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)