Ethyl 2-methylvalerate

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:

29 March to 19 Apr 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed accoding to GLP, OECD Guidelines followed and no deviations reported

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 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: SPF (Specific Pathogen Free) Sprague-Dawley -Crl:OFA (SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratoires France - Domaine des Oncins, 69210 L’Arbresle Cedex.
- Age at study initiation: 9 weeks at the time of administration.
- Weight at study initiation: Within ± 20% of the mean weight of any previously dosed animals.
- Housing: Daily observations were undertaken at the time of delivery of the animals and during the period of acclimatisation. Animals were housed in groups of 5 at maximum, in cages of standard dimensions with sawdust bedding.
- Diet (e.g. ad libitum): Feeding: RM1 (E)-SQC SDS/DIETEX feed (quality controlled) was available ad libitum except during the fasting experimental period. The certificate of analysis concerning this feed product is included in Appendix B, page 30 of attached report. The criteria for acceptable levels of contaminant, in the feed supply were thin the limits of the analytical specifications established by the diet manufacturer.
- Water (e.g. ad libitum): Drinking water: Drinking water was available ad libitum in polvcarbonate bottles with a stainless steel nipple. A specimen of water is obtained approximately every 6 months and sent to the LAEASE Region Sud Est - 5, avenue Achille Maureau – B. P. 95 - 84703 Sorgues Cedex - France, for analysis. The certificate of analysis are included in Appendix C, page 32 of attached report. The criteria for acceptable levels of contaminants in the water supplied were within the limits of the analytical specifications.
- Acclimation period: Acclimatisation: Five days before treament in the laboratory animal house where the experiment took place.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 - No deviations outside of the temperature or hygrometry ranges were reported by the Study Director according to the SOP 5.36.
- Humidity (%): Relative humidity between 45% and 65% (except during the cleaning slot)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): The artificial day/night cycle involved 12 hours light and 12 hours darkness with light on at 7.30 am.

- Other:
- Identification: Animals were identified individually by marking the tail with a felt tip marker.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: Corn oil was chosen after the solubility trial, on the basis of the physico-chemical characteristics of the test item
- Lot/batch no. (if required): SIGMA, Batch No. MKBF8603V, Expiry date: 5 Mar 2017

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not provided

Doses:

2000 mg/kg.

No. of animals per sex per dose:

Female: 6 animals with 3 animals per step.

Control animals:

no

Details on study design:

Examination:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed on the following days:
- on D1, day of administration
- on D4, D7, D10 and D14 during the study
- on D15, day of necropsy (not exsanguinated)
- Necropsy of survivors performed: yes - All animals surviving to the end of the 14-day monitoring period were euthanased on D15 by subtotal exsanguination, after isoflurane inhalation. All animals were subjected to gross necropsy and their organs (brain, liver, spleen, kidneys, stomach, intestines, gonads/reproductive tact, lungs and heart) were examined macroscopically.

- Other examinations performed:
- Mortality - Morbidity: Mortality was recorded twice a day, i.e. in the morning and at the end of the working day.
- Clinical signs:
- General examination: Animals were examined clinically once before dosing and twice on the day of treatment (30 minutes ± 2 minutes post-dose and then again between 3 and 4 hours post-dose). Thereafter they were examined clinically at least once a day for 14 days. The general disposition, behaviour and activity were observed (See Section 1, page 10 of attached report).
- Functional and neurobehavioural tests: On D1 (30 minutes ± 1 minutes post-dose), on D7 and on D14, animals were observed according to a standardised observation battery for general clinical signs, neurobehavioural, neurovegetative or psychotropic signs or neurotoxic effects. The method is based on the Irwin screen* modified by suppressing the graduation of intensity of clinical signs. Animals were observed individually in a cage with out sawdust in a quiet room. Clinical signs were observed according to Table 1.1, page 21 of attached report.
- Food and water consumption, fasted periods: Food and water consumption were not measured. Animals were fasted during the night before treatment and remain deprived of food for 3 to 4 hours post-dose.

- Pathology: Euthanasia were performed by CERB under the responsibility of P. Pradeau, DVM, AnatomopathoIogist.

- Method of administration:
- Timing, frequency and duration of administration: EMV was administered to animals deprived of food since the previous day. It was administered to the animals as a single dose, by gavage, using a cannuIa of appropriate size.
- Volume to be administered: The dose volume was 10 mL/kg.

* Irwin S. Comprehensive observational assessment: A ystematic quantitative procedure fo assessing the behavioural and physiological state of the mouse. Psychopharmacologica. 1968; 13:222-257.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: No deaths and no evidence of toxicity at 2000 mg/kg

Mortality:

MORTALITY: No mortality occurred during the study.

