Registration Dossier

Administrative data

Endpoint:
acute 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: see 'Remark'
Remarks:
The study was not conducted to a specific test guideline, no claim of GLP complaince was included in the test report, and the level of detail provided in the report was lacking for certain aspects or the study, so the study cannot be considered reliable without restrictions. The methodology described does, however, seem essentialy reliable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Five male and five female rats were exposed to an atmosphere containing the test material for 4 hours. During the exposure period the rats were observed for changes in appearance or behaviour, and after the exposure period they were observed for pharmacodynamic or toxic signs. The rats were observed for 14 days following the exposure period, then any surviving animals were sacrificed.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Benzoflex 9-88 (Dipropylene glycol dibenzoate DPGDB)
- Physical state: viscous brown liquid
- Lot: A3-342-33, Net 44

Test animals

Species:
rat
Strain:
other: Spartan
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: 212 to 235 g
- Housing: Rats were housed in groups of 5 in metal cages above the droppings.
- Diet (e.g. ad libitum): Purina Laboratory Chow was available ad libitum
- Water (e.g. ad libitum): Water was available ad libitum.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature was controlled (note that the temperature range was not reported)
- Humidity (%): Humidity was controlled (note that the humidity range was not reported)

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Sealed glass chamber, test material addition controlled by a Dual Syringe Feeder.
- Exposure chamber volume: 59.1 L

TEST ATMOSPHERE
- Brief description of analytical method used: None reported
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
Approximately 200 mg/L. of DPGDB
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During the 4 hour exposure to the test compound the rats were observed continuously for changes in behavior and or appearance.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 200 mg/L air
Exp. duration:
4 h
Remarks on result:
other: No deaths seen during exposure or observation periods
Mortality:
All the rats exposed to DPGDB for the 4-hour exposure duration survived until the end of the observation period.
Clinical signs:
Signs seen during the 4 hour exposure period included decreased motor activity, eye squint, erythema, clear nasal discharge, salivation, lacrimation, tachypnea and slight dyspnea. In addition, at the termination of the exposure period both ocular and nasal porphyrin discharge, flaccidity and ataxia were observed.
At 24 hours and for the remainder of the 14 day observation period, several rats exhibited flaccidity. Other signs recorded during the study period were; hypersensitivity to touch in two rats at 24 through 72 hours and in one rat at 4 days.
Ataxia in one or two rats at 24 through 72 hours and 6, 12, 13 and 14 days. Drying of the corneal surface in one rat at 6, and 7 days; corneal opacity in one to three rats from 7 through 14 days, and chemosis in one or two rats from 9 through 12 days.
Lacrimation in a few rats at 7, 8 and 9 days and clear nasal discharge in a few rats at 9, 10, 11 and 14 days.
Body weight:
All rats exhibited normal body weight gains during the study period.
Gross pathology:
None.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information According to Directive 67/548/EEC Criteria used for interpretation of results: EU
Conclusions:
No deaths were seen in rats exposed to a 200 mg/L atmosphere of DPGDB in air for four hours. On this basis, DPGDB would not be considered a toxic material by the inhalation route of administration.
Executive summary:

A study was performed to assess the acute inhalation toxicity of the test material DPGDB when administered to rats. The study, conducted in 1975, was not performed according to any specific testing guideline, and not in compliance with GLP.

The acute inhaled toxicity assessment was performed in groups of five female and five male rats, exposed to a whole-body aerosol atmosphere containing approximately 200 mg/L. of DPGDB for four hours, then observed for 14 days post exposure.  Clinical signs seen during the 4 hour exposure period included decreased motor activity, eye squint, erythema, clear nasal discharge, salivation, lacrimation, tachypnea and slight dyspnea.  In addition, at the termination of the exposure period both ocular and nasal porphyrin discharge, flaccidity and ataxia were observed.

At 24 hours and for the remainder of the 14 day observation period, several rats exhibited flaccidity. Other signs recorded during the study period were; hypersensitivity to touch in two rats at 24 through 72 hours and in one rat at 4 days.

Ataxia was present in one or two rats at 24 through 72 hours and 6, 12, 13 and 14 days. Drying of the corneal surface in one rat at 6, and 7 days; corneal opacity in one to three rats from 7 through 14 days, and chemosis in one or two rats from 9 through 12 days.

Lacrimation in a few rats at 7, 8 and 9 days and clear nasal discharge in a few rats at 9, 10, 11 and 14 days.

None of the rats exposed to the test material died during the course of the observation period. On this basis, DPGDB would not be considered a toxic material by the inhalation route of administration.