Distillates (coal tar), heavy oils

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

0.002 mg/m³

Most sensitive endpoint:

carcinogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1.4

Modified dose descriptor starting point:

other: Unit concentration for benzo(a)pyrene as marker substance derived by meta-analysis of epidemiological studies

Value:

2.5 µg/m³

Explanation for the modification of the dose descriptor starting point:

not relevant

AF for dose response relationship:

1.4

Justification:

extrapolation to target exposure related to excess lifetime risk (2.5/1.8)

AF for differences in duration of exposure:

1

Justification:

not applicable: DMEL covers working life

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable: DMEL relates directly to the target group

AF for other interspecies differences:

1

Justification:

not applicable: DMEL directly related to the target group

AF for intraspecies differences:

1

Justification:

not applicable: covered by epidemiological meta-analysis

AF for the quality of the whole database:

1

Justification:

not applicable: Database considered to be the best fit for deriving the unit relative risk (URR) for exposed workers.

AF for remaining uncertainties:

1

Justification:

not applicable: Database considered to be the best fit for deriving the excess lifetime-risk of exposed workers

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

0.001 mg/m³

Most sensitive endpoint:

carcinogenicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3.6

Dose descriptor:

other: 2.5 µg/m³ - unit concentration for benzo(a)pyrene as marker substance derived by meta-analysis of epidemiological studies.

AF for dose response relationship:

3.6

Justification:

Extrapolation to target exposure related to excess lifetime risk (2.5/0.7)

AF for differences in duration of exposure:

1

Justification:

not applicable: DMEL covers working life

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable: DMEL directly related to the target group

AF for other interspecies differences:

1

Justification:

not applicable: DMEL directly related to the target group

AF for intraspecies differences:

1

Justification:

not applicable: covered by epidemiological meta-analysis

AF for the quality of the whole database:

1

Justification:

not applicable: Database considered to be the best fit for deriving the unit relative risk (URR) of exposed workers.

AF for remaining uncertainties:

1

Justification:

not applicable: Database considered to be the best fit for deriving the excess lifetime-risk of exposed workers

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

0.2 mg/kg bw/day

Most sensitive endpoint:

carcinogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: A virtually safe oral dose (see below) is adapted to intake via dermal route and adjusted to an risk level of 4*10^-3.

Modified dose descriptor starting point:

other: Virtually safe dermal dose of benzo(a)pyrene, related to a risk level of 10E-5 (human)

Value:

0.5 µg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Dermal bioavailability is limited due to penetration inhibition by the skin barrier as well as by a matrix effect of the tar oil. The virtually safe oral dose for humans of 5 ng BaP/(kg bw*d) was modified by an adjustment factor of 1/100 (division by 0.01) to account for reduced absorption of BaP from tar oil through human skin compared to oral uptake (see Discussion – B. Explanations concerning systemic cancer (dermal exposure)).

Justification:

divisor of 0.0025: extrapolation from risk level of 10E-5 to 4*10E-3

AF for differences in duration of exposure:

1

Justification:

not adjusted to working time

AF for interspecies differences (allometric scaling):

1

Justification:

included in in the starting point

AF for other interspecies differences:

1

Justification:

included in in the starting point

AF for intraspecies differences:

1

Justification:

included in the starting point

AF for the quality of the whole database:

1

Justification:

not applicable, considered to be included in the starting point

AF for remaining uncertainties:

1

Justification:

considered to be sufficiently conservative

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

40 µg/cm²

Most sensitive endpoint:

carcinogenicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

62.5

Dose descriptor:

other: adjusted T25 = 2.5 mg/(cm²*d) (according to Guidance document R.8.5.2.1 b)

AF for dose response relationship:

62.5

Justification:

Extrapolation from 0.25 (exptl. T25) to risk level of 4*10E-3

AF for differences in duration of exposure:

1

Justification:

accounted for in modification of dose descriptor to adjusted starting point.