Clinical signs:

other: CLINICAL FINDINGS: There was no clinical sign during the study.

Gross pathology:

MACROSCOPIC FINDINGS: Individual data are presented in Table 2.5, page 26 of attached report. No findings were seen at necropsy.

DISCUSSION: Since the body weight change was minimal (at maximum -2%) and because body weight increased or remained stable in three other animals between D7 and D10 and in all animals on D14, this change was not attributed to an effect of the test item.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions adopted, EMV administered once by oral route in the Sprague Dawley rat at 2000 mg/kg did not induce any sign of toxicity.

Executive summary:

The aim of this study was to determine the acute toxicity of EMV at 2000 mg/kg after single dose administration by the oral (gavage) route in the rat.

 

Experimental procedure:

- 6 animals were treated at 2000 mg/kg.

- Mortality was recorded twice a day for 14 days. Clinical observations were performed before the dosing then daily. Functional and neurobehavioural tests were performed on D1, D7 and D14.

- Body weight was recorded on D1, D4, D7, D10 and D14.

- Animals were subjected to gross necropsy on D15.

 

Results:

- Mortality: No mortality occurred during the study.

- Clinical signs: There was no clinical sign during the study.

- Body weight: There was no treatment-related change in body weight gain.

- Macroscopic examination: No findings were seen at necropsy.

 

Conclusion:

Under the experimental conditions adopted, EMV administered once by oral route in the Sprague Dawley rat at 2000 mg/kg did not induce any sign of toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 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:

22 April 22 to 13 May 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: - Study performed according to GLP - Study performed according to OECD Guideline 403 (Acute Inhalation Toxicity)

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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: Animal Breeding Facility, Jai Research Foundation
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: At the start of the exposure the male rats weighed between 285 and 303 g, while the female rats weighed between 199 and 204 g
- Housing: Three rats/cage in polypropylene rat cages covered with stainless steel grid tops were used.
- Diet (e.g. ad libitum): Teklad certified Global High Fiber Feed for Rat/Mice manufactured by Harlan U.S.A., ad libitum.
- Water (e.g. ad libitum): UV sterilized water filtered through Kent Reverse Osmosis water filtration system, ad libitum.
- Acclimation period: Animals were acclimatised In the experimental room 7 days prior to the exposure. The rats were also acclimatised for a period of 2 hours one day prior to exposure in the rat restrainer tubes.

ENVIRONMENTAL CONDITIONS
(Temperature and relative humidity were recorded daily).
- Temperature (°C): 19 to 22
- Humidity (%):64 to 65
- Air changes (per hr): Minimum 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light and 12 hours darkness

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: None identified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The dynamic inhalation equipment consists of an inhalation chamber, air compressor, air filters, flow meters, spray atomizer, continuous infusion syringe pump, cascade impactor, thermo-hygrometer, carbon dioxide monitor, oxygen monitor, open face sampler, transparent perspex rat exposure tubes and vacuum pump.

- Exposure chamber volume: The total capacity of the chamber is 63.5 litres.

- Method of holding animals in test chamber: Each rat was restrained in a single transparent perspex exposure tube with adjustable unit. The exposure tubes were accommodated in the port-holes of the inhalation chamber. The adjustable unit of the exposure tube was set so that the animals breathed ethyl 2-methylvalerate (ethyl 2- methylpentanoate) aerosols through the window panel of the exposure tube.

- Source and rate of air: The air inflow and outflow rates were maintained at 15 and 20 litres per minute, respectively and were monitored throughout the exposure period. The oxygen concentration inside the chamber was monitored continuously and recorded once per hour using the oxygen monitor, Uniphos 310. The chamber oxygen concentration recorded during the exposure period ranged between 20.6 and 20.8%.

- System of generating particulates/aerosols: Based on the trial exposure, ethyl 2-methylvalerate (ethyl 2-methylpentanoate) (undiluted) (stock concentration of 861.50 mg/mL - Refer Table 1 of the attached report) was loaded into a 60 mL infusion syringe and positioned on the infusion syringe pump. Ethyl 2-methylvalerate (ethyl 2-methylpentanoate) was infused into the spray atomizer where aerosols were formed and distributed into the inhalation chamber. The infusion rate was 40 mL/h.

