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EC number: 940-417-3 | CAS number: -
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Rationale for reliability of 2: scienfically well performed study; well documented report, assessed in official review (i.e.European Comission and OECD SIDS) Rationale for grouping: structural similarity given by the presence of ”butyl-O-CH2CH2 -O-“ at terminal position; systemic exposure to 2-butoxyacetic acid and/or butoxyethoxyacetic acid as common mode of action; comparable toxicity profiles after prolonged exposure
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 000
- Reference Type:
- review article or handbook
- Title:
- Unnamed
- Year:
- 2 008
Materials and methods
- Principles of method if other than guideline:
- Rats were treated with EGBE vapour at concentrations of 0, 31, 62.5 and 125 ppm for 6h/day, 5d/week, 14 weeks. The observation parameters were similar to those required for OECD 413.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2-butoxyethanol
- EC Number:
- 203-905-0
- EC Name:
- 2-butoxyethanol
- Cas Number:
- 111-76-2
- IUPAC Name:
- 2-butoxyethanol
- Reference substance name:
- EGBE
- IUPAC Name:
- EGBE
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Rats were held in the testing laboratory for 11 - 12 days and were 6 weeks old when the study began. They were housed individually, water was available ad libitum and feed was available ad libitum except during the exposure periods.
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- clean air
- Duration of treatment / exposure:
- 14 weeks
- Frequency of treatment:
- 6h/d, 5d/week,
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 31, 62.5, 125, 250, 500 ppm (0, 150, 302, 604, 1208, 2416 mg/m3)
Basis:
nominal conc.
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
Results and discussion
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 62.5 ppm
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Based on the hematotoxic effect at 125 ppm
- Dose descriptor:
- LOAEC
- Effect level:
- 31 ppm
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: hematological effects seen at all doses tested
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Summary of result (cited from EU Risk Assessment):
Six female rats were found moribund and killed during the study: five in the 500 ppm group (four in week 1, one in week 5) and one in the 250 ppm group (in week 8). By the end of the study, body weight gains were significantly reduced in females of the 500 ppm group, but were unaffected in all other groups. Clinical findings were most prevalent in rats of both sexes exposed to 125, 250 or 500 ppm and included abnormal breathing, pallor, red urine stains, nasal and eye discharge, lethargy and either increased salivation or lacrimation. All females of the 500 ppm group, particularly during the first two weeks, developed alternating blue and white bands on their tails that caused them to self-mutilate and loose the distal portion of their tails.
Haematological examination showed that inhalation of EGBE resulted in the development of a persistent and exposure-related macrocytic, normochromic, responsive anaemia, as indicated by decreased haematocrit values, haemoglobin concentrations and erythrocyte counts in the 125 ppm or greater group males and in all groups of exposed females. The effects were dose related. This evidence of a sex difference in the severity of the anaemia was also seen in the 500 ppm group, in which the indicators were slightly more severe in the females than in the males. Evidence of an erythropoietic response was shown by increases in reticulocyte and nucleated erythrocyte counts in males of the 125 ppm or greater groups and females of the 62.5 ppm or greater groups. Other haematological changes were decreases in lymphocyte and monocyte counts in males of the 125 ppm or greater groups and increased platelet counts in females of the 125 or 500 ppm groups. Some organ weight changes were observed. These were: increases of the kidney of males in the 500 ppm group and females in the 125 ppm or greater groups; increases of the liver of males in the 250 or 500 ppm and females in the 125 ppm or greater groups; and decreases of the thymus of females in the 500 ppm group. Thrombosis was observed in the tail vertebrae, femur, incisors, nasal cavity, lung, heart and liver of most females in the 500 ppm group, but not at all in the 250 ppm group. Additionally, in the 500 ppm group females, there was degeneration of the hepatic centrilobular areas and renal tubules (4/5 in each case) and atrophy of the thymus (4/5) and spleen (1/5). Haematopoietic cell proliferation was observed in the spleen of 2/5 group same group. Bone marrow hyperplasia was recorded in males of the 250 and 500 ppm groups and females in all groups from 62.5 ppm. The severity of this response was dose related. In the forestomach of females in the 500 ppm group, but not in lower dose groups, observations made were of inflammation (3/5), necrosis (2/5), ulcers (2/5) and hyperplasia (1/5). Effects also observed in the 250 ppm group females were hepatic necrosis, pigmentation of Kupffer cells and renal tubule cells and bone marrow hyperplasia.
