Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Source: National Toxicological Program, Technical Report Series No. 322. Toxicology and carcinogenesis studies of phenylephrine hydrochloride (CAS No. 61 -76 -7) in F344/N rats and B6C3F1 mice (feed studies).

In NTP studies, phenylephrine hydrochloride was not mutagenic in four tester strains of Salmonella typhimurium (TA100, TA1535, TA1537, and TA98) in the presence or absence of Aroclor 1254-induced male Sprague-Dawley rat or male Syrian hamster liver S9.

The results of mutagenicity studies of phenylephrine hydrochloride were equivocal in the mouse lymphoma L5178Y/TK+/- assay because a positive response, noted in the first trial without metabolic activation, occurred at high doses that were toxic to the cells (relative total growth of 12.2%) and was not reproduced in the second trial. Phenylephrine hydrochloride was not tested in the presence of S9 in the mouse lymphoma assay.

Phenylephrine hydrochloride induced sisterchromatid exchanges (SCEs) but not chromosomal aberrations in Chinese hamster ovary cells. The increase in SCEs was seen only in the absence of metabolic activation with Aroclor 1254- induced male Sprague-Dawley rat liver S9.

In an Micronucleus Test (study ID: A44702), phenylephrine hydrochloride was administered intraperitoneally 3 times to F344 rats. No indications were found for clastogenicity and aneugenicity.

In summary, phenylephrine hydrochloride was not mutagenic in bacteria with or without metabolic activation. The evidence for mutagenicity was equivocal in mammalian cells without metabolic activation at nearly toxic doses, and phenylephrine hydrochloride induced SCEs in mammalian cells in the absence of metabolic activation. Neither numerical nor structural chromosome damages were observed in an in vivo Micronucleus Test after intraperitoneal injection.


Short description of key information:
- AMES: negative
- Mouse lymphoma assay: positive in 1/2 experiments without S9 at cytotoxic concentrations.
- SCE Assay: positive only without S9
- CA in CHO cells: negativ
- MNT (ip) in mice: negative

Endpoint Conclusion:

Justification for classification or non-classification

The available data from secondary sources are not sufficient for classification and labelling of phenylephrine hydrochloride for mutagenicity.