Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guideline study with GLP compliance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
head only
Vehicle:
other: clean dry filtered compressed air
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Single chamber concentration (exposure-dose): 0.687, 1.400, 2.489, 3.365 mg/L by inhalation head only.
the corresponding nominal concentration: 2.726, 6.464, 13.947, 20.167 mg/L
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
A similiar group of 10 rats (5 male and 5 female) was exposed to filtered air as a control

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2.932 mg/L air
95% CL:
> 2.346 - < 4.504
Exp. duration:
4 h
Mortality:
All animals were examined twice daily to detect any which were dead or moribund. Moribund animals were removed and necropsied for human reasons and to prevent autolysis.
Clinical signs:
The animals were observed at hourly intervals during the exposure period, then for the remainder of the working day, and once daily thereafter for 14 days.
Body weight:
The body weight of each animal was recorded immediately before and after exposure, on days 8 and 15 of the study and the necropsy.
Gross pathology:
The following procedure were applied to all animals killed at the end of the study and to those killed in extremis.

Necropsy:
A full internal and external examination was made under the general supervision of a pathologist. The nasal passages were examined and an assessment made of any irritation of the respiratory tract.

Organ weights:
The lungs, bronchi and trachea of the animal were dissected free from fat and other contiguous tissue and weighed together.

Histology:
Sample of all gross lesion were fixed in 10% buffered formalin and retained without further processing.

Any other information on results incl. tables

STATISTICAL RESULT:
-death: Deaths occurred in male and female groups at levels of 2.489 mg/L and above. Overall there was a dose-related relationship between mortality and chamber concentration. All deaths occurred on days one and two of the study.
-body weight gain: Body weight losses occurred in the first week of the study in exposed groups, with a degree of recovery in the second week.
TOXIC EFFECTS:
-clinical chemistry: Marked clinical signs without any specific signs of local lung toxicity were first observed on the day of exposure. The signs included lethargy, ataxia and prostation sometimes accompanied by panting.
-histopathology: There was no treatment-related effect on lung weight in survivors, and only occational increases in lung weight in decedents.
-necroscopy: Animals surviving to termination were unremarkable macrocopically.The only changes in decedents were non-specific pulmonary changes.

Concentration(mg/L)
      mortality on day       Mortality ratio 1 2 3-15 days 1-15
Male control 0 / 5
0.687 0 / 5
1.400 0 / 5
2.489 1 1 / 5
3.365 3 3 / 5
Female control 0 / 5
0.687 0 / 5
1.400 0 / 5
2.489 1 2 3 / 5
3.365 3 3 / 5

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Harmful if inhaled Criteria used for interpretation of results: EU
Conclusions:
LC50 (4 hr, rat inhalation) = 2.932 mg/L
Executive summary:

In the acute inhalation toxicity study, groups of young adultrat, Aprague-Dawley. male/femalewere exposed by inhalation route to

6 -phenyl-1,3,5 -triazine-2,4 -diyldiamine for 4 hours to head only at concentrations of 0.687, 1.400, 2.489, 3.365 mg/L.  Animals then were observed for 14days.

 

LC50Combined =  2.932  mg/L (95% C.I. 2.346 to 4.504)