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12.04.02 Metoder for fastsettelse av administrative normer (OELs) i Norge og EU 1

Metoder for fastsettelse avadministrative normer (OELs)i Norge og EU

Metoder for fastsettelse avMetoder for fastsettelse avadministrative normer (administrative normer (OELsOELs))i Norge og EUi Norge og EU

Steinar Øvrebø, Toksikologisk seksjonStatens arbeidsmiljøinstituttOslo

Steinar ØvrebøSteinar Øvrebø, , Toksikologisk seksjonToksikologisk seksjonStatensStatens arbeidsmiljøinstitutt arbeidsmiljøinstituttOsloOslo

Fredag Fredag 12 12 april april 20022002 12.04.02 Metoder for fastsettelse av administrative normer (OELs) i Norge og EU 2


• Administrative normer, OEL og TLV©

• OEL yrkeseksponeringsgrenser?

• Historien om OEL stammer fra 1886 (MAK)

• Norge har en historie fra 1978 og 1950

Noen definisjoner innledningsvis


• Arbeidsmiljøsektoren tidlig ute medbeskyttelse vha grenser (magiske tall?)

• Kan vi sette et tall er ”regulererenlykkelig”?

• Kan vi i tillegg si at tallet innebærer atvi går fra farlig til helt ufarlig blirpolitikerne glade

• Regulatorisk toksikologi kjedelig?

Kvifor set vi administrative normer?


• Første OELs (MAK) - Karl BernhardLehman in 1886

• Bureau of Mines Technical Paper -1921

• Sovietunionen hadde liste med 900stoffer i 1930

• ACGIH, modell for mange OEL listerførste i 1946


• Arbeidstilsynet benyttet OELs fra ACGIHfra omkring 1950 to 1973

• I 1973/74 publiserte Yrkehygienisk Institutten norsk liste basert på ACGIH verdiene

• I 1978 Arbeidstilsynet publiserte sin førsteegne liste

Norsk OEL historie

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Administrative normer versusgrenseverdier

Normene er satt ut fra tekniske, økonomiske ogmedisinske vurderinger. Selv om normeneoverholdes, er man derfor ikke sikret athelsemessige skader og ubehag ikke kan oppstå.

Juridiske følger av administrative normer

Normene er anbefalinger og i seg selv ikkejuridisk bindende. Normene blir først juridiskbindende når de forekommer i konkrete påleggfra Arbeidstilsynet eller i forskrifter utgitt avArbeidstilsynet.


ACGIH examples of low variability in EuropeSubstances for which indicative limit values exist due to Commission Directive 91/322/EEC10

__________________________________________mg/m3____________________________________Substance CAS* EU Norge Spania Storbritannia Tyskland Sverige Danmark Australia Ungarn USSR JapanNicotine 54-11-5 0,5 0,5 0,5 0,5 0,47 - 0,5 0,5 -Formic acid 64-18-6 9 9 9 9,6 9,5 5 9 9,4 5 STEL 1 9,4Acetic acid 64-19-7 25 25 25 25 25 13 25 25 10 STEL 5 25Methanol 67-56-1 260 130 266 266 270 250 260 262 50 STEL 5 260Acetonitrile 75-05-8 70 50 68 68 68 50 70 70 50 STEL 10Picric acid 88-89-1 0,1 0,1 0,1 0,1 0,1 - 0,1 - 0,1 -Naphthalene 91-20-3 50 50 53 - - - 50 52 40 STEL 20Nitrobenzene 98-95-3 5 5 5 5,1 - 5 5 5 3Resorcinol 108-46-3 45 45 46 46 - 45 45 45 45Diethylamine 109-89-7 30 30 30 30 15 30 15 30 30Pyridine 110-86-1 15 15 16 16 16 7 15 16 5 STEL 5Carbon dioxide 124-38-9 9000 9000 9150 9150 9100 9000 9000 9000 tja9000Oxalic acid 144-62-7 1 1 1 1 - 1 1Cyanamide 420-04-2 2 2 2 2 - 2 2Calcium dihydroxide 1305-62-0 5 5 5 5 - - 5Disphosphorus pentoxide 1314-56-3 1 1 1 2 1 1 1Disphosphorus pentasulphid1314-80-3 1 1 1 1 1 - 1Cresols (all isomers) 1319-77-3 22 22 22 22 22 4,5 22Platinum (metallic) 7440-06-4 1 0,002 1 5 0,002 0,002 0,002Lithium hydride 7580-67-8 0,025 0,025 0,025 0,025 IIb - 0,025Bromine 7726-95-6 0,7 0,7 0,7 0,66 0,66 0,7 0,7Phosphorus pentachloride 10026-156 1 1 0,9 0,87 1 - 1Nitrogen monoxide 10102-43-9 30 30 31 31 - 30 30Pyrethrum 8003-34-7 5 5 5 5 5 - 5Barium (soluble compounds as Ba) 0,5 0,5 0,5 0,5 0,5 0,5 0,5Silver (soluble compound as Ag) 0,01 0,01 0,01 0,01 0,01 0,01 0,01Tin (inorganic compounds as Sn) 2 2 2 2 IIb - 2


