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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-03-06 through 2008-07-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
The humidity in the exposure chamber is lower than recommended by the guideline.
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
yes
Remarks:
The humidity in the exposure chamber is lower than recommended by the guideline.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, Borchen (Germany)
- Age at study initiation: approximately 2 months
- Weight at study initiation: 178-209 g (males); 172-196 g (females)
- Fasting period before study: no
- Housing: single housing, Makrolon cages, low-dust wood granulate bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-60
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2008-04-02 To: 2008-04-23

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
>= 1.67 - <= 1.89 µm
Geometric standard deviation (GSD):
>= 1.64 - <= 1.67
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas exposure tubes applying a directed-flow nose-only exposure principle.
- Exposure chamber volume: 3.8 L
- Method of holding animals in test chamber: plexiglass tubes
- Source and rate of air: Compressed air was supplied by Boge compressors
- Method of conditioning air: Air was conditioned (i.e. freed from water, dust, and oil) automatically by a VIA compressed air dryer.
- System of generating particulates/aerosols: Under dynamic conditions the neat test article was atomized into a baffle (pre-separator) from which the substance was conveyed into the intake of the cylindrical inhalation chamber. Atomization was achieved by using two types of binary nozzles with conditioned compressed air (15 L/min; dispersion pressure approximately 600 kPa). The test substance was fed into the nozzle by a calibrated digital pump (Harvard PHD 2000).
- Method of particle size determination: The particle-size distribution was analyzed using a BERNER-TYPE AERAS low-pressure critical orifice cascade impactor
- Temperature, humidity, pressure in air chamber: < 5%-10%


TEST ATMOSPHERE
- Brief description of analytical method used: The test-substance concentration sampled by gravimetric analysis was eluted from the filter and then determined by HPLC. A sampling train was used to analyze volatilized test article in addition. No test article was found in the gass bubbler.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric analysis / HPLC
Duration of exposure:
4 h
Concentrations:
Nominal: 2227.8, 6733.3 mg/m³
Analytical: 1382.6, 3152.8 mg/m³
Gravimetric: 1505.0, 3362.5 mg/m³
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The appearance and behavior of each rat were examined carefully several times on the day of exposure and at least once daily thereafter. Body weights were measured before exposure, on days 1, 3 and 7, and weekly thereafter. Individual weights are also recorded at death, if applicable.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: rectal temperatures
Statistics:
Necropsy: pair-wise Fisher test after the R X C chi-squared test.
Body weights: one-way ANOVA
LC50: maximum-likelihood method (Bliss)

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3 363 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: No mortality at highest attainable concentration
Mortality:
Mortality did not occur up to the maximum technically attainable concentration.
Clinical signs:
other: Clinical signs suggestive of respiratory tract irritation (labored and irregular breathing patterns, bradypnea, muzzle area with red encrustations) occurred concentration-dependent and were essentially reversible within the first post-exposure week.
Body weight:
Comparisons between the control and the exposure groups revealed a consistent, concentration-dependent decrease in body weights
Gross pathology:
The macroscopic findings were essentially indistinguishable amongst exposure and control groups. In animals of group 3 skin areas with alopecia were observed.
Other findings:
Reflex measurements
A battery of reflex measurements was made on the first post-exposure day. In comparison to the rats of the control group, some rats of group 3 exhibited changes in reflexes

Rectal temperature
Significant decreases in body temperature in groups 2 and 3.

Any other information on results incl. tables

Target Concentration[mg/m³ air]

Toxicological results*

Duration of clinical signs

Time of death

Mortality
[%]

Rectal Temperature [°C]

Males

0

0/0/5

---

---

0

38.1

1500

0/5/5

0d - 10 d

---

0

33.8**

5000

0/5/5

0d - 10d

---

0

33.5**

Females

0

0/0/5

---

---

0

38.2

1500

0/5/5

0d - 12d

---

0

34.2**

5000

0/5/5

0d - 13d

---

0

32.5**

*first number = number of dead animals

 second number = number of animals with signs

 third number = number of animals used

** p < 0.01

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
PETMP is not classified for acute inhalation toxicity because no mortality occurred at the maximum attainable concentration.