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Diss Factsheets

Administrative data

Description of key information

Oral (OECD 401, limit test), rat: LD50 >5000 mg/kg bw (Gloxhuber and Kästner, 1981)
Oral (OECD 401, limit test), rat: LD50 >2000 mg/kg bw (Ohara, 2002)
Inhalation, IRT, rat, 8h: LC50 >1.3682 mg/L air; CAS# 142-62-1, C6 (Smyth et al., 1954)
Dermal (OECD 402, limit test), rat: LD50 >2000 mg/kg bw ; CAS# 112-05-0, C9 (van Otterdijk, 2001)
Dermal (OECD 402, limit test), rat: LD50 >2000 mg/kg bw; CAS# 111-20-6, C10d (Yu, 1999)
Dermal (OECD 402, limit test), rat: LD50 >2000 mg/kg bw; CAS# 334-48-5, C10 (TalviOja, 2006)

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:
experimental study
Adequacy of study:
key study
Study period:
29 Oct - 12 Nov 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
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: Charles River, Japan
- Age at study initiation: 4 weeks
- Weight at study initiation: female: ~90 g; male: ~100 g
- Fasting period before study: 18 hours
- Housing: metal wire floor cage
- Diet (ad libitum): solid food (CE-2, Clea Japan)
- Water (ad libitum): tap water
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.3 - 24.3
- Humidity (%): 54 - 68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Samples were prepared and administered in suspension
- Amount of vehicle (if gavage): 20 % (w/v)
- Justification for choice of vehicle: test substance is insoluble in water
- Lot/batch no.: V6H2050

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations: once daily and weighing: on days 0, 2, 4, 8, 11 and 15
- Necropsy of survivors performed: yes
Preliminary study:
In a preliminary test, three concentrations (20, 200, 2000 mg/kg bw) were tested in male rats. Soft feces excretion was observed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred of either males or females in the treated groups.
Clinical signs:
other: No effects on general condition were found.
Body weight:
other body weight observations
Remarks:
No effects on body weights were found.
Gross pathology:
Nothing abnormal were detected in gross pathology.
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
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: Winkelmann, Hannover, Germany
- Weight at study initiation: mean male rats: 176 g; mean female rats: 138 g
- Fasting period before study: 18 hours (diet only)
- Housing: females separated from males, in Makrolon cages Typ III with soft wood granulated material
- Diet: ad libitum, Laboratory standard 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: 50%
- Amount of vehicle (if gavage): 10 mL/kg bw (warmed-up)


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: symptoms were observed 1, 4 and 24 hours after application and then once a day up to day 14
- The bodyweights were determined directly before the application and then 24 hours, 7 and 14 days after treatment
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study. All rats survived the observation time of 14 days.
Clinical signs:
other: ca. 20 minutes after application: ruffled fur and very diminished activity - these symptoms disappeared within 24 hours
Body weight:
other body weight observations
Remarks:
The body weight was hardly affected. Mean body weights prior to dosing and on days 1, 7 and 14 after dosing: Males: 176, 177, 195, 214 g; Females: 138, 144, 150, 156 g
Gross pathology:
Stomach mucosa was found to be reddened and swollen, remnants of substance remained in stomach.
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 1) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
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

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-Guideline study tested with the source substance CAS 112-05-0. In accordance to 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 this study was conducted on a read-across substance.
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
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: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: mean males: 369 g; females: 239 g
- Housing: singly
- Diet: standard laboratory diet ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-3
- Humidity (%): 30-70
- Air changes per hour: 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: males 25 cm², females 18 cm²,
- % coverage: 10% of body surface
- Type of wrap if used: surgical gauze, covered with aluminium foil and flexible bandage


REMOVAL OF TEST SUBSTANCE
- Washing: residual test substance was removed using a tissue moistened with water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Constant volume or concentration used: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): apporx. 8 mL/kg bw
- Concentration (if solution): approx. 80%
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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: observations: daily. Weighing: days 1 (pre-treatment), 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: Hunched posture in all treated animals up to day 4.
Body weight:
other body weight observations
Remarks:
No effects on body weight were noted.
Gross pathology:
No findngs noted.
Other findings:
- Other observations: Skin reactions: general erythema, scales and scabs were noted in all animals. Grades 1 and 2 (slight, moderate) prevailed. In 6 of 10 animals, skin reactions persisted until the end of the observation period on day 15.

Skin: not examined histopathologically

Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
10 Oct - 03 Nov 2006
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-Guideline study tested with the source substance CAS 334-48-5. In accordance to 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 this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in Feb 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted in Jul 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Federal Office of Public Health, the Swiss Agency for Therapeutic Products and the Swiss Agency for the Environment, Forests and Landscape, Switzerland
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HanRcc:WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, Füllinsdorf, Switzerland
- Age at study initiation: males: 8 weeks; females: 11 weeks
- Weight at study initiation: males: 264.7-273.6 g; females: 192.7-214.2 g
- Housing: individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation
- Diet: pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet (Provimi Kliba AG, Kaiseraugst, Switzerland), ad libitum
- Water: community tap water, ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10 Oct 2006 To: 03 Nov 2006
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of the back
- % coverage: 10
- Type of wrap if used: The test item was covered with a semiocclusive dressing, which was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 8 mL/kg bw
- Concentration (if solution): 0.25 g/mL
- Dose Formulation: The test item was prepared in the vehicle, PEG 300, to ensure good skin contact. The test item was weighed into a tared glass beaker and the vehicle added (w/v). The formulation was prepared shortly before the application using either a magnetic stirrer and a spatula alone or combined to an Ultra-Turrax as homogenizers. Consistency of dose formulation was considered suitable for dermal application.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
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: Observations for mortality and clinical signs were performed during the first 30 minutes and at approx. 1, 2, 3 and 5 h after administration on test day 1. Thereafter observations for mortality were performed twice daily and for clinical signs once daily, respectively. Body weights were determined on test day 1 (prior to administration) and on days 8 and 15. Local signs were looked at once daily during days 2-15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
other:
Body weight:
other body weight observations
Remarks:
No changes in body weight were noted except one female, which lost 2.3% of body weight during the the first week afer treatment. This female rat showed recovery during the last week of observation.
Gross pathology:
No macroscopic findings were noted at necropsy.
Other findings:
After removal of the dressing, slight to moderate erythema was noted in all animals. The local effects developed into slight to moderate scaling in all animals and slight scabs were observed in all animals except one female. Scaling and/or scabs were reversible within day 5 and 13 in the animals (see table 1).

Table 1: local signs observed after test substance application for 24 h

Animal No. (sex)

Local effect

Test days
(Day 1 = day of application; Day 15 = end of observation period; on day 2 patch was removed)

2

3

4

5

6

7

8

9

10

11

12

13

14

15

1 (m)

erythema

2

1

- 

 -

 -

 -

 -

 -

 -

 -

- 

- 

- 

 -

scaling

- 

2

1

1

1

1

 -

- 

 -

 -

 -

- 

 -

- 

scabs

 -

 -

1

1

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

2 (m)

erythema

2

1

1

 -

- 

 -

 -

- 

 -

 -

- 

 -

- 

 -

scaling

 -

2

2

1

1

1

 -

 -

 -

 -

 -

 -

 -

 -

scabs

 -

 -

 -

1

1

1

 -

- 

 -

 -

 -

- 

 -

 -

3 (m)

erythema

2

1

1

 -

 -

 -

 -

 -

- 

 -

 -

 -

- 

 -

scaling

 -

2

2

1

- 

 -

 -

 -

 -

 -

 -

 -

 -

 -

scabs

 -

 -

 -

1

1

1

- 

 -

 -

 -

 -

 -

 -

 -

4 (m)

erythema

2

1

1

- 

 -

 -

 -

 -

 -

 -

 -

- 

 -

 -

scaling

 -

2

2

1

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

scabs

 -

- 

 -

1

1

1

 -

 -

- 

 -

 -

 -

 -

 -

5 (m)

erythema

2

1

1

1

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

scaling

 -

1

1

1

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

scabs

 -

 -

 -

1

1

 -

 -

 -

 -

 -

- 

 -

 -

- 

6 (f)

erythema

2

1

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

scaling

 -

2

1

1

1

1

 -

 -

 -

 -

- 

 -

 -

 -

scabs

 -

 -

1

1

1

1

- 

 -

- 

 -

 -

 -

 -

 -

7 (f)

erythema

2

1

1

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

scaling

1

2

2

1

- 

 -

 -

 -

 -

- 

 -

 -

 -

 -

scabs

 -

 -

 -

 -

 -

- 

- 

 -

- 

 -

 -

 -

 -

 -

8 (f)

erythema

1

1

1

 -

- 

 -

 -

 -

 -

 -

 -

 -

 -

 -

scaling

- 

 -

1

1

 -

 -

 -

 -

 -

 -

 -

 -

 -

 -

scabs

 -

 -

 -

1

1

1

1

1

1

1

1

1

- 

 -

9 (f)

erythema

1

1

1

 -

 -

 -

- 

 -

 -

 -

 -

 -

 -

 

scaling

 -

 -

1

2

1

1

 -

 -

 -

 -

 -

 -

 -

 -

scabs

 -

 -

 -

 -

 -

 -

 -

1

1

1

1

1

 -

 -

10 (f)

erythema

1

- 

1

 -

- 

- 

 -

 -

 -

 -

 -

 -

 -

 

