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Safe&Healthy

Members of the 3M Medical DepartmentMay 24, 2011

REACH Panel Presentations & Discussion: An Industry Perspective

© 3M 2011. All Rights Reserved.

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Panel Members▪ All panel presenters are from the Medical Department

within 3M.▪ The 3M Medical Department is a corporate staff group

that provides technical support to the various business units and subsidiaries that compose 3M.

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Panel Members▪ Nathan Pechacek, MS, DABT – Toxicologist

● Involved in health hazard assessments and developing DN(M)ELs for REACH registrations

▪ Cheri Kedrowski, MS – Technical Manager, Regulatory Services● Corporate project manager for 3M’s REACH Chemical Safety Reports

▪ Catherine Jacobson, PhD, DABT – Toxicologist● Leads 3M’s health hazard assessment project; responsible for

classification and labeling for REACH registrations

▪ Robert Roy, PhD, DABT – Toxicologist● Leads the 3M team that develops DN(M)ELs for REACH registrations

▪ Josie Walton, MPH – Industrial Hygienist● Technical lead of Chemical Safety Report team; responsibilities include

use collection, exposure assessments, and exposure scenarios

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Disclaimer▪ While the information presented is believed to be

correct, it is presented without representation or warranty by the authors or 3M Company. Informed, independent judgment must be exercised in applying the information presented to any particular situation. Any opinions expressed are those of the authors and not 3M Company.


Safe&Healthy

Cheri Kedrowski3M’s Preparation for REACH

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REACH Impact to Industry▪ Preparation for REACH▪ Compliance with REACH▪ Case Studies

● Acrylate monomer case study● HCl case study

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Preparation for REACH (2001-2003)▪ 3M’s preparation for REACH began in February 2001 when the

European Commission (EC) unveiled its “white paper”describing a new system for chemical regulation● EU and U.S. regulatory specialists assigned to track progress and

interface with trade associations

▪ Draft proposed regulations May 2003 (1,100 pages!)● 3M submitted 37 pages of corporate comments in July 2003 on topics

ranging from handling of polymers to protection of CBI to downstream user responsibilities

● 3M Germany also submitted separate comments on medical devices● 6000 submissions received by EC

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Preparation for REACH (2004-2005)▪ EC released proposed REACH regulations in October

2003● Review by European Parliament and European Council● Continued monitoring by regulatory specialists● In 2005, 3M created global REACH Steering Team

• Assigned a management champion in 3M Europe• Assigned a project leader in 3M Europe• Hired new REACH technical staff in Europe• Assigned additional U.S. corporate EHS staff to REACH, including

environmental scientists, toxicologists, industrial hygienists, and regulatory specialists

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Preparation for REACH (2006)▪ European Parliament adopted numerous amendments

to the proposed text of REACH on November 17, 2005● Many favorable changes for industry, but European Council

committees offered different version● Many varied readings and efforts to arrive at common

position in 2006● During uncertainty in 2006, 3M:

• Continued to track regulatory developments• Continued to realign resources with REACH• Communicated extensively with business units regarding regulatory

developments and anticipated business impacts

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Compliance with REACH (2007)▪ Final REACH regulation released in December 2006

and entered into force on June 1, 2007● Established REACH Coordination Center in Europe

• Pre-registration (and eventually registration)

● Established REACH Program Office in U.S.• Determine monomers used to manufacture polymers• Obtain data on articles with intended release• Develop volume tracking system• Coordinate with U.S. staff groups

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Compliance with REACH (2008)▪ Pre-registration due December 2008 (2005-2007 data)

● Pre-registered over 500 substances and 1500 substance-Legal Entity combinations (out of 140,000 pre-registrations received from 65,000 companies)

▪ Composition data● Continue to work with suppliers to define monomers● Conduct analytical testing to define monomers and ratios● Identification of Substances of Very High Concern (SVHCs) in products (first list

