Propane-1,3-diol

Endpoint summary

Description of key information

The substance has low oral toxicity with a rat LD50 value of greater than 2000 mg/kg, low inhalation toxicity with a rat acute lethal dose greater than the highest dose tested of 1800 mg/m³, and low dermal toxicity with a rat LD50 of greater than 4200 mg/kg/day. Acute toxicity by the oral route of exposure was associated with sluggishness, ataxia, and sedation at high concentrations. Acute toxicity by the inhalation route of exposure was associated with wet fur/perineum and ocular discharge at high concentrations. The acute effects were associated with exposure concentration. Systemic activity was not observed with inhalation and dermal routes of exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

ACC PDO panel assigned reliability of 2. PDO from chemical process.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Remarks:

Acclimatization, humidity, lighting. no controls

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: albino (Wistar-derived)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Institute's colony.
- Age at study initiation: Adult
- Weight at study initiation: Males 206 - 292 grams, Females 102 - 139 grams.
- Fasting period before study: Overnight.
- Housing: Housed in groups of five in screen-bottomed, stainless steel cages in a well-ventilated room.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24°C
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Single doses of 9.0, 10.8, 13.0, 15.6, or 18.7 ml per kg body weight

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequency of observations not reported. Body weights not recorded.
- Necropsy of survivors performed: yes

Statistics:

The LD50 was calculated according to the method of Weil (Biometrics (1952) 8:249-263).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 14.9 mL/kg bw

95% CL:

13.7 - 16.3

Mortality:

Most of the deaths occurred between 8 and 23 hours after treatment. One female died on the 4th and one male on the 7th post-treatment day.

Clinical signs:

other: Within a few hours after dosing, the rats showed sluggishness, sedation and ataxia. Unconsciousness was frequently observed and preceded death. After 7 days the survivors recovered gradually and looked quite healthy again at the end of the observation pe

Gross pathology:

Macroscopic examination of the survivors did not reveal any treatment-related gross alterations.

Dose (mL/kg)	Mortality
	Males	Females	%
9.0	0/5	0/5	0
10.8	0/5	1/5	10
13.0	2/5	0/5	20
15.6	3/5	2/5	50
18.7	5/5	5/5	100

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (rat): 14.9 mL/kg

Executive summary:

The acute oral toxicity of 1,3-propanediol was tested in five rats/gender at dose levels of 9.0, 10.8, 13.0, 15.6, or 18.7 mL/kg. The animals were observed for 14 days post-exposure. The LD50 was calculated to be 14.9 mL/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

PDO from chemical process.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Six male rats were exposed nose-only for a single 4-hour period to 1,3-propanediol aerosol in air. Rats were weighed and observed for clinical signs of toxicity during a 14-day observation period.

GLP compliance:

no

Test type:

other: Inhalation Approximate Lethal Concentration

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Raleigh, North Carolina
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 239 to 307 grams
- Housing: Housed either singly or in pairs in suspended, stainless steel, wire-mesh cages
- Diet: Certified Rodent Chow #5002, ad libitum
- Water: Tap water from United Water Delaware, ad libitum
- Acclimation period: Rats were quarantined after arrival for at least 6 days prior to testing.

ENVIROMENTAL CONDITIONS
- Temperature (°C): 23±2
- Humidity (%): 50±10
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Spraying Systems Nebulizer with a Harvard Model 22 Syringe Infusion Pump.
- Exposure chamber volume: 29-L
- Method of holding animals in test chamber: Individually restrained in perforated stainless steel cylinders with conical nose pieces
- Source and rate of air: Filtered Houseline Air and 15 L/min
- Method of conditioning air: chamber airflow was set at the beginning of each exposure and adjusted to maintain desired atmospheric concentration. Airflow was monitored continually with a Brooks model 1355 Sho-Rate Rotometer. Temperature, relative humidity, and oxygen were measured two times during the exposure.
- System of generating particulates/aerosols: Polycarbonate dispersion plate located near the chamber inlet was used to promote uniform aerosol distribution throughout the chamber.
- Method of particle size determination: Gravimetric Analysis (preweighed 25 mm Gelman glass fiber Type A/E filter. Weighed on a Cahn model C-30 Microbalance
- Treatment of exhaust air: Pair of liquid traps (water scrubbers) and MSA charcoal/HEPA filter cartridge
- Temperature, humidity, pressure in air chamber: 23±2°C, 48 to 54%

