BACKGROUND: Rosemary (Rosmarinus officinalis) contains alkaloids, phenolic acids, saponins, tannins, diterpenes, flavonoids, and essential oils and has antioxidant, anti-inflammatory, antibacterial, anticancer, neuroprotective, cardioprotective, and hepatoprotective effects. While rosemary is generally considered safe for consumption and topical application, allergic reactions and dermatitis have been reported in some individuals. This paper provides an in-depth review of the current studies on rosemary toxicity, shedding light on its potential adverse effects and underlying mechanisms.
METHODS: Google Scholar, PubMed, Scopus, and Web of Science were used to perform extensive research from the inception of these databases until February 2024.
RESULTS: The toxicological effects explored include affecting several organs such as the liver and kidney by causing atrophic and degenerative changes, increasing blood urea nitrogen (BUN), aspartate aminotransferase (AST), and reducing total serum protein levels. Rosemary may induce reproductive toxicity by decreasing spermatogenesis in the testes, testosterone, sperm density, and motility. It might also trigger genotoxicity and anomalies in fetuses by increasing cytoplasmic membrane shrinkage, the formation of apoptotic bodies, internucleosomal deoxyribonucleic acid (DNA) fragmentation, and DNA ladder formation.
CONCLUSIONS: While rosemary is considered safe for food preservation, caution is warranted regarding chronic and high doses due to potential adverse effects on the kidneys, liver, reproductive system, and teratology. Additionally, it underscores the significance of considering drug interactions. The article also highlights the importance of considering toxicological data in realistic exposure situations and discusses the relevance of these findings for human health. Hence, further research is recommended to enhance our understanding of the toxicity profile associated with rosemary.

Micro(nano)plastics (MNPs) have been detected in various ecological environments and are widely used due to their stable properties, raising widespread concern about their potential human reproductive toxicity. Currently, infertility affects approximately 10-30% of couples of reproductive age globally. MNPs, as environmental pollutants, have been shown to exhibit reproductive toxicity through intrinsic mechanisms or as carriers of other hazardous substances. Numerous studies have established that MNPs of varying sizes and types can penetrate biological barriers, and enter tissues and even organelles of organisms through four main routes: dietary ingestion, inhalation, dermal contact, and medical interventions. However, historical research on the toxic effects of MNPs on reproduction mainly focused on lower and aquatic species. We conducted an inclusive review of studies involving terrestrial mammals, revealing that MNPs can induce reproductive toxicity via various mechanisms such as oxidative stress, inflammation, fibrosis, apoptosis, autophagy, disruption of intestinal flora, endocrine disruption, endoplasmic reticulum stress, and DNA damage. In terrestrial mammals, reproductive toxicity predominantly manifests as disruption in the blood-testis barrier (BTB), impaired spermatogenesis, sperm malformation, sperm DNA damage, reduced sperm fertilizing capacity, compromised oocyte maturation, impaired follicular growth, granulosa cell apoptosis, diminished ovarian reserve function, uterine and ovarian fibrosis, and endocrine disruption, among other effects. Furthermore, MNPs can traverse the maternal-fetal interface, potentially impacting offspring reproductive health. To gain a comprehensive understanding of the potential reproductive toxicity and underlying mechanisms of MNPs with different sizes, polymer types, shapes, and carried toxins, as well as to explore effective protective interventions for mitigating reproductive damage, further in-depth animal studies, clinical trials, and large-scale epidemiological studies are urgently required.

