Registration Dossier

Administrative data

Description of key information

Oral: LD50 (rat, m/f) = >300 mg/kg bw <2000 mg/kg bw
Inhalation: LC50 (rat, m/f) > 12.3 mg/L
Dermal: LD50 (rat, m/f) = >2000 mg/kg bw/d

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:
04 Sept - 04 Oct 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
adopted 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
adopted 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom
Test type:
fixed dose procedure
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 57033
- Expiration date of the lot/batch: 25 November 2014

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark.
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK (RccHanTM:WIST strain)
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 150 - 170 g
- Fasting period before study: over night and 3-4 hours after dosing
- Housing: in groups of up to four in suspended solid floorpolypropylene cages furnished with wood flakes
- Diet: 2014C Teklad Global Rodent Diet supplied by Harlan Laboratories Ltd., ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: unchanged no vehicle for 2000 mg/kg bw and water for 300 mg/kg bw
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:
sighting study: 2000 and 300 mg/kg bw
main study: 300 mg/kg bw
No. of animals per sex per dose:
sighting study: 1
main study: 4
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4 hours after dosing and daily thereafter, weighing was done on day of dosing and on day 7 and day 14 or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
test mat.
Mortality:
In the sighting study the one female animal dosed with 2000 mg/kg bw was killed for humane reason one day after dosing, since the occurrence of clinical signs of toxicity exceeded the severity limit. No other animal at 300 mg/kg bw died or was killed due to humane reasons.
Clinical signs:
Clinical signs included hunched posture, lethargy, pilo-erection, ptosis and laboured respiration, blood stained urine was also noted. There were no signs of systemic toxicity in the one animal treated at a dose level of 300 mg/kg.
Body weight:
Surviving animals showed expected gains in bodyweight.
Gross pathology:
Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were pale liver, dark spleen, dark kidneys, gaseous distension of the stomach, haemorrhage and pallor of the gastric mucosa and red coloured fluid filled bladder. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Cat. 4 H302
DSD: Xn, R22
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
300 mg/kg bw

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:
23 Jul - 06 Sep 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 57033
- Expiration date of the lot/batch: 25 November 2014

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark.
Species:
rat
Strain:
other: RccHan™:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 200-350 g
- Housing: animals were housed in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks and cardboard "fun tunnels" (Datesand Ltd., Cheshire, UK).
- Diet: Harlan 2014C Rodent Diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: main drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber
- Exposure chamber volume: 30 L (28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: animals were individually held in a tapered, polycrbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber "O" ring.
- Source and rate of air: compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the nebuliser. The chamber flow rate was maintained at 40 L/min providing 80 air changes per hour.
- System of generating aerosols: the test item was aerosolised using a glass concentric jet nebuliser (Radleys, Saffron Walden, UK).
- Method of particle size determination:
- Temperature, humidity, pressure in air chamber: temperature, relative humidity and oxygen levels were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds, UK) or oxygen analyser (Servomex Ltd, Crowborough, UK) located in a vacant port in the animals’ breathing zone of the chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: the actual concentration of the test item was measured off-line by gas chromatography (GC).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: Inhalable fraction
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC
Duration of exposure:
4 h
Concentrations:
12.3 mg/L (mean achieved concentration)
35.6 mg/L (nominal concentration)
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: bodyweights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: animals were observed for clinical signs and the respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
Preliminary study:
In a preliminary study, two rats (one male, one female) were exposed to an atmosphere of the test item at a mean achieved atmosphere concentration of 2.83 mg/L for approx. 4 hours. No significant effects were noted in either animal.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 12.3 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No animal died at the limit dose of 12.3 mg/L.
Mortality:
No mortality occurred during the study period.
Clinical signs:
The following abnormalities were detected: (during exposure and directly after exposure): increased respiratory rate; (one day after exposure): hunched posture, pilo-erection (all animals), increased respiratory rate and red/brown staining around the eyes and/or snouts (frequent instances), decreased respiratory rate and isolated occurences of ptosis and red fur staining of the stomach or leg (occasional instances), animals recoverd to appear normal from days 7 to 10 post-exposure.

Hunched posture, pilo-erection and red/browen staining around the eyes and snout are commonly seen in animals for short periods on removal from the chamber in inhalation studies. Wet fur is commonly recorded both during and for a short period after exposure. These observations are considered to be associated with the restraint procedure and, in isolation, are not indicative of toxicity.
Body weight:
5/5 males and 4/5 females exhibited bodyweight losses on the first day post-exposure. Further bodyweight losses or no bodyweight gain were noted in 4 males and 3 females from days 1 to 3 post-expossure. Reasonable bodyweight development was noted in all animals during the remainder of the recovery period.
Gross pathology:
No macroscopic abnormalities were detected in any animal at necropsy.

