Creosote oil, acenaphthene fraction

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

0.24 mg/m³

Most sensitive endpoint:

carcinogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

62.5

Modified dose descriptor starting point:

T25

Value:

15.04 mg/m³

Explanation for the modification of the dose descriptor starting point:

Dose descriptor is an oral T25 for rats. This value is converted to the corrected dose descriptor starting point by route to route extrapolation (oral rat to inhalation worker) and allowing for differences between occupational and lifetime conditions of exposure according to ECHA guidance documents (see below under Discussion).

AF for dose response relationship:

62.5

Justification:

high to low dose extrapolation factor (from T25 to risk level of 4x10E-3; 0.25/0.004)

AF for differences in duration of exposure:

1

Justification:

not required; T25 originates from a chronic carcinogenicity study

AF for interspecies differences (allometric scaling):

1

Justification:

not required; already accounted for in route to route extrapolation

AF for other interspecies differences:

1

Justification:

not required for non-threshold effects

AF for intraspecies differences:

1

Justification:

not required for non-threshold effects

AF for the quality of the whole database:

1

Justification:

not required, database quality is adequate

AF for remaining uncertainties:

1

Justification:

not required

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

neurotoxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

irritation (respiratory tract)

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:

0.068 mg/kg bw/day

Most sensitive endpoint:

carcinogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

250

Modified dose descriptor starting point:

T25

Value:

17.06 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Dose descriptor is an oral T25 for rats. This value is converted to the corrected dose descriptor starting point by route to route extrapolation (oral rat to dermal worker) and allowing for differences between occupational and lifetime conditions of exposure according to ECHA guidance documents (see below under Discussion).

AF for dose response relationship:

62.5

Justification:

high to low dose extrapolation factor (from T25 to risk level of 4x10E-3; 0.25/0.004)

AF for differences in duration of exposure:

1

Justification:

not required; T25 originates from a chronic carcinogenicity study

AF for interspecies differences (allometric scaling):

4

Justification:

adjustment from rat to humans

AF for other interspecies differences:

1

Justification:

not required for non-threshold effects

AF for intraspecies differences:

1

Justification:

not required for non-threshold effects

AF for the quality of the whole database:

1

Justification:

not required, database quality is adequate

AF for remaining uncertainties:

1

Justification:

not required

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

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

Creosote oil, acenaphthene fraction (wash oil) is a liquid UVCB substance mainly consisting of 2- and 3-ring aromatic compounds, some 50 % of which composed of naphthalene (Naph) (ca. 11 - 13 %), 2-methylnaphthalene (2-MN) (ca. 17 - 20 %), 1-methylnaphthalene (1-MN) (ca. 7 - 9 %) and acenaphthene (ca. 13 - 15 %). Up to 8 % may comprise of quinoline.

The vapour pressure of wash oil is approx. 40 Pa at 20 °C, mainly dominated by the volatility (vapour pressure) of the mentioned components: vapour pressures of Naph ca. 11 Pa (5°C), 2-MN ca. 9 Pa (25°C), 1-MN ca. 8 Pa (25°C), and quinoline ca. 11 Pa (25 °C). With regard to wash oil (constituents) vapour pressure, inhalation has to be considered as the main potential route of exposure of workers. These constituents are expected to largely represent the physico-chemical and toxicological properties of wash oil.

Long-term effects - derivation of DMELs

Quinoline is classified as carcinogen thus also triggering classification of wash oil as carcinogenic (CLP Carc. Cat. 1B). This identifies carcinogenicity as the leading health effect of wash oil. Therefore, quinoline has been adopted as marker substance for long-term systemic effects in workers by the inhalation and dermal route. DMELs (inhalation and dermal exposure) will be derived based on an oral T25 of 6 mg/kg bw/day as dose descriptor obtained from a carcinogenicity study with rats (Hirao et al 1976, see Chapter 5.8. - Carcinogenicity). DMELs are derived using the linearised approach according to ECHA guidance on IR&CSA Chapter R.8: Characterisation of dose [concentration]-response for human health.

Justification for the risk level adopted

In order to derive a DMEL an 'acceptable/tolerable' risk level has to be defined. For worker exposure, a range of risk levels (in the order of 10^-3- 10^-5) has been discussed by several institutions (ECHA guidance on IR&CSA Chapter R.8: Characterisation of dose [concentration]-response for human health, Appendix R.8-14 - Evaluating carcinogenicity risk levels; a review of decision points). In the decision on an 'acceptable' or 'tolerable' risk for workers, technical and socioeconomic reasons can be taken into account. After having implemented effective risk management measures following the principles of good occupational hygiene practice (as required in the Carcinogens and Mutagens Directive - 2004/37/EC), the remaining risk is assessed and it is decided on the level of a tolerable or acceptable risk.

