Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Remarks:
The study on acute inhalation was conducted solely to comply with a non-EU national registration requirement, and has been provided here in accordance with REACH, Article 22(1)e.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 21 October 2014 to 10 December 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

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))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
traditional method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

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 GmbH, Sandhofer Weg 7, D-
97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 - 11 weeks old
- Weight at study initiation: males: 366-452g; females: 219-235g
- Fasting period before study: No
- Housing: Animals were grouped by sex (up to 5 animals per cage) in Type III solid floor cages with stainless steel mesh lids.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 30-70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
3.71 µm
Geometric standard deviation (GSD):
2.52
Details on inhalation exposure:
The animals were exposed, nose-only, to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprised of 2 concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers. Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was
distributed to the individual exposure ports. The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal’s nares to enter the exposure port. After passing through the animal’s breathing zone, used aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic. Airflows and relative pressures within the system were constantly monitored and controlled by the computer system thus ensuring a uniform distribution and constant flow of fresh aerosol to each exposure port (breathing zone). The flow of air through each port was at least 0.7 L/min. This flow rate was considered adequate to minimise re-breathing of the test atmosphere as it is about twice the respiratory minute volume of a rat. Homogeneity of the test atmosphere within the test chamber and amongst the exposure ports was not specifically determined during this study. However, chambers of this design have been fully validated and have shown to produce evenly distributed atmospheres in the animals’ breathing zones.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5 mg/L
No. of animals per sex per dose:
10 rats (5 male and 5 female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- all animals observed individually at hourly intervals during exposure, as soon as possible following removal from restrains at the end of exposure, 1 hour after exposure and twice daily for 14 days
- Individual bodyweights were recorded prior to treatment on the day of exposure (Day 0) and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes macroscopic examination and special attention given to the respiratory tract.

Results and discussion

Preliminary study:
A single sighting exposure was performed prior to the main study with 2 males and 2 females at the target concentration of 5 mg/L. No significant clinical signs were recorded on day of exposure and during whole two weeks of the observation period.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.01 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived until the end of the observation period.
Clinical signs:
No significant clinical signs were recorded on day of exposure and during whole two weeks of the observation period. Wet fur and/or fur staining were recorded in animals on the day of exposure and day following exposure. These observations were considered to be related to the restraint and exposure procedures and, in isolation, were considered not to be of toxicological relevance.
Body weight:
Normal bodyweight gain was noted for all exposed animals during the observation period. Slight bodyweight loss was noted during period Days 1-3 in some animals from the sighting (1/4) and main groups (3/10).
Gross pathology:
No necropsy findings were observed in any animals

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, no deaths occurred in a group of 10 rats (5/sex) exposed to the mean achieved concentration of 5.01 mg/L for 4 hours. The acute inhalation median lethal concentration of the test item, in CRL: (WI) Wistar strain rats is therefore considered to be greater than 5.01 mg/L.
Executive summary:

The acute inhalation toxicity of the test substance was assessed in 10 (5 male and 5 female) CRL: (WI) Wistar strain rats according to the OECD guideline 403.

The animals were exposed to the mean achieved concentration of 5.01 mg/L test item during 4 hours using a nose-only exposure system. The animals were observed during 14 days after exposure.

The mean achieved atmosphere concentration was 5.01 mg/L. The MMAD (Mean Mass Aerodynamic Diameter) was 3.71 μm ± 2.52 (GSD [Geometric Standard Deviation]).

No mortality occurred during the course of the study. No significant clinical signs were recorded on day of exposure and during whole two weeks of the observation period. No necropsy findings were observed in any animals exposed to the test substance.

The acute inhalation median lethal concentration of test item, in CRL: (WI) Wistar strain rats is therefore considered to be greater than 5.01 mg/L.