AF for interspecies differences (allometric scaling):

1

Justification:

not required for non-threshold local effect

AF for other interspecies differences:

1

Justification:

not required for non-threshold local effect

AF for intraspecies differences:

1

Justification:

not required for non-threshold effects

AF for the quality of the whole database:

1

Justification:

default AF

AF for remaining uncertainties:

1

Justification:

default AF

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

BACKGROUND INFORMATION

The main hazardous effects of coal-tar borne materials on human health are related to the carcinogenic potential of certain polycyclic aromatic hydrocarbons (PAH) that are constituents in coal tar and fractions derived thereof. Benzo(a)pyrene is accepted as the best investigated key component and, therefore, serves as marker substance for deriving relevant DMEL values.

A. Explanations concerning lung and bladder cancer (inhalation, local and systemic)

1.     The derivation of the DMELs for inhalation are based on benzo(a)pyrene [BaP] as a representative marker, because published data on workers´ exposure to complex PAH mixtures generally relate to this key constituent. 

2.     The source of a quantitative dose-response relationship in workers is the comprehensive meta-analysis of epidemiological studies (Armstrong et al 2003, 2004), performed for the British HSE.

3.  The results have been used by various expert groups/committees for deriving excess lifetime risks (ELR) and acceptable/tolerable exposure levels for workers exposed to PAH volatiles at workplaces. Among them are: RIVM/NL (EU 2008); Dutch expert committee (DECOS/NL) (HCN 2006); Ausschuss für Gefahrstoffe/DE (Committee on Hazardous Substances/DE) (AGS 2011).

4.     The starting point is the so-called Unit Relative Risk (URR) of 1.2 (CI95% 1.11-1.29) which was calculated for the development of lung cancer in workers exposed to complex volatile PAH mixtures for a working life. For the development of bladder cancer, the corresponding URR was 1.33 (CI95% 1.16-1.52) supported by a less robust database than for lung cancer (Armstrong et al. 2003, 2004). The average URR was related to an estimated cumulative exposure to 100 µg BaP/m³-years, which corresponds to an average of 2.5 µg BaP/m³for a working life of 40 years.

5.     The excess lifetime risks (ELR) that correlate with these URRs are extrapolated to the target risk level to calculate the final DMELs. As target risk threshold, the risk level of 4 *10^-3 has been adopted in compliance with the tolerance risk level of various national regulations (e.g. DE, NL). This meets the general procedure also addressed in the REACH Guidance R.8:

“…. some EU Member States have applied lifetime cancer risk estimates in judging tolerable risk levels for workers. For instance, a lifetime cancer risk of 4·10^-5(which corresponds to 10^-6per working year, assuming 40 years employment) is the starting point in setting occupational limit values in the NL (by the Health Council), although this level may be proposed to be (temporarily) adjusted upwards (with 4·10^-3as an upper limit) depending on economical or technical reasons (by the Social Economic Council)…

……In summary, the decision point for 'acceptable'lifetime(i.e. a working life of 40 years) cancer risk levels used for workers are generally around10^-5but higher or lower levels have been considered to be tolerable under certain circumstances.” (APPENDIX R.8-14). 

6.     For the purpose of deriving specific exposure-risk correlations, one needs to transform the relative risk into an absolute risk which is expressed as excess lifetime risk (ELR = number of cases above background risk (BG) in a population): ELR = [RR –1] *BG with RR = relative risk and BG = lifelong background risk. The excess lifetime risk at the target risk level, ELR(T), has to be defined by the applicant, here 4 in 1000 = 0.004. In the first step, RR(T) can be calculated, and in the second step, the target exposure concentration X can be derived (see below 7.) 

The background risk (BG) may slightly vary, depending on the national statistics employed. Hence, likewise the target exposure concentration T varies to a certain extent. For the prevalence of lung cancer in the male population, data of health reports of the German Federal government (Fed. Stat. Office 2009: see AGS 2011) were consulted (BG_lung= 7.4 %), while for the prevalence of bladder cancer in the male population, the 1997 background figures for British males were adopted (BG_bladder= 1.8 %) [used in the papers of Armstrong et al. 2003; 2004; see also EU 2008]. 

7.     Calculation of the target exposure concentration X:

The relative risk at the target risk level, RR(T), results from above mentioned equation: RR(T) = ELR(T) / BG + 1.
By introducing RR(T), the exposure concentration related to the target risk level can be calculated, using the log-normal (A) or the linear model (B). For low concentrations, there is no big difference between either approach.

