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Critical windows of exposure to household pesticides and risk of childhood leukemia. (Children's Health Articles).


The potential etiologic e·ti·ol·o·gy also ae·ti·ol·o·gy  
n. pl. e·ti·ol·o·gies
1.
a. The study of causes or origins.

b. The branch of medicine that deals with the causes or origins of disease.

2.
a.
 role of household pesticide pesticide, biological, physical, or chemical agent used to kill plants or animals that are harmful to people; in practice, the term pesticide is often applied only to chemical agents.  exposures was examined in the Northern California Northern California, sometimes referred to as NorCal, is the northern portion of the U.S. state of California. The region contains the San Francisco Bay Area, the state capital, Sacramento; as well as the substantial natural beauty of the redwood forests, the northern  Childhood Leukemia leukemia (lkē`mēə), cancerous disorder of the blood-forming tissues (bone marrow, lymphatics, liver, spleen) characterized by excessive production of immature or mature  Study. A total of 162 patients (0-14 years old) with newly diagnosed leukemia were rapidly ascertained as·cer·tain  
tr.v. as·cer·tained, as·cer·tain·ing, as·cer·tains
1. To discover with certainty, as through examination or experimentation. See Synonyms at discover.

2.
 during 1995-1999, and 162 matched control matched study, matched control

a comparison between groups in which each subject animal is matched by a comparable animal in terms of age and all other measurable parameters. Called also matched or paired control.
 subjects were randomly selected from the birth registry. The use of professional pest control pest control ncontrol m de plagas

pest control nlutte f contre les nuisibles

pest control pest n
 services at any time from 1 year before birth to 3 years after was associated with a significantly increased risk of childhood leukemia [odds ratio (OR) = 2.8; 95% confidence interval confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%.
 (CI), 1.4-5.7], and the exposure during year 2 was associated with the highest risk (OR = 3.6; 95% CI, 1.6-8.3). The ORs for exposure to insecticides insecticides, chemical, biological, or other agents used to destroy insect pests; the term commonly refers to chemical agents only. Chemical Insecticides
 during the 3 months before pregnancy, pregnancy, and years 1, 2, and 3 were 1.8 (95% CI, 1.1-3.1), 2.1 (95% CI, 1.3-3.5), 1.7 (95% CI, 1.0-2.9), 1.6 (95% CI, 1.0-2.7), and 1.2 (95% CI, 0.7-2.1), respectively. Insecticide insecticide

Any of a large group of substances used to kill insects. Such substances are mainly used to control pests that infest cultivated plants and crops or to eliminate disease-carrying insects in specific areas.
 exposures early in life appear to be more significant than later exposures, and the highest risk was observed for exposure during pregnancy. Additionally, more frequent exposure to insecticides was associated with a higher risk. In contrast to insecticides, the association between herbicides and leukemia was weak and nonsignificant non·sig·nif·i·cant  
adj.
1. Not significant.

2. Having, producing, or being a value obtained from a statistical test that lies within the limits for being of random occurrence.
. Pesticides were also grouped based on where they were applied. Exposure to indoor pesticides was associated with an increased risk, whereas no significant association was observed for exposure to outdoor pesticides. The findings suggest that exposure to household pesticides is associated with an elevated risk of childhood leukemia and further indicate the importance of the timing and location of exposure. Key words: case-control studies case-control study,
n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population.
, child, herbicides, insecticides, leukemia, pesticides. Environ en·vi·ron  
tr.v. en·vi·roned, en·vi·ron·ing, en·vi·rons
To encircle; surround. See Synonyms at surround.



[Middle English envirounen, from Old French environner
 Health Perspect 110:955-960 (2002). [Online 14 August 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110p955-960ma/abstract.html

**********

Most studies evaluating the relationship between household pesticide exposures and childhood leukemia suggest that an increased risk of leukemia is associated with in utero in utero (in u´ter-o) [L.] within the uterus.

in u·ter·o
adj.
In the uterus.



in utero adv.
 and postnatal postnatal /post·na·tal/ (-na´t'l) occurring after birth, with reference to the newborn.

post·na·tal
adj.
Of or occurring after birth, especially in the period immediately after birth.
 pesticide exposures (1,2). Nevertheless, previous studies have a number of limitations. Some of the estimated odds ratios (ORs) are not precise; that is, they have wide confidence intervals (3-5). Some studies have relatively low response rates (5-7) or are based on small numbers of cases (3,4,6,8,9). In addition, several study design issues could have contributed to problems in recall and reporting of household pesticide exposures, including source and recruitment of controls, matching criteria, method and timing of data collection, imprecise im·pre·cise  
adj.
Not precise.



impre·cisely adv.
 time intervals for which exposure data were collected, definition of exposure, and use of surrogate surrogate n. 1) a person acting on behalf of another or a substitute, including a woman who gives birth to a baby of a mother who is unable to carry the child. 2) a judge in some states (notably New York) responsible only for probates, estates, and adoptions.  respondents In the context of marketing research, a representative sample drawn from a larger population of people from whom information is collected and used to develop or confirm marketing strategy. . Because of the uncertainties in existing data, there is a compelling need to evaluate further the relationship between pesticide exposures and childhood leukemia, and to do so in studies with improved exposure classification and reduced differential reporting.

Methods

Study population. During the first phase (1995-1999) of the Northern California Childhood Leukemia Study (NCCLS NCCLS National Committee for Clinical Laboratory Standards ), patients (0-14 years old) with newly diagnosed leukemia were rapidly ascertained from major clinical centers, usually within 24 hr after diagnosis. Although case ascertainment ascertainment /as·cer·tain·ment/ (a?ser-tan´ment) in genetics, the method by which persons with a trait are selected or discovered by an investigator.  was hospital based, we compared the cases with those ascertained by the statewide population-based registry (10) and found that the NCCLS protocol successfully identified 88% of all newly diagnosed childhood leukemia cases in the San Francisco-Oakland metropolitan statistical area. Controls were randomly selected from the statewide birth certificate files maintained by the California Department of Health Services Department of Health Services may refer to:
  • Los Angeles County Department of Health Services
  • California Department of Health Services a California state agency
 (Sacramento, CA) and 1:1 matched to cases on date of birth, sex, mother's race (white, black, or other), Hispanicity (either parent is Hispanic), and mother's county of residence at the time of child's birth. These controls were then traced by using commercially available searching tools. For cases not born in California (< 10% of all cases), county of residence at diagnosis was used for the matching. For each case, the search continued until an eligible control subject consented to participate in the study.

