Occupational Medicine Prof. Francesco S. Violante Chemical agents and pesticides.

Occupational MedicineProf. Francesco S. Violante

Chemical agents and pesticides

Chemical AgentsSolvents Organic compounds, normally liquid at ambient temperature, that

can dissolve several organic substances, which are not water-soluble, without modifying their properties

The solvents used in industry belong to different classes of organic substances:

Aliphatic Hydrocarbons saturated – alkanes or paraffins (C-C and CnH2n+2) unsaturated – alkenes (C=C and CnH2n) and alkynes (C≡C CnH2n-2)

Alicyclic Hydrocarbons (Chains of C atoms bond together to form rings) cycloalkanes (CnH2n) cycloalkenes (CnH2n-2) cycloalkynes ( CnH2n-4)

Aromatic Hydrocarbons or arenes (having one or more benzene rings) monocyclic or mononuclear polycyclic or polynuclear

halogenated derivatives of aliphatic and aromatic hydrocarbons Alcohols and glycols Aldehydes and ketones Esters and ethers of alcohols and glycols Amides

Federchimica 2005: solvents widely used in Italy

chetoni; 180000; 25%

aromatici; 150000; 20%

alifatici ; 130000; 17%

esteri; 120000; 16%

alcoli; 100000; 13%

clorurati ; 70000; 9%

chetoni aromatici alifatici

esteri alcoli clorurati

Consumption in Italy Significant examples

ketones

180.000 T/y

ACETONE and CYCLOHEXANONE

aromatic solvents 150.000 T/y

TOLUENE and XYLENE

aliphatic solvents 130.000 T/y

CYCLOHEXANE and HEPTANE

esters

120.000 T/y

BUTYLACETATE and ETHYLACETATE

alcohols

100.000 T/y

BUTANOL and ETHANOL

chlorinated solvents 70.000 T/y

METHYLENE CHLORIDE and DICHLOROETHANE

Chemical Agents

Aromatic Hydrocarbons: industrial usesPERCENTAGE USES

50% Products: Varnishes Diluents Inks Perfumes

20% Rubber industry

20% Pesticide industry

9% Metal degreasing and dry-cleaning

1% Explosive industry

Chemical Agents

BENZENE

Clear, colourless and highly flammable liquid, with typical pungent and aromatic odour;

Extremely volatile at ambient temperature (vapour tension=100 mmHg at 26.1C);

Scarcely soluble in water and highly soluble in organic solvents; it is a powerful fat solvent

Chemical Agents

BENZENE

Occupational Exposure

Workers engaged in the oil processing industry

Distillation and distribution of petrols (pump operators)

Chemical Agents

BENZENE

Exposure

Use of benzene and its analogues in work

processes: Decree 10th December 1996, no. 707

“Viene prescritto il divieto di uso di benzene e di sostanze e

preparati contenenti benzene in concentrazione pari o

superiore allo 0,1% della massa: da tale divieto sono esclusi i

carburanti di cui al D.M. 214/88, le sostanze e i preparati

adoperati in processi che non permettono l’emissione di

benzene oltre le quantità prescritte, i residui previsti dalla

normativa sui rifiuti”

Chemical Agents

BENZENE

Extra-occupational Exposure

Natural sources (e.g. Volcanic activities) Tobacco smoke (active and passive) Indoor pollution due to usage of domestic

products Motor vehicles emissions

Chemical Agents

BENZENE


Air quality objectives: Decree 2nd April 2002, no.60. The Ministry of Environment andTerritory Protection in agreement with theministry of Health:

“Stabilisce per gli inquinanti biossido di zolfo, biossido di azoto eossidi di azoto, materiale particolato, piombo, benzene e monossido di Carbonio: valori limite e soglie di allarme\ margine di tolleranza e modalità di riduzione\ termine entro cui si deve raggiungere il limite stabilito\ criteri per la raccolta dati, tecniche di misurazione….\ soglie divalutazione\ modalità di informazione al pubblico\ formato per la comunicazione dei dati”

Chemical Agents

Annex V: Benzene threshold limit value

Averaging Period

Limit Value

Tolerance Margin

Date by which limit value is to be met

Limit value for the protection of human health

Calendar Year

5 µg/m3 100% of the limit value, i.e. 5 µg/m3, on the entry into force of Directive 2000/69 (13/12/2000).

This value was reduced as of January, 1, 2006 and every 12 months thereafter by equal annual percentages to reach 0% by 1 January 2010

1st January 2010

Chemical Agents

BENZENE

Exposure limit valuesIn 2000, ACGIH proposed:

a TLV-TWA of 0.5 ppm (1.6 mg/m3)

a TLV-STEL of 2.5 ppm (8 mg/m3)

Biological exposure indices (BEI) have been

proposed for occupationally exposed subjects: 25 μg/g creatinine for SPMA 500 μg/g creatinine for t,t-MA in urine samples

collected at the end of the work shift

Chemical Agents

BENZENE

Toxicokinetics Absorption: mainly by inhalation, but also by

transcutaneous route Distribution: adipose tissue and bone marrow Metabolism and elimination after absorption:

0 to 50% of the absorbed benzene is excreted unchanged in the exhaled air, (in relation to metabolic activity and body fat)

A small quantity of benzene (<1 %) is excreted unchanged in urine

The remaining part is metabolised

Chemical Agents

BENZENE

Toxicokinetics

Chemical Agents

BENZENE

Acute Toxicity

Skin irritation and irritation of ocular and respiratory mucosae

CNS: excitement followed by worsening depression (depression worsens as exposure increases)

Myocardium: arrhythmias leading to ventricular fibrillation

Chemical Agents

BENZENE

Chronic Toxicity

Hemopoietic System:

Modifications of the hematic crasis, including pancytopenia

Myeloblastic leukemia and hemocytoblastic leukemia

Chemical Agents

BENZENE

Toxicological MechanismsThe carcinogenic effects of benzene are mainly induced by itsmetabolic intermediates, which can act by:

Inhibition of mitosis associated with inhibition of mitotic spindle formation

Disrupting the covalent bonds of proteins, including hemoglobin, and DNA

Inhibition of DNA polymerase and chromosome damage (including aberrations)

Chemical Agents

BENZENE

Biological Monitoring of Exposure Relationship between organic and total sulfates in

urine: this was the first proposed test, which was subsequently abandoned due to its poor sensibility and specificity

Urinary phenol concentrations do not correlate with benzene exposures below 10 ppm. For this reason, urinary phenol is not suitable as a biomarker of exposure in current industrial settings

Benzene in blood: although able to detect exposure, benzene in blood is not a useful biomarker of exposure extent, because its hematic concentration rapidly decreases after the end of exposure

Benzene in inhaled air reflects the extent of a recent exposure

Chemical Agents

BENZENE

Biological Monitoring of Exposure

Urinary benzene: benzene concentration in end-shift urine reflects exposure during the work shiftUrinary trans,trans-muconic acid (t,t-MA): Urinary trans,trans-muconic acid concentration in end-shift urine is an index of low-level exposure to benzene (≥0.5 ppm) for equal levels of exposure, t,t-MA urinary concentrations vary widely Hypothesis: genetic polymorphism\ other absorption sourcesUrinary S-phenylmercapturic acid (SPMA):It is equally sensitive, but more specific than t,t-MA and is not affected by dietary factors

