Abschlussarbeit im Postgradualstudium Toxikologie und Umweltschutz
der Universität Leipzig
Thema:
Preparation of
consolidated exposure scenarios for mixtures under REACh
Verfasser:
Dr. Monica Sica (Biologin)
Leverkusen, 13.09.2012
TABLE OF CONTENTS
1 INTRODUCTION 3
1.1 Main obligations under REACh 3
1.2 Exposure scenario (ES) and safety data sheet (SDS) for substances 4
1.3 ESs and eSDS for mixture 6
1.4.1 CCA 8
1.4.2 DPD+ methodology 8
2. AIM OF THE WORK 10
3. METHODS 11
3.1 Mixtures employed 11
3.2 Application of the DPD+ methodology 12
3.3 Application of the CCA methodology 13
3.4 Derivation of DNELs and risk assessment the whole mixture 13
4. RESULTS 15
4.1 Application of the DPD+ methodology 15
4.2 Application of the CCA 20
4.3 Risk assessment of the mixtures 31
4.4 Comparison of the outcome of the assessment with results obtained from DPD+ and CCA methodology 39
5. DISCUSSION AND CONCLUSIONS 41
6. REFERENCES 47
List of Tables
Table 1 Composition of adhesive mixture ... 11
Table 2 Composition of toluene mixture ... 11
Table 3 Composition of industrial cleaner mixture ... 12
Table 4 Composition of zinc sulphate mixture ... 12
Table 5 LS determination for the adhesive mixture ... 15
Table 6 Exposure estimation for adhesive mixture after application of DPD+ methodology ... 17
Table 7 LS determination for the toluene mixture... 18
Table 8 Exposure estimation for toluene mixture after application of DPD+ methodology ... 19
Table 9 Identification of critical substance for the adhesive mixture ... 20
Table 10 Exposure estimation of the adhesive mixture after application of the CCA ... 21
Table 11 Identification of critical substance for the toluene mixture ... 22
Table 12 Exposure estimation of the toluene mixture after application of the CCA ... 23
Table 13 Identification of critical substance for the industrial cleaner mixture ... 25
Table 14 Exposure estimation of the industrial cleaner mixture after application of the CCA ... 26
Table 15 Identification of critical substance for the zinc sulphate mixture ... 28
Table 16 Exposure estimation of the zinc sulphate mixture after application of the CCA ... 29
Table 17 Exposure estimation of the adhesive mixture ... 32
Table 18 Exposure estimation of the toluene mixture ... 33
Table 19 Exposure estimation of the industrial cleaner mixture ... 34
Table 20 Exposure estimation of the zinc sulphate mixture ... 37
1 INTRODUCTION
1.1 Main obligations under REACh
REACh stands for Registration, Evaluation, Authorization and Restriction of Chemicals and replaced several existing EU regulations and directives concerning the regulation of existing substances and the notification of new substances.
The main objective of the REACh regulation is the safe use of chemicals ensuring a high level of protection of human health and the environment. In this context, manufacturers and importers of substances in quantities of one tonnes or more per year must register these substances at the European Chemical Agency (ECHA) in Helsinki (Finland) to be able to place them on the European market.
ECHA established three deadlines for the registration of chemicals which are regulated by quantities manufactured or imported. Chemicals in quantities > 1000 tonnes/year, > 100 tonnes/year, and substance > 1 tonne/year are required to be registered respectively by 1 December 2010; by 1 June 2013, and by 1 June 2018. In addition, chemicals of higher concern toxicity (Carcinogenic, mutagenic and reprotoxic (CMR) and dangerous for the environment) also have to meet the 2010 deadline.
Manufacturers and importers of substances are obliged to collect detailed information on the properties of the substances that they manufacture or provide at or above 1 tonnes per year. This information is used to carry out an assessment of the hazard and risk that a substance may pose and to set the modality how to control a potential risk. To this purpose the registrant needs to submit a technical dossier for substances of 1 tonnes or more per year and a chemical safety report (CSR) for substance above 10 tons per year. The technical dossier contains information on the identity, manufacture and use, classification and labeling of the substance, guidance on its safe use, (robust) study summaries of the information on the properties (physical chemical properties, information of toxicity, ecotoxicology and environmental fate), proposals for further testing, if relevant (ECHA 2012a). The requested information that determines the properties of a substance differs according to the quantities in which substance is manufactured or imported.
The higher the tonnage the more information on the chemical must be provided. The information requirements are lay out in the Annex VI to IX of the REACh Regulation.
The CSR documents the results of the chemical safety assessment (CSA) (ECHA 2008a).
It contains the hazards assessment (human and environmental), the classification of a substance on accordance with the Directive 67/548/EEC and/or CLP, and determines whether a substance is PBT or vPvB (very Persistent very Bioaccumulative) (ECHA 2009).
The human hazard assessment consists of the evaluation of non-human and human information, classification and labelling and derivation of limit values as Derived No-Effect Level (DNEL), which represents the level of exposure to the substance above which humans should not be exposed. The environmental hazard assessment contains evaluation of information, the classification and labelling and the derivation of limits below which no harmful effects are expected for the environment. These limit values are identified with predicted no effect concentrations (PNECs) (CEFIC 2010a). If the substance is classified as dangerous or is PBT or vPvB, then an exposure assessment and risk characterisation are going to be carried out to ensure that the risks are sufficiently controlled.
