Registration Dossier

Administrative data

Description of key information

one study on acute toxicity by oral route and one study on acute toxicity by inhalative route available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
unknown
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
Only abstract with species and LD50 value given.
A handwritten report is available, language japanese
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
not available
Species:
mouse
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not available
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not available
Doses:
not available
No. of animals per sex per dose:
not available
Control animals:
not specified
Details on study design:
not available
Statistics:
not available
Preliminary study:
not available
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 6 000 mg/kg bw
Mortality:
description not available
Clinical signs:
description not available
Body weight:
description not available
Gross pathology:
description not available
Other findings:
description not available
Interpretation of results:
GHS criteria not met
Conclusions:
An LD50 (orally in mice) is available, it is stated to be over 6000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
acute toxic class method
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male
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.
Housing
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.
Identification
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.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
4.5 µm
Geometric standard deviation (GSD):
2.2
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
hood.
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:
yes
Duration of exposure:
4 h
Concentrations:
9.3 mg/L
Range: 6.8-15 mg/L3 (SD:3.2, n=6)
No. of animals per sex per dose:
6
Control animals:
no
Key result
Sex:
male
Dose descriptor:
other: ALC
Remarks:
Approximate Lethal Concentration
Effect level:
9.3 mg/L air
Exp. duration:
4 h
Mortality:
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.
Interpretation of results:
GHS criteria not met
Conclusions:
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
9.3 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The available information is conclusive but not sufficient for classification.