Oral Dose Toxicity Research Articles

Long–term oral dose toxicity study of domperidone with pantoprazole in male wistar rats

Long–term oral dose toxicity study of domperidone with pantoprazole in male wistar rats

Safety profile of Naga Bhasma prepared by two classical methods

Abstract Background: Naga Bhasma (NB) (incinerated lead) has been indicated as a remedy for the treatment of a wide range of diseases including Prameha (diabetes), Kasa (cough), Raktapradara (menorrhagia), Shukradosha (defects in semen), etc., However, improperly prepared NB can cause harmful effects on the human body. In modern science also, lead consumption has been accepted to produce toxicity. Aim: The present study was undertaken to elucidate and compare the toxicity profile of two samples of NB prepared by two different methods to ascertain the safety aspects. Materials and methods: In the first method, NB was prepared by using Parada (mercury), Gandhaka (sulfur), and Nimbu Swarasa (juice of Citrus medica var acida of Watt). In the second method, NB was prepared by using Ashwattha-Twaka-Churna (Ficus religiosa L.), Manahshila (realgar) (Ariloha), and Nimbu Swarasa. In both methods, 30 calcination cycles were given. Charles foster albino rats were used for the pharmacological study. Acute oral toxicity study was carried out as per organization for economic cooperation and development (OECD) 425 and chronic oral toxicity study was carried out as per OECD 408 (90-day oral repeated dose toxicity study). Acute oral toxicity study was conducted at five dose levels, namely 100, 250, 500, 1000, and 2000 mg/kg body weight. Chronic toxicity was carried out at a dose level of 62.5 mg/kg body weight. Animals were sacrificed on the 91st day by cervical dislocation. Blood was collected from the jugular vein and sent for hematological and biochemical investigations were done. Organs were used for histopathological studies. The data were analyzed by unpaired t-test. Results: No mortality was observed in the acute toxicity study. Chronic toxicity study shows that both the test drugs do not produce significant toxicity, but both were not completely free from adverse effects at the dose level studied. Conclusion: The study shows that both the test drugs do not produce significant toxicity, but they are not completely free from adverse effects at the dose level studied.

Risks for animal and human health related to the presence of polychlorinated naphthalenes (PCNs) in feed and food.

EFSA was asked for a scientific opinion on the risks for animal and human health related to the presence of polychlorinated naphthalenes (PCNs) in feed and food. The assessment focused on hexaCNs due to very limited data on other PCN congeners. For hexaCNs in feed, 217 analytical results were used to estimate dietary exposures for food-producing and non-food-producing animals; however, a risk characterisation could not be performed because none of the toxicological studies allowed identification of reference points. The oral repeated dose toxicity studies performed in rats with a hexaCN mixture containing all 10 hexaCNs indicated that the critical target was the haematological system. A BMDL20 of 0.05 mg/kg body weight (bw) per day was identified for a considerable decrease in the platelet count. For hexaCNs in food, 2317 analytical results were used to estimate dietary exposures across dietary surveys and age groups. The highest exposure ranged from 0.91 to 29.8 pg/kg bw per day in general population and from 220 to 559 pg/kg bw per day for breast-fed infants with the highest consumption of breast milk. Applying a margin of exposure (MOE) approach, the estimated MOEs for the high dietary exposures ranged from 1,700,000 to 55,000,000 for the general population and from 90,000 to 230,000 for breast-fed infants with the highest consumption of breast milk. These MOEs are far above the minimum MOE of 2000 that does not raise a health concern. Taking account of the uncertainties affecting the assessment, the Panel concluded with at least 99% certainty that dietary exposure to hexaCNs does not raise a health concern for any of the population groups considered. Due to major limitations in the available data, no assessment was possible for genotoxic effects or for health risks of PCNs other than hexaCNs.

A 90-day repeated oral dose toxicity study of p-cymene in rats

A 90-day repeated oral dose toxicity study of p-cymene in rats

The antimicrobial effect of Curcuma longa and Allium sativum decoction in rats explains its utility in wound care.

