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: see 'Remark'
Remarks:
Although the study report did not cite the test guideline followed (OECD test guidelines were not available then), the brief description of the experiment appear reasonable. The test item's identity was not clearly identified by CAS number in the report, and had to be inferred. Only one concentration of the test item was tested and for an hour. These approaches differ from the currently acceptable test guidelines. Therefore the experimental value cannot be used for DNEL derivation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1965
Report Date:
1965

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Rats were exposed to a single continuous aerosol mist of the test compound for an hour in a dynamic inhalation chamber. Exposure was made by metering the test material into a nebulizer. Animals were observed for 9 days followed by necropsy.
GLP compliance:
no
Remarks:
This is an old study (1965), OECD test guidelines were not available at that time.
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Aerosol mist
Details on test material:
The compound was received from the Lucidol Division, Wallace and Tiernan Incorporated, Buffalo, New York, on December 21, 1964. It was a clear viscous liquid in a plastic bottle bearing the label "SN4-l38-38". Aerosol mist of the test item was generated by the use of appropriate apparatus including the use of a nebulizer.

Test animals

Species:
rat
Strain:
other: Albino Charles River rats were used.
Sex:
male
Details on test animals and environmental conditions:
Ten male albino Charles River rats, weighing from 264 to 296 grams, were used in this study. The animals were individually housed in wire mesh cages elevated above the droppings and maintained in airconditioned quarters throughout the pre-exposure and 2-week postexposure period. Except for the period of exposure, food and water were available to all animals ad libitum.

Administration / exposure

Route of administration:
other: Aerosol mist
Type of inhalation exposure:
whole body
Remarks:
The aerosol formed was carried directly into the exposure chamber containing the test material.
Vehicle:
not specified
Details on inhalation exposure:
The test animals were placed in an 18 liter, dynamic inhalation chamber and exposed, for a single continuous one-hour period, to the aerosol mist of the test material. Exposure was made by metering the test materials into a nebulizer (DeVilbiss No. 40) through which a known airflow was produced. The aerosol thus formed was carried directly into the exposure chamber containing the test animals.

The apparatus used was fitted with a rotameter and a Dow Dual Syringe Feeder, permitting variable airflow and an alteration of the flow of the test material into the nebulizer. Calculations of the theoretical concentrations were based on the values obtained from these instruments.

The atmospheric concentration used during this exposure (13.1 mg./liter) was the maximum possible using the apparatus described.
Analytical verification of test atmosphere concentrations:
no
Concentrations:
The test compound, SN4-l38-38, was administered as an aerosol mist at a calculated atmospheric concentration of 13.1 mg./liter of air. The atmospheric concentration used during this exposure (13.1 mg./liter) was the maximum possible using the apparatus described.
No. of animals per sex per dose:
Ten male rats were used. Only one dose was tested.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 9 days. During the l-hour exposure to an atmosphere containing an aerosol mist of the test compound, all animals were observed continuously for changes in behavior and appearance.. Following the exposure, the animals were examined closely for pharmacodynamic and/or toxic signs.

- Frequency of observations and weighing: Prior to the initiation of the exposure, and at 7 and 9 days thereafter, individual body weight measurements were obtained.

- Necropsy of survivors performed: yes. After 9 days of observations, all rats were sacrificed by means of an intraperitoneal injection of 5 per cent sodium pentobarbital and necropsied.

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
discriminating conc.
Effect level:
> 13.1 mg/L air
Based on:
test mat.
Exp. duration:
60 min
Mortality:
No mortalities occurred.
Clinical signs:
other: Behavior, and Appearance: Gross observation of the test animals after 10 minutes of the exposure period had lapsed revealed 3-of-10 with moderate ptyalism and a general increased grooming activity throughout the group. After 30 minutes of exposure, all ra
Body weight:
Individual body weights taken initially and at 7 and 9 days after treatment did not reflect unusual alterations and compared favorably to control rats of the same age and strain maintained in the testing laboratory from time-to-time.
Gross pathology:
Necropsy Findings: No lesions were observed at necropsy which could be attributed to the inhalation exposure with the test compound.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
Exposure of rats for one continuous hour to an atmospheric concentration of a mist of the test agent (13.1 mg./liter of air) failed to cause adverse pharmacotoxic signs, mortality, or gross evidence of damage at necropsy 9 days after exposure.
Executive summary:

Ten male albino Charles River rats, weighing from 264 to 296 grams, were used in this study. The test compound, SN4-l38-38, was administered as an aerosol mist at a calculated atmospheric concentration of 13.1 mg./liter of air. During the l-hour exposure all animals were observed continuously for changes in behavior and appearance. Following the exposure, the animals were examined closely for pharmacodynamic and/or toxic signs. After 9 days of observations, and body weight measurements on days 7 and 9, animals were necropsied.

Exposure of rats for one continuous hour to an atmospheric concentration of a mist of the test agent (13.1 mg./liter of air) failed to cause adverse pharmacotoxic signs, mortality, or gross evidence of damage at necropsy 9 days after exposure. Based on the results of this study, it was concluded that the results indicate that the test compound does not present a hazard to rats when a saturated atmosphere is inhaled over a continuous period of one hour. The report also concluded that dependent upon the use of this agent, there does not appear to be a hazard to man by the route of inhalation provided ordinary care is exercised in the handling of this material.

Only one concentration of the test item was tested and for an hour. These approaches differ from the currently acceptable test guidelines. Therefore the experimental value cannot be used for DNEL derivation.