Amides, C16-C18 (even) , N,N'-ethylenebis

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

analytical purity of test substance not specified, only 4 days acclimatisation time, particle size of 5.2 µm MMAD in accordance to former guideline

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Amides, C16-C18 (even) , N,N'-ethylenebis

EC Number:

931-299-4

Cas Number:

68390-94-3

Molecular formula:

not available UVCB

IUPAC Name:

Amides, C16-C18 (even) , N,N'-ethylenebis

Constituent 2

Reference substance name:

Amides, C16-C18 (even), N,N’-ethylenebis

IUPAC Name:

Amides, C16-C18 (even), N,N’-ethylenebis

Test material form:

not specified

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc.
- Age at study initiation: young adult
- Weight at study initiation: 180 - 300 g
- Housing: All animal housing and care conformed to AAALAC standards and to those published in the "Guide for the CareI and Use of Laboratory Animals," NIH Publication N0. 85-23. The animals were individually housed in suspended stainless steel wire mesh bottom cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Mass median aerodynamic diameter (MMAD):

5.2 µm

Geometric standard deviation (GSD):

1.7

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rochester type inhalation chamber
- Exposure chamber volume: 270 L
- Method of holding animals in test chamber: The animals were individually housed during the exposure in wire mesh cages without access to food or water.
- Source and rate of air: High pressure external air source, 75 L/min
- System of generating particulates/aerosols: Particle generator (Model FD-100. Unifab Corporation, Kalamazoo. Michigan)
- Method of particle size determination: Particle size analysis was performed once per hour during the exposure using an Anderson 2000 impactor (Model 20-800). Stages one to eight of the impactor, and the final filter stage were fitted with pre-weighed glass fiber filters. A known volume of chamber air (30 L) was drawn through the impactor and the change in weight of each filter was then determined and recorded.
- Treatment of exhaust air: Air treatment system which consisted of a HEPA filter, a charcoal filter and a water scrubber
- Temperature, humidity, pressure in air chamber: The test atmosphere temperature, relative humidity and percent oxygen content, and the air flow rate to the chamber were recorded at approximately 30 min intervals during the exposure. Average temperature, relative humidity, and oxygen content of the test atmosphere were 21°C, 56.8% and 21.0%, respectively.

TEST ATMOSPHERE
The inhalation chamber was maintained at a slightly negative pressure at all times during operation. Air flow rate to the chamber was monitored continuously during the exposure using calibrated Dwyer air flow meters (Dwyer Instruments, Inc.).
- Brief description of analytical method used: The average actual concentration of the test atmosphere was determined by gravimetric sampling. At the time of theoretical chamber equilibration a test atmosphere sample was drawn from the breathing zone of the chamber (5 L) through a pre·weighed glass fiber filter. The change in weight of the filter (mg) was determined and this value was divided by the volume of test atmosphere sampled (5 L) to yield the actual test atmosphere concentration. Additional gravimetric samples were obtained at approximately 30 minute intervals during the exposure. The average actual concentration of the test atmosphere was calculated for the exposure based on the initial and subsequent concentration analyses.
- Samples taken from breathing zone: yes
- MMAD: The mass median aerodynamic diameter of the generated particles was 5.2 µm and the standard geometric deviation was 1.7. Approximately 87% of the particles were less than 10 µm in size.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

by gravimetric sampling

Duration of exposure:

240 min

Concentrations:

The average actual test atmosphere concentration was determined to be 6.3 mg/L. The calculated nominal concentration was 27 mg/L. Thus, the average actual concentration was approximately 23.3% of the calculated nominal test atmosphere concentration.

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: Mortality checks were performed twice daily, a minimum of 5 h apart. The animals were observed for outward signs of toxicity 3 times on study day 1 (post exposure) and once daily thereafter for the duration of the study (day 15). Due to the density of the test atmosphere, an accurate observation of the study animals could not be performed during the actual exposure. Individual body weights were determined and recorded on study days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

not determined

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 6.3 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

240 min

Mortality:

1 male, necropsy findings suggest that death was caused by asphyxiation.

Clinical signs:

other: Labored breathing and/or rales, dark material around nose or mouth, decreased activity, urine stain, thrashing (in cage), for details see Table 1 under 'Any other information on results'.

Body weight:

Decreased body weight gain and/or weight loss were observed in both the male and female animals. No net change in mean body weight was observed in the male rats between days 1 and 15. In the female animals, mean body weight was decreased approximately 5% during the period of the study.

Gross pathology:

Necropsy examinations of the surviving animals revealed yellow material in the stomach (4 females), pale lungs (one male) and multifocal dark red foci on the lungs (one male). The significance of the above findings, if any, was not determined in this study.

Other findings:

- Histopathology: No microscopic lesions were observed in the kidneys or liver of any animal.

Any other information on results incl. tables

Table 1: Clinical signs during the 4 day observation period after exposure; because of the death of one male, 4 males and 5 females (9 animals) were examined

	Incidence of animals exhibiting finding / number of total animals on day
Finding	1	2	3	4
Labored breathing and/or rales	7 / 9	7 / 9	3 / 9	2 / 9
Dark material around nose or mouth	3 / 9	4 / 9	1 / 9	0 / 9
Decreased activity	0 / 9	3 / 9	0 / 9	0 / 9
Urine stain	0 / 9	1 / 9	0 / 9	0 / 9
Thrashing (in cage)	1 / 9	0 / 9	0 / 9	0 / 9

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Executive summary:

Based on the results of this study, the acute inhalation LC50 of the registered substance in rats is estimated to be greater than 6.3 mg/L. According to the criteria laid down in Regulation (EC) No. 1272/2008 the registered substance does not have to be classified for acute toxicity via the inhalation route.