Effects of Low Levels of Lead Exposure The Centers for Disease Control (CDC) have published a major revision (I) of their 1985 statement Preventing h a d Poisoning in Young Children (2). The new CDC statement (2) relies heavily on the advice of the CDC Advisory Committee on Childhood Lead Poisoning Prevention. As the chairperson of this committee, I am writing on behalf of 11 committee members* to respond to inaccurate or outdated assertions in Joseph Palca's News &Comment article of 23 August 1991 (p. 842) and a letter by Claire B. Emhart and Sandra Scarr (14 Feb., p. 783). Our advisory committee examined new evidence on lead at low exposures as a public health problem, particularly studies conducted since issuance of the 1985 CDC statement. This evidence encompasses areas of epidemiology, experimental animal models of lead's toxic actions, and mechanistic rationales for its potent effects. The CDC committee concurs with Department of Health and Human Services Secretary Louis Sullivan's recent finding that lead is the number one environmental health threat to American children, and it concluded that the evidence linking low levels of lead exposure [ l o micrograms (kg) or more per deciliter (dl) of whole blood] and a constellation of neurotoxic and other adverse effects in young children is compelling. Convincing data are contained in the recent international prospective studies of children reported in Boston (3), Cincinnati (4), and Port Pirie, Australia (5). Such studies have changed how our committee and public health agencies approach childhood lead poisoning. To characterize the pioneering study of Herbert L. Needleman and his co-workers (6), based on measurement of dentine lead in children with blood lead levels (BPb's) between 30 and 50 kg/dl (6), as the "backbone" of current public health policy relating to the definition, treatment, and prevention of this pervasive disease in American children ignores progress in this field during the past decade plus. The studies in Boston (3), Cincinnati (4), and Port Pirie (5) found neurobehavioral and cognitive deficits in infants exposed to lead at BPb's as low as 7 ygldl. The Cincinnati study (4) found effects of prenatal exposure on Mental Developmental Index scores that amounted to an 8-point deficit for each 10 kg/dl increase in BPb. The study in Port Pirie (5) assessed children up to 4 years of age and related the integrated BPb's to the McCarthy Scales of Children's Abilities. The BPb's were observed to be inversely related at age 4, with children having cognitive scores 7.2 points less, once BPb reached 30 kg/dl, compared with children with a BPb less than or equal
to 10 kgldl (5). These and a dozen crosssectional studies are remarkably consistent in identifying the link between low levels of lead exposure during early development and neurobehavioral performance reflected in deficits in indices of early childhood development. In its day, the study by Needleman et al. (6) produced important information of considerable public health relevance. However, to say that Needleman et al.'s 1979 article (6) is the centerpiece of public health policy today is erroneous. A consensus, based on the consistency and strength of the science (1, 3- 5, 7, 8 ) , has been readily achieved by federal agencies (1, 7, 8) concerning the adverse effects of low levels of lead [much lower levels that those examined in Needleman et al.'s initial study (6)] on IQ and neurobehavioral development. John F. Rosen Albert Einstein College of Medicine and Montefiore Medical Center, I 1 1 East 210th Street, Bronx, NY 10467 REFERENCES 1. Preventing Lead Poisoning in Young Children: A Statement b y the Centers for Disease Control (Centers for Disease Control, Atlanta, GA, 1991). 2. Preventing Lead Poisoning in Young Children. A Statement b y the Centers for Disease Control, (DHHS #99-2230, Centers for Disease Control, Atlanta, GA, 1985) 3. D. Bellinger et al., N. Engl. J. Med. 316, 1037 (1987). 4. K. N. Dietrich et al., in Lead Exposure and Child Development: An International Asessment, M Smith, L. D. Grant, A Sors, Eds. (MTP Press, Lancaster, United Kingdom, 1989), pp. 320-331 5. A. J. McMichael et al., N. Engl. J. Med. 319, 468 (1988). 6. H. L. Needleman et al., ibid. 300, 689 (1979). 7. The Nature and Extent of Childhood Lead Poisoning in the United States: A Report to Congress (Agency For Toxic Substances and Disease Registry, Public Health Service, Atlanta, GA, 1988). 8. Air Quality Criteria for Lead: Supplement to the 1986 Addendum (EPN600-8-89-049f, Environmental Criteria and Assessment Office, Office of Research and Development, Environmental Protection Agency, Research Triangle Park, NC, August 1990)
