Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
It is concluded that the substance2-(2-(2-butoxyethoxy)ethoxy)ethanol does not meet the criteria to be classified for human health hazards for Reproductive toxicity
Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 257 mg/kg bw/day
Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
54.7 mg/m³
Effect on fertility: via dermal route
Dose descriptor:
NOAEL
31.5 mg/kg bw/day
Additional information

Oral exposure

Correcting for molecular weight, a conservative NOAEL(oral) of 1257 mg/kg bw/day can be derived.

(720 x 206.28) / 118.17 =1257 mg/kg bw/day

Dermal exposure:

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

1257mg/kg bw/day0.025 kg =                  

 NOAELrat  = 31.5mg/kg bw/day

Inhalation exposure:

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.

NOAEL rat            

 1257mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat  =  54.7mg/m3 



Short description of key information:
There are conclusive but not suffcient data for the classification of substance 2-(2-(2-butoxyethoxy)ethoxy)ethanol with regard to reproduction.
It is concluded that the substance2-(2-(2-butoxyethoxy)ethoxy)ethanol does not meet the criteria to be classified for human health hazards for Reproductive toxicity

Effects on developmental toxicity

Description of key information
There are conclusive but not suffcient data for the classification of substance 2-(2-(2-butoxyethoxy)ethoxy)ethanol with regard to Developmental toxicity / teratogenicity 
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
43.5 mg/m³
Effect on developmental toxicity: via dermal route
Dose descriptor:
NOAEL
25 mg/kg bw/day
Additional information

Oral exposure

NOAEL=1000 mg/kg bw/day

Dermal exposure:

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

 1000mg/kg bw/day x.0.025 kg =                  

 NOAELrat =  25mg/kg bw/day

 

Inhalation exposure:

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.

NOAEL rat             1000mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat    43.5 mg/m3

Toxicity to reproduction: other studies

Additional information

In a developmental toxicity study designed to establish the mechanism of toxicity of the anti-inflammatory drug, diflunisal, pregnant rabbits were given a single 100mg/kg dose of the drug on GD5. The known metabolism of the drug meant that it would be cleared from the bloodstream by GD9, which is known to be the critical day for the induction of axial skeletal defects by hypoxia. Diflunisal also causes anaemia, which is persistent to GD15 and the study produced the same axial skeletal defects that were seen in a conventional developmental toxicity study. The results provided strong support for the hypothesis that, for this drug, the developmental toxicity was primarily caused by anaemia rather than directly by the drug itself.

Justification for classification or non-classification

 

Based on the hazard assessment of2-(2-(2-butoxyethoxy)ethoxy)ethanolin section 2.1 and 2.2. in IUCLID 5.3., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99) and according to the criteria described in Directive 67/548 and in the CLP Regulation:

Directive 67/548

Toxicity to reproduction/development

Repr. Cat. 1; R61 May cause harm to the unborn child.

Repr. Cat. 2; R61 May cause harm to the unborn child.

Repr. Cat. 3; R63 Possible risk of harm to the unborn child.

Toxicity to reproduction/fertility

 Repr. Cat. 1; R60 May impair fertility.

Repr. Cat. 2; R60 May impair fertility.

Repr. Cat. 3; R62 Possible risk of impaired fertility

 

CLP

Reproductive toxicity

Repr. 1A

Repr. 1B

Repr. 2

H360: May damage fertility or the unborn child <state specific effect if known > <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H361: Suspected of damaging fertility or the unborn child <state specific effect if known> <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

It is concluded that the substance2-(2-(2-butoxyethoxy)ethoxy)ethanol does not meet the criteria to be classified for human health hazards for Reproductive toxicity