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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 Jul 2013 - 02 Aug 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(hexyloxy)propane-1,2-diol
EC Number:
600-386-6
Cas Number:
10305-38-1
Molecular formula:
C9H20O3
IUPAC Name:
3-(hexyloxy)propane-1,2-diol
Details on test material:
- Name of test material (as cited in study report): SDX-3255
- Physical state: liquid
- Analytical purity: 99.4%
- Lot/batch No.: 03053
- Expiration date of the lot/batch: May 2014
- Storage condition of test material: room temperature (17.2 to 21.7 °C) in tight, light-resistant containers
- Other: specific gravity: 0.972

Test animals

Species:
rat
Strain:
other: Sprague-Dawley (Crl:CD(SD)), SPF
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Orientbio INC., Korea
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 170.6 - 227.3 g
- 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
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 - 22.3
- Humidity (%): 43.0 - 66.3
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 02 Jul 2013 To: 17 Jul - 02 Aug 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 60 and 400 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg bw

- Lot/batch no.: MKBG0329V and MKBH4894V


MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

DOSAGE PREPARATION: a small amount of corn oil was added and mixed using a vortex mixer until dissolved. Additional vehicle
was gradually added to yield the desired concentration

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the starting dose level for this study was selected at 300 mg/kg (step 1 and 2) because there was no available information on the toxicity of the test substance. The following sequential dosing steps (step 3 and 4) were based on the mortality and clinical observations of animals three to four days after the previous dose level.
Doses:
300 mg/kg bw (step 1 and step 2) and 2000 mg/kg bw (step 3 and 4)
No. of animals per sex per dose:
6 (3 per step)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations - 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). Weighing - prior to dosing (day 0), on day 1, 3, and 7 and on the day pf necropsy, day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and histopathology (in the case of gross findings)
Statistics:
Statistical analysis was not performed. Mean scores and values are presented.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off according to OECD TG 423
Mortality:
300 mg/kg bw: 0/6 animals died
2000 mg/kg bw: 2/6 animals died (at 6 h and on day 1 post-dose)
Clinical signs:
300 mg/kg bw: no clinical signs of toxicity were observed in the animals up to the end of the 14-d observation period.
2000 mg/kg bw: in the two animals which died, irregular respiration, lacrimation, loss of locomotor activity, prone position and/or decreased respiration were evident from 30 min to 6 h after dosing. These animals were then found dead in a state of lacrimation and/or prone position at 6 h and on day 1 after dosing respectively. In the four surviving animals, irregular respiration, abnormal gait and/or tremor were evident from 30 min to 6 h after dosing. Decrease of fecal volume, soiled perineal region, no stool and/or irregular respiration were evident on day 1 after dosing. These animals then returned to a normal state on day 2 after dosing.
Body weight:
300 mg/kg bw: no effect on body weight was noted in the animals during the study.
2000 mg/kg bw: a tendency to suppress body weight gain and/or a decrease in body weight was evident in two surviving animals at 2000 mg/kg bw on day 1 after dosing. These animals then returned to normal on day 3 after dosing.
Gross pathology:
No grossly visible evidence of morphologic abnormalities was evident in the animals dosed with 300 and 2000 mg/kg bw of the test substance respectively.

Applicant's summary and conclusion

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