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EC number: 500-012-0 | CAS number: 9004-77-7
- Life Cycle description
- Uses advised against
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- Appearance / physical state / colour
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- Endpoint summary
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- 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
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- Additional toxicological data

Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1998
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: A published study that is reported in sufficient detail to judge it as sufficiently reliable to add to the overall understanding of the toxicokinetic assessment of this substance.
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Toxicokinetics of inhaled 2-butoxyethanol and its major metabolite 2-butoxyacetic acid, in F344 rats and B6C3F1 mice.
- Author:
- Dill JA, Lee KM, Bates DJ, Anderson DJ, Johnson RE, Chou BJ, Burka LT, Roycroft JH.
- Year:
- 1 998
- Bibliographic source:
- Tox Appl Pharmac, 153, 227-42
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- As part of a chronic study, the rate of elimination of butoxyethanol exposure was followed over the lifetime of exposure of the animals to establish the effect of animal age on toxicokinetics of elimination.
- GLP compliance:
- not specified
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:
- - Analytical purity: 99%
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- no data
Administration / exposure
- Route of administration:
- inhalation: vapour
- Details on exposure:
- no data
- Duration and frequency of treatment / exposure:
- 6h/day, 5 days/week, 104 weeks
Doses / concentrations
- Remarks:
- Doses / Concentrations:
31.2, 62.5, 125ppm
- No. of animals per sex per dose / concentration:
- between 5-12 per time point/sex/dose
- Control animals:
- no
- Positive control reference chemical:
- none
- Details on study design:
- no further data
- Details on dosing and sampling:
- no further data
- Statistics:
- no data
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on excretion:
- The 2-butoxyethanol blood concentrations showed a rapid drop after the cessation of exposure. The elimination t1/2 for 2-butoxyethanol after 1 day of exposure was < 10 min, this t1/2 does not depend on the dose level. Increases in the initial blood concentration of 2-butoxyethanol and Area Under the Curve (AUC) were proportional to exposure concentration, supporting that elimination of 2-butoxyethanol from the blood follows linear kinetics. The rate of 2-butoxyethanol elimination from blood slowed with increasing days of exposure, but not markedly. Male rats generally exhibited larger AUC than females, indicating a lower blood clearance of 2-butoxyethanol. The rate constant was not significantly different between sexes, implying that the volume of distribution, rather than the rate of elimination may be responsible for the sex-related difference in 2-butoxyethanol clearance. Unlike 2-butoxyethanol, butoxyacetic acid was not rapidly cleared from the systemic circulation. The butoxyacetic acid concentrations in the blood did not start to decline until 20 to 80 min post exposure. It seems that butoxyacetic acid was eliminated from blood following saturable, nonlinear kinetics. The rate constant was not constant, decreasing as 2-butoxyethanol exposure concentrations increased. As the rate of butoxyacetic acid production reflects the 2-butoxyethanol elimination, it seems that the nonlinear characteristics of butoxyacetic acid kinetics likely result from butoxyacetic acid distribution or elimination processes. When the number of exposure days increased, the rate of butoxyacetic acid elimination tended to decrease. Females eliminated butoxyacetic acid more slowly than males (smaller k, longer t1/2 and larger AUC). The maximum blood concentration was also higher in females at each exposure concentration. In mice, elimination of butoxyacetic acid was faster than rats when compared at common exposure concentrations. Female rats excreted less butoxyacetic acid than males regardless of exposure concentration. Excretion of butoxyacetic acid tended to increase with time.
