Pesticides and health in India

Epidemiologist, Senior Scientific OfficerCentre for Chronic Conditions & Injuries

Public Health Foundation of India

Preet K. Dhillon, MPH, PhD

Pesticides2

Definition:

Pesticides are used for preventing, destroying, repelling or mitigating a pest or in use as a plant regulator, defoliant or dessicant.

They include herbicides, insecticides and fungicides.

• Large, heterogeneous group• Mutagenic, carcinogenic, immunotoxic properties

Clapp RW, Howe GK, Jacobs MM. Environmental and Occupational Causes of Cancer; A Review of Recent Scientific Literature. Lowell: UMass, Lowell 2005

Evidence on pesticides on health in India3

◊ ‘pesticides’ AND ‘India’ (n=6007)

Evidence on pesticides on health in India4

◊ ‘pesticides’ AND ‘India’ (n=6007)

◊ ‘pesticides’ AND ‘India’ AND cancer (n=142)

◊ ‘pesticides’ AND ‘India’ AND cancer AND humans (n=75)

◊ ‘pesticides’ AND ‘India’ AND diabetes (n=10)

◊ ‘pesticides’ AND ‘India’ AND hypertension (n=7)

◊ ‘pesticides’ AND ‘India’ AND fertility (n=10)

◊ ‘pesticides’ AND ‘India’ AND reproductive (n=78)

Reproductive outcomes & pesticides 5

◊ organochlorine, placental tissue/maternal blood, pre-term

◊ small for gestational age, CYP17A1

◊ DDT, lindane and semen quality

◊ still births, neonatal deaths, congenital defects

◊ inflammatory pathway proteins & pre-term birth

◊ inflammatory genes – COX2, MnSOD, CAT – pre-term birth

International evidence6

◊ Pesticides have been linked to cancers of the:

brain/CNS stomach breast lungcolon testesovaries Hodgkin’s diseasepancreas Non-Hodgkin’s diseasekidneys multiple myeloma leukemia soft tissue sarcoma

◊Mixed evidence of causal links depending on the site

Classification of carcinogens7

• International Agency for Research on Cancer (IARC), WHO

• Environmental Protection Agency (EPA), USA

• European Union (EU)

• Integrated Risk Information System, EPA

Review the evidence: India8

◊ Few, well-conducted epidemiological studies

◊ Lung, brain, prostate, breast, gall bladder, hematological malignancies

◊ 1 death certificate review, 1 occupational study, 3 comparing pesticide levels in blood of cases & controls

◊ No reproducibility of results

◊ No dose-response relationships

Slide courtesy of V. Cogliano (IARC)

Policies/Acts on the Environment10

Environment Protection Act, 1986

National Forest Policy, 1988

National Conservation Strategy and Policy Statement on

Environment and Development, 1992

Policy Statement on Abatement of Pollution, 1992

Vision Statement on Environment & Human Health 2003

National Environment Policy, 2006

Environmental protection/performance11

1. Environmental Performance Index (EPI) ranks countries ona. Protection of human health from environmental harmb. Protection of ecosystems

2. Top 5 countries (2014): Switzerland (87.7), Luxembourg, Australia, Singapore (81.8)

3. India (31.2) ranks 155 out 178

4. % GDP on the environment:Japan – 1.0%, US – 0.4%, Netherlands – 0.3%, India - .012%

Environmental protection in India12

Rao KS, Dong J Methods Mol Biol 2013

Ministry of Environment and Forestry-plans, promotes, coordinates, oversees environment and

forestry programmes

a. Conservation & survey of flora, fauna, forests, wildlife

b. Prevention & control of pollution, afforestation, regeneration of degraded areas

c. Protection of environment

Ways Forward13

1. Improve quantity, quality & representatives of

evidence on pesticides and health, cover range of

health outcomes – MCH, NCD’s, & polluted areas

2. Improve national monitoring - Health experts on

advisory boards (SDGs)