Per- and polyfluoroalkyl substances (PFAS) have already drawn a lot of attention for their accumulation and reproductive toxicity in organisms. Perfluorooctanoic acid (PFOA) and perfluorooctanoic sulfonate (PFOS), two representative PFAS, are toxic to humans and animals. Due to their widespread use in environmental media with multiple toxicities, PFOA and PFOS have been banned in numerous countries, and many substitutes have been produced to meet market requirements. Unfortunately, most alternatives to PFOA and PFOS have proven to be cumulative and highly toxic. Of the reported multiple organ toxicities, reproductive toxicity deserves special attention. It has been confirmed through epidemiological studies that PFOS and PFOA are not only associated with reduced testosterone levels in humans, but also with an association with damage to the integrity of the blood testicular barrier. In addition, for women, PFOA and PFOS are correlated with abnormal sex hormone levels, and increase the risk of infertility and abnormal menstrual cycle. Nevertheless, there is controversial evidence on the epidemiological relationship that exists between PFOA and PFOS as well as sperm quality and reproductive hormones, while the evidence from animal studies is relatively consistent. Based on the published papers, the potential toxicity mechanisms for PFOA, PFOS and their substitutes were reviewed. For males, PFOA and PFOS may produce reproductive toxicity in the following five ways: (1) Apoptosis and autophagy in spermatogenic cells; (2) Apoptosis and differentiation disorders of Leydig cells; (3) Oxidative stress in sperm and disturbance of Ca2+ channels in sperm membrane; (4) Degradation of delicate intercellular junctions between Sertoli cells; (5) Activation of brain nuclei and shift of hypothalamic metabolome. For females, PFOA and PFOS may produce reproductive toxicity in the following five ways: (1) Damage to oocytes through oxidative stress; (2) Inhibition of corpus luteum function; (3) Inhibition of steroid hormone synthesis; (4) Damage to follicles by affecting gap junction intercellular communication (GJIC); (5) Inhibition of placental function. Besides, PFAS substitutes show similar reproductive toxicity with PFOA and PFOS, and are even more toxic to the placenta. Finally, based on the existing knowledge, future developments and direction of efforts in this field are suggested.

As the most widely used polybrominated diphenyl ether, BDE-209 is commonly used in polymer-based commercial and household products. Due to its unique physicochemical properties, BDE-209 is ubiquitous in a variety of environmental compartments and can be exposed to organisms in various ways and cause toxic effects. The present review outlines the current state of knowledge on the occurrence of BDE-209 in the environment, influencing factors, toxicity, and degradation. BDE-209 has been detected in various environmental matrices including air, soil, water, and sediment. Additionally, environmental factors such as organic matter, total suspended particulate, hydrodynamic, wind, and temperature affecting BDE-209 are specifically discussed. Toxicity studies suggest BDE-209 may cause systemic toxic effects on living organisms, reproductive toxicity, embryo-fetal toxicity, genetic toxicity, endocrine toxicity, neurotoxicity, immunotoxicity, and developmental toxicity, or even be carcinogenic. BDE-209 has toxic effects on organisms mainly through epigenetic regulation and induction of oxidative stress. Evidence regarding the degradation of BDE-209, including biodegradation, photodegradation, Fenton degradation, zero-valent iron degradation, chemical oxidative degradation, and microwave radiation degradation is summarized. This review may contribute to assessing the environmental risks of BDE-209 to help develop rational management plans.

Tebuconazole has been widely applied over three decades because of its high efficiency, low toxicity, and broad spectrum, and it is still one of the most popular fungicides worldwide. Tebuconazole residues have been frequently detected in environmental samples and food, posing potential hazards for humans. Understanding the toxicity of pesticides is crucial to ensuring human and ecosystem health, but the toxic mechanisms and toxicity of tebuconazole are still unclear. Moreover, pesticides could transform into transformation products (TPs) that may be more persistent and toxic than their parents. Herein, the toxicities of tebuconazole to humans, mammals, aquatic organisms, soil animals, amphibians, soil microorganisms, birds, honeybees, and plants were summarized, and its TPs were reviewed. In addition, the toxicity of tebuconazole TPs to aquatic organisms and mammals was predicted. Tebuconazole posed potential developmental toxicity, genotoxicity, reproductive toxicity, mutagenicity, hepatotoxicity, neurotoxicity, cardiotoxicity, and nephrotoxicity, which were induced via reactive oxygen species-mediated apoptosis, metabolism and hormone perturbation, DNA damage, and transcriptional abnormalities. In addition, tebuconazole exhibited apparent endocrine-disrupting effects by modulating hormone levels and gene transcription. The toxicity of some TPs was equivalent to and higher than tebuconazole. Therefore, further investigation is necessary into the toxicological mechanisms of tebuconazole and the combined toxicity of a mixture of tebuconazole and its TPs.

For the potential health benefits and nutritional value, polyphenols are one of the secondary metabolites of plants that have received extensive research. It has anti-inflammatory and cytotoxicity-reducing properties in addition to a high antioxidant content. Macromolecular polyphenols and polysaccharides are biologically active natural polymers with antioxidant and anti-inflammatory potential. Arsenic is an ecologically toxic metalloid. Arsenic in drinking water is the most common way people come into contact with this metalloid. While arsenic is known to cause cancer, it is also used to treat acute promyelocytic leukemia (APL). The treatment\'s effectiveness is hampered by the adverse effects it can cause on the body. Oxidative stress, inflammation, and the inability to regulate cell death cause the most adverse effects. Polyphenols and other macromolecules like polysaccharides act as neuroprotectants by mitigating free radical damage, inhibiting nitric oxide (NO) production, lowering A42 fibril formation, boosting antioxidant levels, and controlling apoptosis and inflammation. To prevent the harmful effects of toxins, polyphenols and pectin lower oxidative stress, boost antioxidant levels, improve mitochondrial function, control apoptosis, and suppress inflammation. Therefore, it prevents damage to the heart, liver, kidneys, and reproductive system. This review aims to identify the effects of the polyphenols in conjugation with polysaccharides as an ameliorative strategy for arsenic-induced toxicity in various organs.

