Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of five male and five female rats were exposed for four hours in a 160-liter glass and stainless steel chamber to vapors and aerosols of ABBOTT-48832. The highest feasible nominal concentration was 22,5mg/L (actual concentration was not determined at this level). Both nominal and actual exposure concentrations were determined for the LC50 study. The exposure concentrations were as follows :


Actual Concentration Nominal Concentration
(mg/L) (mg/L)
1.1 3.6
1.7 6.3
2.3 8.3
2.4 9.6
2.8 11.3

Aerosols of the test material were generated by metering the liquid with a FMI pump into a spraying system atomizer. An air pressure of 10 psig with an airflow rate of 8 or 10 L/min was applied to the atomizer which aerosolized the liquid for rapid vaporization.
The vapors and aerosols emerging from the atomizer were diluted by the incoming chamber air to the desired concentration.
The size range of aerosol particles was 3.1 + 1.9 mcm.

Observations for signs of toxicity and mortality were made during the 4-hour exposure period and twice daily thereafter for 14 days.

Body weights were recorded on days 0 (prior to exposure), 1, 3, 7 and 14.

Animals that died during the study were necropsied. The surviving animals were necropsied at the end of the 14-day observation period.
GLP compliance:
no
Test type:
fixed concentration procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
gas under pressure: refrigerated liquefied gas

Test animals

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

Administration / exposure

Route of administration:
other: Inhalation - vapour and aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Aerosols of the test material were generated by metering the liquid with a FMI pump into a spraying system atomizer. An air pressure of 10 psig with an airflow rate of 8 or 10 L/min was applied to the atomizer which aerosolized the liquid for rapid vaporization.
The vapors and aerosols emerging from the atomizer were diluted by the incoming chamber air to the desired concentration.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
Actual Nominal
(mg/L) (mg/L)
1.1 3.6
1.7 6.3
2.3 8.3
2.4 9.6
2.8 11.3
No. of animals per sex per dose:
5
Control animals:
no

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
2 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
1.8 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Up to 0-100% mortality in dosed groups.

Clinical signs:
other: Clinical signs observed were dyspnea, nasal discharge, salivation, evidence of red matter around the face, alopecia and dermal irritation.
Body weight:
All animals exposed demonstrated body weight loss sometime during the first week of the postexposure period.
Gross pathology:
At necropsy red lungs were observed in a few animals from each group. Scattered red patches on the lungs were also observed in a few animals from each group with the exception of Group 111, where the lesion was not observed. Black patches in the thymus was observed in three males and three females during the necropsy.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the nominal concentrations the calculated 4-hour LC50 for males was 7.4 mg/L, while for the females it was 6.4 mg/L. In terms of actual concentrations, the 4-hour LC50 for males was 2.0 mg/L, while for the females it was 1.8 mg/L.
Executive summary:

Both nominal and actual exposure concentrations were determined for the LC50 study. Nominal concentrations were determined by weighing the amount of test material placed in the generator reservoir prior to exposure and then again following exposure. The difference in weight was divided by the total air passed through the chamber during the exposure period. Actual exposure concentrations were determined by standard gravimetric techniques.

The results indicated that nominal concentrations were higher than actual concentrations, e.g. 11.3 mg/L versus 2.8 mg/L for the highest concentration. Since B.P.>200°C, and vapour pressure=0.172 lb/inch3) this is a liquid material with low volatility, the actual measured concentrations seem more appropriate for evaluation of toxicity.

In conclusion, at actual exposure concentrations of 1.1-2.8 mg/L (nominal concentrations of 3.6-11.3 mg/L) for four hours produced signs of toxicity and deaths in rats. The combined male and female 4-hour LC50 values for actual measured concentrations and nominal concentrations were estimated to be 1.9 mg/L and 6.9 mg/L, respectively.