Propane-1,2-diol

Endpoint summary

Description of key information

Acute toxicity of monopropylene glycol by oral and dermal routes of exposure is low. The reported oral LD50 in rats exceeded 20000 mg/kg bw. The values of similar order of magnitude were reported for mice and guinea pigs. The dermal LD50 in rabbits is above 2000 mg/kg bw. Although no conventional acute inhalation studies were available for assessment, no mortalities were observed in rabbits exposed to an aerosol of 10% of monopropylene glycol in air (317042 mg/m3) for 2 hours. Also no mortalities were evidenced in rats exposed to monopropylene glycol aerosol up to concentrations of 2200 mg/m3 for 6 hours/day, 5 days/week for 90 days.

A number of acute animal and human studies have been included, assessing amongst other parameters the potential effects of monopropylene glycol as a respiratory irritant in rats, rabbits, dogs and humans (acute human data located in section 7.10.5 of IUCLID). Although some minor effects were noted in some of these acute studies, these did not provide conclusive evidence that monopropylene glycol is a respiratory irritant; some of the studies had confounding factors or were of insufficient quality to draw definitive conclusions.

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:

other: Study predates GLP and OECD guidelines, clear reporting of technical methods, data analysis (probit) and results, but no characterization of test species or test substance.

Principles of method if other than guideline:

Groups of 9 or 10 rats were administered propylene glycol by gavage in two independent experiments at dose levels ranging from 15 to 25 ml/kg bw and the LD50 was determined.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: different sources
- Weight at study initiation: 250 ± 75 g
- Fasting period before study: ca. 18 hours (overnight)

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

1st experiment (serie A): 15, 17.5, 20, 22.5 and 25 ml/kg bw
2nd experiment (serie B): 17.6, 18,6, 20.0, 21.4 and 22.6 ml/kg bw

No. of animals per sex per dose:

10/dose in experiment 1; 9/dose in experiment B

Control animals:

not specified

Details on study design:

All animals that died were necropsied and those showing evidence of mechanical injury were excluded from calculation of the LD50. The liver and kidneys were examined by light microscopy.

Statistics:

In brief, a straight line was fitted to a plot of the log dose versus the percentage mortality (expressed in probits) using a least-squares method. The log dose corresponding to a 50% mortality was then determined by inspection of these graphical data.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

22 000 mg/kg bw

Remarks on result:

other: This value corresponds to 21.0 ml/kg bw, with standard errors of 19.2-23.9 ml/kg bw.

Mortality:

Mortalities were observed at all dose levels.

Clinical signs:

other: General signs of toxicity included loss of equilibrium, marked depression, analgesia, coma and finally death after a prolonged moribund state shortly after administration of large doses of propylene glycol. 

Gross pathology:

Gross examination of the internal organs were essentially negative except for hemorrhagic areas in the small intestine. Microscopic changes in kidney were minimal, with nuclear pyknosis and vacuolar degeneration of the cytoplasm. A few cortical tubules contained protein debris or loose casts. The liver showed only slight congestion and hyperemia with no fatty changes.

Endpoint conclusion

Dose descriptor:

LD50

Value:

22 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Limit test. No effects seen at maximum tested dose of 2000mg/kg

Additional information

Acute oral toxicity of monopropylene glycol is very low. Laug et al., 1939 reported LD50 values of 22000, 24900 and 19700 mg/kg bw for rats, mice and guinea pigs, respectively, administered monopropylene glycol by gavage. General signs of toxicity in all species included loss of equilibrium, marked depression, analgesia, coma and finally death after a prolonged moribund state shortly after administration of large doses of monopropylene glycol. Gross examinations of the internal organs were essentially negative except for hemorrhagic areas in the small intestine. Microscopic changes in kidney were minimal, with nuclear pyknosis and vacuolar degeneration of the cytoplasm. A few cortical tubules contained protein debris or loose casts. The liver showed only slight congestion and hyperemia with no fatty changes.

Acute dermal toxicity of monopropylene glycol was investigated in a study with 10 rabbits applied a single dose of 2000 mg/kg bw under occlusive conditions for 24 hours (MB Research Laboratories, 1982). The hair was clipped prior to the application and the skin was abraded in 1/2 of the animals. There were no deaths. Clinical signs were limited to lethargy, diarrhea, few feces and/or ptosis in isolated cases. Dermal responses, generally slight on day 1, were minimal on day 7 and absent on day 14. The dermal LD50 was established to exceed 2000 mg/kg bw.

No studies specifically investigating acute inhalation toxicity of monopropylene glycol were available for assessment; however, Konradova et al. (1978) evaluated the influence of exposure to monopropylene glycol on the respiratory tract epithelium in rabbits, by exposing groups of 3 rabbits for 20 minutes or 2 hours to 10% (100000 ppm, 317042 mg/m3) monopropylene glycol in air. No mortalities were reported, indicating that acute inhalation toxicity of monopropylene glycol is very low. 20 minutes inhalation of 10% propylene glycol produced minimal alteration of ciliated cells, but it represented a strong secretory impuls for the goblet ones. After shorter inhalation 16.5% of goblet cells filled with large pale mucous granules, 31% of mucus discharging and 52% of completely exhausted ones with highly electron dense degenerated cytoplasm were observed. After 2 hours inhalation of monopropylene glycol signs of ciliated cells' alteration were more pronounced and a slight drop in the number of intact mucus filled (12%) and mucus discharging goblet cells (19%) was accompanied by an increase in the number of exhausted degenerated ones (69%). The degenerated goblet cells were gradually expelled from the epithelium. Even after 2 hours inhalation the signs of increased differentiation of new goblet cells were not noticed. Furthermore, no treatment-related mortalities were reported by Suber et al. (1989), who exposed rats to propylene glycol aerosol at dose levels of 0.0, 0.16, 1.0 and 2.2 mg/L air for 6 hr/day, 5 days/week for 90 days (see Section on Repeated dose toxicity for further details). The adverse clinical signs were the reduced body weight and decreased food consumption in high-dose females, based on which a NOAEL of 1000 mg/m3 for systemic effects was established, and the reported nasal haemorrhaging in all dose groups. The data indicate that LC50 for monopropylene glycol exceeds 2200 mg/m3/6h.

The acute studies discussing potential respiratory effects of monopropylene glycol, are detailed and critiqued in full in the endpoint study summary for irritation / corrosion (IUCLID section 7.3).

Justification for selection of acute toxicity – inhalation endpoint

No key study available.

Justification for classification or non-classification

Based on the oral LD50 of 22000 mg/kg bw in rats, dermal LD50 > 2000 mg/kg bw in rabbits and inhalation LC50/2 h of > 317042 mg/m³in rabbits, classification of monopropylene glycol for acute oral and inhalation toxicity is not warranted in accordance with Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC).