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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from data from a guideline study.
Justification for type of information:
MTDID 22327 is a member of the Perfluorinated Organic Chemicals, C5-C18, category. Unlike most members of the category, MTDID 22327 is a UVCB consisting mostly of perfluoro-N-methylmorpholine, a mixture of C5-C7 perfluoroamines, and perfluorohexane isomers. However, all of these chemicals stem from the same manufacturing process, have similar physicochemical properties including high vapor pressure and low water solubility relative to the hydrocarbon analogs (e.g., hexanes v. perfluorohexanes), and also lack any chemically reactive groups, which forms the technical basis for the category.  Members of this category are fully fluorinated, meaning that fluorine, rather than hydrogen, is bonded to all carbon atoms in the molecule.  Fluorine is the most electronegative of the elements (fluorine has an electronegativity of 3.98 on the Pauling scale, as compared to 2.55 for carbon, 3.04 for nitrogen or 2.20 for hydrogen).  This electronegativity is expected to dominate over all other aspects of substance chemistry and is the underlying basis for similarity of substances in this category.  For example, strong electron withdrawing in perfluorinated tertiary amines results in a molecule with essentially no lone pair influence, and which has chemistry more similar to a branched, perfluorinated alkane than any other structure.  Because these substances exhibit similar physicochemical properties they can be considered to constitute a chemical category. The data gap for Ames mutagenicity can therefore be addressed by many-to-one read-across between category members.

Because these substances exhibit similarity in their physicochemical properties and toxicological properties in mammals, and because available data indicates that parent molecules are not reactive toward biological molecules and cannot undergo bioactivation by normal enzymatic processes, they can be considered to constitute a chemical category. Data gaps for partitioning properties, mammalian and ecological toxicity can therefore be addressed by read-across and/or trend analysis between category members.  The readacross is considered reliable with restrictions and the result is suitable for use in Risk Assessment, Classification & Labelling, and PBT Analysis. See section 13 for a fuller discussion of the category approach.

Data source

Reference
Reference Type:
other: Read-Across from other internal studies
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs and grouping of chemicals
Version / remarks:
May/July 2008
Deviations:
no
GLP compliance:
no
Remarks:
Source study was conducted under GLP conditions.
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
Reaction mass of perfluoro(dimethyl - N - Butylamine ) and perfluoro (methyl - di - N - propylamine) and perfluoro (dimethyl - N - propylamine and 2,2,3,3,5,5,6,6, octafluoro-4-(trifluoromethyl)morpholine and perfluoro-N-pentane
EC Number:
908-205-5
Cas Number:
2187449-42-7
IUPAC Name:
Reaction mass of perfluoro(dimethyl - N - Butylamine ) and perfluoro (methyl - di - N - propylamine) and perfluoro (dimethyl - N - propylamine and 2,2,3,3,5,5,6,6, octafluoro-4-(trifluoromethyl)morpholine and perfluoro-N-pentane
Specific details on test material used for the study:
Read-across from category members:
-Perfluorotributyl amines, CAS# 1064698-37-8
-Perfluoro-N-C1,3-alkyl morpholines, CAS# 1093615-61-2

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Based on the results of the studies, the chemical category of Perfluorinated Organic Chemicals, C5-C18 are negative in the reverse mutation assay in the presence and absence of metabolic activation.
Executive summary:

Ames assays were conducted on category members to determine bacterial mutagenicity potential.  Selective agar plates containing bacterial cells Salmonella typhimurium strains and Escherichia coli were prepared.  Increasing doses of the category members were spotted in the culture of the selective agar plate containing the indicator organisms with the presence or absence of metabolic activation.  Plates were incubated at 37C for 48 hours and revertants were counted.  The category members did not demonstrate mutagenic activity in any of the assays conducted.  Based on these results the category members are considered not mutagenic under the test conditions.

Because these substances exhibit similarity in their physicochemical properties and toxicological properties in mammals, and because available data indicates that parent molecules are not reactive toward biological molecules and cannot undergo bioactivation by normal enzymatic processes, they can be considered to constitute a chemical category. Data gaps for partitioning properties, mammalian and ecological toxicity can therefore be addressed by read-across and/or trend analysis between category members.  The readacross is considered reliable with restrictions and the result is suitable for use in Risk Assessment, Classification & Labelling, and PBT Analysis.