The role of ∝2u globulin synthesis in the production of renal hyaline droplets by iso-octane

Carruthers, L.B.; Reeves, Kate; Paul, Moses; Searle, A.G.; Templeton, W; Paine, Alan J.

doi:10.1016/0006-2952(87)90534-x

Cited by 7 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hyaline droplet nephropathy is a well‐characterized male rat‐specific finding and is caused by the reversible binding of lipophilic xenobiotics to α G. Interference with α G degradation has also been implicated in this nephropathy (Carruthers et al ., ).…”

Section: Discussionmentioning

confidence: 97%

“…Hyaline droplet nephropathy is a well-characterized male rat-specific finding and is caused by the reversible binding of lipophilic xenobiotics to aG. Interference with aG degradation has also been implicated in this nephropathy (Carruthers et al, 1987). The present research investigated kidney HD accumulation and damage induced by a single injection of HCBD in the male Wistar rats in relation to the age of the animals, the dose level administered and the time after dosing.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hyaline droplet accumulation in kidney of rats treated with hexachloro‐1:3‐butadiene: influence of age, dose and time‐course

Cristofori

Defazio

Chiusolo

et al. 2011

J of Applied Toxicology

View full text Add to dashboard Cite

The present research investigates the occurrence of hyaline droplet (HD) accumulation related to age, dose and time after treatment in male Wistar rats given a single i.p. injection of hexachloro-1:3-butadiene (HCBD). In the study on age, rats from 1 to 12 months of age were treated with 100 mg kg(-1) body weight (b.w.) HCBD dose. Rats treated at 2 months of age showed a greater accumulation of HD than the other age groups; HD accumulation was not observed in 1-month-old rats. In the dose-response study, the treatment with 25, 50 and 100 mg kg(-1) b.w. at 2 months of age caused HD accumulation in the proximal convoluted tubule at all doses, with the 100 mg kg(-1) b.w. group slightly more affected. Finally, in the time-course study, rats treated with a 100 mg kg(-1) b.w. dose at 2 months of age and sacrificed at 6, 12, 24, 48, 72 and 96 h post-dosing showed a time-related HD accumulation in terms of incidence and severity, after 6 h, with a peak at 24 and 48 h and decreasing at 72 and 96 h. The present results show that HD accumulation is an early finding, and is unrelated to dose level and particularly evident in rats of 2 month of age. These findings in male rats treated with HCBD emphasize the importance of considering the age of rats at the start of a study. The more sensitive model was used in the detection of nephrotoxic effects of chemicals.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Hyaline droplet accumulation in kidney of rats treated with hexachloro‐1:3‐butadiene: influence of age, dose and time‐course

Cristofori

Defazio

Chiusolo

et al. 2011

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…For a rapidly perfused tissue, this is a high value that suggests that uptake into this tissue is most likely dependent on solubility and an active process such as binding, which was the case for MTBE by Poet and Borghoff (1997). As such, the partition coefficient in kidney was set to rapidly perfused tissues and binding of ETBE to α2u–globulin described within the male, but not female rat kidney.iValues in literature range from ~160 to 1000 μ m for α2u–globulin kidney concentration (Carruthers et al ., 1987; Charbonneau et al ., 1987; Olson, Garg et al ., 1987; Stonard et al ., 1986). …”

Section: Methodsmentioning

confidence: 99%

“…iValues in literature range from ~160 to 1000 μ m for α2u–globulin kidney concentration (Carruthers et al ., 1987; Charbonneau et al ., 1987; Olson, Garg et al ., 1987; Stonard et al ., 1986). …”

Section: Methodsmentioning

confidence: 99%

Physiologically based pharmacokinetic model for ethyl tertiary‐butyl ether and tertiary‐butyl alcohol in rats: Contribution of binding to α2u–globulin in male rats and high‐exposure nonlinear kinetics to toxicity and cancer outcomes

Borghoff

Ring

Banton

et al. 2016

J of Applied Toxicology

View full text Add to dashboard Cite

In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary‐butyl ether (ETBE), caused liver tumors in male rats, while tertiary‐butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary‐butyl ether, a structurally similar chemical, and verified against the literature and study report data. The model included ETBE and TBA binding to the male rat‐specific protein α2u–globulin, which plays a role in the ETBE and TBA kidney response observed in male rats. Metabolism of ETBE and TBA was described as a single, saturable pathway in the liver. The model predicted similar kidney AUC0–∞ for TBA for various exposure scenarios from ETBE and TBA cancer bioassays, supporting a male‐rat‐specific mode of action for TBA‐induced kidney tumors. The model also predicted nonlinear kinetics at ETBE inhalation exposure concentrations above ~2000 ppm, based on blood AUC0–∞ for ETBE and TBA. The shift from linear to nonlinear kinetics at exposure concentrations below the concentration associated with liver tumors in rats (5000 ppm) suggests the mode of action for liver tumors operates under nonlinear kinetics following chronic exposure and is not relevant for assessing human risk. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd

show abstract

2,2,4‐Trimethylpentan [MAK Value Documentation in German language, 1989]

2012

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 15. Lieferung, Ausgabe 1989 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Angaben zur Pharmakokinetik Erfahrungen beim Menschen Tierexperimentelle Befunde Untersuchungen zur gentoxischen Wirkung Untersuchungen zur kanzerogenen Wirkung Zur Frage eines MAK‐Wertes

show abstract

The role of ∝2u globulin synthesis in the production of renal hyaline droplets by iso-octane

Cited by 7 publications

References 10 publications

Hyaline droplet accumulation in kidney of rats treated with hexachloro‐1:3‐butadiene: influence of age, dose and time‐course

Hyaline droplet accumulation in kidney of rats treated with hexachloro‐1:3‐butadiene: influence of age, dose and time‐course

Physiologically based pharmacokinetic model for ethyl tertiary‐butyl ether and tertiary‐butyl alcohol in rats: Contribution of binding to α2u–globulin in male rats and high‐exposure nonlinear kinetics to toxicity and cancer outcomes

2,2,4‐Trimethylpentan [MAK Value Documentation in German language, 1989]

Contact Info

Product

Resources

About