Document ZJ7o9QOZQMYJLbq0O982zBGy7

TERWATIOSMAL'LEAO 251'iSC RESEARCH ORGARUZATIOW, ifUC SOS MADISON AVI I-IUE, NEW YORK, N.Y. 1QC* ^ TEtGPHONE: fOC-tJri?CI (AREA CODE &1!* CABLE ADOflEBS: MYfLERO MEW YORK July 30, 1970 To: All Members of the Environmental Health Committee From: J. F. Cole, Sc. D. . ' Gentlemen: ' ' . Enclosed are two reports for yoilr interest: 1) ' LH-151 Study Atmospheric Contaminants in Animals and Man Three Month Progress Report - This report includes initial data on the exposure of rats and monkeys in preparation for the human vol unteer study, - 2) Toxicity of Orally - Administered lead - Program Summary This recently completed program was sponsored by the American Pet- . ' roleura Institute at Hazelton Laboratories. Through the kind per mission of Dr. R. H. Gols, Medical Director of the API, we are diS' trfbuting copies.to members of the'ILZBO Environmental Health Com mittee'. This report is for your personal use only. It should not .' 'be cited .as a reference since it will be published in the near future by Hazelton and the API. . .... ,, ;! c . -Manager, Environmental Health . JFCjls ' - ' Enc.- - * ' .' ' . ; RECEIVED AUG 4 1970 HASKELL LABORATORY N36901 L.H-1 & I July 13, 1970 INSTITUTE OF EXPERIMENTAL PATHOLOGY & TOXICOLOGY ALBANY MEDICAL COLLEGE ALBANY, NEW YORK IN54 - LEAD i THREE-MONTH PROGRESS REPORT Exposure of animals - rats and rhesus monkeys - to an atmosphere containing lead particulates was begun on March 12, 1970. In the experiment, the animals are exposed daily, 7 days a week, to lead sesguioxide particles at a nominal concentration of 20 jjg per cubic m'eter. These particles are generated by burning tetraethyllead in propane. Periodically, samples of chamber air, diet, water, blood, urine and feces have been obtained for estimation of lead content. Additionally^blood and urine samples have been subjected to certain routine clinical examinations and certain special tests which'are indicative of lead intoxication. The following is a brief discussion of the results obtained to date. Chamber. The chamber is operated from 11:00 A.M, each morning until 9:00 A.M. the following morning. During the'daily two-hour shut-down period ; all necessary . maintenance of the animals within the chamber is performed. Concentrations of atmospheric lead within the chamber are determined several times daily during the week and at least once each day on Saturday and Sunday. Measured volumes of air are withdrawn from the chamber through a filter having 0.2 micron sized pores. Material on the filter is then dissolved in dilute nitric acid and lead is estimated by atomic absorption spectrophotometry. The mean of the several determinations performed during each day is recorded as the lead concentration for that day. The average daily concentration of lead in the chamber during the first'three months of operation was 20.2 t fig per cubic meter. DUP050312330 1 . 2 Since the production of lead sesquioxide particles in the chamber has been by way of a heat generating process, careful monitoring of temperatures within the chamber has been performed. Both an industrial recording thermometer and a laboratory thermometer.have been employed. The highest daily temperature observed has ranged from 79-86 F. The "usual" maximum is 81-82 F and during the 5 days that the temperature rose to 86, there was a failure of the air condition ing system in the facility. Lead in Blood. Periodic estimations of the lead content of blood have been performed on the animals in the chamber and the control animals. The results of these deter minations are shown in Table 1. It is apparant that lead concentrations in both rats and monkeys are significantly greater in the animals housed in this chamber. Blood levels of rats in the chamber are nearly ten times the concentration of lead in the control animals . It is not yet possible to ascertain whether the levels are *. . t continually rising or whether they haye reached a maximum, though fluctuating level. It is also of interest to note the blood lead levels in the control animals. Levels in the monkeys have continually decreased since they were brought