Comparative toxicity of arsine gas in B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters: system organ studies and comparison of clinical indices of exposure.
In order to examine possible species differences in response to arsine exposure, multiple inhalation studies consisting of acute (1-day), subacute (14- and 28-day), and subchronic (90-day) exposures to this agent were conducted using three different species of rodents. Evaluations of hematopoietic organs and alterations in the heme biosynthetic pathway were the focus of these studies. Species used were B6C3F1 mice (exposed 1, 14, or 90 days), Fischer 344 rats (exposed 14, 28, or 90 days), and Syrian Golden hamsters (exposed 28 days). All arsine exposures were at concentrations of 0.5, 2.5, or 5.0 ppm except for 90-day studies, in which concentrations were lowered to 0.025, 0.5, or 2.5 ppm. No changes in body weight gain were observed in either sex of mice or hamsters. The only decrease in body weight gain occurred in male rats exposed to 5.0 ppm arsine for 28 days. Significant exposure-related increases in relative spleen weights occurred in both sexes of mice and rats in the 0.5 (except 14-day female rats), 2.5, and 5.0 ppm exposure groups from all studies and in hamsters in the 2.5 and 5.0 ppm exposure groups. Generally, increases in relative liver weight occurred in fewer exposure groups and were of a lesser magnitude than increases in spleen weight. Other parameters affected included decreased packed cell volumes (mice, rats, and hamsters), hematology profiles (rats), and an increase in delta-aminolevulinic acid dehydratase activity in all species. Arsenic content was measured in livers of rats after 90 days of exposure. Concentrations increased in relation to atmospheric concentrations of arsine. Histopathologic changes included increased hemosiderosis and extramedullary hematopoiesis in spleen and intracanalicular bile stasis (mice only) in liver. Additionally, bone marrow hyperplasia was observed in rats. Effects on other organs were not observed, suggesting that the hematopoietic system is the primary target for arsine. In conclusion, we have determined that the effects of arsine exposure upon mice, rats, and hamsters are similar. Most importantly, even though no effects on the hematopoietic system were observed following a single exposure to 0.5 ppm arsine which is 10 times the Threshold Limit Value (TLV) set by the American Conference of Governmental Industrial Hygienists, repeated exposure to 0.025 ppm (one-half the TLV) caused a significant anemia in rats.
Blair
P C
PC
Chemical Pathology Branch, NIEHS, Research Triangle Park, North Carolina 27709.
Thompson
M B
MB
Morrissey
R E
RE
Moorman
M P
MP
Sloane
R A
RA
Fowler
B A
BA
D000280:Administration, Inhalation; D000818:Animals; D001151:Arsenic / Q000008:administration & dosage / Q000633:toxicity*; D001152:Arsenicals; D001835:Body Weight / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006400:Hematocrit; D006413:Hematopoietic System / Q000187:drug effects; D006418:Heme / Q000096:biosynthesis; D008099:Liver / Q000032:analysis / Q000033:anatomy & histology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D000623:Porphobilinogen Synthase / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000033:anatomy & histology; D013997:Time Factors
D001152:Arsenicals; D006418:Heme; D000623:Porphobilinogen Synthase; D001151:Arsenic; C006633:arsine