Fatty acids, C14-18 and C16-18-unsatd., ammonium salts

Endpoint summary

Description of key information

oral: Based on read across studies for acute oral toxicity on chemically similar substances, the LD50(oral) for Fatty acids, C14-18 and C16-18-unsatd., ammonium salts is estimated to be >5000 mg/kg.

dermal: Based on read across studies for acute dermal toxicity on chemically similar substances and the weight of evidence approach, the LD50(dermal) for Fatty acids, C14-18 and C16-18-unsatd., ammonium salts is estimated to be >5000 mg/kg.

inhalation - vapours: Based on the low acute oral toxicity (LD50(oral): >5000mg/kg) and the tiny vapour pressure (Vapour pressure(25°C): <0.01 Pa) of Fatty acids, C14-18 and C16-18-unsatd., ammonium salts, no acute inhalation toxicity of a at 25°C saturated atmosphere of vapours of this substances is expected.

inhalation - dust/mist: data lacking; (Based on the intended use of the products containing Fatty acids, C14-18 and C16-18-unsatd., ammonium salts, exposition to dust/mist of this substance are not expected.).

intravenous: After intravenous application, a LD50 of approximately 267 mg/kg bw was determined for a analogue substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Read-across (analogue): For justification of read-across see section 13.2.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

42 097 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Value of oleic acid.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on GHS criteria the target substance "Fatty acids, C14-18 and C16-18-unsatd., ammonium salts" is not considered to be classified for acute oral toxicity.
Based upon the DSD classification criteria (67/548/EEC) the target substance is not considered to be classified for Harmful, Toxic or Very toxic if swallowed.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not given

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
2 groups with 5 male and female rats each.
- Source: raiser: Winkelmann, Hannover.
- Weight at study initiation: 168g (male rats), 143g (female rats).
- Fasting period before study: 18 hours
- Housing: 5 animals per cage, separated by sexes.
- Diet: laboratory standard diet (altromin) and water water ad libitum.
The test animals were provided food (ad libitum) 3 hours after application.

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C;
- Humidity (%): 45-60%;
- Air changes (per hr): not given;
- Photoperiod (hrs dark / hrs light): 12 hours.

Route of administration:

oral: gavage

Vehicle:

other: 25% aqueous suspension

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25%;
- Amount of vehicle (if gavage): 20ml/kg.

MAXIMUM DOSE VOLUME APPLIED: 5g/kg.

DOSAGE PREPARATION (if unusual): for preparation of the suspention were used lukewarm aqua dest.. The supension was kept in movement with magnetic stirrer for applying an even mixed suspension to the test animals.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on chemical composition a less acute toxicity of the test item was expected. Because of that a limit test with a dosis of 5g/kg body weight was proved.

Doses:

5 g/kg bw

No. of animals per sex per dose:

10 animals per dose including both male and female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days;
- Frequency of observations and weighing: daily observations;
- Necropsy of survivors performed: yes;
Other examinations performed: clinical signs, body weight.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

All 10 rats survived the 14 days of observation.

Clinical signs:

No symptoms of poisoning were found during the observation.

Body weight:

see table below.

Gross pathology:

No symptoms of poisoning or inflammations neither on the inner organs nor the visceral cavities were found.

Body weight average in g of each 5 test animals before and after application:

dose	sex	before application	24 h after application	7 d after application	14 d after application
5 g/kg	male	168.0	180.0	202.0	218.0
5 g/kg	female	143.0	152.0	159.0	164.0

As its seen in the table the application of 5 g/kg had no impact on the body weight progress of the test animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item proves to be low acute toxicity. The LD50 can be declared for male and female rats: >5 g/kg.

Executive summary:

The carboxylic acid Edenor Ti (Edenor Talg A) was tested for acute oral toxicity according to OECD guidline 401 by limit test. It was proved to be less acute toxic at peroral application on rats (LD50 >5 g/kg bw).

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1970-05-21- to 1970-06-01

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: non-GLP study, similar to OECD Guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: 24 hours
- Weight at study initiation: 200-300 g
- Housing: 5 animals per cage

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

4, 8, 16, 32, 48, 64 mL/kg, these values correlate to the following: 5262.125, 10524.25, 21048.5, 42097, 63145.5, 84194 mg/kg bw

No. of animals per sex per dose:

5 animals per dose including both male and female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD0

Effect level:

32 mL/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

47.3 mL/kg bw

Based on:

test mat.