A.   log-normal:

     RR(T) = URR^X/U, with X = unknown target concentration; Unit Risk concentration, here 100/40 = 2.5 µg/m³.

B.    Linear: RR(T) = (URR – 1)*X/U + 1, with X = unknown target concentration; Unit Risk concentration, here 100/40 = 2.5 µg/m³. CALCULATION RESULTS

• DMEL for systemic effect: - Calculation of the relative risk URR(T) related to the target(T) risk level 4 *10^-3:

URR(T) = [BG + ELR(T)] / BG = (0.018 + 0.004) / 0.018 = 1.22, with BG = 0.018. - Calculation using the log-normal model (AGS 2011, p.21/22: RR(T) = 1.22 = 1.33^(X/2.5) (note: 100 µg/m³ for 40 years) => log1.22 = X/2.5 *log1.33 => X = 1.77 µg/m³ (rounded to 1.8).

• DMEL for local effect: - Calculation of the relative risk URR(T) related to the target risk level 4 *10^-3:

URR(T) = [BG + ELR(T)] / BG = (0.074 + 0.004) / 0.074 = 1.054, with BG = 0.074.

- Calculation of the exposure concentration using the log-normal model - RR(T) = 1.054 = 1.2^(X/2.5): (note: 100 µg/m³ for 40 years);

=> log1.054 = X/2.5 *log1.2 X = 0.72 µg/m³ (rounded to 0.7).

ad A.       REFERENCES for inhalation exposure and cancer:

Ausschuss für Gefahrstoffe (AGS) (2011)Exposure-risk relationship for benzo[a]pyrene-in BekGS 910, Germany, April 2011 (Engl. version)

Armstrong, B.; Hutchinson, E.; Fletcher, T. (2003)Cancer risk following exposure to polycyclic aromatic hydrocarbons (PAHs): a meta-analysis. Sudbury, UKL Health and Safety Executive (HSE) [http://www.hse.gov.uk (accessed 2005)]

Armstrong, B.; Hutchinson, E.; Unwin, J.; Fletcher, T. (2004)Lung Cancer Risk after Exposure to Polycyclic Aromatic Hydrocarbons: A Review and Meta-Analysis. Environ. Health Perspect. 112, 970-978

EU (2008)Coal Tar Pitch, high temperature, CAS 65996-93-2, Risk Assessment Report, NL 2008 [http://esis.jrc.ec.europa.eu/]

HCN (2006)BaP and PAH from coal-derived sources: Health-based calculated occupational cancer risk values of benzo(a)pyrene and unsubstituted non-heterocyclic polycyclic aromatic hydrocarbons from coal-derived sources. Dutch Expert Committee on Occupational Standards (DECOS), Health Council of the Netherlands (Gezoodheitsraad), 21 Feb. 2006

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B. Explanations concerning systemic cancer (dermal exposure)

For oral uptake, BaP serves as marker substance for PAH mixtures (EU 2008: RAR on coal-tar pitch) (Scientific Committee on Food, SCF 2002: SCF/CS/CNTM/PAH/29 Final, 4 December 2002).

The method used for deriving the DMEL is different from the method depicted in the ECHA Document "Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health": Starting point for DMEL deduction is the "virtually safe dose" related to an excess lifetime risk of 10^-5 [5 ng BaP/(kg bw*d)] derived for humans as pointed out below. This value is adapted regarding bioavailability for the dermal exposure route and the acceptable excess lifetime risk (see below).

Kroese et al. (2001) calculated from the results of their long-term study with rats receiving pure BaP by gavage a “virtually safe dose” of 5 - 19 ng BaP/(kg bw*d) concerning fore-stomach tumours and number of tumour-bearing animals. Based on a 2-years study with mice receiving coal-tar material in the diet [Culp et al. 1998: NOAEL ca. 12, LOAEL ca. 36 mg/(kg bw*d)], they estimated a "virtually safe dose" of about 0.5 ng BaP/(kg bw*d) for humans at the excess life-time risk level of 10^-6 (Kroese et al. 2001, Chapter 5.5).

