1,4-dithiane-2,5-diol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-07-13 to 2004-08-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 December, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,4-dithiane-2,5-diol

EC Number:

254-751-6

EC Name:

1,4-dithiane-2,5-diol

Cas Number:

40018-26-6

Molecular formula:

C4H8O2S2

IUPAC Name:

1,4-dithiane-2,5-diol

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

other: Crl; CD® (SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 186.67 ± 20%
- Fasting period before study: overnight
- Housing: groups of three in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum, except the overnight fast before the administration and 3 to 4 h after dosing; Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK
- Water (e.g. ad libitum): ad libitum, except the overnight fast before the administration and 3 to 4 h after dosing
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

BP

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL; 5 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As recommended by OECD guideline

Doses:

one group with 300 mg/kg bw and 2 groups with 50 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to dosing and seven and fourteen days after treatment or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality

Results and discussion

Preliminary study:

Initially, animals were treated with 300 mg/kg bw. Since all animals died within the first 4 h after administration the dose was reduced to 50 mg/kg bw.

Effect levels

Key result

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 50 - <= 200 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No premature deaths were observed at a dose level of 50 mg/kg bw

Mortality:

All animals treated at a dose level of 300 mg/kg bw were found dead four hours after dosing. There were no deaths noted in animals treated at a dose level of 50 mg/kg bw.

Clinical signs:

other: Signs of systemic toxicity noted during the study were hunched posture, lethargy, ataxia and diarrhoea in the 300 mg/kg bw group. The animals treated with 50 mg/kg bw exhibited no clinical signs of toxicity.

Gross pathology:

No abnormalties were detected.

Any other information on results incl. tables

Table 1: Mortality data

Dose level mg/kg	Sex	Number of animals treated	Deaths during day of dosing (hours)				Deaths during period after dosing (days)								Deaths
			½	1	2	4	1	2	3	4	5	6	7	8-14
300	female	3	0	0	0	3	-	-	-	-	-	-	-	-	3/3
50	female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
	female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In the present study conducted according to OECD guideline 423 (adopted 17 December 2001), GLP, three female Sprague-Dawley rats were administered 300 mg/kg bw of the test substance by oral gavage and observed for 14 days. All animals of this dosage group died within 4h after administration, thus, the dose was reduced to 50 mg/kg bw. No clinical signs of intoxication or premature death were observed in the 50 mg/kg bw dosage group. Based on these results and according to Regulation (EC) 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) the test substance needs to be classified into Category 3 and labeled with "Toxic if swallowed" with respect to acute oral toxicity.