Dioctadecyl 3,3'-thiodipropionate

Endpoint summary

Description of key information

The test substance was found to cause no mortality upon acute oral and dermal exposure to rats of 5000 and 2000 mg/kg bw, respectively. Similarly, no mortality was observed in rats in the acute oral toxicity study with 5000 mg/kg bw of the C12-analogue. No findings were noted regarding body weight development or gross pathology. Transient mild clinical signs resolved within the observation period. All three studies are adequately reported and in their design equivalent or similar to the respective OECD testing guidelines.

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:

1975-10

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

Limited details on test design and observations were reported. Body weight not recorded, no individual data

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In house bred
- Age at study initiation: 7 -8 weeks
- Weight at study initiation: 265 g (males); 167 g (females)
- Housing: Individually
- Diet: Ad libitum, commercial pelleted diet (Oakes Special Diet with added Vit. E)
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 50 % aqueous solution of polyethylene glycol

Doses:

A 25 % (w/v) solution of the compound in a 50 % aqueous solution of polyethylene glycol was administered as a single dose to rats which had been fasted for 18 hours, at a rate of 20 mL/kg (equivalent to 5 g compound/kg).

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 5 000 mg/kg bw

Mortality:

No deaths occurred during the 14 day observation period.

Clinical signs:

other: No clinical symptoms were recorded

Gross pathology:

At autopsy no changes in organs or tissues caused by the administration of the test compound were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test article in rats is greater than 5 g/kg body weight. No clinical symptoms were recorded and no deaths occurred during the 14 day observation period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-04-28 - 1992-06-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Ltd., Animal Production, Stein, Switzerland
- Weight at study initiation: 201 - 286 g
- Housing: Individually in Macrolon cages type 3, with standardized soft wood bedding (Societe Parisienne des Sciures, Pantin, France)
- Diet: Ad libitum, NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland
- Water: Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- % coverage: About 10% of the body surface
- Type of wrap if used: gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With lukewarm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 g (corresponding to approx. 4 ml)
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Signs and symptoms (daily); mortality (twice a day); body weight (immediately before application and on days 7 and 14)
- Necropsy of survivors performed: yes
- Other examinations performed: The animals were submitted to a gross necropsy at the end of the observation period.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Mortality:

No mortalities occurred in this study.

Clinical signs:

other: Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute dermal tests. The animals recovered within 2 to 3 days.

Gross pathology:

No deviations from normal morphology were found.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is not toxic upon dermal application to rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral Toxicity

In the key study each five male and female Sprague-Dawley rats were given a single gavage dose of 5000 mg/kg bw in 50% polyethylene glycol. No clinical symptoms were recorded and no deaths occurred during the 14 day observation period. At autopsy no changes in organs or tissues caused by the administration of the test compound were seen. This study contains less detail on experimental performance than the second study with a structural analogue but is otherwise considered adequate for hazard assessment.

The findings of the key study are consistent with the results of a second acute oral toxicity study performed with a structural analogue. This study was performed and reported similar to the requirements of OECD testing guideline 423. It was performed prior to the introduction of GLP. The test item is an analogue substance that differs in having two C12 alkyl chains instead of two C18 alkyl chains. The shorter alkyl chain is expected to result in slightly more favourable solubility and absorption after uptake. Considering the 1.3 fold difference in molecular weight, application of the C12 analogue results in a higher number of molecules so that overall, any hazard identified for the analogue is considered relevant for the target substance. The read-across study was performed in five male and five female Tif:RAIf(SPF) rats with a limit dose of 5000 mg/kg bw that was applied by gavage using CMPS80 as vehicle. No mortality occurred. Dyspnea was observed between day 1 and day 10; ruffled fur between day 1 and day 9; body position-curved between day 1 and 6. The animals recovered within 11 days.

Dermal Toxicity

The key study for acute dermal toxicity was performed with a well-characterized test material according to GLP and a protocol similar to OECD Guideline 402. In this study the substance was applied as a paste in arachis oil to the skin of 5 male and 5 female rats (Tif: RAIf (SPF) at a dose of 2000 mg/kg bw and covered with a semi-occlusive dressing for 24 hours. There were no deaths during the 14-day observation period. Piloerection, hunched posture, and dyspnea were seen. The animals recovered within 2 to 3 days. No deviations from normal morphology were found upon necropsy. The LD50was higher than 2000 mg/kg bw.

InhalationToxicity

No experimental data is available regarding acute inhalation toxicity.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008.