- Method of particle size determination:
- Gravimetric Concentration Analysis: An open face sampler with glass microfibre papers was used to assess the breathing zone concentration. A suitable measured volume of air (1.77 litres per minute) was drawn twice from the inhalation chamber at the level of the breathing zone after an equilibration of the chamber for 15 minutes (at 30 and 150 minutes after the start of exposure). At the end of air sampling (1 minute), the glass microfibre papers with the test item were weighed to determine the concentration of ethyl 2-methylvalerate (ethyl 2-methylpentanoate) aerosols at the breathing zone of the rats (Table 2 of the attached report).
- Particle collection using a Seven Stage Cascade Impactor: The particle size was determined by using a seven-stage cascade impactor. Aerosols from the chamber are drawn into the cascade impactor (7 stages) with pre-weighed stainless steel collection plates using a vacuum pump. The sampling speed is maintained at 1.77 litres per minute. At the end of air sampling (1 minute), the collection plates with test item are disassembled and weighed. The increase in the weight of each collection plate is the mass of particles in the size range of that impact stage. The total mass of particles and the percent mass of particles in each size range is calculated. The mean cumulative percent particle size is calculated for a required particle size by adding the mean particle size distribution from 0 to that required particle size. Mass median aerodynamic diameter (MMAD) is calculated directly from percent particle size distribution (Figure 3 of the attached report).

- Treatment of exhaust air: No details provided in report -

- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the chamber were monitored and recorded once per hour with the thermo-hygrometer. The chamber temperature during the exposure period was between 22.4 and 22.6°C, while the relative humidity was between 43.7 and 44.4%.

TEST ATMOSPHERE
- Brief description of analytical method used: Breathing zone concentration was analysed gravimetrically with an open face sampler using glass microfiber filters (GF/A).
- Samples taken from breathing zone: yes

VEHICLE
-No vehicle identified

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: See Table 4 of the attached report
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The mass median aerodynamic diameter (MMAD) of ethyl 2-methylvalerate (ethyl 2-methylpentanoate) aerosols was determined to be 2.25 µm with a geometric standard deviation (GSD) of 2.63 (Table 4, Appendix 2 and Figure 3 of the attached report).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: A trial exposure was conducted without rats for determining the breathing zone concentration and particle size of the test item for the main study. Study protocol states that for the limit study “rats will be exposed to an exposure concentration of 5 mg/L or greater”. Initially the infusion rate was 40 mL/h and air flow rate was 15 litres/minute. At 40 mL/h infusion rate breathing zone concentration and particle size were checked. Breathing zone concentration was found to be greater than 5 mg/L air and 50% particles were in the range of I to 4 micron. Thus an infusion rate of 40 mL/h for the test item and air flow rate of 15 litres/minute were selected for the main study.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric analysis of experimental test atmospheres was conducted

Duration of exposure:

4 h

Concentrations:

5.967 mg/L air

No. of animals per sex per dose:

- Three male and three female healthy Wistar rats
- Females were nulliparous and non-pregnant

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Toxic Signs: All rats were observed for any signs of toxicity and mortality at hourly intervals during the 4 h exposure period and at 1 and 2 h after the exposure on the day of exposure. Subsequently, the surviving rats were observed twice a day for morbidity and mortality for a period of 14 days following exposure. The clinical signs were recorded once a day.
- Body weights: Body weights were recorded prior to exposure on day 0 and on days 1, 3, 7 and 14 post exposure.
- Necropsy of survivors performed: yes - All the rats at the end of the 14-day observation period were sacrificed by intraperitoneal administration of thiopentone sodium and subjected to gross pathological examination.

Statistics:

Statistical Analysis of Result: As this study was conducted as a limit study at the breathing zone concentration of 5.967 mg/L air, no statistical analysis was required to calculate the LC50.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.967 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality was observed

Clinical signs:

other: No signs of toxicity were observed

Body weight:

Necropsy (Macroscopic Findings): External and internal examination of sacrificed rats revealed no abnormalities

Other findings:

Concentration Details of Ethyl 2-Methylvalerate (Ethyl 2-Methylpentanoate) in the Inhalation Chamber: The mean concentration of ethyl 2-metlylvalerate (ethyl 2-methylpentanoate) in the air at breathing zone for rats was 5.967 mg/L air. The mass median aerodynamic diameter (MMAD) of ethyl 2-methylvalerate (ethyl 2-methylpentanoate) aerosols was determined to be 2.25 µm with a geometric standard deviation (GSD) of 2.63

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No mortality was observed in the treatment group rats (group I) exposed to the breathing zone concentration (5.967 mg/L air) of ethyl 2-methylvalerate (ethyl 2-methylpentanoate and the acute median lethal concentration (LC50) of ethyl 2-methylvalerate (ethyl 2-methylpentanoate) was found to be greater than 5.967 mg/L air. Ethyl 2-methylvalerate (ethyl 2-methylpentanoate) is being classified as follows:

Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2011): Not Classified

Executive summary:

This study was performed to assess the acute inhalation toxicity (LC50) of ethyl 2-methylvalerate (ethyl 2-methylpentanoate) in Wistar rats. The method followed was as per the guidelines of the OECD No. 403 (September, 2009).

