Registration Dossier

Administrative data

Description of key information

GLP-studies according to OECD guidelines 401, 403 and 402 (limit test) are available for PnB. Those key studies are supported by several non-GLP studies similar to the OECD guidelines.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no
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
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
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.
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
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.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 26.06.2001 To 09.10.2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Remarks:
Department of Experimental Toxicology and Ecology, BASF AG
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, 97633 Sulzfeld
- Age at study initiation: male animals approx. 8-12 weeks, female animals approx. 14 -18 weeks
- Weight at study initiation: mean 215 g (males), 208 g (females)
- Fasting period before study: at least 16 hours before admínístratíon, but water was available ad libitum
- Housing: single housing in stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG)
- Diet (e.g. ad libitum): Kliba-Labordiät; Provimi Kliba SA, Kaiseraugst, Switzerland; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 g/100 ml
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on the physical and chemical characteristics of the test substance and its composition, no pronounced acute oral toxicity was expected
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals. Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study (before fasting
period). Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One female animal and 1 male animal died during hour 2 and on study day 3, respectively.
Clinical signs:
Males: impaired and poor general state, dyspnoea, apathy, squatting posture, abdominal and lateral position, staggering, ataxia, atonia, paresis, narcotic-like state, absent pain and corneal reflex, piloerection, and smeared fur were observed from hour 0 until including study day 2 after administration
Females: poor general state, dyspnoea, apathy, abdominal position, staggering, ataxia, atonia, narcotic-like state, exsiccosis, lacrimation, brown and yellow green discolored urine, piloerection, smeared fur and red smeared fur in the anogenital area and were observed from hour 0 until including study day 3 after administration
Body weight:
Males: 215 g (d0), 234 g(d7), 250 g (d13)
Females: 208 g (d0), 211 g (d7), 218 g (d13)
Gross pathology:
Several black erosions/ulcers of the glandular stomach were observed in males that died.
No histopathological abnormalities were found in the other animals.
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 300 mg/kg bw
Quality of whole database:
Good (Klimisch 1)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10/1987 to 01/1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Method: other: Protocol guideline not specified in report. However, protocol meets criteria specified in OECD 403 "Acute Inhalation Toxicity."
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory, Kingston, NY
- Age at study initiation: 11 weeks
- Weight at study initiation: ca. 150 g (females) and ca. 240 g (males)
- Fasting period before study: none
- Housing: 2 per cage in suspended stainless steel wire mesh cages
- Diet (e.g. ad libitum): ad libitum except during exposure
- Water (e.g. ad libitum): ad libitum except during exposure
- Acclimation period: 4 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25°C (during exposure)
- Humidity (%): 48% (during exposure)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: none
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rochester-type stainless steel and glass exposure chambers under dynamic air flow conditions
- Exposure chamber volume: 112 liter
- Source and rate of air: 30 l/min
- Method of conditioning air: Vapors of PnB were generated using a glass J-tube method. Liquid test material was metered into the J-tube. Compressed air, heated with a flameless torch (FHT-4, Master Appliance, Racine, WI) to the minimum extent necessary, passed through the J-tube to volatilize the test material.
- Treatment of exhaust air:
- Temperature, humidity: 25°C, 48%

TEST ATMOSPHERE
Air flow through each chamber was determined with a rotameter. The rotameter was calibrated with an AL-1400 gas meter prior to the start of the study. The temperature in the chamber was controlled by a system designed to maintain temperature at approximately 22°C. Temperature, air flow and relative humidity values were recorded every 30 minutes during the four-hour exposure period.
The analytical concentration of PnB in the breathing zone of the animals was determined by gas chromatography using a flame ionization detector. The gas chromatographic conditions were as follows: helium flow = 30 ml/min, hydrogen flow = 30 ml/min, air flow = 300 ml/min, oven = 110°C and detector = 180°C. A 6 foot x 1/8 inch stainless steel column packed with 10% OV-101 on 100/120 mesh Chromosorb WHP was used for separation of the test material from air. The gas chromatographwas calibrated with air standards of PnB which were prepared by injecting measured volumes of PnB into SARAN bags containing measured volumes of dry, compressed air.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
651 ppm
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for overt signs of toxicity during the exposure period (day 1) and after for 14 additional days.  Rats were weighed prior to exposure and on days 2, 4, 8, 11 and 15.
- Necropsy of survivors performed: yes (including examination of the eyes)
- Other examinations performed: clinical signs, body weight, ophthalmological examination, behaviour pattern and nervous system activity
Statistics:
Means and standard deviations of animal body weights, chamber temperatures, relative humidities, and chamber air flows were calculated for descriptive purposes.
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 651 ppm
Exp. duration:
4 h
Mortality:
no deaths
Clinical signs:
other: No clinical signs were observed either during the exposure or throughout the subsequent two-week observation period.
Body weight:
Body weights appeared normal during the observation period.
Gross pathology:
Gross pathologic examination at the end of the two-week observation period revealed no treatment-related lesions.
Other findings:
none
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC0 is greater than 651 ppm: no EU classification for acute inhalation toxicity.
Executive summary:

A single group of Fischer 344 rats (5/sex) was exposed in whole-body inhalation chambers for 4 hours to vapors of propylene glycol n-butyl ether at a measured concentration of 651 ppm.  Chambers were 112 liters in volume and airflow was 30 liters/min.  Animals were observed for overt signs of toxicity during the exposure period (day 1) and after for 14 additional days.  Rats were weighed prior to exposure and on days 2, 4, 8, 11 and 15.

