Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Description of key information

Based on Phys-Chem characteristics of the non-nanoform which mirror that of the nanoforms (shape of particles, phase of particles as well as surface chemistry) carcinogenic effects are not expected to be greater with the non-nano form than for the nanoforms (treated or not treated). Carbon black, irrespective of form display a similar surface chemistry as the functional groups on surface of their particles are essentially the same but may differ in concentration. On this basis, differences in toxicological outcome is not expected. Hence the data from the nanoforms are read-across to the non-nanoform (for details on key information, see summaries for nanoforms).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Carcinogenicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
carcinogenicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Epidemiological data
Adequacy of study:
key study
Justification for type of information:
see attachment "Endpoint-specific read-across justification" attached under section 13.
Reason / purpose for cross-reference:
read-across source
Qualifier:
no guideline required
Principles of method if other than guideline:
The studies were designed and performed in accordance with standard epidemiological methods taking into criteria the Bradford Hill's criteria for causation
Species:
other: human
Route of administration:
inhalation: dust
Dose descriptor:
NOAEC
Remarks on result:
not determinable
Remarks:
human study
Critical effects observed:
no
Executive summary:

A study on carbon black production workers in the UK (Sorahan et al. 2001) found an increased risk of lung cancer in two of the five plants studied; however, the increase was not related to the dose of carbon black. Thus, the authors did not consider the increased risk in lung cancer to be due to carbon black exposure. A German study of carbon black workers at one plant (Buechte et al. 2006; Morfeld et al. 2006; Wellmann et al 206) found an increase in lung cancer risk but, like in the UK study Sorahan et al. 2001), found no association with carbon black exposure. A large US study of 18 plants showed a reduction in lung cancer risk in carbon black production workers (Dell et al. 2006). Based upon these studies, the 2006 Working Group at the International Agency for Research on Cancer (IARC) concluded that the human evidence for carcinogenicity was inadequate (IARC 2010). Since the IARC evaluation of carbon black, Sorahan and co-workers have re-analysed the UK study data using an alternative "lugging" exposure hypothesis and found a positive association with carbon black exposure in two of five plants taking part in the study (Sorahan and Harrington 2007). The same "lugging"exposure hypothesis was applied by Morfeld and McCunney to the German cohort; in contrast, they found no association between carbon black exposure and lung cancer risk and, thus, no support for the alternative exposure hypothesis used by Sorahan and Harrington (Morfeld and McCunney 2007; Morfeld and McCunney 2009).

An update and extension of the retrospective mortality study of US carbon black workers evaluated a cohort of 6634 workers employed in the carbon black industry dating back to the 1930s (Dell et al. 2015). The results showed no increase in lung cancer or any other malignancy. In summary, the authors of the study concluded:“Regardless of whether exposure was based on lagged, lugged, or total cumulative estimates, no consistent association was seen with lung cancer or non-malignant respiratory disease”. This lack of an association between carbon black exposure and lung cancer mortality was recently confirmed in a meta-analysis of the three large cohort studies (UK, US and Germany) of carbon black workers (Yong et al 2019). 

Overall, as a result of these detailed and extensive investigations, no causative link between carbon black exposure and cancer risk in humans has been demonstrated.

In conclusion, the evaluation by IARC that carbon black is“possibly carcinogenic to humans (Group 2B)”is based solely on the observation that rats develop lung tumours under conditions of “lung overload”. The reliability of lung tumours induced in rats by inert poorly soluble particles, such as carbon black, as a predictor of hazard to humans is highly questionable. Overall, the epidemiological evidence from well-conducted investigations has not shown that exposure to carbon black has a carcinogenic potential for humans an does not support a conclusion that the results in rat studies are predictive for humans. Applying the guidelines of self-classification under CLP, carbon black, including nanoforms, is not classifiable as a carcinogen. 

Reference:

Bevan RJ, Kreiling R, Levy LS, Warheit DB (2018). Toxicity testing of poorly soluble particles, lung overload and lung cancer Regulatory Toxicology and Pharmacology 100 (2018) 80–91

Kevin E. Driscoll & Paul J. A. Borm (2020): Expert workshop on the hazards and risks of poorly soluble low toxicity particles, Inhalation Toxicology, DOI:10.1080/08958378.2020.1735581:https://doi.org/10.1080/08958378.2020.1735581

