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EC number: - | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- other toxicological threshold
- Value:
- 0.8 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- other: based on other data
- Dose descriptor starting point:
- other: Not applicable
- Modified dose descriptor starting point:
- other: Not applicable
- Explanation for the modification of the dose descriptor starting point:
Not applicable
- Justification:
- See explanation for hazard conclusion.
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.34 mg/kg bw/day
DNEL related information
- Overall assessment factor (AF):
- 42
- Modified dose descriptor starting point:
- LOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Acute/short term exposure
- Hazard assessment conclusion:
- no-threshold effect and/or no dose-response information available
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - workers
Compositional information:
These hydrocarbon streams meet the regulatory definition of UVCB substances, with inherent variations in composition present due to differences in manufacturing history. This variability is documented in the Category Justification (appended to IUCLID section 13), which lists the chemical marker substances present along with an indicative concentration range for each e.g.
· Dicyclopentadiene:<80%
· Benzene: <0 - 3%
· n-Hexane: <0 – 0.2%
· Toluene: up to 20%
· Styrene: up to 25%
· C8 Aromatics (xylene, ethylbenzene) up to 20%
The approach developed by the ExWG on the selection of category constituents for use in human health exposure assessments was implemented for Category L. The primary constituents used are benzene and DCPD. A full description of this approach is available in Section 13.
Uses:
These hydrocarbon streams are used as intermediates, in manufacture and hence no exposure to the general population is likely. These DNELs address concerns linked to the CMR properties of the marker substances or their potential to cause other long-term health effects leading to an equivalent level of concern.
Substance selection for risk characterization:
See "Selection of constituents for HH exposure" in section 13.2.
Intrinsic hazards of marker substances and associated DN(M)ELs:
The following hazard information and DNELs are available for marker substances present in this Category.
Dicyclopentadiene
The potential of dicyclopentadiene to cause long-term systemic effects can judged based on the results of repeated dose toxicity and reproductive (fertility, developmental) testing.
For DCPD, the following NOAEL/NOAECs are available:
Oral:
sub-chronic effects: male rat NOAEL = 4 mg/kg bw/d
reproductive effects: rat NOAEL = 50 mg/kg bw/d
developmental toxicity: rat NOAEL = 60 mg/kg bw/d
Inhalation:
sub-chronic effects: mouse NOAEC = 27.6 mg/m3
sub-chronic effects: rat NOAEC = 276 mg/m3
Worker – long-term systemic inhalation DNEL
Dose descriptor
A mouse inhalation NOAEC of 27.6 mg/m3will be used to derive the DNELl-t inhalation.
Modification of dose descriptor
Correct the NOAEC to adjust for differences in duration in the animal study (6 h) and the worker (8 h) and light work following the TGD Figure R.8-2:
27.6 mg/m3x [6 h / 8 h] x [6.7 m3/ 10 m3] = 13.9 mg/m3
It is assumed that DCPD is similarly and efficiently (100%) absorbed after inhalation by mice and humans.
Assessment factors
An assessment factor of 6is used based onworkerintraspecies differences (3)and correction for duration of exposure (sub-chronic to chronic = 2).
DNELl-t inhal= 13.9 mg/m3/ 6 = 2.3 mg/m3
Worker - long-term systemic dermal DNEL
Dose descriptor
A mouse inhalation NOAEC of 27.6 mg/m3will be used to derive the DNELl-t dermal.
Modification of dose descriptor
Correct the NOAEC to adjust for differences in duration of exposure; then convert the corrected mouse inhalation NOAEC (mg/m3) into a human dermal NOAEL (mg/kg bwt/d) after adjusting for differences in uptake between the two routes of exposure (TGD, Appendix R.8-2, Example B.4).
