Sodium 2-ethylhexanoate

Endpoint summary

Description of key information

According to the results of valid GLP OECD Guideline studies,the source substance of this read across approach, 2-Ethylhexanoic acid, is practically non-toxic via the oral, dermal and inhalative route (for read across justification please refer to the attached document, IUCLID Chapter 13). The following values are taken into account for the risk assessment: LD50 (oral;rat): 2043 mg/kg bw; LD50 (dermal,rat) >2000 mg/kg bw; no acute toxicity from inhalative exposure to saturated vapor.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP, non-guideline, limitations in design and/or reporting

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Kingston, NY
- Age at study initiation: 8 weeks
- Weight at study initiation: 106-124 g


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71-75
- Humidity (%): 51-52
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg b.w.

Doses:

0, 90, 722, 1445, 2890 mg/kg b.w.

No. of animals per sex per dose:

4

Control animals:

yes

Details on study design:

Animals were observed several times during the first 24 hours after dosing and once each workday thereafter for the duration of the test
(a total of 14 calendar days). Body weights were collected on the day of dosing and 1, 2, 3, 7, and 14 days after dosing.
All animals were necropsied . Animals which died after administration of the test article were necropsied promptly . All animals surviving the scheduled observation period were euthanetized and necropsied 14 days after test article administration.

Statistics:

none

Sex:

female

Dose descriptor:

LD50

Effect level:

2 043 mg/kg bw

Based on:

test mat.

95% CL:

1 445 - 2 890

Mortality:

Dose (mg/kg b.w.):
90 mg/kg b.w.: 0/4
722 mg/kg b.w.: 0/4
1445 mg/kg b.w.: 0/4
2890 mg/kg b.w.: 4/4

Clinical signs:

other: weakness (90, 722, 1445 mg/kg b.w.) prostration (2890 mg/kg b.w.)

Gross pathology:

90, 722 and 1445 mg/kg b.w. dose groups: no treatment-related changes were observed. No tissue was collected for microscopic examination.
2890 mg/kg b.w.: the cause of death for rats dying after exposure to the test material was not determined. Treatment-related changes consisted of compuond present in the duodenum(1/4), jejunum (3/4), ileum (3/4), cecum (4/4), colon (4/4) and fecal discoloration (1/4) and wetness (1/4) of the inguinal hair.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of 2-ethylhexanoic acid was 2043 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification according to regulatory requirements.
Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be acute orally toxic and is therefore not subjected for labelling and classification requirements according to regulatory requirements.

Executive summary:

A read across was performed from the source substance 2 -ethylhexanoic acid to the target substance sodium 2 -ethylhexanoate (for read across justification please refer to attached document, IUCLID Chapter 13).

2 -Ethylhexanoic aicd was tested for its acute oral toxicity potential. 4 female rats were treated with doses of 90, 722, 1445 or 2890 mg/kg bw and observed for 14 days.

The median lethal dose of test item (LD50) was 2043 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification according to regulatory requirements.

Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be acute orally toxic and is therefore not subjected for labelling and classification requirements according to regulatory requirements.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 043 mg/kg bw

Quality of whole database:

reliable with restrictions

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

Feb 1967

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is comparable with the inhalation hazard test described in the Annex of OECD Guideline 403 (adopted 1981) with acceptable restrictions (partly limited documentation; post exposure observation period 7 days; low number of rats)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

Inhalation hazard test

Deviations:

no

GLP compliance:

no

Test type:

other: Inhalation hazard test

Species:

rat

Strain:

not specified

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
Rats exposed for 8 h, respectively, to a vapour saturated atmosphere. Vapour was generated by bubbling 200 l/h dry air (no CO2) through the liquid substance column (volume ca. 50 ml) of about 5 cm above a fritted glass disc in a glass cylinder. The glas cylinder was heated in a water bath. Temperature in the exposure chamber was 20°C. Concentration was stated in the raw data to be 0.11 mg/l. this was calculated based on the substance loss. Base on a vapor pressure 0f 0.04 mbar and a molecular weight of 144.21 saturated vapor concentration of 2-Ethylhexanoic acid is 0.24 mg/l. Concentration of 0.11 mg/l may be regarded as reliable therefore

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

0.11 mg/l (nominal)

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days

Statistics:

not necessary

Sex:

male/female

Dose descriptor:

LC0

Effect level:

0.11 mg/L air (nominal)

Exp. duration:

8 h

Remarks on result:

other: inhalation hazard test

Mortality:

No Mortality was observed.

Clinical signs:

other: no clinical signs were noted

Body weight:

no data

Gross pathology:

no substance related findings. In one animal bronchitis was detected.

The inhalation risk test demonstrates that there is no hazard from 2 -ethylhexanoic acid to be expected at room temperature.

