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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
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 from 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 eye irritation 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:
Perfluorohexanes, CAS# 1064697-81-9
Perfluoroheptanes, CAS# 1064698-16-3
Perfluorotributylamines, CAS# 1064698-37-8
Perfluorotripropylamines, CAS# 338-83-0
Perfluoro-N-methylmorpholine, CAS# 382-28-5
Perfluoro-N-C1,3-alkyl morpholines, CAS# 1093615-61-2
Perfluoro-C6,8-furans, pyrans and acyclic ethers , CAS# 1064698-52-7

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
other: Read-across from in vivo results from category members.
Score:
ca. 0 - ca. 2
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
No signs of eye irritation, corrosion or toxicity were observed.
Irritant / corrosive response data:
Scores of 1 and 2 were noted at several timepoints but were fully reversible.

Any other information on results incl. tables

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 eye irritation 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.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
No eye irriation was caused by exposure to the category members.
Executive summary:

Primary eye irritation studies were performed on category members.  New Zealand albino rabbits were exposed to the category members by instillation into one eye with the other being used as a concurrent control  Eye irritation was evaluated at several time points in each study.  An eye irritation score was reported for each observation time.  The highest score observed in any study was 2/4 however this result was fully reversible within 24 hours.  There was no indication of lethality or systemic toxicity during the testing preiod.  Based on these results the category members do not have to be classified and have no obligatory labeling requirement of eye irritation according to the Globally Harmonized System of Classification and Labeling of Chemicals (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.