It is assumed that uptake of DCPD after inhalation is 100% and, in the absence of data, dermal absorption is assumed to be the default of 100%.
correctedDermal NOAEL = NOAECinhalationx sRVmouse[1]x [ABSinhal-mouse/ABSdermal-human]
correctedDermal NOAEL = 27.6 x 0.514 x [100/100] = 14.19 mg/kg bwt/d
Assessment factors
An assessment factor of 42is used based on interspecies differences for themouse (7), workerintraspecies differences (3)and correction for duration of exposure (sub-chronic to chronic = 2).
DNELl-t dermal= 14.19 mg/kg bwt/d / 42 = 0.34 mg/kg bw/d
Benzene
An Explanation for the Worker DNEL at 0.25 ppm (0.8 mg/m3) as an 8-hour TWA
Background
The DMEL used in the original versions of the REACH benzene dossier was based on the EU BOELV of 1 ppm which was derived from the position on benzene toxicology presented by SCOEL in SUM 140 (SCOEL, 1991). Our analysis of the body of research that has developed since then agrees with the conclusion of DECOS (Netherlands) that the evidence on benzene justifies the setting of a DNEL rather than a DMEL (DECOS, 2014). This position is based on the view that benzene is not a direct-acting mutagen, that clastogenic events will have a threshold and that the key toxicity is haematotoxicity. If haematotoxicity is avoided, then progression to oncological disease would not be expected (LOA 2017).
The use of the EU BOELV as a basis for a DMEL was based on the provision in REACH guidance that allows a DNEL/DMEL to be based on accepted formal workplace limits providing that no data exist that would contradict the basis of the formal workplace limit. (ECHA Guidance R8 Appendix 13). Pending the setting of a new EU BOELV value for benzene, LOA believes that the DECOS document and other recent literature provide enough justification to contradict the 1 ppm 8h TWA EU BOELV. As an interim position LOA previously saw that haematological data reviewed by the DECOS, as well as more recent research provided justification for a DNEL of 0.6 ppm as an 8h TWA.
In 2017, ECHA’s Risk Assessment Committee (RAC) was tasked with providing an Opinion on a Benzene OEL. This was provided in March 2018 and proposed an OEL of 0.05 ppm as an 8h TWA. RAC also believed that benzene could be seen as a threshold carcinogen, where avoidance of structural and numerical chromosomal aberrations and micronuclei would protect against cancer risk. (ECHA 2018) During and subsequent to this RAC review of the benzene OEL by the Risk Assessment Committee of ECHA (RAC), LOA have reassessed the data on benzene in greater detail.
0.25 ppm/8h TWA OEL Recommendation based on LOA’s Detailed work 2017-2020
Using a Study Quality Assessment tool to decide the studies that are the of the highest quality for OEL setting, LOA have judged that the weight of evidence LOAEC for haematological and genotoxic effects (i.e. chromosomal aberrations, aneuploidy, and micronucleus formation) in high-quality studies of workers is 2 ppm/8h TWA and that the NOAEC for these effects is ~0.5 ppm/8h TWA. The basis for this decision is summarized in the Annex below and is presented in full in Schnatter et al 2020.
Given the high quality of studies used for LOAEC and NOAEC derivation, the significant number of workers covered by these studies (including from potentially more sensitive populations) and a more conservative LOAEC selection LOA believe that an assessment factor of 4 is sufficient for LOAEC to NOAEC extrapolation (2) and intraspecies differences (2). This would give an OEL of 0.5 ppm / 8h which is in line with the actual NOAEC observed. However, given uncertainties raised in the RAC assessment about whether the bone marrow is potentially more susceptible to damage than can be ascertained by examining effects in peripheral blood (i.e. in the available studies in workers) an extra assessment factor of 2 could apply until further research clarifies this issue. Thus, an interim proposed OEL of 0.25 ppm/8h TWA is recommended.
The scientific case for these values has been presented at a conference (Cefic APA , Helsinki. 11thSeptember 2019) and is elaborated in the peer -reviewed paper Schnatter et al 2020.
