Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Enzyme proteins including alpha-amylase are not regarded as either genotoxic and/or carcinogenic substances. Genotoxicity testing is in general performed to confirm that the production strain does not produce any genotoxic or carcinogenic metabolites. Basically all enzyme substances have therefore been tested in the Ames test and in the Chromosome Aberration test in vitro and/or an in vitro micronucleus test, and a few enzyme substances also in the Mouse Lymphoma test (ref. 11-40). In none of these test systems did enzyme proteins show evidence of genotoxicity.

 

Enzymatic drugs have been used since the 19th century without providing any evidence of a genotoxic or carcinogenic effect (ref. 2-10; 41-44).

 

Review of the extensive literature concerned with the safety of enzymes from microbial sources strongly supports the general assumption that enzymes from non-toxigenic, non-pathogenic organisms are safe. Numerous tests for in vitro genotoxicity have failed to reveal the presence of a single mutagen or clastogen. These aspects were reviewed by Pariza and Johnson (ref. 1), who presented a compelling argument for the position that tests for genotoxic potential of enzyme preparations produced by well-characterized non-toxigenic microorganisms are unnecessary for safety evaluation.

 

In conclusion, the large amount of data on genotoxicity available together with structural knowledge, toxicokinetic and human data provide no evidence for genotoxic or carcinogenic potential of enzymes.

 

The low exposure to enzymes, the low bioavailability in case of exposure, the lack of genotoxic potential and the consequent absence of any evidence of carcinogenic properties from both human and animal data does not justify any requirement for conducting carcinogenicity studies.

 

References

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Justification for selection of carcinogenicity via oral route endpoint:
See discussion below.

Justification for selection of carcinogenicity via inhalation route endpoint:
See discussion below.

Justification for selection of carcinogenicity via dermal route endpoint:
See discussion below.

Justification for classification or non-classification

Alpha-amylase should not be classified as carcinogenic. (For further justification see discussion above).