Chemical Agents

TOLUENE

Colourless, flammable liquid, with typical aromatic odour

Boiling point: 110.4 °C Scarcely soluble in water and soluble in

alcohol, ethyl-ether, benzene, chloroform It is less volatile than benzene, but it

produces flammable vapours

Chemical Agents

TOLUENE


Solvent for oils, resins, natural and synthetic rubber, tar, asphalt;

Thinner for paints, varnishes and inks; Manufacturing of explosives, colouring

agents and phenol synthesis; Employed in the production of car and

plane fuel for its detonation properties

Chemical Agents

TOLUENE


Environmental pollution caused by traffic Contaminated waters Tobacco smoke

Chemical Agents

TOLUENE

Toxicokinetics

Absorption and distribution:same as for benzene

Metabolism and elimination: 20% is excreted unchanged in exhaled air A small amount is excreted unchanged in urine The remaining part is metabolised in the liver

Chemical Agents

Toluene is subsequently converted into benzoic acid andhippuric acid (about 80%), which are excreted in urine with

minor amounts of o-cresol.

Metabolism and elimination:It is less toxic than benzene and has no mutagenic effects; (unlike benzene, which is oxidized at the ring) it is primarily oxidized at the side chain: P450 monooxygenase enzyme P450 displays high selectivity for the methyl group of toluene. Oxidation produces few epoxides, which are responsible for the carcinogenic effect. Moreover, the small quantities of epoxide produced are further reduced by conjugation with glutathione, by spontaneous phenol rearrangements or by diol enzymatic hydrolisis.

Chemical Agents

TOLUENE

Acute Toxicity

Acute irritation of the skin and irritation of the mucosae with which it comes to contact

CNS: asthenia, dizziness, drowsiness, balance and motor coordination disorders

Isolated cases of sudden death after inhalation

Chemical Agents

TOLUENE

Chronic Toxicity

Skin irritation Dyspeptic disorders and abdominal pain,

intolerance to alcohol, symptoms of the CNS Hepatotoxicity Leukemogenic and carcinogenic effect?

Chemical Agents

TOLUENE

Biological Monitoring

Toluene in blood shows good correlation with environmental exposure level and urinary concentration of hippuric acid

Ortho-cresol in urine is a sensitive index of exposure, but shows a wide range of interindividual variability

Hippuric acid in urine is a fairly sensitive index when measured in end-shift urine, although the interpretation of personal monitoring is uncertain

S-benzyl-mercapturic acid (a BLV is not yet available)

Chemical Agents

TOLUENE

Exposure limit values

In 2000, ACGIH proposed:

a TLV-TWA of 50 ppm (188 mg/m3)

The following biological exposure indices (BEI) have

been proposed for occupationally exposed subjects: 0.5 mg/l for end-shift urinary o-cresol 1.6 g/g creatinine for end-shift urinary hippuric acid 0.05 mg/l for toluene in blood collected before the

last shift of the working week

Chemical Agents

XYLENE

Colourless liquid, with a typical aromatic odour

Highly soluble in alcohol and ether, insoluble in water

Commercial formulations contain a mixture of its three isomers (para-, ortho-, and, to a large extent, meta-xylenes) and other aromatic hydrocarbons as possible impurities (ethylbenzene, benzene, toluene)

Chemical Agents

XYLENE


Rubber, colouring and varnish industry Graphic industry Degreaser for dry-cleaning of fabrics Raw material in the synthesis of plastic materials

and synthetic fibres Production of aviation fuel Solvents for paraffin, Canadian balm, polystyrene

(histology laboratories)

Chemical Agents

XYLENE


Contaminated waters (close to fuel collection and storage areas)

Tobacco smoke, active and passive

Chemical Agents

XYLENE

Toxicokinetics

Absorption and distribution:same as for benzene

Metabolism and elimination: Partially excreted unchanged through respiration; during

desaturation (after end of exposure), about 5% of absorbed hydrocarbon is excreted through the lungs and a minor fraction is excreted in urine (about 1%)

The remaining part (95%) undergoes oxidative biotransformation mainly to methylhippuric derivatives (methylbenzoic acids)

Chemical Agents

Metabolism and elimination: In humans, these substances are mainly conjugated with

glycine, forming ortho-, meta and para-methylhippuric acids, which are subsequently excreted through the urinary system

Non-conjugated methylhippuric derivatives are quickly excreted through two different metabolic routes: a relatively rapid one (elimination from the muscles) and a slower one (elimination from adipose tissue); excretion is considered to be complete after two days from the end of exposure

Chemical Agents

XYLENE

Acute Toxicity

Same effects of toluene Severe effects are rare due to the low

olfactory threshold (0.17 ppm) and to the easy detectability of highly irritating vapours

Chemical Agents

XYLENE

Chronic Toxicity

Alteration of hepatic and renal function Irritative lesions of the skin and mucosae CNS Myelodepressive effect

Chemical Agents

XYLENE


Xylene in blood End-shift urinary xylene End-shift urinary methylhippuric acid

Chemical Agents

XYLENE


In 2000, ACGIH proposed: a TLV-TWA (mixture of isomers) of 100 ppm(350 mg/m3)

Biological exposure index (BEI) suggested:

methylhippuric acids ≤ 1.5 g/g end-shift

urinary creatinine

Chemical Agents

CYCLOHEXANE (C6H12)

Aliphatic solvent, colourless liquid at 25°, highly flammable

Pleasant, sweet odour, similar to that of petrol and chloroform (pungent when impure)

Insoluble in water

Chemical Agents

CYCLOHEXANE (C6H12)

Industrial Uses Benzene hydrogenation and oil fractioning

processes Glue solvent in the footwear industry Solvent for fats, oils, waxes and resins in the

chemical and cosmetic industry Solvent for colours paintwork Printing materials It has replaced benzene and toluene in several

manufacturing processes It was present in petrol vapours in 1983 (NOES

Survey 1983)

Chemical Agents

CYCLOHEXANE (C6H12)

Toxicokinetics

Absorption Pulmonary: predominant route (22-34% of inhaled dose,

according to studies conducted with personal samplers) Cutaneous: in theory, given its high liposolubility, it is not

characterised by a “significant percutaneous absorption, unlike other substances with similar chemico-physical properties like n-hexan and n-heptane”

Gastroenteric: it can be well absorbed

Chemical Agents

CYCLOHEXANE (C6H12)

Toxicokinetics

Distribution It tends to accumulate in the adipose tissue, where it

reaches higher concentrations (up to 20-fold higher) than in other tissues including the CNS

hematic concentration values are similar to alveolar values (consistently with the blood/air partition coefficient close to unity)

Biotransformation Degradation by oxidative processes leads to the formation of

molecules with hydroxyl radicals, which are subsequently conjugated to glucuronic acid

Chemical Agents

CYCLOHEXANE (C6H12)

Toxicokinetics

Elimination It is mainly excreted in urine (cyclohexane <1%,

cyclohexanol 0,1-0,2%, and cyclohexanediols 20-40%) and, to a lesser extent, via the pulmonary route

Chemical Agents

CYCLOHEXANE (C6H12)

Acute exposure

At high concentrations (300 ppm), the substance and the vapour are irritating to the eyes and mucosae

It is irritating to the respiratory tract. At higher concentrations, dumbness, nausea,

vomiting, loss of coordination and other narcotic effects can occur

If the liquid is ingested, aspiration into the lungs can lead to chemical pneumonia.

