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EC number: 219-698-5 | CAS number: 2499-95-8
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
Oral NOAEL 84 mg/kg (male) and 111 mg/kg (female) Rat; equivalent or similar to OECD Guideline 408 (Read-across to N-butyl Acrylate)
Inhalation NOAEC 2.86 mg/L (male/female) Rat; equivalent or similar to OECD Guideline 413 (Read-across to N-butyl Acrylate)
Link to relevant study records
- Endpoint:
- reproductive toxicity, other
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
- Deviations:
- no
- Principles of method if other than guideline:
- Groups of rats (15 male and 15 female per dose and control group) were exposed to butyl acrylate over a period of 13 weeks at concentrations (analytically measured) of 0.015, 0.09 or 0.15 % in drinking water. Animals were observed for clinical signs, body weight gain, hematological and biochemical parameters. Necropsies were performed on all animals and weight of the testes were measured. Tissues, including
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA.
- Age at study initiation: 63-64 days
- Housing: singly in suspended wire-mesh bottomed stainless steel cages
- Diet (e.g. ad libitum): Purina Laboratory Chow
- Water: The test solutions were the only sources of water for the rats.
- Acclimation period: 3 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: drinking water
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Stability studies of butyl acrylate in water indicated some loss of the test material over a 4-day period (McCollister, et al, 1980). To compensate for the loss, the drinking water solutions containing butyl acrylate were prepared fresh daily, and at concentrations higher than those selected for test levels, as shown below:
Target Conc (w/v)
0.015%
0.09%
0.15%
Conc Prepared (w/v)
0.02%
0.12%
0.22%
The solutions were prepared by adding 0.81 ml, 4.85 ml, or 8.9 ml of butyl acrylate to 3600 ml of fresh tap water in a one-gallon amber glass bottle in which a teflon rod was placed to facilitate mixing. Each bottle was mixed by rotation for approximately 1.5 hours.
McCollister, S. B. et al. Report No. HET K 23114- (6). The Dow Chemical Company, 1980. - Details on mating procedure:
- not applicable
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The approximate actual concentrations for target levels of 0.015, 0.09 or 0.15 % butyl acrylate were 0.0162, 0.0997 or 0.1229 %, respectively.
- Duration of treatment / exposure:
- 96-97 days
- Frequency of treatment:
- In an attempt to maximize ingestion of the test material, access to the drinking water was restricted to the time period from 4 p.m. to 8 a.m.
- Dose / conc.:
- 12 mg/kg bw/day (nominal)
- Remarks:
- 0.015 % in drinking water; males
- Dose / conc.:
- 73 mg/kg bw/day (nominal)
- Remarks:
- 0.09% in drinking water; males
- Dose / conc.:
- 84 mg/kg bw/day (nominal)
- Remarks:
- 0.15% in drinking water; males
- Dose / conc.:
- 15 mg/kg bw/day (nominal)
- Remarks:
- 0.015% in drinking water; females
- Dose / conc.:
- 91 mg/kg bw/day (nominal)
- Remarks:
- 0.09% in drinking water; females
- Dose / conc.:
- 111 mg/kg bw/day (nominal)
- Remarks:
- 0.15% in drinking water; females
- No. of animals per sex per dose:
- 15
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
Based on the results of preliminary toxicity studies (McCollister, et al, 1980), levels of 0.015, 0.09 and 0.15% were selected as target concentrations.
McCollister, S. B. et al. Report No. HET K 23114- (6). The Dow Chemical Company, 1980. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 111 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: no effects on reproductive organs
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 84 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: no effect on reproductive organs
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- not specified
- Executive summary:
In a 13 week-study, F344-rats (15 animals per sex and dose) received n-butyl acrylate via drinking water in concentrations of 0, 0.015, 0.09 and 0.15 % (0, 12, 73, 84 mg/kg body weight per day for males and 0, 15, 91, 111 mg/kg body weight per day for females). A satellite group (5 male and 5 female rats) was given 150 mg/kg bw butyl acrylate (in corn oil) via gavage 5 days a week for 13 weeks. The only effects reported were a slight reduction in water consumption, which occurred in all dose groups, and a decrease in weight gain for male rats in the highest dose group. No abnormal histopathology findings in either male or female reproductive organs were reported.
- Endpoint:
- reproductive toxicity, other
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- See attached for Read-Across Justification
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 111 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No effects on reproductive organs
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 84 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No effects on reproductive organs
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- not specified
- Executive summary:
N-hexyl acrylate was evaluated for its potential toxicity to reproduction based on read-across to data of a structurally similar substance, N-butyl Acrylate. This read-across approach is based on the hypothesis that the hydrolysis of both substances to acrylic acid and the respective alcohols would show similar toxicity patterns. The effect of the parent compound from the target substance is also predicted based on the worst case approach as data indicate the parent structure of the source substance would be expected to have a higher electrophilic capacity. In a 13 week-study, F344-rats (15 animals per sex and dose) received n-butyl acrylate via drinking water in concentrations of 0, 0.015, 0.09 and 0.15 % (0, 12, 73, 84 mg/kg body weight per day for males and 0, 15, 91, 111 mg/kg body weight per day for females). A satellite group (5 male and 5 female rats) was given 150 mg/kg bw butyl acrylate (in corn oil) via gavage 5 days a week for 13 weeks. The only effects reported were a slight reduction in water consumption, which occurred in all dose groups, and a decrease in weight gain for male rats in the highest dose group. No abnormal histopathology findings in either male or female reproductive organs were reported.
