1,2-Propanediol, 3-(cyclohexyloxy)-

Acute Toxicity: oral

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

Test material information

Constituent 1

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