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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
No information is available on the study period, other than the date the report was finalized (6 April 1978).
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was performed prior to the implementation of Good Laboratory Practice standards and prior to the adoption of of OECD Test No. 403 Acute Inhalation Toxicity. The test parameters are, however, well documented and scientifically acceptable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1972

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
Animals were exposed (whole body) to aerosolized test material for one hour. Nominal exposure concentrations were determined by the weight difference of the flask, nebulizer, and tubing pre- and post-exposure. Animals were monitored for toxic signs continuously during the exposure period, hourly post-exposure up to four hours, and daily thereafter for 14 days. Individual body weight data were obtained on day 0, 1, 2, 4, 7, and 14. Gross necropsies were performed on all surviving animals at study termination.
GLP compliance:
no
Remarks:
This study was performed prior to the implementation of GLP standards.
Test type:
fixed concentration procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test material was in the form of a dark brown, viscous liquid.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The test animals were received from Charles River Breeding Laboratories and consisted of five male and five female Sprague-Dawley rats, weighing between 206 and 274 grams. No further details were reported.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The test material was placed in a 500-ml, 3-neck flask fitted with a Laskin nebulizer. Dry air was passed through the nebulizer at a flow rate of 7.0 liters per minute and the resulting aerosol was then passed directly into a 26.5-liter, glass exposure chamber containing the test animals. The exposure lasted for 1.0 hour. The 3-neck flask, including the test material, nebulizer and air tubing, was weighed before and after the exposure period to determine the nominal exposure concentration.

Analytical verification of test atmosphere concentrations:
yes
Remarks:
The 3-neck flask, including the test material, nebulizer and air tubing, was weighed before and after the exposure period to determine the nominal exposure concentration.
Duration of exposure:
>= 1 h
Concentrations:
Nominal exposure concentration of 2.45 milligrams per liter.
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
Whole body exposure to the test article took place for one hour, during which time the animals were observed for signs of toxicity. Upon removal from the exposure chamber, hourly post-exposure observations were made for four hours and daily thereafter for 14 days. Individual body weight data were recorded on Days 0 (day of exposure), 1, 2, 4, 7 and 14 (terminus). On Day 14, all animals were sacrificed (ethyl ether) and gross necrops examinations were performed.
Statistics:
No statistics were reported.

Results and discussion

Preliminary study:
During the exposure period, a total of 1.03 grams of test material was delivered, yielding a nominal exposure concentration ot 2.45 milligrams per liter.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.45 mg/L air (nominal)
Exp. duration:
1 h
Mortality:
No mortalities occurred during the study.
Clinical signs:
By 15 minutes into the exposure, nearly all of the test animals exhibited excessive salivation, excessive lacrimation and mucoid nasal discharge. By 30 minutes all were inactive and some test animals exhibited labored breathing. These signs continued for the remainder of the exposure.

Upon removal from the exposure chamber, when the rats could be observed individually, all animals exhibited salivation and eight of ten rats exhibited excessive lacrimation. Other toxic signs which occurred less frequently included yellow staining of the ano-genital fur (two of ten rats), mucoid nasal discharge (two of ten rats) and dry rales (one of ten rats).

Most of the signs observed during the exposure disappeared during the four hour post-exposure period. Only dry rales persisted, but was seen infrequently (one to three of ten rats during this period).

During the 14-day observation period, nine of ten rats exhibited dry rales sporadically. The occurrence of dry rales was generally low (one to three days per rat), but two of the rats exhibited this for six to eight days. Red nasal discharge was also observed sporadically (six of ten rats) and, again, at a low incidence level (one to three days per rat). Chromodacryorrhea of the right eye was observed in rat #10 on Day 1.
Body weight:
Individual body weight data were considered to be normal. Male and female rats gained an average of 76 or 20 grams, respectively, from day 0 to day 14.
Gross pathology:
Necropsy examination revealed lung discoloration (mottled light and dark red, occassionally with red or white spotting) in seven of ten animals.

Applicant's summary and conclusion

Conclusions:
A one-hour whole-body exposure to 2.45 mg/l (336 ppm) was not acutely toxic to male or female rats.
Executive summary:

A 1.0 hour exposure to an aerosol of DETDA at a nominal exposure concentration of 2.45 milligrams per liter (336 ppm), did not produce mortality in rats so exposed. The exposure did produce signs of immediate toxicity, which tended toward recovery when the animals were removed from the chamber. A high incidence of lung discoloration at the necropsy indicated the possibility of some residual effects.