Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
OECDTG412 with GLP. Particle size of this product is more than 355 um and this product is practically not including any respirable fraction. This test substance is micronized into less than 10 um in order to make a respirable fraction.Particle size of this product is more than 355 um and this product is practically not including any respirable fraction. This test substance is micronized into less than 10 um in order to make a respirable fraction.Particle size of this product is more than 355 um and this product is practically not including any respirable fraction. This test substance is micronized into less than 10 um in order to make a respirable fraction.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.5%
Test substance is micronized from this substance.
The commertial product (>355 um) has practically no micronized particle size (<10 um .

Test animals

Species:
rat
Strain:
other: CD(Sprague-Dawley) ab. for SD of Charls River colony
Sex:
male/female

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: acetone-water (80:20 by wt)
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
nominal : 3 ug/L, 1 ug/L and 0.3 ug/L
measured: 2.27, 0.87, 0.21 ug/L
Duration of treatment / exposure:
28 days
5 days of each week for 4 consecutive weeks
Frequency of treatment:
6 hours a day, 5days a week for 4 consecutive weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.3, 1.0, 3.0 mg/m3
Basis:

No. of animals per sex per dose:
5
Control animals:
yes
yes, concurrent vehicle
Details on study design:
Post-exposure period: none
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:at least twice each day
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:at least twice each day

BODY WEIGHT: Yes
- Time schedule for examinations: weekly interval

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

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: Yes

WATER CONSUMPTION: No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes
- Time schedule for collection of blood:
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.

URINALYSIS: No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

OTHER:
CAGE SIDE OBSERVATIONS: Yes / No / No data
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

BODY WEIGHT: Yes / No / No data
- Time schedule for examinations:

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

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: Yes / No / No data

WATER CONSUMPTION: Yes / No / No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: Yes / No / No data
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes / No / No data
- Time schedule for collection of blood:
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes / No / No data
- Time schedule for collection of blood:
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.

URINALYSIS: Yes / No / No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: Yes / No / No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

OTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
Organ weight
Statistics:
t-test

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
During exposure signs of irritation typified by: half-closed eyes, hunched posture, rubbing snout with paws, agitated grooming, red ears, licking the inside of the mouth, mild convulsions and irregular breathing were seen in rats from inter. dose and high
Mortality:
mortality observed, treatment-related
Description (incidence):
During exposure signs of irritation typified by: half-closed eyes, hunched posture, rubbing snout with paws, agitated grooming, red ears, licking the inside of the mouth, mild convulsions and irregular breathing were seen in rats from inter. dose and high
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
A small reduction in weight gain in male rats from inter. dose and high dose groups may be exposure-related. No other treatment-related effects were seen.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Reduced consumption in male rats from inter. dose and male and female rats from high dose groups may be exposure-related. No other treatment-related effects were seen.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
effects observed, treatment-related
Description (incidence and severity):
No differences were seen that were considered of toxicological significance.
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
No differences were seen that were considered of toxicological significance.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
No differences were seen that were considered of toxicological significance.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
No differences were seen that were considered of toxicological significance.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
No treatment-related abnormalities were seen.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
No treatment-related abnormalities were seen
Histopathological findings: neoplastic:
effects observed, treatment-related
Description (incidence and severity):
No treatment-related abnormalities were seen
Details on results:
MORTALITY
No death occured during the study.

CLINICAL SIGNS
During exposure signs of irritation typified by: half-closed eyes, hunched posture, rubbing snout with paws, agitated grooming, red ears,
licking the inside of the mouth, mild convulsions and irregular breathing were seen in rats from Inter. dose and High dose.
At other times red ears and saivitation were observed in Intr.dose and High dose. No other treatment-related effects were seen.

BODY WEIGHT AND WEIGHT GAIN
A small reduction in wt gain in male rats from Inter dose and High dose and female rats from High dose may be exposure-related.

FOOD CONSUMPTION
Reduced consumption in male rats from Inter. dose and male and female rats from High dose may be exposue-related.

FOOD EFFICIENCY


WATER CONSUMPTION


OPHTHALMOSCOPIC EXAMINATION


HAEMATOLOGY
No differences were seen that were considered of toxicological significance.

CLINICAL CHEMISTRY
No differences were seen that were considered of toxicological significance.

URINALYSIS


NEUROBEHAVIOUR


ORGAN WEIGHTS
No differences were seen that were considered of toxicological significance.

GROSS PATHOLOGY
No differences were seen that were considered of toxicological significance.

HISTOPATHOLOGY: NON-NEOPLASTIC
No differences were seen that were considered of toxicological significance.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)


HISTORICAL CONTROL DATA (if applicable)


OTHER FINDINGS

Effect levels

Dose descriptor:
NOAEC
Effect level:
0.21 mg/m³ air
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The NOAEL is 0.21 mg/m3 based on 28 -day inhalation study in rats.
Executive summary:
In a subchronic inhalation toxicity study, this substance was administered to 5 of CD rats (Spraque-Dawley) /sex/concentration by dynamic whole body exposure at concentrations of 0, 0.21, 0.87, 2.27 mg/m3 for 6 hours per day,  5 days/week for 4 consecutive weeks.

The NOAEL is 0.21 mg/m3 based on 28 -day inhalation study in rats.

 

The commercial product (>355 um) has practically no micronized particle size (<10 um).

However, we should consider the DNEL for inhalation for workers because of any accidental release of this product at polymer manufacturers plant site.