Registrants should also be aware that consequent to deliberations by DG Employment’s Working Party on Chemicals, the Advisory Committee on Safety and Health has proposed that an OEL of 0.5 ppm/8hTWA should be adopted in the short term (within 2 years of the entry into force of the Directive amendment) with this reducing to an OEL of 0.2 ppm (within 4 years of the Directive amendment entering force). It is also proposed that another review of the benzene OEL for the EU should start in 2028. Given that the exact timing of these regulatory changes depends on the regulatory process Registrants are advised to monitor the situation via trade associations and other channels.
LOA believe that the available data show that an OEL of 0.25 ppm/8hTWA is sufficient to protect all aspects of worker health (i.e. cancer, haematological and genotoxic effects). The protection for carcinogenic effects is driven by the evidence for benzene having a thresholded mode of action of cancer, thus the OEL would protect against benzene induced cancer (i.e. Acute Myeloid Leukemia).
Note that Registrants referring to a DNEL of 0.25 ppm (8h TWA) will still be subject to the requirements of the Carcinogens and Mutagens Directive (Council Directive 1999/38/EC as amended) which requires substitution where feasible, exposure minimisation and monitoring of workers. (For references see section 13 "Worker DNEL Explanation").”
Annex: Summary of the Scientific Basis for LOA’s 0.25 ppm/8h TWA OEL Recommendation
The scientific case for these values has been presented at a conference (Cefic APA 2019) and in a peer-reviewed paper. (Schnatter et al 2020) Additionally papers on the mode of action of benzene and on considerations of cancer risk have been written. (North et al 2020a, 2020b).
However, in summary, after identifying relevant haematotoxicity and genotoxicity studies in workers by means of literature searches and accessing existing reviews, 43 haematotoxicity and 94 genotoxicity studies were screened for eligibility to be scored for study quality. This was achieved by a trained panel of scientists from appropriate disciplines using a tool modified from that proposed by Vlaanderen et al 2008 to make it appropriate to the task. Thirty-six haematology studies from 31 unique study populations and 77 genotoxicity studies from 56 unique study populations were scored using this tool. Studies were ranked by the quality score to give a haematotoxicity ranking and a genotoxicity ranking, and these rankings were divided into tertiles. For each ranking, the high-quality studies were identified as being in the top tertile or above the median of study quality value.
Where the data allowed, LOAECs and NOAECs were assigned to studies in the top tertile and above the median quality score. LOAECs and NOAECs were additionally characterised as being more certain or less certain based on key characteristics of the study from which the value was derived. Genotoxicity studies were further characterised by the specificity of the exposure context for benzene with “Factory” exposures having a predominant exposure to benzene being seen as more specific than “Fuel” (i.e. petroleum product exposure) and that in turn being more specific than exposure to “Ambient Air” ( polluted urban air). LOAECs and NOAECs were assigned to genetic toxicology endpoints shown to be relevant to cancer (structural and numerical chromosomal aberrations and micronuclei).
Consideration of the high-quality haematotoxicity studies with more certain LOAECs gave a cluster with LOAECs in the range 2-3.5 ppm ( 3 studies – Lan et al 2004 - >2 ppm [~ 2.2 ppm]; Qu et al 2003 – 2.26 ppm and Zhang et al 2016 – >2.1 ppm ) and a cluster with LOAECs in the range 7-8 ppm (4 studies - Schnatter et al 2010- 7.8 ppm, Ward et al 1996- 7.2 ppm- Rothman et al 1996- 7.6 ppm and Bogadi-Sare et al 2003 – 8.0 ppm). Similarly, analysis of NOAECs from the high-quality studies gave clusters indicating possible NOAECs in the ranges 2-3.5 ppm, 0.6-0.8 ppm and 0.2-3 ppm. Sensitivity analysis and selecting the lowest LOAEC pointed to a LOAEC of 2 ppm/8h and a NOAEC of 0.5 ppm/8h as being a robust position.
