Extracts (petroleum), light naphtha solvent

Carcinogenicity

Description of key information

Long term experimental carcinogenicity bioassays have shown that benzene is a carcinogen producing a variety of tumours in animals (including lymphomas and leukaemia). Human epidemiological studies indicate a causal relationship between benzene exposure and acute non-lymphatic leukaemia.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

25 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

Adequate information is available to characterise the oral carcinogenicity of benzene in animals.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEC

960 mg/m³

Study duration:

subchronic

Species:

mouse

Quality of whole database:

Adequate information is available to characterise the oral carcinogenicity of benzene in animals and humans.

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

It is concluded that benzene is carcinogenic in animals and humans and therefore is classified as follows: Carcinogenic Cat 1A, H350 under Regulation (EC) No 1272/2008 of the European Parliament.

Additional information

Non-human data

Oral

Oral cancer studies showed increased tumour rates in multiple organs, some of which were also tumour sites in the inhalation studies. The majority of tumour types at sites other than the haematopoietic system are of epithelial origin. In mice benzene produced increased tumour incidences in Zymbal gland, (Cronkite et al,1985; Farris et al, 1993; NTP, 1986; Maltoni et al, 1989), lung (Farris et al, 1993; NTP, 1986; Maltoni et al, 1989), Harderian gland (NTP, 1986), preputial gland (Farris et al,1993; NTP, 1986), forestomach (Farris et al, 1993; NTP, 1996), mammary gland (NTP, 1986; Maltoni et al, 1989), liver (Maltoni et al, 1989) and ovaries (Cronkite et al, 1985; NTP, 1986). In rats, benzene treatment was associated to increased tumour incidences in the Zymbal gland (NTP, 1986; Maltoni et al, 1989), oral cavity (NTP, 1986; Maltoni et al, 1989), forestomach (Maltoni et al, 1989), nasal cavity (Maltoni et al, 1989), and skin (NTP, 1986; Maltoni et al, 1989).

Dermal

No published data are available.

Inhalation

From several animal studies with inhalation and oral exposure there is evidence that benzene is carcinogenic. Target organs were similar in several studies irrespective of the application route and include the haematopoietic system and tissues of epithelial origin. The predominant tumours induced in the inhalation studies were located in the haematopoietic system, particularly lymphomas in mice (Farris et al, 1993; NTP 1986; Cronkite, 1985). In rats, increased frequencies of leukaemia in comparison to controls were found in benzene-exposed Sprague-Dawley rats and Wistar rats (Maltoni et al, 1989) and one case (out of 40 animals) of chronic myelogenous leukaemia was reported in Sprague-Dawley rats exposed to benzene (Goldstein et al, 1982).

Human data

For updated Human data (see section 7.10 Endpoint Summary). This section will be revised in the next the next dossier update.

References

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Justification for selection of carcinogenicity via oral route endpoint:
Rodent oral cancer studies showed increased tumour rates in multiple organs, some of which were also tumour sites after inhalation. The majority of tumour types at sites other than the haematopoietic system are of epithelial origin.

Justification for selection of carcinogenicity via inhalation route endpoint:
The predominant tumours induced in animal inhalation studies were located in the haematopoietic system, particularly lymphomas in mice. In rats, increased frequencies of leukaemia in comparison to controls were found in benzene-exposed Sprague-Dawley rats and Wistar rats, with one report of chronic myelogenous leukaemia. In humans, benzene causes acute myelogenous (non-lymphocytic) leukaemia (AML or ANLL), however IARC has concluded that evidence of an association between benzene exposure and acute lymphocytic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), multiple myeloma and non-Hodgkin’s lymphoma (NHL) is limited, while evidence for chronic myeloid leukaemia (CML) is inadequate.

Carcinogenicity: via oral route (target organ): other: all gross lesions and masses

Carcinogenicity: via inhalation route (target organ): cardiovascular / hematological: bone marrow