TTS 2005

Chemical risks in agriculture

Benoit Nemery, MD, PhDOccupational, Environmental & Insurance Medicine

& Pneumology

K.U.Leuven, Belgiumben.nemery@med.kuleuven.ac.be

Respiratory diseases in agriculture

1. Infectious micro-organisms2. Organic dusts (+ microbial products)3. Inorganic dusts (silica, ...)4. Chemicals

Literature

Schenker M.B. (Chair) et al. American Thoracic Society: Respiratory Health Hazards in Agriculture.Am J Respir Crit Care Med, 1998, 158, S1-S76.

Chemical exposures in agriculture

1. Toxic gases2. Biocides and pesticides3. Fertilizers4. Feed additives

Toxic gases

• Combustion • Decomposition gases

• Manure• Silo gases

Pleura

Respiratory uptake of gasesWater solubility

+++ NH3, SO2 , HCl, R-CHO, ...

++ Cl2, CH3NCO, ...

+ O3, NO2, COCl2, ...

lipid soluble solvents, anaestheticsC6H6, CHCl3, F3C-CHBrCl, ...

→ irritation

rapid

slow

Carbon monoxide (CO)

all types of combustion when O2 supply < exhaust of gases

indoor burning of biomass, wood, charcoal, coal, kerosene, diesel, gas, …

fires, stoves, ovens, heaters, vehicles, engines, compressors, … + insufficient ventilation (indoor confined spaces)

! also NOx and particles

Decomposition gases

• Storage & putrefaction of organic matter• Liquid manure (pigs, cattle)• Solid manure (poultry)

production of H2S, CH4, NH3, CO2, CO accidental exposure (agitation + pumping

of liquid manure, repairs) chronic exposure in animal confinement

buildings

Liquid manure storage

• Hydrogen sulfide (H2S)– heavier than air– odour +++ (except > 150 ppm); irritant ++– neurotoxicity (→ coma)– respiratory toxicity (→ lung oedema)

“dung lung”

• + CH4, CO2, … → O2 depletion– asphyxia

Irritant gases

• Ammonia (NH3)– highly water soluble and potent irritant– affects mainly eyes, nose, upper airways– exposure levels often exceed recommended TLV

(25 ppm, 8 h), but no evidence that NH3 leads to excess symptoms or chronic airways disease

– possible accidental exposure to high amounts when use of anhydrous ammonia (fertilizer)

Acute inhalation of NH3

Leduc et al. Thorax, 1992, 47, 755-7

Man, 28 y• explosion of tank in refrigeration

plant (NH3)• acute:

• corneal & dermal lesions• tracheobronchitis• respiratory insufficency

• 12 y later:• severe airway obstruction• bronchiectases

Storage of forage/grain in silos

• Open silo - Trench or bunker• Sealed siloFermentation of silage

multiplying bacteria consume oxygen generation of CO2 and organic acids generation of nitrogen oxides

plant nitrates → NO → NO2, …

! Rapid process (hours)

Irritant gases

• Nitrogen dioxide (NO2)– Heavier than air– Invisible → yellowish → orange-brown– (Sweet smell) – Poorly water soluble– Poor warning properties (mild irritation)– Potent oxidant– May cause delayed lung injury (permeability

lung oedema)

Douglas W.M., Hepper N.G.G., Colby T.V.Silo-Filler’s Disease. Mayo Clin Proc 1989, 64, 291-304

Silo-filler’s disease

Upon entering recently filled silo– asphyxia– airway irritation– after 4-24 h: non-cardiogenic lung oedema

- chemical pneumonitis (“silo filler’s disease”)

– after 3-4 weeks: bronchiolitis obliterans (+ malaise, fever, … DD. Miliary TB)

Case

• Man, 34 y, smoker• Worker in small company making printed circuits• Friday: cleaning galvanisation baths with

concentrated HNO3 (instead of diluted solution)

• During work: mild irritation • At home: progressive cough and dyspnoea

“I could not lay down”• During night: hospitalization in respiratory

distress

NO2-induced pneumonitis

Case

Chemical exposures in agriculture

1. Toxic gases2. Biocides and pesticides3. Fertilizers4. Feed additives

Biocides and pesticides

• Disinfectants• Fumigants• Pesticides

Disinfectants

• Bleach• Quaternary ammonium compounds• Chloramine T• Aldehydes (formaldehyde, glutaraldehyde,

glyoxal)

airway irritation allergic sensitization

Bleach• Bleach (HClO) or “Bleach tablets” + water

! Mixing incompatibilities Bleach + acids → Cl2, HCl Bleach + ammonia → chloramines

NH2Cl, NHCl2, NCl3

– tracheo-bronchial irritation – chemical pneumonia– irritant-induced asthma

Repeated exposure to cleaning agents

• Higher risk of asthma in female cleaners• Zock et al. SJWEH 2001, 27, 76-81: P.R. 1.7• Karjalainen et al. ERJ 2002, 19, 90-5: R.R. 1.50• Medina-Ramon et al. Thorax 2003, 58, 950-4: O.R. 1.46

exposure to irritants and sprays ? “hidden sensitizers”?