The exposure assessment is a quantitative estimation of dose/concentration of the substance to which humans and environment are exposed and is conducted in two steps: 1) development of exposure scenarios (ESs) (for details refer to section 1.2) for each use of the substance; 2) exposure estimation. The exposure estimation for environment relies on the estimation of substance release, assessment of the fate and behaviour of the substance in the environment, and estimation of the exposure level. The exposure estimation of workers and consumers is based on the release of the substances and the predictable exposure levels.
In the risk characterization the expected exposure for humans and environment are compared to the DNEL and PNEC respectively. The quotient of the exposure estimate for humans and environment and the respective DNEL/PNEC is called risk characterization ratio (RCR). In case that the RCR is below 1, the risk is considered to be adequately controlled. If the initial RCR is above 1, further measures are necessary to demonstrate a safe use of the substance (ECHA 2008b)
1.2 Exposure scenario (ES) and safety data sheet (SDS) for substances
An Exposure Scenario describes the conditions under which a substance is manufactured or used and communicates the safe use of a substance as such or in preparations in association with identified use(s). It poses a particular focus on the conditions of use (operational conditions, OCs; e.g. the duration or frequency of use; the amount use; the process temperature, the pH) and the risk management measures (RMMs; e.g. local exhaust ventilation, LEV; certain type of gloves; waste water; gas treatment) to cover exposure to humans and environment (CEFIC
2010b, ECHA 2008c). The ES covers the complete life cycle of a substance: manufacturing, formulation, industrial end-use, professional end-use and consumer end-use .
In order to promote the understating of the ESs ECHA has developed the “Use descriptor system”. It has the purpose to structure and standardize the description of the various uses of substances and preparations, which helps to facilitate the communication between supplier and user. The use descriptor system is based on five separate descriptor-lists (ECHA 2010a):
1) Sector of Use Category(SU): describes in which sector of the economy the substance is used.
This includes mixing or re-packing of substances at formulator’s level as well as industrial, professional and consumer end-uses.
2) Product Category (PC): describes in which types of chemical products ( substances as such or in mixtures) the substance is finally contained when it is supplied to end-uses (by industrial, professional or consumer users).
3) Process Category (PROC); describes the application techniques or process types defined from the occupational perspective.
4) Environmental Release Category (ERC): describes the broad conditions of use from the environmental perspective.
5) Article Category(AC): describes the type of article into which the substance has eventually been processed. This also includes mixtures in their dried or cured form (e.g. dried printing ink in newspapers; dried coatings on various surfaces).
Exposure scenarios generally need to be developed by manufactures and importers as a part of their registration dossier for substances that are dangerous and produced/imported in an amount of 10 tonnes per year or more. They are compiled in the context of the CSA and documented in the CSR and in the safety data sheet (SDS) (ECHA2008c, and ECHA 2011a).
Safety Data Sheets play a key part in transmitting information about the hazardous properties of chemical products to the users. They contain 16 sections which give information about first aid, physical data, toxicity, health effects, reactivity, storage, disposal, protective equipment, and spill-handling procedures to the reader. SDSs were already required under the previous EU
legislation on chemicals (Dangerous Substances Directive (67/548/EEC), Dangerous Preparations Directive (88/379/EEC) and now in the context of REACh have been made an integral part of the regulation system. The SDS must be supplied in an official language of the Member State(s) where the substance or mixture is placed on the market, unless the Member State(s) concerned provide(s) otherwise (Art. 31(5) of REACh) (ECHA 2011a).
In addition, they do not have to be provided where dangerous substances or mixtures are sold to general public with sufficient information to enable to use them safely (REACH Art 31(4), CEFIC 2010c)
Under REACh, downstream users (DUs) are not allowed to place on the market or use substances that are not registered in accordance to REACh. DUs receive information on dangerous substance or mixtures (together with risks for their uses and RMMs to cover such risks) from their suppliers by means of extended SDS (eSDS) containing ESs in form of an annex. DUs have the obligation to verify whether their own uses are covered by the ESs received from their suppliers. In case their use is not covered, DUs should communicate with the suppliers to have the use covered by an ES or alternately they may need to generate their own CSR (ECHA 2008c, CEFIC 2010b).
1.3 ESs and eSDS for mixture
Often the substances are used in mixtures (e.g. chemical products), during their life cycle. Under REACh (Art. 31(1)), formulators of mixtures/preparations need to include substance-related information into extended safety data sheets (eSDS), if mixtures are classified as dangerous according to the Dangerous Preparation Directive (Directive 1999/45/EC). However, even if a mixture is not classified as dangerous but one or more substances in the preparation poses human health or environmental hazards and is present in concentration of 1% (by weight) or more for non-gaseous preparations and 0.2% or more (by volume) for gaseous preparation; or meets the criteria for Persistent Bioaccumulative and Toxic (PBT) or very Persistent and very Bioccumulative (vPvB) substances (Annex XIII of REACh Regulation); or has been included in the candidate list for inclusion in the Annex XIV of REACh Regulation, and the concentration is 0.1% or more, a SDS has to be delivered on request. This means that also substances which do not have to be registered under REACh have to be included into eSDS.
Extended Safety Data Sheets for mixtures may have ESs attached that refer to the mixture itself, or to the individual dangerous components contained in the mixture, or both (ECHA 2008c).
One way to add information on substances (risk determining substances so-called “lead substances” or “critical components”) into eSDS of mixtures is to consolidate ESs for mixtures.
The main tasks of a formulator of a mixture/preparation when preparing an eSDS and generating of ESs are the following (CEFIC, 2010c):
1) List and identify the relevant (dangerous) substances in the mixture and collect sufficient knowledge about the mixture itself, taking into consideration the concentration limits.
2) Document the modification of the determinants of the exposure (e.g. physical-chemical, human health, environmental properties; interaction between substances and consequent increase/decrease of exposures; specific interaction of substances for specific endpoints).
3) Carry out the classification of the mixture according to Dangerous Preparation Directive (Directive 1999/45/EC).
4) Document differences between classification of the mixture and classification of the components.
5) Verify if the identification of a lead substance(s)/critical component(s) is useful.
6) If YES: proceed with the identification of the lead substance(s)/critical component(s).
7) Proceed with the collection of required information (e.g. description of the adequate RMM and OCs) for ES/ eSDS for the mixture.
8) Compile ES for the mixture or integrate information into chapter 1-16 (main body) of the eSDS.
1.4 Available methodologies for exposure assessment for mixtures
Until now approaches have been developed for the identification of the risk-determining substances in the mixtures, for specific exposure routes: the critical component approach (CCA), recommended by ECHA and the DPD+ methodology developed by the industry.
The CCA which is discussed in the ECHA Guidance for downstream users (ECHA 2008c) is based on the availability of DNELs and PNECs for all substances and on concentrations of substances in the mixtures. In addition substance- and use - specific availability parameters are taken into consideration (ECHA 2008c). ECHA recommends to identify the critical components in the mixture and to communicate the OCs and RMMs for the critical components.
Beside these approaches a risk assessment for the complete mixture could also be run.
1.4.1 CCA
The method identifies the risk-determining substances for each route of exposure with the aim to select the most appropriate RMMs. The critical components of a mixture are selected by deriving a risk indicator (RI).
Based on the ranking (the component with the highest RI is the critical component), it is possible to select one or more risk-determining substances per exposure route. Thus, for these critical substances, it is necessary to control the exposure to ensure a safe use of the mixture.
In the case that more than one risk-determining substance per exposure route is identified, it may be necessary to add together their influence on the risk. Addition should be applied if additivity principles were applied to identify hazard effects of the substances during the classification of the mixture. Besides, if it is known that two or more substances will act additively on a target, it may be necessary to apply the additivity principle to guarantee that the risks are properly controlled (ECHA 2008c, CEFIC 2010c).
1.4.2 DPD+ methodology
In the Industry´s opinion the CCA is of limited practical value at least for the time being because of the lack of information on many substances (potential component for mixtures) that have been not yet registered under REACh. Therefore the DPD+ method has been developed.
The DPD+ method is based on the legislation for classification of preparations (Directive 1999/45/EC, DPD), revised (+) with respect to the volatility of a substance, and defines a lead substance (LS) for each route of human exposure and for the aquatic environment (CEFIC, 2010c).
Depending on the classification of the substances, either the general concentration limits for a specific R phrase (Annexes II, III and V of the Directive 1999/45/EC) or, if available, the specific concentration limits (Annex VI of Regulation (EC) No. 1272/2008) are used.
The ratio calculated from the component concentration Ci and the concentration limit CL is called Lead Substance Indicator (LSI).
The LSIs are calculated for each dangerous substance and for each exposure pathway/emission route: e.g. ingestion, inhalation, skin/eye contact, and emission to aquatic environment. The substance with the highest LSI per exposure route is the LS for a certain exposure or emission pathway.
As described by CEFIC (CEFIC, 2010c) if LSIs of two substances differ by less than 10%, for the same exposure route, both substances have to be considered as LSs.
In addition also in this case as for the CCA, when two or more substances are contained in a mixture, which may lead to additive effects for a specific health endpoint (e.g. acute toxicity, skin/eye irritation) the sum of these substances has to be considered when detecting suitable RMMs.
It is important to mention that the identification of a definite lead substance does not necessarily result in the classification of the preparation for that specific effect.
Once that the LSs have been identified, the information provided in the respective substance’s ESs for the relevant use(s) is used to assemble the mixture’s ES.
2. AIM OF THE WORK
The aim of the present work is to illustrate and compare the different methods for the development of mixtures´ ESs under REACh, and to improve the preparation of consolidated ESs for a number of mixtures by providing information about their safe use, focusing on the human health endpoints. To this end, information on RMMs and OCs of the lead or risk determining substances were adopted by using the DPD+ methodology and CCA.
