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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April-November 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study equivalent to OECD guideline 403
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Method: other: Protocol guideline not specified in report. However, protocol meets criteria in OECD 403 "Acute Inhalation Toxicity."
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identity: Dowanol-DPnB (n-butoxypropoxypropanol or
dipropylene glycol normal-butyl ether).
CAS # 29911-28-2
Batch No.: EB 891115
Purity: 99.7% (0.17% dipropylene glycol)
Appearance: Clear liquid.
Administered as: Aerosol
Vapor pressure: 0.06 mmHg at 25°C (79 ppm at 1 atm)
Specific Gravity: 0.91 g/ml.
Solubility: 5% in water.
Stability: Stable up to 200°C.

Dipropylene glycol n-butyl ether (DPnB) is a mixture of 4
possible isomers with the major isomers being
1-(1-n-butoxy-2-propoxy)-2-propanol and
2-(1-n-butoxy-2-propoxy)-1-propanol.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 9 weeks
- Weight at study initiation: males: around 200 g, females: 120-130 g.
- Fasting period before study: none
- Housing: 2 per stainless steel wire cage prior to exposure and 1 per cage post exposure
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 3 weeks in house. prior to exposure, animals were acclimated in nose-only apparatus without test material exposure for 4 hours.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): as regulated
- Humidity (%): as regulated
- Air changes (per hr): n/a
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To: n/a

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
In an acute inhalation toxicity study, a single group of 5 male and 5 female young adult Fischer 344 rats were exposed to an aerosol atmosphere of DPnB, at a concentration of 2040 mg/m3, by nose-only exposure for a period of 4 hours.  

Polycarbonate tubes containing the subjects (nose cones) were attached to a 42-liter ADG nose-only inhalation chamber (30 x 60 cm) with an airflow of 30 liters/min.  Aerosol was generated by metering DPnB into a stainless steel ¼ J spray nozzle using a FMI pump.  DPnB was mixed with air in the spray nozzle and test material was sprayed into the chamber as an aerosol.  Aerosol total mass concentrations were measured gravimetrically five times over the 4-hour exposure.  Aerodynamic particle size was characterized using a 6-stage cascade impactor with increasingly diminishing pore sizes in the 6 stages.  Temperature and humidity were monitored at ½ hour intervals over the 4-hour exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2040 mg/m3
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Rats were observed for mortality and clinical signs of toxicity on the day of exposure (day 1) and 14 days thereafter.  The subjects were weighed on days 1, 2, 4, 8, 11, and 15 of the study.  All animals were subjected to gross necropsy.
Statistics:
Means and standard deviations of body weights, chamber temperatures, relative humidity and airflows, and chamber concentrations were calculated for descriptive purpose.

Results and discussion

Preliminary study:
n/a
Effect levels
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 2.04 mg/L air
Exp. duration:
4 h
Mortality:
All rats survived the first day of exposure as well as the subsequent 14-day observation period (i.e., until the scheduled sacrifice on day 15).  
Clinical signs:
Immediately after exposure, rats were soiled with urine and feces from being in the nose cones. 
Body weight:
Body weights for both sexes were slightly decreased (3%) on the day after exposure but gained weight steadily thereafter (not unusual with nose-only exposures).
Gross pathology:
No gross pathological changes were noted in any subjects at necropsy.
Other findings:
Characterization of the aerosol atmosphere:  The time weighted average concentration of the aerosol over the 4-hour exposure period was 2.04 mg/liter or 2,040 mg/m3. Forty-eight percent of the aerosol had an aerodynamic mass median diameter of less than 3 microns, indicating that a high percentage of the aerosol was respirable within the deep lung.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The lethal concentration of DPnB is greater than 2.04 mg/liter (2,040 mg/m3). If DPnB had sufficient vapor pressure, this concentration would correspond to 262 ppm.
Executive summary:

In an acute inhalation toxicity study, a single group of 5 male and 5 female young adult Fischer 344 rats were exposed
to an aerosol atmosphere of DPnB, at a concentration of 2040 mg/m3, by nose-only exposure for a period of 4 hours.  Rats
were observed for mortality and clinical signs of toxicity on the day of exposure (day 1) and 14 days thereafter.  The
subjects were weighed on days 1, 2, 4, 8, 11, and 15 of the study.  All animals were subjected to gross necropsy.

Polycarbonate tubes containing the subjects (nose cones) were attached to a 42-liter ADG nose-only inhalation chamber
(30 x 60 cm) with an airflow of 30 liters/min.  Aerosol was generated by metering DPnB into a stainless steel ¼ J spray
nozzle using a FMI pump.  DPnB was mixed with air in the spray nozzle and test material was sprayed into the chamber
as an aerosol.  Aerosol total mass concentrations were measured gravimetrically five times over the 4-hour
exposure.  Aerodynamic particle size was characterized using a 6-stage cascade impactor with increasingly diminishing
pore sizes in the 6 stages.  Temperature and humidity were monitored at ½ hour intervals over the 4-hour exposure.

Rats were acclimated to the nose-only polycarbonate tubes for four hours the day prior to exposure.  Rats showed
typical transient weight loss due to stress from being confined in the tubes.

All rats survived the first day of exposure as well as the subsequent 14-day observation period (i.e., until the scheduled sacrifice on day 15).  Immediately after exposure, rats were soiled with urine and feces from being in the nose
cones.  Body weights for both sexes were slightly decreased (3%) on the day after exposure but gained weight steadily
thereafter (not unusual with nose-only exposures).  No gross pathological changes were noted in any subjects at necropsy.

Characterization of the aerosol atmosphere:  The time weighted average concentration of the aerosol over the 4-hour exposure period was 2.04 mg/liter or 2,040 mg/m3. Forty-eight percent of the aerosol had an aerodynamic mass
median diameter of less than 3 microns, indicating that a high percentage of the aerosol was respirable within the deep lung.

The lethal concentration of DPnB is greater than 2.04 mg/liter (2,040 mg/m3). If DPnB had sufficient vapor pressure, this concentration would correspond to 262 ppm.


This study was identified as key for this toxicity endpoint because of the methods followed (which were comprehensively
documented in the report).  The report included GLP and Quality Assurance statements, signed by the Study Director
and Head of the QA Unit, respectively.  Although the study report did not specify that OECD Protocol 403: "Acute
Inhalation Toxicity"  was followed, the study satisfied the methods stipulated in Protocol 403.  Specifically, the numbers and type of test animals used and their husbandry conditions were as prescribed in the guidance.  Test
material characterization was adequate.  The dose level tested (in this limit test) satisfied the appropriate OECD
upper limit, the length of the observation period (14 days) was sufficient, and the toxicity endpoints monitored were
typical for this type assay and adequately recorded.