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EC number: 248-363-6 | CAS number: 27247-96-7
- 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:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Experiment using the rapidly formed hydrolysis product of the target chemical conducted according to a protocol comparable to guideline OECD TG 414; publication meets generally accepted standards and is reported in sufficient detail
- Justification for type of information:
- Source substance, 2-ethyl-1-hexanol is the rapidly formed hydrolysis product of the target substance, 2-EHN.
Data source
Reference
- Reference Type:
- publication
- Title:
- Developmental toxicology evaluation of 1-pentanol, 1-hexanol, and 2-ethyl-1-hexanol administered by inhalation to rats
- Author:
- BK Nelson, WS Brightwell, A Khan, EF Krieg, AM Hoberman
- Year:
- 1 989
- Bibliographic source:
- Journal of the American College of Toxicology, Vol 8, Number 2, 405-410
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- 15 female test animals (instead of 25)
- GLP compliance:
- not specified
- Limit test:
- yes
Test material
- Reference substance name:
- 2-ethylhexan-1-ol
- EC Number:
- 203-234-3
- EC Name:
- 2-ethylhexan-1-ol
- Cas Number:
- 104-76-7
- Molecular formula:
- C8H18O
- IUPAC Name:
- 2-ethylhexan-1-ol
Constituent 1
Test animals
- Species:
- rat
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI, U.S.A.
- Age at study initiation: No data
- Weight at study initiation: 200-300 g at beginning of pregnancy
- Fasting period before study: No
- Housing: singly, in stainless steel mesh wire cages during gestation and exposure
- Diet: Ad libitum (during exposure-free periods)
- Water: Ad libitum (during exposure-free periods)
- Acclimation period: 1-2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±2
- Humidity (%): 50±10
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- air
- Remarks:
- Constant flow of test item mixed with a defined volume of heated air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Hinners-type 0.5 m³ exposure chamber
- Method of holding animals in test chamber: In cages
- Source and rate of air: Compressed ambient air
- Method of conditioning air: Heating
- Temperature and humidity in air chamber: 77±2 F° (i.e. 25°C), 50±15 %
- Air flow rate: 0.5 m³/min
- Air change rate: 60/h
TEST ATMOSPHERE
- Brief description of analytical method used: Hourly by infrared analyzer, twice a week by GC of charcoal tubes from the exposure chamber
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- - A Miran 1A infrared analyzer was constantly used for hourly measurement.
- Additionally the Exposure concentrations were
verified weekly by a secondary analysis. Charcoal tube samples were drawn 2 days/week and analyzed by gas chromatography, with partial verification by samples spiked with known concentrations - Details on mating procedure:
- - Proof of pregnancy: Sperm in vaginal smear referred to as day 0
- Duration of treatment / exposure:
- Gestation days 1-19
- Frequency of treatment:
- 7 h every day
- Duration of test:
- 19 days (dams were sacrificed on day 20)
Doses / concentrations
- Remarks:
- Doses / Concentrations:
850 mg/m³ air
Basis:
analytical conc.
- No. of animals per sex per dose:
- 15 (only females included)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Probably in expectation of absence of effects, the experimental equipment was used to provide the highest achievable concentration while keeping the mixing chamber temperature below 80 °F (ca. 27 °C)>
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: Daily for the first week and weekly thereafter
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No, calculated on a weekly basis
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: uterus, ovaries - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Not reported
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes, all animals per litter
- Soft tissue examinations: Yes, half of the animals per litter
- Skeletal examinations: Yes, half of the animals per litter
- Head examinations: No - Statistics:
- Multivariate analysis of variance (MANOVA) and analysis of variance (ANOVA)
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects. Remark: Overall feed consumption was approximatley 10-15% lower than in control animals.
Details on maternal toxic effects:
Although the weight gain appeared to be lower these difference did not reach statistical significance.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEC
- Remarks:
- Discriminating level = sole test concentration, 7 h/day, gd 1-19
- Effect level:
- >= 850 mg/m³ air
- Based on:
- test mat.
- Remarks:
- 2-Ethylhexan-1-ol
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEC
- Remarks:
- Discriminating level
- Effect level:
- >= 160 ppm
- Based on:
- test mat.
- Remarks:
- 2-Ethylhexan-1-ol
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEC
- Remarks:
- Discriminating level
- Effect level:
- >= 1 148 mg/m³ air
- Based on:
- other: conversion to target chemical 2-Ethylhexyl Nitrate
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEC
- Remarks:
- Discriminating level
- Effect level:
- >= 6.5 other: mmol/m³
- Based on:
- other: molar concentration of source and target chemical
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Remarks:
- Discriminating dose
- Effect level:
- >= 193 other: mg/kg bw/day (inhalation-to-oral extrapolation)
- Based on:
- other: conversion to target chemical 2-Ethylhexyl Nitrate
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Remarks:
- Discriminating dose
- Effect level:
- >= 1.1 other: mmol/kg bw/day (inhalation-to-oral extrapolation)
- Based on:
- other: conversion to target chemical 2-Ethylhexyl Nitrate
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No indication of malformations induced after exposure of pregnant rats were found.