To be eligible, each case or control had to reside in the study area, be under 15 years of age at the time of diagnosis (or corresponding date for the control), have at least one parent or guardian who speaks English or Spanish, and have no previous history of any malignancy malignancy: see cancer. . Approximately 83% of the eligible cases consented to participate. Among all the eligible controls approached, 69% consented to participate. The study protocol was approved by the Institutional Review Boards of all collaborating institutions, and written informed consents were obtained for all participating subjects. A total of 162 matched case-control pairs are included in this analysis. Of the 162 patients, 135 had a diagnosis of acute lymphoblastic leukemia acute lymphoblastic leukemia
n. Abbr. ALL
Lymphoblastic leukemia occurring mainly in older adults, characterized by rapid onset and progression of symptoms. Also called acute lymphocytic leukemia.
 (ALL).

Data collection. In the NCCLS, detailed information on household pesticide use, including the name of each product, intended purpose (e.g., cockroach cockroach or roach, name applied to approximately 3,500 species of flat-bodied, oval insects forming the order Blattodea. Cockroaches have long antennae, long legs adapted to running, and a flat extension of the upper body wall that conceals the  control), frequency of use, and time window of use (3 months before pregnancy, pregnancy, and years 1, 2, and 3), was collected through in-home personal interviews with the primary care giver, usually the biologic mother, shortly after diagnosis (corresponding dates for controls). For cases, the mean interval between diagnosis and in-home interview was 4.8 months. Because potential birth certificate controls needed to be identified from the birth registry and traced, the interview of a case usually preceded the interview of the corresponding control, with a mean lag time of 9.5 months.

Different types of pesticides were grouped for analysis. Unless the use of professional services (job) professional services - A department of a supplier providing consultancy and programming manpower for the supplier's products.  was explicitly stated, all products were assumed to be personally applied. As defined in this article, insecticide exposures include professional pest control services, insect repellents insect repellent, substance applied to the skin in order to provide protection against biting insects, primarily mosquitoes, ticks, chiggers, fleas, and certain flies. , and the use of various products to control ants, flies, cockroaches cockroaches

insects which may carry Salmonella spp. in their gut and play a part in the spread of the disease.
, spiders, termites, and plant/tree insects Insects
See also ants; bees; biology; butterflies; zoology.

acarophobia

a fear of itching or of the mites or ticks that cause it.

aeroscepsy, aeroscepsis

perception by means of the air, said to be a function of the antennae of insects.
; herbicide herbicide (hr`bəsīd'), chemical compound that kills plants or inhibits their normal growth. A herbicide in a particular formulation and application can be described as selective or nonselective.  exposures include professional lawn service and the use of weed control Weed control is the botanical component of pest control, stopping weeds from reaching a mature stage of growth when they could be harmful to domesticated plants and livestock by physical and chemical methods.  products; flea control products include indoor loggers, flea collars flea collar
n.
A collar, as for a cat or dog, containing a substance that repels or kills fleas.
, flea soaps or shampoos, and sprays, dusts, or powders for fleas. The use of flea control products is directly related to the presence of cats and/or dogs in the households, and the percentage of households in which the child had regular contact with cats and/or dogs during years 1 and 2 was different in cases (57%) and controls (65%). Therefore, flea control products were grouped as a separate category.

Individual products were also combined based on whether they were probably applied indoors or outdoors, although the questionnaire did not include specific questions about the exact location of pesticide application. As defined, indoor pesticide exposures include professional pest control service; products used to control ants, flies, cockroaches, spiders, or termites; insect repellent; and indoor foggers for fleas. Outdoor pesticide exposures include rat, mouse, gopher, or mole control products, slug or snail snail, name commonly used for a gastropod mollusk with a shell. Included in the thousands of species are terrestrial, freshwater, and marine forms. Some eat both plant and animal matter; others eat only one type of food.  bait bait

a preparation containing a palatable food substance such as raw meat, carrot or bran and a pharmaceutical or poisonous substance. The purpose is to introduce the medicament or poison into the unsuspecting animal.
, and plant/tree insect control products.

Frequency indexes for insecticides and indoor pesticides, which were commonly administered in households, were calculated based on how often the products were used during a defined time window. For each product, scores of 0, 1, and 2 were assigned as·sign  
tr.v. as·signed, as·sign·ing, as·signs
1. To set apart for a particular purpose; designate: assigned a day for the inspection.

2.
 to "did not use," "used less than 5 times," and "used 5 or more times," respectively. Occasionally, when a respondent In Equity practice, the party who answers a bill or other proceeding in equity. The party against whom an appeal or motion, an application for a court order, is instituted and who is required to answer in order to protect his or her interests.  could not recall the exact frequency of use (~0.6% of all products), a score of 1.5 was assigned. The scores of individual products in each category (i.e., insecticides or indoor pesticides) were added to obtain a summary frequency index.

Statistical analysis. We performed analyses for overall leukemia and ALL separately. We used conditional logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors.  to estimate ORs and 95% confidence intervals (CI), adjusting for annual household income in U.S. dollars (three categories: < 30,000, 30,000-75,000, > 75,000).

We separated exposure history by specific periods of interest. Patients who were diagnosed during year 1 and their controls were excluded from the analysis of household pesticide exposures during year 1 and the risk of childhood leukemia, because it would be difficult to decide whether the exposures, if any, occurred before diagnosis. Similar exclusions were made for pesticide exposures during the years 2 and 3 as well, producing a smaller study population for subgroup sub·group  
n.
1. A distinct group within a group; a subdivision of a group.

2. A subordinate group.

3. Mathematics A group that is a subset of a group.

tr.v.
 analyses.

Results

Cases and controls were similar regarding age, sex, race, Hispanicity, maternal MATERNAL. That which belongs to, or comes from the mother: as, maternal authority, maternal relation, maternal estate, maternal line. Vide Line.  education, and maternal age maternal age,
n the age of the mother at the period of conception.
 (Table 1). Controls have a somewhat higher annual household income.

The percentages of a variety of pesticide exposures during the index child's first year are shown in Table 2. Approximately 40% of the households used pesticides to control ants, flies, or cockroaches, whereas few families administered spider or termite termite or white ant, common name for a soft-bodied social insect of the order Isoptera. Termites are easily distinguished from ants by comparison of the base of the abdomen, which is broadly joined to the thorax in termites; in ants, there is  control products. Individual products were grouped into several categories, including insecticides, flea control products, herbicides, indoor pesticides, and outdoor pesticides. More than half of households used insecticides or indoor pesticides during the 1-year period. The percentage of pesticide exposures during other periods varied (detailed data not shown).