October 2008)▪ IT Systems

● Improvements to volume tracking (automation of certain supply chain categories)● Development of Chemical Safety Report (CSR) / Safety Data Sheet (SDS) annex

tool to store and report use, exposure scenario, and assessment data▪ Engagement of staff groups per their specialty, as needed (toxicology,

industrial hygiene, environmental science)

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Compliance with REACH (2009)▪ REACH CSR and SDS Teams established – led out of 3M Medical

Department, with global members▪ Substance teams established for all substances in Phase I of registration and

new substances – led out of Europe with global members▪ Volume updates (2006-2008)▪ Ongoing SVHC identification in products (list additions)▪ Establishment of 3M’s roles in Substance Information Exchange Fora

(SIEFs) (more later)▪ Manufacturing use collection for all substances in Phase I of registration

● Identifying downstream facilities and customers● Training of plant industrial hygiene professionals● Basic data for IUCLID (REACH registration database)● Historical monitoring data for exposure assessment

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Compliance with REACH (2009)▪ Customer use collection

● Identifying product groupings● Training of EU Technical Service Reps● Basic data for IUCLID ● Detailed modeling data for exposure assessment

▪ Hazard assessment (more later)● Placement of studies● Waiving arguments● Robust study summaries● Endpoint summaries

▪ Continued development of CSR/SDS annex tool

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Compliance with REACH (2010)▪ Ongoing SVHC identification in products (list additions)▪ Analytical testing▪ Volume updates (2007-2009), including new

substances▪ Continued hazard assessment (results received from

placed studies)▪ Classification and labeling (more later)▪ Derived No Effect Levels (DNELs) and Predicted No

Effect Concentrations (PNECs) (more later)

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Compliance with REACH (2010)▪ Exposure assessment (more later)

● Exposure scenario development● Modeling and monitoring● Risk characterization

▪ Finalization of CSR/SDS annex tool to store and report use, exposure scenario, and assessment data

▪ Assembly of CSRs (4 “full” and 12 partial)● 3M as lead registrant and as co-registrant

▪ Assembly and submittal of registration dossiers! (28)● 3M as lead registrant and as co-registrant

▪ Preparation of SDS annexes

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Case Study: An Acrylate Monomer▪ High volume

● CSR required● Exposure assessment for man-via-the-environment

▪ 3M Subsidiary lead registrant (manufacture) and 3M Europe co-registrant (import)● Use collection from 3M facilities and end customers● More human exposure pathways to consider for DNEL

derivation● Exposure assessment by modeling and monitoring

▪ Exposure assessment stops once polymerized

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Case Study: Hydrochloric Acid (HCl)▪ High volume

● CSR required● Exposure assessment for man-via-the-environment

▪ 3M Subsidiary co-registrant (manufacture as by-product)● 3M could not use entire joint CSR because Hydrofluoric Acid (HF)

impurity• Additional classification and labeling• Needed to derive HF DNELs in addition to HCl DNELs• Separate exposure assessment

● Use collection from 3M facilities and industrial customers● Fewer human exposure pathways to consider for DNEL derivation (no

dermal)● Exposure assessment primarily by monitoring● Measurement of both HCl and HF in monitoring samples, with separate

risk characterization for each


Safe&Healthy

Hazard AssessmentCatherine Jacobson

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Hazard Assessment▪ Evaluate and integrate available data

● Gather and share existing data● Consider data needs: Annexes VII to XI of REACH● Identify data gaps● Generate new data, propose testing strategy, or present a

waiving argument

▪ Derive hazard thresholds for human health and the environment

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Hazard Assessment▪ Establish classification and labeling

● According to criteria in the CLP• Classification is, e.g., Eye Irrit. 2, Repr. 1B, STOT RE 2• Labeling includes signal word, pictograms, hazard statements, and

precautionary statements

● However, Harmonised classification has to be respected and you should not modify

any of those hazard classes/differentiations. If the substance has a harmonised classification for some hazard classes/differentiations you should classify for other hazards according to available and reliable data.

