Di-tert-dodecyl disulphide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 December 2015 -- 02 February 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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 (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Di-tert-dodecyl disulphide

EC Number:

248-468-7

EC Name:

Di-tert-dodecyl disulphide

Cas Number:

27458-90-8

Molecular formula:

C22H46S2 to C24H50S2

IUPAC Name:

2-ethyl-5,6,6-trimethyl-1-[(3,5,6,6-tetramethylheptyl)disulfanyl]heptane; 2-ethyl-5,6,6-trimethyl-1-[(5,6,6-trimethylheptyl)disulfanyl]heptane; 3-ethyl-1-[(2-ethyl-5,6,6-trimethylheptyl)disulfanyl]-5,6,6-trimethylheptane

Test material form:

other: light yellow liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age/Weight: on the day of treatment, the females were 8 weeks old and had a mean body weight of 216 g (range: 200 g to 230 g).
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: for a period of 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 8 to 15 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 12 January 2016 to 02 February 2016

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: in the absence of recommendation from the Sponsor, the solubility assay first started at the concentration of 200 mg/mL, and the first choice vehicle was drinking water treated by reverse osmosis.
As unsatisfactory solubility of the test item was obtained in this vehicle (i.e. heterogeneous emulsion at the concentration of 200 mg/mL was obtained), another vehicle was chosen from the following organic solvents (in order of preference): 0.5% methylcellulose aqueous solution and corn oil.
A heterogeneous emulsion was observed with 0.5% methylcellulose aqueous solution, and corn oil was chosen since it allowed obtaining a homogeneous emulsion at the concentration of 200 mg/mL.

- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION (if unusual): fresh dose formulations were prepared by the CiToxLAB France Pharmacy on the day of each administration.
The dose formulations were stored at room temperature and delivered to the study room in glass flasks.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 (2x3 females per treatment step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: At 2000 mg/kg, piloerection together with dyspnea were observed on Day 1, 1 to 3 hours after treatment in 2/6 females. These signs persisted 4 hours after treatment and were also observed in a third female at the 4 hours time-point only. No clinical signs

Gross pathology:

No macroscopic findings were observed at the end of treatment period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Under the experimental conditions of this study, the oral LD0 of the test item was higher than 2000 mg/kg in rats.

Executive summary:

The potential acute toxicity of DI-TERT-DODECYL DISULPHIDE was evaluated following a single oral administration (gavage) to rats. This study was conducted in compliance with OECD Guideline No. 423 and the principles of Good Laboratory Practices. The test item was administered once by oral route (gavage) to two groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in corn oil. Based on the expected low toxicity of the test item data, the starting dose-level of 2000 mg/kg was chosen. After the first assay, as no mortality was observed, the results were confirmed in other females treated at the same dose-level. Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15. On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. No tissues were preserved.

No unscheduled deaths occurred during the study. At 2000 mg/kg, piloerection together with dyspnea were observed on Day 1, in the first 4 hours after treatment in 3/6 females. No clinical signs were noted in the remaining 3/6 females treated at the same dose-level. Compared to historical control data, body weight change and body weight of the animals were considered to be unaffected by the test item treatment. At the end of the observation period, there were no macroscopic findings at necropsy. Under the experimental conditions of this study, the oral LD0 of DI-TERT-DODECYL DISULPHIDE was higher than 2000 mg/kg in rats.