Generally, the analyses of overall childhood leukemia and ALL yielded similar results. The use of professional pest control services in each of the five time frames (3 months before pregnancy, pregnancy, and years 1, 2, and 3) was more common in cases than in controls (Table 3). The ORs associated with the use of professional pest control service were > 2 for all periods except for the 3 months before pregnancy. Although the ORs for different periods were not exactly the same, a statistically significant elevated risk of leukemia was observed among children whose houses were professionally treated for pests any time during the 4-year period (OR = 2.8; 95% CI, 1.4-5.7).

The relationship between exposure to insecticides (excluding flea control products) and leukemia risk varied across the five individual time frames, with the highest OR (2.1) observed for exposure during pregnancy and the lowest OR (1.2) for exposure during year 3 (Table 3). Exposure to insecticides (excluding flea control products) any time during the 4-year period was associated with a significantly increased risk of childhood leukemia (OR = 2.1; 95% CI, 1.1-4.3). ORs for each increment To add a number to another number. Incrementing a counter means adding 1 to its current value.  in frequency index in all time frames were > 1, which is consistent with the results based on binary Meaning two. The principle behind digital computers. All input to the computer is converted into binary numbers made up of the two digits 0 and 1 (bits). For example, when you press the "A" key on your keyboard, the keyboard circuit generates and transfers the number 01000001 to the  categorization of exposures. Compared with ORs for children who were not exposed to insecticides during the 4-year period (i.e., those who were assigned a frequency index of 0), the ORs for children who had a frequency index of 1-5 or > 5 were 1.5 (95% CI, 0.6-3.6) and 2.4 (95% CI, 1.2-5.1), respectively.

The families of controls used more flea control products than did case families, which may be due to the fact that more control families owned cats and/or dogs. The ORs associated with the use of flea control products were smaller than 1, but none were statistically significant.

Exposure to herbicides during the 4-year period was not associated with the risk of childhood leukemia, although the ORs for exposure during the 3 months before pregnancy or pregnancy were 1.8 and 1.6, respectively.

Cases were exposed to more indoor pesticides than were the controls in each of the five time frames (Figure 1). The highest OR (OR = 2.2; 95% CI, 1.3-3.6) was seen for indoor pesticide exposures during pregnancy. The association with indoor pesticide exposure during year 2 or 3 was weaker and not statistically significant. When all five time frames were combined, children who were exposed to indoor pesticides had an increased risk of leukemia (OR = 1.8; 95% CI, 1.0-3.4). Compared with ORs for children who were not exposed to indoor pesticides during the 4-year period (i.e., those who were assigned a frequency index of 0), the ORs for children who had a frequency index of 1 to 5 or > 5 were 1.4 (95% CI, 0.6-3.1) and 2.0 (1.0-4.0), respectively. Conversely con·verse 1  
intr.v. con·versed, con·vers·ing, con·vers·es
1. To engage in a spoken exchange of thoughts, ideas, or feelings; talk. See Synonyms at speak.

2.
, the magnitude of association between exposure to outdoor pesticides and the risk of childhood leukemia was small, and all the 95% confidence intervals of the ORs included 1 (Figure 1).

[FIGURE 1 OMITTED]

Discussion

Existing studies have generated relatively consistent results, indicating that exposure to household pesticides is associated with an increased risk of childhood leukemia, although the subtype (programming) subtype - If S is a subtype of T then an expression of type S may be used anywhere that one of type T can and an implicit type conversion will be applied to convert it to type T.  of cases included, definition of exposure, and exposure period of interest differed (4-7,9-13). The results from the NCCLS provide additional strong support to the previous observations by distinguishing between the risks associated with different types of pest control, demonstrating a dose-response relationship The Dose-response relationship describes the change in effect on an organism caused by differing levels of exposure (or doses) to a stressor (usually a chemical). This may apply to individuals (eg: a small amount has no observable effect, a large amount is fatal), or to populations  and indicating the importance of the timing and location of exposure.

In the NCCLS, the use of professional pest control services was significantly associated with an increased risk of childhood leukemia, and the magnitude of association was larger than what was seen for general insecticide or indoor pesticide exposures. It is possible that professional pest control agencies used more concentrated and more persistent compounds, which could also be more carcinogenic carcinogenic

having a capacity for carcinogenesis.
. However, it is also likely that the use of professional pest control services reflects the severity of pest problems in a specific household. Professional pest control services generally apply pesticides throughout the entire house, whereas people who apply pesticides themselves are more inclined to target a specific pest infestation infestation /in·fes·ta·tion/ (-fes-ta´shun) parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. . In addition, it may be easier to remember accurately if the family has engaged a professional pest control service than if some family members applied pesticides themselves. Similarly, elevated ORs in the range of 1.26-2.35 were reported for professional treatment against ants and cockroaches in a recently published study of childhood ALL (12). In contrast to our findings, the use of household insecticides by professional pest control agencies was not associated with the risk of acute childhood leukemia in a German study that included more than 1,000 cases (13). However, the prevalence of the use of professional control services in the German study (2.2% in cases and 1.7% in controls) was markedly lower than what was reported in the NCCLS (33.6% in cases and 21.6% in controls from 3 months before pregnancy through the third birthday), which would result in limited statistical power to detect such an association in Germany.

Exposure to general insecticides during the first few postnatal years is associated with an increased risk of childhood leukemia in the NCCLS, which is consistent with previous studies and showed a dose-response relationship. In addition, the risk for exposure during pregnancy was higher than the risks for exposures after birth. Frequent prenatal prenatal /pre·na·tal/ (-na´tal) preceding birth.

pre·na·tal
adj.
Preceding birth. Also called antenatal.



prenatal

preceding birth.
 use of household pesticides was also linked to an increased risk of ALL in another study (12). It may be inferred that the embryo embryo (ĕm`brēō), name for the developing young of an animal or plant. In its widest definition, the embryo is the young from the moment of fertilization until it has become structurally complete and able to survive as a separate organism.  or fetus fetus, term used to describe the unborn offspring in the uterus of vertebrate animals after the embryonic stage (see embryo). In humans, the fetal stage begins seven to eight weeks after fertilization of the egg, when the embryo assumes the basic shape of the newborn  is especially sensitive or susceptible to carcinogens Carcinogens
Substances in the environment that cause cancer, presumably by inducing mutations, with prolonged exposure.

