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EC number: 266-028-2
CAS number: 65996-93-2
The residue from the distillation of high temperature coal tar. A black solid with an approximate softening point from 30°C to 180°C (86°F to 356°F). Composed primarily of a complex mixture of three or more membered condensed ring aromatic hydrocarbons.
Dermal bioavailability is limited due to penetration inhibition by the
skin barrier as well as by a matrix effect of pitch. 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 coal tar pitch through human skin compared to oral uptake (see
Discussion – B. Explanations concerning systemic cancer (dermal
hazardous effects of pitch on human health are related to the
carcinogenic potential of certain polycyclic aromatic hydrocarbons (PAH)
that are constituents in pitch. Benzo[a]pyrene is accepted as the best
investigated key component and, therefore, serves as marker substance
for deriving relevant DMEL values.
Explanations concerning lung and bladder cancer (inhalation, local and
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.
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.
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).
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.
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*10E-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:
EU Member States have applied lifetime cancer risk estimates in judging
tolerable risk levels for workers. For instance, a lifetime cancer risk
of 4*10E-5 (which
corresponds to 10E-6 per 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*10E-3
an upper limit) depending on economical or technical reasons (by the
Social Economic Council)…
summary, the decision point for 'acceptable' lifetime
a working life of 40 years) cancer risk levels used for workers are
generally around 10E-5,
higher or lower levels have been considered to be tolerable under
certain circumstances.” (APPENDIX R.8-14).
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.)
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 (BGlung=
7.4%), while for the prevalence of bladder cancer in the male
population, the 1997 background figures for British males were adopted
(BGbladder= 1.8%) [used in the papers of Armstrong et al.
2003; 2004; see also EU 2008].
of the target exposure concentration X:
relative risk at the target risk level, RR(T), results from above
mentioned equation: RR(T)
= ELR(T)/BG + 1.
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
with X = unknown target concentration; Unit Risk concentration, here
100/40 = 2.5 µg/m³.
= (URR – 1)*X/U
+ 1, with X = unknown target concentration; Unit Risk concentration,
here 100/40 = 2.5 µg/m³.
ad A. REFERENCES
inhalation exposure and cancer:
für Gefahrstoffe (AGS) (2011) Exposure-risk
relationship for benzo[a]pyrene-in BekGS 910, Germany, April 2011
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)]
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
Tar Pitch, high temperature, CAS 65996-93-2, Risk Assessment Report, NL
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
Explanations concerning systemic cancer (dermal exposure)
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).
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 10E-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
10E-6 (Kroese et al. 2001, Chapter 5.5).
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 1*10E-5.
This would correspond to a “virtually safe
dose” of 0.57 ng BaP/kg bw/day calculated for a risk level of
1*10E-6(see SCF 2002, p. 56).
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
1*10E-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.
of tumours is attached to this range of a life-long oral BaP dose.
of the DMEL(dermal):
The upper “virtually safe dose” for humans of 5 ng BaP/(kg bw*d) on a
risk level of 10E-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*10E-3, resulting in the dermal DMEL, long-term, for systemic
effects of 0.2 mg BaP/(cm²*d).
dermal exposure and systemic cancer
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).
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
(Scientific Committee for Toxicity, Ecotoxicity and the Environment)
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.
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
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]
Explanations concerning local cancer (dermal exposure)
DMEL relates to benzo[a]pyrene as marker substance representing total
coal tar pitch. 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).
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
value has been adopted as skin-area specific dose that produced skin
tumours in 25 % of treated mice (relevant dose descriptor T25).
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.220.127.116.11 "The linearised approach".
the relevant dose-descriptor(s), i.e. T25 and BMD(L)10
relevant dose descriptor, an experimental T25 value of 60
ng/(cm²*d) was identified (see above).
when necessary, the relevant dose descriptor to the correct starting
in the skin barrier between rodent and human skin
of BaP from coal tar pitch for local dermal effects is determined by two
variables, dermal absorption and release/availability of BaP from the
pitch matrix or semi-solid tar oils.
absorption in rodents and humans is quite different. For a 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.
differences between test material and technical product
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
pitch-like substances, a matrix factor of 0.01 has been applied
in order to compensate for diffusion inhibition from the matrix of the
in human and experimental exposure conditions
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.
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).
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).
between occupational and lifetime conditions of exposure
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.)
of the correct starting point
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
T25adjusted= 0.06/0.000024 µg/(cm²*d) = 2500 µg/(cm²*d).
from the correct starting point a DMEL essentially by linear high to low
dose extrapolation, and by application of assessment factors (when
required for non-threshold local effect)
(not required for non-threshold effects)
in duration of exposure: 1
(not required; life-long exposure or already accounted for
under Step b) no 4.)
related to dose-response: 62.5
(see high to low risk extrapolation factor)
of whole database 1
high to low dose risk extrapolation
acceptable target risk level for workers exposed to coal tar pitch has
been discussed and determined above under "A. Explanations concerning
lung and bladder cancer (inhalation)". Using this risk level (4*10E-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*10E-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
pitch-like substances has been assessed to be 40 µg/cm²/d
(deposited BaP dose).
ad C. REFERENCES
for dermal exposure and skin cancer
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
HaskellSMLaboratories (sponsored by Creosote Council III Inc./USA)
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
HaskellSMLaboratories (sponsored by Creosote Council III Inc./USA)
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)
The main hazardous effects of coal tar pitch, high temp. on human
health are related to the carcinogenic potential of certain polycyclic
aromatic hydrocarbons (PAH) that are constituents in pitch, coal tar,
high-temp. Benzo[a]pyrene is accepted as the best investigated key
component and, therefore, serves as marker substance for deriving
relevant DMEL values.
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
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 10E-5 to 10E-6 (see
ECHA Guidance Document R.8, Appendix R.8-14). For pitch, coal tar,
high-temp., an excess lifetime risk for lifelong exposure of 7*10E-6 is
adopted. This risk is in the range of 10E-5 to 10E-6 and takes into
account that risk may be somewhat overestimated by the result of the
meta-analysis as coal tar pitch, high temp. does not contain
carcinogenic PAH in such amounts as the tars representing working areas
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
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 coal tar
pitch, high temp. 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.
Lifetime risk (background)
DMEL Derivation (Inhalation)
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
= (7*10E-6/ 0.0086) + 1 = 1.000814
= 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%
= (7*10E-6/ 0.055) + 1 = 1.0001273
= log 1.0001273 / log 1.20 * 1.43
DMEL = 1 ng/m³
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