Note. All limits were obtained from one of the following publications: WHO (1977), Cook (1986), AIHA (1990), ACGIH (1989, 1992). C, ceiling value (maximum instantaneous concentration). STEL, short-term exposure limit (15 min; up to 4 times per day). TWA, time-weighted average (8 h/d).

Worldwide occupational exposure limits (OEL) for formaldehyde in 1994

NIOSH 0.1 C (15 min)World Health Organization (WHO) 0.24 TWAACGIH (1991) 0.3 CDenmark 0.3 CGermany 0.4 STELUSSR (former) 0.4 TWAGermany 0.5 TWAU.S. Occupational Safety and Health Administration 0.75 TWA (OSHA, 1992)Hungary, Yugoslavia 0.8 TWAFinland, Norway, Sweden 1.0 CACGIH (1990), AIHA, Australia, Austria, Germany, 1.0 TWA Italy, the Netherlands, Switzerland/OSHABrazil, Chile 1.6 TWABulgaria 0.8 STELAustralia, Belgium, India, Japan, the Netherlands, 2.0 C VenezuelaACGIH (1990), AIHA, Argentina, France, 2.0 STEL the Netherlands, OSHA, United KingdomHungary 1.6 STELCzech Republic, Poland 1.6 TWAArgentina, Mexico, United Kingdom 2.0 TWAPeople's Republic of China 2.5 TWAAustralia 3.0 STELRumania 3.2 CCzech Republic 4.1 CIndonesia 5.0 CEgypt, Republic of China 5.0 TWA


• Basert på data fra epidemiologiskeundersøkelser, forsøk med mennesker ellerdyreforsøk

• Setter så en grense basert på dissedataene der ingen skader på kort eller langsikt oppstår - er det mulig?

Framgangsmåter for å sette OELsog administrative normer

12.04.02 Metoder for fastsettelse av administrative normer (OELs) i Norge og EU 11 12.04.02 Metoder for fastsettelse av administrative normer (OELs) i Norge og EU 12

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Megamusforsøket

Egentlig ’kilo’ mus forsøkca 23.000 mus eksponertfor 2-actylaminofluorene




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Begrensninger i beskyttelse• ACGIH

...a small percentage of workers may experiencediscomfort ....

• EU...may not provide adequate protection for everyindividual...

Grenser med og uten terskel EUHealth based OELs ...clear threshold dose below whichexposure to the substance in question is not expected tolead to adverse effects...

Pragmatic OELs ...for some adverse effects (in particulargenotoxicity, carcinogenicity and respiratorysensitisation) it may not be possible on presentknowledge to define a threshold..


General principlesgraduation of effects

• No effects observed• Compensatory effects or early effects of

dubious significance without adverse healthconsequences

• Early health impairment (clear adverseeffects)

• Overt disease, possible death


Responses to irritantsgraduation

• No effects observed; no awareness ofexposure

• Very slight effects; awareness ofexposure

• Slight irritant effects or nuisance(e.g. smell); easily tolerable

• Significant irritation/nuicance, overthealth effects; barely tolerable

• Serious health effects (e.g. Pulmonaryoedema); intolerable


(1) General procedure for settingOELs

• Assemble all available data on hazard of the substance• Determine whether the database adequate for the

setting of an OEL• Identify the adverse effects that may arise from

exposure to the substance• Establish which adverse effect(s) is (are) considered to

be crucial in deriving the level of the OEL• Identify the relevant studies (in humans or animals)

which characterise these key effects. Carefully reviewthe quality of these studies

• Establish whether the substance acts via a non-threshold mechanism or whether a conventional(threshold) toxicological model can be used

