Intratracheal instillation of zinc-cadmium sulfide (ZnCdS) in Fischer 344 rats.
The purpose of this study was to assess the bioavailability and pulmonary toxicity of ZnCdS in rats. Groups of 30 male Fischer 344 rats each were anesthetized and dosed via intratracheal instillation with 5 mg of either ZnCdS, quartz (positive control), or titanium dioxide (TiO(2), negative control) suspended in 0.5 ml saline. A vehicle control group received 0.5 ml saline. Ten animals from each test group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for bronchoalveolar lavage fluid (BALF) analysis and histopathology. The BALF was analyzed for alkaline phosphatase, acid phosphatase, lactate dehydrogenase (LDH), beta-glucuronidase (beta-glu), total protein, and cell counts. Two separate groups of 24 rats each were dosed as already described with either ZnCdS or saline. Eight rats from each group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for determination of cadmium (Cd) and zinc (Zn) concentrations in the lung, liver, kidney, and blood. Results indicate that at 1 day after dosing, all enzyme activities (except acid phosphatase) and cell counts in BALF from the quartz and ZnCdS groups were significantly higher than in the TiO(2) and saline groups. At 7 days after dosing, high enzyme activity persisted in the quartz group, while the ZnCdS group showed only LDH and total protein levels significantly higher than the saline group. At 14 wk after dosing, LDH, total protein, beta-glu, and cell counts in the quartz group were significantly higher than all other groups. Histologic examination revealed interstitial inflammation and accumulation of foreign material in the lungs and mediastinal lymph nodes of quartz-, TiO(2)-, and ZnCdS-treated rats. Metal analyses in tissues showed profuse Cd and Zn concentrations in the lung 1 day after dosing, followed by a successive decline at 7 days and 14 wk after dosing. A very small, but statistically significant, amount of Cd and Zn was found in the kidneys at 14 wk after dosing. In conclusion, ZnCdS appears to cause temporary lung inflammation, is cleared slowly, and is poorly bioavailable.
Bergmann
J D
JD
U.S. Army Center for Health Promotion and Preventive Medicine, 5158 Blackhawk Rd., Aberdeen Proving Ground, MD 21010-5403, USA. Jeffrey.Bergmann@apg.amedd.army.mil
Metker
L W
LW
McCain
W C
WC
Beall
P A
PA
Michie
M W
MW
Lee
R B
RB
D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001682:Biological Availability; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity; D002452:Cell Count; D005240:Feasibility Studies; D005966:Glucuronidase / Q000378:metabolism; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011009:Pneumoconiosis / Q000209:etiology / Q000473:pathology; D011791:Quartz / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013440:Sulfides / Q000008:administration & dosage / Q000633:toxicity*; D014025:Titanium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D014132:Trachea / Q000187:drug effects*; D015032:Zinc / Q000008:administration & dosage / Q000633:toxicity
D013440:Sulfides; D002104:Cadmium; D011791:Quartz; C009495:titanium dioxide; D014025:Titanium; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D005966:Glucuronidase; D015032:Zinc