Systemic and Developmental Toxicity of Dermally Applied Syntower Bottoms in Rats

Feuston, Maureen H.

doi:10.1006/faat.1996.2262

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…Refinery streams and crude oils are complex mixtures of hydrocarbons, and certain streams are known systemic and developmental toxicants, mutagens, and carcinogens (Blackburn et al, 1986;Feuston et al, , 1997aFeuston et al, , 1997bFeuston et al, , 1997cRoy et al, 1988). The class of compounds primarily responsible for the toxicity, mutagenicity, and carcinogenicity is the three-to seven-ring PACs (Roy et al, 1988;Feuston et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Antiestrogenicity of Clarified Slurry Oil and Two Crude Oils in a Human Breast-Cancer Cell Assay

Arcaro

Gierthy

Mackerer³

2001

Journal of Toxicology and Environmental Health, Part A

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Exposure to crude oil and certain petroleum products can be a serious health hazard. Clarified slurry oil (CSO) is a complex mixture of hydrocarbons derived from the processing of crude oil, and is a known systemic and developmental toxicant, mutagen, and carcinogen. In the present study, CSO and two crude oils, Belridge heavy crude oil (BHCO) and Lost Hills light crude oil (LHLCO), were examined for their estrogenic and antiestrogenic properties in a human breast-cancer cell (MCF-7) assay. The MCF-7 focus assay is based on postconfluent cell growth and tissue restructuring, measured as the postconfluent development of multicellular nodules or foci. The mutagenicity indices of BHCO and LHLCO also were determined in a modified Ames Salmonella assay. Oil samples were prepared in dimethyl sulfoxide, resulting in extraction of virtually all of the aromatic compounds including the sulfur- and nitrogen-substituted three- to seven-ring polycyclic aromatic compounds comprising 62.2% of the CSO, 9% of the BHCO, and 2% of the LHLCO by total weight. None of the three samples was estrogenic in the MCF-7 focus assay. In contrast, all of the samples were antiestrogenic; that is, they inhibited the development of foci induced by 1 nM 17beta-estradiol (E2). The potencies of the oil samples for both antiestrogenicity and mutagenicity were correlated with the percent of polycyclic aromatic compounds they contained. Two potential mechanisms for the observed antiestrogenicity were examined. Radiometric analysis of the catabolism of [3H]E2 in MCF-7 cell cultures demonstrated that all three samples increased catabolism of E2. Results from a whole-cell estrogen-receptor (ER) binding assay suggested that metabolites of compounds in the oil samples might have competed with [3H]E2 for ER in the MCF-7 cultures. Thus the antiestrogenicity of the oil samples may occur through at least two mechanisms, increased catabolism of E2 and antagonistic binding to ER.

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Section: Discussionmentioning

confidence: 99%

Antiestrogenicity of Clarified Slurry Oil and Two Crude Oils in a Human Breast-Cancer Cell Assay

Arcaro

Gierthy

Mackerer³

2001

Journal of Toxicology and Environmental Health, Part A

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“…When CSO samples are tested in developmental toxicity studies, they typically produce severe developmental effects (resorptions, reduced fetal body weight, and cleft palate) at levels below 5 mg/kg/d. 57,58 In contrast, in screening studies to assess the potential for CSO to affect male and female reproductive parameters, 59 there were no effects at levels up to 250 mg/kg/d, the highest dose tested. These studies add additional weight to the view that further tests of the potential for unrefined LOBs to cause reproductive effects are not justified, because the critical effects, carcinogenicity and developmental toxicity, which would be used to assess the adequacy of current hazard control practices, have already been characterized.…”

Section: Discussionmentioning

confidence: 86%

Acute, Subchronic, and Developmental Toxicological Properties of Lubricating Oil Base Stocks

Dalbey¹,

McKee

Goyak

et al. 2014

Int J Toxicol

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Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

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“…When samples of CSO are tested in developmental toxicity studies, they typically produce developmental effects (resorptions, reduced fetal body weight, and cleft palate) at levels below 5 mg/kg/d. 42,43 In contrast, in screening studies to assess the potential for CSO to affect male and female reproductive parameters, 44 there were no effects at levels up to 250 mg/kg/d, the highest dose tested.…”

Section: Reproductive Toxicitymentioning

confidence: 88%

Subchronic and Developmental Toxicity of Aromatic Extracts

Dalbey¹,

McKee

Goyak

et al. 2014

Int J Toxicol

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Aromatic extracts (AEs; distillate AEs [DAEs] and residual AEs [RAEs]) are complex, highly viscous liquid petroleum streams with variable compositions derived by extraction of aromatic compounds from distillate and residual petroleum fractions from a vacuum distillation tower, respectively. The DAEs generally contain significant amounts of polycyclic aromatic compounds (PACs) and are carcinogenic. The RAEs typically contain lower concentrations of biologically active PACs. The PACs in refinery streams can cause effects in repeated-dose and developmental toxicity studies. In a 13-week dermal study, light paraffinic DAE had several dose-related effects involving multiple organs; no-observed-effect level was <5 mg/kg/d, with no overt toxicity. Predicted dose-responses at 10% (PDR10s), modeled doses causing a 10% effect on sensitive end points based on PAC content, ranged from 25 to 78 mg/kg/d for untested paraffinic DAEs. The no observed adverse effect level (NOAEL) for developmental toxicity for light paraffinic DAE was 5 mg/kg/d. Statistically significant developmental effects at higher doses were associated with maternal effects. The PDR10s for developmental toxicity of paraffinic DAEs ranged from 7 to >2000 mg/kg/d, reflecting differences due to variation in PACs. The NOAELs for RAEs were 500 mg/kg for 90-day studies and 2000 mg/kg for developmental toxicity. Reproductive toxicity is not considered to be a sensitive end point for AEs based on the toxicity tests with DAEs, RAEs, and other PAC-containing petroleum substances. In vivo micronucleus tests on heavy paraffinic DAE, RAEs, and a range of other petroleum substances have been negative. The exception to this general trend was a marginally positive response with light paraffinic DAE. Most DAEs are considered unlikely to produce chromosomal effects in vivo.

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Systemic and Developmental Toxicity of Dermally Applied Syntower Bottoms in Rats

Cited by 8 publications

References 16 publications

Antiestrogenicity of Clarified Slurry Oil and Two Crude Oils in a Human Breast-Cancer Cell Assay

Antiestrogenicity of Clarified Slurry Oil and Two Crude Oils in a Human Breast-Cancer Cell Assay

Acute, Subchronic, and Developmental Toxicological Properties of Lubricating Oil Base Stocks

Subchronic and Developmental Toxicity of Aromatic Extracts

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