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EC number: 203-113-5 | CAS number: 103-45-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- published in 1993
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Published literature study
- Justification for type of information:
- Based on structural, physicochemical and toxicity data, similarities between benzyl acetate is considered appropriate for use of the information by read across to phenyl ethyl acetate - see review attached in IUCLID section 13.2.
Cross-reference
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- published in 1993
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Published literature study
- Justification for type of information:
- Based on structural, physicochemical and toxicity data, similarities between benzyl acetate is considered appropriate for use of the information by read across to phenyl ethyl acetate - see review attached in IUCLID section 13.2.
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Keari Inc.
- Age at study initiation: Females: 10 to 15 weeks
Males: 12 to 17 weeks.
- Weight at study initiation: Not documented
- Fasting period before study: Not documented
- Housing: Not documented
- Diet (e.g. ad libitum): Solid food purchased form Japan Kurea
- Water (e.g. ad libitum): Tap water
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 50 ± 10%
- Air changes (per hr): Not documented
- Photoperiod (hrs dark / hrs light): 12 hours light/dark
IN-LIFE DATES: From: To: Not documented - Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test susbtance, benzyl acetate, was mixed with olive oil to achieve concentration levels of 1000, 500, 100, 10 and 0 mg/ml
VEHICLE
- Justification for use and choice of vehicle (if other than water): olive oil
- Concentration in vehicle: Not documented
- Amount of vehicle (if gavage): Not documented
- Lot/batch no. (if required): VDR7446
- Purity: Not documented - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No information provided
- Details on mating procedure:
- On confirmation of the oestrous cycle of the females, 12-17 week old male rats were introduced and the males and females were co-housed from 5pm until the next morning when the presence of sperm in the vagina was considered to be successful mating. This was considered to be day zero of pregnancy. Based on their weight, pregnant rats were separated into 6 groups and relocated to separate cages.
- Duration of treatment / exposure:
- 10 days
- Frequency of treatment:
- Once each day from days 6 to 15 of gestation
- Duration of test:
- Animals terminated on Day 20 of gestation
- Remarks:
- Doses / Concentrations:
0, 10, 100, 500, 1000 mg/kg bw/d
Basis:
actual ingested - No. of animals per sex per dose:
- 20-22 mated females per group
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: No information
- Rationale for animal assignment (if not random): random
- Other: no other information - Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: Every 2 days
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
Examined every 2 days.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: Not documented
OTHER: The implantation in the womb, corpus lutea quantity, the implantation quantity, the resorption embryo count and the living or dead foetuses. The weight of the placenta was measured. - Ovaries and uterine content:
- Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data - Fetal examinations:
- - External examinations: Yes: all living foetuses
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes:
- Head examinations: No data - Statistics:
- One way layout dispersion method if equal dispersion detected. The Kruskal-Wallis method was used to verify significance in the case of equal dispersion. The multi-comparison verification method of Scheffe and Dunnett was used to verify the significance of subjected groups. An X2 verification method was also performed to determine the frequency of of the bone changes, internal organs of the foetuses and the gender comparison of the surviving foetuses.
- Indices:
- Not documented
- Historical control data:
- No information provided
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
There were no specific changes observed in the general condition or behaviour of the animals throughout the course of the study. No mortalities were observed in any treatment group. There were no significant differences in body weight observed between treatment groups. However, there was a tendency for the body weight to decrease in 1000mg/kg dose group from day 16 to day 20 of test substance administration and during the course of the pregnancy to day 20. A slight effect was also apparent at 500 mg/kg bw/d. There were no significant changes in food consumption in any of the treatment groups from the start to the end of pregnancy. On gross examination, there were no visible abnormalities in the internal organs examined - Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
Numbers of corpora lutea were comparable in all groups; the numbers of implantations and live foetuses were marginally lower at 1000 mg/kg bw/d. A single dead foetus was observed at 1000 mg/kg bw/d. Resorptions were comparable in al groups. Mean male foetal weight was marginally but significantly higher at 10 and 100 mg/kg bw/d; mean male and female foetal weights were significantly lower at 1000 mg/kg bw/d.
