Registration Dossier

Administrative data

Description of key information

A Primary Skin Irritation study has been conducted on perfluoro-N-methylmorpholine and found to be non-irritating.  In addition, six skin irritation studies on five members of the category resulted in no signs of primary skin irritation.
Perfluoro-N-methylmorpholine results: Non-irritating
Perflfuorotributylamine results: 2 studies showed no signs of skin irritation
Perfluoroisopropylmorpholine results: No signs of skin irritation
Perfluorotripropylamine results: No signs of skin irritation
Perfluorohexane results: No signs of skin irritation
Perfluoroheptane results: Minimally irritating to skin
An eye irritation study has been conducted on perfluoro-N-methylmorpholine and was found to be non-irritating. In addition, six eye irritation studies on 5 other members of the Fluoroinert Category resulted in no signs eye irritation at 24, 48 and 72 hours.
Perfluoro-N-methylmorpholine: Non-irritating
Perfluorotributylamine results: 2 studies showed no signs of eye irritation
Perfluorotripropylamine results: No signs of eye irritation
Perfluoroisopropylmorpholine results: No signs of eye irritation
Perfluorohexane results: No signs of eye irritation
Perfluoroheptane results: No signs of eye irritation
Classification for category members is based on experimental results for certain members of the class. Since one of the defining characteristics of the class is a lack of biological effects based on chemical and electronic properties, the results from tests (mammalian toxicity, environmental and ecotoxicity) are applicable to all members of the category.
These results are considered to be applicable to perfluoro-N-methylmorpholine.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Perfluoro-N-methylmorpholine

A primary dermal irritation study (OECD Guideline 404) was conducted using three albino rabbits (New Zealand White strain). Each rabbit received a 0.5 milliliter application of the test article to an intact skin test site. The test sites were covered with a semi-occlusive dressing for 4 hours and washed after test article removal. The sites were evaluated for irritation immediately after test article removal (4 hour), 24, 48 and 72 hours. Application of the test article to the skin of albino rabbits under 4 hour semi-occluded conditions resulted in no dermal irritation. An average primary dermal irritation score of 0.0 of a possible 8.0 was assigned at all evaluations. The test article is considered non-irritating to the skin under the conditions of this study.

Two studies conducted on Perfluorotributylamine showed no signs of irritation at 24 and 72 hours after being applied to intact and abraded skin. 

Perfluorotripropylamine showed no signs of skin irritation 24, 48 and 72 hours after being applied to intact skin. 

A primary skin/irritation study was performed with FC-770 according to OECD Study Guideline No. 404 (2002). Three New Zealand albino rabbits (male) were exposed to 0.5 ml (undiluted) of the test article 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 test article. Neither, was there any lethality or any indication of systemic toxicity during testing period.

A primary dermal irritation study was conducted on perfluorohexane according to OECD guideline 404. One male and two female acclimated animals were selected and maintained during the study period. Within 24 hours before treatment, the hair was clipped from the back and flanks of each animal. The test article was applied to the shaved intact skin on each animal's back in the amount of 0.5 mL. The area of application was covered with 2.5-cm x 2.5-cm gauze patch secured with paper tape, loosely overwrapped with Saran Wrap to provide a semiocclusive dressing. At the end of the 4-hour exposure period the patches were removed and the test sites washed with tap water. Thirty minutes after removal of the test material, the degree of erythema and edema was read according to the Draize technique (recorded as the 4-hour score). Subsequent examinations were made at 24, 48, and 72 hours after patch removal. The average of the 4, 24, 48, and 72 hour scores was 0.0. Perfluorohexane is considered to be nonirritating.

The primary skin irritation of perfluoroheptane was assessed in female New Zealand White albino rabbits. Hair was shaved on the back and flanks of each rabbits (two test sites approximately 10 centimeters apart). One of the two sites was abraded by making four epidermal incisions, two perpendicular to the other two, while the other sites remained intact. Undiluted test article (0.5 ml) was applied to each of the test sites on each rabbit and then covered by square gauze patches. The patches were secured with gauze wrap, which was then wrapped with impervious plastic sheeting for one day. Treated sites were examined one hour and 48 hours after removal of the test article and scored using the draize technique for erythema and edema. The primary irritation index and average irritation scores were calculated. The results of the primary skin irritation test indicated that perfluoroheptane is minimally irritating to the skin of female albino rabbits (primary irritation index score= 0.1 and average erythema score of 0.2). Minimal erythema was noted at the one hour evaluation and subsided by the 48 hour evaluation. Edema was not produced following a 24 hour occluded contact period.

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. All members of the category are considered non-irritating to the skin.