Consideration of the high-quality genotoxicity studies with more certain LOAECs gave LOAECs in the range >1.6 – 3.07 ppm (4 studies – Qu et al 2003-3.07 ppm. Xing et al 2010- >1.6 ppm (calculated arithmetic mean), Zhang et al 2012 - >2.64 ppm and Zhang et al 2014-2 ppm) after the exclusion of a study with a higher LOAEC value of 13.6 ppm (Zhang et al 2007). The mean LOAEC was 2.33 ppm / 8h. The best available NOAEC values came from two “Fuel” studies (Carere et al 1995 = 0.47 ppm and Pandey et al 2008 = 0.9 ppm) giving a mean NOAEC from quality studies of 0.69 ppm.
Comparison of data from the haematotoxicity and the genotoxicity LOAEC/NOAEC analyses indicated that an overall LOAEC of 2.0 ppm/8h and a NOAEC of 0.5 ppm/8h should be appropriate based on the highest quality literature on both endpoints.
Given the high quality of studies used for LOAEC and NOAEC derivation, the significant number of workers covered by these studies (including from potentially more sensitive populations) and a more conservative LOAEC selection LOA believe that an assessment factor of 4 is sufficient for LOAEC to NOAEC extrapolation (2) and intraspecies differences (2). This would give an OEL of 0.5 ppm / 8h which is in line with the actual NOAEC observed. However, given uncertainties raised in the RAC assessment about whether the bone marrow is potentially more susceptible to damage than can be ascertained by examining effects in peripheral blood (i.e. in the available studies in workers) an extra assessment factor of 2 could apply until further research clarifies this issue. Thus, an interim proposed OEL of 0.25 ppm/8h TWA is recommended.
References
Carere A, Antoccia A, Crebelli R, Degrassi F, Fiore M, Iavarone I, Isacchi G, Lagorio S, Leopardi P, Marcon F, et al (1995) Genetic effects of petroleum fuels: cytogenetic monitoring of gasoline station attendants. Mutat Res 332: 17-26.
Bogadi-Sare A, Zavalic M, Turk R. (2003) Utility of a routine medical surveillance program with benzene exposed workers. Am J Ind Med 44(5):467-73.
DECOS [Dutch Expert Committee on Occupational Safety of the Health Council of the Netherlands] (2014) Benzene, Health-based recommended occupational exposure limit, No. 2014/03, The Hague: The Health Council of the
Netherlands, February 21, 2014. Accessed:https://www.gezondheidsraad.nl/en/task-and-procedure/areas-of-activity/healthyworking-conditions/benzene-health-based-recommended
ECHA (2018) Committee for Risk Assessment RAC Opinion on scientific evaluation of occupational exposure limits for Benzene ECHA/RAC/ O-000000-1412-86-187/F Adopted 9 March 2018 Accessed:https://echa.europa.eu/documents/10162/13641/benzene_opinion_en.pdf/4fec9aac-9ed5-2aae-7b70-5226705358c7
Lan Q et al. (2004). Haematotoxicity in workers exposed to low levels of benzene. Science 306: 1774-1776.
LOA (2017). Potential derived no effect level (DNEL) for benzene based on haematotoxicity. Published in 2017 REACH Dossier for Benzene (2017-11-07).
North CM et al (2020a) Modes of Action Considerations in Threshold Expectations for Health Effects of Benzene Toxicology Letters (submitted). Preprint:https://doi.org/10.5281/zenodo.3784971
North CM et al (2020b) Event-informed Risk Models for Benzene-induced Acute Myeloid Leukemia Toxicology Letters (in preparation)
Pandey AK, Bajpayee M, Parmar D, Kumar R, Rastogi SK, Mathur N, Thorning P, de Matas M, Shao Q, Anderson D, Dhawan A (2008) Multipronged evaluation of genotoxicity in Indian petrol-pump workers. Environ Mol Mutagen 49: 695-707.
Qu Q, et al. (2003). Validation and evaluation of biomarkers in workers exposed to benzene in China. Res Rep Health Eff Inst 115: 1-72; discussion 73-87.
Rothman N et al. (1996). Hematotoxicity among Chinese workers heavily exposed to benzene. Am J Ind Med. 29(3):236-46.
