Childhood cancer and agricultural pesticide use: an ecologic study in California. (Children's Health Article).We analyzed population-based childhood cancer incidence rates throughout California in relation to agricultural 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. use. During 1988-1994, a total of 7,143 cases of invasive cancer were diagnosed among children under 15 years of age in California. Building on the availability of high-quality population-based cancer incidence information from the 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 , population data from the U.S. Census, and uniquely comprehensive agricultural pesticide use information from California's Department of Pesticide Regulation, we used a geographic information system geographic information system (GIS) Computerized system that relates and displays data collected from a geographic entity in the form of a map. The ability of GIS to overlay existing data with new information and display it in colour on a computer screen is used primarily to to assign summary population, exposure, and outcome attributes at the block group level. We used Poisson regression In statistics, the Poisson regression model attributes to a response variable Y a Poisson distribution whose expected value depends on a predictor variable x, typically in the following way: 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), 0.80-1.13] for block groups in the 90th percentile percentile, n the number in a frequency distribution below which a certain percentage of fees will fall. E.g., the ninetieth percentile is the number that divides the distribution of fees into the lower 90% and the upper 10%, or that fee level and above for use of pesticides classified as probable carcinogens Carcinogens Substances in the environment that cause cancer, presumably by inducing mutations, with prolonged exposure. Mentioned in: Colon Cancer, Rectal Cancer , compared to the block groups with use of < 1 lb/[mi.sup.2]. The RRs were similar for leukemia leukemia (l  kē`mēə), cancerous disorder of the blood-forming tissues (bone marrow, lymphatics, liver, spleen) characterized by excessive production of immature or mature and central nervous
system cancers. Childhood leukemia rates were significantly elevated (RR
= 1.48; 95% CI, 1.03-2.13) in block groups with the highest use of
propargite, although we saw no dose-response trend with increasing
exposure categories. Results were unchanged by further adjustment for
socioeconomic status socioeconomic status,n the position of an individual on a socio-economic scale that measures such factors as education, income, type of occupation, place of residence, and in some populations, ethnicity and religion. and urbanization. Key words: agriculture, childhood cancer, ecologic study, epidemiologic study epidemiologic study A study that compares 2 groups of people who are alike except for one factor, such as exposure to a chemical or the presence of a health effect; the investigators try to determine if any factor is associated with the health effect , exposure assessment, geographic information system, pesticides, risk assessment. http://ehpnet1.niehs.nih.gov/docs/2002/110p319-324reynolds /abstract.html ********** Cancer is the second leading cause of death among children 5-14 years of age in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. (1). Few risk factors have been established for childhood cancers other than ionizing radiation i·on·i·zing radiation n. High-energy radiation capable of producing ionization in substances through which it passes. Ionizing radiation (2,3), chemotherapy agents (2), and certain inherited inherited received by inheritance. inherited achondroplastic dwarfism see achondroplastic dwarfism. inherited combined immunodeficiency see combined immune deficiency syndrome (disease). genetic disorders The following is a list of genetic disorders and their origins. Beside most disorders is a code that indicates the type of fertilization and the chromosome involved.
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. between pesticide use in the home or garden and childhood leukemia (6-9) and brain cancer (10,11). Parental occupational exposure to pesticides, determined by occupation from birth certificates or questionnaire, has also been associated with childhood cancer (6,7,12-15). Two recent reviews of childhood cancer and pesticides concluded that multiple studies show a modest increased risk, particularly for leukemia and brain cancer, but these studies have been limited by small numbers, nonspecific nonspecific /non·spe·cif·ic/ (non?spi-sif´ik) 1. not due to any single known cause. 2. not directed against a particular agent, but rather having a general effect. nonspecific 1. pesticide information, and potential case-response bias (16,17). California is the largest agricultural state in the nation, with an average of $20 billion per year in farm revenues during the 1990s (18,19). California also consistently ranked highest in agricultural pesticide use based on national surveys conducted in the 1990s, accounting for about 25% of use nationwide (20,21). The potential for pesticide exposure in agricultural communities has been a major source of public concern (22-24). Children living in agricultural communities have a broad range of potential exposure pathways to pesticides, including inhalation inhalation /in·ha·la·tion/ (in?hah-la´shun) 1. the drawing of air or other substances into the lungs.inhala´tional 2. the drawing of an aerosolized drug into the lungs with the breath. 3. of ambient Surrounding. For example, ambient temperature and humidity are atmospheric conditions that exist at the moment. See ambient lighting. air, ingestion ingestion /in·ges·tion/ (-chun) the taking of food, drugs, etc., into the body by mouth. in·ges·tion n. 1. The act of taking food and drink into the body by the mouth. 2. of contaminated contaminated, v 1. made radioactive by the addition of small quantities of radioactive material. 2. made contaminated by adding infective or radiographic materials. 3. an infective surface or object. household dust, parental occupational "take-home" exposures, and playing in or eating produce from treated fields (25-30). Proximity to treated fields has been correlated with pesticide concentrations in ambient air (31) and to pesticide metabolite metabolite, organic compound that is a starting material in, an intermediate in, or an end product of metabolism. Starting materials are substances, usually small and of simple structure, absorbed by the organism as food. levels in biologic monitoring of children (32,33). In 1990, the California Department of Pesticide Regulation began the Pesticide Use Report (PUR) system, requiring growers and applicators to report all agricultural pesticide use. Previously, we used the PUR data and a geographic information system (GIS (1) (Geographic Information System) An information system that deals with spatial information. Often called "mapping software," it links attributes and characteristics of an area to its geographic location. ) to prioritize pri·or·i·tize v. pri·or·i·tized, pri·or·i·tiz·ing, pri·or·i·tiz·es Usage Problem v.tr. To arrange or deal with in order of importance. v.intr. and classify the over 850 chemicals reported to the PUR and to assess the geographic distribution of agricultural pesticide use (34). Although pesticide use in most block groups (77%) averaged < 1 lb/[mi.sup.2] for 1991 through 1994, approximately 170,000 children under 15 years of age were living in block groups with [greater than or equal to] 569 lbs of probable carcinogens per square mile of block group. The range of values reported was suitable for a statewide study of childhood cancer incidence rates by agricultural pesticide use density. The California Department of Health Services Department of Health Services may refer to:
