Butane-1,2-diol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 April – 16 June 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

Adopted 17th December 2001

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Butane-1,2-diol

EC Number:

209-527-2

EC Name:

Butane-1,2-diol

Cas Number:

584-03-2

Molecular formula:

C4H10O2

IUPAC Name:

butane-1,2-diol

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ORIENTBIO INC., Republic of Korea
- Age at study initiation: 8 weeks
- Weight at study initiation: 187.4-201.2 g
- Fasting period before study: animals were fasted overnight prior to administration
- Housing: One animal per cage, stainless wire mesh cage
- Diet : Pelleted rodent chow, ad libitum
- Water : Public tap water, ad libitum
- Acclimation period: quarantine 3 days and acclimation 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0-23.1
- Humidity (%): 43.7-53.2
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle : 200 mg/mL
- Lot/batch no.: DBA7001,15016

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: 2000 mg/kg was selected as the starting dose for this study based on the information supplied by the sponsor.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

1 (sighting study)
4 (main study)

Control animals:

other: Sprague-Dawley rats are commonly used in toxicity studies, having a large historical control database.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, general condition and clinical signs (type, severity, time of onset and recovery) at 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days (Day 1−Day 14). The body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes

Statistics:

Statistical analysis was not performed. Mean scores and values are presented.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths of animals at 2000 mg/kg throughout the study.

Clinical signs:

other: Abnormal gait was observed in all animals at 2000 mg/kg from 0.5 to 4 hours after dosing, and it disappeared at 6 hours after dosing.

Gross pathology:

No grossly visible findings were observed in any animal at 2000 mg/kg.

Any other information on results incl. tables

Individual clinical signs

-: No observable abnormality

+: Observable abnormality

Dose [mg/kg bw]	Animal ID	Clinical sign	Hours (Day 0) after dosing
			0.5	1	2	4	6
Step 1 (Sighting Study)
2000	2101	Abnormal gait	+	+	+	+	+
Step 2 (Main study)
2000	2201	Abnormal gait	+	+	+	+	+
2000	2202	Abnormal gait	+	+	+	+	+
2000	2203	Abnormal gait	+	+	+	+	+
2000	2204	Abnormal gait	+	+	+	+	+

Dose [mg/kg bw]	Animal ID	Clinical sign	Days after dosing
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
Step 1 (Sighting Study)
2000	2101		-	-	-	-	-	-	-	-	-	-	-	-	-	-
Step 2 (Main study)
2000	2201		-	-	-	-	-	-	-	-	-	-	-	-	-	-
2000	2202		-	-	-	-	-	-	-	-	-	-	-	-	-	-
2000	2203		-	-	-	-	-	-	-	-	-	-	-	-	-	-
2000	2204		-	-	-	-	-	-	-	-	-	-	-	-	-	-

Applicant's summary and conclusion

Interpretation of results:

other: CLP: not classified

Conclusions:

CLP: not classified