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EC number: 248-570-1 | CAS number: 27610-92-0
- 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:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1997-03-24 - 1997-04-9
- Reliability:
- 2 (reliable with restrictions)
- Justification for type of information:
- please see category approach
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 2-butyloctanoic acid
- EC Number:
- 248-570-1
- EC Name:
- 2-butyloctanoic acid
- Cas Number:
- 27610-92-0
- Molecular formula:
- C12H24O2
- IUPAC Name:
- 2-butyloctanoic acid
- Test material form:
- liquid
- Details on test material:
- - Name of test material: 2-butyl octanoic acid
- Molecular formula: C12H24O2
- Molecular weight: 200.32 g/mole
- Smiles notation: O=C(O)C(CCCCCC)CCCC
Constituent 1
Test animals
- Species:
- rat
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:Charles River (UK) Limited, Margate, Kent, England on 21 March 1997
- Age at study initiation: ca 9 weeks of age on arrival
- Weight at study initiation: 196-274 g
- Fasting period before study: not mentioned
- Housing: The females were housed singly in polypropylene cages with stainless steel grid bottoms and mesh tops, measuring 42 x 27 x 20 cm. A separate stainless steel food hopper and a polycarbonate water bottle were provided for each cage. Excreta were collected on a tray, lined with absorbent paper, suspended beneath each cage. The cages were suspended on racks, each full rack containing 6 rows of 4 cages.
Cages, tray paper and water bottles were changed as required.
- Diet (e.g. ad libitum): Rat and Mouse Breeder Diet No. 3 (Expanded) SQC, the diet was supplied with a batch analysis for nutritive constituents and a range of significant contaminants.
- Water (e.g. ad libitum): domestic mains water
- Acclimation period: for 3-5 days prior to commencement of treatment.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 ± 15
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 1997-02-21 To: 1997-04-09
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: sodium hydroxide solution in water, adjusted at pH 9.5
- Details on exposure:
- The test material was administered orally (by gavage) because this is a likely route of exposure in man. Dosing was performed once daily at approximately the same time each day. The highest concentration of dose formulation was prepared by mixing equimolar amounts of test material and sodium hydroxide (diluted in water for irrigation). Lower dose concentrations were then prepared by serial dilutions in water for irrigation and adjusted to approximately pH 9.5 with sodium hydroxide. All solutions were mixed by manual inversion until visibly homogenous. The Control animals received water for irrigation.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analysed concentrations of the dose formulations were within 4 % of the nominal indicating accurate formulation of the test material, the low coefficients of variation indicated that the formulation were homogenous. In the proposed method, samples of gavage dosing solutions are spiked with Lauric Acid as internal standard, diluted with mobile phase as necessary and analysed by HPLC with UV detection at 212 nm.
The limit of quantification was investigated and shown to be ca. 11 µg/ml. The chromatographic system has been shown to be linear over a range of ca. 0-165 µg/ml for the test substance in solution. The coefficient of correlation obtained was 0.9996. The overall accuracy was 101% and the assay precision, expressed as a coefficient of variation (n=10) was 2.9 %. Determination of the system precision showed a coefficient of variation of 0.7 % for samples equivalent to ca. 99 µg/ml. The stability test indicated that the test substance is stable at least 11 days in mobile phase when stored at ambient laboratory temperature in the dark. Gavage solutions containing ca 1 mg/ml and ca 100 mg/ml test substance were shown to be accurately and homogenously formulated. Gavage solutions were shown to be stable for at least 1 day, when stored at ambient laboratory temperature in the dark at least 7 days, when stored at 2-8 °C. - Details on mating procedure:
- No more than 2 females were inseminated by the same male, and the identity of each male was provided.
- Duration of treatment / exposure:
- The animals were dosed once daily at approximately the same time each day over days 6-19 (inclusive) of gestation.
- Frequency of treatment:
- once daily at a volume of 10 ml dosing formulation per kg of body weight, using a steel dosing cannula.
