**2. Survey of crop protection compounds currently used in Uruguay**

The agriculture is one of the most important economic activities in Uruguay, and in the past decades, the summer rain-fed crops have experienced an important expansion and intensification process. In this way, the soybean crop occupied 1,140,000 ha and its exportable volumes exceed 3 million tons/year [21]. This process implied an increase in the use of crop protection compounds, mainly herbicides [22].

that interferes with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body, which are responsible for the maintenance of homeostasis,

Throughout the 1990s, the concern about the adverse effects on human and wildlife resulting from interaction between environmental chemicals and endocrine system has been increasing. However, given that hundreds of synthetic compounds have been released into the environment, the possible mechanisms for disruption and their physiological effects are enormous and not well understood. In this way, several regulatory agencies have developed different screening and testing strategies to assess the potential of crop protection compounds

In Uruguay, the registry and use of these chemical compounds are regulated by the General Direction of Agricultural Services (Res DGSA N° 01/2009 y Dec. 294/2004), but the authorization process does not consider the potential to induce adverse effects in humans and wildlife via interaction endocrine system. In this way, some laboratory and field studies have detected masculinization process [17], induction of the synthesis of plasmatic vitellogenin in immature organism and changes in somatic index in fish exposed to potential sources of endocrine disruptors [18, 19]. In order to bridge the gap between authorization process of crop protection compounds and

**1.** to identify the crop protection compounds used in Uruguay that have a documented or

**2.** to identify the main geographical areas potentially affected by endocrine disrupting

**3.** to propose a research strategy to guide the effort and identify the potential scope of the

We do this by an eco-epidemiological analysis of the Uruguayan database of crop protection compound imported in 2017 (DGSA database), the use guidelines (SATA Guide 2016) [20], the national agricultural census [21] as well as the public endocrine disruptor databases (PAN Pesticide Database (PANNA) and Pesticide Properties Database (PPDB)). The main class of crop protection compounds (herbicides, insecticides and fungicides) was ranked according to the imported volumes, and the top 10 of each class were contrasted with the endocrine disruptor databases and scientific articles. In function of the use guidelines (recommended doses) and the geographical localization of the main crops, the hot spot areas and the crop protection compound priorities were identified due its potential effects on endocrine system.

**2. Survey of crop protection compounds currently used in Uruguay**

The agriculture is one of the most important economic activities in Uruguay, and in the past decades, the summer rain-fed crops have experienced an important expansion and

environmental protection policies, the aims of this study were as follows:

reproduction, development and or behavior."

to interfere with the endocrine system.

presumed effect on endocrine functions,

compounds, and

problem.

36 Endocrine Disruptors

The survey of crop protection compounds currently used in Uruguay was conducted based on the active ingredients (AI) imported in 2017 and considered only herbicides, insecticides and fungicides. A total of 175 AI (11,358,732 kg), corresponding to 48% herbicides, 29% insecticides and 23% fungicides, were analyzed [22]. In **Table 1**, top 10 compounds for each class ranked in function to the imported volumes are shown.



Elaborated with data from DGSA-MGAP 2017.

**Table 1.** List of active ingredients with the highest import volume for each main class.


The status regulatory according to international agencies as well as the potential to interfere with the endocrine system functioning were analyzed and the results are presented in **Table 2**. From the regulatory point of view, a total of 18 compounds present a status "Approved," 7 "Approved with restricted use" and 5 "Not approved." The last status regulatory includes three herbicides, one fungicide and one insecticide. Whereas in relation to potentially endocrine disrupting compounds, six fungicides, five herbicides and five insecticides were identified. The analysis of effects on endocrine system was complemented with information from several scientific articles [9, 10, 23–26] and according to the crop protection compound priorities are: acetochlor, chlorpyrifos methyl, mancozeb, metolachlor and tebuconazole (**Table 3**).

**Table 2.** List of active ingredients according to the categorization of the US EPA and the European Commission (EC).

Suspicion of endocrine disruption effects according to the PAN Pesticide Database (PANNA) and the Pesticide Properties

Database (PPDB) is noted. If the active ingredient is not found in any database, it is reported as n/d.

