2,4,8,10-tetraoxa-3λ6,9λ6-dithiaspiro[5.5]undecane 3,3,9,9-tetraoxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(17th December 2001)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

2,4,8,10-tetraoxa-3λ⁶,9λ⁶-dithiaspiro[5.5]undecane-3,3,9,9-tetrone

EC Number:

859-869-7

Cas Number:

201419-80-9

Molecular formula:

C5H8O8S2

IUPAC Name:

2,4,8,10-tetraoxa-3λ⁶,9λ⁶-dithiaspiro[5.5]undecane-3,3,9,9-tetrone

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Test item: 2,4,8,10-Tetraoxa-3,9-dithiaspiro[5.5]undecane, 3,3,9,9-
tetraoxide
CAS: 201419-80-9
Lot number: AZ08AVL1
Active component: >99%
Appearance: crystalline solid, white
Expiration date: 21 September 2021
Storage conditions: room temperature, protected from humidity, well-closed
container

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Experimental Animals
Species and strain: Han:WIST rats
Source: TOXI COOP ZRT.
Cserkesz u. 90.
1103 Budapest, Hungary
Hygienic level at arrival: SPF
Hygienic level during the study: Good conventional
Justification of strain: The Wistar rats as a rodent is one of the standard species
of acute toxicity studies
Number of animals: 3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8 weeks old in first, second and third step
Body weight range
at starting (first step): 171 - 174 g
Body weight range
at starting (second step): 169 - 174 g
Body weight range
at starting (third step): 170 - 175 g
Acclimatization time: 5 days in first step, 6 days in second step and 7 days in
third step

Husbandry
Animal health: Only healthy animals were used for the study. Health
status was certified by the study director.
Room: 13/1
Housing: Group caging (3 animals/cage)
Cage type: Type III polypropylene/polycarbonate
Bedding: Certified laboratory bedding
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: above 10 air exchanges/hour by central air-condition system.
The temperature and relative humidity parameters were recorded daily during the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sunflower oil

Remarks:

Name: Helianthi annui oleum raffinatum Batch number: 8006332001 Produced by: Magilab Kft. Date of expiration: 30.09.2021

Details on oral exposure:

Formulation
All doses were formulated in the vehicle. Concentration of formulations was adjusted to
maintain a treatment volume of 10 mL/kg bw. The test item was applied in a concentration
of 0.5 and 5 mg/mL. Formulations were prepared just before the administration and were
stirred continuously during the treatment.

Justification of the doses
Starting dose was selected on the basis of the available information about the test item. The
LD50 value is between 5 and 50 mg/kg bw according to the safety data sheet. The acute toxic
class method was carried out involving a stepwise procedure with the use of 5 mg/kg bw as
the starting dose in three female rats. No animal died in first step, so further three female rats
were treated with the same dose. No animal died in second step, too, so further three female
rats were treated with the higher dose (50 mg/kg bw). All animals died in third step, so the test
was finished, because the stopping criteria of Annex 2a of OECD Guideline No. 423
(presented in Appendix VII) was met.

Doses:

5 mg/kg bw
50 mg/kg bw

No. of animals per sex per dose:

3 female rats / dose

Control animals:

no

Details on study design:

Starting dose was selected on the basis of the available information about the test item. The
LD50 value is between 5 and 50 mg/kg bw according to the safety data sheet. The acute toxic
class method was carried out involving a stepwise procedure with the use of 5 mg/kg bw as
the starting dose in three female rats. No animal died in first step, so further three female rats
were treated with the same dose. No animal died in second step, too, so further three female
rats were treated with the higher dose (50 mg/kg bw). All animals died in third step, so the test
was finished, because the stopping criteria of Annex 2a of OECD Guideline No. 423
(presented in Appendix VII) was met.
Animals were weighed, observed for lethality and toxic symptoms for 14 days after the
treatment. Gross pathological examination was carried out in animals died on the treatment
day, as well as 15th day after the treatment in surviving animals.

Statistics:

The method used is not intended to allow the calculation of a precise LD50 value.

Results and discussion

Preliminary study:

na

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

ca. 25 mg/kg bw

Based on:

test mat.