No external or visceral malformations were observed in any group. The number of visceral variations was significantly higher at 500 and 1000 mg/kg bw/d; increased incidences of ventricular dilation and renal pelvis dilation indicate an effect of treatment at 1000 mg/kg bw/d but not at 500 mg/kg bw/d. A single skeletal malformation (fused rib) was seen at 1000 mg/kg bw/d but is not considered to be clearly related to treatment. The incidence of skeletal variations was significantly increased at 1000 mg/kg bw/d; incidences of wavy rib, lumbar rib and other parameters indicative of reduced ossification were increased at this dose level. - Remarks on result:
- other: Not specified
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Maternal and developmental NOAELs of 500 mg/kg bw/d are derived for this study.
- Executive summary:
In a guideline-comparable developmental toxicity study, mated female Wistar rats (20 -22/group) were gavaged with benzyl acetate at dose levels of 10, 100, 500 or 1000 mg/kg bw/d on days 6 -15 of gestation. Additional groups were administered the vehicle alone or were untreated. Animals were terminated on Day 20 of gestation and the uterine contents examined: foetuses were assessed for external, visceral and skeletal findings.
A tendency to reduced weight gain was seen in females at 1000 mg/kg bw/d and to a lesser extent at 500 mg/kg bw/d. Numbers of corpora lutea were comparable in all groups; the numbers of implantations and live foetuses were marginally lower at 1000 mg/kg bw/d. A single dead foetus was observed at 1000 mg/kg bw/d. Resorptions were comparable in al groups. Mean male foetal weight was marginally but significantly higher at 10 and 100 mg/kg bw/d; mean male and female foetal weights were significantly lower at 1000 mg/kg bw/d. No external or visceral malformations were observed in any group. The number of visceral variations was significantly higher at 500 and 1000 mg/kg bw/d; increased incidences of ventricular dilation and renal pelvis dilation indicate an effect of treatment at 1000 mg/kg bw/d but not at 500 mg/kg bw/d. A single skeletal malformation (fused rib) was seen at 1000 mg/kg bw/d but is not considered to be clearly related to treatment. The incidence of skeletal variations was significantly increased at 1000 mg/kg bw/d; incidences of wavy rib, lumbar rib and other parameters indicative of reduced ossification were increased at this dose level.
Maternal and developmental toxicity was observed in this study at the highest dose level of 1000 mg/kg bw/d. Maternal and developmental NOAELs of 500 mg/kg bw/d are therefore derived.
Maternal findings
Group |
Untreated controls |
Vehicle controls |
10 mg/kg bw/d |
100 mg/kg bw/d |
500 mg/kg bw/d |
1000 mg/kg bw/d |
N |
20 |
20 |
21 |
21 |
20 |
22 |
Overall maternal weight gain (g) D0 -20 |
157.6 |
160.7 |
159.0 |
166.3 |
151.3 |
149.1 |
Weight gain (g) D16 -20 | 65.4 | 66.4 | 64.5 | 67.2 | 60.9 | 56.8 |
Litter parameters
Group |
Untreated controls |
Vehicle controls |
10 mg/kg bw/d |
100 mg/kg bw/d |
500 mg/kg bw/d |
1000 mg/kg bw/d |
Corpora lutea (#) |
17.1 |
18.1 |
18.2 |
17.2 |
17.7 |
17.4 |
Implantations (#) |
15.5 |
15.2 |
15.2 |
15.7 |
15.6 |
14.6 |
Live foetuses (#) |
15.0 |
14.5 |
14.7 |
15.1 |
14.6 |
13.9 |
Dead foetuses (total) |
0 |
0 |
0 |
0 |
0 |
1 |
Resorptions (#) |
0.6 |
0.7 |
0.6 |
0.5 |
1.0 |
0.7 |
Foetal weight M (g) |
4.09 |
3.91 |
4.21* |
4.12* |
4.05 |
3.35* |