The substances are listed in alphabetical order. F-fungicide, H-herbicide, I-insecticide.

**Active ingredients US EPA** 

Glyphosate, ammonium

dimethylammonium salt (H)

Glyphosate, isopropylamine

Glyphosate, potassium salt

n/e: reported without evidence.

Lambda-cyhalothrin + thiamethoxam (I)

salt (H)

salt (H)

(H)

Glyphosate,

**status**

Chlorpyrifos ethyl (I) Restricted use Approved Suspected Suspected Chlorpyrifos-methyl (I) Restricted use Approved No Suspected Copper oxide (F) Not classified Approved No No Emamectin benzoate (I) Restricted use Approved No n/d Folpet (F) Not classified Approved No n/e

Mancozeb (F) Not classified Approved Suspected Suspected Mancozeb + metalaxyl (F) Not classified Approved/approved Suspected/no Suspected/no Metolachlor (H) Restricted use Not approved Suspected Suspected Paraffin oil (I) Not classified Approved No No Paraquat (H) Restricted use Not approved No No S-Metolachlor (H) Restricted use Approved Suspected Suspected Sodium metabisulfite (F) Not classified Not approved No n/d Sulfur (F) Not classified Approved No n/e Tebuconazole (F) Not classified Approved Suspected n/e Triflumuron (I) Not classified Approved No No

**EC status PANNA PPBD**

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Not classified Approved No n/d

Not classified Approved No n/d

Not classified Approved No No

Not classified Approved No No

Restricted use Approved/approved Suspected/no No/no


Suspicion of endocrine disruption effects according to the PAN Pesticide Database (PANNA) and the Pesticide Properties Database (PPDB) is noted. If the active ingredient is not found in any database, it is reported as n/d.

n/e: reported without evidence.

**Active ingredients Category Kg imported** Copper oxide Fungicide 68,264 Captan Fungicide 67,115 Folpet Fungicide 43,008 Sulfur Fungicide 36,032 Azoxystrobin + cyproconazole Fungicide 20,275 Tebuconazole Fungicide 18,812 Mancozeb + metalaxyl Fungicide 15,600

Chlorpyrifos Insecticide 181,795 Triflumuron Insecticide 53,478 Lambda-cyhalothrin + Thiamethoxam Insecticide 26,453 Paraffin oil Insecticide 24,226 Aluminum phosphide Insecticide 19,536 Acephate Insecticide 17,423 Chlorpyrifos-methyl Insecticide 15,360 Emamectin benzoate Insecticide 9,873 Chlorantraniliprole Insecticide 8,816 Bifenthrin + thiamethoxam Insecticide 8,650

Elaborated with data from DGSA-MGAP 2017.

**Active ingredients US EPA** 

2,4-D, dimethylamine salt

Bifenthrin + thiamethoxam

Azoxystrobin + cyproconazole (F)

38 Endocrine Disruptors

(H)

(I)

**Table 1.** List of active ingredients with the highest import volume for each main class.

2,4 DB Butyl ester (H) Not classified Approved Suspected Suspected

Captan (F) Not classified Approved Suspected Suspected Chlorantraniliprole (I) Not classified Approved No No Chlorothalonil (F) Restricted use Approved Suspected Suspected

Acephate (I) Not classified Not approved Suspected Yes Acetochlor (H) Restricted use Not approved Suspected Suspected Aluminum phosphide (I) Restricted use Approved No n/e

**status**

Total 622,650

Total 365,610

**EC status PANNA PPBD**

Not classified Approved Suspected n/d

Not classified Approved/approved No/no No/suspected

Not classified Approved/approved Suspected/no Yes/no

The substances are listed in alphabetical order. F-fungicide, H-herbicide, I-insecticide.

**Table 2.** List of active ingredients according to the categorization of the US EPA and the European Commission (EC).

The status regulatory according to international agencies as well as the potential to interfere with the endocrine system functioning were analyzed and the results are presented in **Table 2**.

From the regulatory point of view, a total of 18 compounds present a status "Approved," 7 "Approved with restricted use" and 5 "Not approved." The last status regulatory includes three herbicides, one fungicide and one insecticide. Whereas in relation to potentially endocrine disrupting compounds, six fungicides, five herbicides and five insecticides were identified. The analysis of effects on endocrine system was complemented with information from several scientific articles [9, 10, 23–26] and according to the crop protection compound priorities are: acetochlor, chlorpyrifos methyl, mancozeb, metolachlor and tebuconazole (**Table 3**).


**Active ingredients Crops Recommended dose Units** 2,4 Butyl ester (50%) (H) 1, 3–4 2–2.5 L/ha 2,4-D, dimethylamine salt (50%) (H) 1, 3–7, 11 0.6–3 L/ha Acephate (75%) (I) 2 0.5–1 kg/ha Acetochlor (H) 2, 6, 11 0.8–3.8 L/ha Azoxystrobin + cyproconazole (200/80) (F) 2–5 0.2–0.4 L/ha Bifenthrin + thiamethoxam (6%/13%) (I) 2 0.20 L/ha Captan (80%) (F) 9–10 0.8–1.5 kg/ha Chlorothalonil (72%) (F) 8–10 1.5–5 L/ha Chlorpyrifos (50%) (I) 1–4, 6–7, 9 0.3–2.5 L/ha Chlorpyrifos-methyl (I) 1, 3–4 0.35–1 L/ha Lambda-cyhalothrin + thiamethoxam (I) 2–7 0.05–0.25 L/ha Mancozeb (80%) (F) 8–10 1–5 L/ha Mancozeb + metalaxyl (F) 9 2–3 kg/ha Metolachlor (H) 2, 6–7 0.8–1.6 L/ha S-Metolachlor (90%) (H) 2, 6–7 0.8–1.6 L/ha Tebuconazole (25%) (F) 2–5 0.5–2 L/ha

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The substances are listed in alphabetical order. F-fungicide, H-herbicide, I-insecticide.

**dose**

**Active ingredients Recommended average** 

1-pastures, 2-soybean, 3-wheat, 4-barley, 5-rice, 6-corn, 7-sorghum, 8-citrus, 9-vegetable, 10-fruit, 11-sugarcane.

2,4 Butyl ester (50%) (H) 2,3 L/ha 2,905,000 **6,536,250** 2,4-D, dimethylamine salt (50%) (H) 1,8 L/ha 3,227,000 **5,808,600** Acephate (75%) (I) 0,8 kg/ha 1,140,000 855,000 Acetochlor (H) 2,3 L/ha 1,230,600 **2,830,380**

Captan (80%) (F) 1,2 kg/ha 26,387 30,345 Chlorothalonil (72%) (F) 3,3 L/ha 27,000 87,750 Chlorpyrifos (50%) (I) 1,4 L/ha 4,209,187 **5,892,862** Chlorpyrifos-methyl (I) 0,7 L/ha 2,905,000 **1,960,875**

**Table 4.** Crops and recommended doses of the compounds cataloged as suspect of generating endocrine disruption

**Units Total cultivated area (ha)**

0.3 L/ha 1,709,400 555,555

0,2 L/ha 1,140,000 228,000

0,2 L/ha 1,859,400 278,910

**Estimated AI added (L** 

**or kg)**

Source: SATA Guide.

Azoxystrobin + cyproconazole

Bifenthrin + thiamethoxam

Lambda-cyhalothrin + thiamethoxam (I)

effects.

(200/80) (F)

(6%/13%) (I)

Target effect metabolism is included as follows: 1-estrogen, 2-thyroid hormones, 3-aromatase, 4-pregnane receptor, 5-androgen. The substances are listed in alphabetical order.

**Table 3.** List of active ingredients suspected of generating endocrine disruption effects in at least one of the consulted databases (F-fungicide, H-herbicide, I-insecticide).
