Toxicological Evaluation and Pain Assessment of Four Minor Cannabinoids Following 14-Day Oral Administration in Rats.

Despite growing consumer interest and market availability, the safety of minor cannabinoids, generally present in low concentrations in L., is not well understood. Cannabichromene (CBC; 3.

Cannabidiol safety considerations: Development of a potential acceptable daily intake value and recommended upper intake limits for dietary supplement use.

Consumer use of hemp-derived products continues to rise, underscoring the need to establish evidence-based safety guidance. The present study sought to develop recommendations for oral upper intake limits of cannabidiol (CBD) isolate. Sufficiently robust and reliable data for this purpose were identified from published human clinical trials and guideline-compliant toxicity studies in animal models.

Genotoxicity evaluation of cannabidiol.

Consumer use of cannabidiol (CBD) for personal wellness purposes has garnered much public interest. However, safety-related data on CBD in the public domain are limited, including a lack of quality studies evaluating its genotoxic potential. The quality of available studies is limited due to the test material used (e.

Oral toxicity evaluation of cannabidiol.

Use of cannabidiol (CBD) in humans has increased considerably in recent years. While currently available studies suggest that CBD is relatively safe for human consumption, data from publicly available studies on CBD conducted according to modern testing guidelines are lacking. In the current study, the potential for toxicity following repeated oral exposure to hemp-derived CBD isolate was evaluated in male and female Sprague Dawley rats.

Reproductive and developmental toxicity evaluation of cannabidiol.

An important data gap in determining a safe level of cannabidiol (CBD) intake for consumer use is determination of CBD's potential to cause reproductive or developmental toxicity. We conducted an OECD Test Guideline 421 GLP-compliant study in rats, with extended postnatal dosing and hormone analysis, where hemp-derived CBD isolate (0, 30, 100, or 300 mg/kg-bw/d) was administered orally. Treatment-related mortality, moribundity, and decreased body weight and food consumption were observed in high-dose F adult animals, consistent with severe maternal toxicity.

Cannabidiol Safety Data: A Systematic Mapping Study.

Robust assessment of potential adverse outcomes is needed to determine a safe cannabidiol (CBD) intake level for consumer use. To assist in identifying knowledge gaps and inform future decision making regarding systematic development of health-based benchmarks, we have developed the first systematic map of the safety-related information available for CBD in the peer-reviewed literature. Literature searching conducted according to a published protocol yielded a total of 4186 unique titles and abstracts published through 2020.

Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children.

To date, one of the most heavily cited assessments of caffeine safety in the peer-reviewed literature is that issued by Health Canada (Nawrot et al., 2003). Since then, >10,000 papers have been published related to caffeine, including hundreds of reviews on specific human health effects; however, to date, none have compared the wide range of topics evaluated by Nawrot et al.

Inter-laboratory validation of bioaccessibility testing for metals.

Bioelution assays are fast, simple alternatives to in vivo testing. In this study, the intra- and inter-laboratory variability in bioaccessibility data generated by bioelution tests were evaluated in synthetic fluids relevant to oral, inhalation, and dermal exposure. Using one defined protocol, five laboratories measured metal release from cobalt oxide, cobalt powder, copper concentrate, Inconel alloy, leaded brass alloy, and nickel sulfate hexahydrate.

Oral bioaccessibility testing and read-across hazard assessment of nickel compounds.

In vitro metal ion bioaccessibility, as a measure of bioavailability, can be used to read-across toxicity information from data-rich, source substances to data-poor, target substances. To meet the data requirements for oral systemic toxicity endpoints under the REACH Regulation in Europe, 12 nickel substances underwent bioaccessibility testing in stomach and intestinal fluids. A read-across paradigm was developed based on the correlation between gastric bioaccessibility and in vivo acute oral toxicity.

Acute oral toxicity of nickel compounds.

Acute oral toxicity studies were conducted on samples of nine unique nickel compounds and two complex materials to comply with the data and classification requirements of the new Registration, Evaluation, and Authorization of Chemicals Regulation (REACH) in Europe. The samples tested in this study confirmed the overall low oral toxicity of nickel substances and demonstrated a wide range of LD(50) values extending from 310 to >11,000 mg/kg. This variation highlights the differences in toxicological properties between various forms of nickel and underscores the importance of Ni(II) ion bioavailability in determining toxicity.

Temperature effect on nickel release in ammonium citrate.

Leaching in ammonium citrate has been extensively used to assess the fraction of water-soluble nickel compounds present in nickel producing and using workplace aerosols. Leaching in ammonium citrate according to the first step of the Zatka protocol was found to overestimate the water-soluble nickel fraction by more than ten-fold compared to synthetic lung fluid (37 degrees C), when nickel carbonate and subsulfide were present. These results suggest that exposure matrices based on this method should be reexamined.

Comparison of nickel release in solutions used for the identification of water-soluble nickel exposures and in synthetic lung fluids.

Chemical speciation of workplace nickel exposures is critical because nickel-containing substances often differ in toxicological properties. Exposure matrices based on leaching methods have been used to ascertain which chemical forms of nickel are primarily associated with adverse respiratory effects after inhalation. Misjudgments in the relative proportion of each of the main fractions of nickel in workplace exposures could translate into possible misattributions of risk to the various forms of nickel.