- Endpoint:
- reproductive toxicity, other
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1978
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Principles of method if other than guideline:
- Group of rats (20 male and 20 female per dose and control group) were exposed to butyl acrylate vapors (6 h/ day) over a period of 13 weeks at concentrations(analytically measured) of 21, 108, 211, and 546 ppm. Animals were observed for clinical signs, body weight gain, hematological and biochemical parameters. Necropsies were performed on all animals and weight of the testes were measured. Tissues, including seminal vesicles, prostate, epididymis/uterus, testes and ovary were examined histologically from all animals.
- GLP compliance:
- no
- Remarks:
- Study conducted prior to GLP
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SPF breed supplied, WIGA, Sulzfeld
- Age at study initiation: 42 days
- Weight at study initiation: males-159 g and females-130 g
- Housing: 2-3 rats per cage
- Diet (e.g. ad libitum): Altromin-R supplied by Altrogge, Lage/Lippe
- Water (e.g. ad libitum): tap water - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
By means of a continuous infusion pump, the liquid product was metered onto a heated vaporizer (temperature about 80 °C) at a constant rate and vaporized there. A stream of supply air measured by means of a rotameter took up the vapors. This vapor-air mixture, after passing through a mixing device, was introduced into an inhalation chamber with a volume of 200 liters.
TEST ATMOSPHERE
- Brief description of analytical method used: The n-butyl acrylate air mixture was measured continuously using a flame ionization detector (FID). Apparatus used was FID total hydrocarbons analyzer (CARLO ERBA, mod. 370).
- Samples taken from breathing zone: yes. Sampling was carried out by means of a diaphragm pump which continuously passes the n-butyl acrylate air mixture to the FID. A second diaphragm pump continuously sweeped the sample tubes that were not needed for measurement in the chamber up to the pneumatic valve. The duration of measurement was 10 minutes per chamber, and the sweeping time 7 minutes (measuring cycle). - Details on mating procedure:
- not applciable
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analytical measurements were 21, 108, 221 and 546 ppm, respectively.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hr/day, 5 dy/week for 13 weeks
- Dose / conc.:
- 0 ppm (analytical)
- Dose / conc.:
- 21 ppm (analytical)
- Remarks:
- Corresponds to 0.11 mg/L
- Dose / conc.:
- 108 ppm (analytical)
- Remarks:
- Corresponds to 0.57 mg/L
- Dose / conc.:
- 211 ppm (analytical)
- Remarks:
- Corresponds to 1.11 mg/L
- Dose / conc.:
- 546 ppm (analytical)
- Remarks:
- Corresponds to 2.86 mg/L
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, sham-exposed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 2.86 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects on reproductive organs
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- not specified
- Executive summary:
In a sub-chronic study, Sprague-Dawley rats (20 animals per sex and dose) were exposed to butyl acrylate vapours 6 hrs/day, 5 dys/week for 13 weeks. Mortality and treatment-related effects were reported in the highest dose group (546 ppm). Local effects were also observed such as histological changes in the nasal mucosa due to the irritating nature of the test substance. A NOAEC of 570 mg/m3 (108 ppm) was established based on systemic effects. The respective LOAEC of 1100 mg/m3 (211 ppm) was based on reduced body weight and clinical biochemistry changes (females). No effects on reproductive organs in either sex were reported up to the highest dose tested in this study.
- Endpoint:
- reproductive toxicity, other
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- See attached for Read-Across Justification
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 2.86 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effects on reproductive organs
- Remarks on result:
- not measured/tested
- Reproductive effects observed:
- not specified
- Executive summary:
N-hexyl acrylate was evaluated for its potential toxicity to reproduction based on read-across to data of a structurally similar substance, N-butyl Acrylate. This read-across approach is based on the hypothesis that the hydrolysis of both substances to acrylic acid and the respective alcohols would show similar toxicity patterns. The effect of the parent compound from the target substance is also predicted based on the worst case approach as data indicate the parent structure of the source substance would be expected to have a higher electrophilic capacity. In a sub-chronic study, Sprague-Dawley rats (20 animals per sex and dose) were exposed to butyl acrylate vapours 6 hrs/day, 5 dys/week for 13 weeks. Mortality and treatment-related effects were reported in the highest dose group (546 ppm). Local effects were also observed such as histological changes in the nasal mucosa due to the irritating nature of the test substance. A NOAEC of 570 mg/m3 (108 ppm) was established based on systemic effects. The respective LOAEC of 1100 mg/m3 (211 ppm) was based on reduced body weight and clinical biochemistry changes (females). No effects on reproductive organs in either sex were reported up to the highest dose tested in this study.
