Propane-1,2-diol, propoxylated

Endpoint summary

Description of key information

No data on acute toxicity of ‘propane-1,2-diol, propoxylated’are available. 
For oral and dermal routes, measured data is available for all the components except Pentapropylene glycol.  None the components for which data are available show any indications of lethality in animal tests at doses of 2000 mg/kg bw.
For the inhalation route, measured data is available for all the components of ‘propane-1,2-diol, propoxylated’except Pentapropylene glycol.   None the components for which data are available show any indications of lethality in animal tests when tested at the highest attainable concentrations well in excess of the saturated vapour concentration (i.e implying exposure to aerosol).
None of the components of ‘propane-1,2-diol, propoxylated’ for which data are available show any evidence of acute toxicity by the oral, inhalation or dermal routes of exposure.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

No data on acute toxicity of ‘propane-1,2-diol, propoxylated’ are available. However, Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across.

Reliable acute toxicity data are available on structural analogues of ‘propane-1,2-diol, propoxylated’, mono-, di-, tri- and tetrapropylene glycol. All four substances are also the constituents of ‘propane-1,2-diol, propoxylated’ (a multi-constituent substance), usually present in the commercial product at following concentrations: 0-2% monopropylene glycol, 0 -50% dipropylene glycol, 10 -80% tripropylene glycol and 0 -90% tetrapropylene glycol. Therefore it is considered acceptable to derive the data on acute toxicity of ‘propane-1,2-diol, propoxylated’ by read-across from its constituents.

Oral route of exposure

Acute oral toxicity of monopropylene glycol is very low. Laug et al., 1939 reported LD50 value of 22000 mg/kg bw for rats administered monopropylene glycol by gavage. 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 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.

For dipropylene glycol, LD50 > 5000 mg/kg bw was obtained in a GLP-compliant study with rats performed in accordance with EPA OPP 81-1 (Acute Oral Toxicity) guideline (Cosmopolitan Safety Evaluation, Inc., 1995a). There were no mortalities. At one hour after dosing two males showed decreased locomotor activity and the remainder of the group (3 male, 5 female) were ataxic. Similar signs persisted at three hours. At five hours following dosing several rats (4 male, 1 female) also showed yellow perineal staining, By Day 1 all rats appeared normal and remained so through the duration of the study.

For tripropylene glycol, oral LD50 > 2000 mg/kg bw was established in the study with rats conducted in accordance with OECD guideline 401 and with GLP (MHW Japan, 1993a). No deaths occurred and no abnormal clinical signs or necropsy findings were noted.

In the acute oral toxicity study with tetrapropylene glycol (Dow Chemical Company, 1996), three male rats were administered 2000 mg/kg bw of the neat test material by single dose oral gavage. The animals were observed for 14 days and body weights and clinical signs were recorded. There were no mortalities. Two rats were incoordinated, and one was laterally recumbent and had decreased activity on the day of dosing. Two of the three rats had urine soiling on test days 1 and 2. All observations were resolved by test day 3, and the rats appeared normal through the duration of the study. Based on the results, oral LD50 was established to exceed 2000 mg/kg bw/day.

Dermal route of exposure

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.

For dipropylene glycol, one acute dermal toxicity study with rabbits, performed under GLP and in accordance with EPA OPP 81-2 (Acute Dermal Toxicity) was available for assessment (Cosmopolitan Safety Evaluation, Inc., 1995c). Animals were exposed via the dermal route to 5.01 g/kg bw under occlusion. No animals died. Cageside observation of the rabbits during the study did not reveal any overt signs of systemic pharmacologic or toxic effects. Approximately three quarters of an hour after removal of the wraps and cleaning the skin there was very slight irritation characterized by erythema at five sites. By day 2 the application sites were free of erythema and all sites appeared normal. On day 14 all sites appeared normal. There was no corrosive effect or evidence of injury in depth at any time. Based on the results of the test, the LD50 value in rats was determined to be > 5010 mg/kg bw.

For tripropylene glycol, one acute dermal toxicity study with rabbits, predating OECD guidelines and GLP, was available for assessment (Chemical Hygiene Fellowship, 1974). 16.0 mL of tripropylene glycol was administered to the intact skin of the trunk of male albino rabbits for 24 h under occlusive dressing. No animals died and no clinical signs were noted. The necropsy of survivors revealed mottled livers with prominent acini, congested spleens and pale and mottled kidneys. Based on the results of the test, the LD50 value in rabbits was determined to be > 16320 mg/kg bw (calculated based on the density of tripropylene glycol of 1.02 g/cm³).

