Registration Dossier

Administrative data

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

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
equivalent or similar to
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
Test type:
acute toxic class method

Test material

Test material form:
solid: granular

Test animals

Crj: CD(SD)
Details on test animals and environmental conditions:
Quarantine and Animal Selection
were quarantined after arrival for 6 days prior to testing. During the quarantine period rats
were weighed and observed for clinical signs of disease 3 times. Rats were obtained from the
general population of stock rats released from quarantine and were selected for use on this study fiom those rats exhibiting a normal pattern of weight gain and no overt signs of disease.
Rats were housed either singly or in pairs in suspended, stainless steel, wire-mesh cages.
Animal Room Environment
Animal rooms were maintained on a timer-controlled, 12-hour light/12-hour dark cycle.
Environmental conditions of the rooms were targeted to be within a temperature range of 23 +/- 1°C and a relative humidity range d 50 +/-10%. Excursions outside these ranges were of insufficient magnitude and/or duration to have adversely affected the validity of the study.
IEach rat was assigned a unique 6-digit identification number which corresponded to a numbered card affixed to the cage. Prior to exposure, the tail of each rat was numbered with waterinsoluble markers so that individual rats could be identified after exposure.
Feed and Water
Exkept during exposure, PMI Feeds. Lnc. Certified Rodent Diet #5002 and tap water fromUnited Water Delaware were available ad libitum.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Mass median aerodynamic diameter (MMAD):
4.5 µm
Geometric standard deviation (GSD):
Details on inhalation exposure:
Atmosphere Generation
Chamber atmospheres of the substance were generated by suspending the particulate test substance in
tered into the jetmill with a K-Tron model T-20 Twin Screw Volumetric Feeder. Filtered,
high-pressure air (60 Umin) introduced into the jetmill carried the resulting atmosphere into the exposure chamber. Chamber concentrations of the substance were controlled by varying the test.
Test atmospheres were exhausted through a high-capacity particle filter followed by an MSA charcoal/HEPA filter cartridge prior to discharge into the fume
Chamber Construction and Design
The exposure chamber was constructed of glass with a nominal internal volume of 34 L. A b fle positioned immediately inside the chamber inlet promoted
uniform chamber distribution ofthe test atmosphere.
Exposure Mode
During exposure, rats were individually restrained in stainless steel cylinders with conical nose pieces. The restrainers were inserted into the polymethylmethacrylate faceplate of the exposure chamber so that only the nose of each rat extended into the chamber.
Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
9.3 mg/L
Range: 6.8-15 mg/L3 (SD:3.2, n=6)
No. of animals per sex per dose:
Control animals:

Results and discussion

Effect levels
Key result
Dose descriptor:
other: ALC
Approximate Lethal Concentration
Effect level:
9.3 mg/L air
Exp. duration:
4 h
One rat died during exposure to H-22860 at a concentration of 9.3 mgL.
All remaining animals survived the exposure and were sacrificed at the conclusion of the I4-day recovery period.
Clinical signs:
After the exposure, when the rats were removed from the restrainers. clinical signs included nasal and ocular discharges and stained and/or wet fur. In addition rats had test substance on their faces. These clinical signs are typically observed in rats subjected to nose-only inhalation
exposures employing aerosols.

During the recovery period, 1 rat exhibited hunched posture I day after the exposure. This
clinical observation had resolved by 2 days after exposure. All other clinical signs observed durig the recovery period were considered not to be substance related and typical of rats that had undergone a nose-only inhalation exposure.
Body weight:
Four of 5 surviving rats experienced slight to servere weight losses (ranging from I .8 to 15% of initial body weight ) within 1 day of exposure.
The I remaining rat gained weight. Body weights of rats began to increase by study day 3 and increased over the remainder of the 14day recovery period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Under the conditions of this study, the approximate lethal concentration (ALC)for the substance is 9.3 mg/L. On an acute inhalation basis. The substance is considered to have very low toxicity (ALC greater tban 2 mg/L).
Executive summary:

One group of 6 d e Cd:CD@(SD)BR rats was exposed nose-only for a single, 4-how period to the substance in air. The test atmosphere was generated by suspending the dry powder in air. The concentration of the substance

was determined by gravimetric analysis. Rats were weighed and observed far clinical signs of toxicity during a 14-day recovery period. Rats were exposed to a chamber concentration of 9.3 mg/L

the substance.

The mass median aerodynamic diameter (MMAD) of the dust generated was 4.5 pm. One rat died during the exposure to

the substance.

With the exception of 1 rat with hunched posture the day after exposure, no notable clinical signs of toxicity were evident on this study. Rats generally exhibited slight to severe body-weight losses within 1 day of exposure but began to regain weight by test day 3.