Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not applicable
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to test guidelines and in accordance with GLP.
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:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to guideline
Guideline:
other: TSCA Testing Guidelines; EEC Method No. B.2; MAFF Testing Guidelines
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method

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:
Lot number: TA960822B
Composition: 99.33% diethylenetriamine, 0.25% monoethanolamine, and 0.25% aminoethyl piperazine
Appearance: colorless to straw yellow liquid
Vapor pressure:0.202 mm Hg @ 25°C; 0.135 mm Hg @ 20°C
Saturated atmosphere:~222 ppm @ 22.5°C (calculated from the vapor pressure)
Boiling point:199°C (MSDS sheet)
Density:0.947-0.951 @ 25/25"C (MSDS sheet)
Flash point: 102°C (MSDS sheet)
Flammability limits: 1.9-11.6% @ 150°C (MSDS sheet)

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston, NY. USA
- Age at study initiation: approximately 9 weeks of age
- Weight at study initiation:
- Fasting period before study: No
- Housing: The animals were housed two per cage in stainless steel wire cage. Animals were singly housed during a 2-week post-exposure period.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: The animals were acclimated to the laboratory approximately two weeks prior to exposure. The animals were acclimated to the nose cones for a single two-hour period on the day preceding exposure to the test material.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):
ENVIRONMENTAL CONDITIONS
Prior to and after exposure, animals were housed in a room designed to maintain adequate environmental conditions concerning temperature and
relative humidity and regulated for the specific species under study.
- Photoperiod (hrs dark / hrs light): 12-hour photoperiod

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Chambers: A 42-liter, Dow-modified ADG nose-only chamber [30 centimeters (cm) in diameter by 60 cm high] was used for the studies. Compressed air supplied to the chamber was at ambient temperature. The chamber airflow was maintained at approximately 30 liters per minute, which was sufficient to provide the normal concentration of oxygen to the animals and approximately 43 air changes per hour. The chamber was operated at a slightly negative pressure relative to the surrounding area and was contained within a secondary vented area. Chamber temperature and humidity were recorded during the exposures from a thermometer and hygrometer stationed in the interior of the chamber. Temperature above the nose cones was recorded from a thermometer stationed on the exterior of several nose cones. Low relative humidity values were expected for exposures of this type, since dry, compressed air was the only source of air supplied to the chamber.

Generation System. Liquid aerosol of DETA was generated by metering the test material with an FMI pump (Fluid Metering, Inc., Oyster Bay, NY) into a stainless steel Model 970 Schlick spray nozzle (Orthos, Inc., Schaumburg, IL). The test material was mixed with compressed air in the spray nozzle and aerosol was sprayed into the chamber. The test material was not recycled. Spray system conditions that would generate a suitable atmosphere were determined during preliminary work.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.07 or 0.30 mg diethylenetriamine/liter of a respirable test atmosphere
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
Groups of five male and five female Fischer 344 rats were nose-only exposed for a single, four-hour period, to chamber concentrations of 0.07 or 0.30 mg/L aerosolized DETA. Animals were acclimated to the nose cones for a single two-hour period on the day preceding exposure to the test material. The nose-only exposures occurred under dynamic airflow conditions. The animals were observed daily and weighed on test days 1, 2, 4, 8, 11 and 15.
Statistics:
Means and standard deviations were calculated for descriptive purposes: chamber concentration (mean only), animal body weights, chamber temperature, relative humidity, airflow and temperature above the nose cones. The range of the animal room temperatures and humidities was reported.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
other: NOEL for lethality
Effect level:
0.07 mg/L air
Remarks on result:
other: aerosolized air
Mortality:
0.07 mg/L Exposure: No mortality. All animals survived the four-hour exposure and the two-week post exposure period with no treatment-related effects noted.

0.30 mg/L Exposure: All animals survived the four-hour exposure. Four male rats were dead by test day two and the surviving male rat was dead by test day six. All females were dead by test day 11.
Clinical signs:
other: 0.07 mg/L Exposure: There were no treatment-related in-life observations made during the two-week postexposure period for animals exposed to 0.07 mg/L DETA. 0.30 mg/L Exposure: No treatment-related observations were noted during the exposure. Treatment-
Body weight:
0.07 mg/L Exposure: Mean body weights of male and female rats were decreased by approximately 4 and 3%, respectively. The mean body weights exceeded pre-exposure values by test days 11 and 15, respectively.

