Registration Dossier
Registration Dossier
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EC number: 940-417-3 | CAS number: -
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
The registration substance is expected to be readily bioavailable for oral/dermal/inhalation routes and to undergo extensive metabolism. No bioaccumulating property can be predicted based on the findings in the subacute toxicity study (OECD 422) and based on the kinetic/metabolism data on the read-across supporting substances.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
The toxicokinetic profile of the registration substance is derived based on the available toxicity data and on the kinetic/metabolism data on the read-across supporting substances. The discussion will be given in the following order.
a) Justification for the applied read-across approach: basis for the grouping of chemicals
a1) Group members and the structural similarity
a2) Mode of action
a3) Comparable toxicity profiles after prolonged exposure
a4) Conclusion
b) Toxicokinetic profile based on molecular size, physico-chemical parameters and the findings in the OECD 422 study
c) Toxicokinetic profile based on grouping of chemicals
d) Overall assessment
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.
b) Toxicokinetic profile based on molecular size, physico-chemical parameters and the findings in the OECD 422 study
The registration substance is expected to be readily bioavailable for oral/dermal/respiration routes based on its molecular size (MW of main component: 263 g/mol), water solubility (23 g/L) and octanol-water partition coefficient (LogPow 2.21). No bioaccumulation is expected.
The repeated dose toxicity of the registration substance was investigated according to the OECD Guideline 422 (study provided in corresponding endpoint study record). The primary findings comprised hemolysis and indications of metabolic adaptation. These effects were reversible within 14 days of recovery. Based on these findings, it can be concluded that the registration substance is bioavailable, undergoes extensive metabolism and is not bioaccumulating.
c) Toxicokinetic profile based on grouping of chemicals
The 28 -day study with DEGDBE comprised collection of urine samples after 8 and 28 days exposure and after recovery of 1 and 14 days. These samples were analyzed for the presumed toxic metabolite 2-butoxyacetic acid (2-BAA). Comparable values were obtained in the samples of 8 and 28-day treatment and very low levels in the samples of recovery animals. These values are demonstrating that the steady state of the systemic exposure was already established within 8 days. Also the obtained very low levels in the recovery animals, especially already after one day of recovery, are indicative of an efficient elimination profile. DEGDBE is a non-bioaccumulating substance.
Deisinger and Guest (1989) investigated the in-vitro hydrolysis in rat blood and the in vivo metabolism in rats of DEGBE-Acetate. It was found that DEGBE-acetate undergoes hydrolysis and that butoxyethoxyacetic acid (BEAA) is the major metabolite.
The hemolytic effect of 2-BAA and BEAA in rat and human blood was demonstrated by Udden (2002 and 2005), whereas 2-BAA was more potent and the rat blood was more susceptible.
2-BAA is the major urinary metabolite and the ultimate toxicant of EGBE (summarized in EU risk assessment, 2008)
d) Overall assessment
The registration substance is readily bioavailable via oral/dermal/respiratory routes and undergoes extensive metabolism. The biotransformation pathway includes the formation of 2 -butoxyacetic acid (2 -BAA) and probably also butoxyethoxyacetic acid (BEAA), thereby causing hemolytic effect. No bioaccumulating property can be predicted.
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