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EC number: 203-905-0 | CAS number: 111-76-2
- 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
Endpoint summary
Administrative data
Description of key information
See tables in discussion section
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Dose descriptor:
- LOAEL
- 69 mg/kg bw/day
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Dose descriptor:
- LOAEC
- 152 mg/m³
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
Additional information
ORAL
A small number of reliable studies on rats and a single study on mice are available. Rats were clearly more sensitive than mice to the toxic effects of the substance. Effects seen by oral route were body weight reduction, haemolysis, hepatic effects and local irritation effects. Irritation to the forestomach was seen after gavage dosing have also be reported and, to a far lesser extent, after subcutaneous and intraperitoneal injection (not reported in this section - see mechanistic study by Poet in chapter 7.9.3). This difference is most likely due to the higher local concentration after gavage dosing. Overall, a LOAEL of 69 and 82 mg/kg bw/d (in males and females respectively) can be obtained from the data based on a three-month study in rats and based on slight changes observed in hepatocytes at this dose.
NOAEL (mg/kg bw/d) |
Effects |
Reference |
|
Rats |
|||
6 weeks gavage |
0, 222, 443 and 885 mg/kg LOAEL = 222 mg/kg |
Haematological effects at all doses and irritant effects on the stomach |
Eastman Kodak, 1982 |
13 weeks in drinking water |
69, 129, 281, 367 and 452 mg/kg/day for males and 82, 151, 304, 363 and 470 mg/kg/day for females LOAEL of 69 and 82 mg/kg bw/day for males and females respectively. |
Slight decrease in body weight gain and haematological effects.NOAEL based on liver effects(minimal to mild cytoplasmic changes in hepatocytes). |
NTP, 1993 |
Mice |
|||
14 weeks in drinking water |
118, 223, 553, 676 and 694 mg/kg/day for males and 185, 370, 676, 861 and 1306 mg/kg/day for females. NOAEL = >694 and 370 mg/kg bw/d for males and females respectively LOAEL = 676 mg/kg bw/d for females |
Slight decrease in body weight gain |
NTP, 1993 |
INHALATION
Numerous studies, including relatively recent ones have been conducted on rats, and mice. Some older studies using dogs, guinea-pigs and non human primates have also been performed. In rats and mice, the common toxicity signs are similar to those observed following acute administration. In general, rats are more sensitive than mice and females are more sensitive than males. The main and critical effect was haemolysis, which was consistently observed and sometimes associated with secondary hepatic effects (Kupffer cells pigmentation and absolute and relative liver weight increases). Other effects observed at similar or higher doses were deemed to be either secondary to the haemolytic effects or not as a result of treatment. In these studies, a NOAEC of 25 ppm in rats in a 90 day study and and a LOAEC of 31 ppm (152mg/m3) rats in a chronic study were established based on haemolysis, as the only significant primary effect. The LOAEC of 31 ppm ( from a six month satellite group in the NTP, 2000 104-week study) is taken into account for the risk characterisation. However, it needs to be borne in mind that the no effect level for haemolysis is not time dependent and likely to be no lower in a chronic study compared to a sub-chronic study and that the LOAEC is likely to be close to the NOAEC, an observation supported by the 25ppm NOAEC.
