Acute toxicity of conventional versus shale-derived JP5 jet fuel: light microscopic, hematologic, and serum chemistry studies

Parker, George A.; Bogo, Victor; Young, Robert W.

doi:10.1016/0041-008x(81)90231-3

Cited by 34 publications

(10 citation statements)

References 22 publications

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“…Increased severity of progressive rat nephropathy, the presence of tubular mineralization, and urothelial hyperplasia are consistent with changes previously reported in rats treated with JP-5 (Parker et al, 1981;Gaworski et al, 1985) and similar volatile hydrocarbons (Carpenter et al, 1975a(Carpenter et al, , 1975bAlden et al, 1983).…”

supporting

confidence: 79%

Tumorigenic Evaluation of Jet Fuels JP-TS and JP-7.

Harris¹,

Witt²,

Davis³

et al. 1991

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Approved REPOT D CUMETATON PGE0MB NO. 0704-0188Pubi~c reportingj burden to' chsoli~e".i.n of information iieuriteo t,-fg hour Pei retpeonie ri~dn4lic 1the Utie for r"etoih knwttrnMWte ching e-tigd ata sources. gathering ad maintaining the data needed. adn compleung and retie-ng the collect-ion of ,nto-at,on Send onme~ntt regrding tht b.,den estmhte or anV other atpec-t of I Approved for public release, distribution is unlimited.j ABSTRACT (Maximum 200 words)Fischer 344 rats and C57BIlJ6 mice were exposed for one year to inhalation concentrations of either 200 or 1000 Ing JP-TS/in3 or 150 or 750 mig JP-7/m~l. A common control group of rats and mice exposed to air alone was maintained under similar exposure conditions. Six animals of each species, sex, and group were sacrificed at the termination of the one-year exposure period. All survivors were maintained for an additional one-year observation period. Significant microscopic findings following the one-year inhalation study were primarily restricted to renal lesions found in male rats. The renal lesions were consistent with changes reported following other hydrocarbon inhalation exposures. Renal neoplasms were slightly increased in number in male rats following the postexposure observation period. No exposu re-related degenerative changes or increased carcinogenesis was noted in mice. SUBJECTTERMS 15. NUMBEROFPAGES

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supporting

confidence: 79%

Tumorigenic Evaluation of Jet Fuels JP-TS and JP-7.

Harris¹,

Witt²,

Davis³

et al. 1991

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“…Animals that died during the 40-day holding period had swollen, mottled livers and histopathologic evaluation of the survivors indicated hepatic periportal fatty changes. Similar studies using single oral doses of JP-5 followed by sacrifices over the next three days showed a clear pattern of liver injury accompanied by increased serum lactate dehydrogenase, glutamic-transaminase, and glutamic-pyruvate transaminase levels (53,44,54). Inhalation exposures of beagle dogs, F344 rats, and C57BL/6 mice were conducted as part of the Wright-Patterson studies (55).…”

Section: Systems To Be Modeledmentioning

confidence: 84%

A proposed approach to study the toxicology of complex mixtures of petroleum products: the integrated use of QSAR, lumping analysis and PBPK/PD modeling.

