Development of pesticides in India-A case study of Paddy [Rice] insecticides

     

Rice crop in Nov 2022

Pesticides are important component of crop protection. They have played an important role in reducing crop losses by controlling pests and diseases. Over the years, pesticide consumption has been on increase. About 60,000 tons of pesticides are consumed in India. In view of increasing awareness of environment and human health, pesticides are under constant scrutiny for their efficacy and safety. In India, 339 pesticides are registered for use as insecticides, fungicides, rodenticides, weedicides and others under the Insecticide Act 1968. Assessing the development of pesticides over the past seven decades has become a priority. Paddy [Rice] insecticides are used herein to track this developmental path. Forty-one insecticides and their more than seventy formulations, besides 46 combinations of insecticides with other pesticides are registered for control of pests of paddy in the country. These insecticides belong to as many as 13 major groups based upon mode of action at target sites [Table 1a]. It is reported that more than 20% insecticide consumption in the country is for controlling pest insects in paddy. And hence, they represent the microcosm of pesticide usage in the country. I have therefore restricted my study to the paddy-centric insecticides to answer the following questions.

1.      Are we using more effective pesticides?

2.      Are we using safer insecticides? 

To answer the first question, I have tabulated registered insecticides with their application rates/doses group-wise based upon their mode of action [Table 1]. Most insecticides based upon inhibition of acetylcholinesterase enzyme belong to organophosphate and carbamate derivatives developed in early 1950s through 1980s. Synthetic pyrethroids which are modulators of sodium channels in the axonic nerve transmission were developed in 1980s through 1990s. It is in mid-1980s that non-steroidal ecdysone agonists based on benzoyl hydrazide were developed as insecticides through 1990s. Similarly, a prominent group of neonicotinoids acting as nicotinic acetylcholine [nACh] receptor competitive modulator was developed in 1990s through 2000s. Some are of recent origin. Perusal shows that while carbamate and organophosphate groups developed about five decades ago are effective at doses ranging from 500 to more than 1000 gm ai/ha, newly developed insecticides are effective at much lower field doses. Over the past seven decades, doses have declined more than 10-fold, thereby leading to development of more effective pesticides.

In view of development of insecticides acting on specific target sites, insecticides were found to be highly selective. For e.g. neonicotinoids like acetamiprid, imidacloprid are highly effective against mostly sucking pests like brown planthopper, white-backed plant hopper. Similarly, diamide group of insecticides like chlorantraniliprole, cyclaniliprole are highly effective against mostly lepidopteran pest insects like stem borer, leaf folders. On the contrary, organophosphates and carbamates have a broad spectrum of activity against defoliators as well as sucking pests.

Most of recently developed insecticides are selective and offer an advantage of safety towards environment, especially reducing indiscriminate killing of other arthropod fauna which include pollinators, natural enemies of pest insects and other beneficial and useful insects. As these insecticides are applied in small quantities, their dissipation on the crop is likely to be fast.

Another aspect of development of insecticides is that of combination products which increase the spectrum of insecticidal action as well as aim at controlling evolution of insecticide resistance in the target species. Rice is the best example where many combination products are registered for use. The combination products help in reducing the cost of application. However, combination products are difficult to be judged on safety aspects, since dissipation and metabolism may differ a lot and so also their combined effect could complicate estimates of safety in terms of MRL and waiting periods [Table 1b]. Furthermore, they may prove to be more harmful to the environment as in some cases, one of the components is not registered on its own for control of paddy insect pests. 

Are we using safer pesticides? Yes, we are to some extent. With reduced doses, we are in position to achieve effective control of pests and diseases. and reduce the environmental load with these new pesticides.

As far safety to human, presence of pesticide below its prescribed maximum residue limit [MRL] in the harvest is considered a safety criterion. This is based upon the no-observed-adverse effect in test animal and acceptable daily intake with a safety margin of 100 extended to humans. MRL has an international consensus and hence, is used while exporting or importing commodities. To ensure that produce has less than MRL of pesticides, waiting period or post-harvest interval is prescribed for the farmers by the regulatory bodies of each country. Waiting period is indirectly a criterion for safety. Lower the waiting period, more is the safety as pesticide applied gets dissipated quickly below MRL in the harvest. Table 1a also shows waiting periods for different groups of rice insecticides. Perusal of data does not show any definite trend of waiting period for different groups of insecticides. Since some of these insecticides are used at the transplanting stage, it seems illogical to estimate waiting period or post-harvest interval when crop is harvested only on maturity, many weeks or some months later.

