Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
96 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
96 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 005 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
400 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.65 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.35 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor starting point:
other: NOAEL

Workers - Hazard for the eyes

Additional information - workers

2-(2-(2-butoxyethoxy)ethoxy)ethanol

Workers

Humans differ in sensitivity due to a number of biological factors (such as age, gender, genetic composition and nutritional status). The intraspecies variation in humans is greater than in the more homogeneous experimental animal population

The data from animal studies are the starting point for risk characterisation.The default assumption in general is that humans are more sensitive than experimental animals.The traditional default AF(Assessment factor) suggested for interspecies extrapolation is 5 for workers and 10 for general population should be applied to the concentration/dose descriptor.

A lower default factor is generally suggested for the worker population, because the very young and very old are not part of this population.

To cover the intra-species variation, the default AF(Assessment factor)of 5 for workers was applied to the concentration/dose descriptor(NOAEL or NOAEC).

 

The dose descriptor for dermal irritation/corrosion come fromdermalacutestudyand dermal Repeated toxicity study. In thesestudies, the dose is reported in the unit mg/kg of body weight/day. This needs to be modified to enable comparison with the human exposure, generally expressed in mg/cm2/day.

We have taken that:

• the average weight of rats is 250g (200-300g), and the average weight of New Zealand White rabbit is2.65kg used by Moreno O.M..1976 andCorley RA, Ciesslak, Breslin WJ, Lomax,1990

• the dose is applied over an area which is approximately 10% of the total body surface, and

• the total body surface of rats is on the average 445 cm2  (363 to 527 cm2) and 1270 cm2of New Zealand White rabbit

used by Moreno O.M..1976 andCorley RA, Ciesslak, Breslin WJ, Lomax,1990

 

 

The generic modification from the NOAELtest(in mg/kg of body weight) to NOAELmodified(in mg/cm2/day) will be

 

NOAELtest*3.0/127= NOAELmodified

 

Local effects in animals after dermal exposure:

-The highest dose not causing irritation/corrosion was 2000mg/kg bw in the acute study of O.M..1976, the modified dose descriptor would be

2000mg/kg*2.65 kg/127cm2=41.73mg/cm2

 

-The highest dose not causing irritation/corrosion was 5025mg/kg bw in the Repeated toxicity study of Corley RA, Ciesslak, Breslin WJ, Lomax,1990, the modified dose descriptor would be5025mg/kg*0.25kg/44.5cm2=28.23mg/cm2

 

The substance triethylene glycol butyl ether (TEGBE or 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol, the subject of this dossier) is expected to exhibit very similar toxicity due to its close structural similarity to TEGME. Comparable metabolism would occur. On a molecular weight scaled basis, the NOAEL would be 5025.1mg/kgbw/day.

(4000 x 206.28) / 164.2 =5025.1 mg/kg bw/day

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
48 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.252 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
48 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
502.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
200 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.823 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.173 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor starting point:
other: NOAEL

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
103.4 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Additional information - General Population

General population

Following the “Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health”, the data from animal studies are the starting point for risk characterisation.The default assumption in general is that humans are more sensitive than experimental animals. The traditional default AF(Assessment factor)suggested for interspecies extrapolation is 5 for workers and 10 for general population should be applied to the concentration/dose descriptor.

Although other values have been proposed, defaults typically suggested for the general population (representing all age groups, including children and elderly) are a factor of 10.

To cover the intra-species variation, the default AF (Assessment factor)of10for General population was applied to the concentration/dose descriptor (NOAEL or NOAEC).

The dose descriptor for dermal irritation/corrosion come from dermal acute study. In this study, the dose is reported in the unit mg/kg of body weight/day. This needs to be modified to enable comparison with the human exposure, generally expressed in mg/cm2/day.

 

 

We have taken that:

• the average weight of rats is 250g (200-300g), and the average weight of New Zealand White rabbit is2.65kg used by Moreno O.M..1976 andCorley RA, Ciesslak, Breslin WJ, Lomax,1990

• the dose is applied over an area which is approximately 10% of the total body surface, and

• the total body surface of rats is on the average 445 cm2  (363 to 527 cm2) and 1270 cm2of New Zealand White rabbit

used by Moreno O.M..1976 andCorley RA, Ciesslak, Breslin WJ, Lomax,1990

 

 

The generic modification from the NOAELtest(in mg/kg of body weight) to NOAELmodified(in mg/cm2/day) will be

 

NOAELtest*3.0/127= NOAELmodified

 

Local effects in animals after dermal exposure:

-The highest dose not causing irritation/corrosion was 2000mg/kg bw in the acute study of O.M..1976, the modified dose descriptor would be

2000mg/kg*2.65 kg/127cm2=41.73mg/cm2

 

-The highest dose not causing irritation/corrosion was5025mg/kg bw in the Repeated toxicity study of Corley RA, Ciesslak, Breslin WJ, Lomax,1990, the modified dose descriptor would be5025mg/kg*0.25kg/44.5cm2=28.23mg/cm2

 

The substance triethylene glycol butyl ether (TEGBE or 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol, the subject of this dossier) is expected to exhibit very similar toxicity due to its close structural similarity to TEGME. Comparable metabolism would occur. On a molecular weight scaled basis, the NOAEL would be 5025.1mg/kgbw/day.

(4000 x 206.28) / 164.2 =5025.1 mg/kg bw/day