In South Asia, Curcuma longa and Allium sativum are extensively used as household remedies for wound care for veterinary and human infectious diseases. However, little pharmacologic data is present to support this folklore. A series of in vitro and in vivo experiments were conducted to validate the folkloric practice of these herbs. In vitro experiments, phytochemistry, polyphenolic content, acute dose dermal toxicity, antimicrobial activity, and antioxidant assays were conducted. For in vivo experiments, the decoction was prepared and tested for a wound cure against an experimentally induced excision wound on the dorsal region of rats under ketamine anesthesia. Rats were divided into five groups (5 rats in each). Group 1 was treated with standard Povidone-Iodine, Group 2 was treated with distilled water, group 3 received topical application of the decoction, Group 4 received topical as well as 1 mL oral decoction, and Group 5 received topical as well as oral 1 mL water. Histopathology, leukocyte count and acute oral dose toxicity were estimated. After the ninth post-wounding day, the wound contractions recorded in each group were group-1 (83.11%), group-2 (19.21%), group-3 (91.01%), group-4 (100%), and group-5 (16.55%) similarly less cytoarchitectural damage and more promising cellular repair were observed in both decoctions treated groups as compared to standard and control. A less exaggerated WBC profile was recorded in decoction-treated groups compared to standard and control, while decoction showed significant antibacterial potential even against the resistance strains of standard antibiotics. Decoction showed no dermal and oral toxicity in the animals tested. Decoction of A. sativum and C. longa possesses excellent wound healing potential because of the variety of phytoconstituents linked to the antibacterial, antioxidant, and immunomodulator spectrum and can be used as an effective household remedy for wound healing with no notable toxicity.

Uncertainty in the results from oral repeated dose toxicity tests: Impact on regulatory classifications

The Lowest Observed (Adverse) Effect Level (LO(A)EL) values are point-of-departure (PoD) values that quantify repeat dose toxicity (RDT). Here, the uncertainty in the regulatory classification of these PoDs is investigated. In the application stage, the dose-response was approximated for a large set of series, giving an account of the possible presence of a hormesis zone. The minimal effect dose (MED) or dose was computed, and the ratio MED/LO(A)EL was used to represent the two components of the experimental uncertainty. The uncertainty estimations were calculated for any combination of gender and reported examination item. Subsequently, how this uncertainty affects the possible classifications was analyzed, and the percentage of the chemicals receiving ambiguous classification was determined. It was shown that more than 40% of the investigated chemicals cannot be classified unambiguously in the Globally Harmonized System (GHS) classification scheme and bear a potential for misclassification when a regulatory decision is based on a single LO(A)EL value. A table containing grey zones for different risk levels and a table with GHS classification distributions for various LO(A)EL values were prepared to facilitate the use of the RDT uncertainty in the practice.

Safety Assessment of AYUSH SC-3 through Acute and 90 Days Repeated Dose Oral Toxicity Study

The present study is focused on establishing the safety of the formulation through acute and 90 days of repeated oral dose toxicity as per the Organization for Economic Cooperation and Development (OECD) guidelines. During the acute toxicity test, the drug was orally administered at a limited test dose of 2000 mg/kg. Clinical signs, feed and body weight were recorded. At the end of 14 days, the animals were euthanized and subjected to a detailed post-mortem examination (necropsy). As per OECD, 408 the 90 days repeated dose oral toxicity study was carried out with three different doses of test drug i.e., 1500, 1000 and 500 mg/kg. Cage side observations, body weight and feed intake were recorded. Upon termination of the study, urine analysis, haematology and clinical biochemical examinations were performed. Finally, the rats were subjected to euthanasia, a gross necropsy was conducted and vital organs were weighed and made prone for histopathological evaluation. Cage-side observation of AYUSH-SC-3 treated animals showed no signs of toxicity, and the mortality or moribund state was observed in both of the studies. No significant change in body weight and feed intake was seen in AYUSH-SC-3 treated animals. Gross morphology and necropsy findings of the animals revealed no treatment-related. Haematological and biochemical parameters of rats treated with AYUSH-SC-3 were found to be non-significant when compared to the control group. Necropsy findings and relative organ weights did not change significantly. Further, the histopathological analysis of major organs showed no major lesions and treatment-related changes. The LD50 of AYUSH SC-3 is greater than 2000 mg/kg and NOAEL is up to 1500 mg/kg.