Materials and Methods Pesticide data. California's Department of Pesticide Regulation maintains a pesticide use reporting (PUR) database that includes detailed information on the active ingredient An active ingredient, also active pharmaceutical ingredient (or API), is the substance in a drug that is pharmaceutically active. Some medications may contain more than one active ingredient. , quantity applied, acres treated, crop treated, and location (in square mile sections) for all agricultural pesticide applications in the state. For this study, we used reported PUR data from 1991 through 1994 to calculate the annual average pesticide use in each square mile section (36), and we used a GIS to identify all sections located within each census block group A census block group is a geographical unit used by the United States Census Bureau which is between the census tract and the census block. It is the smallest geographical unit for which the bureau publishes sample data, i. (37). If a section fell into more than one block group, we allocated the pesticide use based on the percentage of area of the section in each block group. In 1990, California block groups had a median land area of 0.2 [mi.sup.2], with a range between 0.0001 and 3,610 [mi.sup.2] (38). We estimated average annual agricultural pesticide use for the study period for each block group by summing the average pounds applied in all relevant sections, then dividing by the block group area to obtain pesticide use density in pounds per square mile. We combined pesticides reported to the PUR system during the study period into four toxicologic groups (probable carcinogens, possible carcinogens Definition "Possible" carcinogen is a category of the dangers of chemical exposure as recognized by the EPA. This is as opposed to "probable" or "known" carcinogen under EPA classifications of carcinogenicity. , genotoxic genotoxic /ge·no·tox·ic/ (je´no-tok?sik) damaging to DNA: pertaining to agents known to damage DNA, thereby causing mutations, which can result in cancer. ge·no·tox·ic adj. compounds, and reproductive or developmental toxicants) and four chemical classes (organochlorides, organophosphates, carbamates carbamates effective insecticides which exert their effect by temporarily inhibiting cholinesterase activity. They are also capable of poisoning. Clinical signs are pupillary constriction, muscle tremor, salivation, ataxia and dyspnea. , and dithiocarbamates). All pesticides classified as known human carcinogens were banned or severely restricted in California before the time of this study. Probable and possible carcinogens are determined almost exclusively from laboratory animal studies (39). Genotoxic chemicals directly damage DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. and may be important for a study of childhood cancer. We chose pesticides with at least two positive results in genetic toxicity toxicity /tox·ic·i·ty/ (tok-sis´i-te) the quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. assays for this analysis (40). We selected reproductive and developmental toxicants based on studies conducted in laboratory animals (41). We prioritized individual pesticides for analysis on the basis of a combination of statewide use in pounds, the U.S. 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 cancer class, the carcinogenic carcinogenic having a capacity for carcinogenesis. potency potency /po·ten·cy/ (po´ten-se) 1. the ability of the male to perform coitus. 2. the relationship between the therapeutic effect of a drug and the dose necessary to achieve that effect. 3. , field volatilization volatilization /vol·a·til·iza·tion/ (vol?ah-til-i-za´shun) conversion into vapor or gas without chemical change. vol·a·til·i·za·tion n. See evaporation. flux, and persistence (34). The top seven ranked pesticides that had a use density of > 1 lb/[mi.sup.2] in at least 1,000 block groups were selected for individual evaluation: propargite, methyl bromide methyl bromide Toxicology An insecticide and rodenticide, which is a volatile fumigant 3-fold denser than air and absorbed through skin, producing narcosis, pulmonary edema, renal tubule damage, jacksonian convulsions, CNS depression, peripheral neuropathy; , trifluralin trifluralin a dinitroaniline compound used as a weedicide. Excessive, accidental access causes diarrhea, anorexia, nervousness. trifluralin Parasitology A dinitroaniline herbicide, which at micromolar concentrations selectively inhibits the , simazine simazine a triazine weedkiller that is toxic if livestock are allowed access shortly after the plants have been sprayed. Signs of toxicity include staggering in sheep and colic in horses. , metam sodium, dicofol di·co·fol n. A pesticide, C14H9Cl5O, containing a small percentage of DDT and used primarily to control mites on crops. , and chlorothalonil chlo·ro·thal·o·nil n. A colorless crystalline compound, C8Cl4N2,used as a fungicide on a variety of vegetable crops, peanuts, lawns, and turfs and as a preservative in paints and adhesives. . Cancer incidence data. We obtained all cases of invasive cancer diagnosed in children under 15 years of age from California's population-based cancer registry for 1988 through 1994 (reported by April 1997). The statewide registry routinely records race, age, sex, and residence at the time of diagnosis. We assigned census block group designations to cases based on the geocoded location of residence at the time of diagnosis. We completed this task using a GIS to automatically match addresses with a road network and determine the corresponding census block group. We reviewed all addresses that could not be automatically linked and manually located them when possible. Census data. We obtained population data for each census block group from the 1990 census (42) and multiplied population estimates by 7 to account for the person-risk time during the pericensal time period of the study. However, during this time period the population growth rate varied by age groups and race/ethnicity groups. To calculate the different rates of growth by age group and race/ethnicity, we determined the statewide population changes that occurred in each group between 1988 and 1994 (43) and then multiplied the age- and race-specific population for each census block group in 1990 by 7 and the applicable growth factor for that age/race group. To examine potential confounding confounding when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies. confounding factor by socioeconomic status and urbanization, we used additional census information (42). We used quartiles of median family income in the block group as a proxy for neighborhood socioeconomic status and based the degree of urbanization of each block group on the census definition of an urbanized area and on census-defined metropolitan statistical areas. Data analysis. We allocated block groups to agricultural pesticide use categories for four toxicologic groups, four chemical classes, and seven individual pesticides on the basis of statewide distributions of pesticide use density. We based these distributions on only those block groups with > 1 lb/[mi.sup.2] of use for that group or pesticide. For each analysis, the reference group was all block groups with no applications or with < 1 lb/[mi.sup.2] of pesticide use for that group or individual pesticide. We based the other three usage categories on the distributions of pesticide use densities among block groups in the state with > 1 lb/[mi.sup.2] of use density: 1st to 74th percentiles, 75th to 89th percentiles, and [greater than or equal to] 90th percentile. We calculated age-, sex-, and race-adjusted rate ratios (RRs) for childhood cancer incidence and pesticide use density using Poisson regression. For these initial analyses, all types of childhood cancer were analyzed together and the two most common cancer types, leukemias and gliomas (brain cancer), were analyzed separately. We also examined these relationships for the two major leukemia subtypes, acute lymphocytic leukemia acute lymphocytic leukemia n. See acute lymphoblastic leukemia. acute lymphocytic leukemia Acute lymphoblastic leukemia, ALL A malignant lymphoproliferative process that commonly affects children and young adults (ALL) and acute nonlymphocytic leukemia acute non·lym·pho·cyt·ic leukemia n. See acute myelogenous leukemia. (ANLL ANLL Acute nonlymphocytic leukemia ), because associations with pesticides have been reported for these leukemia