Referenceopen allclose all
Data on reproductive organ toxicity were derived from a 90-day oral drinking water exposure to n-butyl acrylate. Respective results from animals exposed to the highest dose level of 84 mg/kg and 11 mg/kg for males and females respectively did not produce evidence of any impairment in the reproductive organs evaluated from both sexes in this study.
Data on reproductive organ toxicity were derived from a 90-day oral drinking water exposure to n-butyl acrylate. Respective results from animals exposed to the highest dose level of 84 mg/kg and 11 mg/kg for males and females respectively did not produce evidence of any impairment in the reproductive organs evaluated from both sexes in this study.
Data on reproductive organ toxicity were derived from a 90-day inhalation study. Respective results from animals exposed to the highest dose level of 546 ppm (2.86 mg/L) did not produce evidence of any impairment in the reproductive organs evaluated from both sexes in this study.
Data on reproductive organ toxicity were derived from a 90-day inhalation study. Respective results from animals exposed to the highest dose level of 546 ppm (2.86 mg/L) did not produce evidence of any impairment in the reproductive organs evaluated from both sexes in this study.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 84 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 2 860 mg/m³
- Study duration:
- subchronic
- Species:
- rat
Additional information
Reproductive toxicity: Oral
In a 13 week-study, F344-rats (15 animals per sex and dose) received n-butyl acrylate via drinking water in concentrations of 0, 0.015, 0.09 and 0.15 % (0, 12, 73, 84 mg/kg body weight per day for males and 0, 15, 91, 111 mg/kg body weight per day for females). A satellite group (5 male and 5 female rats) was given 150 mg/kg bw butyl acrylate (in corn oil) via gavage 5 days a week for 13 weeks. The only effects reported were a slight reduction in water consumption, which occurred in all dose groups, and a decrease in weight gain for male rats in the highest dose group. No abnormal histopathology findings in either male or female reproductive organs were reported.
Reproductive toxicity: Inhalation
In a sub-chronic study, Sprague-Dawley rats (20 animals per sex and dose) were exposed to butyl acrylate vapours 6 hrs/day, 5 dys/week for 13 weeks. Mortality and treatment-related effects were reported in the highest dose group (546 ppm). Local effects were also observed such as histological changes in the nasal mucosa due to the irritating nature of the test substance. A NOAEC of 570 mg/m3 (108 ppm) was established based on systemic effects. The respective LOAEC of 1100 mg/m3 (211 ppm) was based on reduced body weight and clinical biochemistry changes (females). No effects on reproductive organs in either sex were reported up to the highest dose tested in this study.
Effects on developmental toxicity
Description of key information
Inhalation NOAEC 0.52 mg/L Rat; based on maternal toxicity and fetal body weight
Inhalation NOAEC 0.13 mg/L Rat; based on maternal toxicity and fetal resorptions; according to the Guidelines for reproduction studies for safety evaluation of drugs for human use, FDA, Jan. 1966 and Guidance on reproduction studies from the Association of the British Pharmaceutical Industry, 1975.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- See attached for Read-Across Justification
- Reason / purpose for cross-reference:
- read-across source
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- During the entire exposure period, maternal weight gain was signifciantly reduced at 200 ppm and above compared to the control group. Absolute weight gains (expressed as the day 21 body weight minus the gravid uterus weight and minus the day 6 body weight) were reduced in a dose-rependent manner in all exposure groups.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Decreases in food consumption was observed during the first half of the study for the females in the 100 ppm dose group and throught the exposure period at 200 and 300 ppm. The maximum decrease was 40-50% at the highest concentration.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined - Changes in number of pregnant:
- no effects observed
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 0.52 mg/L air (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Fetal body weight was significantly reduced at 200 ppm (for both sexes combined and males) and at 300 ppm (both sexes combined, males and females). These decreases amounted to 7-8 % (p<0.05) and 26-28 % (p<0.01) of control values for the 200 and 300 ppm groups, respectively.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- A few sporadic malformations were seen in the 300 ppm and the control group. The incidence of indivi dual skeletal variations (mainly incomplete ossification of sternebrae and of vertebral centra) was similar in the control and treated groups.
