Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
September 30 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Expert Judgement
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Reference
Reference Type:
other: expert judgement
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Risk Assessment
GLP compliance:
no
Test type:
other: expert judgement

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-ethylhexyl) maleate
EC Number:
205-524-5
EC Name:
Bis(2-ethylhexyl) maleate
Cas Number:
142-16-5
Molecular formula:
C20H36O4
IUPAC Name:
1,4-bis(2-ethylhexyl) (2Z)-but-2-enedioate
Constituent 2
Chemical structure
Reference substance name:
Dioctyl maleate
EC Number:
220-835-6
EC Name:
Dioctyl maleate
Cas Number:
2915-53-9
Molecular formula:
C20H36O4
IUPAC Name:
dioctyl but-2-enedioate
Details on test material:
not applicable

Test animals

Species:
other: not applicable
Details on test animals or test system and environmental conditions:
not applicable

Administration / exposure

Route of administration:
other: expert judgement
Type of inhalation exposure:
other: expert judgement
Details on inhalation exposure:
expert judgement
Concentrations:
not applicable
No. of animals per sex per dose:
not applicable
Details on study design:
not applicable

Results and discussion

Effect levels
Dose descriptor:
discriminating conc.
Effect level:
2 500 mg/m³ air
Mortality:
not applicable
Clinical signs:
other: not applicable
Body weight:
not applicable
Gross pathology:
not applicable

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Based on physico-chemical properties, chemical characteristics, available toxicological profile and structural commonalities between bis(2-ethylhexyl) maleate and dibutyl maleate, and the lack of significant effects seen with this substance in the workplace, data for acute inhalation with dibutyl maleate is enough to fulfill this endpoint for bis(2-ethylhexyl) maleate and to avoid unnecessary testing on vertebrate animals (recital of 47 of REACH). The acute inhalation LC50 value of >5000 mg/m³ for dibutyl maleate can be used as surrogate for the purpose of this risk assessment.
Executive summary:

Diesters are generally produced from reaction of dicarboxylic acids and monoalcohols. Dibutyl maleate and bis(2-ethylhexyl) maleate are diester derivatives of the common diacid known as maleic acid (C4). The alcohol portion of these diesters falls in the C4-C8 carbon number range. Dibutyl maleate is derived from a linear alcohol (C4 = butanol) while bis(2-ethylhexyl) maleate is from a branched alcohol (not C8 = octonol but C6 = hexanol branched at C2 with C2 ethanol). According to the chemical structure bis(2-ethylhexyl) maleate is much more polar which would explain the lower water solubility and the different log Pow.

Data for inhalation exposure with bis(2-ethylhexyl) maleate in animals are not available. The relatively high boiling point (156°C @ 9 hPa) and very low vapor pressure (0.00022 Pa @ 20°C) of bis(2-ethylhexyl) maleate are indicative that the substance is essentially non volatile, and it is very likely that the substance will not reach the nasopharyngeal region or subsequently the tracheobronchial region via inhalation. Its very low hydrophilic character (log Pow 7.24) is not favorable for crossing the alveolar and capillary membranes and the relatively low water solubility of bis(2-ethylhexyl) maleate is not favorable for dissolution of the substance in the mucus lining of the respiratory tract. If bis(2-ethylhexyl) maleate is inhaled, none or very little significant absorption of the substance is to be expected. Therefore, bis(2-ethylhexyl) maleate does not present an inhalation hazard if exposure occurs. The acute inhalation LC50 value of dibutyl maleate (>5000 mg/m³) can be used as surrogate for the purpose of this risk assessment.