Mentioned in: Colon Cancer, Rectal Cancer
 in the environment. There is evidence that ALL is initiated in utero (14), and it has been shown that some chromosome translocation translocation /trans·lo·ca·tion/ (trans?lo-ka´shun) the attachment of a fragment of one chromosome to a nonhomologous chromosome. Abbreviated t.  events related to the incidence of childhood ALL have a prenatal origin (15,16). An ongoing activity of the NCCLS is to determine whether selected translocations can be backtracked to birth. Correlating environmental exposures during pregnancy with chromosome translocations present at birth will likely help illustrate the natural history of childhood leukemia and the timing of key exposures and mutational mu·ta·tion  
n.
1. The act or process of being altered or changed.

2. An alteration or change, as in nature, form, or quality.

3. Genetics
a.
 events.

There is a considerable overlap between the definitions of insecticides and indoor pesticides, and the results regarding indoor pesticide use were similar to what was seen for insecticides. Reported exposure to herbicides during the 4-year period was not associated with leukemia risk, although an elevated and insignificant risk was observed for exposure before and during pregnancy. Consistent with a newly completed ecologic e·col·o·gy  
n. pl. e·col·o·gies
1.
a. The science of the relationships between organisms and their environments. Also called bionomics.

b. The relationship between organisms and their environment.
 assessment of agricultural pesticide use and childhood leukemia conducted in California (17), no significant association between outdoor pesticide exposures and leukemia risk was observed. There could have been some misclassification in terms of indoor and outdoor pesticide use. For example, pesticides used to control rats and mice are usually applied outside of the house, but it is also possible that they are sometimes applied inside. Misclassification between indoor and outdoor exposures would have made the differences between these two categories smaller.

The NCCLS has several design features that are improvements over existing studies. Unlike several previous studies that used random digit dialing Random digit dialing (RDD) is a method for selecting people for involvement in telephone statistical surveys by generating telephone numbers at random. Random digit dialing has the advantage that it includes unlisted numbers that would be missed if the numbers were selected from a  to select controls, the NCCLS employed a new protocol to select population-based controls. Controls were randomly selected from the California statewide birth registry, and a methodologic evaluation indicated that the birth certificate controls well represented the population base from which the cases arose (18). Only incident cases were included in the NCCLS, and controls were selected concurrently, which significantly reduced the lag time between diagnosis (corresponding date for controls) and interview. This should have made the reported exposure history more reliable. In contrast to many previous studies that collected data through mailed questionnaire or telephone interview, detailed history on household pesticides exposure was obtained through in-home personal interviews in the NCCLS. In addition, the NCCLS was one of the first studies specifically designed to address critical windows of exposure, that is, the timing of household pesticide exposures relative to a child's conception and development.

Recall bias cannot be ruled out in any case-control study that relies on exposures reported by the subjects, and the NCCLS is no exception. It is possible that the respondents, usually the biologic mothers, falsely claimed or forgot to mention certain exposures depending on whether the child was a patient with leukemia. However, mothers of the controls reported more usage of flea control products than the cases, which is consistent with the increased reported contact with cats and/or dogs in controls. In addition, the ORs associated with exposures to several pesticide categories varied by type and across different time frames, which provided some assurance that the observed associations were not due to general overreporting of exposures among mothers of leukemia cases, but instead may provide evidence for the effects of pesticide exposures at critical periods in a child's development.

A difference in annual household income between cases and controls was observed in this study, hence the decision to adjust for it in the analysis. In addition, a separate analysis was conducted excluding subjects with an annual income of less than $30,000, and the results were not systematically different (data not shown).

Results presented here are limited to broad types of pesticides; no specific chemicals are identified at this stage of analysis. It is certainly preferable to identify specific chemicals associated with the risk of leukemia so that preventive preventive /pre·ven·tive/ (pre-vent´iv) prophylactic.

pre·ven·tive or pre·ven·ta·tive
adj.
Preventing or slowing the course of an illness or disease; prophylactic.

n.
 measures could be taken. The names of all products were recorded in the NCCLS, and the Environmental Protection Agency Environmental Protection Agency (EPA), independent agency of the U.S. government, with headquarters in Washington, D.C. It was established in 1970 to reduce and control air and water pollution, noise pollution, and radiation and to ensure the safe handling and  registration number on each of the pesticide containers will be obtained during a follow-up visit to the homes of selected cases and controls, with the ultimate goal of determining the specific chemicals rather than generic types of pesticides associated with increased risks. Based on household inventories conducted in California and Minnesota, the most common home insecticides included piperonyl butoxide piperonyl butoxide

a synergist used with, and as an enhancer for, pyrethrum and rotenone in the control of ectoparasites.
, chlorpyrifos, pyrethrins pyrethrins

the active insecticidal ingredients of the flowers of the pyrethrum plant. Can cause systemic or cutaneous allergic reactions. Are esters of pyrethrolone and cinerolone with chrysanthemum mono- and dicarboxylic acids.
, and propoxur (19,20). In California, the insecticides most frequently applied by professional pest control services for structural pest control purposes are piperonyl butoxide, pyrethrins, chlorpyrifos, and diazinon diazinon

an organophosphorus insecticide, used in ear tags for cattle and in flea collars and rinses for dogs. Called also dimpylate. See also organophosphorus compound.
 (21).

Parental occupational exposure to chemicals such as pesticides and solvents has also been suggested as a risk factor for childhood leukemia (2,13,22). Detailed occupational histories were obtained in the NCCLS, but these data are not yet available for analysis. Children living in agricultural communities can also be exposed to pesticides from agricultural use (23). Agricultural pesticide use is high in some areas of California, with over 170,000 children living in communities averaging more than 500 pounds of use per square mile for pesticides classified as probable carcinogens (24). It will be more informative when exposures from household, parental occupations and nearby agricultural applications can be evaluated jointly, which is a goal of the NCCLS. Ultimately, studies with environmental or biologic monitoring are needed to determine the relationship between pesticide exposure and childhood leukemia.

Another potential limitation of the study is the relatively small sample size, which reduces the power of the study to detect low-level risks. On the other hand, this study did consistently detect risks of 2-fold or greater, and the matched design improves the precision of statistical analyses (25). The NCCLS is currently underway and will enroll subjects until 2003. The expansion of the study population, added detail on chemical constituents, and more specific and complete exposure classification will provide more information regarding pesticide exposures and the risk of childhood leukemia.

In summary, the findings from the present study suggest that exposure to household pesticides is associated with an elevated risk of childhood leukemia and further indicate the importance of the timing and location of exposure.
Table 1. Characteristics of cases and controls.

