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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 Aug 2010 - 02 Sep 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted in 1981
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(cyclohexyloxy)propane-1,2-diol
EC Number:
805-622-3
Cas Number:
10305-41-6
Molecular formula:
C9H18O3
IUPAC Name:
3-(cyclohexyloxy)propane-1,2-diol
Constituent 2
Reference substance name:
3-cyclohexyloxy-1,2-propanediol
IUPAC Name:
3-cyclohexyloxy-1,2-propanediol
Details on test material:
- Name of test material (as cited in study report): SDX-3012
- Physical state: liquid
- Analytical purity: > 99%
- Lot/batch No.: 019X9
- Expiration date of the lot/batch: Oct.2010
- Storage condition of test material: room temperature (20.6-21.2 °C), nitrogen substitution
- Other: flash point: 159 °C

Test animals

Species:
rat
Strain:
other: Sprague-Dawley (Crl:CD(SD)), SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Orientbio INC., Korea
- Age at study initiation: 6 weeks old (m/f)
- Weight at study initiation: 160.9-181.0 g (males) and 122.3- 138.3 g (females)
- Fasting period before study: overnight, approximately 16 hours prior to dosing
- Housing: stainless wire mesh cages, 260W x 350D x 210H (mm). 1 animal per cage during the study
- Diet: pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C). The diet was placed in feeders and provided ad libitum
- Water: public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum via a polycarbonate bottle (500 mL) in an quarantine room and by an automatic watering system in the animal room
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS- Temperature (°C): 20.2-23.0
- Humidity (%): 39.4-57.0
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12-07-2010 To: 02-09-2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): a small amount of water was added to the weighed test substance and mixed using a vortex mixer until dissolved. Additional vehicle was gradually added to yield the desired concentration ( 100, 150, and 200 mg/mL).
- Lot/batch no. : GBA0001

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
1000, 1500 and 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to dosing (day 0), 30 min after dosing, 1 h, 2 h, 4 h, 6h and then once daily thereafter for 14 days (days 1 to 14)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights and histopathology (in the case of gross findings)
Statistics:
Statistical analysis was performed using SAS Program (version 9.1.3, SAS Institute Inc., U.S.A). Body weights were analysed utilising Bartlett's test for homogeneity (significance level: 0.05). One-way analysis of variance (ANOVA) was employed on homogenous data; then, if significant, Dunnett's test was applied for multiple comparisons (significance level: 0.05 and 0.01, two-tailed). Kruskal-Wallis test was employed for heterogeneous data; then if significant, Steel test was applied for multiple comparisons (significance level: 0.05 and 0.01, two-tailed).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Glaucosuria in one male and one female, hematuria and/or decrease of fecal volume in two females were evident on day 1 in the animals dosed with 1000 mg kg bw of the test substance, but these signs returned to normal on day 2 after dosing.
Hematuria and/or glaucosuria were also evident in two males and four females on day 1 in the 1500 and 2000 mg/kg bw dose groups, respectively. These signs in males in the 1500 mg/kg bw dose group returned to normal on day 1 after dosing. Furthermore, males in the 2000 mg/kg bw dose groups and females in the 1500 mg/kg bw and 2000 mg/kg bw dose groups returned to normal on day 2 after dosing.
Abnormal gait and/or decreased respiration in all animals and prone position, decrease in locomotor activty and/or loss of locomotor activity in two males and two females were evident on the day of dosing in the 1500 and 2000 mg/kg bw dose groups.
Body weight:
Slight decreases in body weight were evident in two females in the 1000 mg/kg bw dose group on day 1 after dosing, but they returned to normal on day 3. Overall, no statistically significant effect on body weight was noted between the control and dosed groups.
Gross pathology:
Necropsy revealed no substance-related findings.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified

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