Insecticide Absorption from Indoor Surfaces: Hazard Assessment and

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Chapter 24

Insecticide Absorption from Indoor Surfaces Hazard Assessment and Regulatory Requirements 1

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Peter E. Berteau , James B. Knaak , Donald C. Mengle , and Jay B. Schreider 2

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Hazard Evaluation Section, California Department of Health Services, Berkeley, CA 94704 Medical Toxicology Branch, California Department of Food and Agriculture, Sacramento, CA 95814

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Insecticides are often applied indoors where dermal absorption from surfaces as well as inhalation exposure may occur. Children may also have oral exposure due to hand-to-mouth activities. Poison control centers frequently receive complaints of illness following such applica­ tions. These complaints may be coincidental due to odors or to a systemic toxic action from an ingredient. Using an appropriate algorithm, surface exposure and total absorption was calculated for chlorpyrifos, dichlorvos and propoxur. With each of these insecticides, the dose calculated might provide a toxic dose, particularly to an infant. More data are, therefore, needed for these and other insecticides to ensure that the levels in the air and on treated surfaces will not be injurious to health. Such data will include bioavailability of surface residues, rate of transfer from surfaces and dose-response data. Pending such data, risk assessments based upon health-protective assumptions should be used to decide the safety of various components. Pesticides, particularly those containing cholinesterase inhibitors, are often applied to combat insect infestations in indoor environments. The treated sites may include room air, closets, storage areas, baseboards, window sills, cracks, crevices, inaccessible areas, house plants, pets, pet beds, beds, upholstery, carpets and smooth floor areas. Respirable droplets or vapor may be inhaled during or after pesticide spraying and fogging operations. Human exposure may also occur as a result of dermal contact with treated or exposed surfaces followed by percutaneous absorption of the chemicals. In small children, there is also oral exposure through hand-to-mouth transfer. Thus, the cholinesterase-inhibiting pesticides represent a potential acute human health hazard when used indoors, particularly for small children. An appreciable number of persons in California require poison center and medical attention each year following exposure subsequent to treatment of homes, apartments, and offices by structural pest control operators, landlords, or employers as well as by adult household members. In Table I some of the California Department of Food and Agriculture's (CDFA) priority cases for 1984 which involved structural treatment are indicated. In 1984 the San Francisco Poison Control Center and its Toxic Information Center received 1,180 calls on pesticides. Of these calls, 340 involved insecticides and children under the age of 6. The symptoms and history of exposure were in agreement in 41 percent of the cases involving illnesses. The place where the exposure

0097-6156/89/0382-0315$06.00/0 ° 1989 American Chemical Society

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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occurred, indoors or outdoors, was not recorded. The most common symptom was nausea. Large numbers of poisoning cases due to cholinesterase inhibitors are handled each year by the Los Angeles Poison Control Center and the San Diego Poison Information Center. The great majority of the exposures to these pesticides occur in the home. Young children clad in little more than diapers are at risk playing on previously sprayed surfaces such as floors, carpets, furniture, and bedding. The higher body surface area to volume ratios of children compared to adults increases the likelihood that children will receive a toxic dose. Mild cholinergic symptoms are difficult to identify from normal childhood functions such as drooling, diarrhea, or excessive urination. In this connection, it should be noted that not all the subjects exposed are sick from symptoms of cholinesterase depression; many reports of illness may be coincidental due to the unpleasant odor of some of the pesticide chemicals and adjuvants used, resulting in a nauseous response. However, as will be shown, these concerns necessitate an assessment of the potential adverse health effects from the indoor use of these types of pesticides. The use of non-volatile pesticides for crack and crevice treatment is not expected to be hazardous to human health, because dermal contact is minimal and inhalation is not a significant route of exposure. Volatile pesticides such as dichlorvos are especially hazardous if the enclosed area is not adequately ventilated prior to reentry.

TABLE I. EXAMPLES OF REPORTED PESTICIDE ILLNESSES FROM STRUCTURAL APPLICATION

Applicator

Number Sick

Landlord

Circumstances

Pesticide

Two residents and three visitors to an apartment house.

Chlorpyrifos

Employer

13

County office building. Building evacuated.

Chlorpyrifos

Structural Pest Control Operator

10

Hospital employees.