In Vitro, Oral Acute, and Repeated 28-Day Oral Dose Toxicity of a Mixed-Valence Polyoxovanadate Cluster.

Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a mixed-valence polyoxovanadate, pentadecavanadate, (Me4N)6[V15O36Cl], abbreviated as V15. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Artemia salina Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC50 values in PBMC cells and A. salina were 17.5 ± 5.8 μmol L-1, and 17.9 µg L-1, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V15 repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V15 showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V15 toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications.

Acute and sub acute toxicity of Amirdha Gandhi Kukkil Vallathy an effective Siddha herbo mineral formulation used in the treatment of rheumatoid arthritis in wistar albino rat model.

Amirdha Gandhi Kukkil Vallathy (AGKV) is a herbo mineral Siddha formulation which has Sulphur, Kukkil, Seendhil and Serankottai as major ingredients and it is indicated for 80 types of Vatham diseases. Uthiravatha suronitham is one among the vatham diseases and it's clinical symptoms are correlated with Rheumatoid arthritis (RA). Since AGKV is a promising drug for RA, the safety of this drug has been validated by performing the acute and 28days repeated oral dose toxicity study following the OECD guidelines 423 and 407. The acute toxicity study has been performed byadministering orally with a single dose of 300 and 2000 mg/kg body weight in rat models and the animals were observed for 14 consecutive days. Gross pathology was observed and animals were sacrificed at the end of the study. In 28days repeated oral toxicity study, limit test has been carried out with a dose of 1,000 mg/kg body weight. No significant abnormality has been observed in the body weight, organ weight, biochemical parameters and histopathology studies. It has been revealed that this drug is safe upto 2000 mg/kg body weight in single dose study and 1,000 mg is a safer dose in the 28days repeated oral toxicity study. The results of acute and 28days repeated oral toxicity studies revealed no adverse effects in animals and hence this drug AGKV is safe and can be administered in human.

Pharmacokinetics and repeated dose 28-day oral toxicity studies of acetaminophen nanosuspension.

Wide availability and easy accessibility of acetaminophen oral dosage forms increase the risk of intentional poisoning or unintentional organ toxicity, leading to a wide range of liver failure, nephrotoxicity, and neurotoxicity. In this study, an attempt was made to improve oral bioavailability and reduce the toxicity of acetaminophen using nanosuspension technology. The acetaminophen nanosuspensions (APAP-NSs) were prepared by a nano-precipitation method using polyvinyl alcohol and hydroxypropylmethylcellulose as stabilizers. The mean diameter of APAP-NSs was 124 ± 3.8 nm. The dissolution profile of APAP-NSs was significantly point-to-point higher than the coarse drug in simulated gastrointestinal fluids. The in vivo study revealed 1.6- and 2.8-fold increases in the AUC0-inf and Cmax of the drug, respectively, in APAP-NSs-receiving animals compared to the control group. Moreover, no deaths and no abnormalities in clinical signs, body weights, and necropsy findings were detected in the dose groups up to 100 mg/kg of the 28-day repeated oral dose toxicity study in mice.

Four-week repeated oral dose toxicity study of zinc maltol in rats.

Zinc (Zn) is one of the trace elements, and Zn deficiency causes many adverse effects. Zn complexes are used for Zn supplementation, but there are few toxicity reports. Zn maltol (ZM) was orally administered for 4 weeks to male rats at a dose of 0, 200, 600, or 1000 mg/kg to assess its toxicity. As a ligand group, maltol was administered at a dose of 800 mg/kg/day. General conditions, ophthalmology, hematology, blood biochemistry, urinalysis, organ weights, necropsy, histopathology, and plasma Zn concentration were investigated. Plasma Zn concentration increased with dose levels of ZM. The following toxicities were observed at 1000 mg/kg. Pancreatitis was observed with histopathological lesions and increases in white blood cell parameters and creatine kinase. Anemia was observed with changes in red blood cell parameters and extramedullary hematopoiesis in the spleen. Decreases in the trabecula and growth plate in the femur were observed. On the other hand, no toxicities were observed in the ligand group. In conclusion, these toxicities induced by ZM have been reported as Zn-related toxicities. It was considered that these results will be helpful for a creation and development of new Zn complexes as well as supplements.

