Fatty acids, C16-18 and C18-unsatd., compds. with triethanolamine

Endpoint summary

Description of key information

Key studies were available for acute oral and dermal toxicity with test substance containing >95% active ingredient. Acute oral toxicity tested according to OECD TG 423 showed that LD50 was above limit dose of 2000 mg/kg bw. Acute dermal toxicity tested according to OECD TG 402 showed that LD50 was above limit dose of 2000 mg/kg bw. In both studies no signs of systemic toxicity were observed.  Inhalation toxicity testing was waived based upon the fact that acute inhalation exposure as such is very unlikely due to the substance properties.  The available acute toxicity studies demonstrate that the substance is of low acute toxicity and needs no classification.

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:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to internationally accepted test guidelines and is considered relevant, adequate and reliable.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: CD / Cri: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Germany GmbH, Research Models and Services, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at start of administration: Approx. 8 weeks
- Weight at start of administration: 164-180 g
- Fasting period before study: Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Housing: During the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. The cages were changed and cleaned twice a week.
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany) served as food and was offered ad libitum.
- Water (e.g. ad libitum): Drinking water was offered in bottles ad libitum.
- Acclimation period: At least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C (maximum range)
- Humidity (%): 55% ± 15% (maximum range)
- Air changes (per hr): 12-18 fold air change per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: March 11, 2013 To: April 2, 2013

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bw


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
The ATC- test method permits the identification of the 'acute-toxic-class' (ATC), a measurement of the acute toxicity by the oral route.
The test item is administered orally by gavage at a single dose level to a group of experimental animals. The dose used is selected from a series of defined dose levels. Due to the small number of animals used with this method, there is no need to perform a range finding test.
The test item is tested using a stepwise procedure, each step uses three female animals. The results of each step determine if:
- no further testing is needed,
- the next step will be performed with the same dose,
- the next step will be performed at the next higher or next lower dose level.

At 2000 mg/kg bw
- Testing at 2000 mg/kg bw:
Three animals of one sex (preferably females) are treated at 2000 mg/kg bw (first step). If two to three animals die, testing at 300 mg/kg bw should be performed.
If no to one animal dies, the test item should be retested (second step) with 2000 mg/kg bw, using three animals of the same sex.
If, in this second step, two to three animals die, testing at 300 mg/kg bw should be performed. If, in this second step, no to one animal dies, no further testing is necessary.

Doses:

2000 mg/kg bw (limit test)

No. of animals per sex per dose:

6 (3 in the first step, 3 in the second step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed.
During the follow-up period of 2 weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms had subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on deaths were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes.
At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. Autopsy and macroscopic inspection of animals which died prematurely would have been carried out as soon as possible after exitus.
No histopathology was carried out as no macroscopical findings were noted at autopsy.
- Other examinations performed: The LD50 value was ranked exceeding 2000 mg/kg body weight.

Statistics:

No statistical analysis could be performed (The method used is not intended to allow the calculation of a precise LD50 value).

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death was recorded within the test period.

Clinical signs:

other: No clinical signs were recorded within the test period.

Gross pathology:

No pathological changes were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 2000 mg/kg

Executive summary:

Acute oral toxicity, was tested in rats according to OECD guideline 423 and EC method B.1 tris (ATC method). A first group of three females were dosed at 2000 mg active ingredient/kg bw, followed by a second group of 3 females at same dose. The test item, Fatty acids, C16-18 and C18-unsatd., compds. with triethanolamine was suspended in sesame oil and administered by oral gavage at a volume of 10 mL/kg bw.

No-observed-effect level by oral administration was 2000 mg/kg bw. Dose level with first intolerance reactions by oral administration was >2000 mg/kg bw. Lowest lethal dose level by oral administration was >2000 mg/kg bw. LD₅₀was above 2000 mg/kg bw, p.o.

Under the present test conditions, a single oral administration of 2000 mg/kg bw did not reveal any signs of toxicity. No death was recorded within the test period. All animals gained the expected weight throughout the whole study period. No signs or abnormalities were noted at necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

High quality (Klimish 1)

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:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to internationally accepted test guidelines and is considered relevant, adequate and reliable.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CD/Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at dosing: Males: 7 weeks; Females: 9 weeks
- Weight at dosing: Males: 220 – 241 g; Females: 210 – 219 g
- Fasting period before study: Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Housing: During the 14-day observation period the animals were kept singly in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. The cages were changed and cleaned twice a week.
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany) served as food. This food was offered ad libitum.
- Water (e.g. ad libitum): Drinking water was offered in bottles ad libitum.
- Acclimation period: 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8°C -24.8°C
- Humidity (%): 58% -64%
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: March 11, 2013 To: April 3, 2013

