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Administrative data

Description of key information

Acute toxicity:
- oral: LD50 >5000 mg/kg bw (OECD 401; Analogy CAS 57-10-3, CAS 57-11-4, CAS 112-85-6 );
- inhalative: LC50 >0.1521 mg/L (IhT; Analogy CAS 124-07-2);
- dermal: LD50 > 2000 mg/kg bw (Analogy CAS 57-11-4);

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study, tested with the source substance palmitic acid (CAS 57-10-3). In accordance with the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that the study was conducted with a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Supplied by Winkelmann, Hannover, Germany
- Weight at study initiation: Mean body weights of male and female rats were 183 and 137 g, respectively
- Fasting period before study: 18 hours prior to dosing (feeding only)
- Housing: Same sex-groups of five Wistar rats were housed in type III Makrolon-cages containing soft wood granulated material
- Diet: A standard laboratory animal diet (Altromin for rats)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 45 - 60
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Purity: 99%


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed immediately after dosing and 1, 4 and 24 hours after dosing, then once every 24 hours thereafter for the rest of the observation period. Individual bodyweights were measured immediately prior to dosing and 24 hours and 24 hours after dosing as well as 7 and 14 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
Male rats: no mortality occurred during the 14 days observation period
Female rats: one animal died on day 12 after dosing, all other animals survived the 14 days observation period
Clinical signs:
Clinical signs appeared approximately 20 minutes after dosing including slightly diminished activity and ruffled fur. These clinical signs completely subsided within 24 hours after dosing.
Body weight:
Mean body weights prior to dosing and on days 1, 7 and 14 after dosing:
- Males: 183, 195, 214, 234 g
- Females: 137, 143, 149, 160 g
Gross pathology:
Swelling of the gastric mucosa
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats an LD50 value of > 5000 mg/kg bw was determined.
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study, tested with the source substance stearic acid (CAS 112-85-6). In accordance with the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that the study was conducted with a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Supplied by Winkelmann, Hannover, Germany
- Weight at study initiation: Mean body weights of male and female rats were 170 and 146 g, respectively
- Fasting period before study: 18 hours prior to dosing (feeding only)
- Housing: Same sex-groups of five Wistar rats were housed in type III Makrolon-cages containing soft wood granulated material
- Diet: A standard laboratory animal diet (Altromin for rats)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 45 - 60
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Purity: 99%


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed immediately after dosing and 1, 4 and 24 hours after dosing, then once every 24 hours thereafter for the rest of the observation period. Individual bodyweights were measured immediately prior to dosing and 24 hours after dosing as well as 7 and 14 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Female rats: no mortality occurred during the 14 days observation period
Male rats: one animal died on day 13 after dosing, all other animals survived the 14 days observation period
Clinical signs:
Clinical signs appeared approximately 20 minutes after dosing. Ruffled fur, strong salivation and very diminished activity. These clinical signs completely subsided within 24 hours after dosing
Body weight:
Mean body weights prior to dosing and on days 1, 7 and 14 after dosing:
- Males: 170.0, 173.0, 180.0, 203.8 g
- Females: 146, 151, 158, 168 g
Gross pathology:
Swelling of the gastric mucosa. Rests of substance in stomach (surviving and death animals)
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats an LD50 value of > 5000 mg/kg bw was determined.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication which meets basic scientific principles
Principles of method if other than guideline:
Inhalation Risk Test, where animals were exposed to a flowing stream of saturated vapour for up to 8 hours. The inhalation period is defined by killing half of the animals within a 14 day recovery period.
GLP compliance:
no
Test type:
other: Inhalation Risk Test (IRT)
Limit test:
yes
Species:
rat
Strain:
other: Albino
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Source and rate of air: dried room air
- System of generating vapour: by passing 2.5 L/minute dried room air through a fritted glass disc immersed to a deep at least 1 inch in approx. 50 ml of test substance contained in a gas-washing bottle
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
0.1621 mg/l (Danish EPA QSAR database, 2004 )
No. of animals per sex per dose:
6 males or females
Control animals:
other: analogue tests with other substances were also reported
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.162 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: vapour
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this Inhalation Risk Test no mortality in rats was reported after a 4-hour exposure to a saturated vapour atmosphere of the test substance.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
Jan - Feb 1979
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 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
Deviations:
no
Principles of method if other than guideline:
The study was performed in accordance with the Hazleton Manual of Standard Operating Procedures as applied to the client procedure supplied ( Procter and Gamble Standard Procedure No. 10 for Toxicological Evaluation) dated 24th June 1977.
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Buxted Rabbit Co. Ltd, Great Totease Farm, Buxted, Nr. Uckfield, Sussex
- Weight at study initiation: 2.2 - 3.0 kg
- Housing: individually in grid floor cages
- Diet (ad libitum): Standard Rabbit Diet
- Water (ad libitum): drinking water; ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ambient with a lower limit of 14
- Photoperiod: natural lighting conditions
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- Area of exposure: 25% of the total body surface (on the back)
- Type of wrap if used: gauze pads ( 80 x 120 mm) and secured by adhesive strapping. Each animal was placed into a Newman harness.

