Distillates (petroleum), polymd. steam-cracked petroleum distillates, C5-12 fraction

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

3.25 mg/m³

DNEL related information

Overall assessment factor (AF):

1

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

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:<75%

·        Methylcyclopentadiene:<60%

·        Benzene: <0.1 - 25%

·        1,3-butadiene: <0.1 -1%

·        Isoprene: <0.1 – 3%

·        Toluene: up to 22%

·        Naphthalene: up to 48%

·        Styrene: up to 40%

·        C8 Aromatics (xylene, ethylbenzene) up to 25%

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:

In general, risk characterization will be based on the premise that a marker substance with a low DN(M)EL present at high concentration in a stream will possess a greater relative hazard potential than a marker substance with a higher DN(M)EL present at the same or lower concentration.

Against this background, the most hazardous marker substances present in these streams are highlighted in the following table (details of the DN(M)EL derivations follow this table):

 

Marker substance	Indicative concentration (%)	Inhalation		Dermal
		DN(M)EL mg/m^3	Relative hazard potential (max % ÷ DN(M)EL)	DN(M)EL mg/kg bw/d	Relative hazard potential (max % ÷ DN(M)EL)
dicyclopentadiene / methylcyclopentadiene	<75%	2.3	32.6	0.34	220
benzene	<0.1 to 25	3.25	7.69	23.4	1.07
1,3-butadiene	<0.1 to 1	2.21	0.45	na	na
isoprene	<0.1 to 3	8.4	0.36	23.7	0.13
toluene	Up to 22	192	0.11	384	0.06
naphthalene	Up to 48	50	0.96	72	0.67
styrene	Up to 40	85	0.47	406	0.10
xylenes	Up to 25	221	0.11	3182	<0.01
ethylbenzene	Up to 25	77	0.32	180	0.14

Based on this analysis, management of inhalation and dermal hazards associated with the presence of dicyclopentadiene / methylcyclopentadiene should also provide adequate protection against hazards arising from other marker substances present. However this conclusion does not consider the relative volatilities of the substances present, and overlooks the fact that benzene is a human carcinogen requiring an appropriate level of control.

Hence, in order to demonstrate safe use in worker exposure scenarios computed by application of the ECETOC TRA, estimates of inhalation exposure and risk characterisation will use benzene as the marker substance (based on its relatively high volatility and carcinogenicity), while estimates of dermal exposure and risk characterisation will use DCPD as the marker substance (based on its lower volatility and very low dermal DNEL).

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 DNEL_{l-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).

DNEL_{l-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 DNEL_{l-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 = NOAEC_inhalationx sRV_mouse^[1]x [ABS_inhal-mouse/ABS_dermal-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).

DNEL_{l-t dermal}= 14.19 mg/kg bwt/d / 42 = 0.34 mg/kg bw/d

Methylcyclopentadiene

No data were located for this substance, hence hazard identification/risk characterization will be based on dicyclopentadiene.

Benzene

Benzene causes adverse effects on the haematopoietic system of animals and in humans after repeated dose exposure via oral or inhalation routes. Long term experimental carcinogenicity bioassays have shown that it is a carcinogen producing a variety of tumours in animals (including lymphomas and leukaemia). Human epidemiological studiesprovide clear and consistent evidence of a causal association between benzene exposure and acute myelogenous (non-lymphocytic) leukaemia (AML or ANLL). An effect on bone marrow leading to subsequent changes in human blood cell populations is believed to underpin this response.

In accordance with REACH guidance, a science-based Binding Occupational Exposure Limit value (BOELV) can be used in place of a formal DN(M)EL providing no new scientific information exists which challenges the validity of the BOELV. While some information regarding a NOAEC for effects of benzene on human bone marrow (Schnatter et al, 2010; NOAEC = 11.18 mg/m³)^[2]post-date the BOELV, a DNEL based on these bone marrow findings would be higher than the BOELV. The BOELV (EU, 1999) will therefore be used as the basis of the DN(M)EL for long-term systemic effects associated with benzene, including carcinogenicity.

Worker – long-term systemic inhalation DNEL

The BOELV will be used with no further modification

DN(M)EL_{l-t inhalation}=3.25 mg/m³

Worker - long-term systemic dermal DNEL

The dermal DNEL for benzene is based on the internal dose achieved by a worker undertaking light work and exposed to the BOELV for 8 hr,assuming 50% uptake by the lung and 1% by skin for benzene uptake from petroleum streams. The value of 1% is based on experiments with compromised skin and with repeated exposure (Blank and McAuliffe, 1985; Maibach and Anjo, 1981) as well as the general observation that vehicle effects may alter the dermal penetration of aromatic compounds through the skin (Tsuruta et al, 1996).