Perfluoro-N-methylmorpholine

Acute eye irritation/corrosion potential of perfluoro-N-methylmorpholine was evaluated in rabbits following OECD guideline No. 405 “Acute Eye Irritation/Corrosion.” A single dose of 0.1 mL undiluted test material was placed in the lower lid of the right eye of 3 male New Zealand White Albino rabbits. The lower lid was gently pulled away from the eyeball for dosing and the lids were gently held together for approximately 1 second to prevent loss. The untreated left eye of each animal served as the reference control. Animals were observed for eye irritation at approximately 1, 24, 48 and 72 hours after the instillation of the test substance. At the 72 hour observation a solution of 2% fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Animal F39167 had a conjunctivae redness score of 2 at the 1 and 24 hour observation points and conjunctivae chemosis score of 1 at 1 hour (chemosis completely resolved therafter). The animal’s conjunctivae redness had reduced to a score of 1 at 48 hours and completely resolved (score of 0) by 72 hours. Animal F39168 had a conjunctivae redness score of 2 at the 1 hour observation point and conjunctivae chemosis score of 1 at 1 hour (chemosis completely resolved therafter). The animal’s conjunctivae redness had reduced to a score of 1 at 24 and 48 hours and had resolved (score of 0) by 72 hours. Animal F39169 had a conjunctivae redness score of 1 at 1 hour and 24 hours and conjunctivae chemosis score of 1 at 1 hour (chemosis completely resolved therafter).  The animal’s conjunctivae redness had resolved (score of 0) by 48 hours. Based on the observed scores a mean Primary Irriation Index (PII) was calculated for each observation point. At 1 hour the mean PII was 5.3/110, at 24 hours 2.7/110, at 48 hours1.3/110, and at 72 hours 0.0/110. Based on the results of the study and according to EU GHS classification criteria the test article does not need to be classified as an eye irritant.

Two eye irritation studies were conducted on perluorotributylamine. In the first study, an acute eye irritation/corrosion study was conducted on the test article. Six young adult albino rabbits were maintained for this study. 0.1 mL of the test article was instilled into the right eyes of the test animals while the other eyes remained untreated to serve as controls. The test article was not washed from the eyes. The treated eyes were examined at 1, 24, 48 and 72 hours as well as 5 and 7 days following instillation of the test material into the eyes. Irritation scores for all animals at all time points were found to be zero. In the second study, 0.1 mL of undiluted test article was instilled into the conjunctival sac of the right eye of each animal. The left eye of each animal was untreated, serving as a scoring control. At 24 hours any test article remaining in the eye was removed by rinsing the eye with distilled water. The eyes of the animals were examined at 1, 24, 48, 72, 96, and 168 hours after instillation of the test article and the irritation and description of local effects were recorded. Conjunctivae irritation scores of 2 were observed for all six animals at 1 hour after instillation but were completely resolved 24 hours after instillation. No corrosion, staining of ocular tissue, systemic toxicity or mortality were reported during the test period. 

The ocular irritation/corrosion potential of perfluorotripropylamine was assessed in New Zealand White rabbits. The undiluted test article (0.1 mL) was placed into the everted lower lid of the right eye, with the left eye serving as the untreated control. The upper and lower lids were held together for 1 second and then released. The eyes remained unflushed. The treated eyes were observed for ocular irritation at 1, 24, 48 and 72 hours after treatment. Irritation was scored using the Draize technique. A sodium fluorescein examination was used to reveal possible corneal damage at 72 hours. Average primary irritation scores and individual eye irritation scores for cornea, iris, conjunctivae irritation were reported. All animals and all time points had irritation scores of zero.

Acute eye irritation/corrosion potential of FC-770 (liquid, batch 142072:43) was evaluated in rabbits following OECD guideline No. 405 (2002) “Acute Eye Irritation/Corrosion.” A single dose of 0.1 mL undiluted test material was placed on the conjunctival sac of one eye of 3 male 6-week old New Zealand White Albino rabbits. The lower lid was gently pulled away from the eyeball for dosing and the lids were gently held together for approximately 1 second to prevent loss. The untreated eye of each animal served as the reference control. Animals were observed for eye irritation at approximately 1, 24, 48 and 72 hours after the instillation of the test substance. Immediately following the 24-hour observation a solution of 2% fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Animals were euthanatized following the last observation. Immediately after dose administration, irritation (redness) was observed in the conjunctivae of one animal which completely resolved within 24 hours. No further evidence of irritation was observed in any animal. There were no observations of ocular corrosion or corneal epithelial damage in any animals.

For perfluorohexane, an eye irritation/corrosion study was done in three New Zealand White albino rabbits (according to OECD 405). 0.1 mL of the perfluorohexane was instilled in the conjunctival sac of one of the eyes of each animal. The eyes of the animals were examined at 1, 24, 48, and 72 hours after instillation of the test article and the irritation and description of local effects were recorded. At 72 hours fluorescein (2% fluorescein in water) was instilled to observe corneal epithelial damage. No irritation, corrosion, staining of ocular tissue, systemic toxicity or mortality were observed during the test period. Therefore, the test article does not have to be classified and has no obligatory labelling requirements for eye irritation. 

The ocular irritation potential of perfluoroheptane was assessed in female New Zealand White rabbits. The test article (0.1mL) was instilled into the conjunctival sac of the right eye of each rabbit, with the left eye serving as a control. At each scoring interval, the cornea, iris and palperbral conjunctiva were examined and graded for irritation and injury according to a standard scoring system. The irritation potential of the test article was used by determining the maximum mean irritation score at one hour, one, two, or three days after instillation. No animals showed a positive reaction for irritation throughout the study. The results of this study indicate that perfluoroheptane is nonirritating (0.0/110.0) to the eye of the female albino rabbit.

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 members of 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. All members of the category are considered non-irritating to the eye.

Please see IUCLID section 13 for the category justification and a matrix of irritation/corrosion data for members of the Perfluorinated Organic Chemicals C5-C18 category.

Justification for classification or non-classification

The test scores do not meet the criteria for classification.