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• Assess the dose/response data for each key effect.Establish ”no observed adverse effect levels”(NO(A)Els) wherver possible, otherwise establish”lowest observed adverse effect levels” (LO(A)Els)

• Decide whether a short term exposure limit (STEL)is required in addition to an 8 hr time weigthed(TWA) limit

• Establish a numerical value for an 8 hour TWA OEL• Establish a numerical value for STEL (if required)• Document the entire process such the rationale for

the OEL is clear

(2) General procedure for settingOELs


Information relevant to theestablishment of OELs

• Information on non-threshold effects• Information on long term effects and the

effects of repeated exposure by anapropriate route

• Information on short term (acute) effects(effects of a single exposure)

• Information of target organ(s) and thenature of the effects

• Information on the methodology ofmeasurement of airborne levels


Human and animal data andlaboratory studies

• Individual case reports, studies in humanvolunteers, cross-sectional studies andcohort and case-control studies

• Repeated exposure data, single exposuredata, routes of exposure andtoxicokinetic data

• Other information


Developmental toxicity profile of Thalidomide (1)Threshold doses (mg/kg*day oral)

G=growth retardationD=death/abortionM=malformationF=functional alteration*=concordant effect to humana No devolpment toxicity reportedb No development toxicity reported @ 20 mg/kgc Dosage given is unstated in reports, assumedto be in terapeutic range (of 0.5 to 8 mg/Kg/d)

Data fra Schardein and Keller; Potential human developmentaltoxicants and the role of animal testing in their identification andcharacterization CRC Critical Reviews in Toxicologyvol 19(1989)251-339


Growth.r. Death/ab.Malform. Funct.aMouse 50 62 62Rat 50 50 ca67Rabbit 50 *25Hamster ca0.75Cat 500Dog 200 30Armadillo 100Guinea piga

Ferret ?Pig 15Cyno monkey 10 *10Rhesus monkey 12 *12Stump-tailed monkey *5Bonnet monkey *5Japanese Monkey *20Baboon 5 *5Marmoset 45 *45Green monkey 30 *10Bush babyb

Human 0.5c 0.5c 1c 0.5c

Developmental toxicity profile of Thalidomide (2) Threshold doses (mg/kg*day oral)


NH

O

O N

O

O

Thalidomide (50-35-1)


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Growth. Deadt/ab Malform. Funct.Mouse 50 62 62Rat 50 50 ca67Rabbit 50 *25Hamster ca0.75Cat 500Dog 200 30Guinea piga

Pig 15Cyno monkey 10 *10Rhesus monkey 12 *12Stump-tailed monkey *5Bonnet monkey *5Japanese Monkey *20Baboon 5 *5Marmoset 45 *45

Human 0.5c 0.5c 1c 0.5c



“Styret for arbeidstilsynet”

• Myndigheter representert?

• Representanter fra arbeidstakerorganisasjoner

• Representanter from arbeidsgiverorganisasjoner

Treparts

sammensetning


Nye rutiner (1)

1. Identity of the substance2. OELs Norway and other countries3. Chemical and Physical Data4. Toxicological Data and Health effects5. Use and Exposure6. Evaluation7. Recommendation (Conclusion)8. References

Documents


Nye rutiner (2)

• Norway high OEL relative other countries• Missing OEL for important substance• New OEL published by EU• New Criteria document from NEG• Risk evaluation EU• New import Documentation aboutsubstance• Proposal from Institutes, Organisationsetc• Trades in focus

Criteria for priority of substances


Evaluation of hearing

New procedures - new routines (3)1-2

3-4

5-6

7-8

9-10

11-12

13-14

15-16

17-18

19-20

21-22

23-24Timemonths

Boarddecisions

Tripartiteconsultations

HearingDocument production

Collection andpreparation of Data

Proposal ofnormandannotation

Warning

Afterw….


New procedures - new routines (4)

• Summary of important studies• Dose response associations• Critical effect(s)• Recommendations• Establish their own rules, key document

EXPERT

GROUP

TEAN

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New procedures - new routines (5)

???• Still a tripartite system• Not fully health based• Relative transparent system• Weight of health, economy andtechnical considerations?


1978 og 2001


• Improvement of evaluation• Transparency in decisions• Increase the qualifications in Norway toevaluate health risks with chemicals atwork places• Waste of Resources? - European co-operation?


http://folk.uio.no/steinaov

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