4,4'-thiodiethylene hydrogen -2-octadecenylsuccinate

Endpoint summary

Description of key information

One acute oral toxicity studies are available for the Substance. The acute oral toxicity study concluded that the Acute Oral LD50 was > 10000 mg/kg

One acute dermal toxicity studies are available for the Substance. The acute dermal toxicity study concluded that the Acute dermal LD50 was > 3160 mg/kg

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:

20th March 1981 - 8th June 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Not stated but assumed

GLP compliance:

not specified

Remarks:

Unlikely due to the age of the study

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Description: off white, very thick liuid
Density: 0.9981 g/mL at 60-65 oC
Date of Receipt: February 26,1981
Storage: Room temperature

Preparation of Dosing Material Mixture: The test material was warmed to 60-65oC in a water bath to facilitate handling. No mixture was required.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Number: 35 males (5 per group, 7 groups)
Age: Young adults
Weight: 260-359 g
Equilibration period: 36 Days
Observations: All animals were checked for viability twice daily during the equilibration period. Piror to assignement to sutdy all animals were examined to ascertain suitability for study.

Husbandry
Housing: Group-housed (six/cage) during equilibration. individually housed during study.
Cages: Suspended, stainless stell with wire mesh bottoms
Environmental conditions: Temperature: Monitored twice daily temperature range during study: 71 to 74oF
Humidity: Monitored daily
Light cycle:12 hours light, 12 hours dark
Food: Purina laboratory Rodent Diet, ad libitum
Water: Automatic watering system, ad libitum, Municipal water supply
Identification: Each animal was identified with a monel ear tag bearing a unique number prior to testing
Selection: All animals number from this shipment were placed in random order, using random number table. A separate list was generated for each sex. Animals for study were selecte by following these listes. Any animals considered unsuitable because of poor health or outlying body weights were excluded and tge successding number was used.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Doses of 1.0, 1.47, 2.15, 3.16, 4.46, 6.81 and 10.0 g/kg

No. of animals per sex per dose:

35 males (5 per group, 7 groups)

Control animals:

no

Details on study design:

Animals were fasted overnight (for approximately 18 hours) prior to dosing. The test material was administered by oral intubation, using a ball-tipped intubation needle. Doses were calculated using pre-fasted body weights.

Experimental evaluation
Viability check: Twice daily
Pbservation of pharmacologic and toxicologic signs: Approximately 1, 2, and 4 hours after dosing and daily thereafter for fourteen days
Bodyweights: Prefast (weights used for calculation of doses)
Postfast (Just prior to dosing)
Day 7 and Day 14

Post Mortem
All animals surviving at termiantion of the observation period (Day 14) were killed by carbon diocide inhalation and examined grossly. All abnormalities were recorded but no tissues were saved.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

All animal survived at all dose levels

Clinical signs:

other: Nassal discharge, rales, fecal staining and/or soft stool were echibited sporadically by animals at the 1.0 thru 6.81 g/kg dose levels. signs seen during the the twenty-four hours after dosing in animals at the 10.0 g/kg included soft stool, fecal and ur

Gross pathology:

Post-mortem examinations revealed findings similar to those seen in control rats killed by carbon dioxide inhalation in this labortory.

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality was observed in any animal tested up to a dose of10000 mg/kg therefore LD50>10000 mg/kg

Executive summary:

All animals survived at all dose levels; therefore the oral LD50 of Substance is greater than 10.0 q/kg. All animals exhibited body weight gains during the fourteen-day post-dose period with no apparent differences between groups. Nasal discharge, rales, fecal staining and/or soft stool were exhibited sporadically by animals at the 1.0 thru 6.81 (1/10 dose levels. Signs seen during the twenty-four hours after dosing in animals at the 10.0 g/kg included soft stool, fecal and urinary staining, nasal discharge, rales, piloerection and hypoactivity. Some animals at dose levels of 2.15 through 6.81 q/kq also exhibited soft stool and/or fecal staining during the first 24 hours. Other signs occured sporadically in single animals. All animals were free of unusual signs from Day 2 through termination of the study (Day 14). Post-mortem examinations revealed findings similar to those seen in control rats killed by carbon dioxide inhalation in this labortory.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

The study was considered as reliable with restriction as it was conducted on the registered substance (as defined in section 1.1) and meets acceptable scientific standards, but before the implementation of GLP and of the OECD Testing Guideline.