types. Although there have been suggestive sug·ges·tive adj. 1. a. Tending to suggest; evocative: artifacts suggestive of an ancient society. b. studies for neuroblastoma Neuroblastoma Definition Neuroblastoma is a type of cancer that usually originates either in the tissues of the adrenal gland or in the ganglia of the abdomen or in the ganglia of the nervous system. , non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL) describes a group of cancers arising from lymphocytes, a type of white blood cell. It is distinct from Hodgkin lymphoma in its pathologic features, epidemiology, common sites of involvement, clinical behavior, and treatment. , Wilms tumor tumor: see neoplasm. , and Ewing sarcoma Ewing sarcoma Primitive neuroectodermal tumor, PNET Oncology A primitive neuroectodermal tumor, which primarily affects the midshaft of long bones, which is closely related–if not biologically identical to peripheral neuroepitheliomas Clinical Locoregional (16), the number of cases available for analysis was much smaller. We performed all analyses using SAS (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System. software (44). Results From 1988 to 1994, 7,143 cases of childhood cancer were diagnosed in California. We assigned 6,988 (97.8%) to a census block group. The study period included 46 million person-years of observation for children in California. Table 1 shows the number of geocoded cases by age, race/ethnicity, and sex for all sites, leukemias, and gliomas. Over one-third of the cases were leukemias, and 19% were gliomas; 36% of the total cases were Hispanic children, 47% were non-Hispanic white, and 7% were African American African American Multiculture A person having origins in any of the black racial groups of Africa. See Race. . The number of block groups in the state with use density of > 1 lb/[mi.sup.2] for a given pesticide or group ranged from 1,072 (5% of all block groups) for metam sodium (Table 2) to 7,505 (35%) for genotoxic compounds (Table 3). The distributions of pesticide use density in these block groups were highly skewed skewed curve of a usually unimodal distribution with one tail drawn out more than the other and the median will lie above or below the mean. skewed Epidemiology adjective Referring to an asymmetrical distribution of a population or of data , with order of magnitude A change in quantity or volume as measured by the decimal point. For example, from tens to hundreds is one order of magnitude. Tens to thousands is two orders of magnitude; tens to millions is three orders of magnitude, etc. differences between the median and 90th percentile values, and between the 90th percentile and the maximum. A significant number of block groups in the state had > 100 lb/[mi.sup.2] of pesticide use. For example, at the 75th percentile, 1,233 block groups in the state had > 162 lb/[mi.sup.2] of Class B (probable) carcinogenic pesticide use per year. The distributions of use density for the fumigants methyl bromide and metam sodium were much higher than those of the other individual pesticides. We mapped the geographic distribution of pesticide use density by block group for all probable carcinogens using the percentiles of the statewide distribution. By way of illustration, Figure 1 shows details of these distributions for one highly agricultural county in California (San Joaquin San Joaquin (săn wäkēn`), river, c.320 mi (510 km) long, rising in the Sierra Nevada, E Calif., and flowing W then N through the S Central Valley to form a large delta with the Sacramento River near Suisun Bay, an arm of San Francisco Bay. County). These distributions are described in greater detail elsewhere (34). [FIGURE 1 OMITTED] The RRs obtained from the Poisson regression analysis for all cancer sites, all leukemias, and all gliomas are presented in Tables 2, 3, and 4. The age-, race-, and sex-adjusted RRs for all childhood cancer sites combined were close to 1 for all four toxicologic groups at each usage level. For all cancer sites combined, the RR for areas with high propargite usage had a slightly elevated but not statistically significant RR (1.25). For leukemia, the results were statistically significant (p < 0.05) at the highest usage level for propargite (RR = 1.48). For the gliomas, the adjusted RRs were [less than or equal to] 1 for all the groups and individual pesticides examined. The RR for glioma glioma /gli·o·ma/ (gli-o´mah) a tumor composed of neuroglia in any of its states of development; sometimes extended to include all intrinsic neoplasms of the brain and spinal cord, as astrocytomas, ependymomas, etc. in the highest usage areas for genotoxic pesticides was statistically significantly < 1 [RR = 0.71; 95% confidence interval (CI), 0.52-0.96]. We also examined these relationships for the two major leukemia subtypes, ALL and ANLL. In general, the point estimates for the two subtypes were very similar. The RR for ALL in the highest use areas for propargite was elevated (RR = 1.46), but the CI included 1. Very few cases of block groups with high pesticide use density had cases of ANLL, and the resulting point estimates have wide CIs that all included 1 (data not shown). When we added an additional term for median family income of the block group to the multivariate The use of multiple variables in a forecasting model. models to assess the potential for confounding by socioeconomic status, the results were unchanged (data not shown). When we added an additional term for degree of urbanization, all point estimates increased slightly (data not shown). Discussion In this study, which we designed to give an initial overview of pesticide-associated risk relationships, there is little evidence to support an association between childhood cancer incidence rates and residence in areas of high agricultural pesticide use. The general lack of associations in these results stands in contrast to the positive associations reported in most published case-control studies of childhood cancer and pesticides, and in contrast to the general conclusions implicating im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. a risk association (16,17). Importantly, most previous studies have relied on self-reported pesticide use in the home and garden or parental occupational exposure and have had no information on agricultural pesticide use outside the home. Our study, on the other hand, examined agricultural use and had no data on home use. Some frequently used agricultural pesticides, such as trifluralin, simazine, ziram, 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. , have or have had significant home and garden use. We included these compounds in our toxicologic groups where appropriate. We did examine several pesticides (i.e., propargite, methyl bromide, dicofol, and metam sodium) that are either not marketed for domestic use or are legally restricted to agricultural use in California. Census block groups with high use of propargite did have significantly elevated rates of childhood leukemia in this study, but we observed no dose-response trend over categories of increasing pesticide usage. In contrast, block groups with the highest use of genotoxic pesticides had significantly lower rates of glioma. In animal studies, chemical exposures have been shown to increase and decrease both the incidence and size of tumors (45,46). We incorporated a large number of multiple comparisons into these analyses by testing many pesticide categories and cancer sites, which increased the likelihood of observing at least one statistically significant finding by chance. It is interesting to note, however, that propargite was the highest ranked among individual pesticides for potential cancer hazard based on reported use in California weighted by exposure and carcinogenic potential (34). Propargite is an 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. used primarily in orchards and vineyards to control mites. Propargite is classified as a probable human carcinogen carcinogen: see cancer. carcinogen Agent that can cause cancer. Exposure to one or more carcinogens, including certain chemicals, radiation, and certain viruses, can initiate cancer under