CLP: Regulation on Classification, Labelling, and PackagingSTOT RE 2: Specific Target Organ Toxicity, Repeated Exposure, Category 2

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Substance Information Exchange Forum▪ SIEFs are formed for substances with more than one

potential registrant● To facilitate the sharing of hazard data● To avoid duplication of studies

▪ SIEFs jointly● Submit data required under Annexes VII to XI● Establish classification and labeling● Propose further testing

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3M’s Experience▪ 3M plans to register >500 chemicals 2010 - 2018

● Several chemicals on our own● Most chemicals with SIEFs

• Leading• Involved• Passive

▪ Our specified role greatly determines our involvement in hazard determination and in classification and labeling

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3M’s Experience▪ Sole or lead registrant

● Usually - data for each endpoint are limited and are from fairly recent studies conducted according to guidelines

● Example: An acrylate monomer• Acute oral and dermal toxicity data; acute inhalation study waived• Eye and skin irritation studies; skin sensitization study• Repeat-dose (28-day) oral study; may need to do 90-day oral study• In vitro genotoxicity studies and dermal carcinogenicity study• Dermal screening reproductive study and oral teratology study;

may need to do two-generation study

• We’re bound by official classification as eye, skin, and respiratory irritant

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3M’s Experience▪ Involved in a SIEF or passive member of a SIEF

● Data analysis is often more complex• Data may be more plentiful• Data may be older and not from guideline-compliant studies• Data may not be owned by the registrants• Non-manufacturer opinions seem to me to be dismissed

● Many SIEFs are not willing to stray from the harmonized classification

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3M’s Experience▪ Many SIEFs are not willing to stray from the

harmonized classification● Exception: Our substance is slightly different –

Example: Hydrochloric acid with hydrofluoric acid• Deviation is based on official classification of hydrofluoric acid per

the Dangerous Substances Directive (DSD) and per CLP and the DSD thresholds and CLP mixture calculations

>0.1%, <1% HFDangerToxic in contactwith skin

>0.1%, ≤0.25% HFWarningHarmful in contactwith skin

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Outputs of Hazard Assessment Process▪ Robust study summaries

● Submitted as part of registration dossier● Used to generate DNELs

▪ Classification and labeling● Submitted as part of registration dossier● Appears on safety data sheet (SDS) and label● Determines required packaging● Determines need for exposure assessment● Affects customer acceptance● May spur additional regulation

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Available on ECHA’s website: http://apps.echa.europa.eu/registered/registered-sub.aspx

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For each endpoint, classify or state the reason for not classifying:•data lacking, •inconclusive data, or •conclusive data that are not sufficient for classification

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Safe&Healthy

Robert RoyREACH Derived No Effect Levels (DNELs)

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EU REACH: DNELs▪ Derived No-Effect Level (DNEL): The level of

exposure above which humans should not be exposed● Used in REACH risk characterization● Established for the substance based on:

• Population: workers, consumers and the general population (via environment)

• Route: inhalation, dermal and ingestion exposure• Duration: acute and long-term exposure

● Derived for chemicals having a “threshold” mode of action● Potential for many different DNELs because of different

combinations and exposures

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EU REACH - DMELs▪ No DNEL can be derived for non-threshold mutagens

or carcinogens (as per ECHA)● Assumed a no-effect-level cannot be established for these

substances

▪ In such cases, a DMEL (Derived Minimal Effect Level) is derived (if data permit)● DMEL = a reference risk level which is considered to be of

very low concern• Occupational = 1E-05• Consumer/General population = 1E-06

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REACH: DNELsExposure Pattern Worker DNEL/DMEL General Population

DNEL/DMEL

Acute-Inhalation-Systemic effects √ √Acute-Dermal-Local effects √ √Acute-Inhalation-Local effects √ √

Long-term-Dermal-Systemic effects √ √Long-term-Inhalation-Systemic effects √ √Long-term-Oral-Systemic effects Not Relevant √Long-term-Dermal-Local effects √ √Long-term-Inhalation-Local effects √ √

General Population = Consumers (+ subpopulations) and Humans Exposed via the Environment

