Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study written in Japanese with an english abstract and a handwritten translation. Source of the article was not identified. While there was an overall lack of detail presented, a general determination of how the study was conducted could be determined. Conflicting results were identified in the abstract and the translation. Some of the translation was illegible.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1972

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Rats were administered the test substance subcutaneously over a 30 day period and observed for toxicity by evaluating general behavior, food and water intake, body weight change and death, urine tests, blood tests, blood biochemistry, weights of internal organs and pathological examinations.
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): propylene carbonate
- Stability under test conditions: Forms a stable solution in water
- Other: Colorless (transparent)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Approximately 20 g (mice); 180 g (rats)
- Diet: Properly fed for 7 days. During the experiment, food was provided ad libitum.
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-27 C

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
physiological saline
Duration of treatment / exposure:
1 month
Frequency of treatment:
Daily, 6 days a week
Doses / concentrations
Remarks:
Doses / Concentrations:
3.5%, 10.5%, and 17.5% in physiological saline
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes- General behavior
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Once per week

FOOD CONSUMPTION:
- Food consumption for each animal determined once a week.

WATER CONSUMPTION: Yes
- Time schedule for examinations: Weekly

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the experiment
- Parameters examined: Blood taken from the tail was analyzed for red blood cell number, hemoglobin, hematocrit, white blood cell number and white blood cell percentage and these values were compared with the values obtained from the control group. Blood was then taken from the heart and analyzed for transaminase, alkaliphosphatase, blood sugar, and albumin.

URINALYSIS: Yes
- Time schedule for collection of urine: Before animals were dissected
- Metabolism cages used for collection of urine: A urine sampling box was used
- Parameters examined: pH, sugar test, albumin test, urobilinogent (?)
Sacrifice and pathology:
GROSS PATHOLOGY: Yes. The brain, pituitary body, main gland, breast gland, heart, lung, kidney, adrenal bodies, testicle, and testicle-related organs were weighed. The rest of internal organs were examined pathologically, including lower jaw gland, stomach and intestine member lymph nodes.

HISTOPATHOLOGY: Yes. Each organ was treated with formalin, then dyed with hematoxylineosin before tissue examination.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No change in movement or posture were detected in any group.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were conflicting results reported. According to the summary found in the published article, there was no obvious difference in weight gain as compared to the controls. According to the handwritten translation, significant change in weight was observed.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
According to the summary found in the published article, there was no obvious difference in food consumption as compared to the controls.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Description (incidence and severity):
According to the summary found in the published article, there was no obvious difference in water consumption as compared to the controls.
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
Conflicting results were reported for a few parameters: the translation says large changes were observed for red blood cell number, hemaglobulin, and hematocrit values while the summary says no obvious differences in plasma analysis and hematology were observed as compared to controls. For transaminase, even though both GOT and GPT of rats showed a little higher than the values of humans, the correlation with dosage could not be established. No significant change was observed for alkaline phosphatase. Blood sugar and blood albumin showed no change from the control group.
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Description (incidence and severity):
Per the abstract, there was no obvious difference in urinalysis as compared to the controls with the exception of volume (differences in the 3-5 mL range) and pH (differences in the range of 5-7).
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
There was no obvious difference in organ weights as compared to the controls.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
A small number in each group showed bleeding in the lung, while no significant change was observed in other organs.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
In general, no change was observed for brain, lung, heart, kidney, adrenal bodies, stomach, testicle, penis, intestine, lymph joint and main gland. However, for the 17.5% group, congestion of blood was observed in the spleen, while in the lungs of the 10.5% group, cell regeneration seemed to occur. Furthermore, in 17.5% group, lymph cells were inflitration (moderate), with an increase in composite tissue. For the 10.5% and 17.5% groups, the applied area showed hyperkeratosis, lymph cells infiltration (moderate), with an increase in composite tissue. Basal cells, hyperkratosis, and keratinization was observed histologically at the cite of application in a few cases.
Histopathological findings: neoplastic:
not examined
Other effects:
not specified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No obvious signs of systemic toxicity were observed after 30 days of subcutaneous toxicity, however an increase in basal cells, hyperkratosis, and keratinization was observed histologically in a few cases.