No NOAEC was found for female rats. LOAEL was 31 ppm based on haematological effects seen at all doses tested. A NOAEL of 62.5 ppm was found for male rats, based onhaematotoxic effects seen at 125 ppm.
a) Justification for the applied read-across approach: basis for the grouping of chemicals
The applied read-across approach is based on grouping of chemicals, in which the same mode of action can be presumed.
a1) Group members and the structural similarity
The similarity in their structure is given by the presence of ”butyl-O-CH2CH2-O-“ at terminal position.
Grouping of chemicals for the hazard assessment of the registration substance |
||
Chemicals in read-across approach |
Chemical name/ CAS |
Structure |
Read-across supporting substances |
Ethylene glycol butyl ether (EGBE)* CAS 111-76-2 |
Butyl-O-CH2CH2-OH |
Diethylene glycol butyl ether (DEGBE)* CAS 112-34-5 |
Butyl-O-(CH2CH2-O)2-H |
|
Diethylene glycol dibutyl ether (DEGDBE)** CAS 112-73-2 |
Butyl-O- (CH2CH2-O)2-Butyl |
|
Registration substance/ target chemical |
Polyethylene glycol dibutyl ether (PolyEGDBE)*** CAS 31885-97-9 |
Butyl-O- (CH2CH2-O-)n-Butyl n = 2,3,4 |
* EGBE and DEGBE are extensively investigated substances and reviews on their toxicity profiles are available in public domain (i.e. EU Risk Assessment Report, 2-Butoxyethanol (EGBE), CAS 111 -76 -2, 2008; Opinion on Diethylene Glycol Monobutyl Ether (DEGBE), SCCP/1043/06, 2006). ** Clariant substance; relevant data provided in corresponding endpoint study record. *** registration substance; target chemical in the read-across.
a2) Mode of action
The proposed grouping is justified by the common mode of action, namely systemic exposure to 2-butoxyacetic acid (2-BAA) and/or butoxyethoxyacetic acid (BEAA):
- EGBE: 2-BAA is the major urinary metabolite (summarized in EU risk assessment, 2008)
- DEGBE: BEAA is the major urinary metabolite (Deisinger et al. 1989)
- DEGDBE: in 28-day study (Clariant own data; details provided in corresponding endpoint study record), the urinary 2-BAA determination was incorporated; 750 mg/kg bw external dose level corresponded to 1400 mg/L 2-BAA in urine.
- PolyEGDBE: no experimental data on metabolite is available; BEAA and/or 2-BAA as metabolite can be reasonably assumed due to the observed RBC reduction and liver enlargement in the OECD 422 study (Clariant own data; provided in corresponding endpoint study record).
a3) Comparable toxicity profiles after prolonged exposure
The proposed grouping is justified by the comparable toxicity profiles, which reflects the toxicity action of 2-BAA and/or BEAA. Both metabolites are known to induce hemolysis (Udden 2002; Udden 2005).
- EGBE: hemolytic action demonstrated in acute and repeated dose toxicity studies (summarized in EU risk assessment, 2008; selected studies provided in corresponding study record)
- DEGBE: i.e. in 2 and 13 week oral toxicity studies, RBC reduction was evident. (Johnson et al. 2005; provided in corresponding study record)
- DEGDBE: in 28-day study, RBC reduction and hematuria was evident (Clariant own data; provided in corresponding study record)
- PolyEGDBE: in OECD 422, RBC reduction was evident (Clariant own data; provided in corresponding study record)
a4) Conclusion: Based on a2) and a3), the introduced grouping is justified, which in turn justifies the use of the toxicity data of each group members for the hazard assessment of the registration substance.
Applicant's summary and conclusion
- Conclusions:
- Inhalation of EGBE for rats for 14 weeks resulted in the development of hemolytic anemia down to the dose level of 31 ppm (= 150 mg/m3). The LOAEL of 31 ppm was obtained.
- Executive summary:
The repeated dose toxicity of the registration substance was assessed based on read-across method. EGBE is considered to be one of the appropriate source chemical.
Rats were treated with EGBE vapour at concentrations of 0, 31, 62.5, 125, 250 and 500 ppm for 6h/day, 5d/week, 14 weeks. Haemolysis, as indicated by decreased hematocrit values, haemoglobin concentrations and erythrocyte, was observed at all doses tested for females and at 125 mg/kg bw and higher for males. At concentrations of 125 ppm and higher the organ weight changes together with histopathological changes were observed liver, spleen and thymus.
No NOAEC was found for female rats. LOAEL was 31 ppm (= 150 mg/m3) based on haematological effects seen at all doses tested. A NOAEL of 62.5 ppm was found for male rats.
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