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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:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline and GLP-compliant study

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Commercial grade
Specific details on test material used for the study:
Batch no. 52334524U0
Homogeneity: given visual
Storage stability: Expiry date: 15 Sep 2020
Melapur MC25
Identifier: CAS 37640-57-6

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,
- Age at study initiation: about 8 – 12 weeks old
- Weight at study initiation: animals of comparable weight (+/- 20% of the mean body weight)
- Fasting period before study: no
- Housing: single houing or up to 5 animals
- Diet: Kliba laboratory diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20–24 °C
- Humidity: 30-70 %
- Air changes: 15 changes per hour
- Photoperiod: 12 hours light / 12 hours dark

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
>= 3.3 - <= 3.5 µm
Geometric standard deviation (GSD):
>= 2.1 - <= 2.6
Remark on MMAD/GSD:
Two samples were analyzed.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: For each test group the dusts were produced inside the inhalation system with a dust generator and compressed air and passed into the inhalation system. The concentrations were adjusted by varying the apertural width rotation of the dosing wheel of the dust generator.
- Exposure chamber volume: 34 L
- Method of holding animals in test chamber: restraining tubes
- Source and rate of air: central air conditioning system, 0.8 m³/h
- Method of conditioning air: Central air conditioning system provided cold air of about 15°C. This cold air passed through an activated charcoal filter, adjusted to room temperature of 20 to 24°C and passed through a second particle filter (H13 (HEPA) Camfil Farr, Germany). The so generated conditioned air was used to generate inhalation atmospheres.
- System of generating particulates/aerosols: The test item was stirred in its container before a sample for dust generation was taken. The test item was desagglomerated in a mixer (mixing for 10 seconds) before introduction into the dust generator via the dosing wheel (Gericke/BASF).
- Method of particle size determination: Stack Sampler Mark III (Andersen). Before sampling, impactor stages were assembled with preweighed glass fiber collecting discs, and equipped with a backup particle filter. The impactor was connected to a vacuum pump, and for each test group samples were taken from the breathing zone of the animals. Sampling occurred 30 minutes (or later) after the beginning of the exposure.
- Treatment of exhaust air: The exhaust air was filtered and conducted into the exhaust air of the building.

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric, filtration equipment with probe, internal diameter: 7 mm
- Samples taken from breathing zone: yes

VEHICLE
In technical trial runs, various modifications of the dust generation procedure were tested to produce the limit concentration of 5 mg/L. To improve the flowability, 1% AEROSIL® R 972 was added to the test item. AEROSIL® is a brand name of various amorphous silicas produced by Evonik Industries, Frankfurt am Main, Germany. AEROSIL® R 972 is a hydrophobic fused silica, which is used to improve free flow and anti-caking characteristics of powders.

TEST ATMOSPHERE:
- Particle size distribution: Based on cascade impactor measurements. The calculation of particle size distribution was carried out by means of mathematical methods for evaluating particle measurements.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5 mg/L
The actual measured concentration was 5.057 mg/L
No. of animals per sex per dose:
5 rats
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weight was determined once during the acclimatization period, at the start of the exposure period (Day 0) and at least on Days 1, 3 and 7, and weekly thereafter, or before the sacrifice of the animals at the end of the observation period.
- Clinical observations were recorded for each animal before exposure, separately several times during exposure (usually hourly) and after exposure. At least once daily on the preexposure day and during the post exposure observation period.
- Necropsy of survivors performed: yes
Statistics:
LC50 values were calculated for males, females and both sexes combined using a binomial test.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality was observed.
Mortality:
No lethality was observed in male and female animals during the study period of 14 days.
Clinical signs:
Laboured respiration was noted during the exposure period (Hour 2 to Hour 4) and fur contaminated with test item was noted on Day 0. No abnormalities were detected in the animals during the post exposure observation period from Day 1 onwards.
Body weight:
The mean body weights of the animals decreased on the first post exposure observation days but increased thereafter.
Gross pathology:
There were no test item-related macroscopic findings at scheduled necropsy.

Any other information on results incl. tables

Analytical measurements

Exposure conditions: Supply air: 1.5 ± 0.0 m³/h, exhaust air: 0.6 ± 0.0 m³/h,

Test substance preparation: 62.8 g/h, temperature: 22.8 ± 0.3 °C, relative humidity: 22.2 ± 1.3 %

Analytical concentration: 5.075 ± 0.622 mg/L (nominal concentration: 52.3 mg/L)

Particle size analysis: MMAD (µm) / GSD: 3.5 / 2.6 (sample 1), 3.3 / 2.1 (sample 2)

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

In a GLP-compliant acute inhalation toxicity study according to OECD 403 (single 4 -hour exposure, nose only; limit test), male and female Wistar rats were exposed to the test item melamincyanurat as a dust (key study, BASF 13I0834/09I058). Mortality, clinical signs and body weights were recorded during the 14 day observation period. At necropsy, a macroscopical examination was conducted. The actual measured test item concentration was 5.057 mg/L. Particle size distributions were well within the respirable range, with mass median aerodynamic diameters (MMADs) of 3.5 and 3.3 μm and geometrical standard deviations of 2.6 and 2.1. There was no mortality. Clinical signs of toxicity comprised of laboured respiration noted during exposure (Hour 2 to Hour 4) and substance contaminated fur (Day 0). No clinical signs were observed from study Day 1 onwards. Mean body weights decreased on the first post exposure observation days but increased thereafter. No gross pathological abnormalities were detected. The 4 -hour LC50 value was deemed as > 5.1 mg/L (calculated based on analytical concentraton) under the conditions of this study.