Studies on the Toxicological Properties of Ethanol Stem-Bark Extract of Newbouldia laevis (P. Beauv) Seem in Rats

This research aimed at evaluating the toxicological profile of ethanol stem-bark extract of N. laevis in Wistar rats. Repeated oral dose toxicity studies (28 and 90 days) were carried out with 32 rats for 28-day study and 40 rats for 90-day study. The rats were divided into 4 groups (A, B, C and D) of six rats per group and were treated with 250, 500 and 1,000 mg/kg body-weight of the extract for 28 and 90 days respectively. Blood samples were collected at the end of the experiment and were used for Biochemical and Haematological investigations, organs were also collected for histological examination. There was significant (p ≤ 0.05) reduction in WBCs following 28-day treatment and a significant (p ≤ 0.05) increase after 90-day treatment. The RBCs, haemoglobin and haematocrit increased significantly (p ≤ 0.05) at 1,000 mg/kg following 28-day treatment and at all doses for RBCs and haemoglobin after 90-day treatment. A significant (p ≤ 0.05) increase in HDL and a decrease in LDL was observed after 28-day treatment, the 90 days treatment showed significant (p ≤ 0.05) decrease in HDL and an increase in LDL. The AST level also increased significantly (p ≤ 0.05) after 28-day treatment. Histological-examination revealed pathological abnormalities in kidney and liver of the treated rats at all doses. This study showed that extract of N. laevis stem-bark was toxic when used at high doses and for a long period of time in the treated rats.

Evaluation of subchronic oral dose toxicity and allergen of freeze-dried powder of Locusta migratoria (Orthoptera: Acrididae) as a novel food source.

The migratory locust, Locusta migratoria (Orthoptera: Acrididae), is a well-known edible insect which may serve as new source of human food and animal feed. However, potential toxicity and food safety of L. migratoria had not been investigated extensively until now. Therefore, in this study, we aimed to investigate toxicity of freeze-dried powder of L. migratoria (fdLM) and identify allergic components in ELISA and PCR techniques. In this subchronic study, fdLM was administered once daily by oral gavage at the doses of 750, 1500, and 3000mg/kg/day. No toxicological changes were observed in both sexes of rats for 13weeks in accordance with the OECD guidelines and GLP conditions. In addition, fdLM did not induced increases of serum immunoglobulin E and 21 homologous proteins were not detected under our present conditions. In conclusion, the NOAEL (no-observed-adverse-effect level) was 3000mg/kg/day and no target organ was identified in both sexes. In conclusion, we found that fdLM is safe with no adverse effects and offers the potential of its use as an edible ingredient or other biological uses.

Pathological analysis of lesions in the exocrine pancreas of rats induced by Zinc Maltol.

The pancreas plays an important role in the homeostasis of zinc (Zn), a nutritionally essential metal. In several previous studies, Zn ions induced inflammatory changes in the exocrine pancreas; however, little is known about Zn complexes. In this study, we microscopically, immunohistochemically, and ultrastructurally examined pancreatic lesions in Sprague-Dawley (SD) rats induced by a 4-week repeated oral dose toxicity study of Zinc Maltol (ZM), a zinc (II) complex. ZM induces acinar atrophy and increases the number of duct-like structures. Immunohistochemistry revealed a decrease in the number of trypsin-positive cells, and an increase in the number of SOX9-positive cells. Interstitial fibrosis and macrophage infiltration also correlated with the degree of acinar atrophy. Electron microscopic evaluation revealed that the acinar cells that lost granules were surrounded by fibroblasts and collagen fibers. In conclusion, we provided a detailed description of ZM-induced pancreatic lesions in SD rats.

