Phosphatidylcholines, soya, hydrogenated

Repeated dose toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Phosphatidylcholines, soya, hydrogenated

EC Number:

306-549-5

EC Name:

Phosphatidylcholines, soya, hydrogenated

Cas Number:

97281-48-6

Molecular formula:

C44H88NO8P

IUPAC Name:

[(2R)-2,3-di(octadecanoyloxy)propyl] 2-(trimethylazaniumyl)ethyl phosphate

Test material form:

other: Estimation based on CAS number

Details on test material:

CAS number 97281-48-6

Specific details on test material used for the study:

Liposomes were made from hydrogenated soy phosphatidylcholine (50 mg/mL)

Test animals

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

Administration / exposure

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

Doses / concentrations

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

Examinations

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

Results and discussion

Results of examinations

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.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

>= 3 other: µg of lipid inhaled per dosing

Based on:

other:

Basis for effect level:

other: inhalation

Target system / organ toxicity

Key result

Critical effects observed:

no

System:

other: Pulmonary

Organ:

lungs

Applicant's summary and conclusion

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.