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“Default” Human Exposure Patterns▪ Many are possible, but if need to start DN(M)EL

derivation before they are finalized, can start with:● Worker/Inhalation/Long-Term/Systemic health effects● Worker/Dermal/Long-Term/Systemic health effects● Worker/Inhalation/Acute/Systemic health effects ● Consumer/Oral/Long-Term/Systemic health effects● Consumer/Dermal/Long-Term/Systemic health effects● Consumer/Inhalation/Long-Term/Systemic health effects● Consumer/Inhalation/Acute/Systemic health effects

DNELs for systemic effects, local effects, or both

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3M DN(M)EL Derivation Team - Process▪ Gather all available toxicity data for the chemical

● Robust Study Summaries● Other available sources (from electronic databases, etc.)

▪ Draft DN(M)ELs derived using ECHA Guidance (R.8)● For known human exposure patterns (if known)● For default human exposure patterns (data availability)

▪ Peer-Review of Draft DN(M)ELs● By other members of the Team

• Assess data interpretation, methodology used, calculation inputs, etc.

▪ Final DN(M)ELs documented and communicated

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4 Steps to DNEL Derivation▪ STEP 1: Gather typical dose descriptors from all

available studies on the different human health endpoints● Dose Descriptor: A value obtained from a toxicity test or

from other relevant data• NOAEL; LOAEL; BMD; BMDL10

• LD50; LC50; T25 (for carcinogenic response)• Odds Ratio (OR); and Relative Risk (RR) [epidemiological

descriptors]

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4 Steps to DNEL Derivation▪ STEP 2: Decide on the substance’s Mode of Action

(MOA)● Threshold MOA:

• DNEL will have to be derived for that endpoint(s) based on the most relevant dose descriptor(s)

• Non-carcinogens

● Non-Threshold MOA:• Carcinogens• No DNEL will be derived• Derived Minimal Exposure Level (DMEL) will be calculated

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4 Steps to DNEL Derivation▪ STEP 3: Modify, when necessary, the relevant dose

descriptors for each endpoint to the correct starting point for:● Route-to-route extrapolation of toxicity data

• Predict the total amount of a substance administered by one route that produces the same adverse effect obtained for a given amount of that substance administered by another route

• Oral → Dermal; Oral → Inhalation; Inhalation → Oral● Exposure conditions (study to human exposure)● Respiratory volumes (animals to humans)● Details at: ECHA Chapter R.8

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4 Steps to DNEL Derivation▪ STEP 4: Apply Assessment Factors (AFs) to the

“modified” dose descriptor to get endpoint-specific DNEL● AFs used to account for the uncertainties in the extrapolation

procedure and the available data set• AFs are numerical values (defaults provided)

● AF categories:• Interspecies differences (allometric scaling for metabolic rate, etc.)• Intraspecies differences (to “cover” all sub-populations such as kids,

elderly, etc.)• Differences in duration of exposure (sub-acute → subchronic → chronic)• Dose-response issues (to get to the NOAEL)• Quality of the entire database

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Overview – DNEL Derivation

AF TotalDescriptorDose[modified]DNEL =

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EU IOELVs▪ Indicative Occupational Exposure Limit Values

● Directives 91/322/EEC, 2000/39/EC, and 2006/15/EC● Health-based, non-binding values

▪ Member states must take IOELVs into account when they create their National OELs

From ECHA Chapter 8 Appendix R.8-13▪ “When an EU IOELV exists, the registrant may, under

conditions described below, use the IOELV in place of developing a DNEL.”