Verhaar

Morroni

Reardon

et al. 1997

Environ Health Perspect

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Mixture toxicity is a topic that has become a matter of concern during the last two decades. One of the major problems with assessing the toxicity of mixtures and the associated human and environmental risk is the large number of possible mixtures, as well as the fact that the actual mixture effect for a given set of constituents might strongly depend on the actual composition of the mixture, i.e., the ratios of the constituent, as well as their nature. This paper presents a possible approach to describe and thereby better understand the pharmacokinetics and dynamics of complex mixtures by combining quantitative structure-activity relationships to predict needed parameters, lumping to reduce the complexity of the problem, and physiologically based pharmacokinetic/pharmacodynamic modeling to integrate all this information into a complete toxicological description of the mixture. It is our hope that by presenting this conceptual approach we might be able to stimulate some criticisms and discussions in the toxicology community regarding this complex and yet very important area of research.Environ Health Perspect 105(Suppl 1): 179-195 (1997) Key words: QSAR, lumping analysis, PBPK/PD modeling, predictive toxicology, jet fuel, mixture toxicity Introduction Traditionally, both human and environmental toxicologists have studied the toxic effects (both lethal and sublethal, acute and chronic) of single substances. For to dealing with the first problem, that of the existence of too many compounds to test for toxic effects, is the discipline known as predictive toxicology. This is a discipline that tries to predict the biological effects, including but not limited to acute toxicity, of chemicals from considerations of compound structure and knowledge about the target biological systems and subsystems. Two tools predictive toxicology has developed over the years are quantitative structure-activity relationships (QSAR) and physiologically based pharmacokinetic/ pharmacodynamic (PBPK/PD) modeling.QSAR attempts to predict the qualitative structure-activity (SAR) or quantitative QSAR effect of a compound by analogy with a number of similar compounds (9). SARs generally define a common substructure or overall shape similarity between compounds with similar modes of toxic action, using the presence or absence of this substructure in an unknown compound or the similarity of the unknown to the known active compounds to predict the likelihood of the unknown of exhibiting the same toxicity. QSARs attempt to identify quantitative structural parameters that correlate with the actual effect dose or concentration that elicits a common effect level (for example, LD50 or LC50). All three techniques mentioned above will be described in more detail in another section of this paper as will ways in which these techniques might be combined into a comprehensive predictive toxicological approach. These techniques will be illustrated wherever possible by examples using such complex mixtures as JP-5, automotive gasoline, and other petroleum p...

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“…A rapidly growing number of chemicals -principally aliphatic or aromatic hydrocarbons -have been reported to induce a characteristic spectrum of morphological changes in the kidney unique to the male rat (Carpenter et al 1975a(Carpenter et al , b, 1977Parker et al 1981;Alden et al 1984;Phillips and Cockrell 1984;Phillips and Egan 1984;Collins and Manus 1987;James et al 1987;Kanerva et al 1987a;Phillips et al 1987;Bomhard et al 1988Bomhard et al , 1989.…”

Section: Introductionmentioning

confidence: 97%

Relationships between structure and induction of hyaline droplet accumulation in the renal cortex of male rats by aliphatic and alicyclic hydrocarbons

et al. 1990

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A rapidly growing list of hydrocarbons has been reported to induce morphological changes in the kidney of adult male rats, beginning with hyaline droplet accumulation (HDA) followed by the development of granular casts, later on chronic nephrosis as sequela, and finally renal adenomas and carcinomas. The present study focuses on identifying structure-based properties common to HDA-inducing aliphatics and cycloaliphatics. On the basis of rank-ordered activities reported in the literature, a calculated n-octanol-water partition coefficient above 3.5 and the presence of an isopentyl structural moiety appear to be associated with HDA-inducing activity in aliphatics. A binding site model for highly active aliphatics has been derived by superimposing their minimum energy conformations along the common isopentyl substructure and calculating the union volume of their respective van der Waal (VDW) volumes. Generalization of this model to include cycloaliphatics has been achieved by maximizing the steric overlap of the VDW volumes of the compounds with their binding site union volume. HDA-inducing cycloaliphatics are correctly identified on the basis of their negligible excess volume. This approach has been used to predict the HDA-inducing activity of previously untested compounds. Eighteen aliphatic/cycloaliphatic hydrocarbons were screened in a study on adult male Wistar rats treated with 250 mg/kg per day for 5 days. Azan-stained kidney sections were semiquantitatively evaluated for the presence of HDA. The predicted and observed HDA activities were in very good agreement.

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Acute toxicity of conventional versus shale-derived JP5 jet fuel: light microscopic, hematologic, and serum chemistry studies

Cited by 34 publications

References 22 publications

Tumorigenic Evaluation of Jet Fuels JP-TS and JP-7.

Tumorigenic Evaluation of Jet Fuels JP-TS and JP-7.

A proposed approach to study the toxicology of complex mixtures of petroleum products: the integrated use of QSAR, lumping analysis and PBPK/PD modeling.

Relationships between structure and induction of hyaline droplet accumulation in the renal cortex of male rats by aliphatic and alicyclic hydrocarbons

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