                                         Leukemia (162 pairs)

                                                              [chi
                                 Cases       Controls     square] test
Characteristics                 No. (%)      No. (%)         OR (a)

Age (b)                                                        --
  < 12 months                    10 (6)       10 (6)
  12-23.9 months                 12 (7)       12 (7)
  2-5 years                      86 (53)      86 (53)
  6-10 years                     35 (22)      35 (22)
  11-14 years                    19 (12)      19 (12)
  Mean (SE)(years)              5.5 (0.3)    5.5 (0.3)
Sex (b)                                                        --
  Male                           93 (57)      93 (57)
  Female                         69 (43)      69 (43)
Race/ethnicity (b)                                             --
  Hispanic                       48 (30)      49 (30)
  Non-Hispanic white             85 (52)      86 (53)
  Non-Hispanic black              5 (3)        5 (3)
  Other                          24 (15)      22 (15)
Household income                                            p = 0.04
    ($1,000/year)
  < 15                           20 (12)      11 (7)        Referent
  15-29.9                        31 (19)      20 (12)    0.8 (0.3, 2.1)
  30-44.9                        25 (15)      16 (10)    0.8 (0.3, 2.5)
  45-59.9                        21 (13)      25 (15)    0.3 (0.1, 0.8)
  60-74.9                        22 (14)      25 (15)    0.4 (0.1, 1.0)
  [greater than or equal to]     43 (27)      65 (40)    0.2 (0.1, 0.6)
    75
Maternal education                                          p = 0.59
  [less than or equal to]        59 (36)      52 (32)       Referent
    High school
  > High school but              48 (30)      56 (35)    0.8 (0.4, 1.3)
    < Bachelor's
  [greater than or equal to]     55 (34)      54 (33)    0.9 (0.5, 1.6)
    Bachelor's
Maternal age (years)                                        p = 0.52
  < 20                           11 (7)       11 (7)        Referent
  20-24                          33 (21)      23 (14)    1.5 (0.6, 3.9)
  25-29                          44 (27)      49 (30)    0.8 (0.3, 2.0)
  30-34                          55 (34)      54 (33)    1.0 (0.4, 2.5)
  [greater than or equal to]     18 (11)      25 (15)    0.7 (0.2, 2.0)
    35
Unknown                            1            0
Mean (SE)(years)               28.5 (0.4)   29.5 (0.5)

                                          ALL (135 pairs)

                                                              [chi
                                 Cases       Controls     square] test
Characteristics                 No. (%)      No. (%)         OR (a)

Age (b)                                                        --
  < 12 months                     6 (4)        6 (4)
  12-23.9 months                  9 (7)        9 (7)
  2-5 years                      80 (59)      80 (59)
  6-10 years                     29 (22)      29 (22)
  11-14 years                    11 (8)       11 (8)
  Mean (SE)(years)              5.3 (0.3)    5.3 (0.3)
Sex (b)                                                        --
  Male                           79 (59)      79 (59)
  Female                         56 (41)      56 (41)
Race/ethnicity (b)                                             --
  Hispanic                       40 (30)      40 (30)
  Non-Hispanic white             72 (53)      73 (54)
  Non-Hispanic black              2 (1)        2 (1)
  Other                          21 (16)      20 (15)
Household income                                            p = 0.08
    ($1,000/year)
  < 15                           14 (10)      11 (8)        Referent
  15-29.9                        28 (21)      15 (11)    1.3 (0.4, 3.8)
  30-44.9                        18 (13)      13 (10)    0.9 (0.3, 3.0)
  45-59.9                        19 (14)      17 (13)    0.6 (0.2, 1.8)
  60-74.9                        19 (14)      22 (16)    0.5 (0.2, 1.5)
  [greater than or equal to]     37 (28)      57 (42)    0.3 (0.1, 1.0)
    75
Maternal education                                          p = 0.84
  [less than or equal to]        47 (35)      43 (32)       Referent
    High school
  > High school but              44 (33)      48 (36)    0.8 (0.5, 1.5)
    < Bachelor's
  [greater than or equal to]     44 (33)      44 (33)    0.9 (0.5, 1.7)
    Bachelor's
Maternal age (years)                                        p = 0.56
  < 20                            9 (7)       10 (7)        Referent
  20-24                          27 (20)      20 (15)    1.5 (0.5, 4.4)
  25-29                          35 (26)      40 (30)    0.9 (0.4, 2.4)
  30-34                          47 (35)      42 (31)    1.2 (0.4, 3.4)
  [greater than or equal to]     16 (12)      23 (17)    0.8 (0.3, 2.4)
    35
Unknown                            1            0
Mean (SE)(years)               28.6 (0.5)   29.4 (0.5)

(a) The ORs are derived from conditional logistic regression models,
without adjusting for any other factors. Numbers in the parentheses are
95% CIs. (b) These are the matching variables. Age means age at
diagnosis for cases and age at the corresponding dates for controls.

Table 2. Proportion of pesticide exposures during year 1.

                                              Per-
                                 Percent    cent in
                                 in cases   controls      Adjusted
                                 (n = 152   (n = 152       OR (b)
Type of exposure                   (a))       (a))        (95% CI)

Individual exposure
  Professional pest control         16         11      2.3 (1.1-4.9)
    or extermination
  Professional lawn service          9         12      0.9 (0.4-2.0)
  Ant, fly, or cockroach            38         39      1.1 (0.7-1.9)
    control products
  Spider control products            1          1      1.5 (0.1-25.6)
  Termite control products           1          0      Not calculable
  Rat, mouse, gopher, or mole        4          7      0.6 (0.2-1.7)
    control products
  Insect repellent for ticks        11          8      1.7 (0.6-4.4)
    or mosquitoes
  Slug or snail bait                17         16      1.5 (0.8-2.7)
  Plant/tree insect or disease       7         10      0.8 (0.4-1.6)
    control products
  Weed control products             18         23      0.7 (0.3-1.7)
  Indoor foggers for fleas           5          7      0.6 (0.3-1.8)
  Flea collars                      11         16      0.6 (0.3-1.2)
  Flea soaps or shampoos            11         15      0.8 (0.4-1.5)
  Sprays, dusts, or powders          6          7      1.0 (0.4-2.6)
    for fleas
Combined exposure
  Insecticides                      59         50      1.7 (1.0-2.9)
  Flea control products             22         28      0.8 (0.5-1.4)
  Herbicides                        23         33      0.7 (0.4-1.2)
  Indoor pesticides                 59         51      1.6 (1.0-2.7)
  Outdoor pesticides                24         24      1.2 (0.7-2.2)

(a) Ten cases diagnosed under 1 year of age were excluded, as were
their matched controls. (b) The ORs were derived from conditional
logistic regression models, adjusting for annual household income.