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DNELS: Acrylate Monomer▪ DNELs1 were derived (as per Chapter R.8) for routes,

duration and frequency of exposure as defined in the ES:● Worker/Dermal/Long-Term/Systemic● Worker/Inhalation/Long-Term/Systemic● Consumer/Oral/Long-Term/Systemic● Consumer/Dermal/Long-Term/Systemic● Consumer/Inhalation/Long-Term/Systemic

1Data used: Dermal NOAEL from the combined repeat dose and reproductive/developmental study in rats and Oral NOAEL from the 28-day rat gavage study

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DNELS: HCl with HF▪ DNELs1 were derived for HCl (as per Chapter R.8) for

routes, duration and frequency of exposure as defined in the ES:● General Population/Inhalation/Long-Term/Systemic● General Population/Oral/Long-Term/Systemic● Worker/Inhalation/Long-Term/Local = 8-hour TWA IOELV● Worker/Inhalation/Acute/Local =15-min IOELV STEL

1Data used: The NOAEL for systemic toxicity in rats exposed to HCl gas via inhalation for 6 hours/day for 90 days (source: 2002 OECD SIDS Document)

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DNELS: HCl with HF▪ DNELs1 were derived for HF (as per Chapter R.8) for

routes, duration and frequency of exposure as defined in the ES:● Worker/Inhalation/Long-Term/Systemic = 8-hour TWA IOELV● Worker/Inhalation/Acute/Local =15-min IOELV STEL● General Population/Inhalation/Long-Term/Systemic● General Population/Oral/Long-Term/Systemic

1Data used: Occupational inhalation NOAEL and population ingestion NOAEL

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REACH: Use of DNELsCritical to REACH Risk Characterization (RC)▪ Exposure estimate(s) are compared to health hazard

information in the form of the DNEL● Called the Rick Characterization Ratio (RCR)

RCR = Exposure ÷ DNEL

▪ If Exposure < DNEL → Risk adequately controlled▪ If Exposure > DNEL → Risk NOT controlled

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DN(M)ELs and RMMs and OCs▪ DN(M)ELs → used in the REACH risk characterization

process (via the RCR) for establishing:● Risk Management Measures (RMMs) and Operational

Conditions (OCs)

▪ The application of appropriate RMMs and OCs is, in many cases, critical for controlling risk during use of the REACH-regulated substance

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RMMs and OCs▪ RMM: “… any action that is introduced during manufacture or

use … in order to prevent, control, limit or reduce exposure of humans ….”● Containment;● Local exhaust ventilation (LEV);● Gloves; respirators; other PPE

▪ OC: “… any action that prevails during manufacture or use …that as a side effect might lead to or increase exposure ….”● Duration and frequency of use/exposure● Applied amount of chemical used/applied, etc.● Process temperature

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REACH: Your Company Use of DNELs

Case 1: Your Company as a manufacturer (supplier) of REACH-regulated substances:

▪ Obligation to communicate to downstream users (DUs) how to use the substances in a way that risk is adequately controlled (“safe” use)● Communicate the appropriate RMMs and OCs (as part of the

defined Exposure Scenario)

▪ To-date → RMMs and OCs have been presented as both specific and generic

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REACH: Your Company Use of DNELs

Case 2: Your Company as a downstream user (DU) of REACH-regulated substances:

▪ Obligation to use the substances in a manner consistent with the specified RMM(s) and OC(s)● Application of specific RMMs and OCs delineated by your

vendor/supplier

▪ Ultimately it is the responsibility of the DU to decide what RMMs/OCs are necessary to comply with REACH● DU must decide how exactly to follow/implement them

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OELs, DNELs: eSDS Section 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 ….)

• See Table in Slide 7 for potential combinations

● May be a significant source of “confusion” to 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

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DNELs & OELs: Registered SubstancesSubstance Health-Based OEL 1 DNEL2

Diethylene Glycol Monomethyl Ether 6 ppm 6.75 ppm1,6-Hexanediamine 0.5 ppm (TLV®) 0.12 ppmIsoprene 3 ppm 2 ppm1-Bromopropane 10 ppm 17 ppmDimethylformamide (DMF) 10 ppm 5 ppm (IOELV)1,4-Dioxane 20 ppm (UK = 25 ppm) 20 ppm (IOELV)Methyl Mercaptan 0.5 ppm 0.38 ppmN-Vinyl-2-pyrrolidone (NVP) 0.05 and 0.1 ppm 0.02 ppm (DMEL)Naphthalene 10 ppm (IOELV)3 ≈ 5 ppmChlorobenzene 5 ppm (IOELV)4 13.5 ppm