Comment article that are not supported by either data or logic. They neglect to mention that it was they who placed allegations against me with the National Institutes of Health Office of Scientific Integrity. In 1983, Scarr was appointed to an EPA review committee chaired by Lester Grant, Director of the Environmental Protection Agency (EPA) Criteria Office. The committee was asked to suggest possible ways of reanalyzing data on the relationship between low doses of lead and IQ. After examining my printouts and Ernhart's, the committee recommended that I reclassify subjects by mean dentine lead levels, enter age into the model, and reanalyze the data. The reanalysis showed that after age was added in the regression of raw IQ scores, there was a significant association between lead and IQ (P < 0.025). This finding was presented to EPA's Clean Air Science Advisory Council (CASAC) on 27 April 1984 and published in a letter in Science (I). It is well known that IQ scores are adjusted for age. Lead in tooth is correlated with age (r = 0.2). If one adjusts for age in models that use age-adjusted outcomes, one is necessarily subtracting out variance due to lead. Such a classic case of overcontrol is a subject generally dealt with in early statistics courses. Ernhart and Scarr were present when CASAC, having reviewed my testimony and that of EPA statistician Hugh Pitcher, recommended that my studies be included in the Criteria Document and that the Committee report not be published. Grant, noting that the lead industry, through Hill and Knowlton, was disseminating the discarded draft report as official EPA policy, wrote to me as follows (2). I t is unfortunate that the parties concerned apparently choose t o allude t o the 1983 Neurobehavioral Committee Report out o f context and t o ignore later developments [These] include the following widely k n o w n facts: (1) Reanalyses have been carried out by you and your colleagues in response t o criticisms and recommendations [These] confirm your earlier published findings o n significant associations between pediatric lead exposures and decreased IQ. Similar results were found b y reanalyses o f the original data set carried out by EPA's Office o f Policy, Planning and Evaluation. (2) All those reanalyses were made available for public review b y the [ C A S A C ] , w h i c h judged that they adequately resolved issues raised b y the Neurobehavioral Committee Report.
...
...
'Ronald L. Fletcher, Greene Memorlal Hospital, Xenia, OH; Lynn R. Goldman, Department of Health Services, Emeryville, CA; Dwala S. Griffin, Board of Health, Louisville, KY; Richard J. Jackson, Chairman, American Academy of Pediatrics Committee on Environmental Hazards, California Department of Health Services, Berkeley, CA; Rudolph E. Jackson, Morehouse School of Medicine, Atlanta, GA; James C Keck, Lead Tec Servlces, Baltimore, MD; Sergio Piomelli, Columbia University (Bab~es Hosp~tal), New York, NY; Stephanie L. Pollack, Conservation Law Foundation of New England, Boston, MA; Noel V. Stanton, State Laboratory of Hygiene, Madison, WI; Beverly Coleman-Miller, Commission of Public Health, Washington, DC; Knut R~ngen,Laborers' National Health and Safety Fund, Washington, DC.
In their letter of 14 February, Scarr and Ernhart repeat arguments attributed to them in Palca's 23 August 1991 News & SCIENCE
VOL. 256
17 APRIL 1992
In 1974, Emhart published a study that showed a relationship between lead and IQ in 80 preschoolers (3), concluding, "analysis of group data indicate quite clearly that performance on an intelligence test is impaired. . . . [Tlhe criteria set for lead poisoning need re-examination. . . ." In 1981,
she followed up 63 of those subjects (4) and, despite finding a significant relationship between contemporary blood lead and IQ, concluded, "If there are, in fact behavioral and intellectual sequelae at low levels of lead these effects are minimal." Within a year Ernhart was a grantee of the lead industry. EPA's comments (5) are noteworthy.
...