scaling

 -

2

2

1

1

1

 -

 -

 -

 -

 -

 -

 -

- 

scabs

 -

 -

 -

 -

 -

 -

 -

1

1

 -

- 

- 

 -

- 

1: slight; 2: moderate: -: no local finding

Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
14 Jan - 5 Feb 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-Guideline study tested with the source substance CAS 111-20-6. In accordance to 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 this study was conducted on a read-across substance.
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
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A., Calco, Italy
- Age at study initiation: max. 3 months
- Weight at study initiation: males: 290-350 g; females: 247-286 g
- Housing: 5 animals/sex in grill cages (40.5 x 38.5 x 18 cm) with stainless steel feeder
- Diet: GLP 4RF21 top certificate pelleted diet (Mucedola S.r.l., Settimo Milanese, Italy), ad libitum
- Water: filtered municipal water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 Jan 1999 To: 29 Jan 1999 (males); From: 21 Jan 1999 To: 5 Feb 1999 (females)
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped skin of the dorsal surface (6x5 cm²)
- % coverage: 10
- Type of wrap if used: The test material was held in contact with the skin with a porous gauze dressing fixed to the skin with hypoallergenic non-irritating tape. The site was further covered in a suitable manner in order to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was removed with water.
- Time after start of exposure: 24 h

TEST MATERIAL
- The test material was applied uniformely onto a porous gauze which was moistened with 0.9% NaCl solution.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
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: Animals were observed at 30 minutes, 2, 4 and 6 h on the first day after administration (day 1) and then twice daily until the end of the observation period. Weighing was done before administration of the test substance and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: No general or local abnormalities were observed up to the end of the 14-day observation period.
Body weight:
other body weight observations
Remarks:
Body weights of of all rats were found to be unaffected by the test substance administration.
Gross pathology:
Necropsy revealed no appreciable changes.
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional group, common precursors/breakdown productsand similarities in acute toxicity properties. Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

The acute toxicity via the oral route of docosanoic acid has been investigated in rats in two studies.

Acute oral toxicity of docosanoic acid was evaluated in a study with Wistar rats which was performed according to GLP and OECD Guideline 401 (Gloxhuber and Kästner, 1981). Five animals of each sex received an oral application of 10 mL/kg bw of docosanoic acid dissolved in DMSO at a dose level of 5000 mg/kg bw by gavage. No clinical signs were noted during the 14-day observation period except ruffled fur and very diminished activity which was seen 20 min after dosing but disappeared within 24 hours. At gross pathology, reddened and swollen mucosa and remnants of the test substance were noted in the stomach. Since no mortality was noted, the LD50 of docosanoic acid was found to be >5000 mg/kg bw.

A LD50 of >2000 mg/kg bw was found in another study, also performed in accordance to GLP and OECD guideline 401 (Ohara, 2002). Five male and five female Sprague-Dawley rats received an oral dose of 2000 mg/kg bw docosanoic acid dissolved in corn oil to a 20% solution via gavage. No effects on general condition and on body weights were found. Also, no abnormality was detected during gross pathology.

In summary, the oral LD50 value of docosanoic acid was greater than 2000 mg/kg bw.

Inhalation

Only very limited data on acute inhalative toxicity of fatty acids is available. The only available data on acute inhalation toxicity of fatty acids are data of a published inhalation risk test with C6 fatty acid (hexanoic acid). Hexanoic acid (CAS# 142-62-1) has the highest vapour pressure among the members of the fatty acids category. No mortality of rats was reported after an 8-hour exposure to a saturated atmosphere which corresponds to a value of >1.3682 mg hexanoic acid/L air based on QSAR calculation (Danish EPA Database, 2004). However, due to limited information this study is regarded insufficient for assessment.

In general, inhalation of fatty acids as vapour is not expected due to the low vapour pressure of ≤ 0.06 hPa. In addition, exposure to particles of inhalable size can be excluded under normal conditions of use. In case of respiratory uptake long chain fatty acids (>C12) will not cause adverse local or systemic effects but will be absorbed in the lungs and undergo normal metabolism. The likelihood of persistence in the lungs is considered non-existent.

Therefore testing is not justified for the inhalation route in accordance to EC 1907/2006, Annex VIII, Column 2, Section 8.5 and due to animal welfare reasons. No study is required since exposure of humans via inhalation is unlikely taking into account the physico-chemical properties of the substance and the lack of exposure to particles of inhalable size under normal conditions of use. Moreover, in case of respiratory uptake long chain fatty acids (>12) will not cause adverse local or systemic effects but will be absorbed in the lungs and undergo normal metabolism. The likelihood of persistence in the lungs is considered non-existent. Data for the most relevant routes of human exposure (oral and dermal route) are provided for fatty acids.