In order to develop a worker risk level for wash oil, a practice of the Netherlands (Health Council, Social Economic Council) was followed. A starting point acceptable lifetime cancer risk of 4 * 10^-5 is adjusted to a still tolerable level of 4 * 10^-3 for technical and socioeconomic reasons. This risk level is considered still acceptable for workers by European countries (The Netherlands, Germany, Switzerland) (for background on evaluation of risk levels see above ECHA guidance Appendix R.8-14). This risk level (4 * 10^-3 is used in the derivation of the worker DMELs for quinoline.

This risk level is also considered justified for reasons that the carcinogenic potency of quinoline is probably overestimated using experimental data only available from an oral (feeding) study for exposure via inhalation and dermal route. By oral administration, highly toxic intermediates can be produced in the liver (target location) by the 'first pass effect' which is only relevant after oral but not after inhalation or dermal application (see under Carcinogenicity CSR Chapter 5.8.3).

Derivation of DMEL inhalation

In a first step, the dose descriptor (oral T25) is converted to the correct starting point using

a) route-to-route extrapolation including differences in experimental and human exposure conditions and differences in respiratory volume between animals (at rest) and humans (light activity) followed by

b) accounting for differences between occupational and lifetime conditions of exposure.

In a second step, the DMEL is derived by linear high to low dose extrapolation and by application of assessment factors when necessary.

Step 1 - Route-to-route extrapolation and adjustment for differences in exposure

a)  Route-to-route extrapolation includes conversion of the oral T25 for rats to the corresponding inhalation concentration for workers applying the conversion factors of guidance document R.8, Section R.8.4.2, Figure R. 8-3. As worst case, intestinal absorption is set at half of inhalation absorption (see Section r.8.4.2., Ad 2.).

Corrected exposure value           = 6 / 0.38 * (6.7 / 10) * (0.5 / 1) mg/m³

                                                  = 5.29 mg/m³

b)  For conversion regarding differences between occupational and lifetime exposure, the ECHA guidance default values are applied (7 to 5 days per week, 52 to 48 weeks per year, and 75 to 40 years for lifetime).

Dose descriptor starting point   = 5.29 * (7/5) * (52/48) * (75/40) mg/m³

(corrected T25 for inhalation)    = 15.04 mg/m³

Step 2 - Assessment factors and high-to-low dose extrapolation

No assessment factor is needed except high-to-low dose extrapolation. Allometric scaling and differences in exposure conditions are already accounted for in Step 1. Worker risk level was set at 4 * 10^-3. With a T25 as dose descriptor the dose-response extrapolation factor is

high-to-low dose (dose-response) extrapolation factor   = 0.25 / 4x10^-3

= 62.5

As there are no other assessment factors, the overall assessment factor is as well 62.5.

The DMEL is calculate by division of the dose descriptor starting point by the overall assessment factor.

Worker-DMEL inhalation, systemic effects, long-term   = 15.04/62.5 mg/m³

= 0.24 mg/m³

Derivation of DMEL dermal route

In a first step, the dose descriptor (oral T25) is converted to the corrected starting point using

a) route-to-route extrapolation followed by

b) accounting for differences between occupational and lifetime conditions of exposure.

In a second step, the DMEL is derived by linear high to low dose extrapolation and by application of assessment factors when necessary.

Step 1 - Route-to-route extrapolation

a)  As worst case, it is assumed that intestinal absorption in rat is the same as human dermal absorption. In this case, there is no difference between the T25 oral and the T25 dermal.

Corrected exposure value           = 6 * (1 / 1) mg/kg bw/day

= 6 mg/kg bw/day

b)  For conversion regarding differences between occupational and lifetime exposure, the ECHA guidance default values are applied (7 to 5 days per week, 52 to 48 weeks per year, and 75 to 40 years for lifetime).