TEST ATMOSPHERE
- Brief description of analytical method used: Aerosol concentrations determined at 30-minute intervals by gravimetric analysis. Once air sample collected during exposure to determine particle size distribution with a Sierra Series 210 cyclone preseparator/cascade impactor and Sierra Series 110 Constant Flow Air Sampler.
- Samples taken from breathing zone: Yes. Known air volumes drawn from breathing zone through a filter cassette that contained a preweighed 25 mm Gelman glass fiber filter.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD = 3.2 µm GSD 2.1

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5 mg/L

No. of animals per sex per dose:

6 male rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed each day for mortality, and were weighted and observed for clinical signs of toxicity at least four times per week (weekends excluded unless warranted by the health status of the rats).
- Necropsy of survivors performed: no

Sex:

male

Dose descriptor:

other: ALC

Effect level:

> 5 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

There were no mortalities for rats exposed to 5.0 mg/L.

Clinical signs:

other: During the exposure, no abnormal clinical signs were observed. Immediately following the exposure, when rats were removed from the chamber, all rats had wet fur/perineum, and one rat had an ocular discharge. No clinical signs of toxicity were observed i

Body weight:

Slight to moderate weight loss was observed in all rats one day following the exposure. Although one rat had transient body-weight loss during the remainder of the recovery, all rats experienced an overall weight gain by the end of the 14-day recovery period.

Mean Aerosol Concentration (mg/L)	Aerosol Size			Mortality
	MMAD (µm)	Geometric Standard Deviation	Percent < 10µm
5.0	3.2	2.1	94	0/6

Conclusions:

The study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).

Executive summary:

Six male rats were exposed nose-only for a single 4-hour period to 1,3-propanediol aerosol in air. Rats were weighed and observed for clinical signs of toxicity during a 14-day recovery period. The approximate lethal concentration (ALC) was greater than 5.0 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Reliability assigned by ACC in HPV Document

Guideline:

other: Guideline not reported in secondary source

Principles of method if other than guideline:

Undiluted test substance was applied to the shaved dorso-lumbar skin of two rats/sex/group. A bandage was applied to the region using an impermeable dressing of aluminum foil and waterproof plaster. After 24 hours, the bandage was removed, and the area washed with a tepid dilute detergent solution. Rats were deprived of food during the 24-hour exposure. The animals were observed for signs of toxicity over the following 9 days.

GLP compliance:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Fasting period before study: Not reported
- Housing: Not reported
- Diet (e.g. ad libitum): Fasted during exposure
- Water (e.g. ad libitum): Not reported
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

1.0, 2.0, or 4.0 mg/kg

No. of animals per sex per dose:

2/sex/group

Control animals:

no

Details on study design:

Undiluted test substance was applied to the shaved dorso-lumbar skin of two rats/sex/group. A bandage was applied to the region using an impermeable dressing of aluminum foil and waterproof plaster. After 24 hours, the bandage was removed and the area washed with a tepid dilute detergent solution. Rats were deprived of food during the 24-hour exposure. The animals were observed for signs of toxicity over the following 9 days.

Dose descriptor:

LD50

Effect level:

> 4 200 mg/kg bw

Remarks on result:

other: LD50 was determined to be > 4 mL/kg which was equivalent to > 4200 mg/kg.

Mortality:

No deaths occurred prior to scheduled sacrifice.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (rat): >4200 mg/kg

Executive summary:

Undiluted test substance was applied to the shaved dorso-lumbar skin of two rats/sex/group at concentrations of 1.0, 2.0, or 4.0 mL/kg. After 24 hours, the bandage was removed and the area washed with a tepid dilute detergent solution. The animals were observed for signs of toxicity over the following 9 days.  The LD50 was determined to be > 4 mL/kg which was equivalent to > 4200 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

Based on the oral rat LD50 of >2000 mg/kg, inhalation rat LC50 of >1800 mg/m³, and rat dermal LD50 of >4200 mg/kg/day, the substance does not need to be classified for acute toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.