Genetic toxicity studies of glycolipids from Dacryopinax spathularia

Bitzer, Jens; Henkel, Thomas; Nikiforov, Andrey I.; Rihner, Marisa O.; Verspeek-Rip, C.M.; Usta, Birol; Wijngaard, Michèle van den

doi:10.1016/j.fct.2018.10.045

Cited by 5 publications

(7 citation statements)

References 10 publications

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“…Therefore, in the formal experiments of the Ames test, 2500 μ g/plate forsythin was used as the highest dose. After that, the methods of the Ames test were described previously, and the plate incorporation was used for the Ames test [ 18 , 19 ]. Briefly, Salmonella typhimurium (ST) strains TA97, TA98, TA100, TA102, and TA1535 were obtained from the AMES Laboratory, National Center for Drug Safety Evaluation and Research, Beijing, China, and the requirements of these strains for histidine or tryptophan as well as their sensitivity to ampicillin, crystal violet, and ultraviolet radiation were checked.…”

Section: Methodsmentioning

confidence: 99%

Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin

Han

Guo

Meng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Introduction. Forsythin is the main ingredient of Forsythia suspensa and is widely used in treatment of fever, viral cold, gonorrhea, and ulcers clinically. This study aimed to evaluate the potential genetic toxicity of forsythin and its safety for human use. Methods. Based on the Good Laboratory Practice regulations and test guidelines, the genetic toxicity of forsythin was assessed by the Ames test, chromosome aberration (CA) test, and bone marrow micronucleus (MN) test in vivo. In the Ames test, five strains of Salmonella typhimurium were exposed to different concentrations of forsythin in the presence or absence of the S9 mixture, and then, the number of His + revertant colonies was counted. In the CA test, Chinese hamster lung (CHL) fibroblast cells were treated with different concentrations of forsythin, mitomycin C, or cyclophosphamide in the presence or absence of the S9 mixture, and the chromosomal aberrations were determined. In the MN test, bone marrow was isolated from the mice with different treatments, and the ratios of polychromatic erythrocytes (PCE) and erythrocytes (PCE/(PCE + NCE)) were measured. Finally, beagle dogs were divided into four groups (negative control, low dose, medium dose, and high dose groups), and then, a telemetry system was used to evaluate the safe use of forsythin. Results. Ames test results showed that the number of colonies in all test strains with different treatments showed no significantly dose-dependent increase in the presence or absence of the S9 mixture ( p > 0.05 ). In the CA test, the number of cells with aberrations in the CHL fibroblast cells treated with low, medium, and high doses of forsythin for 24/48 h in the absence of the S9 mixture was, respectively, 5.0/2.5, 4.5/1.5, and 5.0/5.0, and in the presence of the S9 mixture, the number was, respectively, 5.0, 5.0, and 4.5. These results showed that there was no significant difference compared to the negative control group either in the presence (2.0) or in the absence (4.0/2.5 for 24/48 h) of the S9 mixture ( p > 0.05 ). The MN test showed that the values of PCE/(PCE + NCE) in the negative, positive controls, and forsythin treatment groups were all more than 20%, which indicated that forsythin had no cytotoxicity. Additionally, no significant toxicological effects of forsythin on blood pressure, respiration, temperature, electrocardiogram, and other physiological indicators in the conscious beagle dogs of different groups were observed by the telemetry method. Conclusion. Our findings showed that forsythin has low probability of genetic toxicity and no significant toxicological effects, which implied that forsythin is suitable for further development and potential application.

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Section: Methodsmentioning

confidence: 99%

Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin

Han

Guo

Meng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…The test substance, described as IM 11, was examined for its possible mutagenic activity in the bacterial reverse mutation test using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and the Escherichia coli strain WP2 uvrA, in the absence and presence of metabolic activation (S9‐mix), in accordance with the OECD guideline 471 (Documentation provided to EFSA No.11; Bitzer et al., 2019).…”

Section: Assessmentmentioning

confidence: 99%

“…The test substance, described as IM 11, was examined for its potential to induce micronuclei in cultured binucleated human lymphocytes from one donor (32 years old), in both the absence and presence of a metabolic activation system (S9‐mix) in accordance with the OECD guideline 487 (Documentation provided to EFSA No. 12; Bitzer et al., 2019).…”

Section: Assessmentmentioning

confidence: 99%

“…The mutagenic activity of the test substance described as IMD AM‐1 was evaluated in an in vitro mammalian cell gene mutation test on L5178Y mouse lymphoma cells (Documentation provided to EFSA No. 13; Bitzer et al., 2019).…”

Section: Assessmentmentioning

confidence: 99%

“…The test substance described as IMD AM ‐1 was evaluated for its ability to induce micronuclei in the bone marrow when administered to ICR mice (Documentation provided to EFSA No. 14; Bitzer et al., 2019). The study was not fully compliant with OECD guideline 474.…”

Section: Assessmentmentioning

confidence: 99%

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Safety evaluation of long‐chain glycolipids from Dacryopinax spathularia

Flavourings¹,

Younes²,

Aquilina³

et al. 2021

EFS2

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The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of long‐chain glycolipids from Dacryopinax spathularia (also called AM‐1) as a food additive. AM‐1 is a purified mixture of long‐chain glycolipid congeners obtained by fermentation of the edible non‐genetically modified fungus Dacryopinax spathularia . AM‐1 glycolipids have very low oral bioavailability and overall available toxicology data do not demonstrate any adverse effects of the proposed food additive. Considering the available data set the Panel established an ADI of 10 mg/kg bw per day based on a range of NOAELs between 1,000 and 1,423 mg/kg bw per day (the highest doses tested), from the reproductive and a prenatal developmental toxicity studies in rats and 90‐day studies in rat and dog. At the proposed maximum use levels, the exposure estimates ranged at the mean from 0.01 to 1.07 mg/kg bw per day and at the p95 from 0 to 3.1 mg/kg mg/kg bw per day. At the proposed typical use levels, the exposure estimates ranged at the mean from < 0.01 mg/kg bw per day to 0.23 mg/kg bw per day and at the p95 from 0 to 0.64 mg/kg bw per day. The Panel noted that the highest estimate of exposure of 3.1 mg/kg bw per day (in toddlers) is within the established ADI of 10 mg/kg bw per day and concluded that the exposure to long‐chain glycolipids from Dacryopinax spathularia does not raise a safety concern at the uses and use levels proposed by the applicant.

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