Chlorpyrifos, bendiocarb, and diazinon

Four-month-old child.

Chlorpyrifos

All five family members.

Methyl bromide

School district office workers.

Propoxur

Structural Pest Control Operator Structural Pest Control Operator Employer

5

15

Mobay Chemical Company submitted two reports to the California Department of Food and Agriculture concerning the use of propoxur for flea control indoors. According to the reports, infant children are expected to be at risk when they come in contact with propoxur-treated floors and carpets. On the basis of these studies, Mobay made a label amendment on their indoor use product containing propoxur that explicitly limited indoor applications to surfaces along baseboards and inacces-

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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sible areas and recommended against the use of propoxur on large floor areas or floor coverings or as a space spray. In Table II an outline of a worst case situation where a scantily clad infant is playing in a room is given. Many of the parameters stated are measured values which can be located in various textbooks. Others are assumptions or "educated guesses" based upon little or no supporting data.

TABLE II. WORST CASE ASSUMPTIONS FOR AN INFANT PLAYING IN A ROOM

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The 50th percentile body weight of a 6—9 month old child is approximately 7.5 kg (I). The body surface area of a 6—9 month old child is approximately 0.45 m (4.8 f t ) (2).

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A n infant's hands account for approximately 4.8 percent of the total body surface area (2). Contact with the carpet will remove the total dislodgeable pesticide (12.9 mg/m ). 2

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2

A child will play on approximately 18.6 m (200 f t ) of treated carpet. A child is in contact with a maximum of 25 percent of the available floor space (4.6 m ) and dermal contact takes place in four hours or less. 2

Dermal exposure is uniformly surface area.

distributed

over 50 percent of the body

It is assumed that all pesticide on the hands is s u b s e q u e n t l y ingested (approximately 9.6 percent of dermal exposure). It is assumed that airborne exposure is c o n t i n u o u s for 24 hours per day. It is assumed that both the inhalation and oral doses are 100 percent absorbed.

The three pesticide chemicals which were initially considered by us were propoxur (Baygon), dichlorvos (DDVP), and chlorpyvifos (Dursban). The calculations which were used in developing an exposure dose are outlined in the forthcoming tables.

Propoxur P r o p o x u r , a carbamate insecticide the structure of which is s h o w n below, was

II

i

,0-C-N-CH3

introduced in 1971 as a low hazard vector control agent to replace D D T in developing

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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countries. Its low dermal toxicity, > 2400 mg/kg, in the rat and reversible inhibitory action on acetylcholinesterase make it a reasonably safe material to use for mosquito control in and around the home. Its high oral toxicity (LD 50, 83 to 86 mg/kg in the rat), however, should be recognized when handling this material indoors. Propoxur is utilized for its rapid knockdown properties due to its vapor toxicity and its long-term residual properties. Villages in developing countries sprayed with p r o p o x u r were protected from mosquitoes for as long as 30 weeks after spraying (3). Propoxur is often used in combination with dichlorvos in pesticide foggers to provide residual insecticidal properties to the registered product. This residual property is the subject of concern as a possible hazard in dwelling places when propoxur is used alone or in combination with dichlorvos in foggers that deposit residues on furniture and carpets. Acceptable levels for propoxur on surfaces that persons might have dermal contact with have not been established by regulatory agencies. A recent risk assessment made by Hackathorn and Eberhart (4), which is summarized in Table III, involved the use of propoxur on carpets for flea control. It indicated that an adequate safety factor does not exist for infants playing on carpets after treatment. If the child spends four hours on the floor, this time would be considered short-term exposure.

TABLE III. CALCULATION OF A WORST CASE EXPOSURE DOSE FOR AN INFANT EXPOSED TO PROPOXUR Total dose

= 100% inh. exp. + 20% dermal exp. + 100% oral exp. body weight = 0.26 mg + 0.2 (53.6 mg) + 5.7 mg 7.5 kg

= 2.2 mg/kg Inhalation exposure

= max. air cone, x resp. min. vol. x exp. period 3

3

0.022 m g / m x 0.5 m / h r x 24 hr = 0.26 mg Dermal exposure

= (carpet area contacted) x (propoxur residue available) — amount of propoxur ingested = 4.6 m

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2

x 12.9 m g / m - 5.7 mg

59.3 - 5.7 mg = 53.6 mg Oral exposure

= (carpet area contacted) x (propoxur residue available) x (0.096) 59.3 mg x 0.096 5.7 mg

Thus, the worst case exposure value is 2.2 mg/kg.

