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Administrative data

Description of key information

Acute toxicity of tripropylene glycol is low. In rats, LD50 value by oral route is >2000 mg/kg bw. In the acute dermal toxicity study with rabbits, LD50 was > 16320 mg/kg bw.  In the acute inhalation toxicity study with rats, LC50 value was > 0.083 mg/L/8h, which corresponded to saturated vapor concentration of tripropylene glycol at ambient temperature and pressure. 

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 conducted in accordance with OECD guideline 401 and GLP by MHW Japan. The original report was requested, but could not be recovered, only the abstract in English was received. However, the study was considered acceptable by OECD SIDS.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
water
Doses:
500, 1000 and 2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no mortalities.
Clinical signs:
No abnormal clinical signs were observed.
Body weight:
Body weight changes of each treated group were virtually the same as those of the control group.
Gross pathology:
No remarkable changes were found in any of the animals necropsied.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study predates OECD guidelines and GLP, minor restrictions in design and reporting, but otherwise adequate for assessment.
Principles of method if other than guideline:
Rats were exposed to saturated vapor of tripropylene glycol generated at room temperature for 8 h.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
The nonfasted animals were maintained on appropriate Rockland diets and water ad libitum except during period of manipulation or confinement.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
Concentrated vapor was generated in a gas washing bottle by passing dried air at 2.5 l/min through a fritted glass disc immersed to a depth of at least 1-1/2 inches in the chemical which is delivered to rats in a 9-liter glass exposure chamber. Mean vapor concentration is calculated from the loss in weight of the liquid or estimated from the vapor pressure at the actual temperature of the chemical during aerosol.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
0.083 mg/l
No. of animals per sex per dose:
6 animals/dose, sex unspecified
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LC50 was calculated by the moving average method based on a 14-day observation period.
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 0.083 mg/L air
Exp. duration:
8 h
Mortality:
There were no mortalities.
Clinical signs:
No clinical signs were observed.
Body weight:
Weight change: 50-80 g
Gross pathology:
No remarkable findings were observed.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
83 mg/m³

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:
other: Study predates OECD guidelines and GLP, minor restrictions in design and reporting, but otherwise adequate for assessment.
Principles of method if other than guideline:
Neat tripropylene glycol was applied to the intact skin of the trunk of male albino rabbits for 24 h under occlusive dressing.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
The nonfasted animals were maintained on appropriate Rockland diets and water ad libitum except during period of manipulation or confinement. Rabbits were 3 to 5 months of age.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test substance was applied undiluted under impervious sheeting on the clipped intact skin of the trunk. Animals were immobilized for 24 hour contact period.
Duration of exposure:
24 h
Doses:
16.0 ml/kg bw
No. of animals per sex per dose:
5 males/dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 was calculated by the moving average method based on a 14-day observation period.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 16 320 mg/kg bw
Remarks on result:
other: Value in mg/kg bw was calculated based on the LD50 > 16 mL/kg bw and the relative density of the substance of 1.02.
Mortality:
There were no mortalities.
Clinical signs:
There were no clinical signs.
Body weight:
Weight change: -45, 75, 140, 145 and 345 g
Gross pathology:
Livers mottled and acini prominent, spleens congested, kidneys pale and mottled.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
16 320 mg/kg bw

Additional information

Two acute oral toxicity studies with rats are available for assessment, both leading to the same conclusion. The more recent study, conducted in accordance with OECD guideline 401 and with GLP, was conducted by the Ministry of Health and Welfare of Japan (MHW, 1993) and only the abstract in English could be recovered, despite the study was requested. Nevertheless, as the study was conducted within the HPV/SIDS framework and considered to be reliable by OECD SIDS (1994), it was selected as a key study. In this study, 5 male and 5 female rats were administered tripropylene glycol at dose levels 500, 1000 and 2000 mg/kg bw. No deaths occurred and no abnormal clinical signs or necropsy findings were noted. The LD50 was established to be over 2000 mg/kg bw/day.The supporting study (Chemical Hygiene Fellowship, 1974) confirmed this result, with LD50 = 11.5 g/kg bw (calculated based on the LD 50 of 11.3 mL/kg bw and density of tripropylene glycol of 1.02 g/cm3).

 Two inhalation toxicity studies with rats have been located, both predating OECD guidelines and GLP. The earlier one, conducted by Dow Chemical Company (1967) used a non-standard method (Lc(t) 50 determination), exposing rats of vapors to tripropylene glycol generated at ca. 200 ˚C, and therefore was found to be unacceptable for assessment. In the most recent one, conducted by Chemical Hygiene Fellowship (1974), 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.

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).

Justification for classification or non-classification

Based on the oral LD50 value of > 2000 mg/kg bw and dermal LD50 value of >16320 mg/kg bw, classification for acute oral and dermal toxicity is not warranted in accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. For acute inhalation toxicity, the LC50 value of >0.083 mg/L/8 h was obtained, which is below the cut-off value of 20 mg/L/4 h,established for classification of vapors. However, as this concentration corresponded to the saturated vapor concentration and based on the absence of mortality and of any clinical signs of toxicity in the study, the classification of tripropylene glycol for acute inhalation toxicity is not warranted in accordance to Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.