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EC number: 203-961-6 | CAS number: 112-34-5
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- toxicity to reproduction
- Remarks:
- other: data from a sub-chronic toxicity study
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1993
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented NTP publication which meets basic scientific principles.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- NTP Technical Report 26 on Toxicity Studies of Ethylene Glycol Ethers 2-Methoxyethanol, 2-Ethoxyethanol, 2-Butoxyethanol Administered in Drinking Water to F344/N Rats and B6C3FX Mice.
- Author:
- US National Institute of Environmental Scientists
- Year:
- 1 993
- Bibliographic source:
- NIH Publication 93-3349
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD repeat dose toxicity 409
- Deviations:
- not applicable
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2-butoxyethanol
- EC Number:
- 203-905-0
- EC Name:
- 2-butoxyethanol
- Cas Number:
- 111-76-2
- Molecular formula:
- C6H14O2
- IUPAC Name:
- 2-butoxyethanol
- Details on test material:
- - Name of test material (as cited in study report): 2-butoxyethanol
- Analytical purity: 99%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on mating procedure:
- not applicable
- Duration of treatment / exposure:
- 13 Weeks
- Frequency of treatment:
- daily
- Details on study schedule:
- not applicable
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 750, 1500, 3000, 4500 or 6000 ppm
Basis:
other: These concentrations provided target dose levels of 0, 100, 150, 250, 400 or 650 mg/kg bw per day (US NTP, 1993).
- Remarks:
- Doses / Concentrations:
0, 69, 129, 281, 367, 452
Basis:
other: actual dose received in mg/kg/day (males)
- Remarks:
- Doses / Concentrations:
0, 82, 151, 304, 363, 470
Basis:
other: actual dose received in mg/kg/day (females)
- No. of animals per sex per dose:
- 10 male and 10 female rats
- Control animals:
- yes, concurrent vehicle
Examinations
- Oestrous cyclicity (parental animals):
- Vaginal cytology was assessed over the 7 days prior to sacrifice. With respect to oestrous cycle evaluations, normally cycling Fischer 344 females have 5-6 day oestrous cycles. While there were 10 females per dose group, 3-4 females per group had estrous cycles longer than 12 days or cycles that were unclear, including the control group. These animals were excluded from the analysis, meaning that only 6-7 females per group were evaluated. Furthermore, given the approximate times in the various stages of estrous (see table below from Zarrow et al., 1964), it appears that the control animals spent an excessive amount of time in estrus. Typically, estrus would comprise approximately 30% of the estrous cycle, rather than the 57.9% reported for the control females. Using Zarrow’s table, if one assumes 2 days for estrus and minimal durations for the other estrous stages, estrus would only comprise 44% of the cycle (2 days out of 4.5 days total estrous cycle). This value is well below the 57.9% reported in the control animals in the study. Vaginal smears were collected only once per day. With only 6-7 rats per group and stages of the cycle that are less than one day in duration, some phases could have gone undetected.
Method: Vaginal vaults were lavaged and the fluid and cells stained with toluidine blue. Relative numbers of leucocytes, nucleated epithelial cells and large squamous epithelial cells were determined and used to ascertain estrous cycle stage (eg. diestrous, proestrus, estrus and metestrus.) - Sperm parameters (parental animals):
- Sperm morphology and motility were estimated from epididymal sperm samples taken at necropsy. The left epididymis was isolated and weighed. The tail of the cauda epididymis was then removed and weighed. Test yolk was applied to slides and a small incision made to distal border of epididymis tail. Sperm effluxing was dispersed in buffer on slide and numbers of motile/non-motile spermatazoa counted (5 views per slide.) After this evaluation, epididymis was minced in buffered saline and incubated before sperm density determined (microscopically with a haematometer.) To quantifiy spermatogenesis, testicular spermatid head count was determined by removing tunica albuginea and homogenising left testis in phosphte buffered saline. Homogenisation resistant spermatid nuclei were then counted as for sperm density.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Reproductive function: sperm measures:
- effects observed, treatment-related
Details on results (P0)
Terminal body weight was decreased by 9 and 14% in males given 4500 and 6000 ppm 2-butoxyethanol. In females, body weights were decreased by 14 and 22% at these concentrations.
REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
There were no significant differences from the control group in oestrous cycle length for treated females, although females treated at 4500 and 6000 ppm spent more time in dioestrous than the other groups. This correlates with the smaller uterine size, which was attributed to a secondary consequence of reduced body weight gain.
REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
The only spermatozoal measurement that showed significant change relative to the control group was sperm concentration which was slightly decreased in all groups of treated males; however, this effect was not dose-related.
ORGAN WEIGHTS (PARENTAL ANIMALS)
There was no treatment effect on testis weights but there was a reduction in the size of the uterus in females at 4500 and 6000 ppm. There was aslo a decreae in the epididymal weights in the top two dose groups. However, changes in uterine and epididymal weights were considered by the authors to be secondary to the reduction in body weight gain rather than a direct effect of 2-butoxyethanol.
HISTOPATHOLOGY (PARENTAL ANIMALS)
In the rat, haematotoxicity was evident in males at doses of and above 3000 ppm and in all female groups.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- > 452 mg/kg bw/day (actual dose received)
- Sex:
- male
- Basis for effect level:
- other: sperm parameters
- Dose descriptor:
- NOAEL
- Effect level:
- > 470 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: estrus cyclicity, vaginal cytology.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Data on estrous cycling
Study parameters |
0 ppm |
3000 ppm |
4500 ppm |
6000 ppm |
n |
7 |
6 |
7 |
6 |
Necropsy body weight (g)1 |
186 + 4 |
172 + 2 |
160 + 2 |
145 + 2 |
Estrous cycle length (days) |
6.50 + 0.70 |
6.83 + 0.95 |
7.57 + 0.53 |
5.83 + 0.70 |
Estrous stages (% of cycle) |
||||
Diestrus |
28.9 |
45.6 |
52.8 |
67.5 |
Proestrus |
8.8 |
11.4 |
13.9 |
7.0 |
Estrus |
57.9 |
38.6 |
20.4 |
17.5 |
Metestrus |
4.4 |
4.4 |
13.0 |
7.9 |
1 Based on n = 10.
Vaginal cytology during the estrous cycle of the rat1
Time (days) |
Stage |
Vaginal smear |
0.5-1 |
Proestrus (P) |
Many rounded epithelial cells, few leukocytes |
1-2 |
Estrus (E) |
Cornified epithelial cells, no leukocytes |
0.5-1 |
Metestrus (M) |
Maximum number of leukocytes, often in clumps surrounding epithelial cells. For our purposes this will be classified as part of Diestrus. |
1.5-2 |
Diestrus (D) |
Few epithelial cells; few to many leukocytes. Sometimes divided into Diestrus I and II |
1 Modified from Zarrow et al. (J Endocrinol, 30, 87 -95, 1964).
Applicant's summary and conclusion
- Conclusions:
- No effects on sperm parameters or estrus cycle/vaginal cytology could be identified that were primarily as a result of treatment with 2-butoxyethanol.
- Executive summary:
In a reliable 90 day repeat dose study using oral exposures via drinking water up to 450 -470mg/kg/day in male and female rats, a number of reproductive parameters were examined in the animals that survived to termination. In males, a decrease in epididymal weights was noticed but this was in proportion to overall reduced body weight. Sperm concentrations were also reduced by approximately 5 -10% in all dose groups but there was no dose response relationship evident. There were no effects on estrous length but some evidence that the two highest dose group animals spent more time in the diestrus stage. This correlated with the smaller uterine size, which was attributed to a secondary consequence of reduced body weight gain. In addition, the lack of effect on overall estrous cycle length and absence of histopathologic lesions suggest that the effects on estrous cycle length are unlikely to indicate a specific treatment-related reproductive effect. Thus, the effects on male and female rat reproductive endpoints are not considered to be indications of selective reproductive system toxicity. The effects seen were minor in nature, not seen in males and only occurred in the presence of other significant systemic toxicity (i.e., decreased body weights, marked haematotoxicity). In conclusion, the study does not indicate any primary effects on fertility that can be directly attributed to treatment.
Synopsis
NOAEL (sperm effects)>452mg/kg/day
NOAEL (oestrus cyclicity) >470mg/kg/day
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