REMOVAL OF TEST SUBSTANCE
- Washing: 24 hours after administration with a wet disposable paper towel
Duration of exposure:
24 hours
Doses:
2000 mg / kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily for mortality and signs of toxicity for the 14 days following administration
- Frequency of observations to evaluate skin reactions: immediately after removal of the patches and daily for the next two weeks
- Frequency of weighing: once before administration of the test substance and thereafter on day 14
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One male animal was found dead on day 7 after treatment. Laboured breathing was noted in this animal on the day before death (Day 6). Severely consolidated lungs were noted at necropsy and death was not considered to be related to treatment.
Clinical signs:
Slight diarrhoea was noted in one female animal ( No. 893) on day 3 after treatment. All other animals appeared normal throughout the observation period.
Body weight:
One animal showed a small loss in body weight at the end of the observation period. All other surviving animals showed small to moderate body weight gains.
Gross pathology:
Necropsy of all surviving animals revealed no macroscopic abnormalities. One animal received for necropsy on day 7 showed severe consolidation of the lungs.
Other findings:
Erythema, ranging from slight to moderate in degree, was noted on removal of the adhesive dressing. The erythema was maintained and became severe in degree in one female animal 7 days after treatment. Four animals showed slight and moderate desquamation.
Slight oedema and eschar formation were also noted in some animals during the first week of observation.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute dermal toxicity study in rabbits an LD50 value of > 2000 mg/kg bw was determined.

Additional information

Oral

Due to the lack of reliable data with fatty acids C16-18 on acute oral toxicity, studies with two of the main constituents, C16 fatty acid (palmitic acid) and C18 fatty acid (stearic acid), are used for hazard assessment. Since fatty acids C16-18, palmitic acid, and stearic acid belong to the same category based on similar structural and toxicological properties, this approach can be regarded as scientifically justified. Thus, read-across is performed based on a category approach (for details refer to IUCLID chapter 13).

 

Acute oral toxicity of palmitic acid was evaluated in a study performed according to OECD guideline 401, where in a limit test five male and five female Wistar rats received an oral application of 10 mL of 5000 mg/kg bw palmitic acid in DMSO (Kästner, 1981). Clinical signs appeared approximately 20 minutes after dosing including slightly diminished activity and ruffled fur, which completely subsided within 24 hours after dosing. While one female died on day 12 after dosing, all males survived the 14 day observation period. Pathological examination revealed a swelling of the gastric mucosa. Based on the results, the LD50 for palmitic acid was found to be >5000 mg/kg bw.

Acute oral toxicity of stearic acid was evaluated in a study performed in accordance to OECD guideline 401, where in a limit test five male and five female Wistar rats received 10 mL/kg bw stearic acid in DMSO at concentration of 5000 mg/kg bw by gavage (Kästner, 1981). Clinical signs including ruffled fur, strong salivation and much diminished activity appeared approximately 20 minutes after dosing, but subsided within 24 hours after dosing. Since only one male died on day 13 after dosing, the LD50 for stearic acid was found to be >5000 mg/kg bw.

 

Due to the similar structural and toxicological properties of the members within the category including fatty acids C16-18 and its main constituents palmitic acid and stearic acid, the LD50 for fatty acids C16-18 can be set as >5000 mg/kg bw.