• Quaternary ammonium compounds (disinfectants / preservatives)• Isothiazolinones (preservatives)• Ethanol amines (wax-removal agents)• d-limonene, terpenes (perfumes)

Quaternary Ammonium Compounds

• In pig farmers with frequent exposure to QAC sprayed under high pressure, higher risk of• asthma-like symptoms• low lung function• atopic sensitization• bronchial hyperreactivity

Preller et al. OEM 1995, 52, 654-660Preller et al. ERJ 1996, 9, 1407-1413Vogelzang et al. IAOEH 1997, 70, 327-333

Fumigation and pest treatmentTreatment of soil, barn, greenhouse, … with highly

toxic volatile compounds • methyl bromide (CH3Br)• hydrogen cyanide (HCN) & other cyanides• carbon disulfide (CS2)• ethylene oxide• acrolein• chloropicrin• zinc phosphide (Zn3P2) → H3P

asphyxia respiratory irritation neurotoxicity

SulfurizationKoksal N. et al. Apricot sulfurization: an occupation that induces an asthma-like syndrome in agricultural environments. Am J Ind Med 2003, 43, 447-453• Malatya (Turkey)• 15 apricot farms, 69 workers (31 y)• 20-25 days in summer• Melting of S → SO2 in sulfurization chambers (8-10 h)• Repeated exposures for ~1 h to 100-700 ppm SO2 Acute eye, nose and airway irritation (including

wheezing in 6) Acute decreases in FEV1 (-0.39 L, >20% in 10) and

FVC (-0.16 L)

Pesticides• Substances intended for preventing, destroying,

repelling, mitigating pests (“toxic by design”) • Target specificity:

• Insecticides• Fungicides• Herbicides• Rodenticides• Acaricides• Nematocides

heterogeneous chemicals

Agricultural pesticidesOccupational and para-occupational exposures

• Mixing and loading• Application (tractor, airplane, backpack)• Field workers (harvesting, handling)• Bystanders (! children)• Residents

• Misuse and accidental exposure• Spills (mass-poisoning)• Accidental ingestion • Suicide• Homicide

Agricultural pesticides

• Most pesticides have low volatility• Inhalation exposure is generally low

• Large size droplets! Indoor spraying (greenhouses)

• Most occupational exposure is by dermal route

! Protective clothing

In general: few serious and specific respiratory effects reported, even after spraying

Agricultural pesticidesHoppin J.A. et al. Chemical predictors of wheeze among farmer pesticide applicators in the Agricultural Health Study. Am J Respir Crit Care Med 2002, 165, 683-689

• Cohort of >20,000 pesticide applicators in Iowa & North Carolina

• Questionnaire: 19% wheeze in past year adjusted OR for wheeze for exposure to

paraquat, three organophosphates (parathion OR=1.5), one thiocarbamate, atrazine

Significance?

Agricultural pesticides

• In general: few serious and specific respiratory effects reported, even after spraying

! Acute intoxication (accident or suicide) with organophosphates or paraquat

Eddleston M. et al. Pesticide poisoning in the developing world - a minimum pesticides list. Lancet 2002, 360:1163-7.

Sri Lanka2 districts

Chandigahr, India

Samoa

Amman, Jordania

Ban of parathionControlled availability

Organophosphates

Parathion (E605, …), ... • Excellent penetration through skin & mucosae inhibition of acetylcholinesterase

• Diarrhoea, sweating, salivation, lachrymation, miosis, bronchospasm, bronchorrhoea (pulmonary oedema)

• Muscle fibrillation → weakness → paralysis • CNS (anxiety, vertigo, tremor) → convulsions →

coma• Delayed neurological effects possible

Paraquat

N-CH3CH3-N++

1,1’-dimethyl-4,4’-bipyridylium chloride

Contact herbicide

• Water-soluble concentrates 100-200 g/L(Gramoxone, Dextrone)

• Granular formulations 25-80 g/kg (Weedol, ...)

Paraquat• Local toxicity: skin, nails, eyes, nose• Systemic toxicity after

• ingestion (accidental, suicidal)• dermal absorption

• poor penetration through intact skin• absorption and (fatal) toxicity possible if

– Prolonged skin contact (leaking spray equipment)– Skin damage– Contact with concentrated solution

• no substantial uptake via inhalation (droplet size > 200 µm)

Paraquat

• Systemic toxicity to various organs, especially lungs• Accumulation in lung tissue: active uptake

in pneumocytes (via polyamine uptake system)

• Oxidative stress

NADPH NADP+

O2O2

_.

NADPHreductase

PQ++

PQ+.

H2O2

OH. Fe

H2O

SOD

CAT

LipidsEnzymes

DNA

GSH

Lipid peroxidation

GSSG

Vit.E, C

NADP+ .

Paraquat

Water-soluble concentrate: 100-200 g/L• < 20 mg PQ/kg:

Mild g-i symptoms• 20-40 mg PQ/kg:

Malaise, g-i symptoms Renal failure Pulmonary fibrosis → death in 2-3 wks

• > 40 mg PQ/kg (15 ml of 20% solution): Multiorgan failure → death in <1 week

Paraquat

Proudfoot et al. Lancet, 1979, 2, 330-332

Paraquat• Long-term effects of chronic paraquat exposure?• Schenker M.B. et al. Pulmonary function and exercise-

associated changes with chronic low-level paraquat exposure. Am J Respir Crit Care Med, 2004, 170, 773-779• Costa Rica• 338 plantation workers (banana, coffee, palm oil), 37 y• 66% paraquat handlers; index of cumulative exposure slight increase in prevalence of chronic cough no significant effect on spirometry and DLco slight effect on gas exchange during maximal exercise (200

subjects < 40y) : SpO2>5% (pulse oximetry) associated with higher PQ index

Subtle long-term effect on lung parenchyma?

Thank you

Teşekkür Ederim

ben.nemery@med.kuleuven.ac.be