Toxicological Assessment of Refined Naphthenic Acids in a Repeated Dose/Developmental Toxicity Screening Test

Abstract

Naphthenic acids (NAs) are primarily cycloaliphatic carboxylic acids with 10 to 16 carbons. To characterize the potential of refined NAs (>70% purity) to cause reproductive and/or developmental effects, Sprague-Dawley rats (12/group) were given oral doses of 100, 300, or 900 mg/kg/d, beginning 14 days prior to mating, then an additional 14 days for males or through lactation day 3 for females (up to 53 days) in a repeated dose/reproductive toxicity test (Organization for Economic Cooperation and Development [OECD] 422). Potential mutagenic effects were assessed using Salmonella (OECD 471) and in in vivo micronucleus tests (OECD 474) using bone marrow taken from treated animals in the screening study described previously. Systemic effects included reduced terminal body weights, increased liver weights, and changes in a number of blood cell parameters. The overall no effect level for all target organ effects was 100 mg/kg/d. In the reproductive/developmental toxicity assessment, there were significant reductions in numbers of live born offspring in groups exposed to 300 and 900 mg/kg/d. The overall no effect level for developmental effects was 100 mg/kg/d. The data from the Salmonella and micronucleus tests provide evidence that refined NAs are not genotoxic.

Human and Aquatic Toxicity Potential of Petroleum Biodegradation Metabolite Mixtures in Groundwater from Fuel Release Sites

“…Additional studies primarily addressing the aquatic toxicity of OCOCs are found in the scientific literature. These include research conducted on: 1) weathered crude oils (Wolfe et al 1995;Neff et al 2000;McGuire et al 2018), 2) crude oilproduced water (Thomas et al 2009;Scarlett et al 2012;Hughes et al 2017), 3) water-accommodated fractions (WAFs) or water-soluble fractions of fresh or artificially weathered crude oils (Barron et al 1999 [WAFs]; Melbye et al 2009 [water-soluble fractions]), 4) WAFs of refined fuels (Neff et al 2000), and 5) oil-sands process water to assess the toxicity of naphthenic acids (Rogers et al 2002;McKee et al 2014).…”

Naphthenic Acid Mixtures from Oil Sands Process-Affected Water Enhance Differentiation of Mouse Embryonic Stem Cells and Affect Development of the Heart

“…A recent report revealed that treatment of rats with refined NAs (>70% purity) at 300 and 900 mg/kg/d would cause a significant reduction in the number of live born pups. Moreover, alive pups born in the high dose group (i.e., 900 mg/kg/d) had a significantly lower body weight and decreased survival rate . However, the cause of embryonic and postnatal lethality remains to be investigated …”

“…Moreover, alive pups born in the high dose group (i.e., 900 mg/kg/d) had a significantly lower body weight and decreased survival rate . However, the cause of embryonic and postnatal lethality remains to be investigated …”

“…Moreover, alive pups born in the high dose group (i.e., 900 mg/kg/d) had a significantly lower body weight and decreased survival rate. 18 However, the cause of embryonic and postnatal lethality remains to be investigated. 18 Mouse embryonic stem cells, which are derived from the inner cell mass of blastocyst are pluripotent (i.e., capable of differentiating into all the three primary germ layers) and can grow indefinitely in vitro.…”

The Mammalian Toxicological Hazards of Petroleum-Derived Substances

“…The overall no-effect levels were approximately 100 mg/kg/d. 92 It should be noted that higher molecular weight naphthenic acids, isolated from waste streams from oil sands operations, produced systemic and developmental effects at levels much lower than those tested in the present study. 93,94 Waste oils are primarily the hydrocarbon constituents collected as wastes in the refinery, particularly from sumps.…”