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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:
08 - 22 Jun 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
(2009)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Swiss Federal Office of Public Health Consumer protection directorate Notification authority for chemicals
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): Erucamide
- Physical state: solid
- Storage condition of test material: room temperature, protected from direct sunlight
- Expiration date of the lot/batch: 17 Feb 2011
- Analytical purity: 99.51%
- Lot/batch No.: 101404

Test animals

Species:
rat
Strain:
other: RccHan:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., NM Horst, Netherlands
- Age at study initiation: 9 weeks (males/females)
- Weight at study initiation: 260.1 – 281.4 (males), 180.5 – 185.7 (females)
- Housing: Animals were housed in groups of 3 of the same sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel" J. Rettenmaier & Söhne GmbH & Co KG, Rosenberg, Germany)
- Diet: 2914C Teklad rat maintenance diet (Provimi Kliba AG, Kaiseraugst, Switzerland), ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow-past, nose-only exposure system
- System of generating particulates/aerosols: A dust aerosol was generated from the test item using a Topas powder generator connected to a micronizing jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutralizer.
- Temperature, humidity, pressure in air chamber: The oxygen concentration of the test atmosphere was measured continuously during exposure using a calibrated device. The results were recorded manually and are reported at 30 minute intervals from the start of exposure. The oxygen concentration was maintained above 19% during each exposure period. The temperature and relative humidity of the test atmosphere was measured continuously during exposure using a calibrated device. The results were recorded manually and are reported at 30 minute intervals from the start of exposure. Airflow Rate The actual airflow rate through the exposure chamber was recorded at approximately 30 minute intervals from the start of the inhalation exposure.

TEST ATMOSPHERE
- Brief description of analytical method used: The test item usage was measured by weighing the generator cylinder containing the test item before and after exposure to determine the quantity of test item used. The weight used was then divided by the total air-flow volume to give the nominal concentration. Gravimetric determinations of aerosol concentration were performed seven times during exposure. The samples were collected on a Millipore®durapore filter, Type HVLP loaded in a 47 mm in-line stainless steel filter sampling device. The filters were weighed before and immediately after sampling using a calibrated balance. The test aerosol concentration was calculated from the amount of test item present on the filter and the sample volume.
- Particle size distribution: The particle size distribution of the test aerosol was determined three times during exposure using a 7 stage cascade Mercer Impactor (Model 02-130, In-Tox. Products Inc., Albuquerque, New Mexico, U.S.A.). The particle size distribution was measured by gravimetrically analyzing the test item deposited on each stage of the cascade impactor. Mass Median Aerodynamic Diameters (MMAD) and Geometric Standard Deviations (GSD) were calculated on the basis of the results from the impactor, using Microsoft Excel Software.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1 - 4 µm / 1.5 - 3 µm

CLASS METHOD
- Rationale for the selection of the starting concentration: The target concentration of 3 mg/L air for 4 hours was the highest feasible aerosol concentration with a respirable MMAD as determined during the technical trials.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric determination
Duration of exposure:
4 h
Concentrations:
2.8 mg/L
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of each animal was recorded on test days 1 (before exposure), 2, 4, 8 and 15 (before necropsy). Each animal was examined three times during exposure, immediately and 1 h after exposure on test day 1 and once daily during the observation period. Observations were detailed and carefully recorded using explicitly defined scales as appropriate. Only grossly abnormal signs were detectable during exposure as the animals were restrained in the exposure tubes.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology
Statistics:
No statistical analysis was performed as only one group was allocated to the study.

Results and discussion

Preliminary study:
The LC50 of erucamide in this study was estimated to be greater than 2.8 mg/L air (gravimetrically determined mean aerosol concentration) which was the highest feasible aerosol concentration with a respirable MMAD.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.8 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived the scheduled observation period.
Clinical signs:
Ruffled fur was recorded in all animals one hour after the end of exposure. There were no clinical signs from test day 2 onwards.
Body weight:
From test day 1 to test day 2, slight body weight loss was noted in all animals. Thereafter normal body weight development was recorded.
Gross pathology:
No macroscopic findings were recorded.

Applicant's summary and conclusion

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

A group of three male and three female albino rats [RccHanTM:WIST(SPF)] was exposed by nose-only, flow-past inhalation for four hours to the test item at a gravimetrically determined mean concentration of 2.8 mg/L air. All animals were observed for clinical signs and mortality during the inhalation exposure and the subsequent 14-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 2, 4, 8 and 15 before necropsy. On test day 15 all animals were sacrificed and necropsied. The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats. All animals survived the scheduled observation period. Ruffled fur was recorded in all animals one hour after the end of exposure. There were no clinical signs from day 2 onwards. There were slight effects on body weight. There were no macroscopic findings. In conclusion, the LC50 of (Z)-docos-13-enamide obtained in this study was estimated to be greater than 2.8 mg/L air (gravimetrically determined mean aerosol concentration) which was the highest feasible aerosol concentration with a respirable MMAD.