Fatty acids, montan-wax, stearyl esters

Endpoint summary

Description of key information

Oral: LD50 (rat, female) > 2000 mg/kg bw

 

Inhalation: LC50 (rat, male/female) > 5.7 mg/L air

Read-across from analogue source substance 2-ethylhexyl octadec-9-enoate (CAS 26399-02-0)

 

Dermal: LD50 m/f rat > 2000 mg/kg bw

Read-across from analogue source substance 2-octyldodecyl isooctadecanoate (CAS 93803-87-3)

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:

02 - 26 Oct 2012

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)

Version / remarks:

adopted Dec 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

1998

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

National Institute for Quality and Organisational Development in Healthcare and Medicines, Budapest, Hungary

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld, Germany
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 11 weeks
- Weight at study initiation: 202 - 220 g
- Fasting period before study: Yes, overnight
- Housing: 3 animals were housed per cage in Type II polypropylene/polycarbonate cages with deep wood sawdust bedding (Lignocel®)
- Diet: Ssniff® SM R/M (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 - 23.1
- Humidity (%): 34 - 64
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 11 Oct 2012 To: 26 Oct 2012

Route of administration:

oral: gavage

Vehicle:

other: Sunflower oil

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg bw
- Lot/batch no.: 5068804

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: Following a grinding to ensure proper of size particles, the test item was freshly formulated at a concentration of 200 mg/mL in the vehicle, in the Central Dispensary Unit of the testing facility on the day of administration. The formulation container was stirred continuously up to finishing the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 in the first and second step, respectively

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: Yes, macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Key result

Sex:

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 toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

Necropsy revealed no substance-related findings.

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 and reliable (Klimisch score 1) studies from reference substances with similar intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile. The selected studies are 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 inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.7 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Interpretation of results:

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

Conclusions:

The acute inhalation toxicity study with the appropriate source substance 2-ethylhexyl octadec-9-enoate (CAS 26399-02-0) revealed a LC50 value > 5.7 mg/L air (analytical). Applying the read across approach, similar results are expected for the target substance Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1) studies from reference substances with similar intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile. The selected studies are 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

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

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.

Interpretation of results:

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

Conclusions:

The acute dermal toxicity study with the appropriate source substance 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) revealed a dermal LD50 value > 2000 mg/kg bw. Applying the read across approach, similar results are expected for the target substance Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1) studies from reference substances with similar intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile. The selected studies are 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.

Additional information

Justification for read-across

Data on acute oral toxicity of Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5) are available. The assessment of acute inhalation and dermal toxicity was based on studies conducted with analogue source substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

The single-dose oral toxicity of Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5) was evaluated according to the acute toxic class method (OECD 423) in CRL:(WI) rats (CiToxLAB, 2013). Two groups of three female CRL:(WI) rats were treated with the test substance at a dose level of 2000 mg/kg bw via gavage (Group 1 and Group 2). Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw of Fatty acids, montan-wax, stearyl esters. The test item did not cause mortality in this group; therefore a confirmatory group (Group 2) was treated at the same dose level. The test item did not cause mortality in the confirmatory group, so no further testing was required according to OECD 423. Clinical signs of toxicity were not observed. All animals were subjected to a necropsy and a macroscopic examination, which revealed no treatment-related findings. As a consequence, the LD50 is set to be > 2000 mg/kg bw.

Acute inhalation toxicity

CAS 26399-02-0

An acute inhalation study was performed with 2-ethylhexyl oleate (CAS 26399-02-0) according to OECD 436 as acute toxic class method in 3 male and 3 female Crl:WI(Han) rats (Notox, 2010). The animals were exposed to an analytical aerosol concentration of 5.7 mg/L of the test substance for 4 hours nose-only. No mortalities were reported during the exposure or within the 14 days observation period. Hunched posture was shown by all animals on Day 2 after exposure. No clinical signs were noted during exposure. Additionally body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study. No abnormalities were found at macroscopic post-mortem examination of the animals. The inhalatory 4 hour LC50 value of 2-ethylhexyl oleate aerosol in Wistar rats was found to exceed 5.7 mg/L.

Acute dermal toxicity

CAS 93803-87-3

The potential acute dermal toxicity of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was assessed in a study (limit test) performed according to a protocol similar to OECD 402 (Notox, 1998). 2000 mg/kg bw of the test substance was applied to the skin of 5 Wistar rats/sex/dose under an occlusive dressing for 24 hours. No mortality occurred. No toxicologically relevant clinical signs were noted during the 14-day observation period. The body weight increases were within the range expected for rats used in this type of study and no treatment-related findings were reported during the necropsy and histopathological examination. The LD50 is considered to be > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The reliable data available for the target and read-across analogue substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 and LC50 values were greater than the recommended guideline limit values, respectively. Therefore, as the available data did not identify any acute toxicity, Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5) is not considered to be hazardous following acute exposure via the oral, inhalation and dermal route.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physico-chemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids, montan-wax, stearyl esters (CAS 68308-30-5) data will be generated from data for source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on acute oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.