Dursban Revisited: Birth Defects
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Dursban Revisited: Birth Defects
Date:
Tue, 17 Sep 2002 11:30:46 -0400
From:
Stephen Tvedten <steve@getipm.com>
Organization: Get Set Inc. (www.getipm.com)
To: Paul Helliker <phelliker@cdpr.ca.gov>
Director, State of California, Department of Pesticide
Regulation
cc: Christine Whitman whitman.christine@epa.gov
Dursban revisited: Birth defects, U.S. Environmental Protection Agency,
and Centers for Disease Control.
(Editorial) - Sherman, Janette D.
Archives of Environmental Health , Volume: 52 , Number: 5 , Page: 332(2) , Sept-Oct 1997 IN EARLY 1996, birth defects were associated with in utero exposure to Dursban.(1,2) In accordance with the U.S. Environmental Protection Agency's (EPA's) Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), DowElanco, the manufacturer of Dursban, reported 10 adverse reproductive outcomes associated with Dursban exposure during pregnancy.(3)
In response to the Dursban-related birth-defects issue, EPA submitted medical data to the Division of Birth Defects and Development Disabilities at the Centers for Disease Control and Prevention (CDC) in Atlanta. A report about the Dursban-related birth defects dated December 18, 1996, and signed by three persons from CDC was sent to EPA. Although no sources were given, in the report it was stated: "Two have been diagnosed with a recessively inherited genetic disorder and it was concluded that "At the present, there does not appear to be a consistent phenotypic pattern of anomalies among the infants whose records we reviewed. In addition, you reported that Dursban is used extensively in the United States. Based upon the available medical records and the likely high frequency of this exposure, we would be hesitant to recommend pursuing major epidemiological studies at this point in time."(4)
The CDC statement "likely high frequency of this exposure" is curious, given the implications for public health. If exposure is indeed extensive, examination of the birth defects issue could result in significant public benefits (i.e., prevention of morbidity and mortality).(5)
Abnormalities found by CDC personnel versus abnormalities obtained from the medical records and physical examinations of the affected children are shown in Table 1. The CDC did not code 21 of 63 abnormalities. If the pattern of anomalies of the brain, eyes, ears, limbs, and genitourinary system shown in Table I are not teratogenic, what are they? If CDC personnel fail to code 21 of a possible positive 63 abnormalities (i.e., a full one-third), how can they, or EPA, or anyone determine if a pattern exists?
Table 1--Comparison of Data from Centers for Disease Control with Medical Record (M.R) Data for Dursban-Exposed Children with Birth Defects CDC M. R.
Defect data data Difference Brain/CNS anomalies 8/9 8/9 0 Eye anomalies 7/9 9/9 -2 Cardiac anomalies 3/9 4/9 -1 Ear anomalies 3/9 5/9 -2 Palate anomalies 2/9 9/9 -7 Cleft 1/9 1/9 0 Limb anomalies 3/9 5/9 -2 Genitourinary 3/9 7/9 -4 Undescended testes 3/4 4/4 -1 Labial abnormality 0 2/5 -2 Additional anomalies present in children and not coded by CDC Microphallus 3/4 Abnormality of corpus callosum 4/9 Nipples widespread or abnormal 7/9 Hypotonia 7/9 Mental retardation 9/9 Note: Excluded from both data columns is child #7, whose sole birth defect was choanal atresia. The record was not available to the author.
The following materials were available to EPA personnel for review medical records of children, spread sheets of findings in eight exposed children, published articles with full toxicology references, and Dow/DowElanco submissions to EPA with respect to Dursban. It is of concern that EPA did not rectify, or at least report, the marked differences between the data created by CDC and data available from the medical records.
On January 14, 1997, the EPA released a report by Dr. Jerome Blondell, who is a health statistician in the Health Effects Division (HED) of EPA charged with review of multiple complaints submitted to EPA concerning the adverse effects that occurred after exposure to Dursban. In the birth-defects issue, trichloropyridinol (TCP), which is (a) used to manufacture chlorpyrifos, (b) found as a by-product in Dursban, and (c) formed during the metabolic breakdown of chlorpyrifos, was addressed. In the report, a memorandum was cited and it was noted that "OPP (Office of Pesticide Programs) review of these two studies found no significant increase in incidence of teratogenic effects in rats. The study of rabbits found 'the suggestion of an increase in central nervous system anomalies (hydrocephaly/dilated cerebral ventricles) in both the number of fetuses and litters at doses of 100 (mid-dose) and 250 (high dose) mg/kg/day.'"(6) The EPA report continued: "Overall, 15.4% and 23.1% of the litters in the mid- and high-dose groups, respectively, exhibited evidence of central nervous system (CNS) abnormalities, compared to 6.7% in the control group and none in the low-dose group."