conditions not completely understood. based on excess sarcomas Sarcomas Definition A sarcoma is a bone tumor that contains cancer (malignant) cells. A benign bone tumor is an abnormal growth of noncancerous cells. Description A primary bone tumor originates in or near a bone. of the jejunum jejunum: see intestine. observed in rats fed propargite in their diet, although excess tumors have not been found in studies in mice (39). Whether or not this agent may impart risk for childhood leukemia will require additional study. Propargite use in California is concentrated in the Central Valley rather than in other agricultural areas of the state. Propargite use is very high in the areas around three Central Valley communities (including McFarland) which were the sites of childhood cancer "cluster" investigations (all [greater than or equal to] the 97th percentile of use for all block groups) (35). In addition to propargite, two chemicals also used heavily in the Central Valley are ziram and azinphos-methyl. The "cluster" towns also ranked [greater than or equal to] the 95th percentile of use for these pesticides among all block groups statewide. When we subsequently analyzed these two chemicals, ziram had an adjusted RR of 1.54 (95% CI, 0.89-2.66) for leukemia, and azinphos-methyl had an adjusted RR of 1.40 (95% CI, 0.86-2.28) for leukemia. Childhood cancer rates and proximity to agricultural use of specific pesticides have not been previously analyzed, although several studies of adult cancer incidence and mortality have been conducted (47-49); one recent study using the California PUR has reported elevations of adverse reproductive outcomes in high pesticide use areas (50). Our study is the first to examine childhood cancer incidence in relation to pesticides using an ecologic study design. This type of study has several limitations, including the lack of data on potential confounding factors, lack of information on residential stability, and the opportunity for misclassification of group level exposures. However, the design also offers some research advantages. The pesticide data we used in this study were based on mandatory reporting mandatory reporting The obligatory reporting of a particular condition to local or state health authorities, as required for communicable disease and substance abuse Infectious disease State boards of health maintain records and collect data resulting from MR of by growers that was not subject to recall bias. The PUR data also provided specific pesticide active ingredients and the amount applied. We were able to summarize sum·ma·rize intr. & tr.v. sum·ma·rized, sum·ma·riz·ing, sum·ma·riz·es To make a summary or make a summary of. sum and evaluate the use of potentially high hazard individual pesticides and groups of pesticides with similar toxicologic properties. Furthermore, because of the records-based nature of the study, we could include nearly all cases occurring in the population and had no problem with response bias. In this particular situation, an ecologic approach is particularly appealing because the exposures of interest are area specific and are not likely to be accurately reported by individual respondents. Nonetheless, there are improvements that could enhance the accuracy and completeness of exposure attributes from these kinds of data. Pesticide use at the block group level was used as a 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. for exposure in this study. We did not conduct environmental or biologic monitoring to assess actual exposure to children. Pesticide use in homes, schools, and parks is not reported with information on location and could not be included in this analysis. To improve exposure classification, biologic or environmental monitoring needs to be conducted to measure the actual exposure to children from agricultural pesticide use and compare this to exposure from pesticide use in the home, in the garden, and at school. A GIS was essential in this study for geocoding cases and assigning pesticide use to census block groups. The PUR data could be improved for use in epidemiologic studies by improving spatial reporting or by incorporating existing GIS layers with land use or crop classifications to increase the spatial resolution (Data West Research Agency definition: see GIS glossary.) A measure of the accuracy or detail of a graphic display, expressed as dots per inch, pixels per line, lines per millimeter, etc. It is a measure of how fine an image is, usually expressed in dots per inch (dpi). of pesticide applications. Such a project has recently been completed in Kern County, California Kern County is a county located in the southern Central Valley of the U.S. state of California. Established in 1866, it extends east beyond the southern slope of the Eastern Sierra Nevada range into the Mojave Desert, and includes parts of the Western Indian Wells Valley, and . Because of the large number of pesticides reported in the PUR data, we were not able to evaluate each individual compound or all possible combinations of pesticides. Further study is needed in laboratory animals to direct future inquiries of possible interaction effects between combinations of pesticides. The address at diagnosis may not be the most relevant time or place for exposure. Because we were limited to the use of registry data, however, we did not have information on residential history for the subjects. This should be less of a concern for childhood cancer than for adult cancer because of the shorter latency periods latency period n. In psychoanalytic theory, the fourth stage of psychosexual development, extending from about age 5 to puberty, when a child apparently represses sexual urges and prefers to associate with members of the same sex. . We are currently conducting a case-control study using the address of mother's residence from birth certificates and the PUR data, which will allow us to evaluate these risk relationships for residences during another important time window. The exposure methods will be refined to assess pesticide use around a geocoded point rather than a census block group. Although follow-up studies that can better address timing of exposure will be important in assessing the 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. significance of pesticide exposures, this study does address the public concern about whether rates of childhood cancer are higher in areas of heavy agricultural pesticide use. This study is the first to examine RRs for childhood cancer associated with patterns of agricultural pesticide use. The observed lack of association in this study stands in contrast to evidence on household use from the case-control literature, but does not necessarily imply a lack of association with pesticide exposures in general. The current study focuses on residence in areas of high agricultural pesticide use. Little is known about timing of exposure and childhood cancer, and it may be that pesticide exposures during other windows of time such as the perinatal period Perinatal defines period occurring around the time of birth (5 months before and 1 month after). The perinatal period commences at 22 completed weeks (154 days) of gestation (the time when birth weight is normally 500 g), and ends seven completed days after birth. are more important. Furthermore, although there is little detail on specific chemicals in the existing literature, it may be that proximity to agents used for household pest control pest control n → control m de plagas pest control n → lutte f contre les nuisibles pest control pest n is more important than to those used in agriculture. It may be reassuring that the overall incidence of these rare diseases in children does not appear to be associated with living in intensely agricultural areas, but it serves only as a preliminary overview. As for the associations of leukemia with propargite, azinphos-methyl, and ziram, whether or not these agents may impart risk will require additional study. There remain many issues to explore using other study designs before we can determine whether proximity to agricultural pesticide use is a risk factor for childhood cancers.
