, both insecticides are considered possible human carcinogens.
We did not present a cancer risk assessment for permethrin and resmethrin in the article (explained on page 367), but we have conducted a risk assessment and determined that the risks were low, ranging from 0.00000017 to 0.00000022, which is less than the EPA level of concern of 0.000001. Our cancer risk assessment assumed exposures to permethrin or resmethrin from mosquito control each day of the year for 30 consecutive years. Therefore, the risks above represent a worst-case lifetime cancer risk.
Q10. Why didn’t you conduct an exposure and risk assessment for applications by airplane? Wouldn’t the exposure by airplane be greater than by ground application?
A10. We are currently conducting research involving human exposure and risk to aerial applications of mosquito insecticides. We did not include this assessment in our article because the purpose of the article was to evaluate reasonable worst-case exposures to humans. All of our initial modeling of human exposures to insecticides applied via aerial applications indicated that the exposures were less than those from ground applications. This is because aerial applications are disseminated between 150 and 200 feet above the ground. There is substantial dispersion of the insecticides when applied from this height, which results in less concentration of the insecticide in both the air and on the ground when compared with ground applications. Therefore, ground applications would represent greater human exposures and would be more conservative than aerial applications for assessing risk. This is discussed in our article (page 367, column 3) and is supported by NYCDOH (2001).
Q11. Why didn’t you assess exposure through contaminated drinking water?
A11. Because of the physical and chemical properties of all of the insecticides, any presence in potable water would be very low and brief. Based on the method of application and their properties, the insecticides are not expected to enter groundwater or other drinking water sources. These insecticides may drift in small quantities onto surface bodies of water such as streams and ponds, but human consumption of that water is not expected.
Other risk assessments evaluated human exposure through drinking water and swimming and have found those routes of exposure to be negligible (see article page 368, column 2). Also see NYCDOH (2001).
Q12. I have heard that exposure to piperonyl butoxide (PBO) is worse than any of the insecticides. Is that true?
A12. No, the current weight of scientific evidence suggests that PBO is much less toxic than the insecticides used for adult mosquito control. For example, the EPA acceptable daily exposure to PBO is 9 to 630 times greater than the insecticides evaluated in our study. PBO is classified as a possible human carcinogen by EPA based on statistically significant increases in hepatocellular tumors in mice. However, because the liver tumors occurred only at excessive doses, the EPA has determined that quantification of cancer risks is not necessary for PBO. Additionally, there is no evidence that PBO causes mutagenicity.
Q13. Why didn’t you examine the risks from exposures to the solvents in the sprayed insecticides?
A13. There has been work on exposure and risk to solvents and other inert ingredients in pesticide formulations. In many cases, the solvents are indeed more toxic than the insecticides themselves. However, many of these solvents are volatile and a person’s exposure and therefore risk would be very low (see article page 371, column 2). Also see NYCDOH (2001).
Q14. Are you suggesting that we should use insecticides against adult mosquitoes all of the time because their risks to people are below EPA levels of concern?
A14. No. Our risk assessment evaluated a reasonable worst-case scenario in which a West Nile virus outbreak was occurring in people. When there is an outbreak of the disease in people, the U.S. Centers for Disease Control recommends that the affected area be treated for adult female mosquitoes with an insecticide. These insecticides, called adulticides, are applied via ground equipment or airplane. We and the Center for Disease Control and Prevention (CDC) recommend an integrated mosquito management approach, which involves managing mosquitoes only when needed.
Q15. Does your assessment mean that there is zero risk from exposure to mosquito insecticides? Are you saying that the mosquito insecticides are safe?
A15. No. There is no such thing as zero risk because everything entails some degree of risk. In our assessment, we concluded that human-health risks from residential exposure to mosquito insecticides are low and are not likely to exceed EPA levels of concern. We did this by comparing our reasonable worst-case estimates of exposure to toxicological endpoints. As such, we determined a mathematical value, the risk quotient (RQ). The RQ is a measure of risk, and in all cases, the RQ’s were below levels of concern.
Asking if mosquito insecticides are safe is an imprecise way to ask the question. Like all substances, activities, and organisms, insecticides have the inherent ability to cause harm. Insecticides, by themselves, are neither acceptably risky nor unacceptably risky. Rather, how insecticides are used can be acceptably or unacceptably risky. For example, spraying mosquito insecticides every other day in the same location throughout an entire summer regardless of the number of adult mosquitoes would be unacceptably risky and the costs would certainly outweigh the benefits. However, the use of mosquito insecticides in the presence of high numbers of disease-carrying adult mosquitoes (such as in a West Nile virus outbreak) would most likely constitute acceptable risk to people based on our risk assessment and the risk assessments of others. The EPA has determined that these insecticides can be used safely as long as they are applied according to label restrictions. Because safety is a value-laden term, we do not (and will not) state that anything is “safe.” We assess, compare, and communicate risks based on established criteria.
NYCDOH (2001) - New York City Department of Health Adult Mosquito Control Programs - http://www.nyc.gov/html/doh/html/wnv/feis.shtml
CDC - West Nile virus guidelines for surveillance, prevention, and control - http://www.cdc.gov/ncidod/dvbid/westnile/resources/wnvguidelines2001.pdf