The Norwegian Food Control Authority also referred to the study by Culp et al. 1998 to perform a hazard characterisation for BaP in food (Alexander and Knutsen 2001, cited in SCF 2002). They used a simple linear extrapolation from T25 (the dose that produces skin tumours in 25 % of the animals). They calculated that a daily intake of 5.7 ng benzo[a]pyrene/kg bw would be associated with an excess lifetime cancer risk of 1x10^-5. This would correspond to a “virtually safe dose” of 0.57 ng BaP/kg bw/day calculated for a risk level of 1x10^-6(see SCF 2002, p. 56).

According to SCF (2002), “the estimated maximum daily intake of benzo[a]pyrene from food is approximately 420 ng benzo[a]pyrene per person, equivalent to approximately 6 ng/kg bw/day for a person weighing 70 kg. This is about 5 – 6 orders of magnitude lower than the daily doses observed to induce tumours in experimental animals.” (according to SCF 2002, p. 62). According to CSTEE (2001), the daily ingestion via food varies between 15 and 360 ng per individual. Furthermore: “From the recent studies in rodents, several authors have estimated “virtually safe doses” of BaP ranging from approximately 0.6 ng/(kg bw*d) to 5 ng/(kg bw*d) for a risk level of 1x10^-6, when based on all tumours combined. 0.5 – 5 ng BaP/(kg bw*d) is in the range of the daily BaP uptake of the general population via food. No evidence of tumours is attached to this range of a life-long oral BaP dose.

Calculation of the DMEL(dermal): The upper “virtually safe dose” for humans of 5 ng BaP/(kg bw*d) on a risk level of 10^-5 has been modified by an adjustment factor (divisor 0.01) in order to account for diffusion limitation due the skin-barrier function and due to structural characteristics of the substance (insoluble/poorly soluble solid or semi-solid): Hence, the dose-descriptor starting point is 5/0.01 ng BaP/(kg bw*d) = 0.5 µg BaP/(kg bw*d). This dose has to be extrapolated to the target risk level of 4 *10^-3, resulting in the dermal DMEL, long-term, for systemic effects of 0.2 mg BaP/(cm²*d).

ad B.        REFERENCES for dermal exposure and systemic cancer

Alexander, J., and Knutsen, A.K. 2001. Evaluation of PAH in olive oil. English translation of a Norwegian assessment September 2001. Unpublished paper submitted to the Committee by J. Alexander on 27 January 2002 (cited in SCF 2002).

Culp, S.J., Gaylor, D.W., Sheldon, W.G., Goldstein, L.S., Beland, F.A. 1998. A comparison of the tumors induced by coal tar and benzo(a)pyrene in a 2-year bioassay. Carcinogenesis 19, 117-124

CSTEE (Scientific Committee for Toxicity, Ecotoxicity and the Environment) 2001. Scientific Questions to the CSTEE on PAHs. Opinion on: Position Paper on Ambient Air Pollution by Polycyclic Aromatic Hydrocarbons (PAH) – Version 4, February 2001. Opinion expressed at the 24th CSTEE plenary meeting, Brussels, 21 June 2001. [http:/europa.eu.int/comm/food/fs/sc/sct/out108_en.htm]

Kroese, E.D., Muller, J.J.A., Mohn, G.R., Dortant, P.M. and Wester, P.W. 2001. Tumorigenic effects in Wistar rats orally administered benzo[a]pyrene for two years (gavage studies). Implications for human cancer risks associated with oral exposure to polycyclic aromatic hydrocarbons. National Institute of Public Health and the Environment,RIVM Report no. 658603 010,November 2001, Bilthoven.

SCF 2002. Opinion of the Scientific Committee on Food on the risks to human health of polycyclic aromatic hydrocarbons in food. SCF/CS/CNTM/PAH/29 Final,04 Dec. 2002, Eur. Commission [http://europa.eu.int/comm/food/fs/sc/scf/index_en.html]

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C. Explanations concerning local cancer (dermal exposure)

The DMEL relates to benzo(a)pyrene as marker substance representing total pitch or tar oil (AOH). The DMEL deduced corresponds to an excess lifetime risk for skin cancer in 4 out of 1000 deceased workers who had been exposed to the indicated dose to the very same skin area for a working time of 40 years (risk level 4 *10^-3).