 

Dermal

No data on acute dermal toxicity is available for docosanoic acid. Therefore acute dermal health effects are predicted from adequate and reliable data for source substances by read-across to the target substance within the group applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006.

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 discussion on toxicokinetics).

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 C9 fatty acid nonanoic acid, C10 fatty acid (decanoic acid) and C10 dicarboxylic fatty acid (sebacic acid).

The acute dermal toxicity of nonanoic acid (CAS# 112-05-1) was examined in Wistar rats according to OECD Guideline 402 and under GLP conditions (van Otterdijk, 2001). The animals were treated with an occlusive patch for 24 hours. All animals survived the 14-day observation period following the application of 2000 mg/kg bw. Clinical signs of toxicity were hunched posture on the treatment day and the following three days. Skin reactions due to the corrosive properties of nonanoic acid were noted in all treated animals and consisted of general erythema, scales and scabs of the treated skin, generally of slight to moderate grade. In 6 of 10 animals, skin reactions persisted until the end of the observation period on day 15. Body weights were not affected, and there were no abnormalities at necropsy after sacrifice on day 15.

After the semiocclusive application of sebacic acid (CAS# 111-20-6) on the skin of Sprague-Dawley rats for 24 hours according to OECD Guideline 402 and under GLP condition, a LD50 of >2000 mg/kg bw was observed (Yu, 1999). No mortality occurred during the 14-day observation period and no clinical signs or body weight abnormalities were noted till the end of the study. Additionally, no macroscopic findings were evident.

The acute dermal toxicity of decanoic acid (CAS# 334-48-5) was investigated in a limit test according to OECD guideline 402 and in compliance with GLP (TalviOja, 2006). In this study, 5 male and 5 female HanRCC: WIST rats were treated with the test substance at a dose of 2000 mg/kg bw. The test substance was dissolved in polyethylene glycol at a concentration of 250 mg/mL and applied onto the clipped skin of the test animals (8 mL/kg bw) for 24 h under semiocclusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No deaths occurred and the body weight of all animals was within the normal range except of one female rat which lost 2.3% of body weight during the first week after treatment. This female rat showed recovery during the last week of observation. 4/5 males and 3/5 females were found slightly or moderately sedated on day 2 of the study after patch removal. Furthermore, at this time point 3 males and 2 females showed deep respiration and 3 males and 1 female revealed hunched posture. From day 3 on no further clinical signs were recorded in any of the treated rats. After removal of the dressing, slight to moderate erythema was noted in all animals. The local effects developed into slight to moderate scaling in all animals and slight scabs were observed in all animals except one female. Scaling and/or scabs were reversible within day 5 and 13 in the animals. At necropsy, no findings were noted. Therefore, the LD50 in male and female rats is > 2000 mg/kg bw.

The dermal absorption of C9 fatty acid (nonanoic acid) with 0.014 mg/cm², of C10 fatty acid (decanoic acid) with 0.009 mg/cm² and of C10 dicarboxylic fatty acid (sebacic acid) with 0.01 mg/cm² is greater compared to fatty acids with longer chain lengths (e.g. C12 fatty acid: 0.005 mg/cm², C22 fatty acid: 0.00005 mg/cm² or C18:1 fatty acid: 0.00033 mg/cm²) and can therefore be considered as “worst case assumption” for acute dermal absorption and consequently for the toxicity of fatty acids.

 

This is being supported by Opdyke et al. (1978, 1979 and 1981 as cited in Cragg, 2001), who reported in a short summary, that the acute dermal LD50 in rabbits for octanoic acid (CAS# 124-07-2), nonanoic acid (CAS# 112-05-0), decanoic acid (CAS# 334-48-5) and stearic acid (CAS# 57-11-4) exceeded 5000 mg/kg bw. In addition, the topical application of commercial grade oleic acid to the skin of guinea pigs at a concentration of 3000 mg/kg bw produced no deaths (CIR, 1987).

In conclusion, based on available data on various representative substances within the fatty acids category, no acute dermal toxicity for members of the fatty acids category are expected.

References

Cragg, S.T. 2001. Aliphatic Carboxylic Acids, Saturated. Patty’s Toxicology

CIR, 1987. Final Report on the Saftey Assessment of Oleic Acid, Lauric Acid, Palmitic Acid, Myristic Acid, and Stearic Acid. Journal of the American College of Toxicology 6(3):321-401

QSAR; Danish EPA Database, 2004: http://130.226.165.14/

 


Justification for classification or non-classification

All available data on acute oral and dermal toxicity of the members of the fatty acids category do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

There is no adequate and reliable study available for assessment of acute inhalation toxicity. The results of the available data on acute inhalation toxicity of hexanoic acid are insufficient for assessment and therefore inconclusive for classification according to Regulation (EC) 1272/2008.