NEW
[Aln amciation between lead and lower Verbal Index scores was nevertheless observed across several of the analyses (at p values ranging from 0.04 to 0.10) and . . . an association between preschool lead levels and General Cognitive Index scores approached significance at P < .09. A t a recent international meeeine. T. G r e e n e and Ernhart reported that children with elevated dentine lead levels had lower verbal IQ scores, after covariate adjustment (5). They appear t o have replicated the study we published 13 years ago. Their bibliography contained n o reference t o the work of my group. Scarr and Ernhart make n o substantive claims against t h e three published metaanalyses of t h e field (6),all of which show a strong lead-IQ association, but they appear to dismiss two because I was t h e senior author. Meta-analysis is relatively free of e x ~ e r i m e n t e rbias if t h e methods are applied properly and t h e arithmetic is correct. Science provides a way to transmute this debate from polemic t o inquiry: Scarr and Ernhart c a n check my arithmetic, and then meta-analyze t h e same data set, including t h e papers published after my analyses. Others c a n then evaluate their conclusions-after checking their arithmetic.
Herbert L. Needleman Western Psychiatric Institute and Clinic, University of Pittsburgh, 381 1 O'Hara Street, Pittsburgh, PA 152 13-2593 REFERENCES 1. H. L Needleman, Science 227, 701 (1985). 2. L. D. Grant, personal communication. 15 May 1986. 3. J. Perino and C. B. Emhart. J. Learn. Disabil. 7,26 (1974). 4. C. B. Emhart, B. Landa, N. B. Schell, Pediatrics 67, 911 (1981). 5. C. 8. Emhart and T. Greene, paper presented at
the Heavy Metals in the Environment meeting, Edinburgh, United Kingdom. 16 to 20 September 1991. 6. H. L. Needleman and D. Bellinger, in Lead Eposure and Child Development: An International Assessment, M. Smith, L. Grant, A. Sors, Eds. (MTP Press. Lancaster. United Kingdom, 1988); H. L. Needlemanand C. A. Gatsonic. J. Am. Med. Asax. 263. 673 (1990); J. Schwartz. H. Pitcher. R. Levin, 6. Ostro, A. L Nicholas, Cost and Benefits of Reducing Lead in Gasoline: Final Regulatory lmpect Analysis (Office of Policy Analysis, Environmental ProtectionAgency, Washington, DC, 1985).
.
GoodNewsfiorm and Windows users! EndNote Plus on the PC is shipping! If you're using Microsoft Word for Windows, WordPerfect, or Wordperfect for Windows, EndNote Plus can save you hours of work! You want to cite a paper? Simply switch to EndNote Plus, s e l a t h e reference and paste it into anv of these word r~rocessors!When you're &ady to submit your paper, select a bibliographic style and EndNote Plus will format both the bibliography and the in-text citations according to the selected style. ~-~
-
~
- ~ - - --
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Whyfs EdNote Plus Better? 'Wsan in the details.'' Most bibliographic software packages include basic features like the abiity to search for references and output them in different formats. But as one of our users told us recently: "It's all in the details". The differences emerge when you ask yourself questions like these: C a n my records include expressions like a or 14C and diacritical marks like 6 or ti? D o e s my software refonnat just the bibliography or also the in-text citations? I Does it work diredlv with Windows word processors? with wordperfect? D o e s it suvuort different reference t m ? (e.g.. j o u r d articles, books, theses; kc.) I Does it output the bibliography in my word proceisor or just a s a n - ~ C Ifile? I I Will it take me less than 5 minutes to teach a student how to enter data? C a n it output authors with full names or initials? with or without periods? with or without spaces? with or without commas? D o e s it have a TSR? If so, does it allow me to add, edit and search references? C a n it output the first author's name as J. Smith and the second author as Johns, G.? W i l l it find records quickly and easily? l C a n I share data with Mac users without loosing Greek characters and diacriticals? C a n I easily create my own style? I s it completely free of copy-protection? I Was it updated in the last 12 months?
Can I easily move between fields even if I'm not 6nished entering one? I Can I add fields for my own use?Are there fields for abstracts and notes?
