Sodium molybdate dihydrate does not exhibit developmental or reproductive toxicity in Sprague-Dawley rats maintained on a marginal copper diet.

Groups of 24 weanling female Sprague-Dawley rats were administered molybdenum (Mo) as sodium molybdate dihydrate (SMD) in drinking water at target dose levels of 0, 20, or 40 mg Mo/kg bw/day and fed a semi-purified marginal copper (6.2 ppm Cu) AIN-93 G diet for 8 weeks prior to mating, through cohabitation and pregnancy until Gestation Day 21. The objective was to confirm the reproductive and developmental effects of SMD reported by Fungwe et al.

A comprehensive weight of evidence assessment of published acetaminophen genotoxicity data: Implications for its carcinogenic hazard potential.

In 2019, the California Office of Environmental Health Hazard Assessment initiated a review of the carcinogenic hazard potential of acetaminophen, including an assessment of its genotoxicity. The objective of this analysis was to inform this review process with a weight-of-evidence assessment of more than 65 acetaminophen genetic toxicology studies that are of widely varying quality and conformance to accepted standards and relevance to humans. In these studies, acetaminophen showed no evidence of induction of point or gene mutations in bacterial and mammalian cell systems or in in vivo studies.

Assessment of the biochemical pathways for acetaminophen toxicity: Implications for its carcinogenic hazard potential.

In 2019 California's Office of Environmental Health Hazard Assessment (OEHHA) initiated a review of the carcinogenic hazard potential of acetaminophen. In parallel with this review, herein we evaluated the mechanistic data related to the steps and timing of cellular events following therapeutic recommended (≤4 g/day) and higher doses of acetaminophen that may cause hepatotoxicity to evaluate whether these changes indicate that acetaminophen is a carcinogenic hazard. At therapeutic recommended doses, acetaminophen forms limited amounts of N-acetyl-p-benzoquinone-imine (NAPQI) without adverse cellular effects.

Application of the DILIsym® Quantitative Systems Toxicology drug-induced liver injury model to evaluate the carcinogenic hazard potential of acetaminophen.

In 2019, the California Office of Environmental Health Hazard Assessment (OEHHA) initiated a review of the carcinogenic hazard potential of acetaminophen. The objective of the analysis herein was to inform this review by assessing whether variability in patient baseline characteristics (e.g.

A two-generation reproductive toxicity study of sodium molybdate dihydrate administered in drinking water or diet to Sprague-Dawley rats.

In an OECD Test Guideline 416 multigenerational study, groups of 24 male and 24 female Sprague-Dawley rats were administered sodium molybdate dihydrate at 0, 5, 17, or 40 mg molybdenum (Mo)/kg bw/day in the drinking water or 40 mg Mo/kg bw/day in the diet over two generations to assess reproductive toxicity. No adverse effect on reproductive function was observed at any dose level in either generation as indicated by no significant dose-related effect on estrus cycles, sperm parameters, mating, fertility, gestation, litter size, pup survival, growth or postnatal development. Systemic toxicity, including decreased body weight, food consumption (males only) and water consumption, was observed among both sexes given 40 mg Mo/kg bw/day in the diet.

Evaluation of the mode of action of mouse lung tumors induced by 4-methylimidazole.

4-Methylimidazole (4-MEI) occurs in certain foods and beverages as a product of browning reactions. An increased incidence of lung tumors was reported in mice, but not rats, exposed to levels of 4-MEI in their diet that far exceed human dietary intake. This investigation evaluated the hypothesis that 4-MEI induces mouse lung tumors by the same mode of action (MOA) as styrene: CYP2F2 metabolic activation and increased BrdU labeling.

Developmental toxicity study of sodium molybdate dihydrate administered in the diet to Sprague Dawley rats.

Molybdenum is an essential nutrient for humans and animals and is a constituent of several important oxidase enzymes. It is normally absorbed from the diet and to a lesser extent from drinking water and the typical human intake is around 2μg/kg bodyweight per day. No developmental toxicity studies to contemporary standards have been published and regulatory decisions have been based primarily on older studies where the nature of the test material, or the actual dose levels consumed is uncertain.

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in rats.

Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME) diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (<1-7mg/m(3), 5min). Dose responsive maternal effects were reduced maternal body weight and/or weight change, and/or reduced food consumption.

Acute, subchronic, and developmental toxicological properties of lubricating oil base stocks.

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.

90-Day subchronic toxicity study of sodium molybdate dihydrate in rats.

This study investigated the subchronic toxicity of molybdenum (Mo) in Sprague-Dawley rats given sodium molybdate dihydrate in the diet for 90days at dose levels of 0, 5, 17 or 60mgMo/kgbw/day. The study complied with OECD Test Guideline (TG) 408, with additional examination of estrus cycles and sperm count, motility, and morphology from OECD TG 416. The overall no-observed-adverse-effect level was 17mgMo/kgbw/day, based on effects on body weight, body weight gain, food conversion efficiency and renal histopathology (females only) at 60mgMo/kgbw/day.

The relationship between repeat-dose toxicity and aromatic-ring class profile of high-boiling petroleum substances.

A study was undertaken within the context of the U.S. EPA HPV Chemical Challenge Program to (1) characterize relationships between PAC content and repeat-dose toxicities of high-boiling petroleum substances (HBPS) and (2) develop statistical models that could be used to predict the repeat-dose toxicity of similar untested substances.

The relationship between developmental toxicity and aromatic-ring class profile of high-boiling petroleum substances.

In response to the US EPA HPV Challenge Program, this study was conducted to: (1) evaluate the relationship between PAC content and the developmental toxicity of high-boiling petroleum substances (HBPS) and (2) develop mathematical models to predict the developmental toxicity of similar untested substances based on their aromatic ring class (ARC) profiles. For this investigation, 68 developmental toxicity studies were reviewed. The ARC models relied on data from 21 rat dermal developmental toxicity studies conducted with similar experimental designs to ensure a consistent data set for comparison.

Evaluating the male and female reproductive toxicity of high-boiling petroleum substances.

To meet the EPA HPV Chemical Challenge Program requirement for reproductive toxicity data on sponsored high-boiling petroleum substances (HBPS), an analysis was conducted using the results of 39 repeat-dose and 59 developmental rat dermal toxicity studies on HBPS samples spanning the boiling range of the sponsored substances, and the results of three one-generation reproductive toxicity studies on two samples spanning the concentration range of polycyclic aromatic compounds of sponsored substances. The analysis found little evidence of male or female reproductive tract toxicity based on histopathology, reproductive organ weight, and sperm parameters, and no evidence of effects on fertility, while significant developmental toxicity and/or systemic repeat-dose toxicity were frequently observed. Among 14 samples of HBPS tested in both repeat-dose toxicity and developmental toxicity studies, there were no studies in which an adverse reproductive tract finding occurred at a dose lower than that producing developmental toxicity or other adverse effects in repeat-dose toxicity studies.

Assessing the mammalian toxicity of high-boiling petroleum substances under the rubric of the HPV program.

In 1998, the US EPA announced the HPV Challenge Program, a voluntary chemical data collection effort. The Petroleum HPV Testing Group (PHPVTG(1)) volunteered to provide data on approximately 110 high boiling petroleum substances (HBPS), i.e.

The development of statistical models to determine the relationship between aromatic-ring class profile and repeat-dose and developmental toxicities of high-boiling petroleum substances.

The repeat-dose and developmental toxicities of certain petroleum refinery streams are related to their polycyclic aromatic compound (PAC) content (Feuston et al., 1994). Building on this foundation, and working within the context of the US EPA High Production Volume (HPV) Chemical Challenge Program, we: (1) characterized relationships between PAC content and repeat-dose and developmental toxicities of high boiling petroleum substances (HBPS), and (2) developed statistical models that can be used to predict critical effects of similar untested substances.

Does 4-methylimidazole have tumor preventive activity in the rat?

4-Methylimidazole (4-MEI) is found in a wide array of food products. The National Toxicology Program (NTP) recently conducted a two-year feeding cancer bioassay of 4-MEI in B6C3F(1) mice and F344/N rats. In rats, NTP found "equivocal evidence of carcinogenic activity" in females based on increased incidences of mononuclear cell leukemia and "no evidence of carcinogenic activity" in males.