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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Based on human exposure, the lowest effect level for a single dose is 0.36 mg/kg which produced mild cholinergic symptoms, stomach discomforts, blurred vision, facial redness, and sweating. In repeated applications 0.15 to 0.20 mg/kg of propoxur was administered orally five times in 30 minutes resulting in 60 percent cholinesterase depression but no symptoms (5). Thus, there is a definite possibility for an adverse reaction in a very young child who plays on a treated carpet. Similar calculations were performed for a 12-year-old child (total dose = 0.04— 0.31 mg/kg) and for an adult (total dose = 0.03-0.11 mg/kg). In these cases the likelihood of a toxic reaction appears to be considerably less. Even less safety would apply to applications to smooth floor surfaces. In the assessment, a number of assumptions were made that may result in estimating more exposure than actually occurs. For instance, studies conducted on the dog by Raabe (6) demonstrated that the lung may absorb only 50 percent of an inhaled air pollutant and not 100 percent. Studies by Knaak and Wilson (7) showed that the rate of absorption of pesticides through skin decreases exponentially as the concentration decreases on the skin. Pesticide concentrations amounting to 1.0 jug/cm of skin are absorbed at rates amounting to 0.01 jug/hr/cm (1.0 percent per hour or less). A t this rate, 100 hours is required to absorb 1.0 jug of propoxur. Feldman and Maibach (8) used a dose of 4.0 Mg/cm on skin in their studies with propoxur. Approximately 20 percent of the topically applied dose was absorbed and eliminated over the study period of five days. Based upon these figures, the average rate of absorption over the five-day period was 0.007 jug/hr/cm . The relationship between the dermal dose of propoxur and its effect (dermal dose cholinesterase response) is not known. Gaines (9) reported a dermal LD50 in the rat of greater than 2400 mg/kg. This work suggests that propoxur is not readily absorbed or the inhibitor-acetylcholinesterase complex is short lived. In any case, data on the relationship of exposure and dermal dose cholinesterase response do not appear to be adequate to assure safe use in households, especially if carpets, open floor areas, furniture, or bedding are treated. 2

2

2

2

Dichlorvos Dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP) the structure of which is shown below was one of the first of the vinyl phosphate insecticides to be discovered.

O CH 0

|| ^ P - 0 - C H = CCl CH 0^ 3

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3

These compounds are formed by the Perkow rearrangement when a dihaloaldehyde or a dihaloketone is allowed to react with a trialkyl phosphite (10). The high vapor pressure of dichlorvos allows the material to penetrate spaces and kill insects. A concentration of 0.015 mg/m (16 m /day) for several hours is sufficient to control flies and mosquitoes in the home. The rapid disappearance of dichlorvos from air and surfaces in the home makes it ideally suited for treating insect infestations. A n airborne exposure level of 30 mg/m is capable of killing rats within a four-hour period. Industrial hygiene guides limit workplaces concentrations to 1.0 m g / m . A safety factor therefore exists for this chemical between the concentration required to control insects and those we 11-tolerated by adult healthy persons in the workplace. For safe use in the home, it would be desirable not to exceed a level of 0.01 m g / m in the room air for long-term exposure. Maddy et al. (VI) monitored dichlorvos residues in a home after fogging. In one or two hours after fogging, airborne residues were below 1.0 m g / m . Wipe samples taken from smooth surfaces during this study indicated that levels as high as 0.8 mg/100 c m were present on smooth surfaces after fogging. 3

3

3

3

3

3

2

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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These surface residues persisted over a period of seven hours. According to the monitoring and efficacy data on hand, the amount of dichlorvos initially released into the rooms, 2.8 to 5.7 m g / m , exceeded the amount, 0.015 m g / m , needed to control insects and might well be hazardous for some persons. A level of 0.015 m g / m was finally reached in one room 24 hours after the aerosol was released into the room. By using the same values as were used for propoxur, a calculation of a worst case exposure for an infant was made and is shown in Table IV. 3

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TABLE IV. CALCULATION OF A WORST CASE EXPOSURE DOSE FOR AN INFANT EXPOSED TO DICHLORVOS