Safety Evaluation and Anti-Inflammatory Efficacy of Lacticaseibacillus paracasei PS23

Lacticaseibacillus paracasei strain PS23 (PS23) exhibits some probiotic properties. In this study, a genomic analysis of PS23 revealed no genes related to virulence or antibiotic resistance. Moreover, ornithine decarboxylase activity was not detected in vitro. In addition, PS23 was sensitive to the tested antibiotics. Genotoxicity tests for PS23 including the Ames test and chromosomal aberrations in vitro using Chinese hamster ovary cells and micronuclei in immature erythrocytes of ICR mice were all negative. Moreover, following a 28-day study involving repeated oral dose toxicity tests (40, 400, and 4000 mg/kg equal 1.28 × 1010, 1.28 × 1011, and 1.28 × 1012 CFU/kg body weight, respectively) using an ICR mouse model, no adverse effects were observed from any doses. In addition, supplementation with live or heat-killed PS23 ameliorates DSS-induced colonic inflammation in mice. Our findings suggest that PS23 is safe and has anti-inflammatory effects and may therefore have therapeutic implications.

The Evaluation of the Acute Toxicity and Safety of Verbenalin in ICR Mice

Background: Verbenalin is an iridoid glucoside, which is among the active components of some medicinal herbs such as Verbena officinalis Linn, and Cornus officinalis Siebold and Zucc. Previous studies have confirmed the antioxidant activity and neuroprotective potential of verbenalin. To confirm the safety of verbenalin, an approximate lethal dose was determined based on a single oral dose toxicity study.Methods: Institute of Cancer Research mice were randomly assigned to three verbenalin exposure groups (250, 500, and 1,000 mg/kg) and a control group (5% methylcellulose solution). There were (5 male and 5 female mice per group). Mortality, clinical signs, and body weight were monitored for 14 days, and necropsies were conducted.Results: No mortalities were observed in the control group or the verbenalin 250 mg/kg group, whereas mortalities were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the observation period, stool abnormalities such as mucous stools were observed. Clinical signs such as loss of locomotor activity were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the study period, significant changes in body weight were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups; however, no gross abnormalities were observed at necropsy. Overall, no toxicity was found in the 250 mg/kg group.Conclusion: The approximate lethal dose of verbenalin was estimated to be 500 mg/kg. For a more accurate assessment of the safety of verbenalin, other types of studies such as repeated-dose toxicity studies should also be conducted.

Safety assessment of the Quercus brantii gall hydroalcoholic extract: Single and repeated oral dose toxicity studies.

Quercus brantii galls (QBGs) are well-known in Iranian traditional medicine for treating various diseases. The aim of study was to assess the acute and repeated oral toxicity of the hydroalcoholic extract of QBG in female rats. The ethanolic extract of QBG was administered in rats by gavage in both acute and repeated dose models. In the acute section of the study, a single oral dose of 2000 mg/kg was administered to female rat which were observed for physical symptoms and behavioral changes for 14 days. In the repeated dose toxicity study, the QBG extract (50, 500, and 1000 mg/kg/day) was administered for a period of 28 days to rats. On 28th day of experiment, blood sampling of animals was done for hematological and biochemical analysis and then sacrificed for histopathological examination of the harvested tissues (liver, heart, kidney, lung, spleen, stomach, ovary and uterus). A single oral administration of the QBG extract (2000 mg/kg) did not produce mortality or significant behavioral changes during 14 days of observation. In repeated oral toxicity models, the extract significantly increased (P<0.05) the levels of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), thyroid-stimulating hormone (TSH) and significantly decreased the levels of triiodothyronine (T3) and thyroxin (T4) in 500 and 1000 mg/kg dosage. The histopathological studies showed the absence of toxic effects of QBG (50 mg/kg dosage) and revealed evidence of microscopic lesions in the liver, kidney, stomach, heart, spleen, lung, uterus, and ovary in the 500- and 1000-mg/kg groups. The results indicate that the oral acute toxicity of QBG extract was of a low order with LD50 being more than 2000 mg/kg in rats. In addition, slight tissue damage was observed in some tissues in the 500 and 1000 mg/kg groups. It was found that prolonged use at higher doses i.e. 500 mg/kg/day of QBG extract should be avoided.