As the BOELV is based on worker life-time cancer risk estimates no assessment factor is needed.

Dermal NOAEL = BOELV xwRV_8-hour[3] x [ABS_inhal-human/ ABS_dermal-human] = 3.25 x 0.144 x [50 / 1] = 23.4

DN(M)EL_{l-t dermal}= 23.4mg/kg bw/d

1,3-Butadiene

1,3-Butadiene is a multi-species carcinogen.In the mouse, it is a potent multi-organ carcinogen. Tumours develop after short durations of exposure, at low exposure concentrations and the carcinogenic response includes rare types of tumours. In the rat, fewer tumour types, mostly benign, develop at exposure concentrations of 100 to1000-times higher than in the mouse. In humans, 1,3-butadiene is a recognised carcinogen. A positive association was demonstrated between workplace exposure to butadiene for men employed in the styrene-butadiene rubber industry and lymphohaematopoietic cancer (leukaemia). Various models have established a dose response-relationship for cumulative exposure to 1,3 -butadiene, especially concentrations above 100 ppm. The estimates for occupational and population human risk are based on these models.

Worker – long-term systemic inhalation DNEL

The association between 1,3-butadiene exposure and leukaemia has been extensively modeled using Cox and Poisson regression models and the excess risk of leukaemia determined. The preferred model for workers is the Cox continuous model (Cheng et al, 2007) as employed by Sielken et al (2008), using the exposure metric that excluded exposure that occurred more than 40 years ago or excluded the 5% of workers with the highest cumulative 1,3-butadiene exposures and included as covariate, the cumulative number of exposures to 1,3-butadiene concentrations > 100 ppm (the number of High Intensity Tasks [HITs]). This model incorporates dose descriptors and assessment factors and therefore further corrected dose descriptors and overall assessment factors are not required. The estimate of the excess risk of death from leukaemia as a result of exposure to a DMEL of 2.21 mg/m³(1 ppm) is 0.33 x 10^-4(with an upper bound of 0.66 x 10^-4based on a one-sided 95% upper confidence limit for the regression parameter).

This estimate is less than 0.4 x 10^-4, which has been proposed as a future limit for acceptable occupational risk (AGS, 2008). Regression coefficients from other Cox regression models reported by Cheng et al (2007) and TCEQ (2008), and estimates from Poisson regression models, indicate that other risk estimates are generally close to 0.4 x 10^-4, even if based on regression models that do not adjust for 1,3-butadiene HITs. All of the estimates are considerably lower than the current limit for acceptable occupational risk of 4 x 10^-4that has recently been proposed (AGS, 2008).

DN(M)EL_{l-t inhalation}=2.21 mg/m³

Worker – long-term systemic dermal DNEL

1,3-Butadiene is a gas at room temperature and thereforeno DNEL is proposed.

Isoprene

Isoprenehas been shown to be carcinogenic to mice and rats. When inhaled in concentrations of 70 ppm and above, it was found to induce tumours in a range of tissues in male mice while tissue responses in females were more limited. No statistically significant increases in tumours were reported in either sex at a dose level of 10ppm. Inhalation by rats of concentrations above 220 ppm caused a significantly increased incidence of mammary gland, testicular and kidney tumours in males, and mammary gland tumours in females. At the lowest dose tested, 220 ppm, a statistically significant increase in only mammary gland fibroadenoma was observed in females.

Worker – long-term systemic inhalation DNEL

In accordance with REACH guidance (Appendix R.8-13), the established MAK (2009) value of 3 ppm (equivalent to 8.4 mg/m³) - 8 hr TWA will form the basis of the inhalation DNEL for workers. It was concluded by the MAK Commission that a maximum admissible concentration can be established for humans and that the carcinogenic and genotoxic effects of isoprene is low. There would be no appreciable increase of carcinogenic risk in humans if this value is not exceeded.

DN(M)EL_{l-t inhalation}= 8.4 mg/m³

Worker - long-term systemic dermal DNEL

The long-term dermal DN(M)EL is calculated from the inhalation DN(M)EL using route-to-route extrapolation, having determined the net inhalation uptake or dose.Filser et al (1996) determined the rates of isoprene metabolism (µmol/hr/kg bw) in humans, rats, and mice at steady-state over a range of atmospheric concentrations to validate a PT model for isoprene. Metabolism of isoprene is linear up to 50 ppm. At the isoprene exposure concentration of interest 8.4 mg/m³(3 ppm), the rate of metabolism (µmol/hr/kg bw) can be determined and subtracted from the rate of metabolism at 0 mg/m³(0 ppm).At an exposure concentration of 3 ppm, the rate of isoprene metabolism is 0.13 µmol/hr/kg bw and in an 8-hr workday, net inhalation uptake (or dose) is: 0.13 µmol/hr/kg bw x 8 hr i.e. 1.04 µmol/kg (equivalent to 71 µg/kg). This value is adjusted for the low absorption factor of 0.003%.

