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EC number: 200-751-6 | CAS number: 71-36-3
- 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 005
- Reference Type:
- review article or handbook
- Title:
- An overview of butanol-induced developmental neurotoxicity and the potential mechanisms related to these observed effects
- Author:
- Bale AS and Lee JS
- Year:
- 2 016
- Bibliographic source:
- Neurotoxicology and Teratology 53 (2016) 33–40
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: Ministry of Health and Welfare, Japan; Guidelines for Toxicity Studies of Drugs
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- Pregnant rats were given drinking water containing 1-butanol at 0.2%, 1.0% or 5.0% (316, 1454 or 5654 mg/kg/day) on days 0–20 of pregnancy. The rats were sacrificed on day 20 of pregnancy and both the dams and fetuses were examined.
- GLP compliance:
- yes
Test material
- Reference substance name:
- Butan-1-ol
- EC Number:
- 200-751-6
- EC Name:
- Butan-1-ol
- Cas Number:
- 71-36-3
- Molecular formula:
- C4H10O
- IUPAC Name:
- butan-1-ol
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Tsukuba Breeding Center
- Age at study initiation: males: 10 weeks; females: 9 weeks
- Weight at study initiation: females: 217-273 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25 °C
- Humidity (%): 40-70 %
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
1-butanol was mixed with water to the according target concentrations. The stability of formulations in a dark and cool place under airtight conditions has been confirmed for up to 3 days. During use, the formulations were maintained under such conditions for no more than 3 days and were 95.7–103.5% of the target concentration. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentrations were determined analytically and were 95.7–103.5% of the target concentration.
- Details on mating procedure:
- - Impregnation procedure: [cohoused]
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: over night
- Verification of same strain and source of both sexes: [yes]
- Proof of pregnancy: [sperm in vaginal smear] referred to as [day 0] of pregnancy - Duration of treatment / exposure:
- day 0 through day 20 of pregnancy
- Frequency of treatment:
- continuous through drinking water
- Duration of test:
- until day 20 of pregnancy
- No. of animals per sex per dose:
- 20 females per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The dosage levels were determined based on the results of our range-finding study in which administration of 1-butanol in the drinking water on days 0–20 of pregnancy caused decreases in maternal body weight gain and food and water consumption and tended to reduce in fetal weight at 4% and 7% in rats.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: not specified
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: not not specified
BODY WEIGHT: Yes
- Time schedule for examinations: once daily
FOOD CONSUMPTION: Yes
- Time schedule for examinations: every 3 or 4 days
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 10
- Organs examined: not specified - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- 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 per litter]
- Soft tissue examinations: Yes: [half per litter]
- Skeletal examinations: Yes: [half per litter]
- Head examinations: Yes: [half per litter] - Statistics:
- The statistical analysis of fetuses was carried out using the litter as the experimental unit. The initial body weight, body weight gain and food and water consumption of pregnant rats, numbers of corpora lutea, implantations and live fetuses per litter, fetal weight and crown-rump length and placental weight were analyzed with Bartlett's test for homogeneity of variance at the 5% level of significance.
If it was homogeneous, the data were analyzed using Dunnett's multiple comparison test to compare the mean of the control group with that of each dosage group, and if it was not homogeneous, the mean rank of the 1-butanol-treated groups was compared with that of the control group with the Dunnett type test. The Dunnett type test was used for the incidences of pre- and postimplantation embryonic loss and fetal anomalies and sex ratio of fetuses to compare the mean rank of groups treated with 1-butanol and that of the control group. The incidence of dams with anomalous fetuses was analyzed by Chi-square test or Fisher's exact test. The significance of differences from the control group was estimated at probability levels of 1% and 5%. - Indices:
- no data
- Historical control data:
- International Genetic Standard (Crj: CD (SD) IGS) rats were used throughout this study. This strain was chosen because it is most commonly used in reproductive and developmental toxicity studies and historical control data are available.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Details on maternal toxic effects:
No death was found in female rats of any group. All females in all groups became pregnant. The body weight gains on days 0–7 of pregnancy were significantly reduced at 5.0%. The body weight gain during the whole period of pregnancy was also significantly decreased at 5.0%. No significant decrease in the body weight gain was noted at 0.2 or 1.0, except for a transient decrease on days 0–2 of pregnancy at 1.0%. The food consumption on days 0–7, days 7–14, days 14–20 and days 0–20 of pregnancy was significantly lower in the 1.0% and 5.0% groups than the control group. The water consumption on days 0–7 at 1.0 and 5.0% and on days 7–14, days 14–20 and days 0–20 at 5.0% was significantly decreased. The mean daily intakes of 1-butanol were 316 mg/kg for the 0.2% group, 1454 mg/kg for the 1.0% group and 5654 mg/kg for the 5.0% group.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- maternal toxicity
- Effect level:
- 1 454 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
No litters totally resorbed were found in any group. No effects of the administration of 1-butanol were observed on the numbers of corpora lutea, implantations, pre- or postimplantation loss, resorptions or dead or live fetuses or sex ratio of live fetuses. The body weights of male and female fetuses were significantly lower in the 5.0% group than in the control group. There was no significant difference in the crown-rump length of male and female fetuses or placental weight between the control and groups treated with 1-butanol.