Assessment of Acute Oral Toxicity of Thiolated Gum Ghatti in Rats

Various drug delivery systems were developed using a modified form of gum ghatti. Modifying gum ghatti using thioglycolic acid improves its mucoadhesive property, and hence, it is a suitable approach for the fabrication and development of controlled drug delivery systems. In accordance with regulatory guidelines, namely, the Organization for Economic Co-operation and Development’s (OECD) 423 guidelines, an acute oral dose toxicity study was performed to examine the toxicological effects of gum ghattiin an animal (Wistar rat) after a single oral dose administration of pure gum ghatti and thiolated gum ghatti. Orally administered pure and thiolated gum ghatti do not reveal any considerable change in the behavioral pattern, food intake, body weight, hematology, or clinical symptoms of treated animals. Furthermore, histopathological studies showed no pathological mutations in the vital organs of Wistar rats after the oral administration of single doses of both types of gumghatti (i.e., 300 mg/kg and 2000 mg/kg body weight). Whole blood clotting studies showed the low absorbance value of the modified gum (thiolated gum ghatti) in contrast to the pure gum and control, hence demonstrating its excellent clotting capability. The aforementioned toxicological study suggested that the oral administration of a single dose of pure and thiolated gum ghatti did not produce any toxicological effects in Wistar rats. Consequently, it could be a suitable and safe candidate for formulating various drug delivery systems.

Repeated oral dose toxicity and genotoxicity of a standardized Quisqualis indica extract.

Quisqualis indica L. of Combretaceae family is a traditional medicine that is widely used for various gastrointestinal discomfort including stomach pain, constipation, and digestive problem. In this study, the potential repeated dose toxicity and genotoxicity of a standardized Quisqualis indica L. extract (HU033) were determined under good laboratory practice conditions. For the repeated dose toxicity test, HU033 was orally administered to Sprague-Dawley (SD) rats at doses of 500, 1000, and 2000mg/kg/day for 13 consecutive weeks. The genotoxicity of HU033 was determined with a standard battery of genotoxicity test, including an in vitro bacterial reverse mutation test, an in vitro chromosomal aberration test, and an in vivo micronucleus test. After 13weeks of repeated dose of HU033 by oral administration, there was no treatment related adverse clinical sign including food consumption, organ weights, and histopathological findings or significant decrement in bodyweight. The no-observed-adverse-effect level of HU033 was higher than 2000mg/kg in both male and female SD rats. No target organs were identified. In addition, no evidence of HU033 genotoxicity was detected based on results from the bacterial reverse mutation test, chromosomal aberration test, and micronucleus test. Based on results of this study, HU033 could be safely used in food and medical products within the tested dose range.

Safety evaluation of mutagenicity, genotoxicity, and cytotoxicity of Lactobacillus spp. isolates as probiotic candidates.

BackgroundProbiotics promote a healthy balance of gut bacteria and have many beneficial effects on human digestive physiology. Although, few side effects of probiotics have been reported. This study aimed to assess the safety of five probiotic candidate Lactobacillus strains isolated from healthy individuals by examining mutagenicity, genotoxicity, and oral toxic effects.MethodsFive selected candidate probiotic (SCPs) strains were evaluated for genotoxicity (Ames test with Salmonella typhimurium), in vitro mammalian chromosome aberration test and an in vivo mouse micronucleus assay on peripheral blood of mice. To evaluate the oral dose toxicity, BALB/c mice models were treated repeatedly (2000, 1000, and 500 mg/kg body weight /day) for 28‐days.ResultsThe Ames test performed for two S. typhimurium strains TA 98 and TA100 (both in the absence and in the presence of S‐9 metabolic activation system) did not show an increase in reverse mutation because of exposure to the SCPs in any of the doses (5.0, 2.5, 1.25, 0.625, and 0.3125 mg/plate). There was no genotoxicity in the SCPs treatment in the vitro chromosome aberration assay with Chinese hamster ovary cells (CHO‐K1). In addition, none of the tested strains increased the frequency of micronucleated reticulocytes in reticulocytes, the SCPs with the studied doses caused no substantial variation in the experimental groups compared to the negative control group (p > 0.05). SCPs were not acutely toxic when administered to male and female BALB/c mice by single gavage at (2000, 1000, and 500 mg/kg b.w/day) with no mortality or clinical signs, change in body weight or macroscopic abnormalities were observed in this dose range.ConclusionAs a result, SCPs did not induce mutagenic potential in vitro with bacterial reverse mutation, clastogenicity, and in vivo tests in the ranges of concentrations evaluated in our study.