Table 1. Number of childhood cancer cases by age, race/ethnicity, and
sex from 1988 through 1994 in California.
All sites Leukemias Gliomas
No. (%) No. (%) No. (%)
Age group (years)
0-4 3,515 (50) 1,351 (55) 604 (45)
5-9 1,752 (25) 673 (27) 421 (31)
10-14 1,721 (25) 419 (17) 326 (24)
Race/ethnicity
African American 491 (7) 108 (4) 114 (8)
Hispanic 2,535 (36) 1,013 (41) 390 (29)
Asian, Native
American, other 694 (10) 262 (11) 117 (9)
Non-Hispanic white 3,268 (47) 1,060 (44) 730 (54)
Sex
Male 3,809 (55) 1,349 (55) 733 (54)
Female 3,179 (45) 1,094 (45) 618 (46)
Total 6,988 (100) 2,443 (100) 1,351 (100)
Table 2. Childhood cancer RRsa [and 95% confidence intervals
(CIs)] by block group agricultural pesticide use density for
individual pesticides.
All sites
Percentile No. No. RR
(lb/[mi.sup.2]) block groups cases (95% CI)
Propargite
< 1 lb/[mi.sup.2] 18,907 6,278 Ref
1st-74th 0.92
(1-69) 1,520 542 (0.83-1.10)
75th-89th 0.81
(70-171) 304 86 (0.64-1.02)
[greater than or equal to] 90th 1.25
(172-926) 204 82 (0.99-1.59)
Methyl bromide
< 1 lb/[mi.sup.2] 17,574 5,720 Ref
1st-74th 1.01
(1-836) 2,524 956 (0.93-1.09)
75th-89th 0.98
(837-2,667) 502 177 (0.83-1.16)
[greater than or equal to] 90th 1.01
(2,668-45,185) 335 135 (0.83-1.22)
Metam Sodium
< 1 lb/[mi.sup.2] 19,777 6,575 Ref
1 st-74th 0.95
(1-499) 871 319 (0.85-1.07)
75th-89th 0.95
(500-1,502) 173 58 (0.73-1.23)
[greater than or equal to] 90th 0.81
(1,502-14,480) 114 36 (0.58-1.12)
Trifluralin
< 1 lb/[mi.sup.2] 19,597 6,547 Ref
1 st-74th 0.94
(1-51) 1,005 354 (0.84-1.07)
75th-89th 0.80
(52-117) 205 55 (0.59-1.08)
[greater than or equal to] 90th 0.85
(118-784) 128 32 (0.57-1.26)
Simazine
<1 lb/[mi.sup.2] 18,853 6,255 Ref
1 st-74th 1.02
(1-44) 1,561 563 (0.92-1.12)
75th-89th 0.94
(45-111) 314 92 (0.74-1.19)
[greater than or equal to] 90th 1.17
(112-582) 207 78 (0.91-1.51)
Dicofol
< 1 lb/[mi.sup.2] 19,609 6,514 Ref
1 st-74th 1.03
(1-25) 994 368 (0.90-1.17)
75th-89th 0.91
(26-72) 200 65 (0.68-1.23)
[greater than or equal to] 90th 0.89
(73-352) 132 41 (0.61-1.29)
Chlorothalonil
< 1 lb/[mi.sup.2] 18,603 6,115 Ref
1st-74th 0.99
(1-43) 1,749 672 (0.91-1.08)
75th-89th 0.89
(44-108) 352 108 (0.72-1.10)
[greater than or equal to] 90th 1.04
(109-2,537) 231 93 (0.83-1.30)
Leukemias
Percentile No. RR
(lb/[mi.sup.2]) cases (95% CI)
Propargite
< 1 lb/[mi.sup.2] 2,191 Ref
1st-74th 0.92
(1-69) 191 (0.78-1.08)
75th-89th 0.68
(70-171) 26 (0.45-1.04)
[greater than or equal to] 90th 1.48
(172-926) 35 (1.03-2.13)
Methyl bromide
< 1 lb/[mi.sup.2] 1,981 Ref
1st-74th 1.02
(1-836) 335 (0.90-1.16)
75th-89th 1.15
(837-2,667) 73 (0.89-1.48)
[greater than or equal to] 90th 1.13
(2,668-45,185) 54 (0.84-1.52)
Metam Sodium
< 1 lb/[mi.sup.2] 2,293 Ref
1 st-74th 0.98
(1-499) 116 (0.78-1.24)
75th-89th 0.87
(500-1,502) 19 (0.50-1.53)
[greater than or equal to] 90th 0.92
(1,502-14,480) 15 (0.48-1.73)
Trifluralin
< 1 lb/[mi.sup.2] 2,286 Ref
1 st-74th 0.96
(1-51) 127 (0.79-1.17)
75th-89th 0.73
(52-117) 18 (0.44-1.23)
[greater than or equal to] 90th 0.87
(118-784) 12 (0.46-1.63)
Simazine
<1 lb/[mi.sup.2] 2,198 Ref
1 st-74th 0.92
(1-44) 179 (0.76-1.12)
75th-89th 1.37
(45-111) 47 (0.95-1.98)
[greater than or equal to] 90th 0.79
(112-582) 19 (0.45-1.40)
Dicofol
< 1 lb/[mi.sup.2] 2,283 Ref
1 st-74th 1.02
(1-25) 130 (0.84-1.24)
75th-89th 0.70
(26-72) 18 (0.42-1.17)
[greater than or equal to] 90th 0.72
(73-352) 12 (0.38-1.34)
Chlorothalonil
< 1 lb/[mi.sup.2] 2,119 Ref
1st-74th 1.02
(1-43) 243 (0.88-1.18)
75th-89th 0.92
(44-108) 40 (0.65-1.32)
[greater than or equal to] 90th 1.27
(109-2,537) 41 (0.90-1.80)
Gliomas
Percentile No. RR
(lb/[mi.sup.2] cases (95% CI)
Propargite
< 1 lb/[mi.sup.2] 1,223 Ref
1st-74th 0.82
(1-69) 95 (0.66-1.02)
75th-89th 1.04
(70-171) 21 (0.66-1.62)
[greater than or equal to] 90th 0.98
(172-926) 12 (0.54-1.76)
Methyl bromide
< 1 lb/[mi.sup.2] 1,122 Ref
1st-74th 0.99
(1-836) 186 (0.84-1.16)
75th-89th 0.77
(837-2,667) 27 (0.52-1.14)
[greater than or equal to] 90th 0.63
(2,668-45,185) 16 (0.38-1.05)
Metam Sodium
< 1 lb/[mi.sup.2] 1,282 Ref
1 st-74th 0.87
(1-499) 57 (0.64-1.20)
75th-89th 0.77
(500-1,502) 9 (0.35-1.67)
[greater than or equal to] 90th 0.37
(1,502-14,480) 3 (0.09-1.41)
Trifluralin
< 1 lb/[mi.sup.2] 1,279 Ref
1 st-74th 0.80
(1-51) 58 (0.65-0.98)
75th-89th 0.75
(52-117) 10 (0.46-1.22)
[greater than or equal to] 90th 0.58
(118-784) 4 (0.27-1.25)
Simazine
<1 lb/[mi.sup.2] 1,205 Ref
1 st-74th 1.02
(1-44) 111 (0.85-1.22)
75th-89th 1.08
(45-111) 21 (0.72-1.60)
[greater than or equal to] 90th 1.12
(112-582) 14 (0.69-1.82)
Dicofol
< 1 lb/[mi.sup.2] 1,270 Ref
1 st-74th 0.92
(1-25) 64 (0.71-1.20)
75th-89th 0.52
(26-72) 7 (0.24-1.13)
[greater than or equal to] 90th 1.16
(73-352) 10 (0.60-2.22)
Chlorothalonil
< 1 lb/[mi.sup.2] 1,198 Ref
1st-74th 0.95
(1-43) 126 (0.79-1.15)
75th-89th 0.83
(44-108) 19 (0.52-1.33)
[greater than or equal to] 90th 0.47
(109-2,537) 8 (0.23-0.97)
Ref, reference level.
(a) All RRs were adjusted for age, race, and sex.
Table 3. Childhood cancer RRsa (and 95% CIs) by block group
agricultural pesticide use density for toxico-logic groups.
All sites
Percentile No. block No. RR
(lb/[mi.sup.2]) groups cases (95% Cl)
Class B (probable carcinogens)
<1 lb/[mi.sup.2] 16,099 5,204 Ref
1st-74th 0.98
(1-161) 3,626 1,373 (0.91-1.04)
75th-89th 0.96
(162-568) 725 239 (0.83-1.11)
[greater than or equal to] 90th 0.95
(569-14,935) 485 172 (0.80-1.13)
Class C (possible carcinogens)
<1 lb/[mi.sup.2] 14,694 4,660 Ref
1st-74th 1.00
(1-131) 4,682 1,807 (0.94-1.07)
75th-89th 0.95
(132-444) 940 329 (0.83-1.08)
[greater than or equal to] 90th 0.91
(445-5,043) 619 192 (0.77-1.08)
Genotoxins
<1 lb/[mi.sup.2] 13,549 4,260 Ref
1st-74th 0.96
(1-467) 5,541 2,043 (0.91-1.02)
75th-89th 1.00
(468-1,843) 1,111 419 (0.90-1.12)
[greater than or equal to] 90th 0.96
(1,844-70,670) 734 266 (0.84-1.10)
Developmental and reproductive toxicants
<1 lb/[mi.sup.2] 14,347 4,554 Ref
1st-74th 0.95
(1-481) 4,942 1,805 (0.90-1.01)
75th-89th 1.04
(482-1,788) 988 384 (0.93-1.17)
[greater than or equal to] 90th 0.99
(1,789-48,784) 658 245 (0.86-1.14)
Leukemias
Percentile No. RR
(lb/[mi.sup.2]) cases (95% CI)
Class B (probable carcinogens)
<1 lb/[mi.sup.2] 1,834 Ref
1st-74th 0.91
(1-161) 455 (0.81-1.03)
75th-89th 1.05
(162-568) 95 (0.83-1.33)
[greater than or equal to] 90th 0.89
(569-14,935) 59 (0.66-1.20)
Class C (possible carcinogens)
<1 lb/[mi.sup.2] 1,639 Ref
1st-74th 0.98
(1-131) 620 (0.87-1.09)
75th-89th 0.92
(132-444) 114 (0.74-1.16)
[greater than or equal to] 90th 0.91
(445-5,043) 70 (0.68-1.21)
Genotoxins
<1 lb/mi2 1,495 Ref
1st-74th 0.93
(1-467) 691 (0.83-1.04)
75th-89th 0.97
(468-1,843) 145 (0.79-1.20)
[greater than or equal to] 90th 1.12
(1,844-70,670) 112 (0.89-1.41)
Developmental and reproductive toxicants
<1 lb/[mi.sup.2] 1,590 Ref
1st-74th 0.93
(1-481) 616 (0.84-1.03)
75th-89th 1.03
(482-1,788) 135 (0.84-1.26)
[greater than or equal to] 90th 1.15
(1,789-48,784) 102 (0.91-1.44)
Gliomas
Percentile No. RR
(lb/[mi.sup.2]) cases (95% CI)