At the same time, the specific conditions of use of the whole mixtures (e.g. spraying, brush painting) were considered. Risk assessments were conducted by deriving DNELs for the whole mixtures (by means of the additivity approach) and using exposure modelling tools recommended under REACh (e.g., ECETOC TRA). Finally, the outcome of these assessments was compared with results obtained from the application of the DPD+ methodology and CCA.
3. METHODS
3.1 Mixtures employed
The DPD+ methodology, CCA and health risk assessment for the risk determining substances and for the complete mixtures have been conducted on exemplary mixtures containing substances already registered under REACh and whose information (physical chemical properties, DNELs, uses, legal classification) have been adopted from ECHA dissemination and ESIS (ECHA Website 2012b; ESIS Website 2012)
Tables 1-4 give an overview on the exemplary mixtures used. Two examples of mixtures described in the present work (adhesive and industrial cleaner see Table 1 and Table 3) have been adopted with minor modifications from CEFIC, 2010c)
Table 1 Composition of adhesive mixture
Chemical Substance CAS-No R-Phrases %
bisphenol-A- epichlorhydrin resins
(BPA)
25068-38-6
Xi; R36/38;
R43;
N; R51-53
60
xylene (X) 1330-20-7 R10; Xn 20/21;
Xi; R38 20
cyclohexylamine (CHA) 108-91-8
R10;
Xn; R21/22;
C;R34;
Repr.Cat 3; R62
8
benzyl alcohol (BA) 100-51-6 Xn; R20/22 10
ethanol 64-17-5 F; R11 2
Table 2 Composition of toluene mixture
Chemical Substance CAS-No R-Phrases %
toluene (T) 108-88-3
F, R11; Xi, R 38;
Xn, R48/20; Repr.Cat. 3;
R63; R67
50
p-xylene (pX) 106-42-3 R10; Xn 20/21;
Xi; R38 25
ethylbenzene (EB) 100-41-4 F, R11;
Xn, R20 20
1,2-dichlorobenzene
(1,2-DB) 95-50-1
Xn, R22;
Xi, R36/37/38; N;
R50/53
5
Table 3 Composition of industrial cleaner mixture
Chemical Substance CAS-No R-Phrases %
sodium tetraborate (ST) 1330-43-4 Repr. Cat. 2, R60, R61 15 sodium metasilicate
(SM) 6834-92-0 C, R34; Xi,R37 15
2-butoxyethanol (BT) 111-76-2 Xn; R20/21/22;
Xi; R38 10
water 60
Table 4 Composition of zinc sulphate mixture
Chemical Substance CAS-No R-Phrases %
diarsenic trioxide (DC) 1327-53-3
Carc. Cat. 1; R45 - T+; R28 - C; R34 -
N; R50-53
5
zinc sulphate (ZS) 7733-02-0
Xn; R22 Xi; R41 N; R50-53
20
water 75
The adhesive and toluene mixtures have been chosen to be analysed with the DPD+
methodology, CCA and risk assessment for the whole mixture, while the industrial cleaner and zinc sulphate have been selected as example of mixtures containing CMR substances (sodium tetraborate and diarsenic trioxide as example of substances toxic to reproduction and threshold carcinogenic respectively) and therefore analysed only with CCA and risk assessment.
3.2 Application of the DPD+ methodology
Available information on RMMs and operational conditions OCs of the lead substances (identified for each relevant human health exposure pathway) were adopted using the results of the DPD+ methodology for two exemplary mixtures containing dangerous-non CMRs substances (adhesive and toluene mixtures).
The ratio calculated from the component concentration Ci and the concentration limit CL is called Lead Substance indicator (LSI) and was derived according to the following formula (CEFIC 2010c):
1) LSI = Ci/CL
For the inhalation exposure:
2) LSI = VP x Ci/CL, VP = vapour pressure
The DPD+ methodology was applied for short term (qualitative risk assessment) and long term effects (quantitative risk assessment by means of ECETOC TRA v.3 (ECETOC 2012)), depending on the classification of the lead substance(s).
3.3 Application of the CCA methodology
The CCA for the identification of critical components in a mixture was applied by calculating the RI on all the four exemplary mixtures analysed) according to the following formula
3) RI= [C x (A)]/ (DNEL or PNEC),
Being C the concentration of substance in the mixture and A the substance- and use specific availability parameters (CEFIC 2010c). As the factor A is not specified in the CEFIC guidance, in the present work it was assumed to be related to the volatility of the substances in the mixture in analogy to the DPD+ methology. Therefore a factor A was adopted only when determining the RI for exposure by inhalation and was assumed to be equal to the vapour pressure (VP).
Thereafter the risk assessment for risk determining substances of each mixture was performed by means of the exposure modelling tool ECETOC TRA v.3 (ECETOC 2012)
3.4 Derivation of DNELs and risk assessment the whole mixture
Inhalation and dermal exposure DNELs for the complete mixtures have been derived using a generalization of the concentration addition (CA) as worse case according to the following formula 4):
4)
DNEL mix = 100 C
ADNEL
A+ C
BDNEL
B+ C
CDNEL
C
Being A, B and C the components of the mixture. Thereafter the risk assessment the whole mixtures was performed by means of the exposure modelling tool ECETOC TRA v.3 (ECETOC 2012) When requested by the calculation system, substance intrinsic properties (e.g. molecular weight) and physical-chemical properties (e.g. VP) have been adopted by using a worse case approach from the information already existing (ECHA Website 2012b) for the each component of the mixture.