- Visceral malformations:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 0.52 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1.57 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: teratogenicity
- Remarks on result:
- other: highest dose tested
- Developmental effects observed:
- not specified
- Executive summary:
N-hexyl acrylate was evaluated for its developmental toxicity potential based on read-across to data of a structurally similar substance, N-butyl Acrylate. This read-across approach is based on the hypothesis that the hydrolysis of both substances to acrylic acid and the respective alcohols would show similar toxicity patterns. The effect of the parent compound from the target substance is also predicted based on the worst case approach as data indicate the parent structure of the source substance would be expected to have a higher electrophilic capacity. In a developmental toxicity study, pregnant Sprague-Dawley female rats (20-29 per dose) were exposed to the compound 6h/day on days 6 through 20 of gestation. Control animals were exposed concurrently to filtered room air. The test concentrations of n-butyl acrylate were 100, 200, and 300 ppm (corresponding to approx. 0.52, 1.05, and 1.57 mg/L). Significant decreases in maternal body weight gain were observed at 200 ppm and 300 ppm, and decreased absolute weight gain were observed in all dose groups through the entire exposure period. Decreased fetal body weight was observed at 200 ppm (7-8%) and 300 ppm (26-28%) in the presence of significant maternal toxicity. No significant increases in malformations was observed in n-butyl acrylate exposed fetuses.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- See attached for Read-Across Justification
- Reason / purpose for cross-reference:
- read-across source
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Distinct discharge from the eyes and noses and ruffled fur was observed in the 135 ppm dose groups, the severity of this effect was increased at 250 ppm.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight gain was significantly decreased in the 135 and 250 ppm dose groups during the period of treatment. Following the end of exposure (GD 16 - 20) body weight gain was similar to that of the control group.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- The number of corpora lutea and the number of implantations did not show any differences between the individual groups. However, the perecentage of live implantations per pregnant animal was decreased in the 135 and 250 ppm dose groups.
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- effects observed, treatment-related
- Description (incidence and severity):
- A significant increase in the percentage of dead resorptions was observed in the 135 and 250 ppm dose groups.
- Dead fetuses:
- not examined
- Changes in pregnancy duration:
- not examined
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined - Changes in number of pregnant:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 0.13 mg/L air (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity body weight, irritation to eyes and nose
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- not examined
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 0.13 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: embryotoxicity resorptions
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1.31 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: teratogenicity
- Key result
- Abnormalities:
- not specified
- Key result
- Developmental effects observed:
- not specified
- Executive summary:
N-hexyl acrylate was evaluated for its developmental toxicity potential based on read-across to data of a structurally similar substance, N-butyl Acrylate. This read-across approach is based on the hypothesis that the hydrolysis of both substances to acrylic acid and the respective alcohols would show similar toxicity patterns. The effect of the parent compound from the target substance is also predicted based on the worst case approach as data indicate the parent structure of the source substance would be expected to have a higher electrophilic capacity. In a developmental toxicity study, pregnant Sprague-Dawley female rats (30 per dose) were exposed to the n-butyl acrylate 6h/day on days 6 through 15 of gestation. Control animals were exposed concurrently to filtered room air. The test concentrations of n-butyl acrylate were 25, 135 and 250 ppm. Significant decreases in maternal body weight gain were observed at 135 and 250 ppm dose groups through the entire exposure period. The number of corpora lutea and the number of implantations did not show any differences between the individual groups. However, the percentage of live implantations per pregnant animal was decreased in the 135 and 250 ppm dose groups. No significant increases in malformations was observed in n-butyl acrylate exposed fetuses.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 Feb 1979 - 13 Mar 1979
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- other: Guidelines for reproduction studies for safety evaluation of drugs for human use, FDA, Jan. 1966 and Guidance on reproduction studies from the Association of the British Pharmaceutical Industry, 1975.
- GLP compliance:
- no
- Remarks:
- Study conducted prior to GLP
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Iffa Credo, Lyon, France
- Body weight at study initiation:
The mean body weight ± SD in dose groups 0, 25, 135 and 250 ppm were 209±12, 214±14, 214±9 and 219±16, respectively.
- Age at study initiation: 9-11 week
- Diet (e.g. ad libitum): Herilan Mrh-Zucht, H. Eggermann KG, Rinteln.
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±5
- Photoperiod (hrs dark / hrs light):12/12
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
By means of a continuous infusion apparatus (UNITA I, B. Braun, Melsungen, Federal Republic Germany) constant amounts of the liquid product were supplied to a heated (about 80°C) evaporator. The n-butyl acrylate vapors were diluted with dust-free, conditioned fresh air and passed through 200 L inhalation chambers (all-glass construction with steel frame) under dynamic airflow conditions at a flow rate of 20 changes of air per hour (4000 L/h; 200 L chamber). A mean temperature of 24.5°C and a mean relative humidity of 53% were measured during exposure.
TEST ATMOSPHERE
- Brief description of analytical method used: The n-butyl acrylate test atmosphere concentrations were monitored analytically by means of a total
hydrocarbon analyzer (R 5 of RATFISCH, Munich). The total hydrocarbon analyzer was calibrated using an infrared analyzer Miran I (WILKS) calibrated with standards of known concentrations of n-butyl acrylate.
- Samples taken from breathing zone: yes
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analytical concentrations (Mean ± SD) of the dose groups 25, 135 and 250 ppm were 25 ± 1, 137 ± 4 and 251 ± 3 ppm, respectively.
- Details on mating procedure:
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- Duration of treatment / exposure:
- days 6-15 of gestation
- Frequency of treatment:
- 6 hours per day
- Duration of test:
- 21 days
- Dose / conc.:
- 0 ppm (nominal)
- Dose / conc.:
- 135 ppm (nominal)
- Dose / conc.:
- 250 ppm (nominal)
- No. of animals per sex per dose:
- 30
- Control animals:
- yes, sham-exposed
- Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: day on which sperm had been detected (day 0) and on the 6th, 16th and 20th days post coitum.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on the 20th day post coitum.