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Using the same assumptions as were used for propoxur but assuming 100 percent absorption from the skin. 3

Maximum air concentration after 30 minutes aeration = 0.75 m g / m . Maximum surface concentration after 30 minutes aeration =0.8 mg/cm Inhalation exposure

For 4.6 m

2

=

cone, x resp. min. vol. x exposure time

=

0.75 m g / m x 0.5 m /hr x 24 hr

=

9 mg

3

2

3

2

(50 ft ) of carpet contacted by the child

Dermal exposure

=

Surface area contacted x dichlorvos residue available

=

4.6 m

=

368 mg — oral exp.

2

x 0.8 mg/100 c m

2

x 100

Assume all dichlorvos on skin of the hands is licked off. Oral exposure

Net dermal exposure

Total dose

=

Dermal exp. x fractional surface area absorbed

=

368 x 0.096

=

35 mg

=

368 — 35 mg

=

333 mg

=

9 + 333 + 55

„ mg/kg

7.5 =

50 mg/kg

It should be noted, however, that this calculation does not take into consideration the rapid metabolic breakdown of dichlorvos; consequently, a value of 50 mg/kg following a day's play on a treated carpet will be unreasonably high. However, the differences in the concentration attained versus the concentration required for insecticidal purposes suggest that dichlorvos should be reevaluated for efficacy as well as safety.

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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Chlorpyrifos Chlorpyrifos, an organic phosphorothioate insecticide, the structure of which is shown

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below,

was introduced into the marketplace by Dow Chemical Company in 1965 for the control of mosquitoes and other household pests. The dermal LD50 of this pesticide was determined to be 202 mg/kg in the rat (9) and the acute oral LD50 in the rat is 135 mg/kg (12). Studies with this cholinesterase inhibitor in several animal species, including man, indicate that plasma cholinesterase activity is depressed to a greater extent than red cell acetylcholinesterase. For example, workers applying chlorpyrifos were exposed to water suspensions (0.25 and 0.5 percent) of wettable powders while spraying mosquitoes. Plasma cholinesterase was reduced more than 50 percent with no commensurate reduction in red cell cholinesterase (13). A daily dose of 0.08 mg/kg for six months failed to depress red cell cholinesterase in the monkey, while levels of 0.4 and 2.0 mg/kg/day depressed plasma and red cell activity. Dogs wearing flea collars containing 8 percent chlorpyrifos lived without detectable clinical symptoms even though plasma cholinesterase was depressed 100 percent below that of preexposure values (14). A dermal absorption study (15) in human volunteers using 0.5 and 5.0 mg/kg of chlorpyrifos indicated that less than 3 percent of the applied dose was absorbed. A treatment area of less than 100 c m was used. The dose was left on the bare skin of the forearm for a period of 12 to 20 hours and then removed by showering. No changes in red cell acetylcholinesterase or plasma cholinesterase activity were seen. The half-life for the absorption into blood was 14 to 31 hours. The elimination halflife was determined from an oral study. The results of the dog flea collar and human volunteer studies need to be considered together. In the dog study the total body surface area was exposed to several milligrams of chlorpyrifos each day, while in the human study an area of only 100 c m was exposed (100 c m divided by 20,000 c m x 100 = 0.5 percent of total surface) to a single dose of the pesticide. In addition, chlorpyrifos was left on the skin of the dog for an extended period of time, while in the human studies chlorpyrifos was washed off 12 to 20 hours after application. The total surface area involved, the concentration per unit of surface area, and the length of the exposure period are important factors that must be considered. A dermal dose cholinesterase-response study is needed to clarify this relationship. 2

2

2

2

In separate studies involving chlorpyrifos, the safe use of chlorpyrifos was investigated in the home environment. Naffziger et al. (16) monitored the application of chlorpyrifos to floor coverings. Standard air sampling/gas chromatograph analytical procedures were used for air residues. Wiping procedures were used for carpets and vinyl floor covers. Table V gives the dose calculation for exposure of infants to chlorpyrifos using the same assumptions as were used for both propoxur and dichlorvos. In a personal communication from Dow sent on June 17, 1985, a lower dose is reported based upon a number of factors including the statement that chlorpyrifos is only 3 percent absorbed through the skin. However, the possibility of a toxic dose being absorbed by an infant under the conditions of application exists for chlorpyrifos as it does for propoxur and dichlorvos. The acceptable daily intake established by the World Health Organization for chlorpyrifos is 0.0015 mg/kg/day, and the minimal human response level has been reported to be 0.03 mg/kg (17).