Endpoint:
carcinogenicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
not reported
Reliability:
3 (not reliable)
Justification for type of information:
Endpoint-specific read-across justification" attached under section 13.2
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
no guideline followed
Species:
rat
Sex:
male/female
Route of administration:
inhalation
Type of inhalation exposure (if applicable):
whole body
Vehicle:
clean air
Gross pathological findings:
not specified
Dose descriptor:
NOAEC
Sex:
male/female
Remarks on result:
not determinable
Key result
Dose descriptor:
LOAEC
Effect level:
2.5 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
gross pathology
histopathology: neoplastic
histopathology: non-neoplastic
mortality
Remarks on result:
other: Mauderly et al
Remarks:
24 months exposure
Key result
Dose descriptor:
LOAEC
Effect level:
6 mg/m³ air
Based on:
test mat.
Sex:
female
Basis for effect level:
gross pathology
histopathology: neoplastic
Remarks on result:
other: Heinrich et al 1994
Remarks:
10 or 20 months exposure
Key result
Dose descriptor:
LOAEC
Effect level:
> 7.5 - < 12 mg/m³ air
Based on:
test mat.
Sex:
female
Basis for effect level:
gross pathology
histopathology: neoplastic
Remarks on result:
other: Heinrich et al 1995
Remarks:
24 months exposure
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
2.5 other: mg/m3
System:
respiratory system: lower respiratory tract
Organ:
lungs
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
no
Executive summary:

Mauderly et al 1994 and Heinrich et al 1994/1995 report finding tumours in rats following chronic exposure to carbon black. For the identification of carcinogenic effects, the studies are considered not reliable and not relevant for the following reason: In the Mauderly study, carbon black was included as a satellite group in an investigation probing an experimental question that lead to a study design, which although apropos for the purpose for which it was intented, that does not conform with regulatory requirements and is laden with significant limitations for hazard and risk assessment; the animals were exposed daily for 16 hours with little respite; the OECD guideline recommends exposure for 6 hours/day. This study has a >2.5 fold higher daily duration of exposure. The Heinrich studies show similar shotcomings; the dosing regime was anomalous; 4 months @ 7 mg/m3 then increased to 12.2 mg/m3 for 20 months. Further, only one sex of animals was used. Most importantly, the animals were exposed daily for 18 hours with little respite; the OECD guideline recommends exposure for 6 hours/day. This study has a 3 fold higher daily duration. Exposure concentration in both studies clearly lead to overload conditions in the lungs, which confound the carcinogenic findings. Relevance of results generated under conditions of lung overload were debated at an expert workshop in Edinburgh in April 2020. The experts concluded that neoplasm noted under conditions of lung overload are not relevant for hazard and risk assessment in humans under conditions of non-overload (Driscoll and Borm, 2020). Kevin E. Driscoll & Paul J. A. Borm (2020): Expert workshop on the hazards and risks of poorly soluble low toxicity particles, Inhalation Toxicology, DOI:10.1080/08958378.2020.1735581: https://doi.org/10.1080/08958378.2020.1735581. Overall, the quality of the animal database is low.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
chronic
Species:
other: human
Quality of whole database:
Mauderly et al 1994 and Heinrich et al 1994/1995 report finding tumours in rats following chronic exposure to carbon black. For the identification of carcinogenic effects, the studies are considered not reliable and not relevant for the following reason: In the Mauderly study, carbon black was included as a satellite group in an investigation probing an experimental question that lead to a study design, which although apropos for the purpose for which it was intented, that does not conform with regulatory requirements and is laden with significant limitations for hazard and risk assessment; the animals were exposed daily for 16 hours with little respite; the OECD guideline recommends exposure for 6 hours/day. This study has a >2.5 fold higher daily duration of exposure. The Henirich studies show similar shotcomings; the dosing regime was anomalous; 4 months @ 7 mg/m3 then increased to 12.2 mg/m3 for 20 months. Further, only one sex of animals was used. Most importantly, the animals were exposed daily for 18 hours with little respite; the OECD guideline recommends exposure for 6 hours/day. This study has a 3 fold higher daily duration. Exposure concentration in both studies clearly lead to overload conditions in the lungs, which confound the carcinogenic findings. Relevance of results generated under conditions of lung overload were debated at an expert workshop in Edinburgh in April 2020. The experts concluded that neoplasm noted under conditions of lung overload are not relevant for hazard and risk assessment in humans under conditions of non-overload (Driscoll and Borm, 2020). Kevin E. Driscoll & Paul J. A. Borm (2020): Expert workshop on the hazards and risks of poorly soluble low toxicity particles, Inhalation Toxicology, DOI:10.1080/08958378.2020.1735581: https://doi.org/10.1080/08958378.2020.1735581. Overall, the quality of the animal database is low.
System:
respiratory system: lower respiratory tract
Organ:
lungs

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Mode of Action Analysis / Human Relevance Framework

see set_not treated

Justification for classification or non-classification

Applying the guidelines of self-classification under CLP, carbon black is not classifiable as a carcinogen.

Additional information

see set_not treated