Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12/2003-05/2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed acording to OECD guideline No. 403 and under GLP regulation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
other: Limit test
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity 99,7%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Temperature (°C) 19-22
Relative Humidity (%RH) 26-51
Light cycle: 12h artificial fluorescent light / 12 h darkness
Music was played 12h /day

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
A dust aerosol was generated from the test item using a rotating brush aerosol generator (CR 3020, CR Equipments SA, CH-1295 Tannay, Switzerland) connected to a micronising jet mill. No diluent air was added. The generated aerosol was discharged into the exposure chamber through a 63Ni charge neutraliser.
Test atmosphere samples for the gravimetric measurements of the test item concentration and particle size distribution, and for the measurement of relative humidity, temperature and oxygen concentration, were collected directly from the feed tube in the breathing zone of the animals, at an empty port of the exposure chamber delivering "fresh" test item to the animal's nose. This approach was chosen in order to obtain representative samples of what was delivered to the animals. Airflow rates were determined for the recording of relative humidity, temperature and oxygen concentration and during the collection of samples for the determination of test item concentration using a dry-test meter and a pressure gauge (Schlumberger Industries SA, City of Geneva and Timeus & Co., Zurich, respectively), calibrated with a reference dry-test meter. Sampling airflow rates during the collection of impactor samples were determined using a calibrated pressure gauge (Timeus & Co., Zurich).
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric measurement
Duration of exposure:
>= 4 h
Concentrations:
mean aerosol concentration = 5.114 mg/L air
Mass Median Aerodynamic Diameter (MMAD) = 2.92 µm
No. of animals per sex per dose:
A group of 5 male and 5 female Wistar rats [HanBrl:WIST(SPF)] was used in this study.
Control animals:
no
Details on study design:
The 10 animals were exposed by nose-only, flow-past inhalation to the test item at a mean aerosol concentration of 5.114 mg/L air for a single 4-hour period. Two gravimetric measurements of particle size distribution during the exposure produced mass median aerodynamic diameters of 2.92 µm and 2.96 µm. All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e. over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8 and 15. On day 15, all animals were sacrificed and necropsied.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Mortality:
no mortality was observed
Clinical signs:
no clinical signs
Body weight:
no relevant adverse effects on body weight development
Gross pathology:
no macroscopic pathology findings
Other findings:
no other findings

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the data of this study, the LC50 value of DHA in rats exceed 5.114 mg/L air. No toxicity was observed in rats after inhalation of DHA up to the limit dose.
Executive summary:

The acute toxicity potential of DHA after inhalation was investigated in Wistar rats after an exposure period of 4 hours using a nose-only inhalation system. Male and female animals were exposed to DHA at a mean aerosol concentration of 5.114 mg/L air with a particle size (MMADs) of ~ 2.9 µm. No deaths, no clinical signs and no relevant adverse effects on body weight gain were observed during the 14-day observation period following exposure. Gross necropsy revealed no macroscopic pathological findings, and specifically, no lung or respiratory tract discoloration was observed.

Based on the results of this study, the maximum non-lethal concentration of DHA in rats after single exposure by inhalation for 4 hours is >5.114 mg/L, and DHA is considered to have no toxicity potential after single administration by the inhalation route.