- Duration of test:
- altogether 16 days, 14 days of exposure
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
25 mg/kg bw/d
Basis:
other: gavage
- Remarks:
- Doses / Concentrations:
200 mg/kg bw/d
Basis:
other: gavage
- Remarks:
- Doses / Concentrations:
400 mg/kg bw/d
Basis:
other: gavage
- No. of animals per sex per dose:
- 25
- Control animals:
- other: water
- Details on study design:
- - Dose selection rationale: A preliminary study was conducted with 125; 250; 500; 1000 mg/kg bw/d. Mated female Sprague-Dawley rats were dosed orally by gavage over days 6-19 inclusive of gestation. They were killed on day 20 of gestation for evaluation of pregnancy outcome. Body weight loss and a marked decrease in food consumption were observed at 1000 mg/kg bw/d. One animal had a premature death, the study was terminated for the highest dose group. There were treatment related clinical observations in all groups, the type and severity of the finding was dependent upon the dose: Staggering, altered respiration, dark and/or partially closed eyes, skin cold to touch, subdued behaviour, hunched appearance, piloerection and transient salivation. At 500 mg/kg bw/d principal findings were the clinical observations. Slightly reductions in group mean foetal weights were observed, but there was no evidence of any effects on foetal survival. At 250 and 100 mg/kg bw/d any changes observed in body weight gain and food consumption were considered too small to be attributed to treatment. There was no effect of treatment on pregnancy perfomace or foetal weight. In conclusion, the findings at 1000 and 500 mg/kg bw/d precluded the use of either of these dose levels in a subsequent developmental toxicity study. However, maternal toxicity at 250 mg/kg bw/d was manifest principically as clinical observations and there was concern that there my be few effects seen at this level. Based on that study for the main study the levels were 0; 25; 200 and 400 mg/kg bw/d (study report Inveresk, 491708).
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: No
DETAILED CLINICAL OBSERVATIONS: Yes, all animals: examined to treatment, the nature, onset, duration and intensity of any signs were recorded, a specific examination being made 1-2 h after dosing.
- Time schedule: at the beginning and and the end of each day
BODY WEIGHT: Yes
- Time schedule for examinations: days 4 and 6-20 of gestation
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, the weight of the food consumed by each animal was recorded daily, commencing on day 4 of gestation (weighed quantity first offered on day 3, residue recorded on day 4).
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20, the females were killed by carbon dioxide asphyxiation, foetuses were killed by chilling at ca. 4 °C for approximately 10 min. - Ovaries and uterine content:
- No data
- Fetal examinations:
- fetal weight, fetal abonormalities, variants, skeletal ossification paramaters
- Statistics:
- mean body weight gains over days 6 to 9, 9 to 13, 13 to 20, 6 to 20 were analysed. Analysation by the Kruskal-Wallis test. Mean foetal weights were analyses by the Kruskal-Wallis test. For the other reproductive parameters no statistical evaluation was done.
- Historical control data:
- Not mentioned
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- clinical observations in all animals, including altered respiration pattern, piloerection, hunched appearance, red/brown staining of coat, and salivation. It was necessary to discontinue dosing for 4 animals, and 2 of these were subsequently killed because of their condition.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- There were decreases in body weight gain and food consumption during the middle part of the dosing period. There were no obvious effects on body weight or food consumption at the lower levels.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Maternal developmental toxicity
- 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:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed - Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
At 400 mg/kg bw/d there were decreases in body weight gain and food consumption during the middle part of the dosing period. There were no obvious effects on body weight or food consumption at the lower levels.
Maternal toxicity at 400 mg/kg bw/d was manifest as clinical observations in all animals, including altered respiration pattern, piloerection, hunched appearance, red/brown staining of coat, and salivation. It was necessary to discontinue dosing for 4 animals, and 2 of these were subsequently killed because of their condition.
At 200 mg/kg bw/d maternal toxicity was limited to clinical observations including altered respiration pattern, hunched appearance and piloerection.
There was no indication of maternal toxicity at 25 mg/kg bw/d.