Table 1. Mean achieved atmosphere concentration

Atmosphere concentration

Mean achieved (mg/L)

Standard deviation

Nominal (mg/L)

12.3

0.15

35.6

 

Table 2. Results of the acute inhalation study: Mortality

Mean achieved atmosphere concentration (mg/L)

Deaths

Male

Female

Total

12.3

0/5

0/5

0/10

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
12 Sept - 26 Sept 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 57033
- Expiration date of the lot/batch: 25 November 2014

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK (strain: RccHanTM:WIST)
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: range of 200 - 300 g
- Housing: in suspended solid-floor polypropylene cages furnished with woodflakes, individual housing during exposure and in in groups of 5 per sex the rest of the study
- Diet: 2014C Teklad Global Rodent diet, ad libitum
- Water: ad libitum
- Acclimation period: st least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 -25°C
- Humidity (%): 30 - 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: at the back and flanks of the animals
- % coverage: 10
- Type of wrap if used: surgical gauze, secured with self-adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing: the exposed area and the surrounding hair was wipped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.13 mL/kg

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were made 0.5, 1, 2 and 4 hours after dosing and subsequently every day, body weights were determined on day of dosing and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: scoring for dermal irritation once daily for fourteen days
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died during the study.
Clinical signs:
No signs of systemic toxicity could be observed.
Body weight:
Animals showed expected gains of body weigth during the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
- Other observations: There were no signs of dermal irritation.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral

A study for acute oral toxicity of 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) was performed in rats in accordance with OECD guideline 420 (Pooles, 2012). In a sighting study, each one female Wistar rat was exposed to 2000 and 300 mg/kg bw of the test substance by gavage. In the main study, a group of 4 female Wistar rats was treated with the 300 mg/kg bw of the test substance in water by gavage. The observation period following administration was 14 days.

In the sighting study, the female dosed with 2000 mg/kg bw was killed for humane reason one day after dosing. Clinical signs included hunched posture, lethargy, pilo-erection, ptosis and laboured respiration, blood and stained urine. At necropsy, the animal dosed with 2000 mg/kg bw showed pale liver, dark spleen, dark kidneys, gaseous distension of the stomach, haemorrhage and pallor of the gastric mucosa and red coloured fluid filled bladder. At 300 mg/kg bw, no mortality, no clinical signs of systemic toxicity and no effects on body weights were observed. No abnormalities were noted at necropsy of animals treated at the dose level of 300 mg/kg.

Therefore, the oral LD50 in male and female rats was greater than 300 mg/kg bw but lower than 2000 mg/kg bw.

 

Acute inhalation toxicity

The acute inhalation toxicity of 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) was evaluated in a study according to OECD guideline 403 under GLP conditions (Griffiths, 2012). A group of 10 male and female RccHan:WIST rats were exposed nose only to the limit concentration 12.3 mg/L (mean achieved concentration) for 4 h. The animals were observed for a period of 14 days following administration.

No mortality was apparent during the study period in any animal. During exposure and directly after exposure an increased respiratory rate; one day after exposure hunched posture, pilo-erection, increased respiratory rate and red/brown staining around the eyes and/or snouts, decreased respiratory rate and isolated occurrences of ptosis and red fur staining of the stomach or leg were observed. The animals recovered to appear normal from Days 7 to 10 post-exposure. Decreased bodyweight was observed in 5/5 males and 4/5 females on the first day post-exposure. Further bodyweight losses or no bodyweight gain were noted in 4 males and 3 females from Days 1 to 3 post-exposure. Necropsy revealed no substance-related adverse findings.

Therefore, the LC50 for male and female rats was greater than the limit dose of 12.3 mg/L air.

 

Acute dermal toxicity

The acute dermal toxicity of 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) was investigated in a limit test according to OECD guideline 402 and in compliance with GLP (Pooles, 2012).

In this study, 5 male and 5 female rats were treated with the test substance at a dose of 2000 mg/kg bw. The undiluted test substance at a concentration of 2000 mg/kg bw was applied onto the shaved skin of the test animals (2.13 mL/kg bw) for 24 h under semiocclusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No mortalities occurred and body weight gain of all animals was within the normal range during the study period. At necropsy, no substance-related findings were noted. There were no signs of dermal irritation.

Therefore, the LD50 in male and female rats is > 2000 mg/kg bw.

 

Conclusion for acute toxicity

In summary, a study with 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) investigating the acute oral toxicity in rats is available and resulted in an oral LD50 value of > 300, but < 2000 mg/kg bw. Thus, evidence of Acute oral toxicity was observed for 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9).

For acute inhalation toxicity, one study is available for 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) resulting in a LC50 value for male and female rats greater than the limit dose of 12.03 mg/L. Thus, the available data indicate a very low level of acute toxicity via inhalation 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) and thus no hazard for acute inhalative toxicity was identified.

An acute dermal toxicity study with 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) resulted in a LD50 value of > 2000 mg/kg bw and thus no hazard for acute dermal toxicity was identified.


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

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

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

Justification for classification or non-classification

Based on the available data on acute oral toxicity, 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) meet the criteria for classification according to Regulation (EC) 1272/2008 for Acute oral toxicity Category 4 (H302) and Harmful (R22) according to Directive 67/548/EEC.

Based on the available data on acute toxicity via the inhalation route 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC and the data are therefore conclusive but not sufficient for classification.

Based on the available data on acute toxicity via the dermal route 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC and the data are therefore conclusive but not sufficient for classification.