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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:
06 Sep 2005 - 17 Feb 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 412
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Mainz
Test type:
other: sub-acute inhalation toxicity
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-phenoxyethanol
- Physical state: liquid/ colourless, clear
- Analytical purity: > 99.9 core peak-area% (GC)
- Lot/batch No.: 41183068E0
- Expiration date of the lot/batch:
- Stability under test conditions: The stability under storage conditions over the exposure period was guaranteed by the sponsor and the sponsor holds the responsibility
- Storage condition of test material: room temperature, under N2, in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany
- Age at study initiation: about 7 weeks
- Weight at study initiation: males: ca. 227 g, females: ca. 163 g
- Housing: animals were housed singly in makrolon-wire cages (type MD III, Becker & Co., Castrop-Rauxel, FRG (floor area about 800 cm²)
- Diet (e.g. ad libitum): milled mouse/rat laboratory diet “GLP”, (Provimi Kliba SA, Kaiseraugst, Basel Switzerland)
- Water (e.g. ad libitum): tap water
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 06 Sep 2005 To: 28 Sep 2005

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Generator systems:
- Continuous infusion pumps PERFUSOR (B. Braun) for test group 1
- Piston metering pumps (Sarstedt DESAGA) for test group 2 and 3
- Two-component atomizers (stainless steel, Schlick mod. 970)
- Glass mixing stages (BASF)
- Glass cyclonic separators (BASF)


Generation procedure:
For each concentration the test substance was supplied to a two-component atomizer at a constant rate by means of a metering pump. The aerosol was generated with compressed air in a mixing stage with conditioned dilution air and passed via the cyclonic separator into the inhalation system. Due to the vapor pressure of the test substance, in all test groups mixtures of vapor and liquid aerosol are tested. The theoretical vapor concentration is up to 40 mg/m3.


TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.)
The target concentration of 40 mg/m3 in test group 1 was the saturation vapor concentration. At this concentration, part of the test substance might condensate in the atmosphere, thus liquid aerosols might be formed. To demonstrate the aerosol formation, two cascade impactor measurements were carried out. These resulted in MMADs between 2.9 and 3.7 μm with GSDs of 4.3 and 4.5. The amount of test substance that was trapped by the cascade impactor was approximately 20 % of that measured in the atmosphere, which was in the expected range for condensation effect. Due to the long sampling time (150 min), the condensation on the cascade stages during the sampling period might be much more pronounced in this group than in the other groups. Therefore, the particle size measurements in test group 1 were considered not to reflect the real particle size distribution, but to describe the liquid aerosol formation in the test atmosphere.
Cascade impactor measurements in the test groups 2 and 3 resulted in MMADs between 0.5 and 1.3 μm that were well within the respirable range. The calculated mass fractions of particles below 3 μm aerodynamic size ranged between 72.0 and 85.2%. The EACD (effective aerodynamic cut-off diameter 50%) of the last impactor stage is 1.2 μm. MMAD values below 1.2 μm are gained by extrapolation outside the effective measuring range of the impactor. Therefore the real value may lie between the calculated one and 1.2 μm.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
> 6 h
Remarks on duration:
6 hours per day, 5 days per week for 14 days (10 exposures)
Concentrations:
0, 40, 200, 1000 mg/m³ (nominal)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days exposure period without post exposure observation period
- Frequency of observations and weighing: once each working day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: examination of blood

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 000 mg/m³ air (nominal)
Mortality:
No deaths were recorded throughout the study up to and including the maximal dose.
Clinical signs:
other: In none of the test groups clinical signs of toxicity were observed.
Body weight:
Treatment related influence on body weight development or food consumption was found in the high concentration group on study day 7.
Gross pathology:
Clinical pathology examinations revealed no treatment-related changes in either males or females. 14 days of aerosol inhalation of the test substance led to histopathologic findings in the respiratory tract. The respiratory epithelium in the nasal cavity was the target tissue in high and mid concentration males and females. In the very anterior part signs of degeneration and metaplasia were noted, whereas in the more posterior parts hyperplasia was observed. Inflammatory cell infiltrates were seen in the mid and top concentration groups as a reaction to treatment. These findings are thought to be substance-related and the top concentration groups were slightly more affected. In the larynx (level I) in the area of the very sensitive epithelium at the base of the epiglottis, three male animals of the high concentration group showed a minimal to slight hyperplasia of the respiratory epithelium. This finding is also considered to be substance-related.
Other findings:
- Organ weights: In males of the mid and top concentration the absolute lung weight (up to 20.4%) and in males of the top concentration the relative lung weight (up to 19.3%) were statistically significantly increased.
- Histopathology: In the lungs there was an increase in thickness of small and terminal bronchi and increased numbers of mucous cells in larger bronchi of mid and top concentration males and females.
- Potential target organs: upper respiratory tract

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified