Fatty acids, C16-18, 2-butyloctyl esters

Endpoint summary

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:

2005-02-07 - 2005-02-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Oeutschland GmbH, 0-97633 Sulzfeld
- Age at study initiation:
- Weight at study initiation: 145-155 g
- Fasting period before study: overnight prior to dosing
- Housing: The rats were kept in transparent polycarbonate cages (macrolone type Ill, floor area 810 cm2) with two or three in each cage. The cages were cleaned and the bedding changed at least twice a week. Bedding was pinewood sawdust "Lignocel-Fasern" from Aliromin, 0-32791 Lage,
Lippe. Regular analyses for relevant possible contaminants are performed. Certificates of analysis are retained.
- Diet (e.g. ad libitum): A pelleted complete rodent diet "Altromin 1314" from Altromin GmbH, 0-32791 Lage, Lippe, was available ad libitum. Analyses for major nutritive components and relevant possible contaminants are performed regularly on the diet and certificates are retained.
- Water (e.g. ad libitum): The animals had free access to bottles with domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth. Analyses for possible contaminants are performed regularly. Certificates of analysis are retained.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):21°C +- 3 °C
- Humidity (%): 55+-15 %
- Air changes (per hr): 10 times/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 2015-02-01 - 2015-02-24

Route of administration:

oral: gavage

Vehicle:

olive oil

Doses:

2000 mg/kg

No. of animals per sex per dose:

1 rat in the preliminary study.
4 rats in the main study.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was observed 30 min., 2, 4 and 6 hours after the administration and
thereafter daily for a period of 14 consecutive days. Body weight was recorded on days 0,7 and 14.
- Necropsy of survivors performed: All rats were killed by inhalation of CO2 on day 14 and subjected to a gross necropsy
examination.
- Other examinations performed: clinical signs

Statistics:

not mentioned

Preliminary study:

One female rat was given ISOLFOL ESTER 1202 in a 2000 mg/kg b.w. dose. Slight signs of toxicosis were observed in this rat. Animal No. 1 showed a hunched posture and piloerection 30 min, 2 and 4 hours after the application of the test item. After 6 hours piloerection was still obseNed. Fromday 1 to the end of the obseNation period on day 14 no abnormalities were revealed. The post mortem inspection revealed no pathological abnormalities.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: limit test, 2000 mg/kg bw is the only dose tested

Mortality:

No mortalities were obserded.

Clinical signs:

Animals No. 2, No. 3, No. 4 and No. 5 showed a hunched posture and piloerection 30 min and 2 hours after the application of the test item. After 4 hours piloerection was still obseNed. On day 0 after 6 hours and from day 1 to the end of the observation period on day 14 no abnormalities were revealed.

Body weight:

no effects, normal body weight gain

Gross pathology:

The post mortem inspection revealed no pathological abnormalities.

Interpretation of results:

not classified

Conclusions:

Under the experimental conditions described in this final report the LD50 of ISOLFOL ESTER 1202 according to OECD 420 was > 2000 mg/kg.

Executive summary:

The acute oral toxicity of Fatty acids, C16-18 (even numbered), 2-butyloctyl esters was determined in 4 female Wistar rats each receiving 2000 mg/kg bw of the test material by oral gavage (limit test). The observation period was 14 days.

 

None of the animals died.

 

The acute oral LD50 was determined to be > 2000 mg/kg bw in rats.

 

This study is considered acceptable. It follows the principles of the retracted OECD test guideline 420 (Acute Oral Toxicity).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 1).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 Jun - 17 Jun 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Read-across

Justification for type of information:

Due to the structural similarities and consistent trend in toxicokinetic and (eco)toxicological behaviour, the selected source substances are considered suitable and systemic human health effects and ecotoxicological effects can be directly read-across in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5.

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

adopted in 2009

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl:WI (Han)

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: 9 weeks old
- Weight at study initiation: max. ± 20% of the sex mean
- Housing: Before exposure-Group housing of maximally 5 animals per sex per cage in labeled Makrolon cages (type IV; height 18cm.) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, UK). After exposure - Group housing as described above, maximally 3 animals per sex per cage.
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäteb GmbH, Soest, Germany), ad libitum except during exposure to the test substance.
- Water: tap-water, ad libitum except during exposure to the test substance.
- Acclimation period: 5 days before the start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To:

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: The design of the exposure chamber is based on the flow past nose-pnly inhalation chamber (Am.Ind.Hyg Assoc.J. 44(12): 923-928, 1983). The chamber consists of animal sections with eight animal ports each. Each animal port has its own atmosphere inlet and exhaust outlet.

