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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:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline

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)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identity: Dowanol-PnB (1-butoxy-2-hydroxypropane or
propylene glycol normal-butyl ether). CAS # 29387-86-8
(also 5131-66-8)

Batch No.: XZ 95410.00
Purity: "More than 98%"
Supplied as: Not reported.
Appearance: Clear liquid.
Administered as: Undiluted liquid.
Specific Gravity: 0.88 g/ml.
Solubility: 6% in water.
Stability: Stable up to 200°C.

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: 8-9 weeks
- Weight at study initiation: 343 to 416 g (males) & 207 to 269 g (females)
- Fasting period before study: Animals were fasted overnight prior to dosing and were not allowed food until 5.5 hr after dosing.
- Housing: polycarbonate cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21°C
- Humidity (%): 50-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: no vehicle; test material was tested indiluted
Details on oral exposure:
substance dosed undiluted via oral gavage
Doses:
1800, 2400, 3200 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 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.
- Frequency of observations and weighing: Body weights were recorded immediately prior to dosing, weekly thereafter, and at death.
- Necropsy of survivors performed: Non-survivors were necropsied as soon as possible and surviving animals were subjected to necropsy on day 14.
- Other examinations performed: clinical signs, body weight

Results and discussion

Preliminary study:
To establish an appropriate dose range four groups of animals, each comprising 1 male and 1 female, were dosed with an oral dose of the test substance at 1000, 1800, 3200 and 5600 mg/kg body weight, respectively. Mortalities occurred in the 3200 and 5600 mg/kg dose group (both animals). Major signs of toxicity were lethargy, hyperpnoea and dacryorrhoea. The observation period was 7 days.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 300 mg/kg bw
Based on:
test mat.
95% CL:
2 800 - 4 500
Sex:
male
Dose descriptor:
LD50
Effect level:
5 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no confidence limits
Sex:
female
Dose descriptor:
LD50
Effect level:
2 700 mg/kg bw
Based on:
test mat.
95% CL:
2 400 - 3 600
Mortality:
1800 mg/kg: 0/10
2400 mg/kg: 1/10
3200 mg/kg: 5/10
Clinical signs:
Signs of toxicity were lethargy, comatose, hypopnoea, gasping respiration amd rough coat. For surviving animals these signs were reversible within 2 days.
Body weight:
Weekly group mean body weight gain was normal.
Gross pathology:
Maroscopic examination of animals at necropsy revealed haemorrhage of the stomach, bloody or yellow content of the small intestines, haemorrhage of the small intestines, bloody content of the bladder, hyperaemia of the bladder.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 of 3300 mg/kg: no EU classification for acute oral toxicity.
Executive summary:

Three groups of Wistar rats (5/sex/dose level) received
single oral doses of 1800, 2400, or 3200 mg/kg propylene
glycol n-butyl ether (PnB), administered undiluted using a
stainless steel stomach cannula attached to a syringe. 

No rats died from a dose of 1800 mg/kg PnB.  One female died
after a dose of 2400 mg/kg.  Four females and one male died
at 3200 mg/kg.  The calculated oral LD50 for males alone was
5500 mg/kg (no 95% confidence limits), for females alone was
2700 mg/kg (95% CL: 2400 - 3600 mg/kg), and for both sexes
combined was 3300 (95% CL: 2800 - 4500 mg/kg).

All deaths occurred within one day of dosing.  Adverse signs
included weight loss, lethargy, coma, hypopnea, gasping, and
dacryorrhea.  Surviving rats showed no adverse signs by day
2.  At necropsy, surviving rats showed no grossly observable
lesions.  Rats dying from treatment exhibited hemorrhage of
the stomach and small intestine, bloody content of the small
intestine and bladder, yellow liquid within the small
intestine, and hyperemia of the bladder.