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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BIOLOGICAL MONITORING FOR PESTICIDE EXPOSURE TABLE V. CALCULATION OF A WORSE CASE EXPOSURE DOSE FOR AN INFANT EXPOSED TO CHLORPYRIFOS Using the same assumptions as were used for propoxur, but assuming 100 percent absorption from the skin. Assume that the 0.5 percent spray is applied undiluted and that one hour is allowed for drying (i.e., prior to contact with the surface). Air concentration

=

0.015 m g / m

3

(kitchen dinette)

Average surface concentration = 0.0433 mg/100 c m

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Inhalation exposure

For 4.6 m

2

2

=

cone, x resp. min. vol. x exposure time

=

0.015 m g / m x 0.5 m / h r x 24 hour

=

0.18 mg

3

3

2

(50 ft ) of surface area contacted

Dermal exposure

=

Surface area contacted x chlorpyrifos res. available

=

4.6 m

=

4.6 x 0.0433 x 100 mg

=

19.9 mg

2

x 0.0433 mg/100 c m

2

Assuming all chlorpyrifos on the skin of the hands is licked off Oral exposure

Net dermal exposure

Total dose

=

Dermal exp. x fractional surface area absorbed

=

19.9x0.096

=

1.91 mg

=

19.9—1.91

=

18.0 mg

=

0.18 + 18.0+

1.91

7.5 =

2.68 mg/kg

Limitations of the Dose Calculations There are limitations in the validity of the doses calculated, which are mainly: 1. They do not consider metabolic breakdown (e.g., as with dichlorvos). 2. They do not consider cumulative effects. 3. The data are very limited (e.g., surface deposition data were located for only three pesticide chemicals). 4. Dermal absorption data are available for only a few pesticide chemicals. It should be noted that more information on rate of metabolic breakdown and extent of dermal absorption would generally result in lower values for the doses. On the other hand, the calculations do not address the probability that a child will continue to play daily on a treated surface. Although it is recognized that with most pesticides the level of chemical on the surface under consideration will attenuate each day, the repeated exposure, albeit to a successively reduced dose, will contribute to the

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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continued lowering of acetylcholinesterase in blood and other tissues and consequent possible development of toxic symptoms.

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Data That Would Be Useful for Setting Safe Levels Should a registrant wish to attempt to develop data which might indicate that a certain level of a cholinesterase inhibitor could be used indoors in room air or on open floor areas, carpets, furniture, or bedding, a considerable amount of new data would be needed. Examples of the kind of data that would be needed are safe indoor levels in the air and on treated surfaces such as smooth floors and carpets as well as furniture and bedding. T o establish these levels for a pesticide, the following information would be required, using standardized methods: 1. Levels of pesticide residues in room air through time after application. 2. Bioavailability of residues on surfaces (smooth floors, carpets, furniture, and bedding) through time after application. 3. Rate of transfer from surfaces (smooth floors, carpets, furniture, and bedding) to the skin and clothing of individuals. 4. Animal dose-response data from dermal and respiratory absorption studies. It would be necessary to determine the dose of a pesticide or mixture of pesticides in a product required to inhibit 50 percent red cell cholinesterase activity. These data should be used to evaluate and establish safe levels based on the procedure used for dislodgeable field foliage residues (18).

