11

OELs vs. DNELS – Why Are They (Not) the Same?

Tracy A. Kimmel, Ph.D., DABTSafeBridge Consultants, Inc.

AIHA Webinar15 June 2011

OEL Methodology

• OEL = Reference level (UF1,2,3 x SF x MF x A x V)

– UF1,2,3 = composite uncertainty factors

– SF = safety factor (severity and confidence)

– MF = modifying factor (bioaccum., sens., etc.)

– A = Absorption (bioavailability) correction factor

– V = Volume of air inhaled in 8-hr shift (10 m3)

DNEL Derivation

AFTotal

DescriptorDose[modified]DNEL

DNEL (Worker-Inhalation-Long-Term) = x mg/m3

What’s The Concern?

• Over 150,000 substances exist in commerce– Of these, only about 1,500 substances (~1%)

have OELs anywhere around the world

• Every substance in commerce in the EU will have a DNEL

• “Safe” level required for risk management

OEL Development Timeframe

• Prioritization of substances needing OELs• Diversity of committee membership• Expertise & Experience required• Availability of data• Perception of committee setting OELs• Resources: time, data, and finance• “Harmonization” of OELs

DNELs and Health-Based OELs

• Both can generally be seen as quantitative estimates of “safe” levels of exposure to chemicals– Health-based OELs for workers only

(inhalation exposure)– DNELs for workers and consumers

(general population) by inhalation, dermal and oral routes of exposure

DNELs and Health-Based OELs (cont’d)

• Processes for derivation show some similarities but also significant differences– Starting dose descriptor; SF/AF differences;

peer-review

• Have different intended purposes

How They Differ

OELs (Health-Based)

• Levels of acceptable risk for workers based on NOAELs and LOAELs with SF (AF)

• Developed by EHS professionals, governmental agencies, from published data– Utilize professional judgment

and ‘weight of evidence’ with peer review by experts who draw comparative analogy between animal and human toxicology parameters

– Target 10 – 50% of the OEL for compliance

DNELs (Not Health-Based)

• Threshold-based non-cancer endpoints considered to be “No Effect Levels” for humans based on NOELs and AFs

• Developed by manufacturers and importers

• Worker DNELs are calculated from Population DNELs

– Prescriptive & conservative – not based on judgment

– May be derived from proprietary data

How They Differ (Cont’d)

OELs (Health-Based)

• Single value, calculated from Point of Departure = effect considered to be most serious/relevant

DNELs (Not Health-Based)

• Multiple calculations for each endpoint and each relevant exposure route; the lowest value is selected as the Leading Effect and used as the final DNEL

More Confusion

• “When applying the REACH guidance (ECHA, 2008),…the summarizing tables and figures only present default values for different AFs. Moreover, these defaults are often the lowest values of a selected range, whereas higher AFs are described as needed for exceptional cases.”

Schenk and Johanson

Toxicol Sci 121(2):408-16, 2011

More Confusion (Cont’d)

• “For instance, the default AF for issues related to the reliability of the dose-response relationship, including extrapolation from LOAEL to NOAEL, is 1…Meanwhile, the body test reads ‘it is suggested to use an AF between 3 (as minimum/majority of cases) and 10 (as maximum exceptional cases) Thus one assessor, reading only the table, might apply an AF of 1, whereas another assessor, reading also the text, might apply an AF of 3, or perhaps even 10…”

Schenk and Johanson

Toxicol Sci 121(2):408-16, 2011

DNEL = OEL (Sometimes)

Registrants can use health-based IOELVs as DNELs, under certain conditions OELs established by regulatory agency cannot

be used as DNELs

DNEL = OEL? (sort of)

OELs, DNELs: eSDS Sect. 8.1

• All DNELs (including DMELs) calculated for the relevant human exposure pathways, as well as applicable Member State1, health-based OELs are required to appear on REACH-compliant eSDSs2

– May have multiple DNELs listed (i.e. for inhalation and dermal exposure for long and acute durations of exposure for both workers and consumers ….)

– Potential source of “confusion” for the eSDS user1Where the eSDS is to be provided2Commission Regulation (EU) No. 453/2010 amending Regulation(EC) No. 1907/2006 (REACH) – effective 12/1/2010

EU CAD

• The…regulation is clear that REACH “…should apply without prejudice to Community workplace and environment legislation.”

