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

Skin irritation / corrosion

Administrative data

Endpoint:

skin 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 of 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 skin 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:

Read-across for Skin Irritation per CRF for Perfluoronated Organic Chemicals, C5-C18

Author:

Anon.

Year:

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

Test material information

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 multiple in vivo studies.

Time point:

other: Read-across from multiple in vivo studies.

Score:

ca. 0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

No signs of skin irritation, corrosion, skin coloring or toxicity was observed. Scores of 0 were noted at all observation points.

Irritant / corrosive response data:

No signs of skin irritation, corrosion, skin coloring or toxicity was observed. Scores of 0 were noted at all timepoints.

Any other information on results incl. tables

Primary skin/irritation studies were performed on multiple category members. New Zealand albino rabbits were exposed to the category members by application onto clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Skin reactions were assessed at least once daily for 4 days after treatment. No skin irritation of any kind was caused by up to 4 hours of exposure to the category members. Neither was there any lethality or any indication of systemic toxicity during testing period. Based on these results the category members do not have to be classified and have no obligatory labeling requirement of skin irritation according to the Globally Harmonized System of Classification and Labeling of Chemicals (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 skin irritation 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:

No skin irritation of any kind was caused by up to 4 hours of exposure to the category members. Neither was there any lethality or any indication of systemic toxicity during testing period. Based on these results the category members do not have to be classified and have no obligatory labeling requirement of skin irritation according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).

Executive summary:

Primary skin/irritation studies were performed on multiple category members,. New Zealand albino rabbits were exposed to the category members by application onto clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Skin reactions were assessed at least once daily for 4 days after treatment. No skin irritation of any kind was caused by up to 4 hours of exposure to the category members. Neither was there any lethality or any indication of systemic toxicity during testing period. Based on these results the category members do not have to be classified and have no obligatory labeling requirement of skin 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.