Technical report 122

Carbon black evaluation IARC (2010)

Carbon black evaluation IARC (2010):

There is inadequate evidence in humans for the carcinogenicity of carbon black.
There is sufficient evidence in experimental animals for the carcinogenicity of carbon black.
Carbon black is possibly carcinogenic to humans (Group 2B).

Rationale IARC (2010): In making this evaluation the Working Group considered the human and animal evidence as well as the evidence on potential mechanisms through which carbon black may cause cancer in humans (IARC, 2010).

The human epidemiological evidence was inconsistent. Two of the three studies of carbon black production workers observed excess risk for lung cancer and other studies provided mixed evidence for an increased risk for lung and other cancers. The few studies that assessed exposure–response for lung cancer, including the two that observed excess risks compared with the general population, provided weak or inconclusive evidence of a dose–response. Overall, these results led the Working Group to conclude that there was inadequate evidence from epidemiological studies to assess whether carbon black causes cancer in humans (IARC, 2010).

Three studies of female rats that inhaled carbon black and three additional studies of female rats exposed intratracheally found significant increases in the incidence of malignant lung tumours, providing sufficient evidence that carbon black can cause cancer in animals. Solvent extracts of carbon black were used in one study of rats in which skin tumours were observed after dermal application and several studies of mice in which sarcomas were seen following subcutaneous injection, providing sufficient evidence that carbon black extracts can cause cancer in animals (IARC, 2010).

The Working Group considered a large body of mechanistic information. For lung cancer in rats, it was concluded that a sequence of events that starts with impaired clearance and accumulation of particles in the lung, causing inflammation, cell injury and production of reactive oxygen species that eventually lead to mutations, was well supported by experimental evidence, although some data also supported alternative pathways. High retained mass lung burdens and decreased lung clearance have been observed in coal miners, which led the Working Group to conclude that animal cancer data obtained under conditions of impaired lung clearance are relevant to humans. There was a minority opinion in the Working Group that would support the classification of carbon black in Group 2A, and invoked the analogy with quartz particles, which are carcinogenic in the lung of rats and humans. However, based on current evidence, the Working Group considered that the degree to which all elements of the above-mentioned mechanism may operate in humans is not clear and, thus, the mechanistic information did not alter the overall evaluation of Group 2B (IARC, 2010).

Numerous epidemiology studies have failed to adequately demonstrate an increased risk of lung cancer due to occupational exposure to carbon black. Carbon black is not carcinogenic to mice (oral, skin or inhalation), hamsters (inhalation or intratracheal), guinea pigs (inhalation), rabbits (skin or inhalation), primates (skin or inhalation) or rats (oral). Only studies conducted by inhalation and intratracheal administration in rats have shown significant increases in benign and malignant lung tumours and lesions described as benign cystic keratinising squamous-cell (KSC) tumours. Carbon black -induced lung tumour formation, including KSC lesions, occurs only in rats. An expert panel reviewing KSC lesions (induced in rats by TiO2 or p-aramid) concluded that KSC lesions are not seen in humans. Lung tumours in humans are primarily located in the bronchial airways, whereas in the rat they occur in the parenchyma and are alveolar in origin. This species-specific response (tumour formation and KSC lesions) by the rat to carbon black, not seen in any other laboratory species and which has not been reported in humans, strongly suggests that the results of the rat inhalation bioassay should not be considered directly relevant when assessing human risk. Therefore, carbon black should not be classified as carcinogenic to humans based on the rodent bioassay data (Rausch et al, 2004).