Contrary to the expected increasing MRL trend, it seems that MRL is highly insecticide-specific. Of rice insecticides, very few insecticides have MRL above 1 mg/kg. Pyrethroids, neonicotinoids and organophosphates seem to have high MRL which means safety to human. Most of new insecticides have MRL ranging from 0.01-0.05 mg/kg again with no definite trend. Acute oral mammalian toxicity of most insecticides didn’t exceed 500 mg/kg bw for rat. And so was the case of acceptable daily intake not more than 0.1 mg/kg bw. This being a case, fixing of lower MRL by many developed countries is suggestive of cautious approach towards human health and possibly trade-related politics. Considering toxicity class as defined by Govt of India [prior to 2023], most of neonicotinoids acting on acetylcholine receptors, chitin synthesis inhibitors, ecdysoid agonists and those acting on Ryanodine receptor belong to Class III and IV, moderately or slightly toxic.

Unfortunately, environmental impact remains inadequately addressed. And glaring example is toxicity of these insecticides to bees. Many insecticides are reportedly harmful to bees with contact lethal dose being less than 1 ug/bee. And the environmental and human safety is far more important for combination products which are being increasingly developed. This highlights need for judicious use of insecticides in the overall context of integrated pest management. 

                  

Table 1a: Paddy [Rice] insecticides	Dose	Wait period	MRL	ADI	Tox class
	gm ai/ha	days	mg/kg	mg/kg/day	for AI, pre-2023
AChE inhibitors
Organophosphate
Acephate [1972]	750	15	1	0.03	III
Chlorpyrifos [1965]	1000	30	NA	0.01	II
Malathion [1952]	575	NA	1	0.3	III
Monocrotophos [1950s]	500	NA	0.03	0.0006	I
Oxydemeton-methyl [1950s]	250	NA	0.02	0.0003	I
Phenthoate [1950s]	500	NA	0.05	0.003	II
Quinalphos [1969]	500	40	0.01	0.01	II
Phosmet [1961]	60	45		0.01	II
	517+/-286	32.5+/-13	0.35+/-0.5
Carbamates
Benfuracarb [1983]	1000	20	0.05	0.01	II
Carbofuran [1979]	1000	14	0.2	0.002	I
Fenobucarb [1968]	750	30	0.01	0.005	III
Carbosulfan [1979]	250	14	NA	0.01	II
	750+/-354	26+/-7.5
Sodium channel modulators
Bifenthrin [1984]	50	21	0.05	0.02	II
Deltamethrin [1984]	20	13	2	0.01	II
Ethofenprox/Etofenprox [1987]	75	15	0.01	0.03	IV
Fenpropathrin [1981]	100	58	0.03	0.03	II
Lambda-cyhalothrin [1984]	50	15	1	0.005	II
	59+/-30	24+/-19	0.62+/-0.9
Voltage-gated Na channel blocker
Indoxacarb [1992]	60	37	NA	0.01	II
nAChR competitive modulators
Acetamiprid [1995]	20	7	0.01	0.07	II
Clothianidin [2002]	12	12	0.5	0.1	IV
Dinotefuran [1998]	61.2	32	8	0.2	III
Imidacloprid [1991]	60	39	0.05	0.06	II
Thiamethoxam [1998]	113	60	0.02	0.08	III
Thiacloprid [2000]	144	52	0.02	0.012	II
Flupyrimin[>2003]	150	77	NA	0.011	IV
Triflumezopyrimin[>2003]	25	21	NA	0.2	IV
Sulfoxaflor[>2003]	90	14	0.01	0.04	III
	75+/-52	34+/-24	1.23+/-3.0
nACh Receptor blocker
Cartap hydrochloride [1967]	1000	NA	0.5	0.01	II
Thiocyclam [2002]	500	30	NA	0.01	IV
nAChR allosteric modulator
Spinetoram [2003]	45	20	NA	0.025	IV
GABA-chloride channel blocker
Fipronil [1993]	75	65	0.01	0.0002	II
GABA-chloride channel allosteric modulator
Isocycloseram [>2003]	60	29	NA	0.02	IV
Glu-chloride channel allosteric modulator
Emamectin benzoate [1997]	8	48	0.05	0.0025	II
Chitin synthesis inhibitor type I
Buprofezin [1981]	200	20	0.05	0.01	III
Benzpyrimoxan [>2003]	100	31	NA	0.01	III
Chordotonal organ TRPV channel modulator
Pymetrozine [1992]	150	19	0.01	0.03	IV
Ryanodine Rec-diamides
Chlorantraniliprole [>2003]	75	NA	0.4	1.56	IV
Cyclaniliprole [>2003]	40	40	NA	0.04	III
Flubendamide [>2003]	100	40	0.1	0.02	IV
Tetraniliprole [>2003]	60	43	NA	2	III
Ecdysone Receptor agonist
Chromofenozide [1999]	100	32	0.03	0.27	IV
Nicotinamidase inhibitor
Flonicamid [2000]	75	36	0.05	0.025	III

