**8. Safety statuses of active ingredients in the open market**

The three geographies surveyed were major agrochemical markets in the state, which were purposefully selected for the study. Pesticides poisoning most often comes from swallowing chemicals, after consuming contaminated foods or beverages. Frequently exposed persons are also susceptible to poisoning that can cause organs or systems damage.

Paraquat is a leading cause of fatal poisoning in parts of Asia, the Pacific Islands, and the South and Central Americas. It is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12–24 hours, the very high case fatality of paraquat is due to inherent toxicity and lack of effective treatments [1]. Paraquat dichloride was shown to be very immobile in the soil, does not hydrolyze nor photodegrade in aqueous solutions, and is resistant to microbial degradation under aerobic and anaerobic conditions. The primary route of environmental dissipation of paraquat is adsorption to biological materials and soil clay particles [2], Paraquat dichloride is highly toxic to birds/may cause severe effects [3]. It is reported that more than 70% of trusted sources of paraquat poisonings result in death. Ingesting small to medium amounts of it can lead to fatal poisoning, lung scarring, and the failure of multiple organs, heart, respiratory, kidney, and liver failure. Ingesting large amounts of paraquat causes confusion, muscle weakness, seizures, difficulty breathing, fast heart rate, and coma [4]. Paraquat dichloride is not an approved active ingredient by the EU standards on safe pesticides. It has been recently listed in PAN as a highly hazardous pesticide in 2019 [5], with restricted use, it is prohibited from use and to be faced out by the year 2024. The effect on humans includes fatality if inhaled and may cause severe effects (SAN, PIC).

Glyphosate and its formulations may not only be considered as having genotoxic, cytotoxic, or endocrine-disrupting properties but a causative agent of reproduction abnormalities in both wildlife and humans. Furthermore, the extensive use of glyphosate-based herbicides in genetically modified glyphosate-resistant plants grown for food and feed should be of grave concern since they can be sources of genotoxicity,

cytotoxicity, and reproductive toxicity in wildlife and humans [6]. Although glyphosate is approved for use by the EU, other standards organizations have listed it as a highly hazardous pesticide in 2011, 2014, and 2019 [5]. This active ingredient has been restricted, only be used under specific and defined conditions. It is also a probable carcinogenic substance to humans and has environmental toxicity by being very persistent in water and sediments [7]. Glyphosate provokes oxidative damage in the liver and kidneys of mammals by disrupting mitochondrial metabolism, disrupting endocrine-signaling systems and residues from glyphosate may pose higher risks to the kidneys and liver, reproductive development impairment [8]. Increases in the frequency of serious, chronic kidney disease were observed among male agricultural workers in some regions with heavy glyphosate use and "hard" water. And that the possible adverse effects of glyphosate exposure on kidney and liver warrant a focused, international research effort [9, 10]. Glyphosate can alter the functioning of hormonal systems and gene expression patterns at various dosage levels. Such effects will sometimes occur at low and likely environmentally-relevant exposures. Contemporary endocrine science has demonstrated that dose-response relationships will sometimes deviate from a linear increase in the frequency and severity of impacts expected as dose levels rise [11]. The timing, nature, and severity of endocrine system impacts will vary depending on the levels and timing of glyphosate exposures, this is pertinent as agrochemical users in Nigeria are indoctrinated in terms of dosage, rate, and timing of application.

Permethrin + Pyriproxyfen is used to kill a large range of pests; fleas, ticks, cockroaches, flies, and mosquitoes. The environmental protection agency (EPA) reviewed the pesticides register showed that permethrin stays a long time in the soil, very low amount stays in the water. Permethrin has some health risks; headaches, dizziness, nausea, shortness of breath, skin irritation, and redness of eyes when used at higher levels [12]. However, it is highly hazardous, with probable carcinogen in humans [13], and highly toxic to honey bees [14], aquatic, pollinator, and wildlife risk [5].