Chemical Agents

CYCLOHEXANE (C6H12)

Chronic Exposure

Skin: dryness, exfoliation, fissuring dermatitis, alteration of lipid cutaneous film

No evidence of hematological alterations similar to those provoked by benzene

Chemical Agents

CYCLOHEXANE (C6H12)


Urinary 1,2 and 1,4 cyclohexanediols are still well detectable at 72 hours after exposure (the concentration of 1,2 cyclohexanediol is almost twice as high as that of 1,4 cyclohexanediol)

Urinary cyclohexanol (glucuronated form), which is is no longer detectable at 6-8 hours, is not useful for biological monitoring

End-shift alveolar concentration is 10-30% of environmental concentrations, used to document point exposures

Chemical Agents

CYCLOHEXANE (C6H12)


In 2006, ACGIH proposed an exposure limit value:


Chemical Agents

ACETONE (C3H6O)

Alicyclic ketone, colourless liquid, miscible in water and easily flammable

Industrial Uses

Chemical synthesis industry (solvent for rubber, plastics, lacquers, silk, fibreglass, resins, cellulose, cellulose acetate, glues, artificial leather, synthetic fibres etc.)

Chemical Agents

ACETONE (C3H6O)

Toxicokinetics

Absorption pulmonary: 70-80% of total inhaled amount Cutaneous

Distribution Uniform, generally more soluble in blood It does not accumulate in the adipose tissue

Chemical Agents

ACETONE (C3H6O)

ToxicokineticsBiotransformation Exogenous acetone is metabolised in various tissues, mainly

in the liver, where it is converted to acetic acid and isopropylic alcohol (excreted in urine)

Elimination (clear discrepancies) Primarily exhaled as CO2 or unaltered (dose-dep.) Renal route (minor pathway) both as acetone and metabolites Poor cutaneous elimination

Chemical Agents

ACETONE (C3H6O)

Acute Toxicityingestion, inhalation and extensive skin contact Neurological disorders: CNS depression of different

severity: excitement, headache, asthenia, sedation and numbness up to loss of consciousness

Cardiovascular disorders: tachycardia and hypotension

Respiratory disorders: irritation, respiratory depression and death can occur after high exposures

Eye irritation Gastrointestinal disorders: nausea, vomiting,

hematemesis due to severe cutaneous and inhalatory exposures

Chemical Agents

Renal damage Hepatic damage Electrolytic disorders: metabolic acidosis

Dermatological disorders: erythema and irritation, nail fragility

Metabolic disorders: hyperglycemia, ketonemia and diabetic-like ketoacidosis. Hyperglycemia, polyurea and polydipsia can persist for several weeks

Development toxicity: it has no tetratogenic effects on experimental animals. Spermatogenesis, morphology and sperm motility and number were tested.

Genotoxicity: sex chromosome loss or non-disjunction during S phase, also evident in cytological studies on fibroblasts

Chemical Agents

ACETONE (C3H6O)

Chronic Toxicity

No episodes of low-concentration chronic inhalation have been reported, causing severe effects in humans

Skin: alteration of lipid cutaneous film

Hematologic disorders: can produce effects on blood and bone marrow

Chemical Agents

ACETONE (C3H6O)

Biological Monitoring Acetone in end-shift urine

Exposure limit values In 2006, ACGIH proposed:


a TLV-STEL of 750 ppm (1782 mg/m3)Classified as A4 (i.e., not classifiable as a human carcinogen)

BEI: 50 mg/l (non-specific)

Chemical Agents

Parasiticides

Plant Protection Products

Pesticides


Active substances and preparations intended for:intended for:

Plant or plant products protection against harmful organisms (insects, acari, nematodes, fungi, etc.) → parasiticides and pesticides

Promoting and regulating plant growth processes. Fertilizers are excluded, because they mainly act on the soil (phytoregulators)

Preserving plant products (e.g. cereals and feedstuff) before industrial processing. Preservative are excluded

Killing undesired plants (weed killers or herbicides)


Since ancient times, man has developed strategies for controlling parasites and insects (e.g. Sulphur as fungicide, strychnine for rodents, arsenic compounds as herbicides or insecticides…)

The synthetic chemistry era begins in the 30s, and several new compounds are introduced

(alkylthiocyanate insecticides, dithiocarbamate fungicides , until DDT)


Despite the risk connected with the use of plant protection products, the cost/benefit ratio is favourable:

They protect crops, increasing product quantity and quality

They allow control of severe epidemics, killing vector insects

Pesticides

Any chemical, physical or biological agent, which is able to kill insects, animals, plants or microorganisms that are undesired or harmful to human beings

(Klaassen CD. Casarett & Doulls’s Tossicologia. I fondamenti dell’azione delle sostanze tossiche. EMSI Roma 2000)

DISEASES TRANSMITTED TO HUMANS BY PATHOGENS THAT CAN BE CONTROLLED BY PARASITICIDES

DISEASE VECTOR ETIOLOGIC AGENT

Malaria Mosquito (Anopheles) Plasmodium Malariae.

Filariasis Mosquito (Culex, Aedes, Anopheles)

Wuchereria Brancofti

Yellow Fever Mosquito (Aedes aegypti) Group B Arbovirus

Viral Encephalitis Mosquito Arbovirus

Petechial Typhus Louse Rickettsia Prowazekii

Bubonic Plague Rat flea Pasteurella Pestis

Rocky Mountain Fever Tick Rickettsia Rickettsii

Pesticides

Consumption

40% North America (1 million kg)

25% Western Europe

35% Other countries

2-3% Italy

The EPA (Enviromental Protection Agency) established an A.D.I. (admissible daily intake)value=NOEL/100 per molecule

Pesticides


Chemical industry workers responsible for the production of plant protection products

Farm operators responsible for phytosanitary treatments

Public health operators responsible for disinfestations

Workers dealing with biological degradation products: leather, paper, wood and varnish industry

Pesticides


Intake of contaminated food and drinks Living in the proximity of agricultural areas and

areas subject to public health interventions

Domestic use (e.g. gardening)

Slow release of parasiticides from treated products (e.g. pentachlorophenol)

Pesticides

Absorption Inhalatory route(main absorption route for chemical industry operators)

Cutaneous route(main absorption route for farm workers)

Oral route(main absorption route for extra-occupational exposure)