UM Optnfon= Obviously, we're a little biased, so here's what the press has said about our products "the clear winner in the bibliographic database management race." -MucGuide "[it does] practically everything except type in the data" -Personal Computer World "The results we got from EndNote Plus were --MacWeek outstandug." "EndNote Plus is a terrific bargain." -4-h Today
We realize that you may have thousands of records in your old program, so we made it easier for vou to switch. We have instructions on &sferring data from several bibliographic programs into EndNote Plus. Call us td see a th-ese instructions cover the software you currently use.
I UpgradeNowforJ169 If you upgrade before 5130192, you'll pay just $169 instead of $249. Send a photocovv of the first page of the manual of any bibliographic software (PCor Mac). Attach it to your check or fax it with your university purchase order to (510)649-8179. If you're not 100% happy with EndNote Plus, simply return it within 30 days and we will refund your money. N i b & Acmck&s, inc. 2000 Hearst Ave. MOO
= Bddey, CA 94709 Pfnnm (510) 649-8176 Fax: (510) 6498179 Purcbxadmrapteddyfrom~tla in the US. AU hodemsdrs.dmowkdged.
Cirde No. 6 on Readers' Service Card
to 10 kgldl (5). These and a dozen crosssectional studies are remarkably consistent in identifying the link between low levels of lead exposure during early development and neurobehavioral performance reflected in deficits in indices of early childhood development. In its day, the study by Needleman et al. (6) produced important information of considerable public health relevance. However, to say that Needleman et al.'s 1979 article (6) is the centerpiece of public health policy today is erroneous. A consensus, based on the consistency and strength of the science (1, 3- 5, 7, 8 ) , has been readily achieved by federal agencies (1, 7, 8) concerning the adverse effects of low levels of lead [much lower levels that those examined in Needleman et al.'s initial study (6)] on IQ and neurobehavioral development. John F. Rosen Albert Einstein College of Medicine and Montefiore Medical Center, I 1 1 East 210th Street, Bronx, NY 10467 REFERENCES 1. Preventing Lead Poisoning in Young Children: A Statement b y the Centers for Disease Control (Centers for Disease Control, Atlanta, GA, 1991). 2. Preventing Lead Poisoning in Young Children. A Statement b y the Centers for Disease Control, (DHHS #99-2230, Centers for Disease Control, Atlanta, GA, 1985) 3. D. Bellinger et al., N. Engl. J. Med. 316, 1037 (1987). 4. K. N. Dietrich et al., in Lead Exposure and Child Development: An International Asessment, M Smith, L. D. Grant, A Sors, Eds. (MTP Press, Lancaster, United Kingdom, 1989), pp. 320-331 5. A. J. McMichael et al., N. Engl. J. Med. 319, 468 (1988). 6. H. L. Needleman et al., ibid. 300, 689 (1979). 7. The Nature and Extent of Childhood Lead Poisoning in the United States: A Report to Congress (Agency For Toxic Substances and Disease Registry, Public Health Service, Atlanta, GA, 1988). 8. Air Quality Criteria for Lead: Supplement to the 1986 Addendum (EPN600-8-89-049f, Environmental Criteria and Assessment Office, Office of Research and Development, Environmental Protection Agency, Research Triangle Park, NC, August 1990)
Comment article that are not supported by either data or logic. They neglect to mention that it was they who placed allegations against me with the National Institutes of Health Office of Scientific Integrity. In 1983, Scarr was appointed to an EPA review committee chaired by Lester Grant, Director of the Environmental Protection Agency (EPA) Criteria Office. The committee was asked to suggest possible ways of reanalyzing data on the relationship between low doses of lead and IQ. After examining my printouts and Ernhart's, the committee recommended that I reclassify subjects by mean dentine lead levels, enter age into the model, and reanalyze the data. The reanalysis showed that after age was added in the regression of raw IQ scores, there was a significant association between lead and IQ (P < 0.025). This finding was presented to EPA's Clean Air Science Advisory Council (CASAC) on 27 April 1984 and published in a letter in Science (I). It is well known that IQ scores are adjusted for age. Lead in tooth is correlated with age (r = 0.2). If one adjusts for age in models that use age-adjusted outcomes, one is necessarily subtracting out variance due to lead. Such a classic case of overcontrol is a subject generally dealt with in early statistics courses. Ernhart and Scarr were present when CASAC, having reviewed my testimony and that of EPA statistician Hugh Pitcher, recommended that my studies be included in the Criteria Document and that the Committee report not be published. Grant, noting that the lead industry, through Hill and Knowlton, was disseminating the discarded draft report as official EPA policy, wrote to me as follows (2). I t is unfortunate that the parties concerned apparently choose t o allude t o the 1983 Neurobehavioral Committee Report out o f context and t o ignore later developments [These] include the following widely k n o w n facts: (1) Reanalyses have been carried out by you and your colleagues in response t o criticisms and recommendations [These] confirm your earlier published findings o n significant associations between pediatric lead exposures and decreased IQ. Similar results were found b y reanalyses o f the original data set carried out by EPA's Office o f Policy, Planning and Evaluation. (2) All those reanalyses were made available for public review b y the [ C A S A C ] , w h i c h judged that they adequately resolved issues raised b y the Neurobehavioral Committee Report.