Table 3. Exposure to insecticides, flea control products, and
herbicides by time and the risk of childhood leukemia.

                                                   Leukemia

                                                 Con-      Adjusted
Type of exposure                         Cases   trols      OR (a)

Professional pest control
  3 months before pregnancy
      (n = 162/135 (b))
    No                                    146     150      Referent
    Yes                                    16      12    1.7 (0.7-3.9)
  During pregnancy (n = 162/135 (b))
    No                                    140     148      Referent
    Yes                                    22      14    2.2 (1.0-4.8)
  Year 1 (n = 152/129 (b))
    No                                    127     136      Referent
    Yes                                    25      16    2.3 (1.1-4.9)
  Year 2 (n = 140/120 (b))
    No                                    109     125      Referent
    Yes                                    31      15    3.6 (1.6-8.3)
  Year 3 (n = 116/98 (b))
    No                                     93     101      Referent
    Yes                                    23      15    2.2 (1.0-4.7)
  3 months before pregnancy to
      3 years old (n = 116/98 (b))
    No                                     77      91      Referent
    Yes                                    39      25    2.8 (1.4-5.7)
Insecticides (excluding flea
    control products)
  3 months before pregnancy
      (n = 162/135 (b))
    No                                     99     113      Referent
    Yes                                    63      49    1.8 (1.1-3.1)
  Each increment in frequency index                      1.2 (1.0-1.5)
  During pregnancy (n = 162/135 (b))
    No                                     83     106      Referent
    Yes                                    79      56    2.1 (1.3-3.5)
  Each increment in frequency index                      1.1 (1.0-1.2)
  Year 1 (n = 152/129 (b))
    No                                     62      76      Referent
    Yes                                    90      76    1.7 (1.0-2.9)
  Each increment in frequency index                      1.2 (1.0-1.4)
  Year 2 (n = 140/120 (b))
    No                                     50      62      Referent
    Yes                                    90      78    1.6 (1.0-2.7)
  Each increment in frequency index                      1.1 (1.0-1.3)
  Year 3 (n = 116/98 (b))
    No                                     40      44      Referent
    Yes                                    76      72    1.2 (0.7-2.1)
  Each increment in frequency index                      1.0 (0.9-1.2)
  3 months before pregnancy to 3 years
      old (n = 116/98 (b))
    No                                     23      36      Referent
    Yes                                    93      80    2.1 (1.1-4.3)
  Each increment in frequency index                      1.0 (1.0-1.1)
Flea control products
  3 months before pregnancy
      (n = 162/135 (b))
    No                                    136     130      Referent
    Yes                                    26      32    0.9 (0.5-1.7)
  During pregnancy (n = 162/135 (b))
    No                                    135     128      Referent
    Yes                                    27      34    0.8 (0.4-1.4)
  Year 1 (n = 152/129 (b))
    No                                    118     110      Referent
    Yes                                    34      42    0.8 (0.5-1.4)
  Year 2 (n = 140/120 (b))
    No                                    105      98      Referent
    Yes                                    35      42    0.9 (0.5-1.5)
  Year 3 (n = 116/98 (b))
    No                                     90      81      Referent
    Yes                                    26      35    0.8 (0.4-1.4)
  3 months before pregnancy to 3 years
      old (n = 116/98 (b))
    No                                     76      71      Referent
    Yes                                    40      45    0.9 (0.5-1.6)
Herbicides
  3 months before pregnancy
      (n = 162/135 (b))
    No                                    131     139      Referent
    Yes                                    31      23    1.8 (0.9-3.5)
  During pregnancy (n = 162/135 (b))
    No                                    128     133      Referent
    Yes                                    34      29    1.6 (0.9-3.0)
  Year 1 (n = 152/129 (b))
    No                                    117     102      Referent
    Yes                                    35      50    0.7 (0.4-1.2)
  Year 2 (n = 140/120 (b))
    No                                    100      95      Referent
    Yes                                    40      45    1.1 (0.7-2.0)
  Year 3 (n = 116/98 (b))
    No                                     83      81      Referent
    Yes                                    33      35    1.1 (0.6-2.1)
  3 months before pregnancy to 3 years
      old (n = 116/98 (b))
    No                                     78      75      Referent
    Yes                                    38      41    1.0 (0.6-1.8)

                                                     ALL

                                                 Con-      Adjusted
Type of exposure                         Cases   trols      OR (a)

