Registration Dossier

Administrative data

Description of key information

Acute toxicity after single oral application was tested in female rats, which received 15,000 mg/kg bw. No animal died or showed clinical symptoms/macroscopic anomalies. The necropsy did not reveal any effect. The LD50 value for acute oral toxicity was considered to be greater than 15,000 mg/kg bw. Due to the findings described above (LD50 oral in rats greater than 15,000 mg/kg bw) dioctadecyl disulphide does not have to be classified as acute orally toxic.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Nov - Dec 1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable; study equivalent to OECD Guideline 401 with minor deviation
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
only females tested
GLP compliance:
no
Remarks:
performed before GLP guidelines
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Hoechst AG Kastengrund - SPF breed
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG Kastengrund - SPF breed
- Weight at study initiation: 93 - 107g
- Fasting period before study: 16 hours before and 2 hours after application
- Housing: in plastic cages, softwood pellets
- Diet (e.g. ad libitum): Altromin 1324 (Altrogge GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): Tap water ad libitum

Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
- concentration in vehicle: 25 % (w/v)
Doses:
15000 mg/kg bw
No. of animals per sex per dose:
10 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations after application / Weighing once weekly
- Necropsy of survivors performed: yes
Statistics:
no
Preliminary study:
An acute oral toxicity study with female rats was performed in 1964. The LD(50) dreived was 15000 mg/kg bw.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Remarks on result:
other: no effects
Mortality:
no deaths occured
Clinical signs:
no symptoms
Body weight:
normal body weight gain
Gross pathology:
no anomalies
Other findings:
no
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of Hostanox SE 10 (LD50) was greater than 15000 mg per kg body weight. Based on the result of this study the test item is not subject for labelling and classification requirements according to regulatory requirements.
Executive summary:

Hostanox SE 10 was tested for its acute toxic properties in female rat via oral route. No animal died or showed clinical symptoms/macroscopic anomalies after application of 15000 mg/kg bw.

Therefore, the median lethal dose of Hostanox SE 10 (LD50) was greater than 15000 mg per kg body weight. Based on the result of this study the test item is not subject for labelling and classification requirements according to regulatory requirements.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
15 000 mg/kg bw
Quality of whole database:
2 (reliable with restrictions)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Based on the results of an oral toxicity study the LD50 value for acute oral toxicity was considered to be greater than 15,000 mg/kg bw.

In accordance with REACH “Column 2” in Annex VIII there is sufficient weight of evidence from several independent sources of information leading to the conclusion that Dioctadecyl disulphide does not exert systemic toxic effects after acute inhalation exposure and thus does not have to be classified, because
- the LD50 value for acute oral toxicity of Dioctadecyl disulphide is greater 15,000 mg/kg bw,
- Dioctadecyl disulphide does not have to be classified as skin irritating,
- inhalation to consumer is very unlikely to occur, since the substance is embedded in polymeric matrices for consumer applications and
- occupational health surveillance data obtained from workers of the production site do not give any hint concerning adverse systemic effects and effects on the respiratory tract (for expert statement please refer to Chapter 7.10.1).
Therefore, it is concluded that testing of acute inhalation toxicity of Dioctadecyl disulphide salt is not scientifically necessary.

It can reasonably be deduced that Dioctadecyl disulphide does not exert systemic toxic effects after dermal application and thus does not have to be classified, because this substance did not cause lethal effects after administration of a single oral dose of up to 15,000 mg/kg bw in rats. Furthermore the substance does not have to be classified as skin irritating. Due to the combination of its polar character (Sulfur bridge in the center of the molecule) and the long extent of the alkyl chain it is unlikely that higher amounts (limit dose of dermal toxicity testing according OECD 402: 2,000 mg/kg bw/d) than tested in the acute oral toxicity study (tested up to 15,000 mg/kg bw/d) will be systemically available via the intact skin barrier even if the most unlikely amount of 100% penetration is assumed. Therefore, testing is not scientifically necessary.


Justification for selection of acute toxicity – oral endpoint
Scientifically acceptable; study equivalent to OECD Guideline 401

Justification for selection of acute toxicity – inhalation endpoint
n.a.

Justification for selection of acute toxicity – dermal endpoint
n.a.

Justification for classification or non-classification

Due to the findings described in the acute oral toxicity study (LD50 oral in rats greater than 15,000 mg/kg bw) Dioctadecyl disulphide does not have to be classified as acute orally toxic. Based on the substance's physico-chemical and non-irritant properties, as well as the unlikeliness of exposure and the experience from occupational health surveillance no higher systemic exposure via inhalation or dermal penetration is expected to occur than that tested in the course of the oral toxicity study. Therefore, Dioctadecyl disulphide does not have to be classified as acute toxic.