...
...
'Ronald L. Fletcher, Greene Memorlal Hospital, Xenia, OH; Lynn R. Goldman, Department of Health Services, Emeryville, CA; Dwala S. Griffin, Board of Health, Louisville, KY; Richard J. Jackson, Chairman, American Academy of Pediatrics Committee on Environmental Hazards, California Department of Health Services, Berkeley, CA; Rudolph E. Jackson, Morehouse School of Medicine, Atlanta, GA; James C Keck, Lead Tec Servlces, Baltimore, MD; Sergio Piomelli, Columbia University (Bab~es Hosp~tal), New York, NY; Stephanie L. Pollack, Conservation Law Foundation of New England, Boston, MA; Noel V. Stanton, State Laboratory of Hygiene, Madison, WI; Beverly Coleman-Miller, Commission of Public Health, Washington, DC; Knut R~ngen,Laborers' National Health and Safety Fund, Washington, DC.
In their letter of 14 February, Scarr and Ernhart repeat arguments attributed to them in Palca's 23 August 1991 News & SCIENCE
VOL. 256
17 APRIL 1992
In 1974, Emhart published a study that showed a relationship between lead and IQ in 80 preschoolers (3), concluding, "analysis of group data indicate quite clearly that performance on an intelligence test is impaired. . . . [Tlhe criteria set for lead poisoning need re-examination. . . ." In 1981,
she followed up 63 of those subjects (4) and, despite finding a significant relationship between contemporary blood lead and IQ, concluded, "If there are, in fact behavioral and intellectual sequelae at low levels of lead these effects are minimal." Within a year Ernhart was a grantee of the lead industry. EPA's comments (5) are noteworthy.
...
NEW
[Aln amciation between lead and lower Verbal Index scores was nevertheless observed across several of the analyses (at p values ranging from 0.04 to 0.10) and . . . an association between preschool lead levels and General Cognitive Index scores approached significance at P < .09. A t a recent international meeeine. T. G r e e n e and Ernhart reported that children with elevated dentine lead levels had lower verbal IQ scores, after covariate adjustment (5). They appear t o have replicated the study we published 13 years ago. Their bibliography contained n o reference t o the work of my group. Scarr and Ernhart make n o substantive claims against t h e three published metaanalyses of t h e field (6),all of which show a strong lead-IQ association, but they appear to dismiss two because I was t h e senior author. Meta-analysis is relatively free of e x ~ e r i m e n t e rbias if t h e methods are applied properly and t h e arithmetic is correct. Science provides a way to transmute this debate from polemic t o inquiry: Scarr and Ernhart c a n check my arithmetic, and then meta-analyze t h e same data set, including t h e papers published after my analyses. Others c a n then evaluate their conclusions-after checking their arithmetic.
