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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February-July 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
n/a
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.: XZ 95411.00
Purity: "More than 95%"
Supplied as: Not reported.
Appearance: Clear liquid.
Administered as: Undiluted liquid.
Specific Gravity: 0.91 kg/liter.
Solubility: 5% in water.
Stability: Stable up to 200°C.
Storage: At ambient temperature in the dark.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 225-304 g (males), 172-201 g (females)
- Fasting period before study: feed was withheld overnight before dosing
- Housing: individually housed in polycarbonate cages 7 days prior to dosing
- Diet (e.g. ad libitum): ad libitum, standard laboratory animal diet (RMH-B)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 50-70%
- Air changes (per hr): n/a
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light


IN-LIFE DATES: From: 1987-Feb-17 (range-finding) and 1987-Feb-24 To: 1987-Feb-24 (range finding) and 1987-March-10

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: n/a
- Amount of vehicle (if gavage): n/a
- Justification for choice of vehicle: n/a
- Lot/batch no. (if required): n/a
- Purity: n/a


MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw for aqueous material


DOSAGE PREPARATION (if unusual): n/a


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: n/a
Doses:
3200, 4200 and 5600 mg/kg bw
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: daily clinical observation except for weekends (observe for death only), Body weights were recorded prior to dosing, at death, or weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
n/a

Results and discussion

Preliminary study:
n/a
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 000 mg/kg bw
95% CL:
3 200 - 4 600
Sex:
male
Dose descriptor:
LD50
Effect level:
4 400 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
3 700 mg/kg bw
95% CL:
2 500 - 4 800
Mortality:
At the low dose of 3200 mg/kg DPnB, one male died on day 0 and one female died on day one (total mortality 2/10).  At 4200 mg/kg, two males and two females died on day 0 and two additional females died on day 1 (total mortality 6/10).  At 5600 mg/kg, four males and four females died on day 0 and one additional female died on day 1 (total mortality 9/10). 
All deaths occurred within two days of dosing.  Females were affected more than males.  
Clinical signs:
Adverse signs included weight loss, lethargy, coma, hypopnea, hyperpnea, dacryorrhea, blood around the eyes, rough coat, and ataxia.  Surviving rats showed no adverse signs by day 2.  
Body weight:
Weight gain appeared normal in survivors.
Gross pathology:
At necropsy, (presumably non-surviving) rats showed 1) enlargement, hemorrhage, and hyperemia of the stomach, 2) hemorrhage of the thymus, 3) dark red lungs, 4) dark red liver, and 5) gas accumulation, bloody content, and watery content of the small intestine.
Other findings:
- Organ weights: n/a
- Histopathology: n/a
- Potential target organs: n/a
- Other observations: n/a

Any other information on results incl. tables

The calculated oral LD50 for males alone was 4400 mg/kg (no 95% confidence limits), for females alone was 3700 mg/kg
(95% CL: 2500 - 4800 mg/kg), and for both sexes combined was 4000 mg/kg (95% CL: 3200 - 4600 mg/kg).

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The substance is not classified for acute oral toxicity according to EU criteria as the lowest LD50 is 3700 mg/kg.
Executive summary:

Three groups of Wistar rats (5/sex/dose level) received single oral doses of 3200, 4200, or 5600 mg/kg dipropylene glycol n-butyl ether (DPnB), administered undiluted using a stainless steel stomach cannula attached to a syringe. 

Animals were fasted overnight prior to dosing and were not allowed food until 4.5-5.0 hr after dosing.  Subjects were observed for mortality and signs of toxicity several times on the day of dosing (Day 0) and on weekdays thereafter for
up to 14 additional days.  Body weights were recorded prior to dosing, at death, or weekly thereafter.  

Non-survivors were necropsied as soon as possible and surviving animals were sacrificed by CO2 asphyxiation and subjected to necropsy on day 15.


At the low dose of 3200 mg/kg DPnB, one male died on day 0 and one female died on day one (total mortality 2/10).  At
4200 mg/kg, two males and two females died on day 0 and two additional females died on day 1 (total mortality 6/10).  At
5600 mg/kg, four males and four females died on day 0 and one additional female died on day 1 (total mortality 9/10). 

The calculated oral LD50 for males alone was 4400 mg/kg (no 95% confidence limits), for females alone was 3700 mg/kg
(95% CL: 2500 - 4800 mg/kg), and for both sexes combined was 4000 mg/kg (95% CL: 3200 - 4600 mg/kg).


All deaths occurred within two days of dosing.  Females were affected more than males.  Adverse signs included weight loss, lethargy, coma, hypopnea, hyperpnea, dacryorrhea, blood around the eyes, rough coat, and ataxia.  Surviving rats showed no adverse signs by day 2.  Weight gain appeared normal in survivors.  At necropsy, (presumably non-surviving) rats showed 1) enlargement, hemorrhage, and hyperemia of the stomach, 2) hemorrhage of the thymus, 3) dark red lungs, 4) dark red liver, and 5) gas accumulation, bloody content, and watery content of the small intestine.

The calculated oral LD50 for males alone was 4400 mg/kg (no 95% confidence limits), for females alone was 3700 mg/kg
(95% CL: 2500 - 4800 mg/kg), and for both sexes combined was 4000 mg/kg (95% CL: 3200 - 4600 mg/kg).

The substance is not classified for acute oral toxicity according to EU criteria as the lowest LD50 is 3700 mg/kg.