Pesticides

Intoxications: WHO data

Developing countries: 3 million pesticide intoxications registered every

year, 220.000 of which are lethal With regard to non-registered cases, it is likely

that 3% of farmers (830 millions) experience one episode of intoxication a year

Pesticides

INTOXICATIONS IN AFRICA

CountryPopulation (millions)

% of workforce employed in agriculture

Cases of pesticide intoxication per year

Sudan 24 80% 384.000

Tanzania 23 85% 368.000

Kenya 22 80% 350.000

Uganda 17 80% 272000

Mozambique 15 70% 240.000

Cameroon 11 80% 175.000

Zimbabwe 10 80% 160.000

Ivory Coast 10 80% 160.000

Malawi 8 85% 128.000

Senegal 7 80% 112.000

Mauritius 2 75% 3.200

Pesticides

INTOXICATIONS IN ASIA

The cases if intoxication per year in Indonesia are estimated to be 30.000, 2.400 of which require hospitalization

In Thailand, the number of cases in 1985 was 4.046, 289 of which were lethal

In Malaysia, the 7% of farm workers faces one intoxication every year

In 1995, pesticide intoxications were the main cause of death in hospital in six rural districts (about 3 million inhabitants) of Sri Lanka

Pesticides

INTOXICATIONS IN SOUTH AMERICA

Between 1980 and 1986, 3.300 hospitalizations and 429 deaths (60% caused by paraquat) were registered in Costa Rica.

In a study conducted in 1988 on a region of Nicaragua, out of 3.300 treated cases, only 1.143 were registered in the Regional Register of Pesticide Intoxications, with an assumed underestimation of 65%

Pesticides

Classification

Parasiticides can be classified according to:

Their target (functional classification)

The chemical structure of their active principle (chemical classification)

Toxicity (toxicological classification)

Pesticides

Functional Classification

Insecticides

Weed killers or herbicides

Fungicides or anticryptogams

Rodenticides

Acaricides

Molluscicides

Nematocides

Pesticides

ClassificationDL 50 (mg/kg)

Oral Cutaneous

Very toxic (T+) ≤25 ≤50

Toxic (T) 25</≤200 50</≤400

Harmful (Xn) 200</≤2000 <400

Toxicological Classification

Current Classification(also based on subacute and chronic toxicity)

Pesticides

Toxicological Classification

In Italy, very toxic, toxic or harmful plant protection products can only be bought by professional certified users (owning a licence provided for by D.P.R. 1255/68)

Interview aimed at assessing knowledge of the hazards associated with the possession and use of plant protection products

Pesticides

Insecticides

Phosphorganic or organophosphoric Compounds

Organic-nitrogen compounds

Chloro-organic or organochlorinated compounds

Vegetable insecticides

Organic sulphur-nitrogen compounds

Insecticidal oils

Inorganic compounds

Phosphorganic or Organophosphoric Csesters of phosphoric, orthophosphoric, pyrophosphoric, thiophosphoric, dithiophosphoric acids with an inorganic radical: Phosphates Thiolophosphates Thionophosphate Dithiophosphates Pyrophosphates Phosphonates Dithiophosphonates Phosphoramidates

the most important are malathion, parathion and tetraethylpyrophosphate (TEPP)

Insecticides

P

OR1

R2 X

NO2O

P

C2H5O

C2H5C

Se.g. Parathion

Basic structure

Phosphorganic or Organophosphoric Cs

Insecticides


Action MechanismThey inhibit Acetylcholinesterase (AChE) in the cholinergic synapses of the CNS they bind to the enzyme active site as competitive substratesof acetylcholine

They inhibit Non-specific Carboxylesterase, called Neuropathy Target Esterase (NTE)

Insecticides

Phosphorganic or Organophosphoric CsFirst step (phosphorylation):

the organophosphoric can be detached from the enzyme

Second step:phosphorylation becomes irreversible ("ageing")

Insecticides


There are two cholinesterases in the human body: Acetylcholinesterase (also called true or red blood cell

cholinesterase) is specific for acetylcholine and is found in:- erythrocytes, nervous system, neuromuscular junctions, suprarenal glands

Pseudocholinesterase (or plasma cholinesterase) is not specific for acetylcholine and also hydrolyses other substrates. It is found in:

- plasma, myocardium, smooth muscle, intestinal mucosa, skin

Insecticides


Acute exposure to high doses

Acute Cholinergic Crisis “Intermediate Syndrome” Delayed Polyneuropathy

Insecticides


Acute Cholinergic Crisis “Muscarinic” symptoms (arising from stimulation of the muscarinic receptors of the parasympathetic postganglionic neurons)

“Nicotinic” symptoms (arising from stimulation of the nicotinic receptors of the sympathetic and parasympathetic ganglia and of the neuromuscular junctions)

Neuro-behavioural effects (arising from stimulation of the nicotinic receptors of the Central nervous System)

Insecticides

MUSCARINIC SYMPTOMS:Respiratory apparatus (bronchospasm, increased secretions, cough, cyanosis, pulmonary edema)\Gastroenteric apparatus (nausea, vomiting, abdominal pain, diarrhea, tenesmus, faecal incontinence\Cardiocirculatory apparatus (arterial hypotension, bradicardia, cardiac arrest)\Urinary apparatus (pollakiuria and incontinence\Visual aparatus (miosis, anisocoria, diplopy)\Exocrine glands (increase in salivation, perspiration and lacrimation)\Locomotor apparatus (muscular asthenia, involuntary tremors, fasciculations and muscular cramps\Cardiocirculatory apparatus (tachicardia, arterial hypertension)

NICOTINIC SYMPTOMS:Metabolism (hyperglicemia)\Skin (intense pallor)

CNS: excitement followed by depression and coma

Insecticides


“Intermediate Syndrome” It develops 24-96 hours after the acute cholinergic

crisis

It is characterised by myastenia of the neck flexor muscles and limb proximal muscles, and by paralysis of the cranial nerves

High risk of death due to severe respiratory depression, which requires respiratory assistance and shows no response either to atropine or to oximes

Insecticides


Delayed Polyneuropathy

Sensory-motor distal axonopathy developing 2-5 weeks after acute cholinergic crisis

Initial myasthenia of the upper and lower limbs distal muscles

It is followed by spasticity, hypertonia and hyperreflexia of the these muscles

Insecticides


Prolonged exposure to low doses Neurotoxicity (Alzheimer's Disease, Parkinson's Disease, etc.) “Endocrine disruption” (reduced fertility, inhibition of GH incretion, increased

melatonine incretion, etc.) Carcinogenity (Non-Hodgkin Lymphoma , Leukemias, Sarcomas, etc.)