1 Examples: EU Member State OELs2 DNEL for W/I/L-T/Systemic or W/I/L-T/Local from the ECHA www site (for registered substances)3 Germany OEL = 0.1 ppm4 Germany OEL = 10 ppm; UK OEL = 1 ppm

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DN(M)ELs and National OELs

▪ Obligation under the Chemical Agents Directive to monitor for compliance with the National (Member State) OEL

▪ DO NOT monitor to the DN(M)EL● No regulatory (or any other) obligation whatsoever to do this● Not what DN(M)ELs are intended to be used for

DN(M)ELs do not displace OELsDN(M)ELs ≠ OELs

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DNELs and Health-Based OELs▪ 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

▪ 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, in Toxicological Sciences (advanced online publication: 3/9/2011)

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Conclusions: DNELs and OELs▪ Derivation of both have similar components as well as

different components● Need to understand how each is derived (including

limitations)

▪ Are derived for different purposes● Need to be aware of regulatory and non-regulatory impacts

▪ Will co-exist with each other● May, however, cause significant confusion to health & safety

professionals

▪ Need to provide training regarding their interpretation and intended use(s)


Safe&Healthy

Exposure Scenario DevelopmentJosie Walton

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AgendaI. REACH Exposure ScenariosII. Two case studies – Acrylate Monomer and HCl w/HFIII. REACH Exposure Assessments


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What is a REACH Exposure Scenario?▪ Defined by a set of Risk Management Measures (RMMs) and

Operating Conditions (OCs), together called Conditions of Use▪ Described by Use Descriptors

● Process Category● Environmental Release Category● Sector of Use● Product Category (for consumer products)● Article Category (for substances incorporated into articles)

▪ Description of Activities further characterizes ES and are givenby “standard” phrases

▪ Set of default OCs usually used to describe “conditions which prevail”

▪ Downstream Users must adhere to Conditions of Use


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Process Category


▪ ECHA has identified 29 Process Categories▪ Will be one of the ways in which customers will

compare their own use▪ Will drive modeling results▪ One Process Category per Use or per Task?▪ Method of assignment may depend on sector and end

use▪ Not always clear as to what activities are included

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Challenges▪ AIHA vs. REACH exposure assessment methods▪ Defining the scope of the exposure scenario▪ Consolidation of Uses into a single exposure scenario▪ Identifying tasks for each Use▪ Identifying determinants of exposure▪ Evaluating IH sampling data▪ Selecting the appropriate Process Category for Tier I

modeling▪ General vs. specific Risk Management Measures


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Exposure Scenario Development▪ Determine scope

● Review data from the field● Discussions with plant IH and EHS staff

▪ Identify Uses and Tasks● Lump Uses together if exposures may be the same● Include only exposure significant tasks for substance of

interest● Apply RMMs and OCs per task when necessary● Consider who is performing the task

• Are tasks performed by a single worker, or are many workers involved?


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Case Study 1: Acrylate Monomer▪ 3M manufactured substance▪ Both environmental and human health classification▪ Uses:

● Synthesized and further processed onsite● Intermediate shipped to other 3M plant where it is further

processed● Intermediate shipped to customer where it is further

processed


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Acrylate Monomer Exposure Scenarios


Use 1: Synthesis

Use 2: Process step

ES 1 – Synthesis and further processing● Same workspace OCs● Same RMMs in workplace● Same Process Category

Tasks● Charging● Sampling● Packaging

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Acrylate Monomer Exposure Scenarios


Process Step 1

Process Step 2

Process Step 3

ES 2 – Three process steps● Same OCs and RMMs● Different Process Categories● Different workers

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Case Study 2: HCl w/HF contamination▪ 3M made substance as byproduct of synthesis process▪ Final product contains <1% HF contamination▪ Physical/Chemical (Corrosive to metal) and Human

Health classification▪ Uses:

● Recovered onsite● Shipped to customer site

• Bleaching agent• Ion regeneration


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Considerations▪ Additive effects of HCl and HF▪ Ancillary tasks (cleaning) ▪ Slight differences in customer use

● One customer performs a single open transfer step

▪ Specific vs. general naming of uses


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HCl Exposure Scenarios


ES 1 – Recovery of byproductClosed systemSamplingCleaning

ES 2 – Processing AidClosed systemSamplingCleaningOpen transfer

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Assigning Use Descriptors▪ Question: Separate uses for cleaning, sampling, and transfer

tasks?