into the laboratory. In the control rats, however, which have always existed in a laboratory environment, the blood lead levels have maintained a constant low level. Lead in Urine. Concentrations of lead found in urine are shown in Table 2. Although the trends are similar to those found in blood, the deviations are greater; This is partly a reflection of the wide variations between individual animals and partly due to the very low levels being estimated. The data a're presented in a different form in Table 3 . In this case the amount of lead excreted in the urine over a 24 hr period is shown. Here again is seen a trend toward higher amounts in the experi mental animals. DU P050312331 Lead in Feces. Concentrations of lead in feces of the rats and monkeys is shown in Table 4. The excretion of fecal lead over a 24 hr period is shown in Table 5. Although the means are generally higher in the feces from animals exposed to lead in the chamber, the variations in results do not permit an unequivocal interpretation. * The lack of highly significant rises in urine and fecal lead in spite of the larger increase in blood lead levels may mean that some deposition of lead in tissues is occurring. This will be examined when samples of tissue are taken at autopsy for lead estimation. ' " Special Chemistry. Samples of urine have also been examined for levels of delta aminolevulinic acid, porphobilinogen and coproporphyrin-substances which are usually indicators of lead toxicity. In neither the rats nor the monkeys were there any differences between the experimental and control animals. Clinical Chemistry and Hematology. Routine clinical and hematological examina tions of blood have not revealed any differences between control and experimental animals. The parameters investigated were serum glucose, sodium, potassium, calcium, phosphorus and glutamic-pyruvic transaminase. No significant differ ences were noted in the hematological examinations. Travis B. Griffin, Ph.D. Project Leader Cameron Russell Alternate KWA DUP050312332 I I ' !/, >' ' Table 1. Concentration of Lead in Blood w- !,/ u! TimelDfv:-!,. ; determination Control no. of animals Pb cone. (pg/100 ml) Chamber no. of animals Pb cone. (pg/100 ml) Monkevs 2 wk Lmb 4 7.8 t 1.7 4 12.8 1.3 4 5.0 0.8 8 11.4 1.3 2; mo' 3'mo 4 4.3 1.3 4 3.3 1.3 7 9.3 2.3 8 ' 12.9 t 3.1 < Rats 1 mo 2 mo 3 mo 8 2.6 0.5 8 2.5 0.8 8 2.9 0.4 8 12.8 2.7 8 9.8 2.2 7 26.6 7,0 DUP050312333 Table 2 . Concentration of Lead in Urine Time of determination Monkeys 0 2 wk 1 mo 2 mo 3 mo Control no. of animals Pb cone. (jig/100 ml) - '- 4 8.9 3.3 . 4 4,6 - 1.2 4 1.6 0.8 2" 2.6 1.7 Chamber no, of animals Pb cone. (jig/100 ml) 7 3.1 1 1.4 8 9.4 4.4 8 4.8 + 0.7 8 4.9 3.5 8 6.0 -t 3.5 Rats V" 1 wk 1 mo 2 mo 4 mo .8 2.5 1.2 `- - 8 1.4 t 1.0 6 3.2 t 2.1 8 2.4 t 2.4 . 8 3,5 1.8 .t 8 1.3 t 0.2 8 5.7 +- 5.7 t. i DUP050312334 o Time of determination Monkeys 0 2 wk 1 mo 2 mo 3 mo Table 3. Excretion of Lead in Urine Control no. of Pb cone. animals (jig/24 hrs) Chamber no. of animals Pb cone. (p.g/24 hrs) -- 7 4 18.8 * 17.8' 8 4 13.5 t 8.7 8 4 1.3 t 0.7 8 2 5.7 t 4.9 8 9.2 7.2 13.4 t 5.5 9.6 t 3.1 12.3 t 10.2 10.3 t 1.8 Rats ,, T' 1 wk 1 mo 2 mo 3 mo 8 0.30 t 0.06 - 8 0.18 t 0.07 6 8 0.22 t 0.08 8 8 0.16 t 0.03 8 - 0.32 t 0.13 0.44 t 0.18 0.49 t 0.?1 i { i $ DUP050312335 Table 4. Concentration of Lead in Feces Time of determination .i Monkeys 0 2 wk 1 mo 2 mo 3 mo Control no. of Pb cone. animals . 0-tg/g) * 4 5.1 t 2,3 4 3.3 t 0.6 4 0.9 t 0.7 2 4.7 t 3.5 Chamber no. of animals Pb cone. (jig/g) 7 2.7 t 1.4 . 8 3.4 t 2.1 8 6.1 t 2.6 8 4.6 t 2.9 6 CO . *H 00 Rats 1 wk 1 mo 2 mo 3 mo 8 4.4 t 1.0 5 8.2 t 6.9 6 7.7 t 6.4 7 7.4 t 7.3 .- 7 . 8.6 t 4.0 7 10.1i,3.1 4 5.3 t 1.4 A ? DUP050312336 Table 5. Excre tion of Lead In Feces Time of determination Control no. of Pb excreted animals (fag/24 hrs) Chamber no. of . animals Pb excreted (pg/24 hrs) Monkevs 0 2 wk 1 mo 2 mo 3- mo ' 4 5.1 + 2.3 4 10.0 4.8 4 9.0"i 5.5 2 10.1 + 4.1 7 12.1 +_ 7.7 8 21.1 i 9.4 8 12.1 i 8.0 8 4.8 + 3.9 . 6 13.0 + 6.1 Rat ` 1 wk . 1 mo 2 mo 3 mo 8 4.6i;i.8 5 4.0 + 2.3 6 4.8 i 2.3 7 4.7 * 2.5 7 6.0 + 2.5 7 6.3 + 4.7 4 5.3 + 2.9 DUP050312337