DN(M)EL_{l-t dermal}=0.071 mg/kg/d / 0.003 = 23.7 mg/kg/d

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)EL_{l-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 wRV_8-hourx [50 / 3.6] = 192 x 0.144 x 13.8]

DN(M)EL_{l-t dermal}= 384 mg/kg bw/d

Naphthalene

The EU RAR (EU, 2003b) identified the key health effects from naphthalene as haemolytic anaemia, repeat dose toxicity and nasal tumours in the rat. Naphthalene is included in the SCOEL (2010) consolidated list of IOELVs, and the 50 mg/m³limit will be used as the basis for calculating DNELs.

Worker – long-term systemic inhalation DNEL

The long-term systemic DNEL for naphthalene will be based upon the IOELV with no further modification

DN(M)EL_{l-t inhalation}= IOELV = 50 mg/m³

Worker – long-term systemic dermal DNEL

The dermal NOAEC is extrapolated from the IOELV. The IOELV (mg/m³) is converted into a human dermal NOAEL (mg/kg bw/d) after adjusting for differences in uptake between the two routes of exposure (TGD, Appendix R.8-2, Example B.4).

The EU RAR and ASTDR (2005) indicate that naphthalene is well absorbed via inhalation and oral routes. Dermal exposure may also result in significant systemic absorption. However, data are insufficient as to the rate and extent of absorption via the different routes. Since no substance-specific data are available a conservative default of 100% uptake via inhalation and 10% via dermal routes will be used.

Dermal NOAEL = IOELV x wRV_8-hour x [ABS_inhal-human/ ABS_dermal-human] = 50 x 0.144 x [100 / 10] = 72mg/kg bw/d

As the IOELV is based on human data no assessment factor is needed.

DN(M)EL_{l-t dermal}= 72 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)EL_{l-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 [ABS_inhal-human/ ABS_dermal-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)EL_{l-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 DNEL_{l-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 wRV_human-8hrx [ABS_inhal-human/ ABS_dermal-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:

DNEL_{l-t inhalation}= 500 mg/m³x [6.7 / 10] x [ABS_inhal-rat/ ABS_inhal-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)EL_{l-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 = NOAEC_{l-t inhalation}x sRV_rat-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)EL_{l-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.

Cheng H, Sathiakumar N, Graff J, Matthews R, Delzell E (2007). 1,3-Butadiene and leukemia among synthetic rubber industry workers: exposure-response relationships. Chem Biol Interact, 166, 15-24.

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.

Filser JG, Csanady GA, Denk B, Hartmann M, Kauffmann A, Kessler W, Kreuzer PE, Putz C, Shen JH, Stei P.(1996). Toxicokinetics of isoprene in rodents and humans. Toxicology 113:278-287.

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

Sielken RL, Valdez-Flores C, Delzell E (2008). Quantitative Risk Assessment of Exposures to Butadiene in European Union Occupational Settings Based on the University of Alabama at Birmingham Epidemiological Study: All Leukemia, Acute Myelogenous Leukemia, Chronic Lymphocytic Leukemia, and Chronic Myelogenous Leukemia. Unpublished report to Lower Olefins Sector Group, Brussels, Belgium.

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.

ten Berge W (2009). A simple dermal absorption model: Derivation and application. Chemosphere, 75, 1440-1445.

TCEQ (2008). Texas Commission on Environmental Quality. Development Support Document. 1,3-Butadiene. Chief Engineer’s Office. Available from:http://tceq.com/assets/public/implementation/tox/dsd/final/butadiene,_1-3-_106-99-0_final.pd

Triebig G, Bruckner T and Seeber A (2009). Occupational styrene exposure and hearing loss: a cohort study with repeated measurements. Int Arch Occup Environ Health, 82 (4), 463-481.

Tsuruta H (1996). Skin absorption of solvent mixtures-effect of vehicle on skin absorption of toluene. Ind. Health 34, 369–3

 

^[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 (wRV_8-hour= (0.2 L/min/kg bw x 1.5 x 60 x 8) / 1000 = 0.144 m³/kg bw

[4]mg/m³values 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

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

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.