Foetal weight F (g) |
3.92 |
3.85 |
3.97 |
3.89 |
3.85 |
3.17* |
Foetal parameters
Group |
Untreated controls |
Vehicle controls |
10 mg/kg bw/d |
100 mg/kg bw/d |
500 mg/kg bw/d |
1000 mg/kg bw/d |
External malformations (#) |
- |
- |
- |
- |
- |
- |
Visceral malformations (#) |
- |
- |
- |
- |
- |
- |
Visceral variations (#) |
3(2) |
5 (2) |
9 (4) |
3 (2) |
14 (4)* |
17 (10)* |
Ventricular dilation (#) |
2 (1) |
3 (2) |
8 (3) |
2 (1) |
7 (3) |
11 (6)* |
Levo-umbilical artery (#) |
- |
- |
2 (1) |
- |
- |
2 (2) |
Renal pelvis dilation (#) |
1 (1) |
3 (2) |
8 (3) |
2 (1) |
7 (3) |
11 (6)* |
Skeletal malformations (#) |
- |
- |
- |
- |
- |
1 (1) |
Fused ribs (#) |
- |
- |
- |
- |
- |
1 (1) |
Skeletal variations (#) |
8 (5) |
29 (12) |
16 (11) |
24 (10) |
22 (11) |
73 (21)* |
Wavy ribs |
1 (1) |
6 (4) |
4 (3) |
5 (3) |
11 (5) |
21 (12)* |
Dumbbell thoracic vertebra |
- |
- |
- |
- |
- |
6 (3)* |
Absent thoracic vertebral body |
- |
- |
- |
- |
- |
10 (4) |
Split thoracic vertebral body |
- |
1 (1) |
1 (1) |
- |
- |
6 (3)* |
Lumbar ribs |
8 (5) |
23 (10) |
12 (8) |
19 (8) |
10 (7) |
48 (17)* |
Absent lumbar vertebral body |
- |
1 (1) |
1 (1) |
- |
1 (1) |
4 (4) |
Dumbbell lumbar vertebra |
- |
- |
- |
- |
- |
1 (1) |
Ossification: cervical vertebrae |
3.36 |
3.44 |
3.44 |
3.24 |
2.72 |
0.78* |
Ossification: caudal vertebrae |
4.33 |
4.15 |
4.32 |
4.19 |
3.87 |
3.24* |
Sternebrae |
5.77 |
5.69 |
5.77 |
5.63 |
5.37 |
4.14* |
Data source
Reference
- Reference Type:
- publication
- Title:
- Teratological Studies on Benzyl Acetate in Pregnant Rats.
- Author:
- Ishiguro, S., Miyamoto, A., Obi, T and Nishio, A.
- Year:
- 1 993
- Bibliographic source:
- Kagoshima University Agricultural Academic Report, No 43, p. 25-31, 1993
- Report date:
- 1993
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Benzyl acetate
- EC Number:
- 205-399-7
- EC Name:
- Benzyl acetate
- Cas Number:
- 140-11-4
- Molecular formula:
- C9H10O2
- IUPAC Name:
- benzyl acetate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Keari Inc.
- Age at study initiation: Females: 10 to 15 weeks
Males: 12 to 17 weeks.
- Weight at study initiation: Not documented
- Fasting period before study: Not documented
- Housing: Not documented
- Diet (e.g. ad libitum): Solid food purchased form Japan Kurea
- Water (e.g. ad libitum): Tap water
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 50 ± 10%
- Air changes (per hr): Not documented
- Photoperiod (hrs dark / hrs light): 12 hours light/dark
IN-LIFE DATES: From: To: Not documented
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test susbtance, benzyl acetate, was mixed with olive oil to achieve concentration levels of 1000, 500, 100, 10 and 0 mg/ml
VEHICLE
- Justification for use and choice of vehicle (if other than water): olive oil
- Concentration in vehicle: Not documented
- Amount of vehicle (if gavage): Not documented
- Lot/batch no. (if required): VDR7446
- Purity: Not documented - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No information provided
- Details on mating procedure:
- On confirmation of the oestrous cycle of the females, 12-17 week old male rats were introduced and the males and females were co-housed from 5pm until the next morning when the presence of sperm in the vagina was considered to be successful mating. This was considered to be day zero of pregnancy. Based on their weight, pregnant rats were separated into 6 groups and relocated to separate cages.
