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Description of key information

Repeated dose toxicity- oral: Two reliable studies were available (Two Klimisch 2 studies). The Huntsman study (1989) is performed with a method similar to OECD guideline 408 (GLP) and was selected as the key study for this endpoint. A NOAEL above 5000 mg/kg bw/d was derived, since the oral administration of propylene carbonate (5 days a week) over a period of 90 days did no exert an apparent toxicological effect that could be related to the test substance.
Repeated dose toxicity- dermal: No reliable studies were available for this route of exposure. However, no further testing is needed since reliable studies are available for repeated toxicity via the oral and inhalatory route (REACH regulation, Column 2 Adaptation, Annex VIII).
Repeated dose toxicity- inhalation: Two reliable studies were available for the inhalation route (Two Klimisch 2 studies). The Huntsman study (1991) was a subchronic test performed similar to OECD guideline 413 (GLP) in which rats were exposed for 93 days. Repeated exposure to propylene carbonate in rats at concentrations up to 1000 mg/m3 produced only signs of minimal irritation to the eyes in rats. A NOAEC (systemic effects) of 1000 mg/m³ air was derived for both male and female rats.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
5 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
1 000 mg/m³
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
100 mg/m³
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: oral

Pharmakon Research International (1989) investigated the oral toxicity of propylene carbonate after repeated exposure (90 days) in male/female Sprague-Dawley rats. Three groups of 30 rats were exposed for 5 days / week to respective doses of 1000, 3000 and 5000 mg/kg bw. The doses were determined in a 28 days dose-range finding test. A 4th group received deionized water and served as negative control. The control group and highest dose group were observed for 28 days post-dosing to determine the reversibility, persistance, or delayed occurance of toxic effects. Statistically significant differences were observed between the control and treated animals (primarily high dose) in the group body weights, daily body weight gains, daily food consumption determinations, absolute organ weights, relative organ to body weights and relative organ to brain weight data. Significant differences were also noted in the evaluated blood chemistry and hematology parameters.

However, none of the noted changes were dose-dependent, and there were no histomorphologic alterations attributed to the oral administration of the test substance of a 90 day period. Thus, the oral administration of propylene carbonate over a period of 90 days did not exert an apparent toxicological effect. The NOAEL was established as being greater than 5000 mg/kg bw. This study was designated as key study.

Repeated dose toxicity: dermal

A short-term (28 days dose-range finding) and sub-chronic (90 days) study are available for the oral route of exposure. In addition, reliable short-term (9 days) and sub-chronic (93 days) study are available for the inhalation route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2 adaptation, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure.

Repeated dose toxicity: inhalation

Bushy Run Research Center (1991) investigated inhalation toxicity of propylene carbonate (aerosol) after repeated whole body exposure for 93 days (6 hours per day, 5 days per week). Fischer 344 male and female rats were exposed to 0 (control), 100, 500 or 1000 mg/m³ (15 males and 15 females/dose). The doses were selected based on the 9 days range finding test by Bushy Run Research Center (1989). The only gross lesion believed to be exposure related was swollen periocular tissue. This lesion, presumed to be a result of irritation from the test substance, was observed in one animal per sex of the 500 mg/m³ group and two animals per sex of the 1000 mg/m³ group. Therefore, the NOAEC (systemic effects) was considered to be be 1000 mg/m³, the highest dose tested. This 93 days study is designated as key study.


Justification for classification or non-classification

The available data do not warrant for classification as STOT RE.