Registration Dossier

Administrative data

Endpoint:
acute 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:
2009
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
liquid: viscous
Details on test material:
- Manufacturers identification: Novares LA 300
- Substance type: organic
- Test material is 'Oligomerisation and alkylation reaction products of 2-phenylpropene and phenol' (OAPP), EC list number 700-960-7 (assigned manually to validated substances from inquiries by ECHA). Originally the substance phenol, methylstyrenated, CAS No. 68512-30-1, EC No. 270-966-8 was submitted for registration. Subsequent to substance validation, the identity of the substance was changed by ECHA.
- for additional information see respective study record
Specific details on test material used for the study:
- Name of test material (as cited in study report): Novares LA 300 (phenol, methylstyrenated)
- Lot/batch No.: 28166
- Composition of test material: composition is specified in IUCLID Sect. 13 - Assessment reports under Certificate of Analysis_Novares LA 300_phenol, methylstyrenated
- Stability under test conditions: no measured data; based on chemical structure assumed to be stable
- Storage condition of test material: room temperature, exclusion of light

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories Ltd, Oxon, UK.
- Age at study initiation: 8 - 12 wks
- Weight at study initiation: 270 - 284 g (m); 199 - 220 (f) [see Appendix 6]
- Fasting period before study: no
- Housing: solid-floor polypropylene cages, groups of 5 by sex
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: >= 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): >= 15x/h
- Photoperiod (hrs dark / hrs light): 12 / 12


Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: diethyl ether
Mass median aerodynamic diameter (MMAD):
2.22 µm
Geometric standard deviation (GSD):
2.83
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Cylindrical exposure chamber
- Exposure chamber volume: approx. 30 litres (dimensions: 28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: individually held in a tapered, polycarbonate restraining tube

- Method of conditioning air: Compressed air supplied by means of an oil free compressor and passed
through a water trap and respiratory quality filters before it was introduced to the nebuliser.
- Air flow through chamber: 60 L/min

- System of generating particulates/aerosols: Glass concentric jet nebuliser located at the top of the exposure chamber /
Nebuliser connected to a glass syringe attached to an infusion pump
providing the material formulation

- Method of particle size determination: 3x during the exposure, using a Marple Personal Cascade Impactor
with six impactor stages (9.0, 6.3, 4.0, 1.7, 0.81 and 0.30 µm cut points).
The collection substrates and backup filter were weighed before and after sampling
and the weight of test material, collected at each stage, calculated by difference
(Results in Report Fig. 3 and 4).

- Method of particle collection: by weighed glass fibre filter placed in a filter holder and temporarily sealed
in a vacant port of the exposure chamber in the animals’ breathing zone.

- Volatile / non-volatile fraction: The mean non-volatile component of the batch used during the study was found to be 98.6 % (n=10).

Procedure: Prior to the start of the study, the non-volatile component of the test material was determined
by adding a small, known amount of test material to glass fibre filters and recording their weights.
The filters were then kept in a desiccator between 19 and 20°C for approx. 24 h and then weighed again.
The difference in the two weights was taken as the volatile content of the test material and the non-volatile component
was calculated as a percentage.

- Treatment of exhaust air: bottom outlet through a "scrubber" trap, connected with a high efficiency filter to a metered exhaust system
- Temperature, humidity, pressure in air chamber: 19 - 20 °C, 39 - 47% (rel.hum.), slight low-pressure [Report, Appendix 9]


TEST ATMOSPHERE
- Brief description of analytical method used: particle/aerosol gravimetric determination
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable): diethyl ether
- Concentration of test material in vehicle (if applicable): 50 % (w/w)
- Justification of choice of vehicle: high viscosity of the TS, to improve aerolisation of the TS


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: ca. 72% (w/w) with aerodynamic diameter < 4 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.22 / 2.38 µm

Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrically (aerosol)
Duration of exposure:
4 h
Concentrations:
Mean: 4.92 +-0.46 mg/L (n = 17) / nominal: 50.3 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
For particle size: arithmetic mean + standard deviation / MMAD derived from probits of stage amounts plotted against Log10 cut-point size + geometric standard deviation / LD50: not relevant

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.92 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Novares LA 300; standard deviation of analytical determination: 0.46 mg/L
Sex:
male/female
Dose descriptor:
LC0
Effect level:
4.92 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Novares LA 300; standard deviation of analytical determination: 0.46 mg/L
Mortality:
none
Clinical signs:
Hunched posture, pilo-erection, and increased respiratory rate commonly seen for short periods following 4h inhalation; isolated instance of lethargy / All female animals exhibited staining of the head and one also showed noisy respiration.
4 - 6 d after exposure, all animals appeared normal.
Body weight:
One male with bw transiently reduced during week 1.
Normal bodyweight development was noted for all other animals during the course of the study.
[see Report Appendix 6]
Gross pathology:
No macroscopic abnormalities

Any other information on results incl. tables

The particle size analysis of the atmosphere drawn from the animals’ breathing zone, was as follows

[see Report Appendices 1 and 2]:

Mean Achieved

Atmosphere

Concentration +-SD [mg/L]

(n = 17)

Mean Mass Median

Aerodynamic Diameter

[µm] (n = 3)

Inhalable Fraction

[wt% <4 µm]

Geometric Standard

Deviation [µm]

4.92 +-0.46

2.22

71.5

2.83

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
No classification required