The following significant Dow Chemical Corporation submissions to EPA were not included in the EPA-OPP report: Hanley's study, in which teratogenicity of TCP was reported(7); and the Material Safety Data Sheet, submitted by Dow to EPA 4 y later, in which the teratogenicity of trichloropyridinol was stated.(8)
These findings should satisfy criteria for teratogenicity of Dursban and its TCP component. But the EPA reviewers stated that "the mid-dose with effects in rabbits is 34,000 times greater than the worst estimates reported for chlorpyrifos exposure in one of the human case reports."
Whatever constituted the "worst-estimate-reported" amount and its source was not cited.
No exposure measurements for any of nine children were made at the time of exposure in utero. It was not until after each of these children underwent extensive evaluation (i.e., search for possible cause of their birth anomalies) that a history of Dursban exposure was obtained. The quantification of "dose" in utero for these children is as elusive as measuring the "dose" of asbestos in victims who developed mesothelioma.
The medical world accepted that in utero exposures were "sufficient" to result in recognized abnormalities: eye, ear, and heart defects resulted from rubella infection,(9,10) and limb, heart, eye, intestinal, and kidney defects resulted from thalidomide exposure.(11)
At the end of EPA's report--in which the disparity between CDC's findings and the medical records was not considered--is the statement "HED concludes the available evidence does not support a finding of teratogenicity based on human epidemiology studies and case reports. On rare occasion, case reports can lead to the identification of a new risk factor for a disease. However, the strength of evidence from case reports reported so far do not support a finding of teratogenicity."(12)
If CDC and EPA fail to consider (a) Dursban exposure, (b) the toxicology of Dursban and its components (including trichloropyridinol), and (c)
the data in the medical records, and instead base their recommendations upon incomplete information, they fail to protect the public's interest.
Of little comfort--and of no help in determining the extent of the problem--is EPAs failure to actively seek additional case reports. At the least, curiosity should drive an inquiry.
The costs of raising one of these children, who burden families, schools, and social services, begin at $500,000.00. Prevention is less costly and morally imperative.
References
(1) Sherman JD. Chlorpyrifos (Dursban) -associated birth defects report of four cases. Arch Environ Health 1996; 51(1):5-8.
(2) Sherman JD. Chlorpyrifos (Dursban) -associated birth defects: a proposed syndrome, report of four cases, and discussion of the toxicicology. Int J Occup Med Toxicol 1995; 4(4):417-31.
(3) Reported by DowElanco to the U.S. Environmental Protection Agency (EPA) in October and November 1994. The cases are identified under DowElanco Research Business Index (DERBI) numbers 9920, 23154, 23178, 23194, 23296, 23397, 23436, 23575, 23577, and 28735, under Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), section 6(a)(2). These are available from EPA under the Freedom of Information Act.
(4) Erickson JD, Moore CA, Roberts HE. Birth Defects and Genetic Diseases Branch, Division of Birth Defects and Developmental Disabilities. Atlanta, GA: Centers for Disease Control and Prevention, December 18, 1996; 2 pp with 1-p attachment.
(5) Rogers JM, Kavlock RJ. Developmental toxicology. In: Casarett and Doull's Toxicology. New York: McGraw-Hill, 1996; p 322 (5th ed).
(6) Blondell J, Dobozy VA. Review of Chlorpyrifos Poisoning Data. Office of Prevention, Pesticides and Toxic Substances: U.S.Environmental Protection Agency, January 14, 1997 (70 pp).
(7) Hanley TR Jr, Zielke Gj, Lomax LG. 3,5,6-Trichloro-2-Pyridinol Oral Teratology Study in New Zealand White Rabbits. Midland, MI: Dow Chemical Co., Mammalian and Environmental Toxicology Research Laboratory, Health and Environmental Sciences; July 23, 1987 (148 pp). (Available from EPA under the Freedom of Information Act)
(8) Dow Chemical Co. MSDS, trichloropyridinol August 2, 1991 (3 pp). (Available from EPA under the Freedom of Information Act)
(9) Gregg NM. Congenital cataract following German measles in the mother. Tr Opthamol Soc Aust 1941; 3:35.
(10) Sever JL. Rubella as a teratogen. Adv Teratol 1983; 2:127-38.
(11) McBride WG. Thalidomide and congenital anomalies. Lancet 1961; 2:1358.
(12) Blondell J, Dobozy VA. Review of Chlorpyrifos Poisoning Data. Office of Prevention, Pesticides and Toxic Substances: U.S. Environmental Protection Agency, January 14, 1997; p 52.
(Note: The author has no financial interest in the cases described herein. The author was paid for her time to examine six of the children as well as for her time to review the medical records of one child who died. The author has not been compensated for her time to review the documents, supplied as a courtesy, for two of the children)
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