- Ovaries and uterine content:
- Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- The weights and the length of fetuses were determined. After fixation in Bouin's solution, 1/3 of the fetuses were examined for organ changes according to the method of Wilson and Warkany (1965), and after staining of the skeleton (Dawson, 1926) 2/3 of the fetuses were investigated for skeletal changes.
Wilson, J.G. and Warkany, J. (1965). Teratology: Principles and Techniques. The University of Chicago Press, Chicago and London.
Dawson, A.B. (1926). Stain Technol. 1:123. - Statistics:
- A trend analysis based on the generalization of the t-test according to Williams (1971, 1972) was carried out for the variables of maternal body weight and body weight gain, fetal weight and length, and placental weight in each case. The U-test (Krauth, 1971; Stucky and Vollmar, 1976) was carried out for the parameters of implantations per pregnant animal, live and dead embryos as percent per pregnant animal, and anomalies, variations and retardations as percent of live fetuses per litter.
Williams, D.A. (1971). Biometrics 27:103-117.
Williams, D.A. (1972). Biometrics 28:519-531.
Krauth, J. (1971). Ann. Math. Statist. 42:1949-1956.
Stucky, W. and Vollmar, J. (1976). J. Statist. Comput. Simul. 5:73-81. - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Distinct discharge from the eyes and noses and ruffled fur was observed in the 135 ppm dose groups, the severity of this effect was increased at 250 ppm.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight gain was significantly decreased in the 135 and 250 ppm dose groups during the period of treatment. Following the end of exposure (GD 16 - 20) body weight gain was similar to that of the control group.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- The number of corpora lutea and the number of implantations did not show any differences between the individual groups. However, the perecentage of live implantations per pregnant animal was decreased in the 135 and 250 ppm dose groups.
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- effects observed, treatment-related
- Description (incidence and severity):
- A significant increase in the percentage of dead resorptions was observed in the 135 and 250 ppm dose groups.
- Dead fetuses:
- not examined
- Changes in pregnancy duration:
- not examined
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined - Changes in number of pregnant:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- ca. 0.13 mg/L air (nominal)
- Basis for effect level:
- other: maternal toxicity
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- not examined
- Changes in sex ratio:
- not examined
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- ca. 0.13 mg/L air (nominal)
- Basis for effect level:
- other: embryotoxicity
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- ca. 1.31 mg/L air (nominal)
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Executive summary:
In a developmental toxicity study, pregnant Sprague-Dawley female rats (30 per dose) were exposed to the n-butyl acrylate 6h/day on days 6 through 15 of gestation. Control animals were exposed concurrently to filtered room air. The test concentrations of n-butyl acrylate were 25, 135 and 250 ppm. Significant decreases in maternal body weight gain were observed at 135 and 250 ppm dose groups through the entire exposure period. The number of corpora lutea and the number of implantations did not show any differences between the individual groups. However, the percentage of live implantations per pregnant animal was decreased in the 135 and 250 ppm dose groups. No significant increases in malformations was observed in n-butyl acrylate exposed fetuses.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Principles of method if other than guideline:
- Groups of 20-29 bred female rats (17-25 pregnant) were exposed to the compound 6h/day on days 6 through 20 of gestation. Control animals were exposed concurrently to filtered room air. The test concentrations of n-butyl acrylate were 100, 200, and 300 ppm (corresponding to approx. 0.52, 1.05, and 1.57 mg/L)*.
* Calculation of concentrations (mg/L) based on Derelanko MJ (2000). Toxicologist's Pocket Handbook, CRC Press, conversion table, p. 57 - GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: IFFA CREDO Breeding Laboratories (Saint-Germain-sur-l' Arbresle, France)
- Age at study initiation: Young, nulliparous females
- Weight at study initiation: 200-220 g
- Housing: Single in clear polycarbonate cages with stainless-steel wire lids and hardwood shaving as bedding.
- Diet: Food pellets (UAR Alimentation Villemoisson, France), ad libitum
- Water: Filtered tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 50 ± 5
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- EXPOSURE
Exposures were conducted in 200-L glass/stainless-steel inhalation chambers with dynamic and adjustable laminar air flow (6-20 m3/h). The chamber temperature was set at 23 ± 2°C, and the relative humidity at 50 ± 5 %. The air-flow rate passed through the fritted disk of a heated bubbler containing the test chemical. Concentrations of acrylate ester were monitored continuously with a gas-chromatograph equipped with a flame ionization detector and an automatic gas-sampling valve. In addition, exposure levels were determined once during each 6-h exposure period by collecting atmosphere samples through glass tubes packed with activated charcoal. The charcoal samples were then desorbed with carbon disulfide. The resulting samples were analyzed by gas chromatography using appropriate internal standards.
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass/stainless-steel inhalation chambers
- Source and rate of air: Test atmospheres were generated through an additional air-flow rate passed through the fritted disk of a heated bubbler containing ethylhexyl acrylate. The vaporized compound was introduced into the main air inlet pipe of the exposure chamber.
