Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to guideline
Guideline:
other: MAFF Japan Agricultural Chemicals Regulation Laws 2-1-3 Notification 12 Nousan 8147 and Notification 13 Seisan 1739 (2000 and 2001)
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Lecithins, acetylated
EC Number:
293-316-5
EC Name:
Lecithins, acetylated
Cas Number:
91053-50-8
Molecular formula:
Not applicable- complex UVCB substance
IUPAC Name:
Lecithins, acetylated
Details on test material:
Purity: Unknown variable composition biological substance (UVCBS)
Composition of test material, percentage of components: Unknown variable composition biological substance (UVCBS)

Test animals

Species:
rat
Strain:
other: Crl:CD® (SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: Males (230-261 grams); Females (185-197 grams)
- Fasting period before study: None
- Housing: Except during exposure, animals were individually housed in solid bottom caging with bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The exposure chamber was constructed of glass (cylindrical). A polycarbonate baffle inside the chamber promoted uniform chamber distribution of the test atmosphere.

- Exposure chamber volume: 34 L

- Method of holding animals in test chamber: During exposure, animals were individually restrained in perforated stainless steel cylinders with conical nose pieces. The restrainers were inserted into a polymethylmethacrylate faceplate attached to the exposure chamber so that the nose of each animal extended into the exposure chamber.

- System of generating particulates/aerosols: Chamber atmospheres were generated by atomization of the vehicle control or test substance in air with a Spraying Systems nebulizer. The vehicle control or test substance was metered into the nebulizer with a Harvard Apparatus model 22 syringe infusion pump. Filtered, high-pressure air, metered into the nebulizer by a Brooks model 5850E mass flow controller, carried the resulting atmosphere into the exposure chamber. Chamber concentrations of vehicle control or test substance were controlled by varying the feed rate to the nebulizer.

Test atmospheres were exhausted through a dry-ice cold trap followed by an MSA filter cartridge prior to discharge into the fume hood.

- Method of particle size determination: Samples to determine particle size distribution (mass median aerodynamic diameter, geometric standard deviation, and percent particles less than 1, 3, and 10 μm diameter) were taken during each exposure with a Sierra® series 210 cyclone preseparator/cascade impactor and Sierra® series 110 constant flow air sampler.

- Temperature, humidity, pressure in air chamber: Chamber temperature was targeted at 20-24°C. Chamber relative humidity was targeted at 30-70%. Chamber airflow was set at the beginning of each exposure to achieve at least 10-12 air changes per hour. Chamber oxygen concentration was targeted to be at least 19%.

TEST ATMOSPHERE
- Brief description of analytical method used: During each exposure, the atmospheric concentration of the vehicle control or test substance was determined by gravimetric analysis at approximately 30-minute intervals in the test chamber. High performance liquid chromatography analysis was used to determine the percentage of the test substance on the gravimetric filters collected during the test substance:corn oil 50:50 (v/v) exposure.
- Samples taken from breathing zone: yes

VEHICLE: Preliminary chamber trials with the test substance revealed that a respirable atmosphere of appreciable concentration could not be generated due to the test substance’s viscosity. Therefore, it was necessary to dilute the test substance in a vehicle to facilitate aerosolization. The vehicle control, corn oil, was purchased commercially.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0, 2.5, 2.9 mg/L (The test substance was diluted with corn oil (1:1) to facilitate atmosphere generation. Based on analysis of air samples from the chamber, the 2.9 mg/L nominal concentration was equivalent to 0.89 mg/L of test substance.)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Body weights and clinical observations were conducted periodically throughout the recovery period.

All animals from this study were given a complete gross pathology examination of their internal organs including observation of the nasal passages. On the last day of the recovery period, all rats were sacrificed by carbon dioxide over-exposure, exsanguinated, and necropsied.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.89 other: mg/L (air) (the maximum practically attainable exposure concentration)
Exp. duration:
4 h
Remarks on result:
other: No adverse effects observed. No deaths, clinical signs, body weight effects, or gross necropsy findings.
Mortality:
No animals died following either the 2.5 mg/L corn oil (vehicle control) exposure or the 2.9 mg/L test substance:corn oil 50:50 (v/v).
Clinical signs:
other: There were no test substance related clinical signs of toxicity observed in this study. Other clinical observations reported in this study included test substance on the rats’ face and/or head immediately following or up to one day post exposure.
Body weight:
No animals in this study demonstrated body weight losses 1, 7 or 14 days following exposure to either the 2.5 mg/L corn oil (vehicle control) or the 2.9 mg/L test substance:corn oil 50:50 (v/v).
Gross pathology:
No gross lesions were present in the rats at necropsy.
Other findings:
The mean mass median aerodynamic diameter (MMAD) measured for the 2.5 mg/L corn oil was 1.9 μm ± 2.1 (MMAD ± geometric standard deviation). A second group of rats was exposed to 2.9 ± 0.62 mg/L test substance:corn oil 50:50 (v/v), the maximum practically attainable atmospheric aerosol concentration, which was characterized by a MMAD of 3.3 μm ± 2.5. HPLC analysis of samples collected from the 2.9 mg/L test substance:corn oil 50:50 (v/v) revealed that animals were exposed to 0.89 ± 0.036 mg/L test substance, the maximum practically attainable exposure atmosphere of the test substance.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
LC50 >0.89 mg/L

The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

Several attempts were made to generate a respirable 2-5 mg/L atmosphere of the test substance. Due to the high viscosity of the test substance, a respirable atmosphere could not be generated. To facilitate test substance atmosphere generation, the test substance was diluted 50:50 (v/v) with corn oil. Chamber trials demonstrated a respirable atmosphere around 2.0 mg/L could be generated with test substance:corn oil 50:50 (v/v).

  

Two groups of 5 male and 5 female Crl:CD(SD) rats were exposed nose-only for a single 4-hour period to either the vehicle corn oil or a 50:50 (v/v) mixture of test substance:corn oil in air. Animals were weighed and observed for clinical signs of toxicity during a 14-day recovery period. Rats were exposed to an aerosol concentration of 2.5 ± 1.2 mg/L corn oil (mean ± standard deviation; vehicle control).

  

All rats exposed to 2.5 mg/L corn oil (vehicle control) survived the exposure and the subsequent 14-day recovery period. Animals demonstrated no loss in body weight, 1, 7 or 14 days post exposure and no clinical signs of toxicity were observed. Gross pathological examination revealed no evidence of organ-specific toxicity in any of the rats 14 days following the 4-hour exposure to 2.5 mg/L corn oil. All rats exposed to 2.9 mg/L test substance:corn oil 50:50 (v/v) survived the exposure and the subsequent 14-day recovery period. Animals demonstrated no loss in body weight 1, 7 or 14 days post exposure and no clinical signs of toxicity were observed.

  

Gross pathological examination revealed no evidence of organ-specific toxicity in any of the rats 14 days following the 2.9 mg/L test substance:corn oil 50:50 (v/v). Under the conditions of this study, the 4-hour inhalation median lethal concentration (LC50) for the test substance in male and female rats was greater than 0.89 mg/L, the maximum practically attainable atmospheric aerosol concentration.