Summary of the studies on animals performed by inhalation route
NOAEC (ppm) |
Effects |
Reference |
|
Rats |
|||
15 exposures to 0, 20, 50 and 100 ppm. 4 exposures to 250 ppm. |
20 ppm (haematological effects). |
Haematological effects |
Gage, 1970 |
13 weeks. Doses: 0, 5, 25, 75 ppm |
25 ppm (haematological effects only) |
Haematological effects only |
Bushy Run Research Center, 1981 |
13 weeks. Doses: 0, 31, 62.5, 125, 250, 500 ppm |
LOAEC of 31 ppm |
Haematological effects. Study performed to describe the vascular and bone lesion observed in moribund female. |
Nyska, 1999. Long, 2000 US NTP, 2000 |
104 weeks. Doses: 0, 31, 62.5, 125ppm |
None identified for haematological effects; 31.2 ppm may be considered as an LOAEC. |
Haematological effects. Effects on liver (Kupffer cell pigmentation). |
NTP, 2000 |
15 days, 537ppm |
None identified |
BASF (1970) |
|
90 days, 50ppm |
None identified. |
Haematological effects |
Shell (1970) |
Mice |
|||
Doses: 0, 100, 200, 400 ppm. Duration: 30, 60 or 90 exposures |
100 ppm |
Haematological effects at all doses |
Mellon Institute of Industrial Research, 1955 |
14 weeks. Doses: 0, 31, 62.5, 125, 250, 500 ppm |
None identified for haematological effects; LOAECof 31 ppm |
Haematological effects. Effect on body weight gain. Irritant effects on the forestomach. |
NTP, 2000 |
104 weeks. Doses 0, 62.5, 125, 250ppm |
none identified LOAEC of 62.5 ppm |
Haematological effects. Effects on liver (Kupffer cell pigmentation). |
NTP, 2000 |
15 days, 537ppm |
None identified |
BASF (1970) |
|
Guinea pigs |
|||
30 days Dose: 0, 375 and 500 ppm |
none identified |
Mortality, effects on body weight and on kidneys. No effects on blood parameters. |
Mellon Institute of Industrial Research, 1955 |
15 days, 537ppm |
NOAEC=537ppm |
BASF (1970) |
|
Rabbits |
|||
15 days, 537ppm |
None identified |
BASF (1970) |
|
Dogs |
|||
Duration between 2 and 90 days. Dose: 0, 100, 200, 385 and 617 |
None identified |
CNS depression, haemolytic anaemia. Effects on lungs, kidneys and liver. |
Mellon Institute of Industrial Research, 1955 |
Cats |
|||
15 days, 537ppm |
None identified |
BASF (1970) |
|
Monkeys |
|||
90 days, Dose: 0, 100, 200 ppm. |
- |
Haematological effects (haemolysis) |
Mellon Institute of industrial research |
In addition to the above, a screening study established that the NOEC for cats, rabbits, rats and mice is well below 537ppm whereas this is a NOEC for guinea pigs. This confirms the observation that guinea pigs are particularly resistance to the toxicological (namely the haematotoxic) effects of this substance.
DERMAL
One sub-chronic study by the dermal route is available. A 13 week subchronic study up to the maximum dose achieved without skin irritancy problems occuring. No adverse effects were observed up to the maximum dose tested of 150 mg/kg bw/d.
Study (rabbits) |
NOAEL (mg/kg bw/d) |
Effects |
Reference |
Rabbits |
|||
13 weeks. Doses: 10 – 50 – 150 mg/kg bw/d |
NOAEL > 150 |
No effects |
Wil Research Lab., 1983 |
As this is in effect a limit dose study it is not suitable for deriving a DNEL and therefore a quantitative DNEL cannot be derived.
OVERALL SUMMARY
In rats and mice, haemolysis was consistently observed (whichever the route of administration) and was sometimes associated with hepatic effects (Kupffer cell pigmentation and absolute and relative liver weight increases), effects on body weight gain, hyaline degeneration of the olfactive epithelium (by inhalation), effects on the forestomach and effects on the WBC sub-populations (T lymphocyte). In these studies and for the inhalation route, no NOAEC was identified for mice, whereas a NOAEC value of 25 ppm (121 mg/m3) in rats was identified. In a separate study a LOAEC value of 31 ppm (150 mg/m3) can be established inrats, based on haemolysis and Kupffer cell pigmentation. Due to the closeness of the apparent LOAEL and NOAEL, it is considered prudent to take the more conservative LOAEL of 31 ppm forward for risk characterisation. However, the likelihood that this figure is close to the NOAEL will be taken into account in deriving appropriate assessment factors.
As humans are far less sensitive than other species (except Guinea Pig) to the haemolytical properties of 2-butoxyethanol, toxic effects other than haemolytical effects and related secondary effects have been sought which could be induced by 2-butoxyethanol. From all the studies, no specific relevant toxic effects, other that haemotoxicity, can be identified that are clearly related to treatment with 2 -butoxyethanol. For risk characterisation purposes therefore, haemotoxicity will be the end point chosen keeping in mind the interspecies differences (human/rodents) to calculate margin of safety. No other lesion has been identified which can be specifically attributed to treatment with 2-butoxyethanol .
Repeated dose toxicity: via oral route - systemic effects
(target organ) digestive: liver
Repeated dose toxicity: inhalation - systemic effects (target organ)
cardiovascular / hematological: other
Justification for classification or non-classification
The main effects seen following repeated exposure to 2 -butoxyethanol are primary haemolysis and secondary effects as a direct consequence of these primary effects. The extensive data reported in chapter 7.9.3 conclusively establishes that these effects seen in the commonly used test species of rat, rabbit and mouse are not seen in humans. Humans are remarkably resistant to haemolysis. No other significant adverse effects were seen following repeated exposure. In terms of classifying 2 -butoxyethanol for repeat dose effects relevant to humans, no classification is warranted.
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