Nonanoic acid

Endpoint summary

Description of key information

The oral LD50 of pelargonic acid was determined to be > 2000 mg/kg bw in male and female rats in a valid GLP study using the Acute Toxic Class Method (OECD TG 423) (NOTOX, 2001).
The inhalation LC50 of pelargonic acid was determined to be > 5.997 mg/L in a valid acute inhalation study (aerosol, nose-only exposure) (Emery, 2014).
The dermal LD50 of pelargonic acid was determined to be > 2000 mg/kg bw in male and female rats in a valid GLP study according to OECD TG 402 (NOTOX, 2001).

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

Test type:

acute toxic class 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. 6 weeks
- Weight at study initiation: mean males: 275 g; females: 176
- Fasting period before study: max. 20 hours
- Housing: in groups of 3
- Diet: ad libitum starting at 4 hours after dosing
- Water: tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/10 mL
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: based ob results of a pretest


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


DOSAGE PREPARATION: purity of test substance was taken in to account. formulations (w/w) were prepare dwithin 4 hours prior to dosing.


CLASS METHOD
- Rationale for the selection of the starting dose: limit dose 2000 mg/kg bw

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 and weighing: observations: twice daily. Weighing: days 1 (pre-treatment), 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

not needed

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred

Clinical signs:

other: Lethargy and uncoordinated movements were seen on days 1 and/or 2. Piloerection in one female on day 1.

Gross pathology:

No abnormalities seen at necropsy.

Interpretation of results:

other: GHS critertia under EU CLP (1272/2008/EC) not met

Conclusions:

The oral LD50 was >2000 mg/kg bw in male and female rats.

Executive summary:

The acute oral toxicity of pelargonic acid was examined in Wistar rats (3/sex) in a toxic class study, performed according to OECD guideline 423 and under GLP conditions. All animals survived the 14-day observation period following the administration of 2000 mg/kg bw by oral gavage. Clinical signs of toxicity were limited to slight to moderate lethargy and uncoordinated movements on the treatment day and/or the following day. Body weights were not affected, and there were no abnormalities at necropsy after sacrifice on day 15. The acute oral LD₅₀ was therefore >2000 mg/kg bw in rats (NOTOX, 2001).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

sufficient for assessment

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2013-11-12 to 2014-02-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animan Breeding Facility, Jai Resaerch Foundation
- Age at study initiation: 10-11 weeks
- Weight at study initiation: males min.: 319.9, max.: 331.6, females min.: 225.3, max.: 225.6
- Housing: Polypropylene rat cages covered with stainless steel grid tops. Autoclaved clean risce husk as bedding material, 3 animal/cage
- Diet: Teklad certified Global High Fiber rat/mice feed manufactured by Harlan USA, ad libitum
- Water: UV sterilized water filtered through Kent Reverse Osmosis water filtration system, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19- 23
- Humidity (%): 64 - 65
- Air changes (per hr): min 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

ca. 3.22 µm

Geometric standard deviation (GSD):

ca. 2.84

Remark on MMAD/GSD:

50 % MMAD: 3.22 µm
84.1 % MMAD: 9.14 µm

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation exposure system from BIO TOX Instrumentations International, New Dehli, India
- Exposure chamber volume: 63.5 L
- Method of holding animals in test chamber: Rat exposure tubens are accomodated in the portholes of the inhalation chamber
- Source and rate of air: 15 -20 L/min
- Method of conditioning air: Compressed filtered air
- System of generating particulates/aerosols: Spray atomizer
- Method of particle size determination: gravimetric concentration analysis
- Treatment of exhaust air: outgoing air passes through an impinger containing 1.0 % sodium hydroxide solution and moisture traps
- Temperature, humidity, pressure in air chamber: 19.5-20.5 °C, relative humidity: 64.2%- 67.2%

TEST ATMOSPHERE
- Brief description of analytical method used: aerosol particles were collected on pre-weighed glass micro fiber filters. this was followed by an gravimetric concentration analysis
- Samples taken from breathing zone: yes

VEHICLE
- 90% Pelargonic acid was the test substance and was not diluted before use.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal concentration was 20.089 mg/L air. After gravimetric determination an actual concentration of 5.997 mg/L air in the breathing zone was determined.

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations twice a day, weighing on observations days 0, 1, 3, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, external observation after necroscopy, opening of the nasal passage, abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.997 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other:

Remarks:

LC50 value could not be calculated because no mortality occurred

Mortality:

No animal died during the exposure time and the 14 days of observation.

Clinical signs:

other: No treatmnet related clinical signs were observed.

Body weight:

Decrease in mean body weight was observed on days 1 and 3 whereas increase in mean body weight was observed on days 7 and 14 when compared with days 0 mean body weight in both sexes.

Gross pathology:

No observations

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The 4 h LC50-value of 90% pelargonic acid in male and female Wistar rats was found to be > 5.997 mg/L air in the breathing zone.

