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Administrative data

Description of key information

Oral (OECD 423): LD50 > 5000 mg/kg bw 
Inhalation (OECD 436): LC50 > 2.8 mg/L air
Dermal (OECD 402): LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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.
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
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
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.
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
2.8 µg/m³
Quality of whole database:
The study was carried out in accordance with an appropriate OECD test guideline and in compliance with GLP.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 - 29 Dec 2009
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.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
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: 8 weeks (males), 12 weeks (females)
- Weight at study initiation: 238 – 250 (males), 196 – 210 (females)
- Housing: Animals were housed in groups of 5 of the same sex in Makrolon® type-4 cages (during acclimatization) and individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel" J. Rettenmaier & Söhne GmbH & Co KG, Rosenberg, Germany)
- Diet: Provimi Kliba 3433 rat/mouse maintenance diet (Provimi Kliba AG, Kaiseraugst, Switzerland), ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- % coverage: 10
- Type of wrap if used: A piece of surgical gauze pad was placed on the exposed site and held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and an elastic adhesive restrainer bandage wrapped around the abdomen

REMOVAL OF TEST SUBSTANCE
- Washing: The dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min, 1, 2, 3, and 5 h post administration of the test substance and twice daily thereafter for 14 days. Individual body weights were determined weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were observed 30 min, 1, 2, 3, and 5 h post administration of the test substance and once daily thereafter for 14 days.
Statistics:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities or clinical signs of toxicity observed
Mortality:
No deaths occurred during the study period.
Clinical signs:
No clinical signs were evident during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age during the study period.
Gross pathology:
No macroscopical changes were evident at necropsy.
Other findings:
Slight desquamation was noted in one male on the observation days 7 and 8. No dermal changes were seen in the females.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Executive summary:

Five male and five female RccHan:WIST (SPF) rats were treated with erucamide at 2000 mg/kg by dermal application. The test item was applied to a gauze patch moistened with water. The application period was 24 hours. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2 - 15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were evident during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. Slight desquamation was noted on day 7 - 8 of observation in a single male. All other animals were without findings. No macroscopical findings were evident. The median lethal dose of erucamide after single dermal administration to rats of both sexes, observed over a period of 14 days, is: LD50 (rat): greater than 2000 mg/kg body weight

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study was carried out in accordance with an appropriate OECD test guideline and in compliance with GLP.

Additional information

Acute oral toxicity

Three studies addressing the acute oral toxicity of CAS 112-84-5 are available.

An acute oral toxicity study with CAS 112-84-5 was performed according to OECD TG 423 and in compliance with GLP (Sanders, 2000). In this limit test three fasted Sprague-Dawley rats of each sex were administered one dose of 2000 mg/kg bw of the test substance in a stepwise procedure via oral gavage. The animals were observed for 14 days after administration. The acute oral LD50 was estimated to be greater than 2500 mg/kg bw according to OECD TG 423 and based on no mortality at 2000 mg/kg bw in both sexes. No signs of clinical toxicity were reported, no mortalities occurred during the observation period. Body weight gain was normal in all animals during the study period.

The second acute oral toxicity study with CAS 112-84-5 was performed according to EU Method B.1 and similar to OECD TG 401 and in compliance with GLP (Reijnders, 1988). In this limit test five fasted Wistar rats of each sex were administered a total dose of 5000 mg/kg bw of the test substance as two single doses of 2500 mg/kg bw within 24 hours via oral gavage. The animals were observed for 14 days after administration. The acute oral LD50 was calculated to be greater than 5000 mg/kg bw. No signs of clinical toxicity were reported, no mortalities occurred during the observation period. All animals showed normal bodyweight gain during the study period.Macroscopic examination at termination did not reveal any abnormalities that were considered to be treatment-related.

Another acute oral toxicity study summary with CAS 112-84-5 was performed according to OECD TG 401 (Whittaker, 1986). Only limited information on test material, analytical purity and test animals is available. In this limit test five Sprague-Dawley rats of each sex were administered a dose of 2000 mg/kg bw of the test substance via oral gavage. The animals were observed for 14 days after administration. The acute oral LD50 was calculated to be greater than 2000 mg/kg bw. No signs of clinical toxicity were reported, no mortalities occurred during the observation period. All animals showed normal bodyweight gain during the study period.Macroscopic examination revealed no abnormalities.

In summary the available data on acute oral toxicity with CAS 112-84-5 does not reveal any sign of toxicity up to a dose of 5000 mg/kg bw; in consequence a LD50 >5000 mg/kg bw was derived. Based on the results of the studies and according to EU classification criteria, the test substance is not to be classified for acute toxicity via the oral route.

Acute inhalation toxicity

An acute inhalation toxicity study with CAS 112-84-5 was performed according to OECD TG 436 and in compliance with GLP (Pothman, 2010). In this limit test a group of three Wistar rats (RccHanTM:WIST) of each sex was exposed to the test material via nose-only, flow-past inhalation for four hours 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. The LC50 was estimated to be greater than 2.8 mg/L air. All animals survived the scheduled observation period. Ruffled fur was recorded in all animals one hour post-exposure. No further clinical signs were recorded in the remaining study period. From day 1 to day 2, slight body weight loss was noted in all animals, followed by normal body weight development thereafter. No macroscopic findings were observed during the entire study period.

Acute dermal toxicity

An acute dermal toxicity study with CAS 112-84-5 was performed according to OECD TG 402 and in compliance with GLP (Braun, 2010). In this limit test five Wistar rats (RccHanTM:WIST) of each sex were exposed to 2000 mg/kg bw test substance for 24 hours via semi-occlusive dressing (10% of the total body surface area) and observed for 14 days post-application. The acute dermal LD50 was estimated to be greater than 2000 mg/kg bw. No signs of clinical toxicity were reported and no mortalities occurred during the study period. The body weight of the animals was within the range commonly recorded for this strain and age during the study period. Moreover, gross pathology revealed no abnormalities during the study period.


Justification for selection of acute toxicity – oral endpoint
Three studies on acute oral toxicity are available. No single study was assessed as a key study, therefore, weight of evidence method was applied.

Justification for selection of acute toxicity – inhalation endpoint
The key study was selected for assessment.

Justification for selection of acute toxicity – dermal endpoint
The key study was selected for assessment.

Justification for classification or non-classification

The available data on acute toxicity of CAS 112-84-5 do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.