- Method of holding animals in test chamber: Animals are placed in restraining tubes, which is then connected to the exposure chamber.

- Source and rate of air: The theoretical air flow was at least 1L/min.

- System of generating aerosols: An aerosol was generated by nebulization of the test substance by means of a nebulizer (type 950,
Hospitak Inc., Lindenhurst, NY, USA). The primary aerosol was diluted with pressurized air before it entered the exposure chamber. The mean total airflow was 16 L/min. From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.

- Method of conditioning air: The direction of the flow of the test atmosphere guarantees a freshly generated atmosphere for each individual animal.

- Temperature, humidity, pressure in air chamber: The temperature of the atmosphere was between 20.0 and 20.7 °C and relative humidity was between 28 and 30%. These conditions were considered appropriate for the relatively short 4 hours exposure duration.


TEST ATMOSPHERE
- Brief description of analytical method used: Samples were drawn through a glass fiber filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount of test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).
- Samples taken from breathing zone: yes


VEHICLE
- The test substance was used as delivered by the sponsor

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD was 2.5 µm (GSD 2.4) and 2.6 µm (GSD 2.3).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Target concentrations were based on the cut off concentration values specified in the UN and EC classification guidelines.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrically

Duration of exposure:

4 h

Concentrations:

The mean actual concentration was 5.7 ± 0.4 mg/L. The nominal concentration was 15.4 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 37%. Data obtained from the opacity monitor showed that the aerosol was sufficiently stable.

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: twice daily
Clinical signs: twice on the day of dosing (1 and 3 hours after exposure); daily thereafter until day 15
Body weight: recorded on day1 (pre-exposure), 2, 4, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
All animals were sacrificed at the end of the observation period by an intraperitoneal injection with Euthasol® (AST Farma BV, Oudewater, The Netherlands).

Statistics:

No statistical analysis was performed (the method used was not intended to calculate a LC50 value).

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.7 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortalities occured. Apart from hunched position observed in all on day2 after exposure, no further signs of adverse toxicity were observed until the end of the 14 day observation period.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 15.4 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occured during the 14-day observation period.

Clinical signs:

other: Hunched posture was shown by all animals on Day 2 after exposure. No clinical signs were noted during exposure.

Body weight:

Body weight gain in males and females were within the range expected for rats of this strain and age used in this type of study.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Executive summary:

Rats were exposed 4 hours with the similar substance 2 -ethylhexyloleate. No mortalities occured. The LC50 was > 5.7 mg/L (analytical). Apart from hunched position observed in all on day 2 after exposure, no further signs of adverse toxicity were observed until the end of the 14 day observation period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 700 mg/m³

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s) and common precursors/breakdown products (refer to endpoint discussion for further details).
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

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Klimisch 2

Additional information

Acute oral toxicity:

The acute oral toxicity of Fatty acids, C16-18 (even numbered), 2 -butyloctyl esters was determined in 4 female Wistar rats each receiving 2000 mg/kg bw of the test material by oral gavage (limit test) according to OECD 420. The observation period was 14 days. None of the animals died. The acute oral LD50 was determined to be > 2000 mg/kg bw in rats.

Acute inhalative toxicity:

Rats were exposed for 4 hours to the similar source substance 2 –ethylhexyl oleate. No mortality occurred. The LC50 was > 5.7 mg/L (analytical). Apart from hunched position observed in all rats on day 2 after exposure, no further signs of adverse toxicity were observed until the end of the 14-day observation period.

Acute dermal toxicity:

Sufficient data are available from alternative routes of exposure. For the oral and inhalation pathways acute data on the target or a source substance is available indicating no acute toxicity. The acute oral toxicity data indicates no acute oral toxicity up to 2000 kg/kg bw and the skin irritation/skin sensitisation data shows no systemic toxicity.

Justification for selection of acute toxicity – oral endpoint
There is only one study conducted with the target substance available.

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The available study is adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment .

Justification for selection of acute toxicity – dermal endpoint
Sufficient data are available from alternative routes of exposure.

Justification for classification or non-classification

Overall, the acute toxicity of the target substance Fatty acid, C16 -18, 2 -Butyloctylester and source substances is low and does not require classification according to Directive 67/548/EEC and Regulation (EC) No 1272/2008.