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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

9 October 2017

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

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,
in well-closed container
pH (measured by
Toxi-Coop Zrt.): 5-6

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Han:WIST rats

Sex:

female

Details on test animals or test system and environmental conditions:

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

Type of coverage:

semiocclusive

Duration of exposure:

The test item was applied in undiluted form after pulverization and left in contact with the
skin for 24 hours, followed by a 14-day observation period.

Doses:

200 mg/kg bw , 1000 mg/kg bw , 2000 mg/kg bw

No. of animals per sex per dose:

1 female animal /200 mg/kg bw ,
3 female animals / 1000 mg/kg bw ,
1 female animals /2000 mg/kg bw

Details on study design:

At first, the range-finding study was performed. The starting dose was 200 mg/kg bw using
one animal. This animal did not die. The other doses were 1000 and 2000 mg/kg bw. The
animal of 1000 mg/kg bw did not die, too. The animal of 2000 mg/kg bw died. Therefore,
1000 mg/kg bw dose was used in main study

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 000 mg/kg bw

Based on:

test mat.

Mortality:

Inspection for signs of morbidity and mortality were made twice daily at the beginning and
end of the working day.
The initial dose was 200 mg/kg bw in the range-finding study. No mortality occurred after
the 24-hour dermal exposure to 2,4,8,10-Tetraoxa-3,9-dithiaspiro[5.5]undecane, 3,3,9,9-
tetraoxide in female rats treated with 200 and 1000 mg/kg bw dose of the range-finding
study. The animal treated with 2000 mg/kg bw dose died on the Day 1 in the range-finding
study.
The dose was 1000 mg/kg bw in main study. Both animals died. Animal No.: 1803 died on
Day 4 and animal No.: 1808 died on Day 2. The deaths seemed to be the consequence of
systemic toxic effects of the test item

Clinical signs:

convulsions

observations of tremors

Body weight:

lower than 10% body weight loss

Remarks:

The body weight of animal treated with 200 mg/kg bw corresponded to its species and age throughout the study. Body weight loss was observed in surviving animal (No.: 1801) of range-finding study between Day 0 and Day 7. Although, the body weight loss was below 10 % (approx. 6.1 %) and the body weight of this animal exceed the original body weight by the end of study, it can be evaluated as a toxic effect of the test item considering systemic clinical symptoms, too

Gross pathology:

One rat (No.: 1802) treated with 2000 mg/kg body weight of the test item spontaneously
died and were necropsied on Day 1. Two rats (No.: 1808, 1803) treated with 1000 mg/kg
body weight of the test item spontaneously died and were necropsied on Day 2 and on Day
4, respectively. One animal (No.: 1801) of the 1000 mg/kg body weight dose group and the
animal No.: 1800 dosed with 200 mg/kg body weight survived until the scheduled necropsy
on Day 15.
Internal necropsy findings were detected in range-finding study at 2000mg/kg bw and
external and internal changes were found in main study at 1000 mg/kg bw dose.
Range-finding study:
2000 mg/kg bw:
The colour of the lungs and liver were darker colour.
Main study:
1000 mg/kg bw:
Bloody and frothy discharge around the nose and mouth as external findings was observed
in animal No.: 1808. Attenuated mucous membrane in the stomach, haemorrhaged fundus,
bloody content in the intestines and autolysed organs were detected in both animals (No.:
1803, 1808). Granular cardia with erosion was recorded in animal No.: 1803. Intestines were
full of gas in animal No.: 1808 and marbled lungs was found in the same animal.

Other findings:

The animal treated with 2000 mg/kg bw died during the range-finding study. Two animals
treated with 1000 mg/kg bw died in the main study. No death occurred in the 200 mg/kg bw
dose.
The observed clinical signs in 1000 and 2000 mg/kg bw dose were related to the systemic
toxic effect of the test item.
There were no local clinical signs in all doses.
There was a change related to the toxic effect of the test item found in body weight and body
weight gain in surviving animal of 1000 mg/kg body weight dose on first week.
The pathological alterations observed in the non-surviving animals treated with 1000 mg/kg
bw or 2000 mg/kg bw were related to the effect of the test item, except autolysis. Autolysis
is a normal process after death. The external findings were consequence of indirect effect of
the test item, these were connected with convulsion.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

H311Toxic in contact with skin.

Conclusions:

Under the experimental conditions applied, the GHS category of the test item 2,4,8,10-
Tetraoxa-3,9-dithiaspiro[5.5]undecane, 3,3,9,9-tetraoxide is 3 in female Han:WIST rats
and the health hazard is H311: Toxic in contact with skin.

Executive summary:

An acute dermal toxicity study was performed with test item 2,4,8,10-Tetraoxa-3,9-
dithiaspiro[5.5]undecane, 3,3,9,9-tetraoxide in Han:WIST rats.
At first, the range-finding study was performed. The starting dose was 200 mg/kg bw using
one animal. This animal did not die. The other doses were 1000 and 2000 mg/kg bw. The
animal of 1000 mg/kg bw did not die, too. The animal of 2000 mg/kg bw died. Therefore,
1000 mg/kg bw dose was used in main study.
The test item was applied in undiluted form after pulverization and left in contact with the
skin for 24 hours, followed by a 14-day observation period.
Results of the main study:
Both animals died on Day 2 and on Day 4, respectively.
Systemic clinical symptoms as CNS (central nervous system) - and emotion symptoms
(decreased activity, tremor, clonic convulsion), disturbances of coordination (abnormal gait,
incoordination) and a disturbance of autonomic functions (piloerection) were observed
between Day 1 and Day 3.
The test item did not cause any dermal irritation symptom.
The body weight development could not be evaluated because of mortalities.
Autopsy revealed treatment related external alterations as bloody and frothy discharge
around the nose and mouth and internal alterations in the stomach (attenuated mucous
membrane, haemorrhage, granular cardia, erosion in the cardia), in the intestines (bloody
content and/or full of gas) and in the lungs (marbled) in died animals.
Under the experimental conditions applied, the GHS category of the test item 2,4,8,10-
Tetraoxa-3,9-dithiaspiro[5.5]undecane, 3,3,9,9-tetraoxide is 3 in female Han:WIST rats
and the health hazard is H311: Toxic in contact with skin.