Decanoic acid

Endpoint summary

Description of key information

Oral (OECD 401, limit test), rat: LD50 >2000 mg/kg bw; CAS# 124-07-2, C8

Oral (OECD 401, limit test), rat: LD50 >5000 mg/kg bw; CAS# 143-07-7, C12

Dermal (OECD 402, limit test), rat: LD50 >2000 mg/kg bw

No data on acute inhalation toxicity available.

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:

Please refer to the category justification provided in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source CAS 124-07-2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source CAS 143-07-7

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Based on available read-across studies, the oral LD50 value for decanoic acid is considered to be >2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

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 Wiga GmbH, Sultzfeld, Germany
- Age at study initiation: 7 weeks
- Weight at study initiation: males: 206-230 g; females: 170-181 g
- Fasting period before study: overnight (prior to dosing) until approximately 3.5 hours after administration
- Housing: individually in polycarbonate cages containing purified sawdust as bedding material
- Diet: standard pelleted laboratory animal diet (RMH-B, Hope Farms, Woerden, The Netherlands)
- Water: tap-water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 50 - 60
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

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: The animals were observed for any signs of toxicity approximately once every two hours after dosing and once daily thereafter for 14 days. Individual bodyweights were measured weekly.
- Necropsy of survivors performed: Yes, at the end of the study (day 14), all animals were anaesthetised by CO2/O2 inhalation, subsequently killed by CO2 and subjected to necropsy
- 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: No signs of systemic toxicity were observed during the 14 day observation period.

Gross pathology:

Macroscopic examination of animals at termination revealed firm and/or small white/greyish irregular patches in the forestomach of all animals.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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:

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 males 164 g, females 133 g
- 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:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 250 mg/mL
- Amount of vehicle (if gavage): 20 mL/kg bw


MAXIMUM DOSE VOLUME APPLIED: 20 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, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Clinical signs appeared approximately 20 minutes after dosing including slightly ruffled fur, which subsided completely within 24 hours. No other effects noted.

Gross pathology:

Slight reddening of the gastric mucosa was seen. No other effects noted.

Interpretation of results:

other: CLP/EU GHS 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

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 1) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional group, common precursors/breakdown products and 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 VII, 8.5, in accordance with Annex XI, 1.5, 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

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 Oct - 03 Nov 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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: 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 n

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: sligth; 2: moderate: -: no local finding

Interpretation of results:

other: CLP/EU GHS 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

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 1) study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5.3, of Regulation (EC) No 1907/2006.

Additional information

Oral

No reliable data on acute oral toxicity are available for decanoic acid. Therefore acute oral toxicity is 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. In particular, the source substances structurally closest to the target substance are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Thus, reliable studies with C8 fatty acid (octanoic acid) and C12 fatty acid (lauric acid) are used for the hazard assessment of decanoic acid in regard to acute oral toxicity.

Acute oral toxicity of octanoic acid (CAS# 124-07-2) was analyzed in a study performed under GLP according to OECD guideline 401 (1988). In this limit test 5 male and 5 female Wistar rats received a dose of 2000 mg/kg bw octanoic acid by gavage. No signs of systemic toxicity and no change in body weight gain were observed during the 14 day observation period. Macroscopic examination of animals at termination revealed only, firm and/or small white/greyish irregular patches in the forestomach of all animals. Since no mortality occurred, the oral LD50 value was found to be >2000 mg/kg bw.

Acute oral toxicity of lauric acid (CAS# 143-07-7) was analyzed in a limit test performed according to OECD guideline 401. 5 male and 5 female Wistar rats received 5000 mg/kg bw by gavage (1981). Clinical signs were ruffled fur which appeared approximately 20 minutes after dosing and subsided completely within 24 hours. Since no other clinical signs and no mortality was noted within the 14-day observation period, an oral LD50 value of >5000 mg/kg bw was determined for lauric acid.

Briggs et al. (1976) reported for decanoic acid an oral LD50 value of >10000 mg/kg bw in male albino rats. The animals demonstrated a weight gain of at least 30% over original body weight during the 14-day test period and were within normal limits for rats of the age, sex and strain used in this study. This publication provided only limited information and is therefore not sufficient for hazard assessment.

In one further study decanoic acid is administered as 5% solution in 40% (w/w) ethanol. This study is not taken into account for hazard assessment, since the test system was unsuitable.

 

In general, all available studies investigating the acute oral toxicity of fatty acids category members resulted in LD50 values >2000 mg/kg bw, indicating no hazard for acute oral toxicity.

Due to the similar structural and toxicological properties of the members within the category including decanoic acid, octanoic acid and lauric acid, the oral LD50 value for decanoic acid can be set as >2000 mg/kg bw.

 

Inhalation

Very limited data on acute inhalative toxicity of fatty acids is available within the fatty acids category.

An inhalation risk test was conducted with hexanoic acid (CAS# 142-62-1; Smyth et al., 1954).No mortality of rats was reported after an 8-hour exposure to a saturated atmosphere which corresponds to a concentration of >1.3682 mg/L air based on QSAR calculations (Danish EPA Database, 2004). A LC50 value of 4.1 mg/L was reported for mice exposed to hexanoic acid for 2 hours (RTECS, 2000). These references are only short abstracts and therefore not sufficient for hazard assessment.

In general, inhalation of fatty acids as vapour is not expected due to the low vapour pressure of ≤ 0.06 hPa (please refer to category justification).Short- and mid-chain fatty acids C6 – C12 are proven irritant/corrosive substances which cause local effects in the respiratory tract. In case of aerosol forming conditions, risk management measures and operational conditions including personal protective equipment have to be implemented in order to avoid inhalation.

In accordance with Column 2 of Annex VIII, Section 8.5, of Regulation (EC) No 1907/2006 and due to animal welfare reasons, further testing by the inhalation route is not appropriate.

 

Dermal

The acute dermal toxicity of decanoic acid was investigated in a limit test according to OECD guideline 402 and in compliance with GLP (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 dermal LD50 value for decanoic acid in male and female rats is >2000 mg/kg bw.

 

References:

RTECS, 2000 as cited in BUA Report 2000

Smyth, H. F. Jr. et al.(1954). RANGE-FINDING TOXICITY DATA - List V. AMA archives of industrial hygiene and occupational medicine, 10/501/51: 61-68.

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) No 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 within the fatty acids category on acute inhalation toxicity of hexanoic acid (inhalation risk test in rats) is insufficient for assessment.