Schnatter AR et al. (2010). Peripheral blood effects in benzene-exposed workers. Chem Biol Interact 184: 174-181.
Schnatter AR et al (2020) Derivation of an Occupational Exposure Limit for Benzene Using Epidemiological Study Quality Assessment Tools. Toxicology Letters https://doi.org/10.1016/j.toxlet.2020.05.036
Vlaanderen, J., Vermeulen, R., Heederik, D., Kromhout, H. (2008). Guidelines to evaluate human observational studies for quantitative risk assessment. Environ Health Perspect. 116(12):1700-5.
Ward, et al. (1996). Risk of low red or white blood cell count related to estimated benzene exposure in a rubber worker cohort (1940-1975). Am J Ind Med. 29(3):247-57.
Toluene
Toluene exposure can produce central nervous system pathology in animals after high oral doses. Repeated inhalation exposure can produce ototoxicity in the rat and high concentrations are associated with local toxicity (nasal erosion). In humans neurophysiological effects and disturbances of auditory function and colour vision have been reported, particularly when exposures are not well controlled and/or associated with noisy environments.
Documentation supporting the IOELV (SCOEL, 2001) concluded that an exposure limit of 50 ppm (192 mg/m3) would protect against chronic effects hence, in accordance with REACH guidance and since no new scientific information has been obtained under REACH which contradicts use of the IOELV for this purpose, the established IOELV of 50 ppm (192 mg/m3)[4]– 8 hr TWA (EU, 2006) will be used as the starting point for calculating the chronic dermal DNEL for workers.
Worker – long-term systemic inhalation DNEL
The IOELV will be used with no further modification
DN(M)ELl-t inhalation= IOELV = 192 mg/m3
Worker – long-term systemic dermal DNEL
The dermal DNEL for toluene is based on the internal dose achieved by a worker undertaking light work and exposed to the IOELV for 8 hr, assuming50% uptake by the lung and 3.6% uptake by skin(ten Berge, 2009).
As the IOELV is based on worker life-time exposure no assessment factor is needed.
Dermal NOAEL = IOELV x wRV8-hourx [50 / 3.6] = 192 x 0.144 x 13.8]
DN(M)ELl-t dermal = 384 mg/kg bw/d
Styrene
The cooperation of the Styrenics REACH consortia in providing DN(M)ELs for styrene is acknowledged.Documentation supporting these values is in the Styrenics REACH consortium dossier for styrene.
The EU transitional RAR(2008c) identified the following end-points as of concern for human health: acute toxicity (CNS depression), skin, eye and respiratory tract irritation, effects on colour vision discrimination following repeated exposure, effects on hearing (ototoxicity) following repeated exposure, developmental toxicity.
Worker – long-term systemic inhalation DNEL
The DN(M)EL is based on ototoxicity in humans(Triebig et al, 2009). A NOAEC for humans of 20 ppm (85 mg/m3) can be derived as starting point from this study. As the DNEL is derived from studies on exposed workers an assessment factor is not necessary.
DN(M)ELl-t inhalation= 85 mg/m3
Worker – long-term systemic dermal DNEL
The DN(M)EL is based on long term inhalation NOAEC of 20 ppm (86 mg/m3) for ototoxicity in workers. The dose descriptor is corrected into a human dermal NOAEL. Using a respiratory volume for workers under light physical activity of 10 m3/person/day and a body weight of 70 kg (ECHA, 2008b) the external exposure would be 86 x 10/70 = 12.3 mg/kg bw/d.
This is then converted to a dermal dose by adjusting for differences in exposure. Absorption of styrene from the respiratory tract is considered to be 66% based on a study in 7 volunteers at 50 ppm under light physical activity (50 Watt) (Engström et al, 1978). In humans only 2% of a dermal dose of liquid styrene is likely to be absorbed (EU, 2008c).
Dermal NOAEL = 12.3 x [ABSinhal-human/ ABSdermal-human]
= 12.3 x [66/2]
= 406 mg/kg/d.
