NCI-Black-Reiter (NBR) Male Rats Fail to Develop Renal Disease following Exposure to Agents That Induce α-2u-Globulin (α_2u) Nephropathy

Abstract

. (1991). Fundam. Appl. Toxicol. 16,[749][750][751][752][753][754][755][756][757][758][759][760][761][762]. The NCI-Black-Reiter (NBR) rat is the only strain of male rat known not to synthesize the hepatic form of the low molecular weight protein, oz,-globulin. In previous studies, NBR rats were shown not to develop renal disease when exposed to decalin, a compound known to induce a,,-globulin nephropathy in other rat strains. The objective of this study was to show that the presence of q,-globulin (01~") is essential for the development of this syndrome in rats exposed to 2,2.4-trimethylpentane (TMP), 1,4dichlorobenzene (DCB), isophorone (IP), PS-6 unleaded gasoline (UC), and d-limonene (d-L). The induction of cuz,-nephropathy in F344 male rats with lindane was used as a positive control and this response was contrasted to male NBR and female F344 rats treated with lindane. Five to seven 1 l-week-old male NBR rats were exposed to TMP (500 mg/kg/day), DCB (500 mg/kg/day), IP (1000 mg/kg/day), UC (500 mg/kg/day), d-L (1650 mg/kg/day), or lindane (10 mg/kg/day) and five 1 l-week-old male and female F344 rats were exposed to lit&me (10 mg/kg/day) by oral gavage on 4 consecutive days. NBR male and F344 male and female rats gavaged with corn oil were incorporated in the study as vehicle controls. The presence of hyaline droplets was assessed in perfusion-fixed kidneys by staining paraffin sections with Mallory-Heidenhein stain and in GMA sections with Lee's methylene basic blue fuchsin stain. Paraffin sections were also analyzed immunohistochemically for the presence of (or". Under exposure conditions that clearly induce cY*,-nephropathy in male F344 rats, no lesions, hyaline droplets, or oZu were detectable in treated or control male NBR and female F344 rats. It is thus concluded that the presence of azu is causal to the development of renal disease in rats exposed to TMP, DCB, IP, UG, d-L, and lindane. o 1991 SocietyofToxicology.

A Comparative Human Health Risk Assessment ofp-Dichlorobenzene-Based Toilet Rimblock Products Versus Fragrance/Surfactant-Based Alternatives

“…Cellular proliferation and other changes were found in the kidney tubular epithelia of male rats, but not in female rats or mice of either gender, following short-term oral exposures to doses ≥150 mg/kg/d (Eldridge et al, 1992;Lake et al, 1997;Sherman et al, 1998;Umemura et al, 1992). The renal effects are consistent with the induction of α 2μ -globulin nephropathy in male rats by similar doses of p-dichlorobenzene in other acute oral studies (Charbonneau et al, 1989;Dietrich & Swenberg, 1991;Saito et al, 1996), but are not relevant to humans, as discussed later with the chronic toxicity and carcinogenicity data.…”

Oncogenicity Studies of Inhaled Methyl Tertiary‐butyl Ether (MTBE) in CD-1 Mice and F-344 Rats

“…other mammalian species, including humans, do not Another possible mechanism to explain the liver synthesize this protein to any extent and do not develop adenomas in female mice is an anti-estrogenic effect this protein nephropathy, [30][31][32][33] the renal tumors are conof MTBE. As shown in Table 2, MTBE at exposure sidered specific to the male rat.…”

Quantitation of α2u-Globulin in Rat Kidney Cytosol by Capillary Electrophoresis

“…4). In addition, ␣ 2u -globulin could not be detected by both methods in kidney cytosol of male NCI-Black Reiter rats, a strain with a genetic lack for ␣ 2u -globulin synthesis (data not shown) (20). All samples were diluted to a protein concentration of 1 mg/ml.…”