- Duration of treatment / exposure:
- 10 days
- Frequency of treatment:
- Once each day from days 6 to 15 of gestation
- Duration of test:
- Animals terminated on Day 20 of gestation
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 10, 100, 500, 1000 mg/kg bw/d
Basis:
actual ingested
- No. of animals per sex per dose:
- 20-22 mated females per group
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: No information
- Rationale for animal assignment (if not random): random
- Other: no other information
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: Every 2 days
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
Examined every 2 days.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: Not documented
OTHER: The implantation in the womb, corpus lutea quantity, the implantation quantity, the resorption embryo count and the living or dead foetuses. The weight of the placenta was measured. - Ovaries and uterine content:
- Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data - Fetal examinations:
- - External examinations: Yes: all living foetuses
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes:
- Head examinations: No data - Statistics:
- One way layout dispersion method if equal dispersion detected. The Kruskal-Wallis method was used to verify significance in the case of equal dispersion. The multi-comparison verification method of Scheffe and Dunnett was used to verify the significance of subjected groups. An X2 verification method was also performed to determine the frequency of of the bone changes, internal organs of the foetuses and the gender comparison of the surviving foetuses.
- Indices:
- Not documented
- Historical control data:
- No information provided
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
There were no specific changes observed in the general condition or behaviour of the animals throughout the course of the study. No mortalities were observed in any treatment group. There were no significant differences in body weight observed between treatment groups. However, there was a tendency for the body weight to decrease in 1000mg/kg dose group from day 16 to day 20 of test substance administration and during the course of the pregnancy to day 20. A slight effect was also apparent at 500 mg/kg bw/d. There were no significant changes in food consumption in any of the treatment groups from the start to the end of pregnancy. On gross examination, there were no visible abnormalities in the internal organs examined
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
Numbers of corpora lutea were comparable in all groups; the numbers of implantations and live foetuses were marginally lower at 1000 mg/kg bw/d. A single dead foetus was observed at 1000 mg/kg bw/d. Resorptions were comparable in al groups. Mean male foetal weight was marginally but significantly higher at 10 and 100 mg/kg bw/d; mean male and female foetal weights were significantly lower at 1000 mg/kg bw/d.
No external or visceral malformations were observed in any group. The number of visceral variations was significantly higher at 500 and 1000 mg/kg bw/d; increased incidences of ventricular dilation and renal pelvis dilation indicate an effect of treatment at 1000 mg/kg bw/d but not at 500 mg/kg bw/d. A single skeletal malformation (fused rib) was seen at 1000 mg/kg bw/d but is not considered to be clearly related to treatment. The incidence of skeletal variations was significantly increased at 1000 mg/kg bw/d; incidences of wavy rib, lumbar rib and other parameters indicative of reduced ossification were increased at this dose level.
Effect levels (fetuses)
- Remarks on result:
- other: Not specified
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Maternal findings
Group |
Untreated controls |
Vehicle controls |
10 mg/kg bw/d |
100 mg/kg bw/d |
500 mg/kg bw/d |
1000 mg/kg bw/d |
N |
20 |
20 |
21 |
21 |
20 |
22 |
Overall maternal weight gain (g) D0 -20 |
157.6 |
160.7 |
159.0 |
166.3 |
151.3 |
149.1 |
