A Five-year Inhalation Study with Natural Uranium Dioxide (UO2) Dust-II. Postexposure Retention and Biologic Effects in the Monkey, Dog and Rat

Abstract

Inhalation studies show that dogs, monkeys and rat9 can breathe a natural uranium dioxide (UO,) aerosol of approximately 1 pm mass median particle diameter (MMD), at a mean concentration of 5 mg U/m3(25 x TLVS or 28 x MpC,$), for periods as long as 5 yr with little evidence of serious injury (L. J. LEACH et al., Health Phys. 18, 599 (1970)).Some of these animals were observed for protracted postexposure periods during which pulmonary neoplasia developed in a high percentage of the dogs examined 2-6 yr after exposure.Pulmonary and tracheobronchial lymph node fibrosis, consistent with radiation effects, apparently dose dependent, and more marked in monkeys than in dogs was also noted.No evidence of uranium toxicity was found in records of body weights, mortality, various hematologic parameters or the histologic condition of the kidneys.

Depleted uranium exposure and health effects in Gulf War veterans

“…Chromosomal aberrations were counted as a measure of clastogenic insult and, more recently, the hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutation assay, the most widely used measure of somatic gene mutations in humans (Cole & Skopek 1994;Robinson et al 1994;Albertini & Hayes 1997;Albertini 2001), was added to our test battery. While there is good biologic plausibility for U to be genotoxic, based on animal data (Hueper et al 1952;Leach et al 1973;Cross et al 1981;Mitchell et al 1999;Hahn et al 2002), some epidemiologic data in exposed workers (Martin et al 1991) and, more recently, the evidence reported from in vitro studies (Lin et al 1993;Miller et al 1998bMiller et al , 2002aMiller et al ,b, 2003Yazzie et al 2003;Stearns et al 2005), the results of our studies are mixed. The HPRT frequency results, when analysed using the U low/ high stratified grouping, are not significantly different, although mean mutation frequency (MF) was higher in the high U group in both 2001(McDiarmid et al 2004a,b, 2006).…”

“…Although in vitro genotoxicity (Lin et al 1993;Miller et al 1998aMiller et al ,b, 2002aMiller et al ,b, 2003Yazzie et al 2003;Stearns et al in press) and in vivo animal carcinogenicity studies (Hueper et al 1952;Leach et al 1973;Cross et al 1981;Mitchel et al 1999;Hahn et al 2002) using natural U and DU raise some concern regarding cancer risks in DU exposed veterans, studies of occupationally exposed cohorts do not support the extrapolation of the results of these studies to humans. There is poor evidence for an increased risk of lung cancer in uranium-exposed cohorts, except for uranium miners whose risk is attributed to their coexposure to radon, a more intensely radioactive constituent than natural uranium by a factor of 10 000 (Kathren & Moore 1986;Samet 1989;Kathren et al 1989;Samet et al 1989).…”

Uranium behaviour in the baboon after the deposition of a ceramic form of uranium dioxide and uranium octoxide in the lungs : implications for human exposure

“…The data in table VII show that the values for U0 2 vary from about 11 to 50 and those for U 3 0 8 from about 3 to 6. It is noteworthy that ratios in excess of 100 have been reported by Leach et al in dogs and monkeys exposed chronically to 5 mg m -3 U0 2 over an interval of 5 y [17][18]. The values reported for humans exposed to uranium are also extremely variable.…”

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure

“…This list was based on the knowledge of the biokinetics and biological effects of uranium gained from experimental studies and also on preliminary evidence from available epidemiological studies. Biomarkers of lung cancer and other lung damage were proposed, since dust inhalation is the primary route of occupational exposure to uranium and results from experimental (Leach et al 1973, Mitchel et al 1999 and epidemiological (Ritz 1999, Guseva Canu et al 2011 studies suggest this is potentially a key issue. Biomarkers of renal and bone damage were also proposed, because uranium accumulates in these organs and tissues and evidence from animal and epidemiological studies indicates uranium related effects in kidney (Prat et al 2011, Gueguen and Rouas 2012, McDiarmid et al 2013 and bone (Kurttio et al 2005).…”