Registration Dossier

Administrative data

acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 2015 - May 2015
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is performed according to OECD/US EPA OPPTS guidelines and according GLP principles.

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guidelineopen allclose all
according to
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
September 2009
according to
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
August 1998
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Test material form:
solid: particulate/powder
migrated information: powder

Test animals

other: Crl:CD(SD)
Details on test animals and environmental conditions:
- Source: Charles River Laboratories, Raleigh, NC, USA
- Age at study initiation: 8 weeks
- Weight at study initiation: males 254 g to 283 g; females 195 g to 217 g
- Fasting period before study: no
- Housing: all animals were housed individually in suspended wire-mesh cages. On the day of exposure, the animals were placed in nose-only exposure holding tubes in the animal room, transported to the exposure room, exposed for the requisite duration then returned to their home cages.
- Diet: PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002 (block) ad libitum, except during acclimation to the nose-only restraint and during the exposure period.
- Water: Reverse osmosis-treated water supplying the facility) ad libitum, except during acclimation to the nose-only restraint and during the exposure period
- Acclimation period: a minimum of 5 days

- Temperature (°C): 21.4 to 21.7
- Humidity (%): 43.4 to 51.3
- Air changes (per hr): a minimum of 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05 May 2015 To: 19 May 2015

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Details on inhalation exposure:
- Exposure apparatus: a stainless steel, conventional nose-only exposure system with rubber grommets in exposure ports to engage the animal holding tubes
- Exposure chamber volume: 7.9-L
- Method of holding animals in test chamber: animals were restrained in nose-only exposure holding tubes during exposure
- Source and rate of air: airflow rates through the exposure system were calculated from the airflow required for aerosol generation and provided a minimum of 12 air changes per hour through the exposure system
- Method of conditioning air: airflow to the exposure system was provided using a dry, breathing quality, in-house, compressed air source. A temperature and relative humidity transmitter probe (model no. HX94C, Omega Engineering, Inc., Stamford, CT) was used with a display unit to monitor temperature and percent relative humidity.
- System of generating particulates/aerosols: The test substance was delivered at a constant rate to a jet mill air micronizer using an auger-type dry material feeder. The Accurate feeder was equipped with two Syntron Vibrators and a ½-inch solid core auger. Dry compressed air was supplied to the micronizing and inlet ports of the jet mill to affect aerosolization of the test substance using 2 regulators. The resulting aerosol from the jet mill was delivered to a 2-inch PVC elbow fitting (position downward) located approximately 11-inches from the bottom of a 4-inch × 44-inch PVC pipe set. This settling pipe was in a vertical orientation to remove large particles from the aerosol atmosphere. The test substance atmosphere was delivered from the top of the settling pipe to a glass cyclone to further reduce particle size. From the cyclone, test substance atmosphere was directed to the nose-only exposure system through 22-mm corrugated respiratory tubing.
- Method of particle size determination: two aerosol particle size measurements were conducted during the exposure using a 7-stage stainless-steel cascade impactor. Pre weighed, 22-mm stainless-steel collection substrates were used as the collection substrates for stages 1 through 7 and a 25-mm glass-fiber filter (Type A/E, PALL Corporation) was used as the collection substrate for the final stage. Samples were collected at approximately 0.9 L/minute for 1.5 minutes. The filters were re-weighed and the particle size was calculated based on the impactor stage cut-offs. The aerosol size was expressed as the MMAD and the GSD.
- Treatment of exhaust air: exhaust atmosphere was filtered using a Solberg filter prior to entering the facility exhaust system, which includes redundant exhaust blowers preceded by activated-charcoal and HEPA-filtration units.
- Temperature, humidity, pressure in air chamber: 19°C, 18%, airflow rate 60.7 L/min

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.5 / 3.13
Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
1.3 mg/L (Maximum Attainable Concentration, MAC)
No. of animals per sex per dose:
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for mortality twice daily, observations for clinical signs one approximately 1 to 2 hours following exposure and once daily thereafter, body weights were measured prior to exposure (day 0) and on exposure days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes: the major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals.

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 1.3 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: 1.3 mg/L is Maximum Attainable Concentration
Mortality was 0/10 animals for the 1.3 mg/L group.
Clinical signs:
other: Significant clinical observations immediately following exposure included rales for 3 males and 4 females and labored respiration rate for 1 female. Significant clinical observations at the 1 to 2 hours post-exposure observation period included rales for
Body weight:
From study day 0 to 1, all males lost 12 to 41 grams and all females lost 7 to 24 grams. All animals surpassed their initial (study day 0) body weight by study day 14 and were considered normal.
Initial body weight decrement followed by body weight gain during the 14-day observation period is common for animals exposed to a dust aerosol for 4 hours by nose-only inhalation.
Gross pathology:
The following macroscopic findings were recorded at the scheduled necropsy:
Blue Discoloration of the Lungs (4m/4f), Blue Discoloration of the Trachea (1m), Blue Discoloration on the Skin (2m/5f), Blue Discoloration on the Tail (4m/5f), Blue Discoloration on the Testes (2m).

Any other information on results incl. tables

nominal concentration data:


Test Substance Used

Exposure Time

Nominal Concentration









Mean actual exposure concentration:

Group (mg/L):


Target Exposure Concentration (mg/L):


Mean Exposure Concentration (mg/L):


Standard Deviation:




Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Migrated information Criteria used for interpretation of results: EU
Based on the results of this study, the LC50 of FAT 20341/A TE was greater than the MAC (Maximum Attainable Concentration; 1.3 mg/L), with a particle size <4 µm, when male and female Crl:CD(SD) albino rats were exposed to a dust aerosol of the test substance as a single, 4-hour, nose-only exposure.
Executive summary:

Acute inhalation toxicity of FAT 20341/A TE was studied according to OECD 403. The test substance was administered to 1 group of 5 male and 5 female rats via 4 hours nose-only inhalation exposure as a dust aerosol at a concentration of 1.3 mg/L, the Maximum Attainable Concentration (MAC) with a particle size <4 µm. The aerosol exposure atmosphere was characterized by a mean particle size of 2.5 ± 3.13 µm (MMAD ± GSD). None of the animals died during exposure or during the 14-day post-exposure observation period. Significant clinical observations immediately following exposure included rales and labored respiration rate. Significant clinical observation at the 1 to 2 hours post-exposure observation period included rales, rapid respiration rate, labored respiration rate, increased respiration rate, and hypoactivity. Significant clinical observations for the surviving animals during the 14-day post-exposure observation period included rales, increased respiration rate, partial closure of the eyes, small feces, and decreased defecation and urination. All animals lost weight from study day 0 to 1. All animals surpassed their initial body (study day 0) weight by study day 14. Macroscopic findings noted for animals at the scheduled necropsy were blue discoloration of the lungs, trachea, skin, tail, and testes.

Based on the results of this study, the LC50of FAT 20341/A TE was greater than the MAC (Maximum Attainable Concentration; 1.3 mg/L), with a particle size <4 µm, when male and femaleCrl:CD(SD)albino rats were exposed to a dust aerosol of the test substance as a single, 4‑hour, nose-only exposure. In accordance with the CLP Regulation FAT 20341/A TE needs not to be classified for acute inhalation toxicity.