Herbert L. Needleman Western Psychiatric Institute and Clinic, University of Pittsburgh, 381 1 O'Hara Street, Pittsburgh, PA 152 13-2593 REFERENCES 1. H. L Needleman, Science 227, 701 (1985). 2. L. D. Grant, personal communication. 15 May 1986. 3. J. Perino and C. B. Emhart. J. Learn. Disabil. 7,26 (1974). 4. C. B. Emhart, B. Landa, N. B. Schell, Pediatrics 67, 911 (1981). 5. C. 8. Emhart and T. Greene, paper presented at
the Heavy Metals in the Environment meeting, Edinburgh, United Kingdom. 16 to 20 September 1991. 6. H. L. Needleman and D. Bellinger, in Lead Eposure and Child Development: An International Assessment, M. Smith, L. Grant, A. Sors, Eds. (MTP Press. Lancaster. United Kingdom, 1988); H. L. Needlemanand C. A. Gatsonic. J. Am. Med. Asax. 263. 673 (1990); J. Schwartz. H. Pitcher. R. Levin, 6. Ostro, A. L Nicholas, Cost and Benefits of Reducing Lead in Gasoline: Final Regulatory lmpect Analysis (Office of Policy Analysis, Environmental ProtectionAgency, Washington, DC, 1985).
.
GoodNewsfiorm and Windows users! EndNote Plus on the PC is shipping! If you're using Microsoft Word for Windows, WordPerfect, or Wordperfect for Windows, EndNote Plus can save you hours of work! You want to cite a paper? Simply switch to EndNote Plus, s e l a t h e reference and paste it into anv of these word r~rocessors!When you're &ady to submit your paper, select a bibliographic style and EndNote Plus will format both the bibliography and the in-text citations according to the selected style. ~-~
-
~
- ~ - - --
-----
Whyfs EdNote Plus Better? 'Wsan in the details.'' Most bibliographic software packages include basic features like the abiity to search for references and output them in different formats. But as one of our users told us recently: "It's all in the details". The differences emerge when you ask yourself questions like these: C a n my records include expressions like a or 14C and diacritical marks like 6 or ti? D o e s my software refonnat just the bibliography or also the in-text citations? I Does it work diredlv with Windows word processors? with wordperfect? D o e s it suvuort different reference t m ? (e.g.. j o u r d articles, books, theses; kc.) I Does it output the bibliography in my word proceisor or just a s a n - ~ C Ifile? I I Will it take me less than 5 minutes to teach a student how to enter data? C a n it output authors with full names or initials? with or without periods? with or without spaces? with or without commas? D o e s it have a TSR? If so, does it allow me to add, edit and search references? C a n it output the first author's name as J. Smith and the second author as Johns, G.? W i l l it find records quickly and easily? l C a n I share data with Mac users without loosing Greek characters and diacriticals? C a n I easily create my own style? I s it completely free of copy-protection? I Was it updated in the last 12 months?
Can I easily move between fields even if I'm not 6nished entering one? I Can I add fields for my own use?Are there fields for abstracts and notes?
UM Optnfon= Obviously, we're a little biased, so here's what the press has said about our products "the clear winner in the bibliographic database management race." -MucGuide "[it does] practically everything except type in the data" -Personal Computer World "The results we got from EndNote Plus were --MacWeek outstandug." "EndNote Plus is a terrific bargain." -4-h Today
We realize that you may have thousands of records in your old program, so we made it easier for vou to switch. We have instructions on &sferring data from several bibliographic programs into EndNote Plus. Call us td see a th-ese instructions cover the software you currently use.
I UpgradeNowforJ169 If you upgrade before 5130192, you'll pay just $169 instead of $249. Send a photocovv of the first page of the manual of any bibliographic software (PCor Mac). Attach it to your check or fax it with your university purchase order to (510)649-8179. If you're not 100% happy with EndNote Plus, simply return it within 30 days and we will refund your money. N i b & Acmck&s, inc. 2000 Hearst Ave. MOO
= Bddey, CA 94709 Pfnnm (510) 649-8176 Fax: (510) 6498179 Purcbxadmrapteddyfrom~tla in the US. AU hodemsdrs.dmowkdged.
Cirde No. 6 on Readers' Service Card
