Dioctadecyl disulphide

Endpoint summary

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

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 or test system 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:

other: no symptoms

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

Value:

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.