Acute, Sub-Acute, Sub-Chronic and Chronic General Toxicity Testing for Preclinical Drug Development

Denny, Kevin H.; Stewart, Charles L.

doi:10.1016/b978-0-12-387815-1.00005-8

Cited by 9 publications

(6 citation statements)

References 10 publications

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“…Toxicological and safety evaluation of herbal preparations are commonly performed in mouse and/or rat models [26][27][28]. The first recommended step to determine the systemic safety and toxicity of unknown compounds often involves identifying the lowest observed adverse effect level (LOEAL) and LC50 using a "single-dose" acute toxicity test [29][30][31]. Subsequently, further subacute and chronic repeated dose toxicity studies may then be performed to provide an accurate picture of the typical use of C. cainito for the treatment of subchronic (inflammation and viral infections) and chronic diseases (diabetes) [10].…”

Section: Discussionmentioning

confidence: 99%

Aqueous extract from Chrysophyllum cainito bark exhibits embryonic toxicity in Danio rerio and negligible acute toxicity in adult wistar rats

Doan

Sritangos

Weeranantanapan

et al. 2021

ARCH BIOL SCI BELGRA

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Chrysophyllum cainito has been used as a traditional medicine to treat a wide range of diseases, but the toxicity profile of this plant remains unknown. This study aimed to evaluate the acute toxicity of the aqueous extract of C. cainito (CE) bark based on OECD guidelines in two different in vivo experimental models: acute single-dose oral toxicity in adult Wistar rats and the zebrafish embryo acute toxicity test. All concentrations of CE (500-4000 mg/kg) tested during a 14-day period in both male and female rats showed no effect on behavior, body weight, organ weights, biochemical and hematological parameters. In contrast, CE significantly delayed zebrafish embryo hatching and decreased embryo survival rates in a dose-dependent manner. Hatched larvae were notably sensitive to CE-induced toxicity compared to unhatched fish embryos. Acridine orange staining showed that CE induced apoptosis in the yolk sac region that is responsible for supplying nutrients to support larval growth and development. According to OECD guidelines, CE was identified as GHS category 5, a substance with low to no acute toxicity. However, as embryotoxicity was observed in zebrafish, CE use during pregnancy should be exercised with caution until further examination of its safety.

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Section: Discussionmentioning

confidence: 99%

Aqueous extract from Chrysophyllum cainito bark exhibits embryonic toxicity in Danio rerio and negligible acute toxicity in adult wistar rats

Doan

Sritangos

Weeranantanapan

et al. 2021

ARCH BIOL SCI BELGRA

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“…Toxicity may further be defined to cover the study of the adverse effects of chemicals on living organisms as well as their symptoms, mechanisms and treatments. Toxicity studies may be classified as acute, subacute/subchronic and chronic effects depending upon the quantity and duration of administration of the agents [14].…”

Section: Toxicity Of Chemicalsmentioning

confidence: 99%

Toxicity and Safety Implications of Herbal Medicines Used in Africa

Mensah¹,

Komlaga²,

Forkuo³

et al. 2019

Herbal Medicine

109

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The use of herbal medicines has seen a great upsurge globally. In developing countries, many patronize them largely due to cultural acceptability, availability and cost. In developed countries, they are used because they are natural and therefore assumed to be safer than allopathic medicines. In recent times, however, there has been a growing concern about their safety. This has created a situation of ambivalence in discussions regarding their use. Some medicinal plants are intrinsically toxic by virtue of their constituents and can cause adverse reactions if inappropriately used. Other factors such as herb-drug interactions, lack of adherence to good manufacturing practice (GMP), poor regulatory measures and adulteration may also lead to adverse events in their use. Many in vivo tests on aqueous extracts largely support the safety of herbal medicines, whereas most in vitro tests on isolated single cells mostly with extracts other than aqueous ones show contrary results and thus continue the debate on herbal medicine safety. It is expected that toxicity studies concerning herbal medicine should reflect their traditional use to allow for rational discussions regarding their safety for their beneficial use. While various attempts continue to establish the safety of various herbal medicines in man, their cautious and responsible use is required.

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“…8 Conventionally, drug administrated through skin, directly bypasses through first pass mechanism, through the stratum corneum, which is the thickest outermost layer of skin 3,9,10 To increase the skin permeability and have the drug retention, diverse approaches have been adopted, such as the use of chemical enhancer, employing iontophoresis, electroporation, and pressure wave generation (using photoacoustic or ultrasound). [18][19][20][21] Hence, there is a need of polymeric MNs, which should be biodegradable, biocompatible, and nontoxic in nature for transdermal drug delivery. Most probable alternative for transdermal drug delivery is the use of biodegradable microneedle (MNs) technology, which offer invasive route of drug administration in sustained and controlled manner delivering the drug to the specific site with less pain and tissue damage.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, toxicological assessment becomes imperative for the purpose of attaining potent and harmless formulations for clinically efficient remedies. [18][19][20][21] Hence, there is a need of polymeric MNs, which should be biodegradable, biocompatible, and nontoxic in nature for transdermal drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Microneedles of chitosan‐porous carbon nanocomposites: Stimuli (pH and electric field)‐initiated drug delivery and toxicological studies

Gaware

Rokade

Bala

et al. 2019

J Biomedical Materials Res

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An array of microneedles (MNs) of chitosan‐graphene assembled in porous carbon (CS‐GAPC) nanocomposites has been synthesized and evaluated. The safety of the formulated system has been ensured using detailed in vivo toxicological studies and efficacy has been ensured by evaluating the stimuli (pH and electric field) initiated drug delivery properties. Drug cephalexin has been incorporated in these MNs. In vivo toxicological studies of CS‐GAPC nanocomposite were performed on Sprague rats, using acute dermal and subacute dermal (ADT& SADT) test, histopathological studies, biochemical studies, and AMES tests. ADT and SADT studies showed that median lethal dose (LD50) was found greater than 2000 mg/kg body weight; with no abnormal weight gain and food consumption, during the study period of 28 days. This study showed that administration of CS‐GAPC did not cause any substantial alterations in hematological and biochemical parameters of the animals. Histopathological studies showed no significant changes in the control and CS‐GAPC administered groups. AMES tests reveal that CS‐GAPC nanocomposite is nonmutagenic against the Salmonella thyphimurium strains. No abnormalities were observed in the animal's chromosomal aberrations and clastogenic values when the animals were treated with CS‐GAPC. At acidic pH of 4, the encapsulated drug was completely released, indicating that the drug release from the prepared nanocomposite is pH dependent. An electric field of 5 V showed optimum drug release, as a function of applied electric pulses. A biologically safe drug encapsulation model system is hence projected for smart drug delivery (pH dependent and electric field triggered) using the microneedle approach. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1582–1596, 2019.

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Acute, Sub-Acute, Sub-Chronic and Chronic General Toxicity Testing for Preclinical Drug Development

Cited by 9 publications

References 10 publications

Aqueous extract from Chrysophyllum cainito bark exhibits embryonic toxicity in Danio rerio and negligible acute toxicity in adult wistar rats

Aqueous extract from Chrysophyllum cainito bark exhibits embryonic toxicity in Danio rerio and negligible acute toxicity in adult wistar rats

Toxicity and Safety Implications of Herbal Medicines Used in Africa

Microneedles of chitosan‐porous carbon nanocomposites: Stimuli (pH and electric field)‐initiated drug delivery and toxicological studies

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