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 25 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- At 400 mg/kg bw/d there was a significant decrease in mean foetal weight. At 25 and 200 mg/kg bw/d mean foetal weights were not signicantly different from Control.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): At 400 mg/kg bw/d there was a significant decrease in mean foetal weight. At 25 and 200 mg/kg bw/d mean foetal weights were not signicantly different from Control. - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Among the minor foetal abnormalities, the incidence of supernumerary (14th) ribs at 400 mg/kg bw/d was greater than Control. The incidences of supernumerary ribs at 25 and 200 mg/kg bw/d were slightly greater than Control, but these incidences were within the recent background range and were not obviously associated with treatment. The incidences of the other minor foetal abnormalities did not indicate any effect of treatment. At 400 mg/kg bw/d there was a slight increase in the number of foetuses with unossified 5th metacarpals and the number of sternebrae incompletely ossified. These findings were considered to reflect the decrease in foetal weight noted at this dose level. The slight changes in the foetal ossification parameters at the lower levels were considered too small to be associated with treatment.
- Visceral malformations:
- not specified
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes. Remark: only minor effects at the hightes dose group, only in maternal toxic dosages
Details on embryotoxic / teratogenic effects:
At 400 mg/kg bw/d there was a significant decrease in mean foetal weight. At 25 and 200 mg/kg bw/d mean foetal weights were not signicantly different from Control. Among the minor foetal abnormalities, the incidence of supernumerary (14th) ribs at 400 mg/kg bw/d was greater than Control. The incidences of supernumerary ribs at 25 and 200 mg/kg bw/d were slightly greater than Control, but these incidences were within the recent background range and were not obviously associated with treatment. The incidences of the other minor foetal abnormalities did not indicate any effect of treatment. At 400 mg/kg bw/d there was a slight increase in the number of foetuses with unossified 5th metacarpals and the number of sternebrae incompletely ossified. These findings were considered to reflect the decrease in foetal weight noted at this dose level. The slight changes in the foetal ossification parameters at the lower levels were considered too small to be associated with treatment.
Effect levels (fetuses)
open allclose all
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 400 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
Fetal abnormalities
- Key result
- Abnormalities:
- not specified
Overall developmental toxicity
- Key result
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In conclusion, under the conditions of this study, the maternal No Effect Level was considered to be 25 mg/kg bw/d and the foetal No Effect Level was considered to be 200 mg/kg bw/d.
- Executive summary:
2-butyl octanoic acid was investigated for developmental toxicity testing in rats. Mated female Sprague-Dawley rats were randomised into 4 treatment groups, each containing 25 animals. These animals were dosed orally by gavage once daily over Days 6-19 inclusive of gestation, where Day 0 was the day of detection of mating. The dose levels applied were 0 (control); 25; 200 and 400 mg/kg bw/d.
The animals were monitored during gestation for clinical signs of toxicity and for body weight, food and water consumption performance. They were killed on Day 20 of gestation for evaluation of pregnancy outcome. The live foetuses were subsequently examined for abnormalities and variants of the viscera and skeleton. Maternal toxicity at 400 mg/kg bw/d 2 -butyloctanoic acid was manifest as clinical observations in all animals, including altered respiration pattern, piloerection, hunched appearance, red/brown staining of coat, and salivation. It was necessary to discontinue dosing for 4 animals, and 2 of these were subsequently killed because of their condition. At 200 mg/kg bw/d maternal toxicity was limited to clinical observations including altered respiration pattern, hunched appearance and piloerection. There was no indication of maternal toxicity at 25 mg/kg bw/d. At 400 mg/kg bw/d there were decreases in body weight gain and food consumption during the middle part of the dosing period. There were no obvious effects on body weight or food consumption at the lower levels. At 400 mg/kg bw/d mean foetal weight was lower than control, and there was an increased incidence of supernumerary ribs. Foetal ossification at 400 mg/kg bw/d was slightly reduced, as indicated by an increased incidence of incomplete ossification affecting the sternebrae and digital bones, probably associated with the decrease in foetal weight. There were no obvious foetal effects at 25 or 200 mg/kg bw/d. There was no obvious effects of treatment on pregnancy performance (including the incidence and survival of implants) at any of the dose levels applied.
In conclusion, under the conditions of this study, the maternal No Effect Level was considered to be 25 mg/kg bw/d and the foetal No Effect Level was considered to be 200 mg/kg bw/d. In not maternal toxic dosages no teratogenic effects were found. Therefore the substance is considered to be not developmental toxic.
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