4. RESULTS
4.1 Application of the DPD+ methodology
The results of the DPD+ methodology for the identification of the LS(s) applied for the mixtures adhesive and toluene are illustrated in Table 5 and Table 7.
With regard to the adhesive mixture BPA resulted to be the LS for the dermal and eye exposure and xylene and cycloxylamine for inhalation and the ingestion route respectively.
Table 5 LS determination for the adhesive mixture
Composition VP Inhalation Dermal Eyes Ingestion
Component % Pa R CL LSI R CL LSI R C
L LS I
R C
L LSI
BPA 60 4.6E-
08
R38 R43
5 1
12 60
R36 5 12
xylene 20 8800 R20 13
%
14080 R38 R21
20 12.
5 1 1.6
cyclohexyl- amine
8 1430 R21
R34 25 10
0.3 2 0.8
R22 25 0.32
benzyl alcohol
10 22.26 R20 25 0.,2 R22 25 0.2
R = R-phrase
The mixture is classified for the human health endpoints as: Xn; R20/21; Xi; R36/R38; R43;
Repr.Cat. 3; R62.
The mixture in contrast to some of its components does not need to be classified with R34 or Xn, R21-22, respectively on the basis of the concentration limit and of the application of the additivity principle in relation to the acute toxicity.
Exposure pathway “ingestion” was considered not relevant as no consumer exposure is foreseen for adhesive. Furthermore, during industrial use, an oral exposure is not expected.
For the inhalation lead substance identified by DPD+, xylene, estimated exposure values were calculated using ECETOC TRA worker v.3. The information is summarized in Table 6.For the dermal and eye lead substances a qualitative assessment can be carried out.
a) Local effects:
The critical effects of the leading substance are irritation and sensitisation. Therefore, the use of protective gloves is recommended.
b) Long term effects:
However as the mixture displays hazards for systemic effects too and for consistence reason a risk assessment for the dermal LS was conducted as well. The information is summarized in Table 6. Results of the risk assessment of the identified dermal and inhalation lead substances show that the safe use of the mixture for the use scenario (Mixing or blending in batch processes, PROC5) is depending on the use of gloves. Table 6, shows that it is possible to obtain a safe use of the mixture for the use scenario “Transfer of chemicals from/to vessels/ large containers at dedicated facilities” (PROC 8b) without the implementation of relevant RMMs.
Moreover, cyclohexylamine results to be classified for systemic effects as Repr.Cat. 3; R62.
Since the amount of the cyclohexylamine is greater as the default classification limit for R62 (≥
5%), it advisable to use the DNEL to perform a substance-specific assessment for inhalation and dermal exposure pathways and to compare the RMMs identified with the ones obtained by identification of the lead substance by DPD+ method.
Table 6 Exposure estimation for adhesive mixture after application of DPD+ methodology
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation mg/m³
Exposure estimate dermal mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo
Safe use
5
Mixing or blending in batch processes
BPA:60%
X:20% < 15 min N X: 13.3 BPA:13.7 X: 0.17 BPA: 1.64 NO
8 b
Transfer of chemicals dedicated facilities
BPA:60%
X:20% 15-1h N X: 26.55 BPA: 6.86 X: 0.36 BPA: 0.82 YES
Table 7 LS determination for the toluene mixture
Composition VP Inhalation Dermal Eyes Ingestion
Component % Pa R CL LSI R. CL LSI R CL LSI R CL LSI
toluene 50 308 9
R38 5 10
xylene 25 116 7
R20 13
%
2244 R38 R21
20 12.5
1.25 2 ethylbenzene 20 952 R20 25 761 R38 20 1
1,2-dichloro- benzene
5 208 R38 20 0.25 R36 20 0.25 R22 25 0.2
R = R-phrase
With regard to the toluene mixture, toluene resulted to be the LS for dermal exposure, xylene for inhalation exposure and 1,2-dichlorobenzene for the eye and ingestion.
The classification the toluene mixture resulted to be the following for the human health endpoints: Xn R20; Xi, R38; Repr.Cat.3; R63; Xn, R48/20, R67.
Exposure pathway “ingestion” was considered not relevant as no consumer exposure is foreseen for adhesive toluene mixture. During industrial use, an oral exposure is not expected.
For the inhalation lead substance identified by DPD+, xylene, estimated exposure values were calculated using ECETOC TRA worker v.3. The information is summarized in Table 8.
