Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data are available for interpretation of results.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1970

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Rats were exposed 6 hours/day for 15 exposures.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-iminodi(ethylamine)
EC Number:
203-865-4
EC Name:
2,2'-iminodi(ethylamine)
Cas Number:
111-40-0
Molecular formula:
C4H13N3
IUPAC Name:
N-(2-aminoethyl)ethane-1,2-diamine
Details on test material:
The sample investigated for inhalation toxicity over this period were submitted by the manufacturing divisions of ICI Ltd.

Test animals

Species:
rat
Strain:
other: Alderley Park specific-pathogen-free
Details on test animals or test system and environmental conditions:
Average weight 200 grams

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: Not applicable
Details on inhalation exposure:
Design of exposure chambers
In all of these experiments the animals have been exposed to dynamic atmospheres, that is, to atmospheres continuously generated and passed through the exposure chamber. The design of exposure chamber has varied with the number of animals involved and with the nature of the substance under investigation. For groups of four or fewer rats a glass desiccator, containing wire mesh partitions to separate the animals, was used. Larger numbers, up to eight rats, were exposed in the chamber described elsewhere (Gage, 1959); usually the inner Perspex chamber of that design was replaced by a glass cylinder, 30 cm diameter and 25 cm high. For atmospheres containing particulate matter a chamber with a more pyramidal top (Gage, 1968) was used.

Generation of the test atmospheres
The air used foi the atmospheres was filtered, dried to a relative humidity of less than 10%, and supplied at a line pressure of 1 atm (1.013 x 10 E5 Nm-2). A nearly saturated vapour obtained by passing air through a liquid contained in a bubbler with a sintered glass air-distributor disc. The volume of the liquid was usually 10-20 ml and, if the size of the sample available permitted, it was replaced daily. Unless otherwise stated, the bubbler was maintained in a water-bath at room temperature, about 20°C.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Measurement of concentration
The nearly saturated concentration was estimated by weighing the sample before and after the day's run, and telating the weight loss to the volume of air passing. This concentration, expressed in milligrammes per litre, was converted to parts per million on the assumption that the sample was pure. Both of these estimates are only approximate.
Duration of treatment / exposure:
The rats were maintained in the exposure chamber for periods of up to 6 hours, and between repeated daily exposures they were returned to their cages where food and water were freely available. In the initial experiments the concentrations were selected to produce, if possible, acute effects after short exposures. Thereafter the exposure period was extended and the concentration lowered until the animals could survive 6-hour exposures, five days a week, for up to four weeks.
Frequency of treatment:
Daily; 15 x 6-hour exposures
Doses / concentrations
Remarks:
Doses / Concentrations:
0-55 mg/litre; 130 ppm
Basis:

No. of animals per sex per dose:
Two/sex/dose
Control animals:
not specified
Details on study design:
- Dose selection rationale: In the initial experiments the concentrations were selected to produce, if possible, acute effects after short exposures.

If at any stage effects were observed which could be attiributed to the exposure, the experiment was repeated with progressively lower concentrations until a concentration was reached which was without effects on the animals. At intervals of about two months, batches of control rats were maintained in a chamber for the exposure period, in order to check the characteristics of the colony.

Positive control:
Not applicable

Examinations

Observations and examinations performed and frequency:
The rats were weighed each morning, and their conditions and behaviour were recorded throughout the exposure period. Urine was collected overnight after the last exposure day for biochemical tests. The animals were left overnight with food and drink. On the following day the rats were anaesthetized with halothane and partially exsanguinated by heart puncture for haematological tests.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

After a gross examination of the organs, the lungs were inflated with formol-saline and immersed in the same fixative. The following organs were also taken for microscopical examination after fixation in formol-corrosive: lungs, liver, kidneys, spleen, and adrenals; and occasionally heart, jejunum, ileum, and thymus.
Other examinations:
Urinalysis
Hematology
Statistics:
No additional information available.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not specified
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
no toxic signs (hair coarsened): autopsy, organs normal

Effect levels

Dose descriptor:
NOEC
Effect level:
0.55 mg/L air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no toxic signs (hair coarsened): autopsy, organs normal

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No additional information available.

Applicant's summary and conclusion

Conclusions:
DETA at 15 X 6-hour exposures produced no toxic signs (hair coarsened). The autopsy and all organs were normal.
Executive summary:

The effects of inhaled DETA were examined in a subacute study. Groups of rats were exposed to an essentially saturated vapor of DETA for 6 hrs/day for 15 exposures. There were no effects based on urinalysis or hematological parameters and gross or histopathological exam.