95% CL:

> 40.9 - < 54.7

Remarks on result:

other: 47.3 mL/ kg bw can be converted to 42097 mg/kg bw using the densitiy of the substance (0.89 g/cm^3 = densitiy of CAS 112- 80-1)

Sex:

male/female

Dose descriptor:

LD100

Effect level:

64 mL/kg bw

Based on:

test mat.

Mortality:

Mortality occured from the 40 mL/kg bw dose group onwards. 1 animal of that dose group died on day 2, 3 animals of the 48 mL/kg bw dose group and all animals of the 64 mL/kg bw dose group died on day 1.

Clinical signs:

All dosage levels from 16 mL/kg and above had nasal hemorrhage, crustated occular areas, oozed urine and appeared to be debilitated prior to death.

Body weight:

no data

Gross pathology:

no data

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

GLP study according to OECD Guideline and non-GLP study, equivalent or similar to OECD Guideline. Please refer to IUCLID section 13.2 for read across justification.

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

Read-across justification / weight of evidence justification:
The target substance Fatty acids, C14-18 and C16-18-unsatd., ammonium salts consists of ammonium salts of the fatty acids Myristic Acid (C14 ), Palmitic acid (C16), Stearic acid (C18), Palmitoleic acid (C16:1), Oleic acid (C18:1), Linoleic acid (C18:2) and Linolenic acid (C18:3). Information on acute dermal toxicity of Ammonium stearate (LD50(dermal): >3000mg/kg), Oleic Acid (LD50(dermal): >3000mg/kg), Stearic acid (LD50(dermal): >5000mg/kg), Linolenic acid (LD50(dermal): >18000mg/kg) and Ammonium sulfate (LD50(dermal): >2000mg/kg) is available. These substances are either the soap Ammonium stearate contained in the target substance, several fatty acids from which the target substance is manufactured or the Ammonium sulfate. Additionally the estimated acute oral toxicity of the target substance is low (LD50(oral): >5000 mg/kg). The effects of acute oral toxicity and acute dermal toxicity are expected to be equal or similiar, based on the low water solubility (< 1 mg/L), the Partition coefficient (log Pow: 3,1 - 5,1) and the molecular weight (245-302g/mol; average 297g/mol).
Based on these available data on acute dermal toxicity and the acute oral toxicity of the target substance, the LD50(dermal) is estimated to >5000mg/kg.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on GHS criteria the target substance "Fatty acids, C14-18 and C16-18-unsatd., ammonium salts" is not considered to be classified for acute dermal toxicity.
Based upon the DSD classification criteria (67/548/EEC) the target substance is not considered to be classified for Harmful, Toxic or Very toxic in contact with skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Estimation based on read across studies on chemically similar substances and weight of evidence approach.

Additional information

No adequate animal data are available and no epidemiological studies investigating the acute toxicity of the test (target) substance were identified. However, data from a structural analogue (read across substance) are available.

Oral:

Several publication are available in which the acute oral toxicity on rats of the analogue substances (Fatty acids, C16-18 and C18-unsatd., Oleic acid) were determined. As results, the following LD50(oral) values were determined: >5000 mg/kg bw for Fatty acids, C16-18 and C18-unsatd. and 47.3 mL/kg bw (which correlates to 42097 mg/kg bw) for Oleic acid. Based on the structural similarity of the target substance to the analogue substances the results of the acute oral toxicity of the source substances can be assigned to the target substance.

The supporting information of the acute oral toxicity of the analogue substances are also available: Ammonium stearate (LD50(oral, rat): > 5 000 mg/kg bw), Sodium stearate  (LD50(oral, rat): > 5 000 mg/kg bw), Oleic Acid (LD50(oral, rat): > 5 000 mg/kg bw and LD50(oral, rat): 57g/kg bw), Myristic Acid (LD50(oral, rat): > 10 000 mg/kg bw), Palmitic Acid (LD50(oral, rat): > 10 000 mg/kg bw), Stearic acid (LD50(oral, rat): > 10 000 mg/kg bw and LD50(oral, rat): >5 000 mg/kg bw), Linoleic acid (LD50(oral, rat/mouse): >3 200 mg/kg bw), Linolenic acid (LD50(oral, rat/mouse): >3 200 mg/kg bw) and Ammonium sulfate (LD50(oral, rat/mouse): > 2 000 mg/kg bw). This support information circumstantiates the result of the read-across projection to acute oral toxicity of the target substance.