One fetus with spina bifida in the control group and one fetus with thread-like tail and anal atresia in the 0.2% group were observed. Skeletal examination revealed one fetus with supernumerary thoracic vertebral bodies and malpositioned thoracic vertebrae at 1.0%. Although the total number of fetuses with skeletal variations was significantly increased at 5.0%, the number of fetuses with individual skeletal variations was not significantly increased, except for fetuses with short supernumerary ribs at 5.0%. A significantly lower number of forepaw proximal phalanges was observed at 5.0%. Membranous ventricular septum defect occurred in one fetus of the control and 0.2% groups and 3 fetuses in 3 dams of the 5.0% group. One fetus with a double aorta in the control group and one fetus with a left umbilical artery in the control and 2.0% groups were observed. Thymic remnants in the neck were found in 4–11 fetuses of the control and groups treated with 1-butanol.
However, there was no significant difference in the incidence of fetuses with internal abnormalities between the control and groups treated with 1-butanol.
Effect levels (fetuses)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- teratogenicity
- Effect level:
- 5 654 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- developmental toxicity
- Effect level:
- 1 454 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
A significant decrease in maternal body weight gain accompanied by reduced food and water consumption was found at 5.0%. No significant increase in the incidence of pre- and postimplantation embryonic loss was observed in any groups treated with 1-butanol. Fetal weight was significantly lowered at 5.0%. Although a significant increase in the incidence of fetuses with skeletal variations and decreased degree of ossification was found at 5.0%, no increase in the incidence of fetuses with external, skeletal and internal abnormalities was detected in any groups treated with 1-butanol. The data demonstrate that 1-butanol is developmental toxic only at maternal toxic doses. No evidence for teratogenicity of 1-butanol was noted in rats. Based on the significant decreases in maternal body weight gain and fetal weight, it is concluded that the no observed adverse effect levels (NOAELs) of 1-butanol for both dams and fetuses are 1.0% (1454 mg/kg/day) in rats.