In the acute dermal toxicity study with tetrapropylene glycol (Dow Chemical Company, 1996), a single dose of 2000 mg/kg bw of neat test substance was applied to the clipped trunks of 2 female rabbits and covered with an elastic rabbit jacket. The bandage was removed 24 hours post-application and the residual test matierial wiped off. Animals were observed for 14 days and clinical signs and body weights were recorded. There were no mortalities. There was erythema and/or oedema observed on test days 2 and 3 at the test sites of both rabbits. The irritation was resolved by test day 4. One rabbit had scaling of the test site from test day 4 through test day 8. The scaling was resolved by test day 11. Based on the results of the study, dermal LD50 was established to exceed 2000 mg/kg bw.

Inhalation route of exposure

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. For dipropylene glycol, one inhalation toxicity study with rats has been located, performed in accordance with EPA OPP 81-3 (Acute inhalation toxicity) guideline and under GLP (Cosmopolitan Safety Evaluation, Inc., 1995b). Five female and five male Sprague-Dawley rats were exposed to dipropylene glycol aerosol concentration of 2.34 mg/l (mean in the breathing zone) for 4 hours, which was the maximum attainable concentration of aerodynamic particles in the study. There were no deaths. The rats remained normal in appearance and behavior during exposure and during the subsequent 14-day observation period. Rats exposed to the test substance remained normal during the exposure period except for "wetting' of the fur due to deposition of test substance, and remained normal during the subsequent 14-day observation. An LC50 value of > 2.34 mg/l/4h was concluded based on the results of this study.

For tripropylene glycol, two inhalation toxicity studies with rats have been located, both predating OECD guidelines and GLP. In the most recent one, conducted by Chemical Hygiene Fellowship (1974) and chosen as a key study, six rats of unspecified strain and sex were exposed to saturated vapors of tripropylene glycol generated at room temperature, corresponding to concentration of 0.083 mg/l for 8 hours. There were no deaths, clinical signs or remarkable necropsy findings. An LC50 value of > 0.083 mg/L/8h was concluded based on the results of this study. Also in this case the value was below the cut-off limit for classification established by regulatory directives; however, as it corresponded to saturated vapour concentration, the classification was considered to be not warranted.

Acute inhalation toxicity of tetrapropylene glycol was studied by exposing 4 male rats to vapours of the test substance generated at room temperature (resulting concentration 0.17 mg/L). There were no mortalities or adverse effects noted. Using modified Haber's law (cⁿx t = const, where c is test substance concentration, t = exposure duration and n = 1 (default value for extrapolation from shorter to longer exposure duration times), the LC50 of > 0.0425 mg/l/4h is obtained for tetrapropylene glycol.

Based on these results, acute toxicity of ‘propane-1,2-diol, propoxylated’ is considered to be low by oral, dermal and inhalation routes of exposure.

The following information is taken into account for any hazard / risk assessment:

For oral and dermal routes, measured data is available for all the components except Pentapropylene glycol. None the components for which data are available show any indications of lethality in animal tests at doses of 2000 mg/kg bw.

For the inhalation route, measured data is available for all the components except Pentapropylene glycol. None the components for which data are available show any indications of lethality in animal tests when tested at the highest attainable concentrations well in excess of the saturated vapour concentration (i.e implying exposure to aerosol).

None of the components of this substance for which data are available show any evidence of acute toxicity by the oral, inhalation or dermal routes of exposure.

Justification for classification or non-classification

None of the components of ‘propane-1,2-diol, propoxylated’ for which data is available show any evidence of acute toxicity. Data on the components can be considered representative of the substance itself, which would lead to the conclusion that the multi-constituent substance of di, tri, tetra and pentapropylene glycol does not need to be classified for acute mammalian toxicity.Based on the results of the available studies with mono-, di-, tri- and tetrapropylene glycol, i. e. oral and dermal LD50 > 2000 mg/kg bw in rats and rabbits, respectively, classification of ‘propane-1,2-diol, propoxylated’ for acute oral and dermal toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. For acute inhalation toxicity, usually no mortalities or adverse signs of toxicity were noted at the highest attainable concentrations with the constituents of ‘propane-1,2-diol, propoxylated’, indicating that itsclassification for acute inhalation toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.