Table 1b: Combination products in India	Dose	Wait period	MRL
Name	gm ai/ha	days	mg/kg
Acephate 50+Fipronil 5 WDG	500 + 50	27	NA
Acephate 50+Imidacloprid 1.8 SP	518	NA	NA
Acetamiprid 0.40+Chlorpyriphos 20 EC	10+500	10	NA
Azoxystrobin 10+Fipronil 5 SC	62.5+ 125	53
Benzpyrimoxan 10+Pymetrozine 20 WG	70+140	36	NA
Benzpyrimoxan 10+Thiamethoxam 3.3 SC	75 + 25	30	NA
Benzpyrimoxan 10+Fipronil 10 SC	60-75 + 40-50	22	NA
Bifenthrin 03+Chlorpyriphos 30 EC	30 + 300	21
Bifenthrin 10+Thiamethoxam 5 SE	50 + 25	39	NA
Buprofezin 9+Acephate 24 WP	187.5 + 437.5	20	NA
Buprofezin 20+Acephate 50 WP	200 + 500	20	NA
Buprofezin 20+Acetamiprid 2 WP	176	15	NA
Buprofezin 22+Fipronil 3 SC	110 + 15	32	NA
Buprofezin 23.10 +Fipronil 3.85 SC	173.25 + 28.88	30	NA
Cartap 50+Buprofezin 10 WP	480	20	NA
Cartap 7.5+Emamectin benzoate 0.25 GR	18.75 + 562.5	35	NA
Cartap 4+Fipronil 0.5 CG	675 – 900	27	NA
Chlorantraniliprole 9.30+Lambda-cyhalothrin 4.60 ZC	28 – 35	53	NA
Chlorantraniliprole 0.50+Thiamethoxam 01 GR	30.0 + 60.0	60	NA
Chlorpyrifos 50+Cypermethrin 5 EC	312 + 32	15	NA
Cyantraniliprole 16.9+Lufenuron 16.9 SC	20 (10+10)	39	NA
Cypermethrin 10+Indoxacarb 10 SC	37.5+37.5	37	NA
Deltamethrin 0.72+Buprofezin 5.65 EC	0.94 + 75.00	30	NA
Dinotefuran 4+Acephate 50 SG	35 + 400	28	NA
Dinotefuran 5+Ethion 50 EC	50 + 500	33	NA
Dinotefuran 11+Pymetrozine 36 WG	164.5	36	NA
Dinotefuran 15 +Pymetrozine 45 WG	200	24	NA
Ethiprole 40+Imidacloprid 40 WG	50 + 50	15	NA
Ethiprole 10.7+Pymetrozine 40 WG	45.48+170	27	NA
Fenobucarb 20+Buprofezin 05 SE	400 + 100	30	NA
Fenobucarb 22.5+Buprofezin 11.25+Acephate 2.5 ME	393.75 +	25	NA
Flubendiamide 3.50+Hexaconazole 5 WG	35 + 50	20	NA
Flubendiamide 7.5+Kresoxim Methyl 37.5 SC	50 + 250	30	NA
Flubendiamide 19.92+Thiacloprid 19.92 SC	60 + 60	33	NA
Fipronil 40+Imidacloprid 40 WG	50+50	7	NA
Fipronil 4+Thiamethoxam 4 SC	44 + 44	45	NA
Fipronil 15+Flonicamid 15 WDG	60 + 60	30	NA
Imidacloprid 6 +Lambda-cyhalothrin 4 SL	18 + 12	10	NA
Indoxacarb 10+Thiamethoxam 10 WG	50 + 50	14	NA
Isoprothiolane 28+Fipronil 5 EC	280+50	58	NA
Novaluron 5.25+Emamectin Benzoate 0.9 SC	78.75 + 13.50	32	NA
Novaluron 5.25+Indoxacarb 4.50 SC	22.97 + 19.69	40	NA
Phenthoate 45+Cypermethrin 6 EC	450+60	end-harvest	NA
Pymetrozine 25+Thiameth. 17.5+Hexaconaz. 12.5WG	100 + 70 + 50	19	NA
Pyraclostrobin 10+Fipronil 5 SC	50+100	53	NA
Tetraniliprole 10.08+Thiacloprid 30.25  SC	37.5 + 112.5	43	NA
Thiocyclam Hydrogen Oxalate 3.0+Clothianidin 1.2GR	375 + 150	56	NA

 Based upon the CIBRC MUP accessed on 10^th May and FSSAI document version V of 19^th Aug 2020. Insecticide groups are as per IRAC’s mode of action. ADI, toxicity classes [as per CIBRC classification prior to 2023] and Years after insecticides relate to years of their patents or commercialisation first time in the world as per Pesticide Manual 13th ed 2003 and other sources. Mean +/_ are standard deviations are given for some groups.