Class B (probable carcinogens)
<1 lb/[mi.sup.2] 1,007 Ref
1st-74th 1.03
(1-161) 283 (0.91-1.17)
75th-89th 0.74
(162-568) 35 (0.54-1.01)
[greater than or equal to] 90th 0.78
(569-14,935) 26 (0.54-1.12)
Class C (possible carcinogens)
<1 lb/[mi.sup.2] 896 Ref
1st-74th 1.05
(1-131) 369 (0.93-1.18)
75th-89th 0.84
(132-444) 56 (0.64-1.10)
[greater than or equal to] 90th 0.78
(445-5,043) 30 (0.54-1.12)
Genotoxins
<1 lb/mi2 808 Ref
1st-74th 1.09
(1-467) 443 (0.98-1.22)
75th-89th 0.81
(468-1,843) 64 (0.64-1.03)
[greater than or equal to] 90th 0.71
(1,844-70,670) 36 (0.52-0.96)
Developmental and reproductive toxicants
<1 lb/[mi.sup.2] 874 Ref
1st-74th 1.04
(1-481) 382 (0.93-1.17)
75th-89th 0.85
(482-1,788) 60 (0.66-1.10)
[greater than or equal to] 90th 0.76
(1,789-48,784) 35 (0.55-1.06)
Ref, reference level.
(a) All RRs were adjusted for age, race, and sex.
Table 4. Childhood cancer [RRs.sup.a] (and 95% Cls) by block group
agricultural pesticide use density for chemical groups.
All sites
Percentile No. block No. RR
(lb/[mi.sup.2) groups cases (95% CI)
Organochlorides
< 1 lb/[mi.sup.2] 19,028 6,316 Ref
1st-74th 1.00
(1-32) 1,429 522 (0.89-1.12)
75th-89th 0.97
(33-85) 289 97 (0.75-1.25)
[greater than or equal to] 90th 0.84
(86-589) 189 53 (0.60-1.18)
Organophosphates
< 1 lb/[mi.sup.2] 14,866 4,734 Ref
1st-74th 1.00
(1-100) 4,554 1,752 (0.94-1.06)
75th-89th 0.94
(101-348) 909 309 (0.82-1.07)
[greater than or equal to] 90th 0.90
(349-7,129) 606 193 (0.76-1.06)
Carbamates
< 1 lb/[mi.sup.2] 16,921 5,449 Ref
1st-74th 1.05
(1-53) 3,001 1,213 (0.97-1.13)
75th-89th 0.86
(54-140) 609 180 (0.72-1.02)
[greater than or equal to] 90th 1.01
(141-1,706) 404 146 (0.83-1.23)
Dithiocarbamates
< 1 lb/[mi.sup.2] 17,768 5,844 Ref
1st-74th 0.99
(1-204) 2,375 879 (0.91-1.07)
75th-89th 0.90
(205-763) 475 160 (0.75-1.07)
[greater than or equal to] 90th 0.91
(764-14,931) 317 105 (0.73-1.13)
Leukemias
Percentile No. RR
(lb/[mi.sup.2) cases (95% CI)
Organochlorides
< 1 lb/[mi.sup.2] 2,200 Ref
1st-74th 1.07
(1-32) 196 (0.90-1.26)
75th-89th 0.86
(33-85) 31 (0.57-1.29)
[greater than or equal to] 90th 0.70
(86-589) 16 (0.39-1.23)
Organophosphates
< 1 lb/[mi.sup.2] 1,662 Ref
1st-74th 0. 97
(1-100) 601 (0.88-1.08)
75th-89th 0.93
(101-348) 109 (0.75-1.16)
[greater than or equal to] 90th 0.91
(349-7,129) 71 (0.70-1.18)
Carbamates
< 1 lb/[mi.sup.2] 1,917 Ref
1st-74th 1.00
(1-53) 411 (0.89-1.14)
75th-89th 0.79
(54-140) 60 (0.59-1.07)
[greater than or equal to] 90th 1.03
(141-1,706) 55 (0.75-1.41)
Dithiocarbamates
< 1 lb/[mi.sup.2] 2,035 Ref
1st-74th 1.00
(1-204) 313 (0.87-1.16)
75th-89th 0.91
(205-763) 58 (0.67-1.23)
[greater than or equal to] 90th 0.89
(764-14,931) 37 (0.61-1.30)
Gliomas
Percentile No. RR
(lb/[mi.sup.2) cases (95% CI)
Organochlorides
< 1 lb/[mi.sup.2] 1,238 Ref
1st-74th 0.87
(1-32) 89 (0.69-1.09)
75th-89th 0.74
(33-85) 14 (0.42-1.30)
[greater than or equal to] 90th 0.86
(86-589) 10 (0.44-1.67)
Organophosphates
< 1 lb/[mi.sup.2] 905 Ref
1st-74th 1.09
(1-100) 368 (0.97-1.22)
75th-89th 0.80
(101-348) 50 (0.61-1.05)
[greater than or equal to] 90th 0.71
(349-7,129) 28 (0.50-1.02)
Carbamates
< 1 lb/[mi.sup.2] 1,051 Ref
1st-74th 1.12
(1-53) 251 (0.97-1.29)
75th-89th 0.73
(54-140) 29 (0.50-1.06)
[greater than or equal to] 90th 0.76
(141-1,706) 20 (0.48-1.19)
Dithiocarbamates
< 1 lb/[mi.sup.2] 1,156 Ref
1st-74th 0.85
(1-204) 150 (0.71-1.01)
75th-89th 0.93
(205-763) 32 (0.64-1.34)
[greater than or equal to] 90th 0.59
(764-14,931) 13 (0.33-1.04)
Ref, reference level.