Mortality:

No lethality was noted at single oral dose of 5 mg/kg bw. ( 0/6 animals)
All female rats in step 3 (50 mg/kg bw) died on the treatment day 30 minutes after the treatment. (3/3 animals)

Clinical signs:

other: In group 1 treated with 5 mg/kg bw dose clinical sign of reaction comprised of decreased activity (6 cases of 57 observations), piloerection (6/57), tremor (4/57) and tonic convulsion (1/57). Decreased activity (score -1) and piloerection (score +1) occur

Gross pathology:

Six animals treated with 5 mg/kg bw dose survived until the scheduled necropsy on Day 15.
All of three rats treated with 50 mg/kg bw dose of the test item were necropsied as dead
animals on the treatment day.
External necropsy findings as froth around the mouth was detected in all animals of group 3
(50 mg/kg bw) and blood around the mouth was recorded in animal No.: 9712 of same
group. No changes were found related to the effect of the test item during the macroscopic
examination of 5 mg/kg bw dose.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Remarks:

H300 CLP classification Acute tox category 2: H300

Conclusions:

CLP classification Acute tox category 2: H300 fatali if swallowed. The LD50 cut- off value is 25 mg/kg bw.
The method used is not intended to allow the calculation of a precise LD50 value.
The test item was ranked into classes of Globally Harmonized Classification System (GHS)
described in the OECD Guideline No. 423 as below:

Executive summary:

ACUTE ORAL TOXICITY STUDY(ACUTE TOXIC CLASS METHOD) OF TEST ITEM 2,4,8,10-TETRAOXA-3,9-DITHIASPIRO[5.5]UNDECANE, 3,3,9,9- TETRAOXIDE HAS BEEN PERFORMED IN WISTAR RATS ACCORDING TO OECD GUIDELINE 423.

Starting dose was selected on the basis of the available information about the test item. The
LD50value is between 5 and 50 mg/kg bw according to the safety data sheet. The acute toxic
class method was carried out involving a stepwise procedure with the use of 5 mg/kg bw as
the starting dose in three female rats. No animal died in first step, so further three female rats
were treated with the same dose. No animal died in second step, too, so further three female
rats were treated with the higher dose (50 mg/kg bw). All animals died in third step, so the test
was finished, because the stopping criteria of Annex 2a of OECD Guideline No. 423
(presented in Appendix VII) was met.
Animals were weighed, observed for lethality and toxic symptoms for 14 days after the
treatment. Gross pathological examination was carried out in animals died on the treatment
day, as well as 15th day after the treatment in surviving animals.
Lethality, Clinical symptoms and Body weight:
No lethality was noted at single oral dose of 5 mg/kg bw.
All female rats in step 3 (50 mg/kg bw) died on the treatment day 30 minutes after the
treatment.
In first step, CNS - and emotion symptoms (decreased activity, tremor, tonic convulsion)
and a disturbance of the autonomic functions (piloerection) were observed in animals on the
treatment day between 1 and 2 hours after the treatment.
In second step, CNS - and emotion symptoms (decreased activity, tremor, tonic convulsion,
clonic convulsion, closed eyes) and a disturbance of the autonomic functions (piloerection)
were observed in animals on the treatment day between 30 minutes and 2 hours after the
treatment.
In third step, CNS - and emotion symptoms (tonic- and clonic convulsion) and a disturbance
of the autonomic functions (dyspnoea) were observed in animals on the treatment day 30
minutes after the treatment. Besides, an indirect effect as frothy salivation was detected in
animals, which was consequence of convulsions.
The body weight development was undisturbed in all surviving animals.
Gross pathology:
All organs of the animals treated with 5 and 50 mg/kg bw proved to be free of treatment
related gross pathological changes, although it is necessary to note, that the external change
as frothy/bloody circumoral region was observed in dead animals.

Evaluation:
The method used is not intended to allow the calculation of a precise LD50value.
The test item was ranked into classes of Globally Harmonized Classification System (GHS)
described in the OECD Guideline No. 423 as below:
Table 1:

Dose (mg/kg bw)	Mortality (dead/treated)	LD50 (mg/kg bw)	GHS category
5	0/6	between 5 and 50	2
50	3/3

The LD50cut- off value is 25 mg/kg bw.