Methods for Collecting Required Data Methods for collecting required data involve extraction procedures and information on the rate of transfer to the subject, which are as follows: 1. Bioavailability a. Solvent wipes b. Solvent extraction procedures 2. Rate of transfer of dislodgeable pesticide residues a. Use of adults with pesticides b. Use of surrogate tracer materials (e.g., fluorescent clothing brighteners) c. Use of household pets such as small dogs Techniques for measuring bioavailability are currently limited to solvent wipes and solvent extraction procedures. Wiping procedures are preferred when it is impossible to remove samples of carpet or fabric for extraction. Carpet with pile not exceeding 1 cm. in depth should be used. In order to minimize the variability inherent in the wipe procedure, it is recommended that samples of carpet (12 x 12 inches) and fabric be used to collect pesticide residues. These samples may be extracted by a continuous solvent (water-surfactant) extraction procedure similar to the one used for dislodgeable residues on foliage (19). This procedure would make it possible for registrants to develop consistent and reliable information on the amount of dislodgeable pesticide deposited on or remaining on smooth floor surfaces (such as vinyl), carpet, furniture fabrics, and bedding through time subsequent to applications. Studies are needed to determine the rate of transfer (jug/hr) of the dislodgeable pesticide residue to the skin or clothing of individuals coming in contact with the treated surfaces. A study was conducted involving the transfer of the organophosphorus pesticide propetamphos (Safrotin) from a furniture fabric to clothing (20). The study involved a single individual repeatedly sitting and standing in order to simulate a typical home-type exposure. This procedure provided information on the rate of transfer of pesticide residues involving adults, but did not address the transfer of residues to young children playing on treated areas. This is a difficult problem, because studies involving the direct transfer of pesticides to the skin and/or clothing of young children are an unacceptable form of human experimentation. It may be quite possible to address this indirectly by using surrogate tracer materials such as nontoxic

Wang et al.; Biological Monitoring for Pesticide Exposure ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

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fluorescent clothing brighteners to quantify the transfer of residues from surfaces to skin or clothing. If this is possible, information on the relationship (ratio of brightener to pesticides) between the tracer and the pesticide under investigation will have to be independently developed. Dogs might be used as animal models for developing such data in a household setting. Procedures already exist for determining the relationship between a dermal dose and cholinesterase inhibition (7). Those procedures could be extended to cover absorption via lungs and the respiratory tract. The data collected (rate of transfer, dislodgeable residue, and dermal dose response information) could be used to set safe levels in a manner described by Knaak and Iwata (21). The procedures of Knaak et al. (22) require that a safe level be known for some pesticides presently in use indoors. A t the present time, the recommended use of propoxur and chlorpyrifos are being re-examined and therefore cannot be used as standards for setting acceptable levels indoors.

Conclusions and Recommendations This chapter indicates that it might be possible for the various regulatory agencies to set acceptable levels for pesticide residues in room air and on treated surfaces subject to considerable skin contact in households. Information from studies performed by the registrants would be needed on household residues deposited from foggers, compressed air sprayers, and other application procedures to determine the amount of the residues remaining in air and on surfaces after each application. The levels should be compared against safe levels still to be established for residues in air and levels for surface residues for each pesticide. Should a registrant wish to justify the use of a cholinesterase inhibitor in treatment of smooth floor surfaces, rugs, furniture, bedding, or entire rooms where people reside, it is recommended that the following data be submitted on each active ingredient such as propoxur, dichlorvos, and chlorpyrifos or any other cholinesterase inhibitor. 1. Information on room air levels of the pesticide and total dislodgeable residues on smooth floors, carpets, furniture, and bedding after application of the product containing the active ingredient of interest. The dissipation of these residues should be followed through time or until the residues completely dissipate (i.e., 2, 4, 8, and 24 hr; 3, 6, 9, 12, 21, 24, 27, and 30 days). 2. Dissipation data plotted in j u g / c m against time (semi-log paper) should be determined and therefore, if possible, the half-life in the room air and of the dislodgeable residue on the surface from which it was taken. 3. Rate of transfer (jug/hr) of the dislodgeable residue from smooth floors, carpet, furniture-fabric, and to the skin of surrogate animals. Five-month-old Beagle dogs should be used to study contact exposure in treated rooms. The same animals should be exposed sequentially to different levels of dislodgeable residues present in the house, starting with the level deposited at application of twice the recommended amount and then exposing the animals at the recommended amount. These exposures should begin just as soon as the application has been completed and any ventilation period on the label has expired. Separate exposure studies should begin when residues are found to be one-half those at the time of application and also when they reach one-fourth those found at the time of application. Dislodgeable residue in / u g / c m versus dose transferred to the animal in //g/hr should be plotted. The slope of the line in c m / h r should be determined. T o remove residues for measurement, the dogs can be washed with soap and water at sampling times. 2

2

2

4.

