Ethyl formate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

concentration-driven

Effects on fertility

Description of key information

Toxicity to reproduction

Based on the experimental studies on test hemical ,No Observed Effect Level (NOEL) was considered to be 1000mg/kg/day in rats for reproductive toxicity as no effects on reproductive organ was observed .Thus, comparing this value with the criteria of CLP regulation test chemical cannot be classified as reproductive toxicant.

 

Link to relevant study records

Reference

Endpoint:

reproductive toxicity, other

Remarks:

chronic toxicity study

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data from peer reviewed journal

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Reproductive toxicity study of test material was performed on Osborne-Mendel rats.

GLP compliance:

not specified

Limit test:

yes

Justification for study design:

No data available

Species:

rat

Strain:

Osborne-Mendel

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing:The animals were housed individually in wire cages
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum

Route of administration:

oral: feed

Vehicle:

other: feed

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg/day).

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Details not specified
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Food
- Concentration in vehicle: 0, 5000, 10000 or 20000 ppm (0, 250, 500 or 1000 mg/Kg/day)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

Details on mating procedure:

No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

17 weeks

Frequency of treatment:

Daily

Details on study schedule:

No data available

Remarks:

0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg bw)

No. of animals per sex per dose:

Total: 80
0 mg/kg bw: 10 males and 10 females
100 mg/kg bw: 10 males and 10 females
250 mg/kg bw: 10 males and 10 females
1000 mg/kg bw: 10 males and 10 females

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Weekly
- Cage side observations checked in table [No.?] were included. General condition

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

No data available

Postmortem examinations (parental animals):

GROSS PATHOLOGY: Yes, The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed.

Postmortem examinations (offspring):

No data available

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Description (incidence and severity):

Hematologic findings were normal.

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

Remarks on result:

other: No effects on reproductive organ

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

not measured/tested

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Description (incidence and severity):

The animals were housed individually in wire cages

Reproductive effects observed:

not specified

Treatment related:

not specified

Conclusions:

The no observed Adverse Effect Level (NOAEL) for the test chemical using Osborne-Mendel rats for a duration of 17 weeks was considered to be 1000 mg/Kg bw.

Executive summary:

Reproductive /chronic oral toxicity study of test chemical was performed on male and female Osborne-Mendel rats.10 male and 10female were used in each dose group.The test material was fed through the diet at a concentration of 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg/day)for 17 weeks.Animals were checked for clinical signs, Food consumption and body weight every week. At the termination of the experiments the rats were sacrificed and exsanguinated.The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin.No treatment-related clinical signs and premature deaths were observed. No relevant necropsy findings were noted. No effects on testes weight was noted in treated rats at dose concentration 1000mg/kg bw, Based on the observations made, the no observed Adverse Effect Level (NOAEL) for the test chemical using Osborne-Mendel rats for a duration of 17 weeks is considered to be 1000 mg/Kg bw

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from peer reviewed journal

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity

The study on test chemical has been investigated for reproductive toxicity .The study is as mentioned below:

Reproductive /chronic oral toxicity study of test chemical was performed on male and female Osborne-Mendel rats.10 male and 10female were used in each dose group.The test material was fed through the diet at a concentration of 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg/day)for 17 weeks.Animals were checked for clinical signs, Food consumption and body weight every week. At the termination of the experiments the rats were sacrificed and exsanguinated.The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10% buffered formalin-saline solution for histopathological examination. For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin.No treatment-related clinical signs and premature deaths were observed. No relevant necropsy findings were noted. No effects on testes weight was noted in treated rats at dose concentration 1000mg/kg bw, Based on the observations made, the no observed Adverse Effect Level (NOAEL) for the Ethyl formate using Osborne-Mendel rats for a duration of 17 weeks is considered to be 1000 mg/Kg bw

Thus, based on the above experimental studies of test chemical , No Observed Effect Level (NOEL) was considered to be 1000mg/kg/day in rats for reproductive toxicity .Thus, comparing this value with the criteria of CLP regulation test chemical cannot be classified as reproductive toxicant.

 

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Toxicity to reproduction: other studies

Description of key information

No compound related effects were observed, the no observed adverse effect level ( NOAEL) value for teretogenicity of test chemical was considered to be 25 mg/egg in chicken embryo.

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data from peer reviewed journal

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Teratogenicity of test Chemicals was performed in the Developing Chicken Embryo

GLP compliance:

not specified

Type of method:

in vitro

Species:

other: Chicken

Strain:

other: Single-Comb White Leghorn

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data avilable

Route of administration:

other: Injection (Via Yolk and via air cell injection)

Vehicle:

not specified

Details on exposure:

No data avilable

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

At two stages of incubation: preincubation (0 hr) and at the fourth day (96 hr)

Frequency of treatment:

At 0h and 96 h

Duration of test:

96 h

Remarks:

0.50 to 75 mg/egg (5 dose level)

No. of animals per sex per dose:

500 eggs (100 eggs per dose)

Control animals:

yes

Statistics:

No data avilable

Dose descriptor:

NOAEL

Effect level:

25 other: mg/egg

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: No teratogenic effect were observed

Remarks on result:

other: No teratogenic effect were observed

Mortality, abnormalities included all structural anomalies as well as toxic responses such as edema, hemorrhage, hypopigmentation of the down, significant growth retardation, cachexia, and other nerve disorders. Structural abnormality of the head, viscera, limbs, or body skeleton were examined.No teratogenic effect were observed

Conclusions:

The NOAEL value for teretogenicity of test chemical was considered to be 25 mg/egg in chicken embryo.

Executive summary:

Teretogenicity study of test chemical was conducted in Fresh fertile eggs from Single-Comb White LeghornChicken.Test chemical was administered by two routes, into tha yolk and through the air cell. For each enjection route, eggs were treated at0h and at 96 h. Five dose level tested range from 0.50 to 75 mg/egg and 100 embryos were treated per dose. Mortality, abnormalities included

all structural anomalies as well as toxic responses such as edema, hemorrhage, hypopigmentation of the down, significant growth retardation, cachexia, and other nerve disorders.Structural abnormality of the head, viscera, limbs, or body skeleton were examined. No teretogenic effect observed at dose level of 25 mg/egg. Hence,the NOAEL value for teretogenicity of test chemical was considered to be 25 mg/egg in chicken embryo.

 

Additional information

Teretogenicity study of test chemical was conducted in Fresh fertile eggs fromSingle-Comb White LeghornChicken. Test chemical was administered by two routes, into tha yolk and through the air cell. For each enjection route, eggs were treated at0h and at 96 h. Five dose level tested range from 0.50 to 75 mg/egg and 100 embryos were treated per dose. Mortality, abnormalities included all structural anomalies as well as toxic responses such as edema, hemorrhage, hypopigmentation of the down, significant growth retardation, cachexia, and other nerve disorders.Structural abnormality of the head, viscera, limbs, or body skeleton were examined. No teretogenic effect observed at dose level of 25 mg/egg. Hence,the NOAEL value for teretogenicity of test chemical was considered to be 25 mg/egg in chicken embryo.

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation test chemical cannot be classified as reproductive toxicant.