0.30 mg/L Exposure: Mean body weights of the surviving male and female rats were decreased by approximately 9% on test day two. The body weights of the surviving female rats continued to decrease to test day 8, with all weights below 100 grams (approximately 30% decrease from test day one).
Gross pathology:
The treatment-related change observed at necropsy in all animals exposed to 0.07 mg/L was atelectasis of the lungs, characterized by a branching pattern of pulmonary collapse involving approximately 25% of the lung parenchyma. Lesions observed in spontaneously dead animals exposed to 0.30 mg/L included pulmonary edema and congestion of the lungs and hydrothorax. These observations were interpreted to be contributing factors to the cause of death.
Other findings:
No additional information available.

Any other information on results incl. tables

Groups of five male and five female Fischer 344 rats were nose-only exposed to 0.07 mg/L of a respirable test atmosphere with an estimated mean MMAD of 0.44 microns for a four-hour period. All animals survived the four-hour exposure and the two week post exposure period with no treatment-related effects noted. Atelectasis of the lungs, characterized by a branching pattern of pulmonary collapse involving approximately 25% of the lung parenchyma, observed at necropsy, was the primary finding.

A second exposure was conducted at a chamber concentration of 0.30 mg/L. All animals survived the four-hour exposure. However, all males had died by test day 6 and all females had died by test day 11. Contributing factors to the cause of death included pulmonary edema, congestion of the lungs and hydrothorax. The 0.07 and 0.30 mg/L concentrations are based on the total DETA species concentration, expressed as DETA. The proportion of DETA/DETA carbamate was estimated based on the difference between total gravimetric determined mass versus the amount of DETA species. The chamber atmospheres consisted of an estimated 15% DETA and 85% DETA carbamate.

This current study is considered to be more definitive than a previous acute aerosol inhalation study because the test atmosphere was more completely characterized. Therefore, the no-observed- effect-level for lethality is considered to be 0.07 mg/L aerosolized total DETA species expressed as DETA.

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The exposure concentrations of 0.07 and 0.30 mg/L represent total DETA species as DETA. Based on the results of the 0.07 and 0.30 mg/L exposures, the no-observed-effect- level for lethality is considered to be 0.07 mg/L aerosolized DETA.
Executive summary:

      The objective of this study was to assess the acute toxicity of aerosolized DETA using a specific analytical method to quantify total DETA species and to determine a NOEL for lethality. Concentrations were selected based on a previous acute study. The current study utilized a better characterization of the test atmosphere.

      Groups of five male and five female Fischer 344 rats were nose-only exposed to 0.07 mg/L of a respirable test atmosphere for a four-hour period. All animals survived the four-hour exposure and the two-week observation period. A second exposure was conducted at a chamber concentration of 0.30 mg/L. All animals survived the four hour exposure. Male rats exposed to 0.30 mg/L DETA were dead by test day 6 and female rats were dead by test day 11. The aerosol particle size distribution mass median aerodynamic diameter (MMAD) averaged 0.44 (estimated) and 2.33 microns for the 0.07 and 0.30 mg/L exposures, respectively. Approximately 67 and 16% of the total mass of particles was less than 1 micron in size and approximately 98 and 94% of the total mass was less than 6 microns in size for the 0.07 and 0.30 mg/L exposures, respectively. The mean results from the chamber analysis for the 0.07 and 0.30 mg/L exposures were similar and indicated that the chamber atmospheres were estimated to be approximately 15% DETA and 85% DETA carbamate.

      In-life observations were made and body weights were taken pre-exposure and during the two-week postexposure

periods. All animals underwent a gross pathologic examination. There were no treatment-related in-life observations made during the two-week postexposure period for animals exposed to 0.07 mg/L DETA. Treatment-related in-life observations made during the two-week post-exposure period in animals exposed to 0.30 mg/L included a combination of the following: shallow and/or rapid respiration, decreased activity, perineal soiling, extensive body soiling, thin appearance and decreased urine and feces. Decreased feces and urination were noted post-exposure during cageside examinations for the 0.30 mg/L exposure. The decreased ingesta observed in both male and female animals was consistent with the lower body weights and reduced food intake noted in postexposure cageside and clinical observations. The treatment-related change observed at necropsy in all animals exposed to 0.07 mg/L was atelectasis of the lungs, characterized by a branching pattern of pulmonary collapse involving approximately 25% of the lung parenchyma. Lesions observed in spontaneously dead animals exposed to 0.30 mg/L included pulmonary edema and congestion of the lungs and hydrothorax. These observations were interpreted to be contributing factors to the cause of death.

      The exposure concentrations of 0.07 and 0.30 mg/L represent total DETA species as DETA. Based on the results of the 0.07 and 0.30 mg/L exposures, the no-observed-effect- level for lethality is considered to be 0.07 mg/L aerosolized DETA.