Dose descriptor starting point                  = 6 * (7/5) * (52/48) * (75/40) mg/kg bw/day

(corrected T25 for dermal route)              = 17.06 mg/kg bw/day

Step 2 - Assessment factors and high to low dose extrapolation

For allometric scaling (rat to man) an assessment factor of 4 is required. Differences in exposure conditions are already accounted for in Step 1. Worker risk level was set at 4 * 10^-3. With a T25 as dose descriptor, the assessment factors are:

Assessment factor for allometric scaling (rat to humans)                             4

High to low dose (dose-response) extrapolation factor   (= 0.25 / 4x10^-3)      62.5

Multiplication of assessment factors results in an overall assessment factor of   250

The DMEL is calculate by division of the dose descriptor starting point by the overall assessment factor.

Worker-DMEL dermal, systemic effects, long-term   = 17.06 / 250 mg/kg bw/day

= 0.068 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DMEL (Derived Minimum Effect Level)

Value:

0.1 µg/m³

Most sensitive endpoint:

carcinogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25 000

Modified dose descriptor starting point:

T25

Value:

2.61 mg/m³

Explanation for the modification of the dose descriptor starting point:

Dose descriptor is a T25 of 6 mg/kg bw/day from an oral carcinogenicity study in rats (Hirao 1976, see Chapter 5.8.). This value is corrected to the dose descriptor starting point by route to route extrapolation according to ECHA guidance allowing for differences in rat oral and man inhalation absorption (dose descriptor / 1.15 * 0.5 / 1 = 2.61 mg/m³).

Justification:

an AF of 25000 is applied for high to low dose risk extrapolation (resulting risk level of 1:100.000).

AF for differences in duration of exposure:

1

Justification:

not required (dose descriptor originates from a chronic (life-long) carcinogenicity study

AF for interspecies differences (allometric scaling):

1

Justification:

not required (already accounted for in route to route extrapolation)

AF for other interspecies differences:

1

Justification:

not required for non-threshold systemic effects

AF for intraspecies differences:

1

Justification:

not required for non-threshold systemic effects

AF for the quality of the whole database:

1

Justification:

not required, database quality is adequate

AF for remaining uncertainties:

1

Justification:

not required

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:

DMEL (Derived Minimum Effect Level)

Value:

0.06 µg/kg bw/day

Most sensitive endpoint:

carcinogenicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100 000

Modified dose descriptor starting point:

T25

Value:

6 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

not required (dose descriptor originates from an oral carcinogenicity study in rats)

Justification:

an AF of 25000 is applied for high to low dose risk extrapolation (resulting risk level of 1:100.000).

AF for differences in duration of exposure:

1

Justification:

not required as experimental and human exposure conditions are the same (lifetime daily oral exposure)

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling factor for interspecies differences (rat to human)

AF for other interspecies differences:

1

Justification:

not required for non-threshold systemic effects

AF for intraspecies differences:

1

Justification:

not required for non-threshold systemic effects

AF for the quality of the whole database:

1

Justification:

not required, database quality is adequate

AF for remaining uncertainties:

1

Justification:

not required

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 general population is not a target group for exposure to creosote oil, acenaphthene fraction (wash oil) as wash oil is not used in consumer products. Exception is exposure of man via environment (inhalation and oral route). As consequence, DN/MELs(general population) are derived only for inhalation route, systemic, long-term and for oral route systemic, long-term. Other hazards have not been identified for the general population.

Toxicological basis for risk assessment of human health is the carcinogenic potency of quinoline (see above Chapter 5.11.2.1. - DN/MELs / hazard conclusion for workers under Discussion). Therefore, quinoline has been adopted as marker substance for long-term systemic effects on the general population by the inhalation and dermal route. DMELs (inhalation and dermal exposure) will be derived based on an oral T25 of 6 mg/kg bw/day as dose descriptor obtained from a carcinogenicity study with rats (Hirao et al 1976, see Chapter 5.8. - Carcinogenicity). DMELs are derived using the linearised approach according to ECHA guidance on IR&CSA Chapter R.8: Characterisation of dose [concentration]-response for human health. Risk level has been adopted to be 10^-5. This is considered an acceptable risk to the general population in the context of the assessment of industrial chemicals in the EU (see ECHA guidance on IR&CSA Chapter R.8: Characterisation of dose [concentration]-response for human health, Appendix R.8-14 - Evaluating carcinogenicity risk levels; a review of decision points).

Derivation of DMELs was carried out according to ECHA guidance. The individual steps are described above under Discussion of the derivation of DMELs for workers. The parameters and the approach applied were those for general population. For starting points and assessment factors see above (CSR Chapter 5.11.2.2.).