In a dermal mouse oncogenicity study (FhI 1997) using tar oil with 10 and 270 ppm BaP (2d/wk for 78 weeks), a T25 value (the dose that produces skin tumours in 25 % of the animals) of 240 ng BaP per animal and day (2d/wk re-calculated to 5d/wk) can be derived. Assuming a treated skin area of 4 cm², the area-specific BaP dose is 60 ng BaP/(cm²*d) in the animal.

This value has been adopted as skin-area specific dose that produced skin tumours in 25 % of treated mice (relevant dose descriptor T25).

The derivation of DMEL follows the procedure outlined in ECHA document Guidance on information requirements and chemical safety assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health - Section R.8.5.2.1 "The linearised approach".

Step a)    Select the relevant dose-descriptor(s), i.e. T25 and BMD(L)10

As relevant dose descriptor an experimentalT25value of 60 ng/(cm²*d) was identified (see above).

Step b)    Modify, when necessary, the relevant dose descriptor to the correct starting point

1.  Differences in the skin barrier between rodent and human skin

Dermal bioavailability of BaP is determined by two variables, dermal absorption and release/availability of BaP from the pitch matrix or semi-solid tar oils.

Dermal absorption in rodents and humans is quite different. For a liquid tar oil, an absorption 8-fold lower in human skin than in rat skin was determined (Fasano 2007a,b). It is assumed this also applies to mouse skin. Therefore, the experimental T25 has been adjusted using a divisor of 0.125 (= 1/8) for the difference in dermal absorption. 

2.  Structural differences between test material and technical product  

The animal study (FhI 1997) was conducted with toluene-diluted samples. For (semi-)solid pitch (tar oils), it is assumed that the availability of active substances is substantially reduced. Less than 1 % of a skin-contamination is estimated to be released to skin from these substance types per shift. Therefore, for local dermal effects of (semi-)solid tar-oil fractions, a matrix factor of 0.01 has been applied in order to compensate for diffusion inhibition from the matrix of the substance.

3.  Differences in human and experimental exposure conditions

In the animal carcinogenicity study, the exposed skin area was covered (brushed) with the test material resulting in permanent direct contact between animal skin and test material.

The human exposure situation is quite different. It is characterised by the working environment in industries processing coal-tar materials with occasional skin contact. (Note: Furthermore, protection standards are high, but taken into account under exposure assessment). 

A factor of 0.1 is used to compensate for the much more stringent experimental exposure conditions compared to the working environment (Modification factor = 0.1).

4.  Differences between occupational and lifetime conditions of exposure

In the experimental study (FhI 1997), the test animals (mouse) had been exposed 2 times per week for 1.5 years, almost for lifetime (practically 24 hours per day:residual dose not removed). The dose descriptor has been adjusted to worker exposure conditions (8 h/d, 5d/wk for 40 years). The correction factor is calculated to be 0.19 (8/24*40/70) (Modification factor = 0.19) (Note: 5d/wk already included in experimental T25.)

5.  Calculation of the correct starting point

To obtain the correct starting point, the tentative dose descriptor (T25) has been divided by the respective modification factors: The overall modification factor obtained from Points 1 to 4 concerning differences in bioavailability and working conditions is 0.125 *0.01 *0.1 *0.19 = 0.000024. Hence, the dose descriptor starting point is T25_adjusted= 0.06/0.000024 µg/(cm²*d) = 2500 µg/(cm²*d).

Step c)    derive from the correct starting point a DMEL essentially by linear high to low dose extrapolation, and by application of assessment factors (when necessary)

1.  Assessment factors

-    Interspecies differences:                           1 (not required for non-threshold local effect)

-    Intraspecies differences:                           1 (not required for non-threshold effects)

-    Differences in duration of exposure:           1 (not required; life-long exposure or already accounted for under Step b) no 4.)