Executive summary:

In this guideline conform study (OECD TG 403, under GLP) 3 male and 3 female Wistar rats were exposed for 4 h to 90% pelargonic acid in a breathing chamber. The concentration in the breathing zone was calculated to be 5.997 mg/L air. After an observation time of 14 days, no animal died, and no clinical effects were observed. Decrease in mean body weight was observed on days 1 and 3 of the observation whereas increase in mean body weight was observed on days 7 and 14 when compared with days 0 mean body weight in both sexes. No effects were observed during gross pathology as well. Based on the findings an LC50 value of > 5.997 mg/L was determined.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 997 mg/m³ air

Quality of whole database:

sufficient for assessment

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

fixed dose procedure

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

Statistics:

not needed

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality occurred

Clinical signs:

other: Hunched posture in all treated animals up to day 4. 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 pe

Gross pathology:

No findings noted

Skin: not examined histopathologically

Interpretation of results:

other: GHS critertia under EU CLP (1272/2008/EC) not met

Executive summary:

The acute dermal toxicity ofpelargonicacid (2000 mg/kgbw) was examined in Wistar rats (5/sex) according to OECD guideline 423 and under GLP conditions. All animals survived the 14-day observation period following the application of 2000 mg/kgbw. Clinical signs of toxicity were hunched posture on the treatment day and the following three days, and skin reactions which were seen in all treated animals. The skin reactions were 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. The acute dermal LD₅₀ was therefore >2000 mg/kg bw in rats (NOTOX, 2001).

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

sufficient for assessment

Additional information

Oral route:

The acute oral toxicity of pelargonic acid was examined in Wistar rats (3/sex/step) in a toxic class study, performed according to OECD guideline 423 and under GLP conditions. All animals survived the 14-day observation period following the administration of 2000 mg/kg bw by oral gavage. Clinical signs of toxicity were limited to slight to moderate lethargy and uncoordinated movements on the treatment day and/or the following day. Body weights were not affected, and there were no abnormalities at necropsy after sacrifice on day 15. The acute oral LD₅₀ was therefore >2000 mg/kg bw in rats (NOTOX, 2001).

Dermal route:

The acute dermal toxicity of pelargonic acid was examined in Wistar rats (5/sex) according to OECD guideline 402 and under GLP conditions. 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, and skin reactions which were seen in all treated animals. The skin reactions were 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. The acute dermal LD₅₀ was therefore >2000 mg/kg bw in rats (NOTOX, 2001).

Inhalation:

Data on acute inhalation toxicity are available from two reliable studies: The Emery study was performed according to OECD TG 403 and GLP with Wistar rats (3 males and 3 females) which were exposed to 5.997 mg n-nonanoic acid/L air using a nose-only inhalation exposure system (Emery, 2014). Rats were exposed for 4 hours and observed for 14 days, test item purity was ca. 90%. No treatment-related mortality, clinical signs or necropsy findings were observed. Decreases in mean body weight were observed on days 2 and 3. Mean body weight was increased on days 7 and 14 when compared with day 0 body weight. Based on the findings of this key study (Emery, 2014; RL1) it is concluded that the acute LC50 for n-nonanoic acid is > 5.997 mg/L.

In the Bio/dynamics study (1990) Sprague-Dawley rats (5 per sex and group) were whole-body exposed to aerosols of the test substance in actual concentrations of 0.46 and 3.8 mg/l for 4 h. No mortality was observed at the lower concentration, 8/10 animals died at 3.8 mg/l. This study points to a LD50 > 0.46 mg/l and <3.8 mg/l. The exposed animals showed signs of respiratory irritation and transient body weight decreases. Post-mortem examination showed no clear signs of treatment-related organ lesions (Bio/dynamics, 1990; RL2). There were great differences between the nominal and gravimetric exposure concentration of the high dose group (31 vs. 3.8 mg/L, respectively). This might be due to impaction or sedimentation of the aerosol on the surfaces in the exposure chamber as discussed by the study authors. This adds some uncertainty to the overall exposure assessment, therefore the study was assigned RL 2. Whereas this study was not regarded as relevant in the RAC-opinion proposing harmonised classification and labelling at EU level of nonanoic acid it is regarded in this context in a weight-of-evidence approach.

The findings of the Emery study are supported by further studies mentioned in the CLH-report of nonanoic acid (2011). These additional acute inhalation studies with nonanoic acid were submitted in the context of the biocide regulation: One study reported a LC50 of > 5.3 mg/L (Copping, 1998) and another study reported a LC50 of > 5.9 mg/L (both studies: 4 h exposure, no information on species, strain, sex, number of animals).

Smyth et al. (1962) reported that no rats died during 8 or 4 h exposure to saturated vapour of decanoic (about 0.003 mg/L) and octanoic acid (about 0.03 mg/L), respectively. No higher concentrations were tested. A LC50 value of > 4.1 mg/L (2 h exposure, no information on species, strain, sex, number of animals) is mentioned in the CLH report for decanoic acid (CLH, 2012).

In summary, it is concluded that the result of the Emery study should become more importance than the Bio/dynamics study, as the result of the Emery study is supported by several other studies and the Bio/dynamics study reveals some uncertainty with respect to the exposure assessment. Based on the findings of the Emery study (LC50 > 5.3 mg/L) it is concluded that n-nonanoic acid does not need to be classified for acute inhalation toxicity under Regulation (EC) No. 1272/2008

Justification for classification or non-classification

Acute oral and dermal toxicity: Classification criteria of Regulation (EC) No. 1272/2008/EC not met (LD50 > 2000 mg/kg).

Acute inhalation toxicity: Based on the findings of the Emery (2014) study with an LC50 > 5.997 mg/L, which is supported by several other studies with n-nonanoic acid and findings from tinformation reported for decanoic and octanoic acid it is concluded that n-nonanoic acid does not need to be classified for acute inhalation toxicity according to Regulation (EC) No. 1272/2008.