Toxicokinetic parameters
- Toxicokinetic parameters:
- half-life 1st: 10-42 mins
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- 2-butoxyacetic acid
Any other information on results incl. tables
2-butoxyethanol elimination rate over time at 62.5ppm exposure
C0 (mg/g) |
Rate constant k |
T1/2 (min) |
AUC (mg/min/g) |
|||||
M |
F |
M |
F |
M |
F |
M |
F |
|
1d |
1.86 |
1.59 |
0.0793 |
0.0809 |
8.74 |
8.56 |
23.5 |
19.6 |
2w |
3.06 |
2.24 |
0.0828 |
0.0839 |
8.37 |
8.26 |
36.9 |
26.8 |
3m |
0.54 |
0.47 |
0.0166 |
0.0248 |
41.66 |
27.9 |
32.3 |
18.9 |
6m |
1.31 |
0.69 |
0.0308 |
0.0230 |
22.51 |
30.20 |
42.5 |
29.9 |
12m |
1.08 |
0.97 |
0.0354 |
0.0439 |
19.6 |
15.79 |
30.5 |
22.0 |
2-butoxyethanol elimination rate over time at 125ppm exposure
C0 (mg/g) |
Rate constant k |
T1/2 (min) |
AUC (mg/min/g) |
|||||
M |
F |
M |
F |
M |
F |
M |
F |
|
1d |
4.27 |
3.11 |
0.0735 |
0.0736 |
9.43 |
9.42 |
58.1 |
42.3 |
2w |
5.36 |
4.10 |
0.082 |
0.0852 |
8.45 |
8.13 |
65.3 |
48.1 |
3m |
3.17 |
2.75 |
0.0379 |
0.0411 |
18.30 |
16.87 |
83.6 |
67 |
6m |
3.58 |
3.58 |
0.0514 |
0.0589 |
13.47 |
11.76 |
69.6 |
60.7 |
12m |
2.23 |
1.33 |
0.0347 |
0.0342 |
19.96 |
20.28 |
64.3 |
38.8 |
C0 is the amount of 2-butoxyethanol in blood immediately post exposure, k is the elimination rate constant (min-1) and AUC is the blood concentration versus time curve in ug/min/g).
Butoxyacetic acid urinary excretion rate at 62.5ppm. Toxicokinetic parameters
k |
T1/2 (min) |
AUC (mg/min/g) |
||||
M |
F |
M |
F |
M |
F |
|
1d |
0.0174 |
0.0109 |
39.9 |
63.7 |
5541 |
8228 |
2w |
0.0168 |
0.0088 |
41.2 |
78.4 |
4849 |
10605 |
3m |
0.0168 |
0.0094 |
41.3 |
73.7 |
- |
- |
6m |
0.0099 |
0.0090 |
70.3 |
76.8 |
- |
- |
12m |
0.0139 |
0.0087 |
49.8 |
79.6 |
7279 |
8445 |
18m |
0.0067 |
0.0122 |
103.3 |
56.7 |
9351 |
8976 |
Butoxyacetic acid urinary excretion rate at 125ppm. Toxicokinetic parameters
k |
T1/2 (min) |
AUC (mg/min/g) |
|||||
M |
F |
M |
F |
M |
F |
||
1d |
0.011 |
0.0031 |
63.2 |
224.1 |
19010 |
33403 |
|
2w |
0.0116 |
0.0053 |
59.5 |
130.2 |
13597 |
37943 |
|
3m |
0.0059 |
0.0039 |
117.9 |
178.8 |
13554 |
29094 |
|
6m |
0.0035 |
0.0018 |
195.9 |
395.8 |
14142 |
26485 |
|
12m |
0.0037 |
0.0024 |
187 |
283.4 |
16649 |
25897 |
|
18m |
0.0023 |
0.0058 |
297.5 |
119.3 |
30768 |
25745 |
|
Note that only the data from the concentrations that were also tested in mice in the same study are included for comparison purposes.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
2-butoxethanol is readily eliminated from the blood stream independent of concentration, i.e. with linear kinetics. The elimination rate of the butoxyacetic metabolite from blood decreased with increased exposure concentration (non linear kinetics.). Older animals seemed to eliminate the substance more slowly than young animals. The half life for elimination is less than 10 minutes in younger animals and follows linear kinetics. However, the metabolite butoxyacetic acid has a much longer half life which increases as exposure increases, suggesting more easily saturated metabolism pathways. - Executive summary:
A toxicokinetic study in male and rats was carried out during a chronic exposure study to assess the impact of age on toxicokinetics. 2-butoxethanol is readily eliminated from the blood stream in a manner independent of concentration, i.e. with linear kinetics. The elimination rate of the butoxyacetic metabolite from blood decreased with increased exposure concentration (non linear kinetics.). Older animals seemed to eliminate the substance more slowly than young animals and females were slower than males. The half life for elimination varied between 8 and 42 minutes and follows linear kinetics. However, the metabolite butoxyacetic acid has a much longer half life which increases as exposure increases, suggesting more easily saturated metabolism pathways. The half life at 62.5ppm exposure varied between 40 and 103 mins and at 125ppm between 60 and 300mins.
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