Ethyl 2-methylbutyrate

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:

03 May 2000

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)

Deviations:

yes

Remarks:

Any occasional deviations from the targets for temperature and humidity were considered not to have affected the purpose or integrity of the study.

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Any occasional deviations from the targets for temperature and humidity were considered not to have affected the purpose or integrity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

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, UK
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: males weighed 206 to 220g, and the females 206 to 217g
- Fasting period before study: An overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: The animals were housed in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse SQC Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum): With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse SQC Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Acclimation period: at least 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 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight

Doses:

2000 mg/kg body weight

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: 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 dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: At the end of the observation period 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 for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

No data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths (Individual mortality data are given in Table 1 of attached report).

Clinical signs:

other: There were no signs of systemic toxicity (Individual clinical observations are given in Tables 2 and 3 of attached report).

Gross pathology:

No abnormalities were noted at necropsy (Individual necropsy findings are given in Tables 6 and 7 of attached report).

Other findings:

None

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material, ETHYL METHYLBUTYRATE-2, in the Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.

No mortalities were noted at 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 Oral Toxicity Study in the Rat - Acute Toxic Class Method

Test Material: Ethyl Methylbutyrate-2

 

1. A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 423 “Acute Oral Toxicity - Acute Toxic Class Method” (adopted 22 March 1996) and Method B1 tris of Commission Directive 96/54/EC (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. Using all available information, 2000 mg/kg bodyweight was selected as the starting dose.

 

A group of three fasted females was treated with the starting dose. This was followed by a group of three fasted animals of the other sex at the same dose level. Dosing was performed sequentially.

 

The test material was administered orally, undiluted. The animals were observed ½, 1, 2 and 4 hours after dosing and then once daily for fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14. At the end of the observation period all animals were killed by cervical dislocation and subjected to gross necropsy.

 

3. There were no deaths.

 

4. There were no signs of systemic toxicity.

 

5. All animals showed expected gains in bodyweight over the study period.

 

6. No abnormalities were noted at necropsy.

 

7. The acute oral median lethal dose, (LD₅₀) of the test material, in the Sprague-Dawley CD strain rat, was estimated as being greater than 2000 mg/kg bodyweight. No mortalities were noted in animals treated with 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:

LD50

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:

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

Adequacy of study:

key study

Study period:

29 April to 19 May 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH


1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Source substance analogue of target substance.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

4. DATA MATRIXREPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target and object substances come from the same series of molecules.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

4. DATA MATRIXREPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target and object substance are part of a recognised series.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

4. DATA MATRIX

Reason / purpose for cross-reference:

read-across source

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:

not specified

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.

Key result

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:

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

Gross pathology:

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

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 (Table 4, Appendix 2 and Figure 3 of the attached report).

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:

LC50

Value:

5 967 mg/m³ air

Quality of whole database:

Klimisch 1, key study for closely related structural analogue

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 May 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

Principles of method if other than guideline:

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.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

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 (Dose level 2000 mg/kg)

Duration of exposure:

24 hours

Doses:

Dose volume: 2.33 ml/kg
Specific gravity: 0.861
Dose level: 2000 mg/kg

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: 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: 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.

Statistics:

No details provided in report

Key result

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:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1

Additional information

Dermal Toxicity: 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.

Oral Toxicity: The acute oral median lethal dose (LD50) of the test material, ETHYL METHYLBUTYRATE-2, in the Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.

By read across to EMV, EMB is not acutely toxic via the inhalation route. An acute inhalation study with EMV resulting in a LC50 >5967mg/m3 in a reliable and relevant OECD 403 acute toxicity study at a limit dose was conducted. No adverse systemic effects were observed in the study up to 14 days after a single 4 hour exposure. EMV does not classify for acute inhalation toxicity. Read-across to EMV is justified since EMB has similar physicochemical properties, chemical reactivity and only differs by a single carbon in an homologous series.

Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – inhalation endpoint
Study is Klimisch 1 study for EMV, a closely related structural analogue

Justification for selection of acute toxicity – dermal endpoint
Key study

Justification for classification or non-classification

This substance, EMB, is not classified for acute toxicity as the results for all studies exceed the threshold values.