Insecticides


Treatment

Atropine to counter muscarinic effects

Oximes to counter nicotinic and CNS effects

Benzodiazepines to control anxiety and toxicity on the CNS and

neuromuscular system, which are resistant to atropine

Insecticides


Biological MonitoringErythrocyte cholinesterase activity Advantages: they are highly sensitive indices of exposure, becausethey can be detected in urine at very low exposure levels Limitations: high interindividual variability (pre-exposure values arenecessary for comparison with post-exposure data)

Alkylphosphates in urineAdvantages: they are highly sensitive indices of exposure, becausethey can be detected in urine at very low exposure levels. Limitations: little is known about the relationship between dose andurine levels; aspecificity

Paranitrophenol in end-shift urineLimitations: aspecific

Insecticides



BEI proposed by ACGIH:

A 70% reduction in erythrocyte cholinesterase activity with respect to basal value

Paranitrophenol in end-shift urine for parathion: 0.5 mg/g creatinine

Insecticides

Organic-nitrogen Cs: carbamatesEsters of carbamic acid:

Aromatic Esters Bendiocarb Carbaryl Carbofuran Carbosulfan Pirimicarb Propoxur

Oximes Aldicarb Methomyl

Urea derivatives Diflubenzuron Triflumuron

Triazines cyromazine

Insecticides

NR2 C

R1

O

O

R3

R2 and R3 groups can be an organic radical or simply a hydrogen atom. Group R3 usually consists of an aromatic ring, sometimes linked to a tertiary amine

Basic structure

O C

O

NH

CH3

es. carbaryl

Organic-nitrogen Cs: carbamates

Insecticides


Action Mechanism

They inhibit Acetylcholinesterase (AChE) in the cholinergic synapses of the CNS. Unlike with organophosphates, inhibition is reversible and short-lived

Insecticides



Symptoms (acute cholinergic crisis and

“intermediate syndrome”) can bedistinguished from those of organophosphatesintoxication by their:

Shorter duration Lower intensity Lack of delayed polyneuropathy

Insecticides


Prolonged exposure to low doses

Neurotoxicity (Alzheimer's Disease, Parkinson's Disease, etc.)

“Endocrine disruption” (reduced fertility, inhibition of FT3 and FT4 incretion, etc.)

Carcinogenity (Non-Hodgkin Lymphoma, Leukemias, Sarcomas, etc.)

Insecticides


Treatment Atropine to counter muscarinic effects

Benzodiazepines to control anxiety and toxicity on the CNS and neuromuscular system, which are resistant to atropine

No Oximes, because they do not interact with carbamylated acetylcholinesterase

Insecticides


Biological Monitoring Hematic cholinesterase activity: monitoring of pre/post-exposure erythrocyte AchE levels (within 4 hours from exposure)

The urinary metabolites of some carbamates are known:

1-urinary naphtol for carbaryl 3-hydroxicarbofuran in urine for carbofuran 2-isopropoxyphenol for propoxur

However, we have no BEI values (the relationship between exposure and urinary levels is unknown)

Insecticides

Chloro-organic or organochlorinated Cs They are chlorinated hydrocarbons belonging to

three distinct chemical classes:

Dichlorodiphenylethanes Cyclodienes Hexachlorocyclohexanes and chlorinated benzenes

They were introduced in the forties, both in the agricultural sector and against insects vectoring infectious diseases

Compounds with exceptional chemical stability and high lipophilia, accumulating in the environment and biological systems

Insecticides

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

Chloro-organic or organochlorinated CsHeterogeneous group of compounds, sharing insecticidal properties and the presence of chlorine atoms

Cl Cl

C(CCl)2

DICHLORODIPHENYLETHANES(DDT, Dicofol, Metolachlor…)

Cyclodienes(Aldrin, Heptaclor, Endosulphane…)

CHLORINATED BENZENES CYCLOHEXANES

1

2

3

Insecticides

Chloro-organic or organochlorinated Cs

Action mechanism

For dichlorodiphenylethanes, four mechanismshave been proposed, which mainly affect the

sensitivenervous fibres of the PNS:

• Reduction of potassium transport• Inactivation of sodium channels• Inhibition of sodium-potassium and calcium-magnesium

ATPases• Interaction with calcium/calmodulin and neurotransmitter

release

Reduction in the velocity of neuronal membrane repolarization

Insecticides


Action mechanism

For cyclodienes, cyclohexanes and chlorinatedbenzenes, two mechanisms have been hypothesised,which mainly occur in the CNS:• Antagonism of the GABA neurotransmitter by blockage of

chlorine channels• Inhibition of Ca2+, Mg2+-ATPase, with cumulation of intercellular

free calcium and increase in calcium-dependent release of neurotransmitters from the vesicles

Reduction in the velocity of neuronal membrane repolarization

Insecticides



Paresthesias (especially facial paresthesias) Hypersensitivity to external stimuli Irritability Tremors (“Kepone shakes”) Tonico-clonic convulsions

Insecticides



Neurotoxicity (Parkinson's Disease) “Endocrine disruption” (estrogenic and antithyroid action) Carcinogenity (leukemia, Non-Hodgkin lymphoma, soft tissues

sarcoma, hepatic and breast tumours )

Insecticides


Treatment

DecontaminationSupport treatmentDiazepam or phenobarbital (for convulsions)Cholestyramine (it reduces enterohepatic

circulation)

Insecticides

Weed killers or Herbicides

Classification

Chlorophenoxy compounds: MCPA (4-chloro-2-methylphenoxyacetic-acid) 2,4 D (2,4 dichlorophenoxyacetic acid) 2,4,5 T (2,4,5 trichlorophenoxy acetic acid)

Bipyridyl compounds: Paraquat Diquat

Triazines: Atrazine Simazine Propazine

2,4,5 T (2,4,5 trichlorophenoxy acetic acid)

Action mechanism mediated by the TCDD contamination

(2,3,7,8,tetrachlorodibenzo-p-dioxin or dioxin), it arises from the synthesis of these compounds when temperature is not strictly controlled

dioxin is teratogenic and carcinogenic to humans

It also causes a severe contact dermatitis called “chemical workers chloracne”




vomiting myalgia headache asthenia chloracne




Neurotoxicity (Lateral Amyotrophic Sclerosis)

“Endocrine disruption” (reduced fertility)

Carcinogenity (Non-Hodgkin lymphoma, soft tissue sarcoma, prostatic carcinoma)


Paraquat

Action mechanisms

Formation of free radicals and peroxydation at the:

Pulmonary (alveolar) level Hepatic level Renal level

Fibrosis Organ failure


Paraquat


Signs and symptoms of acute ventilatory failure

Signs and symptoms of acute renal failure

Signs and symptoms of acute toxic hepatopathy


Paraquat


Neurotoxicity (Parkinson's Disease) No evidence of “Endocrine disruption”

No evidence of Carcinogenity



Occupational Tumours

Tumours are defined as “occupational” when work-related exposure to carcinogenic agents acted as a cause or joint-cause in their genesis



GENERAL CHARACTERISTICS

Target organs Latent period Dose-response relationship Histological type IARC lists Primary sites

TARGET ORGANS

Occupational tumours arise: at the site of carcinogenic contact: Direct carcinogens At the target sites of the carcinogen: Indirect carcinogens

Target organs can be:- entry routes (e.g. skin, bronchial epithelium)- metabolic sites (e.g. liver) - accumulation sites (e.g. Hemopoietic marrow)- routes of elimination of active metabolites (e.g. Urinary pathways)


Latent Period

The time elapsing between the beginning of carcinogen exposure and the clinical appearance of the tumour

Dose-response relationship

It is not known whether threshold levels exist, below which no increase in tumours occurs

Histological Type

From a histological point of view, occupational tumours cannot be distinguished from “spontaneous” neoplasia occurring at the same site.

