Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Test material form:
other: Yellow liquid
Details on test material:
- Name of test material (as cited in study report): Kathon™ 886 MMPA Process
- Physical state: Yellow liquid
- Stability under test conditions: Stable at room temperature
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rohm and Haas, Batch No. SW 82/0169

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dilution in water

OTHER SPECIFICS: Purity of test material was 14% (11% of CMIT and 3% of MIT).

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River-Kingston, Stone Ridge, New York, USA.
- Age at study initiation: Approximately 6 weeks old.
- Weight at study initiation: 135-169 g for males and 117 to 147 g for females.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
1.3 µm
Geometric standard deviation (GSD):
1.9
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2000-L stainless steel and glass chamber
- System of generating particulates/aerosols: all glass Laskin-type nebulizer

TEST ATMOSPHERE
- Brief description of analytical method used: pairs of impingers collected both the vapor and aerosol phases.

VEHICLE (if applicable)
- Concentration of test material in vehicle: 0.34, 1.15 and 2.64 mg a.i./m3
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The Kathon™ 886 concentrations were determined by sampling the chamber atmosphere using pairs of impingers which collected both the vapor and aerosol phases of Kathon™ 886.
Duration of treatment / exposure:
90 days
Frequency of treatment:
5 days per week, 6 hours per day
Doses / concentrationsopen allclose all
Dose / conc.:
0.34 mg/m³ air
Remarks:
Based on a.i. concentration
Dose / conc.:
1.15 mg/m³ air
Remarks:
Based on a.i. concentration
Dose / conc.:
2.64 mg/m³ air
Remarks:
Based on a.i. concentration
No. of animals per sex per dose:
16
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily. Before, during and after each exposure.

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Prior to study start and during the last week of exposure.
- Dose groups that were examined: All groups.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 13 week necropsy.
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- How many animals: 16/sex/group
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At 13 week necropsy.
- How many animals: 16/sex/group
- Parameters checked in table [No.?] were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes (see table)
HISTOPATHOLOGY: Yes (see table)
Other examinations:
None
Statistics:
Body weight, body weight gain, clinical chemistry, hemaglobin and hematocrit were inspected for normality and homogeneity of variance by residual plots and then analyzed with a two-way ANOVA. If a significant p < 0.05 treatment group by sex effect were observed, group means were compared utilizing Dunnett’s t-test.
Hematology and differentials were inspected for normality and homogeneity of variance by stem leaf, boxplot and normal probability plots. If the ANOVA assumptions were satisfied, then the statistical analysis described above for the continuous data was utilized. When ANOVA assumptions were not satisfied, chi-square and Jonckheere tests were applied.
Pathology incidences were compared by Fischer’s Exact Test.
For all comparisons, the null hypothesis was rejected at a probability of 0.05 or less.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
rhinitis
Mortality:
mortality observed, treatment-related
Description (incidence):
rhinitis
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
decreased body weight gains
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Decreased serum protein
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Decreased spleen weights
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
eosinophilic droplets in the anterior respiratory mucosa of the nasal turbinates and slight rhinitis in the lining of the anterior portion of the nasal cavity
Histopathological findings: neoplastic:
not specified
Other effects:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
Rats exposed to 2.64 mg/m3 exhibited signs resulting from exposure consistent with those produced by a sensory irritant (chromorhinorrhea, rhinorrhea, eye squint, bradypnea, dyspnea).

BODY WEIGHT AND WEIGHT GAIN
Decreased body weight gains at 2.64 mg/m3.

CLINICAL CHEMISTRY
Decreased serum protein in females at 2.64 mg/m3.

ORGAN WEIGHTS
Decreased male spleen weights at 2.64 mg/m3.

HISTOPATHOLOGY: NON-NEOPLASTIC
Slight to moderate incidences of eosinophilic droplets in the anterior respiratory mucosa of the nasal turbinates and slight rhinitis in the lining of the anterior portion of the nasal cavity were observed in the 2.64 mg/m3 treated animals. All the histopathologic changes were very minor, potentially reversible, and generally reflective of minimal tissue responses to a very mild, low-grade respiratory irritant. No adverse effects were seen on the histopathology of any tissues/organs distant from the site of dosing.

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
0.34 mg/m³ air (analytical)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
histopathology: non-neoplastic
Dose descriptor:
LOAEL
Effect level:
1.15 mg/m³ air (analytical)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: overall effects clinical signs; gross pathology

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
NO(A)EL = 0.34 mg a.i./m3 (0.00034 mg/L). There were no systemic effects in this study. LOEL = 1.15 mg a.i./m3based on slight, treatment-related rhinitis. Rats at the highest dose (2.64 mg/m3) exhibited very mild, low grade respiratory irritation. No adverse effects on the histopathology of any tissues/organs distant from the site of dosing.
Executive summary:

OECD 413, subchronic inhalation toxicity, 90-day study with analytical confirmation of concentrations of Kathon™886.

LOEL = 1.15 mg a.i./m3based on slight, treatment-related rhinitis. There were no systemic effects in this study. Rats at the highest dose (2.64 mg/m3) exhibited very mild, low grade respiratory irritation. No adverse effects on the histopathology of any tissues/organs distant from the site of dosing.

NO(A)EL = 0.34 mg a.i./m3 (0.00034 mg/L).