3. Engage multiple sectors – Agriculture, Labor, Urban

and Rural Development, Water resources

4. Awareness, advocacy, social initiatives/campaigns

5. To inform occupational health guidelines in the Indian

context

Guidelines14

Rao KS, Dong J Methods Mol Biol 2013

1. ICH testing guidelines for medicinal products not applicable in India & China

2. OECD & USEPA recommendations; India & China differ on reproductive toxicity testing of chemicals and pesticides(China’s new guidelines expected to resemble)

3. Good Laboratory Practice (GLP) inspection, accreditation, monitoring activities (n=23 in India)

4. AALAC credited (n=6 in India)

International evidence15

Home pesticides & Childhood Leukemia : CL Int’l Consortium

• 12 studies of 7,956 ALL cases & 14,494 ALL controls• 9 studies of 740 AML cases & 10,847 AML controls• Exposure types:

- home use & professional pest control• Exposure windows:

-Before conception (5 studies)- During pregnancy (9 studies)- After birth (6 studies)

Bailey HD et al. IJC 2015

Indian evidence16

Endosulfan & hematological malignancies (Rau ATK et al.)

• Hospital-based case-control study• Aged 1-15 yrs at diagnosis • Participating hospitals in Dakshina, Karnataka• 09/2006-03/2008• N=26 cases (23=ALL; 3=AML); N= 26 controls• GCMS measurement of endosulfan residues• Paternal pesticide spraying linked to risk• OR=7.5 (95% CI: 1.34, 176.34) associated with endosulfan levels in marrow (6% vs. 1%)

Rau ATK et al. Indian Pediatrics 2012

Indian evidence17

Occupation & pesticides and brain cancer (Bhat AR et al.)

• Death certificate review• N=432 cases, N=457 controls • Admitted for tx. of primary malig tumors, 2005-08• N=105 children, 7.9%• N=31 children w/parents & school/play orchards• N=23 pregnant & 11 lactating women• Most commonly observed pesticides - endosulfan, chloropyriphos, mancozeb, captan

Bhat AR et al. Ind J Med Ped Oncology 2010

Indian evidence18

Maternal exposures and leukemias (Kumar et al.)

• Case-control study of maternal exposures• N=132 cases & age-/sex-/residence-matched controls• Diagnosed between 2008-12, Rohtak• Interviewer-administered QQ’s• Maternal occupation exposed to agriculture• Pesticide exposure significantly associated with risk• Other factors not associated (eg, fetal loss, radiography, drug intake during pregnancy)

Kumar A et al. Asian Pacific J of Cancer Prevention 2015

Insecticides 19

◊ Insecticides (eg, termite barrier treatments, household surface insecticides)

◊ EPA labelled as ‘possible or likely human carcinogens’:

* bifenthrin* fipronil* permethrin * Tetramethrin* chlorpyrifos* dichlorvos * terbufos

IARC Group 1: Carcinogenic

to humans

Group 2A: Probably carcinogenic to humans

Group 2B: Possibly carcinogenic to humans

Group 3: Not classifiable as to its carcinogenicity to humans

Group 4: Probably not carcinogenic to humans

Group 1: Sufficient evidence in humans or sufficient evidence in animals and strong mechanistic data in humans

Group 2A: Limited evidence in humans and sufficient evidence in animals

Group 2B: Limited evidence in humans and less than sufficient evidence in animals

Group 3: Inadequate in humans and inadequate or limited in animals

Group 4: Lack of carcinogenicity in humans and in animals

EPA Carcinogenic to humans

Likely to be carcinogenic to humans

Suggestive evidence of carcinogenicity, but not sufficient to assess human

Carcinogenic potential data inadequate for assessment of human carcinogenic potential

Not likely to be carcinogenic to humans

Convincing epidemiologic evidence demonstrating causality between human exposure and cancer.

When the available tumor effects and other key data are adequate to demonstrate carcinogenic potential to humans

The evidence from human or animal data is suggestive of carcinogenicity, which raises a concern for carcinogenic effects but is judged not sufficient for a conclusion as to human carcinogenic potential.