International Agency for Research on

Cancer (IARC)

Chemical substances or mixtures of substances that induce occupational tumours and related target organs

Industrial processes responsible for occupational tumours and related target organs


Primary Sites of Occupational Tumours

Skin Respiratory tract Lung Mesothelia (serous membranes) Urinary tract Hemopoietic marrow Liver

Skin and Occupational Tumours

Occupational cutaneous tumours are carcinomas induced by: Chemical agents(e.g. IPA, unrefined mineral oils, arsenic compounds) Physical agents(e.g. Ionizing radiations and UV rays)

Respiratory Tract and Occupational Tumours

Carcinomas of the nasal and paranasal cavities: Nickel compounds, wood dusts (especially from hard woods), Chrome compounds VI

Nasopharynx carcinomas: formaldehyde

Lung and Occupational Tumours

Main causal agents IPA Asbestos Crystalline silica (?) Radon bis(chromomethyl)ether (BCME) As compounds Ni compounds CrVI compounds

Be compounds

Mesothelia and Occupational Tumours

Characteristics of mesotheliomas

Most affected serosa: pleura Latent period: 10-40 years Dose-response relationship: absent Causale agent: asbestos

Urinary Tract and Occupational Tumours

Main causal agents

IPA Aromatic amines Benzidine: production and use of azo colourings 4-aminodiphenyl: only produced in the USA 2-naphthylamine: production and use of azo colourings

production and distillation of gases from coal 0-toluidine: production of 4-chloro-toluidine 4-chloro-toluidine: production of chlordimeform

Hemopoietic System and Occupational Tumours

Main leukemogenic agents

Benzene 1,3-butadiene (group 2A, IARC) Ionizing radiations Ethylene oxide (group 1, IARC)

Liver and Occupational Tumours

Hepatic angiosarcoma

The liver is the main target organ of vinyl chloride monomer (VCM), which induces various types of tumour, in particular angiosarcoma

Conclusions

It is important to identify biomarkers of

exposure to genotoxicants and/or early

biological effects of genotoxicants


Occupational Infections

D. L.vo 626/94 and further modificationsTitolo VIII: Protection against biological agents

Field of application (art. 73)

Any work activity involving risk of exposure to biological agents(excluding genetically modified microorganisms (GMMOs), whose use is regulated by D. L.vo 206/01.)

Regulations

Regulations

Annexes to D. L.vo 626/94 and further modifications

Annex IX: Illustrative list of work activities, which can involve the presence of chemical agents

Annex X: Index of biological risk Annex XI: List of classified biological agents Annex XII: Specifications on control measures and

levels Annex XIII: Specifications for industrial processes

Annex IX: List of work activities, which can involve the presence of chemical agents

Food industries Agriculture Contact with animals and/or animal products Sanitary services, including isolation and post- mortem units Clinical, veterinary and diagnostic laboratories, excluding microbiological diagnosis Potentially infected plants for waste disposal and special waste collection Plants for purifying drain waters

Regulations

MINISTRY OF HEALTH:Chemical Agents, Category A (high priority)

Microbiological characteristics (definition, possible diffusion media, environmental resistance, sources of contagion, methods for the decontamination and disposal of contaminated materials, transport of biological samples)

Epidemiological/clinical characteristics (transmission pathways, duration of incubation and

contagiousness, clinical characteristics, control methods, diagnostics, precautions for the patient, transportation and evacuation of patients, measures for exposed persons, contacts and assistance personnel, treatment)

Regulations

Employer's Obligations:

Risk assessment document (RAD)

Technical, organizational, procedural and hygienic measures

Information and trainingSanitary Surveillance – prevention and

control

Regulations

Workers whose risk assessment evidenced an health risk are submitted to sanitary surveillance.

Upon advice of the occupational physician, the employer adopts special protection measures:

• Effective vaccines• Temporary removal\ascertainments\ RAD revision• He provides information on the sanitary controls they are

submitted to, on the necessity to undergo sanitary checks, even after the end of the activity, and on the disadvantages of vaccination

Regulations

DELIBERATE OR POTENTIAL BIOLOGICAL RISK

Deliberate risk: Biological agents are deliberately introduced into the working cycle either for treatment, manipulation and transformation or to exploit their biological properties

University and research centres, Public Health, Zootechnics and Veterinary practice, Biotechnology and Farmaceutical industry, Food industry, Chemical industry, Energy industry, Environment, Mines, Agriculture, War industry

Potential risk:The presence of chemical agents not intended for a specific use

Food industries, Agriculture, Zootechnics, Meat slaughtering and processing, Veterinary services, Sanitary services, Diagnostic laboratories, Waste collection, processing, and disposal services , Disinfection and disinfestation service, Rain water purification plants


RAD: deliberate risk Gathering information on the microorganism

(infectivity, pathogenicity, etc.) and its related pathologies, epidemiology, mode, volume and frequency of manipulation

Evaluation of diffusion and future in the environment (control measures, assessment of CPDs, environmental monitoring, etc.)

Risk characterisation (incidence and severity of human health damage and environmental impact)

Risk management (training/information, CPD, IPD)

Reduction of risk to an acceptable level


RAD: potential risk

Biological agents can induce:Infections caused by parasites, viruses and

bacteriaAllergies caused by exposure to moulds,

yeasts, and organic dusts (e.g.: flour dusts, acari)

Poisonings or toxicogenic effects


CONTAMINATION SOURCES

External airConditioning systemsPresence either of diseased individuals or

healthy carriersFoodstuffsAnimals

Biological dusts: allergic respiratory diseasesFungi Aspergillus \ Alternarium \ Penicillium Streptomyces albus Bacteria Bacillus subtilis \ Bacillus Cereus\ Euroglyhus\Staphylococcus aureus\Strespococcus pyogenes\ Pseudomonas aeruginosa\Legionella Acari Acarus Dermatophagoides

BIOLOGICAL RISK

FOOD INDUSTRYFood sector

(production of foods and food additives)

ALLERGIESMoulds\ yeasts, bacteria, acari\ Organic dusts\ Powdered milk or flour contaminated by biological agents\ Toxins (e.g.: botulinum toxins, aflatoxins)

FOOD TOXINFECTIONSSalmonella typhi\ Staphylococcus aureus\ Escherichia

coli\Listeria monocytogenes\Clostridium botulinum\Vobrio

cholerae\Hepatic virus A\Gastroenteric viruses

BIOLOGICAL RISK

AGRICULTUREagricultural, forest, horticultural sector and production of animal feedstuff

Traumas: infections caused by pyogenes, vibriones, hookworm larvae, clostridia (tetanus and gas gangrene), anthrax Sewage and water distribution: enterovirus, coli, salmonellae, vibrio cholerae Vectors (cockroaches, rats, ticks): leptospirosis, salmonellae, enterobacteriaceae, coliforms, Lyme disease and Q feverWild animals (foxes, dogs, ferrets, weasels): Rhabdovirus

Respiratory disorders caused by microorganisms/acari in cereal dusts, powdered milk, flours and spices (ODTS – Organic Dust Toxic Syndrome) Specific allergic disorders (“Farmer's lung” or “Bird breeder's lung” due to chronic exposure)

BIOLOGICAL RISK

RISKS ASSOCIATED WITH ZOOTECHNICS Harmful gases and vapours associated with

unpleasant odours (organic compounds with either N and/or S or H2S, NH3) Bacterial or viral infections due to contact

with sewage (bacteria, viruses, eggs of intestinal worms, parasitic fungi) and to inhalation of contaminated aerosol (e.g.: feedstuff contaminated by moulds or

mycetes disorders of the respiratory system or contaminated by BSE prions?)