Since the worker-DNEL long-term for dermal exposure was directly derived from that for inhalation exposure no further assessment factors are necessary.
DN(M)ELl-t dermal= 406 mg/kg bw/d
Xylene isomers
An IOELV (EU, 2000) is available for the xylenes isomers. Significant new hazard data (addressing for example ototoxicity and developmental effects) are available, but it is considered that these data do not impact the overall NOAEC values which would be used for derivation of DNELs and therefore Appendix R. 8-13 applies, allowing IOELVs to be considered as a starting point for derivation of DNELs.
ECETOC guidance for assessment factors and used and the IOELV as starting point for all DNELs (worker and general population).
Worker – long-term systemic inhalation DNEL
The IOELV of 50 ppm (221 mg/m3, 8h) is proposed.
Worker – long-term systemic dermal DNEL
The IOELV of 50 ppm (221 mg/m3, 8h) will be used for derivation of the worker DNELl-t dermal.
The IOELV (mg/m3) is corrected into a human dermal NOAEL (mg/kg bw/d) by adjusting for differences in uptake between the two routes of exposure (TGD, Appendix R.8-2, Example B.4).
It is assumed that uptake of xylenes after inhalation is 100% with a value of 1% for dermal absorption (ten Berge, 2009):
correctedDermal NOAEL = IOELV x wRVhuman-8hrx [ABSinhal-human/ ABSdermal-human]
correctedDermal NOAEL = 221 x 0.144 x (100 / 1) = 3182 mg/kg bw/d
No assessment factor is necessary.
Ethylbenzene
The cooperation of the Styrenics Steering Committee in providing DNELs for ethylbenzene is acknowledged.Documentation supporting these values is in the Styrenics REACH consortium dossier for ethylbenzene.
Worker – long-term systemic inhalation DNEL
There is no IOELV for ethylbenzene, therefore theDNEL is based on sub-chronic effects (ototoxicity) in the rat following inhalation exposure: extrapolated NOAEC = 500 mg/m3(114 ppm). Correct the NOAEC to adjust for activity driven and absorption percentage differences following ECHA TGD (2008b) guidance:
DNELl-t inhalation= 500 mg/m3x [6.7 / 10] x [ABSinhal-rat/ ABSinhal-human] = 500 mg/m3x 0.67 x [45 / 65] = 232 mg/m3
An assessment factor of 3 is used forintraspecies differences within worker population:
DN(M)ELl-t inhalation= 232 mg/m3/ 3 = 77 mg/m3
Worker – long-term systemic dermal DNEL
The DNEL is based on sub-chronic effects (ototoxicity) in the rat following inhalation exposure: extrapolated NOAEC = 500 mg/m3(114 ppm). The NOAEC is corrected into a human dermal NOAEL (mg/kg bw/d) by adjusting for differences in uptake between the two routes of exposure (TGD, Appendix R.8-2, Example B.4). It is assumed that uptake of ethylbenzene after inhalation in rats is 45%.
correctedDermal NOAEL = NOAECl-t inhalationx sRVrat-8hr[5]x 0.45 = 500 x 0.38 mg/kg bw/d = 86 mg/kg bw/d
A value of 4% used for dermal absorption in humans (Susten et al, 1990):
correctedDermal NOAEL = 86 mg/kg bw/d x [100 /4 ] = 2150 mg/kg bw/d
An assessment factor of 12 is used based on interspecies differences for the rat (4) and intraspecies differences within worker populations (3).