Interpretation of results:

other: LC0 after 8 h exposure: 0.11 mg/L (saturated atmosphere)

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

The LC0 of 2-ethylhexanoic acid after 8 h inhalation exposure is 0.11 mg/L (saturated atmosphere).
Based on a read-across approach, sodium 2-ethylhexanoate is not considered to have a similar LC0 value.

Executive summary:

A read across was performed from the source substance 2 -ethylhexanoic acid to the target substance sodium 2 -ethylhexanoate (for read across justification please refer to attached document, IUCLID Chapter 13).

6 rats/sex were exposed to an 2 -ethylhexanoic acid saturated atmosphere at a calculated concentration of 0.11 mg/L for 8 hours. No mortality or clinical signs were reported. The gross necropsy did not reveal any substance related findings.

Based on a read-across approach, sodium 2-ethylhexanoate is not considered to have a similar LC0 value.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

reliable with restrictions

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

Oct - Nov 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

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: Hoechst AG, Kastengrund, SPF
- Age at study initiation: 7 weeks (males) 9 weeks (females
- Weight at study initiation: 208 +/- 4 g (males); 191 +/- 3 g (females
- Fasting period before study: no
- Housing: single in macrolone cages (Type 3) on wooden bedding
- Diet (e.g. ad libitum): ad libitum Altromin 1234 (Altromin GmbH, Lage/Lippe)
- Water (e.g. ad libitum): tab water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20 %
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 x 8 cm
- % coverage:
- Type of wrap if used: alu folie, fixed by tape (Fixomull; Elastoplast; Fa. Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.2 ml pure substance (desity 0.9 g/ml)

Duration of exposure:

24 h

Doses:

2000 mg/kg

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: observation : daily; weighing prior to application on day 7 and day 17 (Study termination)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

not necessary

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality

Clinical signs:

other: no clinical symptoms besides eshar formation in two females from day 5-day 8

Gross pathology:

no substance related macroscopic findings

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dermal dose of 2-ethylhexanoic acid wasgreater than 2000 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification according to regulatory requirements.
Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be acute dermally toxic and is therefore not subjected for labelling and classification requirements according to regulatory requirements.

Executive summary:

A read across was performed from the source substance 2 -ethylhexanoic acid to the target substance sodium 2 -ethylhexanoate (for read across justification please refer to attached document, IUCLID Chapter 13).

2 -Ethylhexanoic aicd was tested for its acute dermal toxicity potential. 5 female and 5 male rats were treated with 2000 mg/kg bw and observed for 14 days.

The median lethal dermal dose of test item (LD50) was greater than 2000 mg per kg body weight. Based on the result of this study the test substance is not subject for labelling and classification according to regulatory requirements.

Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be acute dermally toxic and is therefore not subjected for labelling and classification requirements according to regulatory requirements.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

reliable without restrictions

Additional information

A read across was performed from the source substance 2 -ethylhexanoic acid to the target substance sodium 2 -ethylhexanoate (for read across justification please refer to attached document, IUCLID Chapter 13).

Valid acute toxicity studies after oral, dermal and inhalative exposure are available for 2-ethylhexanoic acid.

In an acute oral toxicity study 4 female rats/dose were dosed with 90, 722, 1445 or 2890 mg/kg bw. No mortality was observed in the 90, 722 and 1445 mg/kg bw dose groups. The test material caused mortality in rats administered a dose of 2890 mg/kg bw (4/4), and transitory weakness at lower doses in a dose-dependent manner. The LD50 was calculated to 2043 mg/kg bw.

 

No mortality was observed in 12 rats (6 m; 6f) after 8 h exposure to saturated 2-ethylhexanoic acid vapor in an inhalation hazard test comparable to OECD 403 Annex 1. Maximal achievable concentration in this test system was 0.11 mg/L (nominal concentration).

 

Dermal toxicity of 2 -ethylhexanoic acid was tested in an OECD 402 guideline study. Five Wistar rats/sex/dose have been exposed dermally (semi-occlusive) to a limit dose of 2000 mg/kg bw 2-ethylhexanoic acid. No mortality and no clinical symptoms beside eshar formation have been observed. Therefore, the dermal LD50 is > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
GLP, non-guideline, limitations in design and/or reporting

Justification for selection of acute toxicity – inhalation endpoint
Study is comparable with the inhalation hazard test described in the Annex of OECD Guideline 403 (adopted 1981) with acceptable restrictions (partly limited documentation; post exposure observation period 7 days; low number
of rats)

Justification for selection of acute toxicity – dermal endpoint
GLP Guideline study

Justification for classification or non-classification

Classification for acute toxicity is not warranted according to the criteria of EU Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Based on a read-across approach, sodium 2-ethylhexanoate is not considered to be acute tocix and is therefore not subjected for labelling and classification requirements according to regulatory requirements.