Cassava (Manihot esculenta Crantz) is a plant native to Brazil (South America), cultivated throughout the tropics for its fleshy roots rich in starch [1] . It feeds more than 700 million people and is cultivated in more than 105 countries worldwide [2] with a global production of 292 million tonnes in 2017 according to the FAO. Approximately 60% of cassava produced is intended for human consumption, 20% for animal feed and 10% is processed into secondary products [3] . The leaves are consumed as vegetables in many parts of Africa. In the Central African Republic, cassava production is 725,000 tonnes of cassava, or 2.9 million tonnes of fresh tuber, followed by yam 450,000 tonnes and maize 167,000 tonnes FAOSTAT, 2017. Despite its benefits, cassava is one of the most toxic food plants in the world. This toxicity is linked to the presence of two cyanogenic glucosides: linamarin (93%) and lautostralin (7%) [4] . These glucosides are not toxic in themselves but following enzymatic hydrolysis release hydrocyanic acid [5] . Many studies seem to establish a link between diet and the appearance of certain pathologies. One of the main explanatory factors would be repeated exposure to low doses of toxic contaminants via food. KONZO disease in Congo is caused by the consumption of cassava, which contains a high level of HCN [6] . The consumption of cassava poorly detoxified in hydrocyanic acid seems to play a role in the genesis of these neuropathies in tropical regions [7] . It feeds 800,000,000 people worldwide [8] (FASTAT 2017) (Poor processing of cassava, including poorly done retting, leaves a by-product containing cyanide unfit for consumption. Regular consumption of this type of product can generate a neuromyelopathy called konzo. It is a form of symmetrical, permanent spastic paraparesis with a sudden onset. It is attributed to exposure to cyanide resulting from a mono-diet of bitter cassava, which is not or poorly “toxic” [9] , as well as a diet low in sulfur amino acids (Ministry of Health of Mozambique, 1984). KONZO presents as an irreversible neurological disorder affecting the upper part of the body, widespread in rural areas of sub-Saharan Africa, whose main crop consists of bitter varieties of cassava. Due to the dangers of chronic toxicity of this plant, there is talk of deploying more intensive efforts to obtain low and acceptable levels of cyanide. The first possibility of reducing the cyanide level in cassava lies in the selection of cultivars free or with low content of HCN [10] . It is difficult to find cyanide-free varieties, but studies will always continue to be done. Cassava varieties that produce less than 50mg/kg of HCN of peeled and fresh roots are considered harmless [11] . CAR is one of the countries where cassava is the staple food and its cultivation is known throughout the country. The leaves are eaten as a vegetable and the roots as the energy support. Since its introduction in the Central African Republic in the 1850s [12] , many studies have been carried out on its improvement [13] (and on varietal selection [14] . An epidemiological survey confirmed the presence of KONZO disease in Health District No. 2 in 2009 [15] . Also, a study reported that during the rainy season, the demand for cassava chips is higher than the supply in most of the country. This deficit sometimes leads some processors to voluntarily shorten the processing time of cassava. As a result, the time for retting and drying operations is often shortened. This leads to risks of toxicity due to the persistence of cyanogenic derivatives in the chips. In order to guarantee food security, it is a question of launching research on the toxicological aspect of this plant. We chose the CAR because cassava is a staple food for the Central African population, that is to say, it is consumed by more than 97% of the population with a daily consumption frequency of 2 times a day for the most part. This could constitute a health risk due to the presence of HCN.

This study can help identify accessions that have a high HCN content in order to consider their withdrawal via a food chain toxicity study. This is why, through this research project, we proposed to evaluate the HCN content in the different cassava accessions in circulation in the Central African Republic to identify varieties with high toxicity potential and to develop a consumer awareness campaign. The aim is to recommend cassava accessions that have a low hydrocyanic acid content to the population.

Do fresh leaves of cassava accessions have significant levels? Are they toxic? What impact can they have on humans? How can a significant release of hydrocyanic acid be achieved using an effective method?

The evaluation of the rate of hydrocyanic acid in the fresh leaves of 58 cassava accessions, allowed to divide the accessions into three groups according to the HCN content: weakly (13 to 49, 33 mg), moderately (50.33 mg to 98.33 mg) and strongly (100.66 mg to 144 mg) These concentrations are mostly very high compared to the FAO threshold which is 10 mg HCN.kg⁻¹. That is to say, the regular consumption of the leaves of these accessions can generate a health problem linked to the high content of HCN. This leads us in the perspectives to evaluate the toxic potential of these accessions through an experiment which will be carried out on moose. In case of problem, the results will be published to the population so that appropriate solutions can be found.

Thus, the results of the student’s t-test on the samples of low and moderately concentrated HCN contents do not suggest a statistically significant difference in high content (t (31) = −11.7; p > 0.05; 95% CI = [−47.1; −33.2]). That is, the low and moderately high average contents are almost negligible, unlike the results of the student’s t-test on the samples of low and high HCN contents which suggest a statistically significant difference in HCN content (t (4) = −10.3; p < 0.05). Thus, the results of the student’s t-test on the samples of moderately concentrated HCN and concentrated HCN contents suggest a significant difference in HCN content (t (4) = −5.7; p < 0.05). The results of the above test show that (i) the HCN content and the pH value of the accessions are negatively correlated (cf −0.05683993 < 0) and (ii) there is no correlation between the HCN content and the pH value of the accessions (cf absolute value of the correlation coefficient less than 0.1). Furthermore, hydrocyanic acid (HCN) is a volatile compound. It evaporates rapidly in air at temperatures above 28˚C and dissolves easily in water. It can easily be lost during transportation, storage and analysis of samples. Cyanogen content of cassava leaves normally ranges between 300 and 1500 mg HCN /kg fresh weight [19] . These concentrations are higher than those obtained in this work. Cyanide concentration often varies widely between accessions or varieties and ecological and cultural conditions [20] . The essential substrates for the conversion of cyanide to thiocyanate are thiosulfate and 3-mercapto-pyruvate, derived mainly from the sulfur-containing amino acids cysteine, cystine, and methionine. Vitamin B12 in the form of hydroxycobalamin likely influences the conversion of cyanide to thiocyanate. Hydroxycobalamin has been reported to increase urinary excretion of thiocyanate in experimental animals ingesting small doses of cyanide [21] [22] . From 60 to 100 percent of injected cyanide in toxic concentrations is converted to thiocyanate within 20 hours, and enzymatic transformation accounts for more than 80 percent of cyanide detoxification [23] . Thiocyanate is widely distributed in body fluids, including saliva, and it can be readily detected. In healthy humans, a dynamic equilibrium between cyanide and thiocyanate is maintained. A low-protein diet, particularly one lacking sulfur-containing amino acids, may reduce the detoxification capacity and thus make a person more vulnerable to the toxic effect of cyanide [24] . Therefore, cyanogenic glycosides as such are not toxic, but once ingested by humans, they undergo decomposition to hydrocyanic acid by enzymes of the intestinal flora [25] . The dose of 1 mg HCN.kg⁻¹ of body weight is considered likely to cause acute poisoning in humans [26] . Other authors such as [27] have placed the minimum lethal dose between 0.5 and 3.5 mg HCN.kg⁻¹ of body weight. In animals, the lethal dose is 1 mg HCN.kg⁻¹ of body weight. The hydrocyanic acid content set by the FAO must be less than or at most equal to 10 mg HCN.kg⁻¹ of product [28] .

Then, the average soil pH for optimal cassava growth and development ranges between 5.5 and 6.5. The pH obtained from the studied accessions ranges from 5.80 to 6.47. Which is within the range of soil pH required [29] . Soils with pH below 5.5 are acidic and can only support cassava growth if treated with lime. Incorporating lime in the soil preparation process helps normalize the soil pH before cassava cultivation. This is a common practice here in Nigeria. Cassava growth can be affected if there is a high salt concentration in the soil with pH as high as 7.8. [30] .

Finally, the incidence of mosaic disease is 5%, which shows a good phytosanitary condition of the collection. The cuttings used to set up the collection were taken from asymptomatic plants, hence the importance of collecting cuttings from healthy plants before replanting to limit the spread of the disease [31] [32] . The collection plot was regularly cleaned, which may partly explain the good phytosanitary condition [33] . This collection constitutes an important source of healthy cassava material that can serve as a basis for a project to multiply and disseminate cuttings of good phytosanitary quality. Previous work has shown that the incidence of mosaic disease at the national level was 85% and that 79% of producers use contaminated cuttings [34] .

From all the above, although cassava is an important crop and a source of food for many populations, it is essential to understand the health risks associated with its consumption. The toxins present in cassava can be dangerous if not properly removed through proper preparation and cooking. It is, therefore, crucial to take the necessary precautions to avoid hydrocyanic acid poisoning. By opting for food alternatives and educating people about the risks associated with cassava, we can protect the health of those who depend on this vital crop. The major problem is the presence of cyanide in cassava, which is poisonous and must be removed before consumption. To date, there is no proper processing method to completely eliminate cyanide in the by-products.

This work has helped us to understand that the cyanide content in the leaves is higher than the FAO standard. This would represent a public health risk through regular consumption of cassava. The information from this work makes it possible to estimate the risks of exposure to cyanide linked to the consumption of cassava. This study requires in-depth work to have reliable conclusions. A work evaluation of toxic potential of the different accessions is necessary. The results will guide major future decisions on the issue to guarantee the health of consumers.

This work was supported, in whole or in part, by the Gates Foundation and the UK Foreign, Commonwealth & Development Office, Grant/Award Number: INV-002969 (formerly OPP1212988) to the Central and West African Virus Epidemiology (WAVE) Program for root and tuber crops—through a subgrant from Université Félix Houphouët-Boigny (UFHB) to the University of Bangui, Central African Republic. The conclusions and opinions expressed in this work are those of the authors alone and shall not be attributed to the Foundation. Under the grant conditions of the Foundation, a Creative Commons Attributions 4.0 License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.