-    Issues related to dose-response:               62.5 (see high to low risk extrapolation factor)

-    Quality of whole database                         1 (default AF)

2.  Linear high to low dose risk extrapolation

The acceptable target risk level for workers exposed to coal tar pitch and related coal-tar fractions has been discussed and determined above under "A. Explanations concerning lung and bladder cancer (inhalation)". Using this risk level (4 *10^-3), an extrapolation factor for dose-response can be derived (extrapolation from high to low doses). To obtain the extrapolation factor, the risk of 0.25 related to the dose descriptor (T25) is divided by the acceptable target risk level of 4 *10^-3 resulting in a factor of 62.5. The DMEL representing the acceptable target risk level is derived by applying the AF on the adjusted starting point. Thus, the DMEL for local dermal long-term exposure of workers to (semi-)solid coal-tar materials has been assessed to be 40 µg/cm²/d (2500 µg/62.5) (deposited BaP dose).

ad C.       REFERENCES for dermal exposure and skin cancer

Fasano WJ (2007a)AWPA P1-P13 Creosote: In vivo dermal absorption in the rat. Report No. DuPont-19622, 02 July 2007, E.I. du Pont de Nemours and Company HaskellSM Laboratories (sponsored by Creosote Council III Inc./USA)

Fasano WJ (2007b)AWPA P1-P13 Creosote: In vitro kinetics in rat and human skin. Report No. DuPont-21647, 30 April 2007, E.I. du Pont de Nemours and Company HaskellSM Laboratories (sponsored by Creosote Council III Inc./USA)

Fraunhofer Institute of Toxicology and Aerosol Research (FhI) (1997) Dermal Carcinogenicity Study of Two Coal Tar Products (CTP) by Chronic Epicutaneous Application in Male CD-1 Mice (78Weeks).Final Report, Hanover, June 1997 (sponsored by the International Tar Association, ITA)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

0 mg/m³

Most sensitive endpoint:

carcinogenicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

357.5

Modified dose descriptor starting point:

other: Unit concentration (BaP) related to lifelong exposure (70 years) derived from a cumulative exposure of 100 µg BaP/m³ year for a unit relative risk of 1.33 (bladder cancer)

Value:

1.43 µg/m³

Justification:

Target exposure (DMEL) is calculated based on a URR of 1.33 for an ELR of 7x10E-6 using a log linear dose response relationship (see discussion below). Hypothetical AF for dose response relationship is 357.5. (0.0014/357.5 mg/m³ = 0.000004 mg/m³)

AF for differences in duration of exposure:

1

Justification:

not applicable: dose descriptor covers lifetime

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable: DMEL derivation is based on human data

AF for other interspecies differences:

1

Justification:

not applicable: DMEL derivation is based on human data

AF for intraspecies differences:

1

Justification:

not relevant for genotoxic carcinogens

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

0 mg/m³

Most sensitive endpoint:

carcinogenicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1 430

Dose descriptor:

other: Unit concentration (BaP) related to lifelong exposure (70 years) derived from a cumulative exposure of 100 µg BaP/m³ years for a unit relative risk of 1.20 (lung cancer)

Justification:

Target exposure (DMEL) is calculated based on a URR of 1.20 for an ELR of 7x10E-6 using a log linear dose response relationship (see discussion below). Hypothetical AF for dose response relationship is 1430. (0.00143/1430 mg/m³ = 0.000001 mg/m³)

AF for differences in duration of exposure:

1

Justification:

not applicable: dose descriptor covers lifetime

AF for interspecies differences (allometric scaling):

1

Justification:

not applicable: DMEL derivation is based on human data

AF for other interspecies differences:

1

Justification:

not applicable: DMEL derivation is based on human data

AF for intraspecies differences:

1

Justification:

not relevant for genotoxic carcinogens

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:

DMEL (Derived Minimum Effect Level)

Value:

0 mg/kg bw/day

Most sensitive endpoint:

carcinogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: Derivation of a virtually safe oral dose by several expert authors based on experimental carcinogenicity tests (see above under Selection of the DNEL(s) or other hazard conclusion - DMELs for workers - Discussion B.)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

The main hazardous effects of distillates (coal tar), heavy oils (anthracene oil high (> 50 ppm) BaP, AOH) on human health are related to the carcinogenic potential of certain polycyclic aromatic hydrocarbons (PAH) that are constituents in AOH. Benzo[a]pyrene (BaP) is accepted as the best investigated key component and, therefore, serves as marker substance for deriving relevant DMEL values.