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 850 mg/m³ air
- Based on:
- test mat.
- Basis for effect level:
- other: No toxicity to highest dose tested
- Dose descriptor:
- NOAEC
- Effect level:
- 6.5 other: mmol/m3
- Based on:
- test mat.
- Basis for effect level:
- other: conversion to molar concentration to conver to 2-EHN concentration
- Dose descriptor:
- NOAEC
- Effect level:
- 1 148 mg/m³ air
- Based on:
- act. ingr.
- Basis for effect level:
- other: conversion from molar concentration to 2-EHN concentration in mg/m3
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Table 1: Summary of data (Litter mean ± standard deviation)
Data |
Test item 2-EH |
Control |
Mean maternal weight [g] |
||
Day 0 |
283 ± 18 |
243 ± 25 |
Day 7 |
286 ± 17 |
262 ± 24 |
Day 14 |
310 ± 17 |
291 ± 26 |
Day 20 |
371 ± 20 |
354 ± 32 |
Overall gain |
88 |
111 |
Mean feed consumption [g] |
||
Week 1 |
97 ± 17 |
108 ± 14 |
Week 2 |
107 ± 12 |
124 ± 12 |
Week 3 |
113 ± 11 |
118 ± 10 |
Overall mean |
106 ± 15 (a) |
117 ± 13 |
Mean water intake [g] |
||
Week 1 |
196 ± 32 |
204 ± 46 |
Week 2 |
203 ± 24 |
276 t 93 |
Week 3 |
248 ± 30 |
265 ± 123 |
Overall mean |
216 ± 36 |
248 ± 96 |
Mean corpora lutea per litter |
15 ± 2 |
14 ± 4 |
Mean resorptions per litter |
0.3 |
0.4 |
Mean number females per litter |
7 ± 2 |
8 ± 2 |
Mean number males per litter |
7 ± 2 |
7 ± 2 |
Mean fetal weight [g] |
|
|
Female |
3.02 ± 0.20 |
3.19 ± 0.20 |
Male |
3.18 ± 0.30 |
3.28 ± 0.27 |
(a) Significantly different from control
Applicant's summary and conclusion
- Conclusions:
- No maternal or foetal toxicity after inhalation exposure using the maximum vapour concentration of 850 mg/m³ air.
- Executive summary:
The prenatal developmental toxicity of the source substance and test item 2-Ethylhexan-1-ol (CAS 104-76-7) via the inhalation route in the rat was measured in a GLP-compliant study using a “Prenatal Developmental Toxicity Study” compliant with OECD TG 414 (2001), with the sole deviation that the number of test animals was reduced (15 female test animals instead of 25). The validity criteria were met and the experiment can be considered relevant and adequate for the endpoint, however a reduced number of test animals were included. Nonetheless it is deemed conclusive and was rated „reliable with restrictions“, i.e. “Klimisch 2” according to the scale of Klimisch et al. (1997). In consideration of possible read-across from this study to metabolic precursors, additional uncertainties have to be taken into account. The rating of the study for use in such analogue or metabolite approach is lower compared to equally rated studies providing direct data from a target substance.
Fifteen sperm-positive female Sprague-Dawley rats were exposed to vapours of the test item through whole body exposure during gestation days 0 -19. Hinners type 0.5m³ exposure chambers to vapours of the test item at a concentration of 850 mg/m³ air was confirmed independently 2 methods; hourly by infrared analyzer and twice weekly by gas chromatography of charcoal tubes from the exposed chamber.
No maternal toxicity or developmental toxicity was noted in a rat inhalation study. The overall feed consumption was approximatley 10 -15% lower in treated animals compared to controls. Although the weight gain appeared to be lower in the treated animals, these differences did not reach statistical significance. The reproduction parameters were unchanged. No malformations were induced after exposure of the pregnant rats to the test substance. The incidences of resorptions, the number of fetuses per litter, the sex ratio, fetal weight, were not different to the control group and no external, skeletal or visceral malformations have been recorded.
In conclusion no substance-related adverse effects of the test item were observed at the highest vapour concentration achievable. Therefore the NOAEL (discriminating dose) was assigned to the highest test concentration. The NOAEL for maternal and developmental toxicity and teratogenicity in the rat is thus ≥ 850 mg/m³ air or ≥ 6.5 mmol/m³ as a basis for equimolar comparison in read-across approaches.
Reading-across to the target substance, 2-Ethylhexyl nitrate (2 -EHN, CAS 27247-96-7) delivers on the same molar concentration an air level of ≥1148 mg/m³ air. Taking the significantly lower vapour pressure of the target chemical (only 27 versus 93 Pa of 2 -EH at 20 °C) into account, an equimolar exposure exceeding saturated vapour concentrations of the target chemical can be concluded to be non-toxic during developmental exposure.
- Klimisch HJ, Andreae M, Tillmann U (1997). A Systematic Approach for Evaluating the Quality of Experimental Toxicological and Ecotoxicological Data. DOI 10.1006/rtph.1996.1076 PMID 9056496 Regul Toxicol Pharmacol 25:1-5.
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