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Administrative data

Endpoint:
acute toxicity: inhalation
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:
guideline study with acceptable restrictions
Remarks:
Read-across data from guideline studies.
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 acute inhalation lethality 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 studies were conducted under GLP conditions.

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

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 20 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Inhalation LC50 values of category members range from > 20 mg/L to > 41 mg/L.

Any other information on results incl. tables

Acute inhalation toxicity studies were performed on category members.  Rats, guinea pigs, and mice were exposed to the category members in exposure chambers for a set period of time.  Upon removal from the chamber several animals were sacrificed to observe sections of their lungs, spleen, liver and kidneys.  The remaining animals were observed for 2 weeks, weighed, sacrificed and grossly examined.  There were no deaths in the studies.  Weight gains were normal and at necropsy no grossly observable lesions were noted. Inhalation LC50 values of category members range from > 20 mg/L to > 41 mg/L. Based on these results, the category members are not classified for acute inhalation toxicity according to GHS.

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 acute inhalation lethality can therefore be addressed by many-to-one read-across between category members.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The category (perfluorinated organic chemicals, C5-C18) has a rat acute inhalation LC50 value of greater than 20 mg/L.
Executive summary:

Acute inhalation toxicity studies were performed on category members.  Rats, guinea pigs, and mice were exposed to the category members in exposure chambers for a set period of time.  Upon removal from the chamber several animals were sacrificed to observe sections of their lungs, spleen, liver and kidneys.  The remaining animals were observed for 2 weeks, weighed, sacrificed and grossly examined.  There were no deaths in the studies.  Weight gains were normal and at necropsy no grossly observable lesions were noted. Inhalation LC50 values of category members range from > 20 mg/L to > 41 mg/L. Based on these results, the category members are not classified for acute inhalation toxicity according to GHS.

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.

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