(a) All RRs were adjusted for age, race, and sex.
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The four county study of childhood cancer: clusters in context. Stat Mod 15(7-9):683-697 (1996). (36.) California Department of Pesticide Regulation. Pesticide Use Report System Data, 1991-1994 (Data File). Sacramento, CA:California Department of Pesticide Regulation, 1996. (37.) Environmental Systems Research Institute. ArcView, version 3.0. Redlands, CA:Environmental Systems Research Institute, 1994. (38.) U.S. Bureau of the Census Noun 1. Bureau of the Census - the bureau of the Commerce Department responsible for taking the census; provides demographic information and analyses about the population of the United States Census Bureau . TIGER Line Files (Data File). Washington, DC:U.S. Bureau of the Census, 1995. (39.) U.S. EPA EPA eicosapentaenoic acid. EPA abbr. eicosapentaenoic acid EPA, n.pr See acid, eicosapentaenoic. EPA, n. . Office of Pesticide Programs. The U.S. EPA Reference Dose Tracking Report. Available: http:// npic.orst.edu/tracking.htm [cited 8 March 2001]. (40.) Gold LS, Zeiger E. Handbook of Carcinogenic Potency and Genotoxicity Genotoxic substances are a type of carcinogen, specifically those capable of causing genetic mutation and of contributing to the development of tumors. This includes both certain chemical compounds and certain types of radiation. Databases. New York:CRC (Cyclical Redundancy Checking) An error checking technique used to ensure the accuracy of transmitting digital data. The transmitted messages are divided into predetermined lengths which, used as dividends, are divided by a fixed divisor. Press, 1997. (41.) California Department of Pesticide Regulation. Summaries of Toxicology toxicology, study of poisons, or toxins, from the standpoint of detection, isolation, identification, and determination of their effects on the human body. Toxicology may be considered the branch of pharmacology devoted to the study of the poisonous effects of drugs. Data. Sacramento, CA:California Department of Pesticide Regulation, Medical Toxicology Branch, 1997. (42.) U.S. Bureau of the Census. Census of Population and Housing, 1990: Modified Age/Race, Sex and Hispanic Origin (MARS) State and County File. Washington, DC:U.S. Bureau of the Census, 1992. (43.) California Department of Finance The California Department of Finance is located in Sacramento, California. It is responsible resource allocation for the state’s annual financial plan. As part of the executive branch of the state, it is within the fold of the governor of California's administration. . Race/Ethnic Population with Age and Sex Detail, 1970-2040. Sacramento, CA:State of California, Department of Finance, 1998. (44.) SAS Institute SAS Institute Inc., headquartered in Cary, North Carolina, USA, has been a major producer of software since it was founded in 1976 by Anthony Barr, James Goodnight, John Sall and Jane Helwig. . SAS Version 7.00. Cary, NC:SAS Institute, 1998. (45.) Lee K, Johnson V, Blakley B. The effect of exposure to e commercial 2,4-D 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. formulation during gestation GESTATION, med. jur. The time during which a female, who has conceived, carries the embryo or foetus in her uterus. By the common consent of mankind, the term of gestation is considered to be ten lunar months, or forty weeks, equal to nine calendar months and a week. on urethan-induced lung adenoma adenoma: see neoplasm. formation in CD-1 mice. Vet Hum hum (hum) a low, steady, prolonged sound. venous hum a continuous blowing, singing, or humming murmur heard on auscultation over the right jugular vein in the sitting or erect position; it is Toxicol 42(3):129-132 (2000). (46.) Anderson LM, Diwan Noun 1. diwan - a Muslim council of state divan privy council - an advisory council to a ruler (especially to the British Crown) 2. diwan - a collection of Persian or Arabic poems (usually by one author) divan BA, Fear NT, Roman E. Critical windows of exposure for children's health Children's Health Definition Children's health encompasses the physical, mental, emotional, and social well-being of children from infancy through adolescence. : cancer in human epidemiological studies An Epidemiological study is a statistical study on human populations, which attempts to link human health effects to a specified cause. and neoplasms in experimental animal models. Environ Health Perspect 108(suppl 3):573-594 (2000). (47.) Mills PK. Correlation analysis of pesticide use data and cancer incidence rates in California counties. Arch Environ Health 53(6):410-413 (1998). (48.) Kettles MA, Browning SR, Prince TS, Horstman SW. Triazine tri·a·zine n. 1. Any of three isomeric compounds, C3H3N3, each having three carbon and three nitrogen atoms in a six-membered ring. 2. A compound derived from one of these isomers. herbicide exposure and breast cancer incidence: an ecologic study of Kentucky counties. Environ Health Perspect 105:1222-1227 (1997). (49.) Schreinemachers DM, Creason JP, Garry VF. Cancer mortality in agricultural regions of Minnesota. Environ Health Perspect 107:205-211 (1999). (50.) Bell EM, Hertz-Picciotto I, Beaumont JJ. A case-control study of pesticides and fetal death due to congenital anomalies congenital anomaly n. See birth defect. . Epidemiology 12(2):148-56 (2001). Address correspondence to P. Reynolds, Environmental Health Investigations Branch, 1515 Clay Street, Suite 1700, Oakland, CA 94612 USA. Telephone: (510) 622-4500. Fax: (510) 622-4505. E-mail: preynold@dhs.ca.gov This study was funded by grant R01 CA71745 from the National Cancer Institute. Received 9 May 2001; accepted 7 August 2001. Peggy Reynolds, (1) Julie Von Behren, (1) Robert B. Gunier, (1) Debbie E. Goldberg, (2) Andrew Hertz, (3) and Martha E. Harnly (1) (1) California Department of Health Services, Environmental Health Investigations Branch, 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; (2) Public Health Institute, Berkeley, California Berkeley is a city on the east shore of San Francisco Bay in Northern California, in the United States. Its neighbors to the south are the cities of Oakland and Emeryville. To the north is the city of Albany and the unincorporated community of Kensington. , USA; (3) Impact Assessment Inc., Oakland, California, USA |
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