- Air flow rate: 6-20 m3/h
TEST ATMOSPHERE
- Brief description of analytical method used: GC/FID
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analytical concentrations (mean ± SD):
103.3 ± 6.7 ppm (nominal: 100 ppm)
202.8 ± 9.7 ppm (nominal: 200 ppm)
302.5 ± 10.1 ppm (nominal: 300 ppm) - Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/2-3
- Length of cohabitation: Overnight
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- days 6 to 20 of gestation
- Frequency of treatment:
- 6 hours/day
- Duration of test:
- until gestation day 21
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale:
Exposure concentrations were based on preliminary studies in which marked decreases in maternal weight gain were observed at 200 and 300 ppm of butyl acrylate. Results from previous prenatal inhalation toxicity studies on butyl acrylate were also considered (Merkle and Klimisch, 1983). The high concentrations of butyl acrylate for the definitive study (200 and 300 ppm, respectively) were chosen to maximize the opportunity of identifying embryolethal or teratogenic potential. - Maternal examinations:
- BODY WEIGHT: Yes
- Time schedule for examinations: On gestation day (GD) 0, 6, 13 and 21.
FOOD CONSUMPTION: YES
Food consumption was measured for the intervals GD 6-13 and 13-21.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Organs examined: The uteri were removed and weighed. The number of implantation sites, resorptions, and dead and live fetuses were recorded. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
The number of implantation sites, resorptions, and dead and live fetuses were recorded. Uteri which had no visible implantation sites were stained with ammonium sulfide (10 %) to detect very early resorptions.
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- Live fetuses were weighed, sexed, and examined for external anomalies including those of the oral cavity. Half of the live fetuses from each litter were preserved in Bouin's solution and examined for internal soft tissue changes. The other half were fixed in ethanol (70 %), eviscerated, and then processed for skeletal staining with alizarin red S for subsequent skeletal examination.
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: all per litter - Statistics:
- Data were presented as mean ± SD. The number of implantation sites and live fetuses and the various body weights were analyzed by one-way analysis of variance (ANOVA), followed by Dunnett's test if differences were found. The percentages of non-live implants and resorptions and the proportions of fetuses with alterations in each litter were evaluated by using the Kruskal-Wallis test, followed by the Dixon-Massey test where appropriate. Rates of pregnancy, fetal sex ratio, and percentage of litters with malformations or external, visceral, or skeletal variations were analyzed by using Fisher's test. Where applicable, least-squares analysis was carried out. For all statistical tests, the level of significance was set a priori at alpha = 0.05.
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- During the entire exposure period, maternal weight gain was signifciantly reduced at 200 ppm and 300 ppm compared to the control group. Absolute weight gains (expressed as the day 21 body weight minus the gravid uterus weight and minus the day 6 body weight) were reduced in a dose-rependent manner in all exposure groups.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Decreases in food consumption was observed during the first half of the study for the females in the 100 ppm dose group and throught the exposure period at 200 and 300 ppm. The maximum decrease was 40-50% at the highest concentration.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not examined
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined - Changes in number of pregnant:
- no effects observed
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- ca. 0.52 mg/L air (nominal)
- Basis for effect level:
- other: maternal toxicity
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Fetal body weight was significantly reduced at 200 ppm (for both sexes combined and males) and at 300 ppm (both sexes combined, males and females). These decreases amounted to 7-8 % (p<0.05) and 26-28 % (p<0.01) of control values for the 200 and 300 ppm groups, respectively.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- A few sporadic malformations were seen in the 300 ppm and the control group. The incidence of individual skeletal variations (mainly incomplete ossification of sternebrae and of vertebral centra) was similar in the control and treated groups.
- Visceral malformations:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- ca. 0.52 mg/L air (nominal)
- Basis for effect level:
- other: fetotoxicity
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- ca. 1.57 mg/L air (nominal)
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Executive summary:
In a developmental toxicity study, pregnant Sprague-Dawley female rats (20-29 per dose) were exposed to the compound 6h/day on days 6 through 20 of gestation. Control animals were exposed concurrently to filtered room air. The test concentrations of n-butyl acrylate were 100, 200, and 300 ppm (corresponding to approx. 0.52, 1.05, and 1.57 mg/L). Significant decreases in maternal body weight gain were observed at 200 ppm and 300 ppm, and decreased absolute weight gain were observed in all dose groups through the entire exposure period. Decreased fetal body weight was observed at 200 ppm (7-8%) and 300 ppm (26-28%) in the presence of significant maternal toxicity. No significant increases in malformations was observed in n-butyl acrylate exposed fetuses.
