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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study conducted before the adoption of GLP. Read-across of data from a category member. 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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: internal protocol
GLP compliance:
no
Remarks:
study conducted prior to adoption of GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):T-1549

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory, Inc., Wilmington, Mass.
- Weight at study initiation:200-220 grams
- Housing: Stainless steel cages with sawdust bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 0.3 cubic meter enamel coated inhalation chamber
- Source and rate of air: 30 liters/min
- Method of conditioning air: Filtered air from a pressure line regulated by a torameter. The flow was calibrated using a wet test meter.
- System of generating particulates/aerosols: The air was bubbled through a large flask containing 250 mL of T-1549
TEST ATMOSPHERE
- Brief description of analytical method used: Weight of T-1549 in the flask at the end of each exposure was recorded to determine amount of material to which the animal was exposed
Duration of treatment / exposure:
The animals were exposed 7 hours a day, 5 days a week for a total of 30 exposures over 6 weeks.
Doses / concentrations
Remarks:
Doses / Concentrations:
The mean vapor concentration during the 30 days of exposure was 7.28 mL/cubic meter
Basis:

No. of animals per sex per dose:
27 male/15 female
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Rats were examined for gross toxic signs daily at transfer to exposure chamber
BODY WEIGHT: Yes
- Time schedule for examinations: Rats were weighted initially and at the ends of weeks 2, 4, and 6

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
BODY WEIGHT AND WEIGHT GAIN: The male test group did not gain as much weight during the course of the experiment as did the male controls. The female experimental rats did, however, gain similar amounts of weight to the female controls.
HAEMATOLOGY: Results did show significant differences between control and test groups in certain idices followed no recognizable pattern and indicated a lack of indentifiable pathological change due to exposure.
GROSS PATHOLOGY: Liver histology results in both control and test groups were comparable and unremarkable. Lung tissue samples showed thickening of alveolar septa to a mild degree, while several liver samples showed a mild degree of focal fatty degeneration.

Effect levels

Dose descriptor:
NOAEL
Effect level:
> 7.28 other: ml/m3
Sex:
male/female
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

FC-3284 is a member of the Perfluorinated Organic Chemicals, C5-C18, category. 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 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. 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 from FC-43.

Applicant's summary and conclusion

Conclusions:
28 day repeat dose inhalation results for FC-43 (PTBA, CAS# 1064698-37-8) are reported for read-across to FC-3284 (PMM, CAS# 382-28-5). After 30 exposures over 6 weeks the male test rats gained less weight than the male control rats. The female test rat weight pattern was similar to the female controls. With the exception of thickened alveolar septa and focal fatty degeneration of liver which was observed in both control and test animals, no pathology was observed which was attributed to the exposure experience.
Executive summary:

28 day repeat dose inhalation results for FC-43 (PTBA, CAS# 1064698-37-8) are reported for read-across to FC-3284 (PMM, CAS# 382-28-5). Twenty-seven male and fifteen female Sprague-Dawley rats were used in the assay, eleven males and five females were used as control animals. The experimental group was exposed to an atmosphere saturated with respect to the test article for sever hours per day, five days per week, for a total of 30 exposures over 6 weeks. A 0.3 cubic meter enamel coated inhalation chamber was supplied with 30 liters/min of filtered air from a pressure line regulated by a rotameter. Before entering the chamber the air was bubbled through a large flask containing 250 ml of the test article heated to 125 degrees Celsius by an oil bath to saturate the air with vapor. Control rats were placed in an exposure chamber on the same schedule as the test rats, but were exposed to room air only. The male test rats gained less weight during the study period than the male control rats. However, the female test rat weight pattern was similar to the female controls. the female test rats had lower mean corpuscular volumes than the female control rats. A reduced serum glutamic oxaloacetic transaminase level was observed in the female test rats. The male test rats exhibited an elevated blood iron level and the female test rats exhibited a lower blood iron level than controls. The lack of any pattern or trend in the above deviations indicated that there is no direct dose-response relationship and questions the significance of the observed changes. No pathology was observed which was attributed to the exposure experience. By read-across, the target substance is also considered to have no have no pathology that could be attributed to an exposure experience. Study conducted prior to the adoption of GLP. 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.