Dermal:

Several publication are available in which the acute dermal toxicity on rats of the analogue substances (Ammonium stearate, Oleic acid, Stearic acid, Linoleic acid, Linolenic acid and Ammonium sulfate) were determined. As results, the following LD50(dermal) values were determined: > 3 000 mg/kg bw for Ammonium stearate, > 3 000 mg/kg bw for Oleic Acid, >5 000 mg/kg bw for Stearic acid, >18 g/kg bw for Linoleic acid,  >18 g/kg bw for Linolenic acid and > 2 000 mg/kg bw for Ammonium sulfate.

Based on the structural similarity of the target substance to the analogue substances, the read across studies for acute dermal toxicity on chemically similar substances and the weight of evidence approach, the LD50(dermal) for Fatty acids, C14-18 and C16-18-unsatd., ammonium salts is estimated to be >5000 mg/kg.

Intravenous:

In a publication an experiment is described in which 9-octadecenoic acid was administered to rats by intravenous injections to investigate the effects on the lungs. Therefore, adult male Fischer 344 rats were used. As injections of about 80 µL (356 mg/kg bw) of the analogue substance led to a high rate of mortality (compared to similar doses administered to larger animals in other studies) and because injecting of smaller amounts was not feasible, the doses were reduced by suspending the read across substance in saline-albumin solution in a ratio of 1:5. A volume of 250 µL of this suspension then was injected via the penile vein in anesthetized rats. They were sacrificed after different time intervals: 10 minutes, 30 minutes, 1 hour, 6 hours, 24 hours, 4 days, 12 days and 4 weeks. Control animals received 1 mg/dL albumin solution. As a result, histologic changes in the lungs (perivascular interstitial and intra-alveolar edema, vascular congestion, intravascular coagulation, intra-alveolar hemorrhage) were found within minutes after application. After 24 hours, an interstitial infiltrate of alveolar lining cells and macrophages was observed. Further development of the lesion was comparable to the respiratory distress syndrome. Chronic pulmonary inflammation or fibrosis was not found. The LD50 of the read across substance as a suspension in albumin was approximately 60 µL. The LD50 value 60 µL (given in the publication) was converted using the substance densitiy (0.89 g/cm3): 60 µL*0.89 g/1 mL=0.06 mL*0.89 g/mL=0.0534 g, weight rats: max. 200 g; 53.4 mg/0.2 kg = 267 mg/kg.

In another publication the effects of intravenous injections of an analogue substance on the lungs of dogs are examined. The substance was administered at two dose levels in a single injection (0.045 g/kg bw or 0.09 g/kg bw). Control animals received normal saline injections. Animals of the single-injection-groups were sacrificed after 1, 2, 4, 6 and 24 hours and 1, 2 and 4 weeks after injection. Additionally, 3 dogs of the 0.09 g/kg group were sacrificed at 3, 12 and 48 hours. As a result, mostly ventral and subpleural hemorrhagic lesions were observed in the early stage. Later yellow-tan patches were seen over the pleura. Lesions occurred mostly on the ventral sides of the lower lobes. Light microscopic examination revealed normal lung areas and damaged areas, these were more distinct in the higher dose group of the single injection-group. Large microcysts were seen in the peripheral portions of the lobe. After 1 week acute lesions had disappeared except for moderate edema. Fibrotic areas scattered over the lungs were found as well as thickened alveolar walls containing macrophages. These macrophages were less numerous after 2 weeks and 1 month, but the extent of fibrosis increased.

Justification for classification or non-classification

Based on GHS criteria the target substance "Fatty acids, C14-18 and C16-18-unsatd., ammonium salts" is not considered to be classified for acute (oral/dermal) toxicity.

Based upon the DSD classification criteria (67/548/EEC) the target substance is not considered to be classified as Harmful, Toxic or Very toxic (if swallowed/in contact with skin).