For the dermal and eye lead substances a qualitative assessment can be carried out.
a) Local effects:
The critical effect of the leading substance is irritation. Therefore, the use of protective gloves is recommended.
b) Long term effects:
However since the mixture presents also hazard for systemic effects and for consistence reason a risk assessment for the dermal LS was conducted as well. The information is summarized in Table 8. Results of the risk assessment of the identified dermal and inhalation lead substances, shows that it is possible to obtain a safe use of the mixture for all the uses scenario taken into consideration (PROC4, Use in batch and other process (synthesis) where opportunity for exposure arises; PROC8b; Transfer of chemicals dedicated facilities PROC 9; Transfer of chemicals into small containers, PROC 10 Roller application or brushing) without the implementation of relevant RMMs.
Table 8 Exposure estimation for toluene mixture after application of DPD+ methodology
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation mg/m³
Exposure estimate dermal mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo Safe use
4
Use in batch and
other process (synthesis)
where opportunity
for exposure
arises
T:50%
X:25% > 4h N X:
53.04
T:
6.8571 X: 0.24 T: 0.017 YES
8b
Transfer of chemicals dedicated facilities
T:50%
X:25%
15 min-
1h N X:
26.54
T:
6.8571 X 0.12 T: 0.017 YES
9
Transfer of chemicals into small containers
T:50%
X:25%
15 min-
1h N X:
26.54
T:
6.8571 X: 0.12 T: 0.017 YES
10
Roller application or brushing
T:50%
X:25% > 4h N X:
132.6
T:
27.42 X 0.6 T: 0.07
YES
4.2 Application of the CCA
The results of the application of the CCA for the determination of the risk determining substances are listed in Table 9-Table 15
Table 9 Identification of critical substance for the adhesive mixture
Chemical
Substance %
Vapour pressure
(VP)
DNEL inhal mg/m³
DNEL dermal mg/kg bw
Risk indicator inhalation
Risk indicator
dermal
BPA 60 4.6E-08 12.25 8.33 2.25E-07 7.2
xylene (X) 20 8800 77 180 2285 0.111
cyclohexylamine
(CHA) 8 1430 5 0.4 2288 20
benzyl alcohol
(BA) 10 22.26 90 9.5 2.47 1.05
For the adhesive mixture the critical substances for the inhalation route are xylene and cyclohexylamine, while the critical substance for dermal exposure pathway is cyclohexylamine.
The risk assessment for the risk determining substances, summarized in
Table 10 shows that the safe use for the adhesive mixture can be obtained for the uses PROC 5 and PROC 8b only adopting LEV and respiration protection with regard of the inhalation exposure. Regarding the dermal exposure the safe use for the adhesive mixture can be obtained for the use PROC 8b only by adopting the use of special dermal protection (e.g. gloves, APF20) against the effects of the dermal exposure.
Table 10 Exposure estimation of the adhesive mixture after application of the CCA
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation mg/m³
Exposure estimate dermal mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo
Safe use
5
Mixing or blending in batch processes
X: 20%);
CHA: 8% ) < 15 min N X: 13.27;
CHA:20.66
CHA: 8.22 X: 0.172;
CHA: 2.47
RCR Total: 2.48 CHA: 20.57 NO
5
Mixing or blending in batch processes
X: 20%);
CHA: 8% < 15 min Y X: 0.13;
CHA 1.23 CHA: 0.41
X: 0.021 CHA 0.25
RCR Total:0.271 CHA 1.03
NO with dermal PPE (APF20)
8b
Transfer of chemicals dedicated facilities
X: 20%);
CHA: 8%
15 min-
1h N X: 26.5425;
CHA: 24.79 CHA: 4.11
X: 0.34 CHA: 4.965
RCR Total: 5.31 CHA: 10.56 NO
8b
Transfer of chemicals dedicated facilities
X: 20%);
CHA: 8%
15 min-
1h Y X: 0.08;
CHA: 0.74 CHA: 0.20
X 0.001 CHA: 0.148 RCR Total:
0.149
CHA: 0.52
YES (with respiratory protection (90%)+
dermal PPE (APF20)
Table 11 Identification of critical substance for the toluene mixture
Chemical
Substance % VP
DNEL inhal mg/m³
DNEL dermal mg/kg bw
Risk indicator inhalation
Risk indicator dermal
toluene (T) 50 3089 192 384 804.43 0.13
p-Xylene (p-X) 25 1167 221 3182 132.01 0.008
ethylbenzene (E) 20 952 77 180 246.27 0.111
1,2- dichlorobenzene
(1,2-DC)
5 208 59 4 17.62 1.25
For the toluene mixture the critical substances are toluene and 1,2-dichlorobenzene for the inhalation and dermal routes, respectively.
Results of the risk assessment for critical components of the toluene mixture shows (Table 12) that is possible with regard to the inhalation exposure to obtain a safe use of the mixture for the PROC 4, 8b and 9 without implementing specific RMMs. Concerning the use scenario PROC10 the use safe of the mixture is obtained only with implementation of LEV and respiratory protection (90%). The risk assessment for the critical component for the dermal exposure (1,2- dichlorobenzene) demonstrated that the safe use of the toluene mixture can achieved for all the uses taken in consideration only by wearing dermal personal protective equipment (PPE) .
