Registration Dossier
Registration Dossier
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EC number: 468-710-7 | CAS number: 754-12-1
Toxicological information
Repeated dose toxicity: inhalation
Currently viewing:
Administrative data
- Endpoint:
- sub-chronic 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:
- 2 007
- Report date:
- 2007
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland
- Age at study initiation: 6 weeks
- Weight at study initiation: Mean weights 231 g (males) and 172 g (female)
- Fasting period before study: None
- Housing: Macrolon cages with wood shaving beding
- Diet: Ad libitum (overnight fast prior to necropsy)
- Water: Ad libitum
- Acclimation period: At least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 37-44
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: March 2006 To: June 2006
Administration / exposure
- Route of administration:
- inhalation: gas
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Cylindrical PVC column with a volume of ~ 70 liters surrounded by a transparent hook. The test atmosphere was introduced at the bottom and exhausted at the top
- Source and rate of air: At least 1 L/min
- Temperature, humidity in air chamber: 20-24C; 30-70%
- Air flow rate: At least 1 L/min
TEST ATMOSPHERE
- Brief description of analytical method used: Total carbon analysis
- Samples taken from breathing zone: Yes
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Total carbon analysis
- Duration of treatment / exposure:
- 6 hours a day
- Frequency of treatment:
- 5 days a week for 13 weeks
Doses / concentrationsopen allclose all
- Dose / conc.:
- 5 000 ppm
- Remarks:
- Group 2: Low dose. Equivalent to 23300 mg/m3.
- Dose / conc.:
- 15 000 ppm
- Remarks:
- Group 3: Mid dose. Equivalent to 69900 mg/m3.
- Dose / conc.:
- 50 000 ppm
- Remarks:
- Group 4: High dose. Equivalent to 233000 mg/m3.
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: 50000 ppm (5%) was chosen as the high dose group to prevent secondary effects due to oxygen deprivation that can occur at higher concentrations
- Post-exposure recovery period in satellite groups: None
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS:
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS:
- Time schedule: daily
BODY WEIGHT:
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for per group determined and mean daily diet consumption was calculated as g food/kg body weight/day
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 was calculated as time-weighted averages from the consumption and body weight gain data
OPHTHALMOSCOPIC EXAMINATION: yes
HAEMATOLOGY:
- Time schedule for collection of blood: At scheduled necropsy
- Anaesthetic used for blood collection: Yes, Nembutal
- Animals fasted: Yes
- How many animals: All survivors
- Parameters listed in OECD guideline were examined.
CLINICAL CHEMISTRY:
- Time schedule for collection of blood: At scheduled necropsy
- Animals fasted: Yes
- How many animals: All survivors
- Parameters listed in OECD guideline were examined. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - those organs listed in the guideline plus nose (6-levels), larynx (3 levels), trachea (3 levels including bifurcation), and each lung lobe at 1 level. - Statistics:
- Data were evaluated by the appropriate statistical test (one-way analysis of variance followed by Dunnett's multiple comparison test, one-way analyis of variance (ANOVA) followed by Dunn't multiole comparison testes, Krisckal-Wallis nonparametric Anova followed by Mann-Whitney U-tests, Fischers exact probability test.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
Effect levels
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- > 50 000 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Remarks:
- Equivalent to 233000 mg/m3.
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Exposure of rats to 5000, 15000 or 50000 ppm (23300, 69900, or 233000 mg/m3) test substance for 6 hours a day, 5 days a week, for 64 or 65 exposure days over a 98 day period did not result in adverse effects in any of the exposure groups. In the present sub-chronic toxicity study, the high concentration level of 50000 ppm was therefore considered the No-Observed-Adverse-Effect-Concentration for male and female rats.
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