No rats died when exposed to 651 ppm propylene glycol n-butyl ether for 4 hours.  No signs of toxicity during or after exposure were noted and no lesions were observed at necropsy except for a unilateral distension of the ovarian
bursa in one female.  This lesion was considered unrelated to exposure since it occasionally occurs in unexposed
females.

The highest attainable concentration of PnB under ambient conditions of exposure was not toxic to rats following a single four-hour exposure. Therefore, the potential for acute inhalation toxicity is very low for this material.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Good (Klimisch 1)

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
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: ca. 8 weeks
- Weight at study initiation: ca. 217 g (females) and 327 g (males)
- Fasting period before study: none
- Housing: individually housed in 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 (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
other: Test material was tested undiluted.
Details on dermal exposure:
TEST SITE
- Area of exposure: upper dorso-lateral area
- % coverage: 10
- Type of wrap if used: surgical gauze fixed to aluminium foil

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After removal of the semi-occlusive bandage the remaining test substance was on the treated surface was gently removed with tissues moistened with tap-water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): dose volume was calculated based on the specific gravity of 0.88 g/ml
- Concentration (if solution): undiluted
- Constant volume or concentration used: constant concentration

VEHICLE
no vehicle used
Duration of exposure:
24 hours
Doses:
2000 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: 14 days
- Frequency of observations and weighing: On the day of treatment (day 0), animals were observed for toxicity and morbidity approximately every two hours.  Subjects were checked once daily thereafter except for weekends and holidays.  Individual body weights were recorded on test days 0, 7, and 14.  The treated areas of skin were examined on test days 4, 7, and 14 for signs of irritation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

  
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no deaths
Clinical signs:
No signs of systemic toxicity were observed during exposure and the following 14-day observation period. The treated skin surface of the animals showed no abnormalities.
Body weight:
Weekly group mean body weight gain was normal.
Gross pathology:
Macroscopic examination of all animals at the end of the study revealed no test substance related gross abnormalities.
Other findings:
none
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 for PnB is >2000 mg/kg bodyweight: no EU classification for acute dermal toxicity.
Executive summary:

A group of 5 male and 5 female Wistar rats was treated with a single application of 2,000 mg/kg propylene glycol n-butyl ether applied topically to the clipped, intact skin under
occlusion for a period of 24 hours.  Subjects were observed for clinical signs of toxicity and mortality during the
application period and for a period of 14 days after removal of the test material.  The skin of the rats at the site of
application was also evaluated for signs of irritation over the course of the study.  The undiluted test material was
applied at a single dose of 2,000 mg/kg to approximately 10% of the total body surface area of skin (clipped,
non-abraded) of the rats.  The test material was applied to gauze patches, which were then affixed to the clipped area
of the skin and covered with foil and wrapped with a bandage around the torso.  The test material was held in contact
with the skin for a period of 24 hours whereupon it was removed and the treated area was washed with water to remove remaining test material.  On the day of treatment (day 0), animals were observed for toxicity and morbidity
approximately every two hours.  Subjects were checked once daily thereafter except for weekends and holidays. 
Individual body weights were recorded on test days 0, 7, and 14.  The treated areas of skin were examined on test days 4, 7, and 14 for signs of irritation. Animals were sacrificed on day 14 and subjected to gross necropsy.

No deaths, clinical signs of toxicity, or skin irritation occurred over the course of the study.  The dermal LD50 for
propylene glycol n-butyl ether is greater than 2,000 mg/kg for male and female Wistar rats.  

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Good (Klimisch 1)

Additional information

The studies with a Klimisch rating 1 have been selected as key studies for the hazard assessment.

Oral - The oral LD50 value for propylene glycol butyl ether in experiments in rats ranges from 2500 to 5200 mg/kg. There are two key studies conducted on rats identified for acute oral toxicity - Dow, 1987 with combined (male and female) LD50 value of 3300 mg/kg and BASF SE (2001) with the combined (male and female) LD50 value of > 2000 mg/kg, based on the most reliable study (Klimisch 1) will be taken forward for the risk assessment.

Inhalation - No mortality was observed in any of the acute inhalation studies in rats. The key study identified is the Dow, 1989 study in rats and the LC0 value was > 651 ppm or 3515 mg/m3 (highest attainable concentration under ambient conditions of exposure), this value will be taken forward for the risk assessment.

Dermal - Dermal LD50 values in rats range from 1400 to 3133 mg/kg. The key study identified for acute dermal toxicity is the Dow, 1989 study in rats with the LD50 value of > 2000 mg/kg, based on the most reliable study (Klimisch 1) will be taken forward for the risk assessment. This was supplemented with one supporting publication (Smyth et al., 1974) in rabbits with a dermal LD50 of 3133 mg/kg body weight.The lowest value of 1400 mg/kg in rabbits is from the Smyth, 1969 publication and there is not much information with regards to the purity of the material tested and hence this value will not be used for risk assessment.


Justification for selection of acute toxicity – oral endpoint
GLP study according to OECD guideline

Justification for selection of acute toxicity – inhalation endpoint
GLP study according to OECD guideline

Justification for selection of acute toxicity – dermal endpoint
GLP study according to OECD guideline

Justification for classification or non-classification

LD50 values for oral and dermal route > 2000 mg/kg/bw.

Inhalation exposure to the highest attainable vapor concentration of PnB (651ppm/3515mg/m3) did not reveal any substance related adverse effects.

According to the EU criteria for classification and labeling, PnB is not classified for acute toxicity for any route of exposure.