Type of coverage:

occlusive

Vehicle:

other: sesame oil

Details on dermal exposure:

TEST SITE
- Area of exposure: The site was situated on the animal's back between the fore and hind extremities.
- % coverage: An area of at least 5 cm x 6 cm = 10% of body surface
- Type of wrap if used: The test patch was occlusive. The test item was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and secured with adhesive plaster strips on the application site.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not necessary (no residuals)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3000 mg/kg bw of the mixture, correlating with 2000 mg test item/ kg bw
- Concentration (if solution): 10000 mg Fatty acids, C16-18 and C18-unsatd., compds. with triethanolamine were moistened with 5000 mg sesame oil
- Constant volume or concentration used: yes, 3000 mg/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw (limit test)

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days.
During the follow-up period (at least 2 weeks) changes in skin and fur, eyes and mucous membranes, and the respiratory, circulatory, autonomic and central nervous system and somatomotor activity and behaviour pattern were observed at least once a day until all symptoms have subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Animals found in a moribund condition and animals showing severe pain or enduring signs of severe distress were humanely killed.
Observations on deaths were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
The skin was observed for the development of erythema and oedema and was rated.
- Necropsy of survivors performed: yes. At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. No histopathology was carried out as no macroscopical findings were noted at autopsy.

Statistics:

The LD50 could not be calculated as no animal died prematurely.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

A single dermal administration of 2000 mg test item/kg bw to rats revealed no deaths.

Clinical signs:

other: A single dermal administration of 2000 mg test item/kg bw to rats revealed no signs of toxicity. A very slight erythema was observed on test day 2 in all 5 of 5 male and 5 of 5 female animals.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

A very slight erythema was observed on test day 2 in all 5 of 5 male and 5 of 5 female animals.
LD50 > 2000 mg/kg bw.

Executive summary:

Acute dermal toxicity was tested in rats according to Council Regulation (EC) No. 440/2008 part B.3 and OECD guideline 402. The test item Fatty acids, C16-18 and C18-unsatd., compds. with triethanolamine was moistened with sesame oil and administered at 2000 mg/kg bw.

No-effect dose level by dermal administration was > 2000 mg/kg bw.  Dose level with first intolerance reactions by dermal administration was > 2000 mg/kg bw. Lowest lethal dose level by dermal administration was > 2000 mg/kg bw. There were no test item-related findings at necropsy.

Under the present test conditions, a single dermal administration of 2000 mg test item/kg bw to rats revealed no signs of toxicity and no deaths. All animals gained the expected body weight throughout the whole experimental period. A very slight erythema was observed on test day 2 in all 5 of 5 male and 5 of 5 female animals. No signs or abnormalities were noted at necropsy. LD₅₀ > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

High quality (Klimish 1)

Additional information

Acute oral toxicity

Acute oral toxicity, was tested in rats according to OECD TG 423 (Haferkorn, 2013a). A first group of three females were dosed at 2000 mg/kg bw, followed by a second group of 3 females at same dose. The test item was suspended in sesame oil and administered by oral gavage at a volume of 10 mL/kg bw. No death or any other clinical signs were recorded within the test period. All animals gained the expected weight throughout the whole study period. No signs or abnormalities were noted at necropsy. LD₅₀ was above 2000 mg/kg bw.

 

Acute dermal toxicity

Acute dermal toxicity was tested in rats according to OECD TG 402 (Haferkorn, 2013b). A group of 5 male and 5 female rats were dosed with the test item moistened with sesame oil and administered under occlusion at 2000 mg/kg bw. A single dermal administration of 2000 mg test item/kg bw to rats revealed no signs of toxicity and no deaths. All animals gained the expected body weight throughout the whole experimental period. A very slight erythema was observed on test day 2 in all 5 of 5 male and 5 of 5 female animals. No signs or abnormalities were noted at necropsy bw. LD₅₀ was above 2000 mg/kg bw.

 

Acute inhalation toxicity

Because the substance is a viscous waxy paste with a low vapour pressure (<550 Pa) inhalation and/or deposition of significant amount of the substance is unlikely. Absorption would be possible due the high logPow (4.86), however, this is only theoretical. Based on these properties, the inhalation route is not appropriate; the oral and dermal route of administration were therefore applied as first and second relevant routes (ECHA R7a Guidance p 342). Additional inhalation testing would neither lead to a better risk assessment, nor improve the safety of applications. On the basis of the argumentation summarized above an acute inhalation toxicity study was waived. 

Justification for classification or non-classification

The available acute toxicity studies demonstrate that substance is of low acute toxicity. Based on these results and according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008), classification is not obligatory for oral and dermal acute toxicity.