Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-conducted study conducted under GLP with no deviations. Reliability was changed from "1" to "2" according to the ECHA guidance document "Practical guide 6: How to report read-across and categories".

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)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class 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:
Conditions: Animals were housed in an Optimal Hygienic Conditions (OHC) inside a barrier system. Air-conditioned with 10 - 15 air changes per hour, continuously monitored environment with a temperature range of 22 ± 3 °C, a relative humidity range of 30 - 70% and a 12 hour fluorescent light / 12 hour dark cycle. A radio program was played during most of the light period.

Accommodation: Animals were housed in groups of 5 of the same sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel" J. Rettenmaier & Söhne GmbH & Co KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) including paper enrichment (Enviro-dri from Lillico, Biotechnology, Surrey, UK).

Diet: Animals had ad libitum access to a pelleted standard Harlan Teklad 2914C rat maintenance diet (Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) batch no. 82/09 except during the period when the animals were restrained in exposure tubes. Results of the analyses for contaminants and their limits of acceptability are archived at Harlan Laboratories Ltd.

Water: Community tap water from Füllinsdorf ad libitum in water bottles, except during the period when they were restrained in exposure tubes. Results of representative analyses for contaminants are archived at Harlan Laboratories Ltd.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
Method of test material administration: Inhalation by nose-only, flow-past exposure.
Rationale for Method: Inhalation is a possible route of human exposure.
Frequency of Administration: Single, 4-hour exposure period. Exposure was interrupted twice for a total of 2 minutes for cleaning; nevertheless, the animals were exposed for a period of 4 hours as those interruptions were accounted for.

Rationale for Aerosol 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.

Duration of Observation Period: 14 days
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:
five
Control animals:
no
Details on study design:
Inhalation exposure was performed using a flow-past, nose-only exposure system. The animals were confined separately in restraint tubes which were positioned radially around the exposure chamber. The exposure system ensured a uniform distribution and provided a constant flow of test material to each exposure tube. The flow of air at each tube was 1.0 L/min, which is sufficient to minimize re-breathing of the test aerosol as it is more than twice the respiratory minute volume of rodents. Before commencement of the exposure of the group, technical trials were conducted (without animals) using the inhalation system foreseen for the study. The technical trials were conducted using established procedures based on GLP, but were not
inspected by the Harlan Laboratories Ltd. Quality Assurance. Technical trial data are retained in the raw data.

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.
Statistics:
None

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:
LC0
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:
other: 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:
There were no macroscopic findings.
Other findings:
None

Any other information on results incl. tables

Temperature, relative humidity and oxygen concentration during exposure were considered to be satisfactory for this type of study. Relative humidity values were low as dry air was used for aerosol generation. The mean gravimetric aerosol concentration determined was 2.8 mg/L air as targeted. The aerosol concentration was stable during the exposure period. The Mass Median Aerodynamic Diameters (MMAD) obtained from three gravimetric measurements of particle size distribution during the exposure were similar (MMAD = 3.02 μm, 3.51 μm and 3.84 μm). This led to the conclusion that the particle size of the generated aerosol was fairly stable during the whole exposure period. The MMADs were within the target range of 1 to 4 μm or at the upper limit (third sample), thus deposition of the particles can be assumed to have occurred in both the upper and the lower respiratory tract. The aerosol concentration was at the technical limit as the third sample was at the upper limit. In addition, the Geometric Standard Deviations (GSD) were within the target range of 1.5 to 3. Hence, the particle size distributions obtained were considered to be appropriate for acute inhalation toxicity testing.

Applicant's summary and conclusion

Conclusions:
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.
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.