Decision for ES 1:Recovery PROC 2

PROC 2 description: Use in closed, continuous process with occasional controlled exposure (e.g. sampling); Industrial setting;

Decision for ES 2:Processing Aid PROC 3

PROC 3 description: Batch manufacture of a chemical or formulation where the predominant handling is in a contained manner, e.g. through enclosed transfers, but where some opportunity for contact with chemicals occurs, e.g. through sampling

In both cases, we assigned one Process Category to cover all tasks, assuming cleaning could be included

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Exposure Assessment per REACH…


From ECHA Guidance Chapter R14: Occupational Exposure Estimate:

•“To address the reasonable worst-case, it is recommended to select the 90th percentile of the exposure distribution …The reasonable worst-case should not include extreme use or misuse…”

• May take into account existing RMM

•Exposure should normally be understood as external exposure

•Preference – measured data, surrogate measured data, modeled data

•Combination of measured and modeled data allowed

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Using Measured Data▪ Find existing sampling data

● Still relevant to process?● Sufficient in size? (at least 6 for an activity/task)● Do samples represent all tasks?● Full or partial shift?● Representative of scenario?

▪ Percentile for reporting● 75th – well defined, high quality data set, RCR well below 1● 90th – to reflect the entire spectrum of use conditions● 95th – acute exposures


“Representative and Robust”

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Inhalation Exposure Assessment: Acrylate Monomer


Task/Sample Description Task/Sample ID.

Conc.(ppm or mg/m3)

Duration of sample/ex

posure (mins)

Notes

Charging material X Task 1 2.38 60 7 samples 90th percentile. LEV applied.

Taking samples (sampling) Task 2 .4081 15 5 samples 90th percentile. LEV applied.

Charging Material Y Task 3 1.5 30 5 samples 90th percentile. LEV applied.

Filling Task 4 .70 60 3 samples 90th percentile. LEV applied.

8 hour TWA calculation:

(2.38 * 60) + (.40*15) + (1.5 * 30) + (.7 * 60) + (0*315) = .49 mg/m3480

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Inhalation Exposure Assessment: HCl▪ Both long-term and acute assessments were conducted▪ Acute assessment because of acute effects▪ No acute sampling data, but referred to ECHA guidance:“Exposure situations without ‘peak exposure’ (i.e. an acute exposure level clearly

higher than the related full shift exposure level) are very rare. Therefore, in most cases a classification for acute effects should lead to an acute DNEL.”

“The relation between parameters of acute and full shift exposure distributions have been calculated (Kumagai and Matsunaga 1994). The 95th percentile of 15 minute exposure data is about twice the 90th percentile and 4 times the 75th percentile of full shift data collected for the same situation.”

▪ Risk Characterization Ratios (RCRs) were reported separately for HCl and HF because of different endpoints.


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Dermal Exposure Assessment: Acyrlate▪ ECETOC model used

● PROC 3● With LEV● >4 hours

▪ Dermal scenario passed without gloves….…. Should we add gloves to the list of RMMs?

▪ No dermal exposure assessment required for HCl/HF


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Final Thoughts…▪ Process Category descriptions not always clear, but

drive modeling results▪ Companies will have very different approaches▪ Defining the exposure scenario clearly will help

downstream users



Safe&Healthy

3M’s Take-Home MessagesNathan Pechacek

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Take-home messages from the panel▪ REACH Compliance

● Is resource intensive● Requires cross-functional teams with various expertise● Presents challenges in timing of activities● Each registered substance is unique and presents it own

challenges● With experience the process does get easier

3M presentations NLSOT (final) - toxicology.org

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