Referenceopen allclose all
Maternal body weight development (mean values ± standard deviation):
Concentration [ppm] |
Maternal body weight GD 0 [g] |
Maternal body weight GD 20 [g] |
Maternal body weight gain GD 0-20 [g] |
0 |
209.38 ± 11.83 |
354.01 ± 36.66 |
144.64 ± 33.08 |
25 |
213.96 ± 13.94 |
359.62 ± 36.81 |
145.66 ± 29.87 |
135 |
213.68 ± 9.30 |
335.54 ± 43.00 |
121.87 ± 37.62* |
250 |
218.64 ± 16.19 |
318.11 ± 42.79** |
99.47± 33.68** |
* p < 0.05
** p < 0.01
Reproductive parameters:
Conc. (ppm) |
no. pregnant/ total animals |
live fetuses/ animal |
resorptions (%) |
weight of fetuses (g) |
0 |
22/30 |
11.5 ± 5.34 |
11.6 |
3.85 ± 0.41 |
25 |
23/30 |
10.6 ± 4.94 |
13.8 |
4.08 ± 0.39 |
135 |
18/30 |
8.8 ± 5.14 |
23.6* |
4.09 ± 0.23 |
250 |
19/30 |
8.4 ± 5.68 |
31.6* |
4.08 ± 0.47 |
*: p<0.05
Conc. (ppm) |
% fetuses per litter with anomalies |
% litters with fetuses showing anomalies |
% fetuses per litter with variations/ retardations |
% litters with fetuses showing variations/ retardations |
0 |
2.7 |
23.8 |
19.7 |
81.0 |
25 |
0.9 |
9.1 |
11.2 |
59.1 |
135 |
1.9 |
18.8 |
10.2 |
43.8 |
250 |
0 |
0 |
8.2 |
43.8 |
|
0 ppm |
25 ppm |
135 ppm |
250 ppm |
Skeletal findings |
||||
Anomalies: |
||||
- Cleft vertebral centra |
7/170 |
2/162 |
4/105 |
0/107 |
Variations/retardations: |
||||
- incomplete ossification of skull bone |
0/170 |
0/162 |
1/105 |
0/107 |
- aplasia of sternebrae |
16/170 |
11/162 |
3/105 |
3/107 |
-incomplete ossification of sternebrae |
30/170 |
18/162 |
14/105 |
9/107 |
- asymmetric sternebrae |
4/170 |
1/162 |
0/105 |
0/107 |
-accessory rib, bilateral |
2/170 |
3/162 |
0/105 |
0/107 |
-accessory rib, bilateral and rudimentary |
1/170 |
0/162 |
0/105 |
0/107 |
-accessory rib, unilateral and rudimentary |
1/170 |
0/162 |
0/105 |
0/107 |
-general incomplete ossification of bones |
1/170 |
2/162 |
1/105 |
1/107 |
Organ findings |
||||
Variations/retardations: |
||||
-dilatation of pelvis, unilateral |
2/82 |
0/81 |
1/54 |
0/53 |
Units given as number found/number examined
Maternal body weight development (mean values ± standard deviation):
Concentration [ppm] |
Maternal body weight GD 0 [g] |
Maternal body weight GD 20 [g] |
Maternal body weight gain GD 0-20 [g] |
0 |
209.38 ± 11.83 |
354.01 ± 36.66 |
144.64 ± 33.08 |
25 |
213.96 ± 13.94 |
359.62 ± 36.81 |
145.66 ± 29.87 |
135 |
213.68 ± 9.30 |
335.54 ± 43.00 |
121.87 ± 37.62* |
250 |
218.64 ± 16.19 |
318.11 ± 42.79** |
99.47± 33.68** |
* p < 0.05
** p < 0.01
Reproductive parameters:
Conc. (ppm) |
no. pregnant/ total animals |
live fetuses/ animal |
resorptions (%) |
weight of fetuses (g) |
0 |
22/30 |
11.5 ± 5.34 |
11.6 |
3.85 ± 0.41 |
25 |
23/30 |
10.6 ± 4.94 |
13.8 |
4.08 ± 0.39 |
135 |
18/30 |
8.8 ± 5.14 |
23.6* |
4.09 ± 0.23 |
250 |
19/30 |
8.4 ± 5.68 |
31.6* |
4.08 ± 0.47 |
*: p<0.05
Conc. (ppm) |
% fetuses per litter with anomalies |
% litters with fetuses showing anomalies |
% fetuses per litter with variations/ retardations |
% litters with fetuses showing variations/ retardations |
0 |
2.7 |
23.8 |
19.7 |
81.0 |
25 |
0.9 |
9.1 |
11.2 |
59.1 |
135 |
1.9 |
18.8 |
10.2 |
43.8 |
250 |
0 |
0 |
8.2 |
43.8 |
|
0 ppm |
25 ppm |
135 ppm |
250 ppm |
Skeletal findings |
||||
Anomalies: |
||||
- Cleft vertebral centra |
7/170 |
2/162 |
4/105 |
0/107 |
Variations/retardations: |
||||
- incomplete ossification of skull bone |
0/170 |
0/162 |
1/105 |
0/107 |
- aplasia of sternebrae |
16/170 |
11/162 |
3/105 |
3/107 |
-incomplete ossification of sternebrae |
30/170 |
18/162 |
14/105 |
9/107 |
- asymmetric sternebrae |
4/170 |
1/162 |
0/105 |
0/107 |
-accessory rib, bilateral |
2/170 |
3/162 |
0/105 |
0/107 |
-accessory rib, bilateral and rudimentary |
1/170 |
0/162 |
0/105 |
0/107 |
-accessory rib, unilateral and rudimentary |
1/170 |
0/162 |
0/105 |
0/107 |
-general incomplete ossification of bones |
1/170 |
2/162 |
1/105 |
1/107 |
Organ findings |
||||
Variations/retardations: |
||||
-dilatation of pelvis, unilateral |
2/82 |
0/81 |
1/54 |
0/53 |
Units given as number found/number examined
Maternal body weights:
Concentration [ppm/6h/d] |
Maternal body weight GD 6 [g] |
Absolute weight gain [g] |
0 |
294 ± 23 |
32 ± 15 |