Table 12 Exposure estimation of the toluene mixture after application of the CCA
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation mg/m³
Exposure estimate dermal mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo Safe use
4
Use in batch and
other process (synthesis)
where opportunity
for exposure
arises
T: 50;
p-X: 25;
E: 20;
1,2-DC: 5
> 4h N T:
76.78 1,2-DC:
4.11
T:
0.40 1,2-DC:
1.02
NO
4
Use in batch and
other process (synthesis)
where opportunity
for exposure
arises
T: 50;
p-X: 25;
E: 20;
1,2-DC: 5
> 4h N T:
76.78 1,2-DC:
0.82
T:
0.40
1,2-DC:
0.2
YES + dermal PPE (APF5)
8b
Transfer of chemicals
at dedicated
facilities
T: 50;
p-X: 25;
E: 20;
1,2-DC: 5
> 4h N T:
38.39 1,2-DC:
4.11
T:
0.20 1,2-DC
: 1.02
NO
8b
Transfer of chemicals
at dedicated
facilities
T: 50;
p-X: 25;
E: 20;
1,2-DC: 5
> 4h N T:
38.39 1,2-DC:
0.82
T:
0.20
1,2-DC:
0.2
YES + dermal PPE (APF5)
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation
mg/m³
Exposure estimate dermal
mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo Safe use
9
Transfer of chemicals into small containers (dedicated filling line)
T: 50;
p-X: 25;
E: 20;
1,2-DC: 5
> 4h N T:
38.39 1,2-DC:
4.11
T;
0.20 1,2-DC:
1.02
NO
9
Transfer of chemicals into small containers (dedicated filling line)
T: 50;
p-X: 25;
E: 20;
1,2-DC: 5
> 4h Y T:
0.39; 1,2-DC:
0.82
T:
0.20
1,2-DC:
0.2
YES + dermal PPE (APF5)
10
Roller application or brushing
T: 50;
p-X: 25;
E: 20;
1,2-DC: 5
> 4h N T:
191.96 1,2-DC:
16.38
T:
1.0 1,2-DC:
4.11
NO
10
Roller application or brushing
T: 50;
p-X: 25;
E: 20;
1,2-DC: 5
> 4h Y T:
1.92 1,2-DC:
3.2
T:
0.01 1,2-DC:
0.82
YES with respiratory
protection (90%)+
dermal PPE (APF5)
Table 13 Identification of critical substance for the industrial cleaner mixture
Chemical
Substance % VP
DNEL inhal mg/m³
DNEL dermal mg/kg bw
Risk indicator inhalation
Risk indicator dermal sodium
tetraborate (ST) 15 not
available 6.7 316.4 2.23E+00 5.00E-03
sodium metasilicate (SM)
15 1.3 6.22 1.49 3.13 10.1
2-butoxyethanol
(2-BT) 10 80 98 75 8.16 0.13
The critical components for the industrial cleaner mixture are sodium metasilicate and 2- butxyethanol for dermal and inhalation exposure pathway respectively.
The risk assessment (see Table 14) conducted on the critical substance for the inhalation exposure demonstrates a safe use of the mixture for the all uses scenarios assessed. On the other hand the risk assessment for the risk determining substance for the dermal route (sodium metasilicate) can only be obtained by adopting proper personal protection (with different protection factor according to the use scenario).
Table 14 Exposure estimation of the industrial cleaner mixture after application of the CCA
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation
mg/m³
Exposure estimate dermal
mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo
Safe use
4
Use in batch and other
process (synthesis)
where opportunity
for exposure
arises
SM (dermal route):
5-25%;
2-BT (inhalative route): 5-25%
> 4h N 2-BT: 14.84 SM: 4.11 0.15 2.76 NO
4
Use in batch and other
process (synthesis)
where opportunity
for exposure
arises
SM (dermal route):
5-25%;
2-BT (inhalative route): 5-25%
> 4h N 2-BT: 14.84 SM: 0.82 0.15 0.55
YES + Dermal
PPE (APF5)
8b
Transfer of chemicals at
dedicated facilities
SM (dermal route):
5-25%;
2-BT (inhalative route): 5-25%
15 min-1h N 2-BT: 2.97 SM: 8.2 0.03 5.55 NO
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation
mg/m³
Exposure estimate dermal
mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo
Safe use
8b
Transfer of chemicals at
dedicated facilities
SM (dermal route):
5-25%;
2-BT (inhalative route): 5-25%
15 min-1h N 2-BT: 2.97 SM: 1.6 0.03 1.1
NO + Dermal
PPE (APF5)
10
Roller application or brushing
SM (dermal route):
5-25%;
2-BT (inhalative route): 5-25%
15 min-1h N 2-BT:5.9 SM: 16.45 0.06 11.04 NO
10
Roller application or brushing
SM (dermal route):
5-25%;
2-BT (inhalative route): 5-25%
15 min-1h Y 2-BT: 5.9 SM: 3.29 0.06 2.2
NO + Dermal
PPE (APF5) 7 Industrial
spraying
SM (dermal route):
5-25%;
2-BT (inhalative route): 5-25%
< 15 min N 2-BT: 29.67 SM:25.7 0.3 17.2 NO
7 Industrial spraying
SM (dermal route):
5-25%;
2-BT (inhalative route): 5-25%
< 15 min N MS:29.67 SM:5.14 0.3 3.5
NO + Dermal
PPE (gloves
APF5)
Table 15 Identification of critical substance for the zinc sulphate mixture
Chemical
Substance % VP
DNEL inhal mg/m³
DNEL dermal mg/kg bw
Risk indicator inhalation
Risk indicator dermal
diarsenic
trioxide (DT) 5 0.033 0.005 0.112 30 44.64
zinc sulphate
(ZS) 20 not
available 1 8.3 20 0.12
As outlined in Table 15, the critical component of the zinc sulphate mixture is diarsenic trioxide for the inhalation and dermal routes of exposure.
