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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

The effects of chronic exposure to liposome aerosols on lung histology and alveolar macrophage function were studied in BALB/C mice. 1 -3µg of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. No histological changes of the lungs or untoward effects on general health or survival of animals were noted. Alveolar macrophage phagocytic function was not affected. Transmission electron microscopy and morphometry showed no treatment related alterations.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation, other
Remarks:
pulmonary effects
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
No reference to guideline reported. The test procedure is in accordance with generally accepted scientific standards
GLP compliance:
no
Specific details on test material used for the study:
Liposomes were made from hydrogenated soy phosphatidylcholine (50 mg/mL)
Species:
mouse
Strain:
Balb/c
Details on species / strain selection:
Virus free 7 week old male BALB/C mice
Sex:
male
Details on test animals or test system and environmental conditions:
n = 30 per group
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
not specified
Details on inhalation exposure:
Mice were exposed to liposome (20 mL total volume, 50 mg lipid/mL PBS) or saline aerosols (control)
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
1 -3 µg of lipid inhaled per dosing per mouse was estimated from fluorescence measurements
Duration of treatment / exposure:
1 hour per day, 5 days per week for 4 weeks
Frequency of treatment:
daily
Dose / conc.:
50 mg/L air (nominal)
Remarks:
20 ml total volume, 50 mg lipid/mL
No. of animals per sex per dose:
30
Control animals:
yes
Observations and examinations performed and frequency:
5 animals were removed weekly (both experimental and control group)
Bronchoaveolar lavage (BAL) was performed through tracheostomy.
In vivo uptake of liposomes by aveolar macrophages was documented by fluorescence microscopy and flow cytometry of BAL
Clinical signs:
no effects observed
Mortality:
mortality observed, non-treatment-related
Description (incidence):
Occasional deaths were observed (A total of three, one in the experimental group and two in the saline control group) all deaths occured within the initial minutes of placing the animals in the module, suggesting and untoward stress reaction to confinement
Body weight and weight changes:
no effects observed
Description (incidence and severity):
All animals exhibited normal growth and appeared healthy and active without evidence of hair loss or unusual behaviour that would indicate ill health
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
animals appeared healthy and active
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Description (incidence and severity):
Pulmonary histopathology revealed no discernable differences between the liposome and the saline groups.
Neuropathological findings:
not specified
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
Pulmonary histopathology revealed no discernible differences between the liposome and the saline groups.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 3 other: µg of lipid inhaled per dosing
Based on:
other:
Basis for effect level:
other: inhalation
Key result
Critical effects observed:
no
System:
other: Pulmonary
Organ:
lungs
Conclusions:
No histological changes of the lungs or untoward effects on general health or survival of animals were noted. Alveolar macrophage phagocytic function was not affected. Transmission electron microscopy and morphometry showed no treatment related alterations.
Executive summary:

The effects of chronic exposure to liposome aerosols on lung histology and alveolar macrophage function were studied in mice. 1 -3 µg of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. No histological changes of the lungs or untoward effects on general health or survival of animals were noted. Alveolar macrophage phagocytic function was not affected. Transmission electron microscopy and morphometry showed no treatment related alterations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

The effects of chronic exposure to liposome aerosols on lung histology and alveolar macrophage function were studied in BALB/C mice. 1 -3µg of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. No histological changes of the lungs or untoward effects on general health or survival of animals were noted. Alveolar macrophage phagocytic function was not affected. Transmission electron microscopy and morphometry showed no treatment related alterations.

The substance should therefore not be classified for repeated dose toxicity.