Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol

Endpoint summary

Description of key information

Oral: LD50 (rat, m/f) = >2000 mg/kg bw
Inhalation: LC50 (rat, m/f) > 5.1 mg/L 
Dermal: no study available

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

Study period:

26 Aug 2003 - 11 Sep 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Japanese test guideline (Acute Oral Toxicity - Acute Toxic Class Method)

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. 9 weeks
- Weight at study initiation: mean 292 g (males), mean 202 g (females)
- Fasting period before study: overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance
- Housing: in groups of three animals per sex per cage in MAcrolon cages (type VI; heigh 18 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany)
- Diet: standard pelleted laboratory animal diet (from Altromin (code VRF1), Lage, Germany); ad libitum
- Water (e.g. ad libitum): tap-water; ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 (acual range: 18.1 - 23.1)
- Humidity (%): 30 - 70 (actual range: 39 - 72)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 26 Aug 2003 To: 09 Sep 2003

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw (2.128 mL/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: Mortality/viability was checked twice daily. Checks for clinical signs were done at periodic intervals on the day of dosing (day 1) and once daily teherafter until day 15. Animals were weighed on days 1 (prior to doing), 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 clinical signs of systemic toxicity were noted.

Gross pathology:

No abnormalites were found.

Other findings:

- Other observations: Brown staining of the fur on the back and neck was observed in one female between days 9 and 12 and in one male between days 7 and 10.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

DSD: not classified
CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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:

March 22nd, 1994 - April 05th, 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: No details on test material

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Alderly Park, Cheshire, UK
- Age at study initiation: approx. 7 weeks

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Source and rate of air: dried and filtered air
- System of generating aerosols: glass concentric jet atomiser
- Method of particle size determination: Marple Cascade Impactor
- Temperature, humidity, pressure in air chamber: 20 l/min


TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrically
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.51 µm/2.51


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: maximum concentration of 5 mg/l (OECD limit test)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

particulate concentrations of the test atmospheres close to the animals breathing zone were measured gravimetrically

Duration of exposure:

4 h

Concentrations:

5.0 mg/l (nominal)
5.10 mg/l (analytical)

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: daily, recording of body weight on days 1, 2, 3, 8 and 15
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.1 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

None

Clinical signs:

other: Reversible and consistent with the use of restraint for exposure to the test atmosphere. Hunched position, chromodacryorrhea, piloerection, stains around the nose and wet fur.

Body weight:

Body weight gain was within normal limits.

Gross pathology:

No treatment related gross pathological findings.

Other findings:

- Organ weights: Lung weight was within normal limits.

Bodiweight, bodyweight gain and lung weights for all treated animals were within normal limits and there were no gross pathological findings. In general, animals showed rapid recovery from effects seen.

The medium lethal concentration in the rat is considered to be in exess of 5.1 mg/l

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 100 mg/m³ air

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional groups, common precursors/breakdown products and similarities in physicochemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus 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.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for grouping of substances and read-across

There are no data available for the acute toxicity of Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol (CAS 92113-48-9). In order to fulfil the standard information requirements set out in Annex VIII, 8.5.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) is selected as source substance for assessment of acute toxicity by inhalation.

Acute Toxicity

CAS	92113-48-9 (a)	68424-31-7 (b)
Chemical name	Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol	Fatty acids, C5-10, esters with pentaerythritol
MW	512.8 – 975.5 g/mol	472.62 - 753.14g/mol
Acute toxicity oral	Experimental result: LD50 > 2000 mg/kg bw	Experimental result: LD50(rat, m/f) > 2000 mg/kg bw
Acute toxicity inhalation	RA: CAS 68424-31-7	Experimental result: LC50(rat, m/f) > 5100 mg/m³
Acute toxicity dermal	--	--

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the similarities in structure, properties and/or activities. The available endpoint information is used to predict the same endpoint for Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol (CAS 92113-48-9).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

Acute toxicity, oral

Acute oral toxicity was evaluated in a limit test performed according to OECD guideline 423 and under GLP conditions (van Hyegevoort, 2003). Groups of three male and female Wistar rats received a single dose of 2000 mg/kg bw of the test substance by oral gavage. No effects on body weight gain were observed and no abnormalities were found after gross pathology. Since neither clinical signs nor mortality occurred during the 14-day observation period, the LD50 was > 2000 mg/kg bw.

Acute toxicity, inhalation

Acute inhalation toxicity is assessed by using data from the structural analogue Fatty acids, C5-10, esters with pentaerythritol, which was tested in a limit test in accordance with OECD guideline 403 and GLP (Parr-Dobrzanski, 1994). Five male and female Alpk:APfSD rats were exposed nose only for 4 hours to approximately 5.1 mg/L (analytical concentration of the aerosol of the test material). No mortality occurred and no signs of systemic toxicity were observed during the 14-day observation period. Other effects observed (hunched posture, chromodacryorrhoea, piloerection, stains around the nose and wet fur) were noticed during or just after exposure. Body weight gain and lung weight were within normal limits and there were no treatment-related gross pathological findings. Based on these data, the LC50 was estimated to be > 5.1 mg/L air.  

Acute toxicity, dermal

No relevant information available.

The physicochemical and toxicological properties of Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol do not suggest potential for a significant rate of absorption through the skin. Therefore, testing by the dermal route is deemed not appropriate.

Conclusion

A LD50 value of >2000 mg/kg bw was observed for the oral route after treatment with Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol. A LC50 >5.1 mg/L was observed after treatment with the analogue substance Fatty acids, C5-10, esters with pentaerythritol after inhalation exposure. In conclusion, Fatty acids, C14-18 and C16-18-unsatd., mixed esters with castor oil, castor oil fatty acids, 2-ethylhexanoic acid and 2,2-bis(hydroxymethyl)-1-butanol is considered to be not acutely toxic via the oral or inhalation route.

Justification for selection of acute toxicity – oral endpoint
There is only one study available.

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on substance-specific studies and read-across from structurally similar substances, the available data on the acute oral and inhalation toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

There are no data available on acute dermal toxicity.