100 |
289 ± 23 |
18 ± 14* |
200 |
299 ± 24 |
-16 ± 20** |
300 |
292 ± 23 |
-60 ± 26** |
Absolute weight gain: (Day 21 body weight) - (gravid uterus weight) - (Day 6 body weight)
Reproductive parameters:
Conc. [ppm/6h/d] |
No. of litters |
No. of implantation sites/litter |
% of non-live implants/litter |
% of resorption sites/litter |
No. of live fetuses/litter |
Average fetal body weight/litter [g] |
0 |
25 |
15.68 ± 3.17 |
10.9 ± 15.49 |
10.64±15.62 |
14.12 ± 4.01 |
5.74 ± 0.43 |
100 |
24 |
15.58 ± 3.05 |
6.82 ± 10.19 |
6.82 ± 10.19 |
14.71 ± 3.57 |
5.71 ± 0.35 |
200 |
24 |
15.08 ± 4.23 |
4.72 ± 5.96 |
4.72 ± 5.96 |
14.46 ± 4.20 |
5.33 ± 0.40* |
300 |
25 |
15.40 ± 5.24 |
6.48 ± 15.94 |
6.48 ± 15.94 |
14.68 ± 5.38 |
4.25 ± 0.94** |
Concentration [ppm/6h/d] |
0 |
100 |
200 |
300 |
Mean % of fetuses with: |
||||
- any malformations/litter |
2.00 ± 7.33 |
0 |
0 |
0.62 ± 2.65 |
- external variations/litter |
1.33 ± 6.67 |
0 |
0 |
0.22 ± 1.11 |
- visceral variations/litter |
8.81 ± 14.64 |
0 |
0 |
4.17 ± 20.41 |
- skeletal variations/litter |
13.70 ± 15.48 |
17.01 ± 14.53 |
18.71 ± 24.21 |
24.65 ± 20.69 |
- any variations/litter |
12.60 ± 10.80 |
13.27 ± 15.07 |
10.10 ± 10.32 |
15.90 ± 19.98 |
* ,** Significant differences from the control (0 ppm) value, p 0.05, and p 0.01, respectively.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 130 mg/m³
- Study duration:
- subacute
- Species:
- rat
Additional information
Developmental Toxicity: Inhalation
In a developmental toxicity study, pregnant Sprague-Dawley female rats (20-29 per dose) were exposed to the compound 6h/day on days 6 through 20 of gestation. Control animals were exposed concurrently to filtered room air. The test concentrations of n-butyl acrylate were 100, 200, and 300 ppm (corresponding to approx. 0.52, 1.05, and 1.57 mg/L). Significant decreases in maternal body weight gain were observed at 200 ppm and 300 ppm, and decreased absolute weight gain were observed in all dose groups through the entire exposure period. Decreased fetal body weight was observed at 200 ppm (7-8%) and 300 ppm (26-28%) in the presence of significant maternal toxicity. No significant increases in malformations was observed in n-butyl acrylate exposed fetuses.
In a developmental toxicity study, pregnant Sprague-Dawley female rats (30 per dose) were exposed to the n-butyl acrylate 6h/day on days 6 through 15 of gestation. Control animals were exposed concurrently to filtered room air. The test concentrations of n-butyl acrylate were 25, 135 and 250 ppm. Significant decreases in maternal body weight gain were observed at 135 and 250 ppm dose groups through the entire exposure period. The number of corpora lutea and the number of implantations did not show any differences between the individual groups. However, the percentage of live implantations per pregnant animal was decreased in the 135 and 250 ppm dose groups. No significant increases in malformations was observed in n-butyl acrylate exposed fetuses.
Justification for classification or non-classification
N-hexyl acrylate was evaluated for its potential toxicity to reproduction based on read-across to data of a structurally similar substance, N-butyl Acrylate. This read-across approach is based on the hypothesis that the hydrolysis of both substances to acrylic acid and the respective alcohols would show similar toxicity patterns. The effect of the parent compound from the target substance is also predicted based on the worst case approach as data indicate the parent structure of the source substance would be expected to have a higher electrophilic capacity. N-butyl acrylate produced no abnormal histopathology findings in either male or female reproductive organs in subchronic studies by the oral or inhalation routes. In two developmental toxicity studies, exposure of fetuses to n-butyl acrylate vapors produced no increase in malformations. As the read-across is considered valid, classification of N-hexyl acrylate as a Reproductive toxicant is not warranted under the Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).
Additional information
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