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:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

23rd February 1981 - 25th May 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

4 animals per group

GLP compliance:

not specified

Remarks:

Unlikely due to the age of the study

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Description: Off white, very thick liquid
Density: 0.9987 g/ml at 60-65 degree C
Date of Receipt: February 26, 1981
Storage: Room temperature
Preparation of Dosing Material Mixtures: The test material was warmed in a water bath to 60°C to facilate handling. P40 mixture was required

The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area.

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Preparation of Animals:
On the day before dosing (approximately 20 hours prior to dosing), the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 20% of the body surface
area. No abrasions were made, I.e., the skin of all the animals remained intact.

Husbandry:
Housing: Individually housed
Cage: Suspended, stainless steel
Environmental Conditions: Temperature: monitored twice daily
Temperature range during study: 62 to 76F
Humidity: monitored daily
light cycle: 12 hours light, 12 hours dark
Food:Purina Rabbit Chow
Water Automatic watering system, ad libitum, Municipal water supply
Identification: Each animal was identified with a monel ear tag bearing a unique number prior to testing
Selection: Animal considered unsuitable for study because of poor health or outlying body weights were exlcuded for slection. Animal for study were selected from those remaining.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area. A layer of 8-ply gauze was then wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve,
designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and Elizabethan collars were placed on all animals.

Duration of exposure:

Following approximately 24 hours of exposure, the wrappings were removed and the amount of residual test material was estimated visually. After 30 minutes, dermal observations were made.

Doses:

Doses groups were 50, 200, 794, 3160 mg/kg

No. of animals per sex per dose:

16 animals (2 animals per sex per dose)

Control animals:

not required

Details on study design:

Preparation of Animals
On the day before dosing (approximately 20 hours prior to dosing), the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 20% of the body surface
area. No abrasions were made, i.e. the skin of all the animals remined intact.

Administration of Test Material:
The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area. A layer of 8-ply gauze was then wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve,
designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and Elizabethan collars were placed on all animals.

Following approximately 24 hours of exposure, the wrappings were removed and the amount of residual test material was estimated visually. After 30 minutes, dermal observations were made.

Experimental Evaluation (In-Life):
Viability Check: Twice Daily
Observations of Pharmacologic and-Toxicologic Signs: Approximately 1, 2, and 4 hours after dosing and daily thereafter for fourteen days.
Body Weights: Pre-cjose, at the time of clipping (weights used for calculation of doses)
Day of Dosing flay 7 and 14
Evaluation of Skin Irritation: Observations or erythema and edema or other evidence of irritation or injury were made approximately 30 minutes after removal of the occlusive wrapping and aqain at Days 3, 7, 10 and 14.

Post Mortem:
All animals surviving at termination of the observation period (Day 14) were killed by an intravenous or intracardiac overdose of sodium pento’arbital and examined grossly. All abnormalities were recorded but no tissues were saved.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 160 mg/kg bw

Based on:

test mat.

Mortality:

All of the animals survived at all dose levels

Clinical signs:

other: Animals at the 50 mg/kg dose level exhibited slight (well-defined) erythema with occasional edema. 3 of the 4 animals were free of signs of dermal irritation by Day 7 and the fourth animal exhibited only barely perceptible erythena on Day 7 and 10. At the

Gross pathology:

One animal (no. 7214, female) in the 50 mg/kg group exhibited a numher of abnormalities in the gastrointestinal tract (red gastric serosa, hardening and thickening of the intestine). The presence of these findings in a single animal in the lowest dose group is not considered to represent an effect of the test material.