Weight gain (g) D16 -20 | 65.4 | 66.4 | 64.5 | 67.2 | 60.9 | 56.8 |
Litter parameters
Group |
Untreated controls |
Vehicle controls |
10 mg/kg bw/d |
100 mg/kg bw/d |
500 mg/kg bw/d |
1000 mg/kg bw/d |
Corpora lutea (#) |
17.1 |
18.1 |
18.2 |
17.2 |
17.7 |
17.4 |
Implantations (#) |
15.5 |
15.2 |
15.2 |
15.7 |
15.6 |
14.6 |
Live foetuses (#) |
15.0 |
14.5 |
14.7 |
15.1 |
14.6 |
13.9 |
Dead foetuses (total) |
0 |
0 |
0 |
0 |
0 |
1 |
Resorptions (#) |
0.6 |
0.7 |
0.6 |
0.5 |
1.0 |
0.7 |
Foetal weight M (g) |
4.09 |
3.91 |
4.21* |
4.12* |
4.05 |
3.35* |
Foetal weight F (g) |
3.92 |
3.85 |
3.97 |
3.89 |
3.85 |
3.17* |
Foetal parameters
Group |
Untreated controls |
Vehicle controls |
10 mg/kg bw/d |
100 mg/kg bw/d |
500 mg/kg bw/d |
1000 mg/kg bw/d |
External malformations (#) |
- |
- |
- |
- |
- |
- |
Visceral malformations (#) |
- |
- |
- |
- |
- |
- |
Visceral variations (#) |
3(2) |
5 (2) |
9 (4) |
3 (2) |
14 (4)* |
17 (10)* |
Ventricular dilation (#) |
2 (1) |
3 (2) |
8 (3) |
2 (1) |
7 (3) |
11 (6)* |
Levo-umbilical artery (#) |
- |
- |
2 (1) |
- |
- |
2 (2) |
Renal pelvis dilation (#) |
1 (1) |
3 (2) |
8 (3) |
2 (1) |
7 (3) |
11 (6)* |
Skeletal malformations (#) |
- |
- |
- |
- |
- |
1 (1) |
Fused ribs (#) |
- |
- |
- |
- |
- |
1 (1) |
Skeletal variations (#) |
8 (5) |
29 (12) |
16 (11) |
24 (10) |
22 (11) |
73 (21)* |
Wavy ribs |
1 (1) |
6 (4) |
4 (3) |
5 (3) |
11 (5) |
21 (12)* |
Dumbbell thoracic vertebra |
- |
- |
- |
- |
- |
6 (3)* |
Absent thoracic vertebral body |
- |
- |
- |
- |
- |
10 (4) |
Split thoracic vertebral body |
- |
1 (1) |
1 (1) |
- |
- |
6 (3)* |
Lumbar ribs |
8 (5) |
23 (10) |
12 (8) |
19 (8) |
10 (7) |
48 (17)* |
Absent lumbar vertebral body |
- |
1 (1) |
1 (1) |
- |
1 (1) |
4 (4) |
Dumbbell lumbar vertebra |
- |
- |
- |
- |
- |
1 (1) |
Ossification: cervical vertebrae |
3.36 |
3.44 |
3.44 |
3.24 |
2.72 |
0.78* |
Ossification: caudal vertebrae |
4.33 |
4.15 |
4.32 |
4.19 |
3.87 |
3.24* |
Sternebrae |
5.77 |
5.69 |
5.77 |
5.63 |
5.37 |
4.14* |
Applicant's summary and conclusion
- Conclusions:
- Maternal and developmental NOAELs of 500 mg/kg bw/d are derived for this study.
- Executive summary:
In a guideline-comparable developmental toxicity study, mated female Wistar rats (20 -22/group) were gavaged with benzyl acetate at dose levels of 10, 100, 500 or 1000 mg/kg bw/d on days 6 -15 of gestation. Additional groups were administered the vehicle alone or were untreated. Animals were terminated on Day 20 of gestation and the uterine contents examined: foetuses were assessed for external, visceral and skeletal findings.
A tendency to reduced weight gain was seen in females at 1000 mg/kg bw/d and to a lesser extent at 500 mg/kg bw/d. Numbers of corpora lutea were comparable in all groups; the numbers of implantations and live foetuses were marginally lower at 1000 mg/kg bw/d. A single dead foetus was observed at 1000 mg/kg bw/d. Resorptions were comparable in al groups. Mean male foetal weight was marginally but significantly higher at 10 and 100 mg/kg bw/d; mean male and female foetal weights were significantly lower at 1000 mg/kg bw/d. No external or visceral malformations were observed in any group. The number of visceral variations was significantly higher at 500 and 1000 mg/kg bw/d; increased incidences of ventricular dilation and renal pelvis dilation indicate an effect of treatment at 1000 mg/kg bw/d but not at 500 mg/kg bw/d. A single skeletal malformation (fused rib) was seen at 1000 mg/kg bw/d but is not considered to be clearly related to treatment. The incidence of skeletal variations was significantly increased at 1000 mg/kg bw/d; incidences of wavy rib, lumbar rib and other parameters indicative of reduced ossification were increased at this dose level.
Maternal and developmental toxicity was observed in this study at the highest dose level of 1000 mg/kg bw/d. Maternal and developmental NOAELs of 500 mg/kg bw/d are therefore derived.
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