Cypermethrin is a pyrethroid insecticide, first synthesized in 1974, widely used to kill insects as it works quickly by affecting the nervous system, toxicity level in animals varies,for example, in rats includes tremors, seizures, and salivation, in cockroaches when exposed to little amount as 0.02 micrograms per gram causes brain paralysis, restlessness, and prostration. Cypermethrin is approved for use to manage agricultural insect pests. It is however listed as a highly hazardous pesticide in 2011 and 2019. It is classified as highly restricted use with mandatory risk-specific mitigation measures [3, 5]. It has highly aquatic toxicity, toxic on honey bees, and also with aquatic and pollinator risk [15]. Effect of cypermethrin in humans when exposed sometimes causes itching and tingling sensations. The half-life of cypermethrin in the environment takes about 30 days, soil microbes easily break it down because of the low potential to move in the soil but poses little to no risk when used responsibly [2].

The toxicity status of Chlorpyrifos is similar to cypermethrin except that it is not indicated in the EU database but UTZ classified it as highly restricted, may only be used under the specific condition with risk-specific mitigation measures, and is potential to be prohibited. Chlorpyrifos classified as highly hazardous in 2011 and 2019, poses inhalation risk to humans, high aquatic toxicity, highly toxic to bees [14], birds with aquatic pollinator, and wildlife risk [3].

Dichlorvos an organophosphate insecticide, also used as a public health vector control for animals, is registered worldwide for varieties of uses, majorly used as a post-harvest fumigant for control of various pests in food, the acceptable daily intake (ADI) for Dichlorvos was established as 0.004mg/kg bw and the acute reference dose

#### *Toxicity Status and Risks of Common Active Ingredients in Open Markets DOI: http://dx.doi.org/10.5772/intechopen.104409*

was 0.1mg/kg bw. It can be applied with aerosols, fogging, and sprays equipment. It also breaks down rapidly in humid air, water, and soil, it takes longer time on wood when exposed to humans through food can be acutely toxic with typical cholinergic signs that are highly hazardous, dichlorvos is not teratogenic in mice and rats' halflives of recovery is about 15days in human and 2 hours in rats [16].

Dichlorvos is not approved for use but found in open markets, it is restricted in use and meant to be phased out by the year 2024 (BCI). It is highly prohibited, may only be used under specific, defined conditions. The active ingredient is classified as highly hazardous to humans [17], it is fatal if inhaled according to the EU and globally harmonized system (EU, GHS). It is a possible and probable carcinogen [2, 7], with high aquatic toxicity and highly toxic to honey bees and birds [15, 18–20].

Dimethoate comes in different forms; dustable powder (DP), wettable powder (WP) soluble concentrate, its toxicity was evaluated in 1992 by (WHO), it is used to control a wide range of insects and pests, in cereals, citrus, coffee, cotton, fruits, grapes, potatoes, beetroot, tea, and vegetables. It can also be used to control flies because of its systemic nature and acaricide the solubility of dimethoate in water at 90% purity has 39.8 at 25<sup>o</sup> C after 4 hours, equilibrium. In rats, the toxicity of dimethoate is mostly acute, such as oral irritation, dermal sensitization, eye irritation in humans, WHO hazard classification of dimethoate is "class moderately hazardous," UN classification is "Toxic class 6.1," US EPA Classification is; (Formulation) 11, EC Classification; Risk Xn (R21/22) Reviews by WHOEHC (1986) concluded that when used in proper level and accordingly exposure of human through the air, food, or water can be negligible.

Nicosulfuron is used as post-emergence in forage maize, found to have low dermal and inhalation toxicity, can be slightly irritating in rats, and has not been evaluated by the FAO, JMPR, and WHO/IPCS, although it is currently under review, it is registered in the U.S.A, the WHO Classification of Nicosulfuron is U; unlikely to cause an acute hazard in normal use. This active ingredient does not meet the criteria established in the UN recommendations on the transport of dangerous goods and therefore is not considered hazardous for transportation purposes. It is also not co-formulated with other active ingredients; toxicity in rats includes acute dermal irritation and eye irritation [21].