The DNEL for long-term dermal exposure is derived as follows:
DN(M)ELl-t dermal= 2150 mg/kg bw/d / 12 = 180 mg/kg bw/d
References
AGS (2008). Committee on Hazardous Substances. Guide for the quantification of cancer risk figures after exposure to carcinogenic hazardous substances for establishing limit values at the workplace.1 Edition. Dortmund: Bundesanstalt für Arbeitsschutz und Arbeitsmedizin. Available from:http://www.baua.de/nn_21712/en/Publications/Expert-Papers/Gd34,xv=vt.pdf
ASTDR (2005). Toxicological profile for naphthalene, 1-methylnaphthalene, and 2-methylnaphthalene.http://www.atsdr.cdc.gov/toxprofiles/tp67.pdf
Blank IH, McAuliffe DJ (1985). Penetration of benzene through human skin. J. Invest. Dermatol. 85, 522–526.
ECHA (2008b). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for for human health.
Engstrom K, Harkonen H, Pekari K and Rantanen J. (1978). Evaluation of occupational styrene exposure by ambient air and urine analysis. Scand. J. Work Environ. Health, 4 (Suppl. 2):121-123.
EU (1999). Council Directive 1999/38/EC of 29 April 1999 amending for the second time Directive 90/394/EEC on the protection of workers from the risks related to exposure to carcinogens at work and extending it to mutagens. Official Journal of the European Communities, L138, 66-69, 1 June 1999.
EU (2000).Council Directive 2000/39/EC of 8 June 2000 establishing a first list of indicative occupational exposure limit values (IOELV) in implementation of Council Directive 98/24/EC on the protection of the health and safety of workers from the risks related to chemical agents at work.Official Journal of the European Communities, L142, 47-50.
EU (2003). Risk assessment report for naphthalene. http://ecb.jrc.ec.europa.eu/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/naphthalenereport020.pdf
EU (2006). Directive 2006/15/EC of 7 February 2006 establishing a second list of indicative occupational exposure limit values in implementation of Council Directive 98/24/EC and amending Directives 91/322/EEC and 2000/39/EC. Official Journal of the European Union, l 38, 36 -39.
Maibach HI, Anjo DM (1981). Percutaneous penetration of benzene and benzene contained in solvents used in the rubber industry. Arch. Environ. Health 36, 256–260.
MAK (2009) MAK Commission. MAK, 46 Lieferung
Schnatter AR, Kerzic P, Zhou Y, Chen M, Nicolich M, Lavelle K, Armstrong T, Bird M, Lin l, Hua F and Irons R (2010). Peripheral blood effects in benzene-exposed workers.Chem Biol Interact184: 174-181.
SCOEL (2001).Recommendation from the Scientific Committee on Occupational Exposure Limits fortoluene108-88-3. http://ec.europa.eu/social/BlobServlet?docId=3816&langId=en
SCOEL (2010) Consolidated Indicative Occupational Exposure Limits Values (IOELVs). Available from http://ec.europa.eu/social/main.jsp?catId=153&langId=en&intPageId=684
Susten, AS et al (1990). In vivo percutaneous absorption studies of volatile organic solvents in hairless mice II; Toluene, ethylbenzene and aniline. J. Appl. Toxicol. 10: 217-225.
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[1] 6 hour value calculated from TGD Table R.8-17 values (as per guidance Appx R.8-2, example B.4) – sRV for mouse (mean male/female) is 1.43 L/min/kg bw = 0.514 m3/kg bw for 6 hours
[2] Data reported as 3.5 ppm, and converted to mg/m3using tool available fromhttp://www.cdc.gov/niosh/docs/2004-101/calc.htm
[3] Worker respiratory volume (wRV) is 50% greater than the resting standard respiratory volume of 0.2 L/min/kg bw (wRV8-hour= (0.2 L/min/kg bw x 1.5 x 60 x 8) / 1000 = 0.144 m3/kg bw
[4] mg/m3 values quoted in this document are as reported in the publication or calculated using a conversion at 25°C as used by ACGIH (http://www.cdc.gov/niosh/docs/2004-101/calc.htm).It is recognized that SCOEL used a different calculation
[5] Standard respiratory volume (sRV) of a 250 g rat = 0.38 m3/kg bw (TGDTable R.8-2)
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
These hydrocarbon streams are used as intermediates, in manufacture and hence no exposure to the general population is likely and no general population DNELs have been developed.
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