Document rBpZk697Dewb3kYO5G7g4d4ye

1,.. ...Abstract. Summary Summary of Study Results The, objective of this study was to determine the effects of expo sure to organic ^ (me inly tetraethyl lead) and inorganic lead on the csr.trsi ar.d peripheral: nervous1" system in workers in the Antiknocks area of DuPcnu's Chambers Works plant. A total of 222 lead-exposed workers and 62 non-exposed controls were tested in March-June 1990. 2, 2. ' : 3. :~'4. Exposure to organic ar.d inorganic lead "was consistently associated with poorer performance on many of the neurcbchavicral measures ` (s*a? t a b J for a summary of the associations). All of the significant e;xosure-oi5toome associations clustered r.vro three specific neurobehavicral functional comeins: verbal memory, attention/concentration, and speed ar.d accuracy cf nrr.tr 1/motor executive functions (see TAB'S E for s '.on of these domains). Expcsurfc tc srgarjc and inorganic "was.. with rr-po/i measured b y Inventory, lation, fcanainavian QuGStjonr;ire 16 (see TAB J)# He cssociati or s were found between organic^ and liborganic 1 cs& pxpcsurr sr.a *'ib'*tf on tnrccbolc. |,g[ measupfe of peripheral r.ervcur? evseem oarage) or olfaplfry function-. The findings noted in numbers 1-4, above,. were not rigr: fioa.nuiy al t^-rai after controlling for important factors confounding vcrio?ec) kno-^n,-tp affect performs nee on these tests /'such er education or .alcohol intake). Multiple linger regression vac psed-tS control fer a group of fjv* confounding ^.irliablM edoczta onal level or vocabulary score, r/ip^ihg hisfory, aaccnol history, and r??., in all Cs. enrol for f-nr ther potent:*3 ronfruudinc variable, expo- svj'p to ether j rurntcy-ur, both occupationally and avocations 12y, 0:d not epperr tc altan the conclusions* Ar.alyrrr with f.rn are envoinc. v *7657 6 Hite:' DUP040010853 Additional Important comments While causal inferences can not be conclusively determined from a cross-sectional epidemiologic study, these results are suggestive that organic and inorganic lead adversely effects the central nervous system. The affected domains correspond to the neuroanatomic areas . 1 iipilp^nyf l|jpM^i;:!:-|^jj^|::||||!ij||^ i ijclprip: ;" 'ajil ' f|o|^b|t>iye. '^b&otlkbtieJ The plots of some of the relations between the outcomes and the exprarure and dos-s variables indicate that some of the associations are r.ct inrcrprstable at this time {e.g., are Ushaped, such That in workers with h,igh exposure neurobehavioral function improves), despite significant findings from the regression model? (TAB F; . The two major competing explana tion?: for these plots--that there is no association or that selection hiss account? fer the results--would have to be sorted out in a prospective study. The interpretation of the U-shaped plots may be facilitated by11 the'sei''jtwjp'ifdrthe'r'pbin'tis: 1) Our understanding of the Antiknocks area is that thousands Of workers have been employed there since its inception. This cross-sectional study of 222 current workers thus reflects the results from a cohort with much out-migration; selection bias nay be a significant problein. 2) Many of the U-shaped associations became more linear aj^||,-adyebsei,;dirif!bt:i.pi,i after elimination bf a group of workers with the highest exposure or internal dose values.' it should be noted that our conclusions are based On exposure to iiitrg^iiisi. ' pgajhio' jlfead':combined only one of the 7 exposure and dose variables cumulates only organic lead. However, we feel that, because organic lead represents the majority of lead exposure in the area and because this species of lead is more lipophilic, the observed associations are more likely due to organic lead. Results from a prospective study would offer critical :evide|nbe:' ^'r"'4etbi*3n|iiiii whether exposure' "to organic and inorganic lead is causally associated with brain dysfunction. Efforts to seek funds for this prospective study are currently underway. 7 DUP040010854 TT^T Tr r  fMsfidisrj rinding 3 1. A number of non-exposure covariates were strongly and consistently associated with outcome measures: increasing age was consistently associated with lower performance on most of the : OffeS.' ' tli ol'edudatie^ performed worse on a number of the outcome measures; and the higher the vocabulary.score (a measure of verbal intelligence) the better the performance on the neurobehavioral tests. 2. Cumulative smoking history and alcohol consumption show no cgns;i^jfei|feji^ bbtai . ^espendlhg' 0*1 outcome). n . 3. The exposed group versus control group comparisons revealed tih^!imdOgapifO jl^f : ^peOyptpneid1 #ptse. bn'.sevpiSai' ' :i! . <|ybwp.:; ''lalisb! control group. These results did not change appreciably when controlling for either education or vocabulary. These findings were1 considered most important when additional analyses documented a dose-e^fedt relation. 4. The results of the analyses using 3 external exposure i L' 'ibiojpd:, ahOi:' ss^iriic p^dtffi|ir^||lji|; ;do4:e^t'e^bbS.|i:' ibbO^!*! :ljelat; :hri<|:: 'b:^v^rai| oiitb|ii|p|!!t i0*1 wpffe0;'ipifObO expbsiites reported significantly more neuropsychiatric symptoms than less exposed workets. These results did not change appreciably when controlling for either education or vocabulary. 5. Based on the large number of regression models performed, by chancy I jallo^e, 2|7 comparisons wpuld be expected to be significant a;0 a * !cj*i05 (lit8 exposure variklblep) x [2 methods for control of Utilising several ' 'Ji'inbaOufc)i, x 0.05). different definitions of statistical significance, more outcomes were associated with the exposure and 8 DUP040010855