Profenofos + Cypermerthrin is a co-formulated organo-phosphorous insecticide, studies have shown its toxicity levels on animals, plants, and even the environment's fate when it comes in contact. Profenofos was evaluated by JMPR in 1990, 1992, 1994, and 1995, toxicological, reviews were also conducted in 2007 when an ADI OF 0 to 0.03mg/kg bw and ARfD of 1mg/kg bw were established, profenofos is a clear liquid with weak odor, its solubility in water at 22o C is 2.8mg/l at a pH of 6.9, profenofos is slowly absorbed in metabolized, it was major residue when crops are harvested several weeks after the last applications, its residues are not expected to occur in succeeding crops. Reviewed by JMPR health risk shows that profenofos is unlikely to present a public health concern.

S-metolachlor is used for varieties of crops for control of grasses, for example, pigweeds (*Amaranthu*s spp.); they are different commercial brands, herbicides that contain metolachlor as active ingredients although formulation and chemical composition may differ, some products metolachlor safeners are added some, no safeners added. A safener is added to metolachlor to reduce injury to crops, such as corn, but injuries to other crops solely depend on the amount of safener used or environmental concerns. Metolachlor has four different isomers but can be grouped into two, which are S-metolachlor isomers and R-metolachlor isomers, both are made from the same

materials but S-metolachlor isomer is more active in herbicidal effects compared to R-metolachlor.

Lambda-cyhalothrin is a synthetic pyrethroid insecticide used in agricultural and public health to control a wide range of insects and pests at developmental stages, it is a nonsystemic chemical, does not stay long in the soil so has an only limited function when used as soil insecticide. Lambda-cyhalothrin can be applied by spree spraying and residual spraying. Additionally, the provided data on acute toxicity, skin irritation, and sensitization. The mutagenic study reviewed that Lambda-cyhalothrin is nonmutagenic, JMPR has defined an acceptable daily intake (ADI) of 0 0.02mg/kg bw, water solubility is 0.005 mg/l. The IPCS hazard classification of Lambda-cyhalothrin is moderately hazardous Class II (WHO). Lambda-cyhalothrin is approved for use in weed management but listed as highly hazardous in 2011 and 2019 [5]. It is to be phased out by the year 2024 and with highly restricted use, only be used under specific conditions, and according to the globally harmonized system (GHS), it poses a fatal risk to humans if inhaled. This active ingredient also poses a long-term health effect as an endocrine disruptor and as having reproductive toxicity [22].

The 2,2-dichlorovinyl dimethyl phosphate is another insecticide that is not listed in the active ingredients database of the EU. It is however listed as a highly hazardous substance in PAN as an endocrine disruptor, has highly aquatic toxicity, is highly toxic to honey bees, aquatic, and pollinator risk [5].

Carbendazim is a very common fungicide but was recently listed as highly hazardous in 2019 [5] and not on the approved list of EU pesticides. It is restricted, prohibited with exceptions for certain pests, in certain crops and regions, and may only be used under specific, defined conditions as recommended by Fairtrade. This active ingredient has a mutagenic effect on humans and it is a reproductive toxin according to EU and GHS [13, 23]. Carbendazim is a widely used systemic fungicide that is mainly used for protective and curative functions. It is used to control a large number of fungal diseases, such as mold, mildew, rot, and blight, in some crops, such as ginger, nuts, legumes, and even fruits. Additionally, carbendazim has been nominated for chemical program review under Australia Pesticide and Veterinary Medicines Authority (APVMA) because of its effect known to cause impaired human fertility and cause birth defects, the review made a conclusion it causes the above effects, the half-life of carbendazim is as long as 6 months, recommended warning for registered carbendazim products that it must contain the following stated warning "Contains carbendazim which causes birth death and irreversible male infertility, in laboratory animals, avoid contact with carbendazim" recommended usage level in drinking water is 0.09 mg/ls [24]. For safety operators mixing and loading carbendazim must wear gloves to avoid skin irritation, respirator face shield should be worn to prevent ingestion. Even with the use of these safety measures the risk cannot be mitigated, the use of carbendazim is no longer supported for occupational health and safety grounds [2].