Professional pest control
  3 months before pregnancy
      (n = 162/135 (b))
    No                                    120     125      Referent
    Yes                                    15      10    1.9 (0.7-4.7)
  During pregnancy (n = 162/135 (b))
    No                                    115     123      Referent
    Yes                                    20      12    2.3 (0.9-5.4)
  Year 1 (n = 152/129 (b))
    No                                    107     104      Referent
    Yes                                    22      15    2.1 (1.0-4.7)
  Year 2 (n = 140/120 (b))
    No                                     91     105      Referent
    Yes                                    29      15    3.3 (1.4-7.7)
  Year 3 (n = 116/98 (b))
    No                                     77      84      Referent
    Yes                                    21      14    2.1 (1.0-4.7)
  3 months before pregnancy to
      3 years old (n = 116/98 (b))
    No                                     62      74      Referent
    Yes                                    36      24    2.6 (1.2-5.4)
Insecticides (excluding flea
    control products)
  3 months before pregnancy
      (n = 162/135 (b))
    No                                     82      93      Referent
    Yes                                    53      42    1.7 (1.0-3.1)
  Each increment in frequency index                      1.2 (0.9-1.6)
  During pregnancy (n = 162/135 (b))
    No                                     67      89      Referent
    Yes                                    68      46    2.3 (1.3-4.0)
  Each increment in frequency index                      1.1 (1.0-1.2)
  Year 1 (n = 152/129 (b))
    No                                     54      66      Referent
    Yes                                    75      63    1.7 (1.0-2.9)
  Each increment in frequency index                      1.2 (1.0-1.4)
  Year 2 (n = 140/120 (b))
    No                                     42      53      Referent
    Yes                                    78      67    1.7 (1.0-2.9)
  Each increment in frequency index                      1.1 (1.0-1.3)
  Year 3 (n = 116/98 (b))
    No                                     33      36      Referent
    Yes                                    65      62    1.1 (0.6-2.1)
  Each increment in frequency index                      1.0 (0.9-1.2)
  3 months before pregnancy to 3 years
      old (n = 116/98 (b))
    No                                     18      30      Referent
    Yes                                    80      68    2.2 (1.0-4.6)
  Each increment in frequency index                      1.0 (1.0-1.1)
Flea control products
  3 months before pregnancy
      (n = 162/135 (b))
    No                                    113     106      Referent
    Yes                                    22      29    0.8 (0.4-1.6)
  During pregnancy (n = 162/135 (b))
    No                                    113     105      Referent
    Yes                                    22      30    0.7 (0.4-1.4)
  Year 1 (n = 152/129 (b))
    No                                     98      91      Referent
    Yes                                    31      38    0.9 (0.5-1.6)
  Year 2 (n = 140/120 (b))
    No                                     88      83      Referent
    Yes                                    32      37    1.0 (1.5-1.8)
  Year 3 (n = 116/98 (b))
    No                                     74      68      Referent
    Yes                                    24      30    0.9 (0.5-1.7)
  3 months before pregnancy to 3 years
      old (n = 116/98 (b))
    No                                     62      59      Referent
    Yes                                    36      39    1.0 (0.5-1.8)
Herbicides
  3 months before pregnancy
      (n = 162/135 (b))
    No                                    111     117      Referent
    Yes                                    24      18    1.6 (0.8-3.3)
  During pregnancy (n = 162/135 (b))
    No                                    105     112      Referent
    Yes                                    30      23    1.8 (0.9-3.5)
  Year 1 (n = 152/129 (b))
    No                                     97      86      Referent
    Yes                                    32      43    0.8 (0.4-1.4)
  Year 2 (n = 140/120 (b))
    No                                     84      80      Referent
    Yes                                    36      40    1.1 (0.6-2.0)
  Year 3 (n = 116/98 (b))
    No                                     67      67      Referent
    Yes                                    31      31    1.2 (0.6-2.3)
  3 months before pregnancy to 3 years
      old (n = 116/98 (b))
    No                                     63      61      Referent
    Yes                                    35      37    1.0 (0.6-1.8)

(a) The ORs were derived from conditional logistic regression models,
adjusting for annual household income; numbers in parentheses are 95%
CIs. (b) Number of case-control pairs available for the specific
analysis.


REFERENCES AND NOTES

(1.) Daniels JL, Olshan AF, Savitz DA. Pesticides and childhood cancers. Environ Health Perspect 105:1068-1077 (1997).

(2.) Zahm SH, Ward MH. Pesticides and childhood cancer. Environ Health Perspect 106(suppl 3):893-908 (1998).

(3.) Davis JR. Childhood Cancer and Pesticide Use in the Home, Garden and Yard [PhD Thesis]. Berkeley, CA: Department of Entomological en·to·mol·o·gy  
n.
The scientific study of insects.



ento·mo·log
 Sciences, University of California, Berkeley The University of California, Berkeley is a public research university located in Berkeley, California, United States. Commonly referred to as UC Berkeley, Berkeley and Cal , 1991.

(4.) Lowengart RA, Peters JM, Cicioni C, Buckley J, Bernstein L, Preston-Martin S, Rappaport E. Childhood leukemia and parents' occupational and home exposures. J Natl Cancer Inst 79:39-45 (1987).

(5.) Schwartzbaum JA, George SL, Pratt CB, Davis B. An exploratory study of environmental and medical factors potentially related to childhood cancer. Med Pediatr Oncol 19:115-121 (1991).

(6.) Leiss JK, Savitz DA. Home pesticide use and childhood cancer: a case-control study. Am J Public Health 85:249-252 (1995).

(7.) Buckley J, Buckley C, Ruccione K, Sather H, Waskerwitz M, Woods W, Robison L. Epidemiological epidemiological

emanating from or pertaining to epidemiology.


epidemiological associations
the associative relationships between the frequency of occurrence of a disease and its determinants, its predisposing and precipitating
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acute lymphocytic leukemia Acute lymphoblastic leukemia, ALL A malignant lymphoproliferative process that commonly affects children and young adults
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(8.) Fajardo-Gutierrez A, Garduno-Espinosa J, Yamamoto-Kimura L, Hernandez-Hernandez DM, Mejia-Arangure M, Gomez-Delgado A, Farfan-Canto JM, Ortiz-Fernandez A, Martinez-Garcia MDC (1) (Mobile Daughter Card) See riser card.

(2) See Meta Data Coalition.
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(9.) Meinert R, Kaatsch P, Kaletsch U, Krummenauer F, Miesner A, Michaelis J. Childhood leukaemia and exposure to pesticides: results of a case-control study in northern Germany Northern Germany is the geographic area in the north of Germany. The native German concept of northern Germany is called Norddeutschland. Northern German States
Norddeutschland is the geographic area of five German states:
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(10.) California Cancer Registry A cancer registry is a systematic collection of data about cancer and tumor diseases. The data is collected by Cancer Registrars. Cancer Registrars capture a complete summary of patient history, diagnosis, treatment, and status for every cancer patient in the United States, and . Unpublished data.

(11.) Buckley JD, Robison LL, Swotinsky R, Garabrant DH, LeBeau M, Manchester P, Nesbit ME, Odom L, Peters JM, Woods WG, et al. Occupational exposures of parents of children with nonlymphocytic leukemia: a report from the Children's Cancer Study Group The Children's Cancer Study Group (CCG) was a U.S. and Canadian clinical trial cooperative group created with the mission of studying childhood cancers. In 2000, CCG merged with several other pediatric cooperative groups to form the Children's Oncology Group (COG). . Cancer Res 49:4030-4037 (1989).

(12.) Infante-Rivard C, Labuda D, Krajinovic M, Sinnett D. Risk of childhood leukemia associated with exposure to pesticides and with gene polymorphisms. Epidemiology epidemiology, field of medicine concerned with the study of epidemics, outbreaks of disease that affect large numbers of people. Epidemiologists, using sophisticated statistical analyses, field investigations, and complex laboratory techniques, investigate the cause  10:481-487 (1999).

(13.) Meinert R, Schuz J, Kaletsch U, Kaatsch P, Michaelis J. Leukemia and non-Hodgkin's lymphoma non-Hodg·kin's lymphoma
n.
Any of various malignant lymphomas characterized by the absence of Reed-Sternberg cells.