When available data are judged inadequate to perform an assessment. This includes a case when there is a lack of pertinent or useful data or when existing evidence is conflicting

Available data are considered robust for deciding there is no basis for human hazard concern.

Chemical Carcinogens22

• Large numbers of chemicals were tested for carcinogenic potential in the 1970-1990s:

- Maximum Tolerated Doses (MTD) were used- 60% of rodent carcinogens were genotoxic- Some are single site, single species carcinogens- Others were multisite, multispecies carcinogens- Dose-response varies from <1/2 to <1/1000 MTD

• Most regulations use straight mathematical extrapolation of high dose rodent data to predict risks

Environment- IARC’s Group 1

Acid mists, strong inorganic

Aluminum production

4-Aminobiphenyl

Aristolochic acid (and plants containing it)

Arsenic

AsbestosAuramine production

Azathioprine

Benzene

Benzidine and dyes metabolized to benzidine

Benzo[a]pyrene

Beryllium and beryllium compounds

Bis(chloromethyl)ether and chloromethyl methyl ether (technical-grade)

Busulfan

1,3-Butadiene

Cadmium and cadmium compounds

Chlorambucil

Chlornaphazine

Chromium (VI) compounds

Indoor emissions from household combustionCoke production

Cyclophosphamide

Cyclosporine

Engine exhaust, dieselErionite

Ethylene oxide

Etoposide

Etoposide in combination with cisplatin and bleomycin

Fission products, including strontium-90

Haematite mining (underground)

Ionizing radiation (all types)

Iron and steel founding (workplace exposure)

Isopropyl alcohol manufacture using strong acids

Leather dust

Magenta production

Melphalan

Methoxsalen (8-methoxypsoralen) plus ultraviolet A radiation

4,4'-Methylenebis(chloroaniline) (MOCA)

Mineral oils, untreated or mildly treated

2-Naphthylamine

Neutron radiation

Nickel compounds

N'-Nitrosonornicotine (NNN) , (NNK)

Outdoor air pollution3,4,5,3',4'-Pentachlorobiphenyl (PCB-126)

2,3,4,7,8-Pentachlorodibenzofuran

Phenacetin (and mixtures containing it)

Phosphorus-32, as phosphate

Plutonium

Radioiodines

Radium, radon

Rubber manufacturing industry

Schistosoma haematobium (flatworm; infection with)

Semustine (methyl-CCNU)

Shale oils

Silica dust, crystalline, in the form of quartz or cristobalite

Solar radiation

Soot (as found in workplace exposure of chimney sweeps)

Sulfur mustard

Thiotepa

Thorium-232 and its decay products

ortho-Toluidine

Treosulfan

Ultraviolet (UV) radiation, including UVA, UVB, and UVC rays

Vinyl chloride

Wood dust

X- and Gamma-radiation

International Agency for Research on Cancer, WHO, www.iarc.fr; IARC Carcinogen Monographs:

http://monographs.iarc.fr

IARC CLASSIFICATION

Group 1 Carcinogenic to humans 113

Group 2A Probably carcinogenic to

humans

66

Group 2B Possibly carcinogenic to humans 285

Group 3 Not classifiable as to its

carcinogenicity to humans

505

Group 4 Probably not carcinogenic to

humans

1

Pesticides in Punjab25

◊ 17-fold increase in pesticide consumption b/w 1955-2005

◊ Punjab – 1.7% of land mass, 17% of pesticide use in India, highest recorded use of agriculturally advanced states

◊ 90% of pesticides used for cotton, rice, vegetables

◊ Low awareness on health effects & little adherence to safety precautions

Reproductive toxicity testing26

Rao KS, Dong J Methods Mol Biol 2013

1. ICH testing guidelines for medicinal products not applicable in India & China

2. OECD & USEPA recommendations; India & China differ on reproductive toxicity testing of chemicals and pesticides(China’s new guidelines expected to resemble)

3. Good Laboratory Practice (GLP) inspection, accreditation, monitoring activities (n=23 in India)

4. AALAC credited (n=6 in India)