• In particular, the text of the REACH regulation goes on to say that the “Regulation shall apply without prejudice to a number of Directives including: “… Directive 98/24/EC….” [the EU Chemical Agents Directive; CAD]– CAD obligates employers to protect the heath and safety of

workers from risks of hazardous chemicals

– CAD defines “OEL”

EU CAD (Cont’d)

• Obligation under the EU CAD to monitor for compliance with the National (Member State) OEL

• DO NOT monitor to the DNEL– No regulatory (or any other) obligation whatsoever to

do this– Not a ‘default” limit for exposure control

– Not what DN(M)ELs are intended to be used for

DNELs do not displace OELs

Margins of Safety

• Comparison between margins of safety used by SCOEL (IOELVs) and those used to derive worker-DNELs by strict adherence to REACH guidance

• Composite safety factors used by SCOEL are generally lower than those used by REACH for worker-DNEL development– Worker-DNELs would generally be lower than health-based OELs

Worker-DNELs ≠ OELs

Schenk and Johanson

Toxicol Sci 121(2):408-16, 2011

Margins of Safety (Cont’d)

Schenk and JohansonToxicol Sci 121(2):408-16, 2011

OEL vs. DNEL: N-Hexane

SCOEL REACH

Point of Departure

Peripheral neuropathy by

inhalation (LOAEL)

Peripheral neuropathy by

inhalation (LOAEL)

Dose 70 ppm 70 ppm

Uncertainty Factor

3.5 (AF of 2 + rounding

convention of 1.75)

15

IOELV/DNEL 20 ppm ~5 ppm

OEL vs. DNEL: DMF

SCOEL REACH

Point of Departure

Liver effects in mice by

inhalation (LOAEL)

Liver effects in mice by

inhalation (LOAEL)

Dose 7.8 ppm/6 hr 3.9 ppm/8 hr (adjusted

value)

Uncertainty Factor

1 12.5

IOELV/DNEL 5 ppm 0.32 ppm

OELs vs. DNELs

• EU Working Party on Chemicals (2010):– “… unanimously agreed that there was no

simple relationship between DNELs and OELs, and that the real issue for employers was how to respond to additional duties imposed by REACH as well as the continuing requirements under occupational health and safety legislation.”

OEL vs. DNELs (Cont’d)

• Both OELs and DNELs are useful in establishing “adequate” control of exposure(s)– Especially for inhalation exposures in the

workplace– DNELs also set for dermal exposures lead

to controls

Sharing The Sandbox

• Co-existence (EU Working Party, 2010):– “Where both a national OEL and a DNEL … have

been derived for a substance, and the risk management measures in the safety data sheet are significantly more restrictive, employers are responsible for the protection of their employees, and should seek to resolve the situation with their suppliers and, as appropriate, with the relevant authorities.”

• Need to be familiar with the purpose of each as part of worker protection

Sharing The Sandbox (Cont’d)

• DNELs and OELs will need to (and do) co-exist…– Already co-exist on REACH eSDSs

(Section 8.1)– Co-exist where IOELVs are used as DNELs

1See Schenk and Johanson, in Toxicological Sciences (advanced online publication: 3/9/2011)

Sharing The Sandbox (Cont’d)

• …However, “differences” between them will undoubtedly create confusion in terms of legal compliance, risk management and risk communication1

– Will be important for EU and National authorities to “…clearly communicate the relation between OELs and worker-DNELs and give guidance on how to handle potential conflicts between different OEL values.”1

1See Schenk and Johanson, inxicological Sciences (advanced online publication: 3/9/2011)

• Although DNELs are not required on MSDSs in USA, they will be available on the internet SDSs– Worker DNELs could become ‘de facto’ OELs for

some companies and possibly some countries– Questions the validity of our historic TLVs, MAKs,

WEELs, and other health-based guideline values– Creates opportunity for litigation against employers

and the OEL-setting bodies (= $$$$$$$$$$$)

Challenging the OEL

Concerns About DNELs and Health-Based OELs

• Most chemicals do not have PELs, TLVs, or a unified, codified exposure limit

• Can regulators use DNELs to demonstrate non-compliance?

• Will EU member-states abandon their current OEL processes and default to the DNELs?

• Will the EU grab hold of the DNELs and turn them into IOELVs?

• Will manufacturers derive overly conservative DNELs to shield themselves from liability?

Concerns About DNELs and Health-Based OELs (Cont’d)

• Will manufacturers “adjust” their DNELs to achieve a favorable RCR?

• Will we see multiple DNELs for the same substance when manufacturers can’t agree?

• Will manufacturers derive overly conservative DNELs to shield themselves from liability?

• Will manufacturers “adjust” their DNELs to achieve a favorable Risk Characterization Ratio?

• Will we see multiple DNELs for the same substance when manufacturers can’t agree?

Resolution?

• Adjust DNELs for use as OELs– That risk typically not quantified, led to

conservatism in IH practice– Along with statistical conservatism if

exposures > 50% OEL– Also embodied in the < 1/2 to 1/10 OEL concept

to prove compliance

Possible Path Forward

• One obstacle for OEL development was lack of data

• REACH will greatly expand the dataset on substances and there will probably be subsequent testing and development of more data

• May become an opportunity for advancement of OELs