 

Inhalation

Inhalation of fatty acids as vapour is not expected due to the low vapour pressure of < 1 mmHg. Therefore, only very limited data on acute inhalative toxicity of fatty acids is available.

However, the identified uses include spraying tasks where exposure to an aerosol of fatty acids can occur like use in cleaning agents.  

The only available data on acute inhalation toxicity of fatty acids are data of a published inhalation risk test with C8 fatty acid (octanoic acid; Smyth, 1962). No mortality of rats was reported after a 4-hour exposure to a saturated atmosphere which corresponds to a value of >0.1521 mg/L air based on QSAR calculation (Danish EPA Database, 2004).

Although not reported in this study, respiratory irritation/corrosion as primary effect is expected for fatty acids with a chain length ≤C12 due to the corrosive/irritation properties of the short- and mid-chain fatty acids C6 – C12, respectively.

In more detail, C8 fatty acids show corrosive properties to the skin at concentrations >70%. C9 fatty acid (at a concentration of >50%) and C10 fatty acid is irritating to skin and eyes, respectively. C12 fatty acid is not irritating to skin but is found to be irritating to eyes when applied with a concentration >73.6%.

Members of the category with a chain length >C12 are only causing negligible effects when applied to the skin or eyes. Their respiratory uptake would therefore not lead to irritation, but they would be included in the pulmonary surfactant of the respiratory tract which is mainly composed of large portions of phospholipids based on long chain fatty acids.

Since in industrial and professional applications inhalation exposure is controlled by ventilation systems, personal protective equipment, and measuring devices, the inhalation exposure can be considered to be sufficiently controlled.

Thus, it can be concluded that acute inhalation of fatty acids can cause irritation of the respiratory tract leading to classification and therefore no further testing shall be performed due to animal welfare reasons.

 

Dermal

Limited data is available on acute dermal toxicity of fatty acids since C8 fatty acid show corrosive properties at concentrations >70%, C9 (at a concentration of >50%) and C10 fatty acids are irritating to skin, respectively. The consequence after dermal application of these substances would therefore be irritation/corrosion as the primary effect. All other members of the category with longer chain length are only causing negligible effects when applied to the skin.

A general prerequisite for systemic toxicity after dermal application is the permeability of the skin for the applied substance. Although the dermal penetration of fatty acids is very variable, in general they do not have significant systemic bioavailability (for details see IUCLID chapter 7.1).

Thus, no acute dermal toxicity by fatty acids is expected as it could be demonstrated by a LD50 value of >2000 mg/kg bw for C18 fatty acid (stearic acid) found in a in limit test performed according to internal company standards (Jones, 1979). Three male and three female New Zealand White rabbits received a dermal application of 2000 mg/kg bw stearic acid to 25% of the total body surface under occlusion for 24 hours. As result, slight diarrhoea was noted in one female animal on day 3 after treatment. All other animals appeared normal throughout the observation period. Laboured breathing on day 6 was noted in one male, which died the next day. Although the pathological examination revealed severe consolidation of the lungs, this finding was not considered to be substance related. Irritating effects were noted on the skin of all animals which were described as ranging from slight to severe. Four animals showed slight and moderate desquamation. Slight oedema and eschar formation were also noted in some animals during the first week of observation. However, these observed effects can be attributed to the severe conditions used for application which are not in line with current guidelines. However, a LD50 of >2000 mg/kg bw was found for stearic acid.

Although the dermal absorption of C18 fatty acid6 (stearic acid) with 0.00026 mg/cm2is lower compared to fatty acids with shorter chain lengths (e.g. C12 fatty acid: 0.005 mg/cm2), even single or repeated oral uptake of C12 fatty acid does not lead to systemic effects due to the physiological function within the body.

Moreover, dermal exposure can be considered to be sufficiently controlled in industrial and professional applications since the employees are wearing gloves and protective clothing. Thus, no acute dermal toxicity by fatty acids is expected and no further testing shall be performed due to animal welfare reasons.

Justification for classification or non-classification

According to CLP (1272/2008/EC) classification criteria for acute toxicity, fatty acids C16 -18 do not fulfill the criteria for classification and thus a non-classification is warranted for this endpoint.