Interpretation of results:

GHS criteria not met

Remarks:

No mortality was observed in any acute study performed. No systemic toxicity was observed in any study that would be linked to mortality. No systemic toxicity to cause lethality by dermal application is expected for doses up to 5000 mg/kg as evident by the high concentration tested in the acute oral. Therefore no classification is required.

Conclusions:

All of the animals survived at all dose levels; therefore the LD50 is greater than 3160 mg/kg.

Executive summary:

This study was conducted in order to evaluate the acute dermal toxicity of the Substance. On the day before dosing (approximately 20 hours prior to dosing), the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper. The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area. A layer of 8-ply gauze was then wrapped around the animal to cover the application site. Doses of 50, 200, 794 and 3160 mg/kg of body weiqht were administered to sixteen rabbits (two per sex per dose level) for 24 hours. Animals were monitored for observation of pharmacologic and toxicologic signs at approximately 1, 2, and 4 hours after dosing and daily thereafter for fourteen days. No mortality, bodyweight effects, pharmacologic and toxicologic signs and treatment related macrospic effects were noted in any animals. Erythema and/or edema were observed in all animals and incidences of necrosis were observed in animals treated at > or equal to 794 mg/kg.

All of the animals survived at all dose levels; therefore the LD50 is considered to be greater than 3160 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 160 mg/kg bw

Quality of whole database:

The study was considered as reliable with restriction as it was conducted on the registered substance (as defined in section 1.1) and meets acceptable scientific standards, but before the implementation of GLP and of the OECD Testing Guideline.

Additional information

Acute Oral:

All animals survived at all dose levels; therefore the oral LD50 of Substance is greater than 10.0 q/kg. All animals exhibited body weight gains during the fourteen-day post-dose period with no apparent differences between groups. Nasal discharge, rales, fecal staining and/or soft stool were exhibited sporadically by animals at the 1.0 thru 6.81 (1/10 dose levels. Signs seen during the twenty-four hours after dosing in animals at the 10.0 g/kg included soft stool, fecal and urinary staining, nasal discharge, rales, piloerection and hypoactivity. Some animals at dose levels of 2.15 through 6.81 q/kq also exhibited soft stool and/or fecal staining during the first 24 hours. Other signs occured sporadically in single animals. All animals were free of unusual signs from Day 2 through termination of the study (Day 14). Post-mortem examinations revealed findings similar to those seen in control rats killed by carbon dioxide inhalation in this labortory.

Acute Dermal:

This study was conducted in order to evaluate the acute dermal toxicity of the Substance. On the day before dosing (approximately 20 hours prior to dosing), the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper. The material was applied directly on to the exposed skin of the anirial, and spread evenly over the entire area. A layer of 8-ply gauze was then wrapped around the animal to cover the application site. Doses of 50, 200, 794 and 3160 mg/kg of body weiqht were administered to sixteen rabbits (two per sex per dose level) for 24 hours. Animals were monitored for observation of pharmacologic and toxicologic signs at approximately 1, 2, and 4 hours after dosing and daily thereafter for fourteen days. No mortality, bodyweight effects, pharmacologic and toxicologic signs and treatment related macrospic effects were noted in any animals. Erythema and/or edema were observed in all animals and incidences of necrosis were observed in animals treated at > or equal to 794 mg/kg.

All of the animals survived at all dose levels; therefore the LD50 is considered to be greater than 3160 mg/kg.

Acute Inhalation:

In accordance with Section 8.5.2. of Column 2 of Annex VIII of the REACH Regulation, the registrant proposes to waive the acute toxicity testing by the inhalation route on the basis that exposure to humans via inhalation is unlikely, taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for classification or non-classification

The acute oral median lethal dose (LD50) of the Substance was estimated to be greater than 10,000 mg/kg body weight. The test substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

 

The acute dermal median lethal dose (LD50) of the Substance was estimated to be 3,160 mg/kg body weight. The test substance did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

 

In accordance with Section 8.5.2. of Column 2 of Annex VIII of the REACH Regulation, the registrant proposes to waive the acute toxicity testing by the inhalation route on the basis that exposure to humans via inhalation is unlikely, taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.