Dose descriptor

The dose descriptor is extracted from a comprehensive meta-analysis of occupational epidemiological studies (n = 39) by Armstrong performed for the British HSE (Armstrong et al 2003, 2004, for details see above under Discussion for Workers). Data used were thoroughly evaluated by the authors. Studies were excluded from the analysis in which risks from carcinogenic co-exposure to carcinogens other than PAH were likely to be substantial.

A quantitative dose-response relationship was established by the authors using a log linear Poisson regression. A unit relative risk (URR) was estimated for lung cancer (1.20; 95%CI: 1.11 - 1.29, local effect) and for bladder cancer (1.33; 95%CI: 1.17 - 1.51, systemic effect). URR is the relative risk corresponding to 100 µg/m³ BaP years cumulative exposure.

Excess lifetime risk (ELR)

Unit relative risk and cumulated dose have to be related to the excess lifetime risk (ELR) acceptable for lifelong exposure to a carcinogen. Lifetime cancer risks, considered as tolerable by various countries, organisations, and committees for lifetime exposure of the general population, are generally in the range of 10^-5to 10^-6(see ECHA Guidance Document R.8, Appendix R.8-14). For AOH, an excess lifetime risk for lifelong exposure of 7x10^-6is adopted. This risk is in the range of 10^-5to 10^-6and takes into account that risk may be somewhat overestimated by the result of the meta-analysis as AOH does not contain carcinogenic PAH in such amounts as the tars representing working area in the epidemiological studies used in the meta-analysis.

Lifetime (background) risk

Lifetime (background) risk for the general population was derived using statistics of the European Commission (eurostat). Mortality data for the general population and number of deaths caused by lung cancer and by bladder cancer were taken from the table "Causes of death - absolute number - annual data (hlth_cd_anr) at the eurostat website (URL: http: //epp. eurostat. ec. europa. eu/portal/page/portal/health/causes_death/data/database). EU 15 data (European Union, 15 countries) for 2009 and 2010 (most recent years reported) were used. The 15 countries are considered to be the best fit with respect to the distribution of sites processing AOH within the European Union. Mean values over the two years were formed and the resulting numbers were used to calculated percentage of death caused by cancer.

 

	Lung cancer	Bladder cancer
Lifetime risk (background)	5.5 %	0.85 %

 

To derive a DMEL, the unit relative risk (URR) has to be converted to a target relative risk RR(T) related to the excess lifetime risk using the following equation:
ELR = lifetime risk (background) * [RR(T) - 1] --> RR(T) = [ELR/lifetime risk (background) ] + 1.

In a second step, DMEL is calculated using the log linear dose response relationship
RR(T) = URR^{(x/unit risk concentration)}converting the unit risk concentration to the concentration related to the target risk level. x represents the wanted (target) concentration (here DMEL), and unit risk concentration stands for the unit risk dose (cumulative unit risk exposure adjusted regarding exposure years and exposure route).

x = log RR(T) / log URR * unit risk concentration (x = DMEL).

Calculation of DMELs

General population - Inhalation route - Systemic effects - Long term exposure (toxicological endpoint bladder cancer)

URR = 1.33 at 100 µg BaP/m³ years

Lifetime risk = 0.86 %

Unit risk concentration = 1.43 µg/m³

I.                URR(T) = (7x10^-6/ 0.0086) + 1 = 1.000814

II.               x = log 1.000814 / log 1.33 * 1.43

DMEL =    4.1 ng/m³

General population - Inhalation route - Local effects - Long term exposure (toxicological endpoint lung cancer)

URR = 1.20 at 100 µg BaP/m³ years

Lifetime risk = 5.5 %

Unit risk concentration = 1.43 µg/m³

I.                URR(T) = (7x10-6/ 0.055) + 1 = 1.0001273

II.               x = log 1.0001273 / log 1.20 * 1.43

DMEL =    1 ng/m³