The unique characteristics of nanoparticles (NPs) have captivated scientists in various fields of research. However, their safety profile has not been fully scrutinized. In this regard, the effects of NPs on the reproductive system of animals and humankind have been a matter of concern. In this article, we will review the potential reproductive toxicity of various types of NPs, including carbon nanomaterials, dendrimers, quantum dots, silica, gold, and magnetic nanoparticles, reported in the literature. We also mention some notable cases where NPs have elicited beneficial effects on the reproductive system. This review provides extensive insight into the effects of various NPs on sperm and ovum and the outcomes of their passage through blood-testis and placental barriers and accumulation in the reproductive organs.

Endocrine disruptor chemicals (EDCs) can have a harmful effect on the human body\'s endocrine system and thus adversely affect the development, reproduction, neurological, cardiovascular, and immune systems and metabolism in humans and wildlife. According to the World Health Organization, EDCs are mostly man-made and found ubiquitously in our daily lives, notably in pesticides, metals, and additives or contaminants in food and personal care products. Human exposure occurs through ingestion, inhalation, and dermal contact. Bisphenol A (BPA) is a proven EDC capable of mimicking or blocking receptors and altering hormone concentrations and metabolism. Although consumed in low doses, it can stimulate cellular responses and affect the body\'s functions. In humans, exposure to BPA has been correlated with the onset or development of several diseases. This literature review aimed to verify the effects of BPA on human male infertility using the most recently published literature. Thus, this review allowed us to conclude that this compound seems to have harmful effects on human male fertility, causing changes in hormonal and semen characteristics. However, these conclusions lack more robust and reproducible scientific studies. Even so, and since male infertility prevalence is increasing, preventive measures must be taken to ensure male fertility.

Microplastics (MPs) and nanoplastics (NPs), as their name suggest, are tiny plastic particles. The negative impact of MPs as an emerging pollutant on humans is not hidden from anyone. Recent research on how this pollutant affects the reproductive system and how it enters the blood, placenta, and semen has attracted the attention of scientists. This review study deals with the reproductive toxicity of MPs particles in terrestrial animals, aquatic animals, soil fauna, human cells, and human placenta. In vitro and in vivo animal studies showed that MPs can lead to reduced fertility in men, reduced ovarian capacity, apoptosis of granulosa cells, or even reduced sperm motility. They cause oxidative stress and cell apoptosis and inflammatory effects. The results of these animal studies show that MPs may have similar effects on the human reproductive system. However, not much research has been done on human reproductive toxicity by MPs. Therefore, special attention should be paid to the toxicity of the reproductive system by MPs. The purpose of this comprehensive study is to express the importance of the impact of MPs on the reproductive system. These results provide new insight into the potential dangers of MPs.

Microplastics (100nm-5 mm) and nanoplastics (1-100 nm) are collectively referred to as micro(nano)plastics (MNPs), which are refractory to degradation, easy to migration, small in size, strong in adsorption, and can widely present in human living environment. A number of studies have confirmed that MNPs can be exposed to the human body through a variety of routes, and can penetrate various barriers to enter the reproductive system, suggesting that MNPs may pose potential harm to human reproductive health. Current studies most were limited to phenotypic studies and their subjects were basically lower marine organisms and mammals. Therefore, in order to provide theoretical base for further exploring the effects of MNPs on the human reproductive system, this paper searched the relevant literature at home and abroad, mainly analyzed rodent experiments, and concluded that the main exposure routes of MNPs are dietary intake, air inhalation, skin contact and medical plastics. After entering the reproductive system, MNPs produce reproductive toxicity mainly through oxidative stress, inflammation, metabolic disorders, cytotoxicity and other mechanisms. More work is required to comprehensively identify the exposure routes, improve the detection methods to evaluate the effective exposure and deeply study the specific mechanisms of toxic effects, withing the aim of conducting relevant studies at the population level in the next step.