Dermal dose-cholinesterase response data in the rat for the technical or active material can be determined using the method of Knaak et al. (22).

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5.

A table of safe levels should be calculated using acceptable daily exposure levels (use results of dermal dose cholinesterase response studies) as indicated by Iwata etal. (18). In addition, for individual products formulated from these active ingredients, data should be required on air and surface residues resulting from the application of the products. Data is needed on the amount of dislodgeable residues that are deposited on smooth flooring, carpet, furniture, and bedding by applying the pesticide product in accordance with label-use instructions. In presenting the data, the registrant should use a dissipation curve developed with the technical material (active ingredient) to estimate when a safe level would be present from the use of a product in the room; the registrant should determine the level of dislodgeable residues at that time. If air and dislodgeable residues are at a safe level for infants to play in the room immediately at the end of a ventilation reentry period specified on the label, then the product should be considered safe to use as directed. In the State of California, regulatory action has already been taken in the form of advice to the registrant of the data needed on insecticide chemicals in products used indoors if registration is to continue to be permitted (reevaluation). The manufacturers and others who sell chlorpyrifos, dichlorvos, and propoxur have been notified. In addition, similar action will probably be taken on indoor use products containing carbaryl (Sevin), propetamphos malathion, and diazinon.

Literature Cited 1. Pomerance, H. H., Growth Standards in Children, Harper and Row, Hagerstown, M D., 1979, 225 pages. 2. Vaughan, V. C., III; McKay, R. J.; Nelson, W. E.; Textbook of Pediatrics, 10th Edition, Saunders, Philadelphia, London, Toronto 1975, 1,876 pages. 3. Wright, J. W.; Fritz, R. F.; Hocking, K. S.; Babione, R.; Gratz, N. G.; Pal, R.; Stiles, A. R.; Vandekar, M. Bull. World Health Org., 1969, 46, 67-90. 4. Hackathorn, D. R.; Eberhart, D. C., 1983, Report No. 1-83-42, Mobay Chemical Corporation. 5. Vandekar, M.; Plestrina, R.; Wilhelm, K. Bull. World Health Org., 1971. 6. Raabe, O. 1985 personal communication. 7. Knaak, J. B.; Wilson, B. W., 1984, American Chemical Society Symposium Series No. 273. 8. Feldman, R. J.; Maibach, H. I. Toxicol. Appl. Pharmacol., 1974, 28, 126-132. 9. Gaines, T. B., Toxicol. Appl. Pharmacol., 1969,14,515-534. 10. Perkow, W., Chem. Ber„ 1954, 87, 755-758. 11. Maddy, K. T.; Edmiston, S.; Fredrickson, A. S., 1981, Calif. Dept. Food Agric. report number HS-897. 12. McCollister, S. B.; Kociba, R. J.; Humiston, C. G.; McCollister, D. D. Food Cosmet. Toxicol., 1974, 12, 45-61. 13. Eliason, D. A.; Cranmer, M. F.; von Windeguth, D. C.; Kilpatrick, J. W.; Suggs, J. E.; Schoof, H. F., Mosquitos News, 1969, 29, 591-595. 14. Boyd, J. Pat, P.A.C.E. International, Dallas, Texas, 1985. 15. Nolan, R. J.; Rick, D. L.; Freshour, N. L.; Sanders, J. H. Toxicol. Appl. Pharmacol., 1984, 73, 8-15. 16. Naffziger, D. H.; Spfenkel, R. J.; Mattler, M. P., Down to Earth. 1985, 41, 7-10. 17. 1972 Evaluations of Some Pesticide Residues in Food. The Monographs. World Health Organization, Geneva, 1973, 161-162. 18. Iwata, Y.; Knaak, J. B.; Carmen, G. E.; Dusch, M. E.; Gunther, F. A., J. Agr. Food Chem., 1982, 30, 215-222. 19. Iwata, Y.; Knaak, J. B.; Spear, R. C.; and Foster, R. J., Bull. Environ Contam. Toxicol., 1977, 18, 649-655. 20. Labriola-Tomkins, T.; Ranion, T., 1982, Safrotin EC Carpet Study, (A) Cholinesterase dose/response; (B) Dislodgeable Residues on Carpets, Sandoz, Inc., Crop Protection, East Hanover, New Jersey, 1977, 18, 649-655.

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