 

This study was conducted as a limit study. One group of rats, comprising three males and three females were used for the study. The rats from group I were exposed to the breathing zone concentration of ethyl 2-methylvalerate (ethyl 2-methylpentanoate) (5.967 mg/L air). The rats were exposed for 4 h followed by observation period of 14 days.

 

No sign of toxicity and no mortality were observed in group I rats exposed to the breathing zone concentration of 5.967 mg/L air.

 

Mean body weight of rats post exposure equalled or increased on days 1, 3, 7 and 14 in both the sexes of the rats when compared with pre-exposure (day 0) mean body weight.

 

All the treated rats at termination were subjected to gross pathological examination. External and visceral examination of terminally sacrificed rats did not reveal any lesion of pathological significance. In the absence of any pathological lesion in terminally sacrificed rats, it is concluded that the test item did not produce any treatment related effect at the dose level used in the present study.

Group No.	Breathing Zone Concentration (mg/L air)	Number of Rates Exposed		Mortality (%)
		Male	Female	Male	Female
1	5.967	3	3	0	0

No mortality was observed in the treatment group rats (group I) exposed to the breathing zone concentration (5.967 mg/L air) of ethyl 2-methylvalerate (ethyl 2-methylpentanoate). The acute median lethal concentration (LC50) of ethyl 2-methylvalerate (ethyl 2-methylpentanoate) was found to be greater than 5.967 mg/L air.

 

Ethyl 2-methylvalerate (ethyl 2-methylpentanoate) is therefore classified as follows:

 

Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2011): Not Classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 967 mg/m³ air

Quality of whole database:

Klimisch 1

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:

23 May to 06 June 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study undertaken to recognised guideline and GLP.

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 (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD (Crl: CD ® (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: approximately 8 to 12 weeks old
- Weight at study initiation: males weighed 222 to 231g, and the females 215 to 226g
- Fasting period before study: No details provided in report
- Housing: The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Acclimation period: minimum acclimatisation period of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
(Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study).
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- The calculated volume of the test material, as received, was applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.
- Time after start of exposure: After the 24-hour contact period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Dose volume 2.33 ml/kg and Specific gravity 0.861

Duration of exposure:

24 hours

Doses:

Dose volume: 2.33 ml/kg and Specific gravity: 0.861

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: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes - At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
- Other examinations performed: After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) “Dermal and Eye Toxicity Tests” In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31 (see attached report for details). Any other skin reactions, if present were also recorded.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No clinical signs of toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No signs of dermal irritation were noted during the study.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material, ETHYL METHYLBUTYRATE-2, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Executive summary:

Study Sponsor: Haarmann & Reimer GmbH

Study Title: Acute Dermal Toxicity (Limit Test) In The Rat

Test Material: Ethyl Methylbutyrate-2

               

1. A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 Acute Dermal Toxicity (adopted 24 February 1987) and Method B3 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

 

2. A group of ten animals (five males and five females) was given a single 24-hour, semi- occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

 

3. There were no deaths. No signs of systemic toxicity or dermal irritation were noted during the study.

 

4. All animals showed expected gain in bodyweight during the study.

 

5. No abnormalities were noted at necropsy.

 

6. The acute dermal median lethal dose (LD₅₀) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 2

Additional information

- Determination of the acute toxicity of Ethyl 2 -Methyl Pentanate in rats: The oral LD50 of ethyl 2-methyl pentanate was found to exceed 5.0 ml per kg body weight.

- Acute oral toxicity study in the rat: Under the experimental conditions adopted, EMV administered once by oral route in the Sprague Dawley rat at 2000 mg/kg did not induce any sign of toxicity.

- Ethyl Methylbutyrate-2: Acute Dermal Toxicity (Limit Test) in the Rat: The acute dermal median lethal dose (LD₅₀) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Justification for selection of acute toxicity – oral endpoint
Most recent study and covered a range of doses.

Justification for selection of acute toxicity – inhalation endpoint
Only study available.

Justification for selection of acute toxicity – dermal endpoint
Only study available.

Justification for classification or non-classification

None of the acute studies gives a result less than the threshold for classification. Therefore this substance is not classified for acute toxicity.