Table 1
Maternal findings in rats given 1-butanol on days 0–20 of pregnancy
Dose (%) |
0 (Control) |
0.2 |
1.0 |
5.0 |
No. of rats |
20 |
20 |
20 |
20 |
No. of pregnant rats |
20 |
20 |
20 |
20 |
No. of dead rats |
0 |
0 |
0 |
0 |
Initial body weight |
245 ± 14 |
247 ± 13 |
245 ± 11 |
244±12 |
Body weight gain during pregnancy (g)a |
|
|
|
|
Days 0–7 |
44 ± 7 |
45 ± 7 |
40 ± 6 |
20 ± 28** |
Days 7–14 |
40±6 |
41±5 |
41±7 |
42±10 |
Days 14–20 |
78±14 |
82 ± 8 |
84 ± 7 |
75 ± 11 |
Days 0–20 |
162 ± 19 |
168 ± 16 |
165 ± 15 |
146 ± 16** |
Food consumption during pregnancy (g)a |
|
|
|
|
Days 0–7 |
179 ± 12 |
180 ± 16 |
164 ± 12* |
138 ± 21** |
Days 7–14 |
193 ± 14 |
194 ± 17 |
177 ± 14** |
160 ± 11** |
Days 14–20 |
176 ± 14 |
175 ± 15 |
161 ± 12** |
143 ± 11** |
Days 0–20 |
548 ± 38 |
548 ± 46 |
503 ± 34** |
441 ± 34** |
Water consumption during pregnancy (ml)a |
|
|
|
|
Days 0–7 |
284 ± 28 |
305 ± 37 |
258 ± 29* |
175 ± 34** |
Days 7–14 |
318 ± 35 |
337 ± 48 |
299 ± 40 |
239 ± 80** |
Days 14–20 |
328 ± 47 |
342 ± 47 |
334 ± 46 |
256 ± 85** |
Days 0–20 |
930 ± 105 |
983 ± 126 |
890 ± 106 |
669 ± 182** |
Mean daily intakes of 1-butanol (mg/kg)a |
0 |
316 ± 30 |
1454 ± 186 |
5654 ± 1402 |
** Significantly different from the control, *P< 0.05 and **P< 0.01.aValues are given as the mean ± SD.
Table 2
Reproductive findings in rats given 1-butanol on days 0–20 of pregnancy
Dose (%) |
0 (Control) |
0.2 |
1.0 |
5.0 |
No. of litters |
20 |
20 |
20 |
20 |
No. of litters totally resorbed |
0 |
0 |
0 |
0 |
No. of corpora lutea per littera |
16.4 ± 3.6 |
16.7 ± 3.0d |
16.1 ± 2.1 |
16.3 ± 2.6 |
No. of implantations per littera |
14.3 ± 2.8 |
15.1 ± 1.7 |
15.2 ± 1.2 |
14.7 ± 2.5 |
% Preimplantation loss per litterb |
9.0 |
9.0d |
4.4 |
9.2 |
% Postimplantation loss per litterc |
6.0 |
5.4 |
3.7 |
8.0 |
No. of live fetuses per littera |
13.4 ± 2.6 |
14.3 ± 1.4 |
14.7 ± 1.5 |
13.5 ± 2.5 |
Sex ratio of live fetuses (male/female) |
128/139 |
145/140 |
149/144 |
131/139 |
Body weight of live fetuses (g)a |
|
|
|
|
Male |
4.18±0.27 |
4.00±0.24 |
4.04±0.25 |
3.83±0.18** |
Female |
3.97 ± 0.25 |
3.86 ± 0.20 |
3.83 ± 0.16 |
3.59 ± 0.17** |
Fetal crown-rump length (mm)a |
|
|
|
|
Male |
40.5 ± 1.2 |
40.3 ± 1.4 |
40.2 ± 1.2 |
39.7 ± 1.3 |
Female |
39.4 ± 1.2 |
39.4 ± 1.2 |
39.3 ± 1.1 |
38.5 ± 1.4 |
Placental weight (g) |
|
|
|
|
Male |
0.50 ± 0.05 |
0.49 ± 0.05 |
0.48 ± 0.06 |
0.50 ± 0.06 |
Female |
0.49 ± 0.05 |
0.48 ± 0.05 |
0.47 ± 0.05 |
0.49 ± 0.06 |
** Significantly different from the control, *P< 0.01
aValues are given as the mean ± SD.
b(No. of preimplantation embryonic loss/no. of corpora lutea)x100.
c(No. of resorptions and dead fetuses/no. implantations)x100.
dValue was obtained from 19 pregnant rats.
Table 3
Morphological examinations in fetuses of rats given 1-butanol on days 0–20 of pregnancy
Dose (%) |
0 (Control) |
0.2 |
1.0 |
5.0 |
External examination |
|
|
|
|
Total no. of fetuses (litters) examined |
267(20) |
285(20) |
293(20) |
270(20) |
Total no. of fetuses (litters) with abnormalities |
1 (1) |
1 (1) |
0 |
0 |
Spina bifida |
1 (1) |
0 |
0 |
0 |
Thread-like tail and anal atresia |
0 |
1 (1) |
0 |
0 |
Skeletal examination |
|
|
|
|
Total no. of fetuses (litters) examined |
139(20) |
147(20) |
152(20) |
140(20) |
Total no. of fetuses (litters) with abnormalities |
0 |
0 |
1 (1) |
0 |
Supernumerary of thoracic vertebral bodies and malpositioned thoracic vertebrae |
0 |
0 |
1 (1) |
0 |
Total no. of fetuses (litters) with variations |
28(11) |
23(12) |
52(17) |
69 (20)** |
Bipartite ossification of thoracic centra |
1 (1) |
1 (1) |
1 (1) |
7(5) |
Dumbbell ossification of thoracic centra |
0 |
1 (1) |
2(2) |
3 (3) |
Bipartite ossification of lumbar centra |
0 |
0 |
0 |
2(2) |
Supernumerary lumbar vertebrae |
4(1) |
1 (1) |
5 (3) |
5 (2) |
Lumbarization |
0 |
0 |
1 (1) |
1 (1) |
Bipartite ossification of sternebrae |
1 (1) |
1 (1) |
1 (1) |
1 (1) |
Misaligned sternebrae |
0 |
0 |
0 |
1 (1) |
Cervical ribs |
2(2) |
3(3) |
3 (3) |
7(5) |
Full supernumerary ribs |
5(2) |
1 (1) |
10 (5) |
9(5) |
Short supernumerary ribs |
20(10) |
18 (9) |
43(16) |
55 (19)** |
Wavy ribs |
0 |
0 |
0 |
1 (1) |
Degree of ossificationa |
|
|
|
|
No. of sacral and caudal vertebrae |
8.4 ± 0.5 |
8.4 ± 0.4 |
8.3 ± 0.5 |
8.1 ± 0.3 |
No. of sternebrae |
5.9 ± 0.2 |
5.8 ± 0.2 |
5.8 ± 0.2 |
5.8 ± 0.2 |
No. of forepaw proximal phalanges |
1.6 ± 1.3 |
1.6 ± 0.9 |
1.2 ± 1.1 |
0.3 ± 0.4** |
Internal examination |
|
|
|
|
Total no. of fetuses (litters) examined |
128(20) |
138(20) |
141 (20) |
130(20) |
Total no. of fetuses (litters) with abnormalities |
7(6) |
9(6) |
11 (8) |
14(9) |
Membranous ventricular septum defect |
1 (1) |
1 (1) |
0 |
3 (3) |
Double aorta |
1(1) |
0 |
0 |
0 |
Left umbilical artery |
1 (1) |
0 |
1 (1) |
0 |
Thymic remnant in neck |
4(4) |
8 (5) |
10 (8) |
11 (8) |
aValues are given as the mean ± SD.
** Significantly different from the control, *P< 0.01
Applicant's summary and conclusion
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