Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A non-GLP study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A group of male rats was exposed to a nominal chamber concentration of test material for a total exposure duration of 6 hours. The animals were repeatedly exposed to test material daily, five days a week, for a period of 2 weeks. All surviving animals were necropsied 7 days following the final exposure.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Amine 30D11
Appearance: bright amber liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 283 g (average)
- Housing: group housed together as a group of 10 animals following daily exposure

No further information is available on test animals and environmental conditions.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
Exposure Equipment
All animals were exposed in a 0.25 m³ stainless steel exposure chamber operated under dynamic conditions. An airflow of 20 L/min was maintained by a Gast rotary pump attached to the exhaust port of the chamber. Airflow through the chamber was monitored by a Vol-o-Flo meter (calibrated against the Sprague dry test meter). The test liquid was generated in a 30 cc syringe driven by a Sage Model 331 syringe pump adjusted so that the liquid dropped into a reflux column which was attached to a round bottom flask. The flask was submerged in a constant temperature water bath maintained at 40° C. The air stream passed down the reflux column and any material not picked up initially in the air stream was volatilized by heat from the water bath.
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Chamber Analysis
Nominal chamber concentrations were determined for the test exposure period. The nominal concentration was calculated as the ratio of the rate of disappearance of the liquid (weight loss per unit time) to the total chamber airflow (litre per unit time).
Duration of treatment / exposure:
The exposures were six hours in duration.
Frequency of treatment:
Repeated daily for two weeks, five days per week.
Doses / concentrations
Remarks:
Doses / Concentrations:
2.04 mg/L
Basis:
nominal conc.
No. of animals per sex per dose:
10 male rats were exosed.
Control animals:
no

Examinations

Observations and examinations performed and frequency:
Biological Parameters
All animals were observed constantly for the first 15 minutes of the six-hour exposure period and approximately once hourly thereafter, for the duration of the six-hour exposure period. The animals were observed daily for a seven-day period following the last exposure.

The animals were observed for any changes in general demeanour, locomotor ability and/or activity, coat condition, respiration, ocular and nasal discharges or any other signs of overt toxicity.
Sacrifice and pathology:
Gross necropsies were performed at the end of the seven-day observation period and the lungs fixed in 10% formalin and held for future reference.

Blood samples were taken at necropsy for blood cytology evaluation.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No overt signs of toxicity or mortality were seen. Three of the 10 animals exposed died during an attempt to perform an intracardial puncture for blood samples three days after the last exposure period.
Mortality:
no mortality observed
Description (incidence):
No overt signs of toxicity or mortality were seen. Three of the 10 animals exposed died during an attempt to perform an intracardial puncture for blood samples three days after the last exposure period.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
A minimal reduction in bodyweight during the exposure period and the seven-day post exposure observation period was seen.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
All were within normal ranges with the exception of one rat which exhibited an elevated white blood cell count and a slightly elevated segmented neutrophil count.
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
See below.
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
Gross Pathology

Necropsies performed on the 3 animals that were accidentally killed revealed no effects on the lungs. The lungs of the remaining seven animals sacrificed approximately seven days after exposure all showed varying degrees of brown to red spots ranging from pinpoint in size to approximately 2 mm in diameter. One of the seven animals had one lobe of the left lung completely brown-red in colour.

Effect levels

Dose descriptor:
NOAEL
Effect level:
2.04 mg/L air (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Test animals showed no overt signs of toxicity or mortality and a minimal reduction in bodyweight.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study, the exposure of male white rats to the test substance by the inhalation route for six hours for a total of 10 exposures over a 2 week period did not result in overt signs of toxicity or mortality in animals exposed to nominal chamber concentrations of 2.04 mg/L.
Executive summary:

Under the conditions of the study, the exposure of male white rats to the test substance by the inhalation route for six hours for a total of 10 exposures over a 2 week period did not result in overt signs of toxicity or mortality in animals exposed to nominal chamber concentrations of 2.04 mg/L.