Hexadecyl dihydrogen phosphate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Although one bacterial gene mutation study resulted in some positive findings in some strains, these responses were typically weak (although statistically significant) and were not always treatment-level related. It is also noted that some strains consistently showed greater cytotoxicity than other strains.

 

An effect was seen in a related substance that led to high toxicity to TA100, but has not been seen in other similar alkyl phosphate substances when bacterial gene mutation testing was performed. None of the assessed fatty alkyl phosphates resulted in positive mutagenic potential. 

 

The potassium salt has been tested at the same time in the same laboratory and no mutagenic potential has been noted and although some toxicity at highest concentrations in some strains, the anomalies were minimal compared to the non-potassium form

 

A review of higher-level testing on similar substances suggests that this class of substance is non-mutagenic in mammalian test systems. 

 

It is concluded that the adverse effects seen are not fully consistent with other similar substances. None of the other substance showed mutagenic potential and as a result, the substance can be considered as not being potentially mutagenic itself.

Link to relevant study records

Reference

Endpoint:

genetic toxicity in vitro, other

Remarks:

Review of different endpoints

Type of information:

experimental study

Remarks:

Based on experimental work

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

Assessment of data on the substance itself, the potassium salt and other alkylphosphates

GLP compliance:

not specified

Type of assay:

other: Review of various test types

Specific details on test material used for the study:

The substanxce to be registred was assessed; this included comparison with similar alkyl phosphates

Target gene:

Bacterial and mammalian cells examined

Metabolic activation:

with and without

Metabolic activation system:

Studies reviewd were with or without S-9 fraction

Species / strain:

other: All assays

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Typcially tested to limits of toxicity

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

not examined

The potassium salt resulted in some toxicity for TA1535, TA 98 and TA100 (TA100 and TA98 were repeated at lower levels and all were negative). And although a slight elevation in revertants in some replicates, only one showed a statistically significant increase. The assay is considered 'negative' in its assessment.

A major review has been undertaken by the Cosmetic Ingredient Review committee, with a publication from 2014 providing a good review of safety.

 

Primary data sources are cited in this review and where publically available (eg through primary publications or from REACH Registration dossiers that also cited these tests), checks were made to look for further details. The objective of looking deeper into the data was to assess whether there are anomalies in the data sets as seen in the Bacterial Gene Mutation assay performed on the substance in 2019.

 

It should also be noted that the CIR committee justified that these fatty-alkyl phosphates and their potassium salt could be considered collectively as a review of the whole group meaning that read-across / grouping can be justified as valid.

Conclusions:

From review of various test types for substances in this class, there is no evidence that the substance a potential mutagen.

Executive summary:

The CIR review and other less thorough summaries seen all indicate that this class of substance is not considered to have mutagenic potential. With the exception of one of the bacterial gene mutation assays, toxicity to the cultures was not remarkable; in all mammalian cultures, the top test concentrations typically led to toxicity, but this is a requirement of the guidelines to test to levels leading to toxicity or precipitation. 

 

Some of the bacterial studies reported toxicity at maximum concentration and most showed consistency between strains and whether with or without S9 activation.

 

Just one bacterial gene mutation showed very high toxicity to limited strains and this was with oleyl phosphate; although there is no explanation for this, it does give some assurance that the latest data is not unique. However, this assay did not appear to give any significant positive responses, including strain TA 1353

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)