Another active ingredient similar to carbendazim is mancozeb, also a fungicide with the recent addition to the highly hazardous list; also has restrictions of use, prohibited, risk-specific mitigation measures are mandatory and may only be used under specific, defined conditions according to FSC, RA, and Fairtrade standards. Mancozeb is a probable carcinogen to humans [13, 23], an endocrine disruptor, and has wildlife risk [3]. Mancozeb is used for a wide range of fungal diseases as protective fungicides for horticultural and agricultural purposes. Mancozeb is a member

#### *Toxicity Status and Risks of Common Active Ingredients in Open Markets DOI: http://dx.doi.org/10.5772/intechopen.104409*

of the ethylenebisdithiocarbamate (EBDC) group of fungicides which maneb and metiram are some of the related active ingredients, used on crops, such as potatoes, apples, grapes, onions, tomatoes, and melons. Its effects on human health can be toxic because it is majorly harmful to thyroid organ, reviewed to cause thyroid toxicity, thyroid lesions, and thyroid tumors, the residual composition of mancozeb is not to a level of concern to the EPA and other effects, such as cancer risk, effects on terrestrial and aquatic species, are feasible by using restrictions [25].

The 2,2dichlorovinyle dimethyl phosphate is also known as (dichlorvos); it is a colorless to amber liquid, an agricultural chemical used to control insects, diseases, and eliminate storage pests and crops. Application of dichlorvos is mainly expelled into the air for household pesticides and it is usually distributed into the water for pesticide control and sprayed on land when used for agricultural purposes. Furthermore, it is eliminated by hydrolysis and biodegradation, some toxic effects on animals and humans include acute effects such as weakness, severe anemia, anticholinergic symptoms other effects on gastrointestinal tracts and nervous system in rabbits, it causes severe skin irritation. The current regulation in Japan for dichlorvos is Deleterious substance, Class I designated chemical substance.

Imidacloprid is a new insecticide that is related to nicotine chemically, just like nicotine, imidacloprid acts on the nervous system, it is used in large quantities in crops, pests, and turf grasses, when imidacloprid is exposed to animals or humans some of the effects includes, Apathy, emaciation, convulsion, labored breathing, when exposed for a long time it causes loss of weight and thyroid lesions in human. It can be acutely toxic in some animals, bird species, and plants by causing decreasing growth levels.

Hexaconazole is a systemic triazole fungicide that is used in the control of a wide range of diseases of crops example of some diseases are black and yellow Sigatoka diseases of banana, used on banana foliar to control diseases, The Health Effects Division Hazard Identification Assessment Reviews Committee (HIARC), evaluated the toxicological level of hexaconazole on human and animals is reviewed to have enhanced sensitivity to infants and children. In animals such as rats, the study revealed a decrease in body weight gains and decreased pub survival, although the aggregate exposure risk is limited to dietary exposure only, hexaconazole has low toxicity by oral, dermal, and inhalation mode of exposure, it can be slightly irritating to the eye and skin sensitization in animals.

Hexaconazole was found in the open market but not approved by the EU, classified as a highly hazardous substance, a possible carcinogen [26] very persistent/water, and highly toxic to bees [5].

Imidacloprid, a fungicide approved by the EU for the management of fungal diseases in crops, although approved, it is however prohibited with an exception for certain pests in certain crops and without exceptions by some other standards. The active ingredient may cause severe effects on humans and be highly toxic to honey bees and birds [5, 14].

A fungicide named dimethoate is not on the approved list of the EU, it is listed as highly hazardous in 2011 and 2019 [5]. Dimethoate is classified as a probable carcinogen and with reproductive toxicity according to globally harmonized system [13, 23]. This active ingredient is recommended as restricted with minima use and potentially to be prohibited according to FSC, RA, UTZ. It also has inhalation risk to humans, highly toxic to honey bees, birds, and aquatic, pollinator, and wildlife risk according to SAN [21].