It is important to mention that for substance diarsenic trioxide the registrant calculated a DNEL, although if classified as carcinogenic. However the substance is not classified as mutagenic.
Since the diarsenic trioxide does not induce DNA damage or mutation, the carcinogenic effect is considered having a threshold and therefore no DMEL needs (Derived Minimum Effect Level) to be derived (See Guidance on information requirements and chemical safety assessment, (ECHA 2010b), Chapter R.8: Characterisation of dose [concentration]-response for human health.R8.1.3 and 8.5).
The risk assessment for the critical substance of the zinc sulphate for the inhalation and dermal route shows (see Table 16that it is possible to obtain a safe use of the mixture for the use scenario PROC 2 (Mixing or blending in batch processes (multistage and/or significant contact)).
On the contrary, a controlled exposure for the mixture (inhalation exposure) for some of the other use scenarios analysed (PROC3, Use in closed batch process (synthesis or formulation);
PROC8b; PROC13, Treatment of articles by dipping and pouring), is only guaranteed when LEV is implemented.
With regard to the risk assessment for the risk determining substance for the dermal exposure, the safe use of the mixture can be gained for PROCs 8b and13 by wearing for dermal protection equipment with the protection factor > 5.
Table 16 Exposure estimation of the zinc sulphate mixture after application of the CCA
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation mg/m³
Exposure estimate dermal mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo
Safe use
2
Mixing or blending in batch processes (multistage
and/or significant
contact)
5 – 25% w/w < 15 min N 0.0006 0.082 0.12 0.73 YES
3
Use in closed batch
process (synthesis
or formulation)
5 – 25% w/w < 15 min N 0.006 0.041 1.20 0.37 NO
3
Use in closed batch
process (synthesis
or formulation)
5 – 25% w/w < 15 min Y 0.0006 0.041 0.12 0.37 YES with
LEV
8b
Transfer of chemicals at
dedicated facilities
5 – 25% w/w 15 min-
1h N 0.012 1.65 2.40 14.7 NO
8b
Transfer of chemicals at
dedicated facilities
5 – 25% w/w 15 min-
1h Y 0.0006 1.65 0.12 2.94
NO + dermal
PPE (APF 5)
Process category
Use
scenario Concentration
Duration of activity
LEV (Y/N)
Exposure estimate inhalation mg/m³
Exposure estimate dermal mg/kg bw
RCR(inhalation):
DNEL/Expo
RCR (dermal):
DNEL/Expo
Safe use
13
Treatment of articles by dipping and pouring
5 – 25% w/w < 15 min N 0.006 0.82 1.20 7.35 NO
13
Treatment of articles by dipping and pouring
5 – 25% w/w < 15 min Y 0.0006 0.64 0.12 1.47
NO with LEV+
dermal PPE (APF 5)
4.3 Risk assessment of the mixtures
The application of the risk assessment for the whole adhesive mixture reveals that it is possible to obtain the safe use of the mixture for the use scenario PROC 5 for what concern the inhalation route. For the use scenario PROC 8b the save use is only guaranteed by the implementation of the LEV and respiratory protection. With regard to the dermal exposure the safe use is warrant by wearing gloves with protection factor of 5 for both scenarios taken in consideration (Table 17). Table 18 shows that it is possible to achieve controlled exposure for the toluene mixture for some the uses analysed (PROC 4, PROC 8b and PROC9) for both routes of exposure. For the use description PROC 10 the use of the toluene mixture is safe for the inhalation exposure only by application of the LEV and respiratory protection, while it is safe for what concerns the dermal exposure route.
The risk assessment for the industrial cleaner mixture (Table 19) demonstrates that a safe use of the mixture is possible for inhalation and dermal exposure for the use scenarios PROC 4, PROC 10 and PROC 7 by implementing LEV and wearing gloves (with different protection factors according to the different use descriptor), respectively. For the exposure scenario PROC 8b the use of the industrial cleaner is safe for the inhalation, while it requires the adoption of RMMs (dermal personal protection).
The application of the risk assessment for the mixture zinc sulphate (Table 20) demonstrates that it is possible to obtain the safe use of the mixture for inhalation exposure for the use descriptors PROC2, PROC 3, PROC 8b, with implementation of LEV and also respiratory protection. With regard to the PROC 13 it was not possible to achieve a safe use of the mixture for the inhalation route.
With regard to the dermal exposure the safe use of the mixture is attained only wearing dermal protection equipment with various protection factors according to the use scenario analysed.
