Cholesterol

Carcinogenicity

Description of key information

Two evaluations performed by WHO-IARC.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity

Remarks:

other: Oral (animal studies and human studies. In addition from animal studies information on subcutaeous administration and bladder implantation has been evaluated.

Type of information:

other: IARC monograph

Adequacy of study:

key study

Study period:

until October 1975

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Evaluation of available information on carcinogenicity potential of cholesterol by WHO-IARC, a well-established organisation for cancer research.

Principles of method if other than guideline:

Overall evaluation of carcinogenic potential of cholesterol by the WHO-IARC.

Species:

other: information on laboratory animals as well as human information

Sex:

male/female

Route of administration:

other: Oral (animal studies and human studies. In addition from animal studies information on subcutaeous administration and bladder implantation has been evaluated.

Details on exposure:

variable exposure duration and exposure conditions in the various animal and human studies.

Duration of treatment / exposure:

variable in the various animal and human studies

Frequency of treatment:

variable in the various studies

Details on results:

Cholesterol was tested for carcinogenicity in mice by administration in the diet, by subcutaneous administration and by bladder implantation. These studies were all inadequate for evaluation. Cholesterol has also been tested in combination with various carcinogens, but the results were inadequate to assess the carcinogenesis-enhancing potential of the compound. Feeding of cholesterol to rats exposed to a mammary carcinogen did not affect the incidence of mammary tumours, while feeding after administartion of a colon carcinogen resulted in a lower incidence of colon tumours. No data were available on the genetic and related effects on cholesterol in humans. It did not transform Syrian hmaster embryo cells and was not mutagenic in bacteria.

Dose descriptor:

other: overall evidence

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: There is no adequate evidence for cholesterol for carcinogenicity to humans.

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Conclusions:

In the IARC monograph it is concluded that cholesterol is not classifiable as to its carcinogenicity to humans, as the evidence for carcinogencity to humans is considered inadequate. Topics that are selected for the IARC monogaphs programme on the evaluation of carcinogenic risks to human concern agents for which there is evidence of human exposure and there is some evidence or suspicion of carcinogenicity. Since 1987, cholesterol has not been re-evaluated by IARC for carcinogenic potential. It can be concluded that since 1987, no significant data on cholesterol has become available which resulted in re-evaluation and revision of the monography. Consequently, there is no adequate evidence for cholesterol for carcinogenicity to humans.

Executive summary:

Cholesterol was evaluated for its carcinogenic potential by IARC in 1976. Based on the available animal carcinogenicity data, IARC concluded that no assessment was possible, due to the absence of adequate feeding studies and the use of various vehicles and variation in parameters unrelated to the dose of cholesterol in the subcutaneous injection studies. Implantation expoerminets using cholesterol were considered difficult to interpret, as the effects of teh physical factors must be taken into consideration.

In 1987 cholesterol was re-evaluated by IARC. For this re-evaluation, animal studies as well as evidence for carcinogenicity to humans was evaluated. In the IARC monograph it is concluded that cholesterol is not classifiable as to its carcinogenicity to humans, as the evidence for carcinogencity to humans is considered inadequate. Topics that are selected for the IARC monogaphs programme on the evaluation of carcinogenic risks to human concern agents for which there is evidence of human exposure and there is some evidence or suspicion of carcinogenicity. Since 1987, cholesterol has not been re-evaluated by IARC for carcinogenic potential. It can be concluded that since 1987, no significant data on cholesterol has become available which resulted in re-evaluation and revision of the monography. Consequently, there is no adequate evidence for cholesterol for carcinogenicity to humans.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Species:

other: animals and humans

Justification for classification or non-classification

Based on the absence of evidence of cholesterol-related carcinogenicity, cholesterol is not considered carcinogenic, and consequently needs not to be classified for carcinogenicity according to:

-Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

-Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures

Additional information

Cholesterol has no genotoxic properties, as demonstrated in several studies from the open literature. Moreover, increased cholesterol levels related to carcinogenicity has been studied intensively, and has been evaluated by the IARC. Based on both data from animal studies and data from human epidemiological studies, no relationship between high cholesterol levels and carcinogenicity could be demonstrated. In the absence of evidence of cholesterol-related carcinogenicity, cholesterol is not considered as carcinogenic.

Justification for selection of carcinogenicity via oral route endpoint:
evaluation of all available information by IARC