Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.84 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA Guidance on Information Requirements R8, ECETOC Guidance on Assessment Factors to Derive a DNEL (2010) and ECETOC TR122, Poorly soluble particles/lung overload (2013)
Overall assessment factor (AF):
2
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
The default assessment factor when the starting point is a NOAEL, in accordance with the ECHA Guidance on Information Requirements R.8.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor from sub-chronic to chronic is 2, in accordance with the ECHA Guidance on Information Requirements R.8, as the effect is due to the removal of accumulated particles by macrophages.
AF for interspecies differences (allometric scaling):
1
Justification:
No assessment factor for allometric scaling is necessary as the study is an inhalation study.
AF for other interspecies differences:
1
Justification:
The default assessment factor for remaining interspecies differences (i.c. by default 2.5) does not always have to be applied for local effects. In this case the local effect is minimal inflammation, which is caused by the increased removal of activated carbon particles from the lung. In an article on inhalation of carbon black in three species (Elder et al., 2005), it appeared that rats are more sensitive to lung inflammation and histopathology than mice and hamsters. The particle surface area was also of concern and increased particle retention significantly. Based on the high sensitivity of rats to lung inflammatory changes associated with removal of particles in the lung, it is deemed justified to reduce the assessment factor for remaining differences to 1.
AF for intraspecies differences:
1
Justification:
In December 2013 ECETOC prepared an extensive evaluation of the scientific literature on Poorly Soluble Particles (PSP) and lung overload (ECETOC TR122, 2013). In this document ECETOC concludes that using an assessment factor of 1 for intraspecies differences is reaonable for PSP. In this case the ECETOC guidance is justified, because: (1) AC-HDS may be considered a PSP of low toxicity; (2) only minimal lung inflammatory changes within the physiological range were seen in a 90-day inhalation toxicity study in rats; (3) AC-HDS appears not to give any significant systemic bioavailability; (4) the minimal lung effects were "port-of-entry" effects. The ECETOC report concludes that for concentration dependent local effects for PSP, an intraspecies AF of 1 is considered sufficient. Therefore, an assessment factor for intraspecies variation of 1 is proposed for the derivation of the DNEL for AC-HDS and AC-LDS.
AF for the quality of the whole database:
1
Justification:
Based on the availability of a study performed in accordance with OECD-guidelines and GLP, no assessment factor for quality of the database has to be taken into account.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties were identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The DNEL (respirable) was derived using the results of the 90 -d repeated dose inhalation toxicity study in which a NOAEL of 7.29 mg/m3 was derived (see endpoint summary for repeated dose toxicity). To derive the inhalation DNEL for worker, the NOAEL of 7.29 mg/m3 should be corrected for the difference between respiratory rates under standard conditions and under conditions of light activity, in accordance with the ECHA Guidance on Information Requirements R.8. Furthermore, as the rats in the study were exposed to 6h per day, a correction factor of 1.33 (8h compared to 6h) should be applied: NOAELcorrected = (7.29 mg/m3/1.33) x 6.7 m3/10 m3 = 3.67 mg/m3. Several assessment factors were taken into account in accordance with the ECHA Guidance on Information Requirements R.8, the ECETOC Guidance on Assessment Factors to Derive a DNEL (2010) and ECETOC TR122 Poorly Soluble Particles/Lung overload (2013).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: ECHA Guidance on Information Requirements R8, ECETOC Guidance on Assessment Factors to Derive a DNEL (2010) and ECETOC TR122 Poorly Soluble Particles/Lung overload (2013)
Overall assessment factor (AF):
2
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
The default assessment factor when the starting point is a NOAEL, in accordance with the ECHA Guidance on Information Requirements R.8.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor from sub-chronic to chronic is 2, in accordance with the ECHA Guidance on Information Requirements R.8, as the effect is due to the removal of accumulated particles by macrophages.
AF for interspecies differences (allometric scaling):
1
Justification:
No assessment factor for allometric scaling is necessary as the study is an inhalation study.
AF for other interspecies differences:
1
Justification:
The default assessment factor for remaining interspecies differences (i.c. by default 2.5) does not always have to be applied for local effects. In this case the local effect is minimal inflammation, which is caused by the increased removal of activated carbon particles from the lung. In an article on inhalation of carbon black in three species (Elder et al., 2005), it appeared that rats are more sensitive to lung inflammation and histopathology than mice and hamsters. The particle surface area was also of concern and increased particle retention significantly. Based on the high sensitivity of rats to lung inflammatory changes associated with removal of particles in the lung, it is deemed justified to reduce the assessment factor for remaining differences to 1.
AF for intraspecies differences:
1
Justification:
In December 2013, ECETOC prepared an extensive evaluation of the scientific literature on Poorly Soluble Particles (PSP) and lung overload (ECETOC TR122, 2013). In this document ECETOC concludes that using an assessment factor of 1 for intraspecies differences is reaonable for PSP. In this case the ECETOC guidance is justified, because: (1) AC-HDS may be considered a PSP of low toxicity; (2) only minimal lung inflammatory changes within the physiological range were seen in a 90-day inhalation toxicity study in rats; (3) AC-HDS appears not to give any significant systemic bioavailability; (4) the minimal lung effects were "port-of-entry" effects. The ECETOC report concludes that for concentration dependent local effects for PSP, an intraspecies AF of 1 is considered sufficient. Therefore, an assessment factor for intraspecies variation of 1 is proposed for the derivation of the DNEL for AC-HDS and AC-LDS.
AF for the quality of the whole database:
1
Justification:
Based on the availability of a study performed in accordance with OECD-guidelines and GLP, no assessment factor for quality of the database has to be taken into account.
AF for remaining uncertainties:
1
Justification:
No remaining differences expected.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The DNEL (respirable) was derived using the results of the 90 -d repeated dose inhalation toxicity study in which a NOAEL of 7.29 mg/m3 was derived (see endpoint summary for repeated dose toxicity). For the derivation of the DNEL for consumers, no correction for differences in respiratory rates is necessary, however, as the rats in the study were exposed to 6h per day, a correction factor of 4 (24h compared to 6h) should be applied to derive a NOAELcorrected for the general public, that in principle may be exposed for 24h/day: NOAELcorrected = 7.29 mg/m3/4 = 1.82 mg/m3. Several assessment factors should be taken into account in accordance with the ECHA Guidance on Information Requirements R.8: The assessment factors are discussed below when different from the assessment factors for workers.