Vectors carrying pathogenic germs (ticks, rats, cockroaches)

Pollution in shallow and deep waters Diseases transmitted by animals (ZOONOSES)

BIOLOGICAL RISK

Zoonoses: diseases transmitted by animals to humans and vice versa. They affect breeders and those who have occasional contact with breeding animals (veterinary doctors, animals traders and transporters, slaughterhouse operators, operators of the animal by-products sector)

Zoonoses in bovine breedingBrucella abortus (brucellosis), Mycobacteria (tuberculosis),

Clostridium tetani (tetanus), Coxiella burnetii (Q fever), mycetes (mycosis)

Zoonoses in swine breedingBrucella suis (brucellosis), Leptospira SPP (leptospirosis), Erysipelothrix

Rhusiopathia (erysipelas), Clostridium tetani (tetanus), mycobacteria

(tuberculosis), Streptococcus suis (streptococcosis)

Zoonoses in the slaughtering sector:brucellosis and TBC (cattle); leptospirosis and erysipelas

(swine)

BIOLOGICAL RISK

Scabies,Ringworm

Rabies,Tetanus

Leptospirosis

Salmonellosis, Hydatidosis, Cutaneous Larva migrans , Visceral Larva Migrans

contact

Bite and scratchesurine

feci

Leptospirosis

Toxoplasmosis

Psittacosis

Scabies, Ringworm

Rabies, cat scratch disease

BIOLOGICAL RISK

zoonoses

HEALTH SECTOR RISKSHospitals , outpatient clinics, dentist surgeries, assistance services Bacterial and viral infections: HIV, viral hepatitis (B\C), tuberculosis, salmonellosis, legionellosis Most frequent accidents: slashes and punctures, contact with biological fluids

RISKS IN DIAGNOSTIC LABORATORIES (excluding microbiology laboratories) Infections and allergies due to the manipulation of m.o. and cell cultures (e.g. Human tissue cells) Most frequent accidents: accidental leakages, needle and glassware injuries

BIOLOGICAL RISK

RISKS IN THE CONSTRUCTION INDUSTRY Moulds and bacteria originating from decay of construction materials Clostridium tetani, leptospires, coliforms, enterobacteriaceae, amoebas, acari, helminths carried by insects or rats or residing in non-hygienic environments

RISKS ASSOCIATED WITH WORK IN ARCHIVES, MUSEUMS AND BOOKSHOPS Moulds/yeasts and bacteria causing allergies and respiratory disorders

BIOLOGICAL RISK

RISKS ASSOCIATED WITH SEWAGETREATMENT

Formation of contaminated aerosolSalmonellae, Vibrio, escherichia, poliovirus, adenovirus, eggs of intestinal parasitesSewage worker’s Syndrome

RISKS ASSOCIATED WITH WASTE DISPOSALRisks vary according to waste type (hospital waste, sewage, etc.)Waste recycling and composting plants: allergic phenomena and respiratory disorders due to the presence of moulds (aspergillosis)

BIOLOGICAL RISK

TRADIZIONAL P.

Fermentative techniques

Modern techniques

AVANZATE Designed biological systems

RISKS ASSOCIATED WITH BIOTECHNOLOGICAL PROCESSES

BIOLOGICAL RISK

RISKS ASSOCIATED WITH

BIOTECHNOLOGICAL PROCESSES Immunopathies: allergies (bronchial asthma and

contact dermatitis – irritative or allergic dermatitis) Toxic effects: e.g. hypovitaminosis, disbacteriosis,

virulence of flora (production of antibiotics and hormones) or reproductive disorders in women working in the production of progestogenic substances

Pathogenic effects: induced by artificially manipulated organisms and vectors like phages, retroviruses, plasmids, etc.

BIOLOGICAL RISK

RISK ASSESSMENT: SAMPLINGS AND ANALYSIS

Each microorganism can be defined by an INFECTING DOSE (DI50) typical of each species

In order to distinguish between presumed and actual risk, risk assessment should include a MINIMUM INFECTING DOSE (DI50) or INFECTIVITY THRESHOLD

The INFECTIVITY THRESHOLD of several microorganisms is close to unity (DI0=1), but in case of high pathogenicity and transmissibility, and low neutralizability, exposure should be eliminated

Risk Estimate

Identifying the production phases in which exposure can occur Attributing a priori preventive and protection measures on the basis of scientific knowledge A posteriori identification of potential contamination sources

A series of control measures and optimized procedures will be developed for each critical phase of the working cycle Setting-up of analytical environmental monitoring or systematic inspections

RISK ASSESSMENT: SAMPLINGS AND ANALYSIS

Environmental Monitoring

BIOAEROSOL = aerodispersed biological particles

Fungal spores

Pollen

Viruses, bacteria, yeasts

Algae and protozoa

Insect fragments or insect excrements

Skin flakes or mammal hairs

Residues or products of organisms like (endotoxic or mycotoxic) bacterial lipopolysaccharides

Estimation of biological contamination

Expression of results Colony-forming unit (CFU/m3) per vital organisms Number of cells, spores or pollen grains, in case vitality is

undetermined Chemical determinations (ng, mg/m3) in the presence of

endotoxins.