Non-Hodgkin's lymphoma 
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(14.) Ford AM, Ridge SA, Cabrera ME, Mahmoud H, Steel CM, Chan LC, Greaves greaves

cracklings, an edible raw fat from the meat trade. The skimmings from the preparation of this fat are also called greaves. They represent a low grade of meat meal.
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Gene that can cause cancer. It is a sequence of DNA that has been altered or mutated from its original form, the proto-oncogene (see mutation). Proto-oncogenes promote the specialization and division of normal cells.
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(15.) Wiemels JL, Cazzaniga G, Daniotti M, Eden OB, Addison GM, Masera G, Saha V, Biondi A, Greaves MF. Prenatal origin of acute lymphoblastic lymphoblastic

pertaining to a lymphoblast; producing lymphocytes.
 leukaemia in children. Lancet lancet /lan·cet/ (lan´set) a small, pointed, two-edged surgical knife.

lan·cet
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(16.) Wiemels JL, Ford AM, Wering ERV ERV expiratory reserve volume.

ERV
abbr.
expiratory reserve volume



ERV

expiratory reserve volume.
, Postma A, Greaves M. Protracted pro·tract  
tr.v. pro·tract·ed, pro·tract·ing, pro·tracts
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2.
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(17.) Reynolds P, Von Behren J, Gunier R, Goldberg D, Hertz hertz (hûrts) [for Heinrich R. Hertz], abbr. Hz, unit of frequency, equal to 1 cycle per second. The term is combined with metric prefixes to denote multiple units such as the kilohertz (1,000 Hz), megahertz (1,000,000 Hz), and gigahertz  A, Harnly M. Childhood cancer and agricultural pesticide use: an ecological ecological

emanating from or pertaining to ecology.


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(19.) Robinson J, Pease pease  
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[Middle English; see pea.
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(20.) Adgate JL, Kukowski A, Stroebel C, Shubat PJ, Morrell S Morrell is a surname, and may refer to:
  • Andy Morrell
  • Arthur Fleming Morrell
  • Cynthia Hedge-Morrell
  • Daniel Johnson Morrell
  • David Morrell
  • Dawn Morrell
  • Edward de Veaux Morrell
  • Frances Morrell
  • Geoff Morrell
  • George Morrell
, Quackenboss JJ, Whitmore RW, Sexton sex·ton  
n.
An employee or officer of a church who is responsible for the care and upkeep of church property and sometimes for ringing bells and digging graves.
 K. Pesticide storage and use patterns in Minnesota households with children. J Expos Anal anal (a´n'l) relating to the anus.

a·nal
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1. Of, relating to, or near the anus.

2.
 Environ Epidemiol 10:159-167 (2000).

(21.) California Department of Pesticide Regulation. Environmental Monitoring and Pest Management Branch. Pesticide Use Reporting Data 1998. Data file. Sacramento, CA:California Department of Pesticide Regulation, 1999.

(22.) Shu XO, Stewart P, Wen W-Q, Hah D, Peter JD, Buckley JD, Heineman E, Robison LL. Parental occupational exposure to hydrocarbons hydrocarbons (hīˈ·drō·kärˑ·bnz),
n.
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1. The progeny or descendants of a person, animal, or plant considered as a group.

2. A child of particular parentage.
. Cancer Epidemiol Biomarkers Prey 8:783-791 (1999).

(23.) Lu C, Fenske RA, Simcox NJ, Kalman D. Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways. Environ Res 84:290-302 (2000).

(24.) Gunier RB, Harnly ME, Reynolds P, Hertz A, Von Behren J. Agricultural pesticide use in California: pesticide prioritization, use densities, and population distributions for a childhood cancer study. Environ Health Perspect 109:1071-1078 (2001).

(25.) Cochran W. Planning and Analysis of Observational Studies observational studies,
n.pl an investigational method involving description of the associations be-tween interventions and outcomes. Outcomes research and practice audits are examples of this investigational method.
. New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of
:John Wiley John Wiley may refer to:
  • John Wiley & Sons, publishing company
  • John C. Wiley, American ambassador
  • John D. Wiley, Chancellor of the University of Wisconsin-Madison
  • John M. Wiley (1846–1912), U.S.
 and Sons, 1983.

Xiaomei Ma, (1) Patricia A. Buffler, (1) Robert B. Gunier, (2) Gary Dahl Gary Dahl, an advertising executive from Los Gatos, California, conceived the idea of selling rocks to people as Pet Rocks, complete with instructions. The 1975 fad only lasted about half a year, but that was enough to make Dahl a millionaire. , (3) Martyn T. Smith, (1) Kyndaron Reinier, (1) and Peggy Peggy may refer to:
  • Peggy (musical), a 1911 musical comedy by Stuart and Bovill
  • Peggy (given name), people with the given name Peggy
See also
  • Peggy-Ann, a 1926 musical comedy by Rodgers and Hart
 Reynolds (2)

(1) School of Public Health, University of California, Berkeley, California, USA; (2) Environmental Health Investigations Branch, California Department of Health Services, Oakland, California “Oakland” redirects here. For other uses, see Oakland (disambiguation).
Oakland (IPA: /ˈoʊklənd/), founded in 1852, is the eighth-largest city in the U.S.
, USA; (3) Stanford University School of Medicine Stanford University School of Medicine is affiliated with Stanford University and is located at Stanford University Medical Center in Stanford, California, adjacent to Palo Alto and Menlo Park. , Stanford, California Stanford is a census-designated place (CDP) in Santa Clara County, California, United States. The population was 13,315 at the 2000 census.

Stanford is an unincorporated area of Santa Clara County and is adjacent to the city of Palo Alto.
, USA

Address correspondence to X. Ma, School of Public Health, University of California, Berkeley, CA 94720-7360 USA. Telephone: (510) 643-3958. Fax: (510) 643-1735. E-mail: xmma@uclink4.berkeley.edu

We thank J. Feusner, K. Matthay, S. Month, V. Crouse, K. Leung, and V. Kiley for assistance with recruiting patients and M. Does for supervising fieldwork field·work  
n.
1. A temporary military fortification erected in the field.

2. Work done or firsthand observations made in the field as opposed to that done or observed in a controlled environment.

3.
.

The study was supported by grants from the National Institute of Environmental Health Sciences The National Institute of Environmental Health Sciences (NIEHS) is one of 27 Institutes and Centers of the National Institutes of Health (NIH),which is a component of the Department of Health and Human Services (DHHS). The Director of the NIEHS is Dr. David A. Schwartz.  (PS42 ES04705 and RO1 ES09137). X.M. was supported by a grant from the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center.  (T01/CCT917644-01).

Received 14 November 2001; accepted 12 March 2002.
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