TYPE MEDIUM SIZE (mm)

Viruses 0.02 – 0.3

Bacteria 0.5 – 10

Endospores 0.5 – 3

Fungal spores 1 – 100

Pollen 10 - 100


Estimation of biological contamination

Bioaerosol analysisCalculation of coloniesATP – bioluminescenceChemiluminescenceFluorescence microscopy Phase contrast MicroscopyImmunological tests

Air Microbial Index (AMI) for surgery rooms and intensive care units:

normal: germs in air from 0 to 15/m3\ uncertain: from 16 to 75/m3\ altered: > 75/m3


EVALUATION OF CONTAMINATION

Contamination of surfaces Verifying the effectiveness of the decontamination

system which is being used Controlling the correspondence between actual

aseptic level and the level of asepsis required for a specific process

Verifying the absence of biological dispersions out of containment areas

Types of surface monitoring

A case/control - Upstream/downstream – Longitudinal analyses of temporal series


Biological Risk Prevention

CONTAMINATION

Direct or indirect contact with an infection source or reservoir Collection, handling or transport of infected biological material (faeces, urine, blood, etc.) and other infected materials (needles, syringes, scalpels, etc.) Genetic engineering practices involving the use of microorganisms or their parts

MAIN TRANSMISSION ROUTES

contact: direct or indirect contactaereal route: extremely small microorganisms

contained in droplets (small respiratory drops expelled from an infected reservoir through coughs, sneezes, singing, etc.)

parenteral route: inoculation or contact of mucosae and injured skin with blood, blood products or other biological material


INFECTION ROUTESVie di penetrazione

Esempi di agenti biologici (classe di rischio)

Protezione dell’operatore

Bocca (ingestione) Salmonella (2), Shigella (2), Clostridium difficile (2), Virus epatite A (2)

• è viet at o aspirare dalla pipet t a con la bocca

• è viet at o m angiare e fum are in laborat orio

• evit are di port are alla bocca qualsiasi ogget t o u t ilizzat o nel laborat orio

Narici ( in alazion e) Mycobact erium t ubercolosis (3), Legionella Pneum ophila (2), Brucella (3), Virus respirat orio sinciziale 2), Cyt om egalovirus (2), St rept ococcus pneum onit e (2)

• evit are di sorvegliare operazion i crit iche com e la sem ina ed l’apert ura delle piast re e delle provet t e, la cent rifugazione, l’om ogenizzazione senza indossare i DPI (disposit ivi di prot ezione individuale)

Pelle ( in iezion e) Virus Epat it e B (3* * ) e C (3* * ), HI V (3* * ) Herpes Sim plex (2), Candida Albicans (2)

• m aneggiare con m olt a at t enzione aghi, pipet t e Past eur, vet reria rot t a

• prot eggere accurat am ent e t agli, ferit e o abrasion i present i su lla pelle

Occh i ( sch izzi) Herpes sim plex (2) • prot eggere sem pre gli occhi • non ut ilizzare lent i a cont at t o


PREVENTION MEASURES

Increasing host resistance (active or passive immunization through vaccines and immunoglobulins)

Inactivating the infective agent (cleansing, disinfection and sterilizing by use of chemical or physical methods)

Interrupting the infection chain (treatment of sanitary materials, waste collection and disposal, standard precautions)


PREVENTION INTERVENTIONS

Environmental intervention Verifying the proper functioning of containment areas Disinfection (formaldehyde, UV, etc) Disinfestation Appropriate air filtration systems Waste and sewage treatment

Individual Intervention Use of IPD Washing and disinfection systems


SAFETY MEASURES

Work organization Training - information Containment measures Access control, safety signs


GENERAL PRECAUTIONS

Any biological sample should be treated as potentially dangerous:

Use of IPDKeeping hands away from face and washing

hands frequentlyDo not eat, drink, or smokeDo not wear make-up/contact lenses


Reducing the use of needles and cutting objects and avoid recapping syringes after use

Decontamination of worktops using effective chemical disinfectants

Mouth pipetting is forbidded; mechanical pipetting devices should be used instead (automatic pipetters) or pipettes with filtered tips

Keeping laboratory clean and tidy


PRECAUTIONS IN HANDLING AND TRANSPORTAT OF BIOLOGICAL SAMPLES

Potentially infected materials should be handled so as to avoid any dispersion


INDIVIDUAL PROTECTION DEVICES (IPD)

Face protectionsurgical masks\breathers

Body protectionwaterproofs gowns\jackets

Gloveslatex, vinyl, nitrile sterile gloves

Eye protectionsafety glasses\screens


EMERGENCY MEASUREMENT

D. Lvo 626/94 – Art. 84 Emergency measures

Qualora si verifichino degli incidenti con A. B. di classe 2, 3 o 4 i lavoratori devono immediatamente lasciare la zona interessata, cui possono accedere solo gli addetti ai necessari interventi, con l’obbligo di indossare i DPI

Il DdL informa al più presto l’organo di vigilanza territorialmente competente nonché i lavoratori, gli RLS delle evento, della cause che lo hanno determinato e delle misure che si sono o si intende adottare

I lavoratori segnalano immediatamente al DdL o al dirigente o al preposto qualsiasi infortunio o incidente relativo all’uso di A.B


Occupational Medicine Prof. Francesco S. Violante Chemical agents and pesticides.

Documents

alkynes c c c n h

paraffins cc

n cycloalkenes c n h

cycloalkynes c n h

rings cycloalkanes c

benzene e monossido

benzene oltre

benzene clear

Transcript of Occupational Medicine Prof. Francesco S. Violante Chemical agents and pesticides.

Francesco Ni

Francesco prandini

Occupational Medicine Prof. Francesco S. Violante General Concepts Evolution of Working Conditions Health and Labour Occupational Injuries and Diseases.

Care Studentesse,...2018/08/01 · Desiderio Alessandro Sciortino Francesco Longo Gabriele Rappresentanti del Personale Tecnico -Amministrati vo Pinzi Giovanna Pirotta Violante 7

POLITECNICO DI TORINOTesi di Laurea Magistrale Android infotainment system A prototype based on Android Automotive Relatore prof. Massimo Violante Candidato Francesco Spissu Settembre

PRESENTED BY: BIANCA VIOLANTE AND CAITLYN MAJOR MARKETING YOUR SMALL NONPROFIT.

PROFICIENCY TESTING PROGRAMS PESTICIDES … · Pesticides in vegetables & fruits (dithiocarbamates) Pesticides in Dairy Products Multi-residue screening of pesticides in Food A =

Pesticides and You - Home â€” Beyond Pesticides

Romania in secolul XX - Francesco Guida - Libris.ro in secolul XX... · Title: Romania in secolul XX - Francesco Guida Author: Francesco Guida Keywords: Romania in secolul XX - Francesco

Laura & Francesco

Attanasio Kitao Violante

Understanding Pesticides Part 1 Pesticides Defined · Minimum Risk Pesticides • Products listed as ―Minimum Risk Pesticides‖ by the Environmental Protection Agency (EPA) are

PESTICIDES IN THE MILITARY - MilitaryNewbie.commilitarynewbie.com/.../2013/...Pesticides-in-the-Military-MD01731.pdf · PESTICIDES IN THE MILITARY ... LESSON 1 Introduction to Pesticides.

Descendants of Francesco Guerriero/ Guerrieriguerrie.com/pdfs/Descendant_Report_Guerriero_Guerrieri.pdf · Descendants of Francesco Guerriero/ Guerrieri Generation 1 1. FRANCESCO

Francesco Chiminello

Francesco Camoletto

Conventional Pesticides in Agriculture: Benefits Versus Risks · Conventional Pesticides in Agriculture: Benefits Versus Risks Conventional pesticides (i.e., only pesticides synthesized

Smarter journeys start here - Francesco Violante

VIOLANTE Numero9abril2013

Francesco Isa