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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.12 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
36
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.67 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
32 µg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Dose descriptor:
other: NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Short term exposure worker (local and systemic effects)

 

2-(2-Aminoethoxy)ethanol is in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 classified as corrosive (Cat. 1B; H318: Causes severe skin burns and eye damage). The performed guideline test is not providing dose-response data that could be used for the derivation of an acute DNEL.According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent eye and skin exposure.

 

 

Long term exposure worker (local and systemic effects)

Inhalatory

The DNELs for inhalatory long term exposure of workers are derived from the NOAEL obtained in an inhalative combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; BASF SE 2010).2-(2-Aminoethoxy)ethanol was administered via inhalation (aerosol) to groups of 10 male and 10 female Wistar rats (F0 animals) at concentrations of 4, 16, and 40 mg/m³. Regarding clinical examinations, no signs of general systemic toxicity were observed in male and female parental animals at any dose level during the entire study period. Fertility indices for male and female animals were not impaired by test-substance administration even at a dose level of 40 mg/m³. In addition, live birth and viability indices of pups in all test groups were not influenced. Concerning clinical pathology no treatment-related, adverse effects were observed up to a dose level of 40 mg/m3. With regard to pathology, treatment-related microscopic changes were observed in larynx (level 1) and consisted of increased squamous metaplasia of the respiratory epithelium and chronic (active) inflammation at level 1 of the larynx only to a marginal or slight degree. This was observed in both sexes. Histopathological examination of the mid- and low-dose groups of the larynx at this level 1 revealed that these treatment-related findings (squamous metaplasia and chronic [active] inflammation) were also observed in the mid-dose group (16 mg/m³), however, to a lesser severity degree compared to the high-dose groups (40 mg/m³). Other macroscopic and/or microscopic changes observed were either non-dose related and/or considered to be normal background changes. No treatment-related changes were observed in both sexes at a concentration of 4 mg/m³. Thus, the no observed adverse effect concentration (NOAEC) for general systemic toxicity as well as reproductive performance, fertility and developmental toxicity was 40 mg/m³. The NOAEC for local effects was 4 mg/m³.

 

Long term worker (systemic effects, inhalation)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 40 mg/m3(OECD 422; inhalative; rat)

 

Step 2) modification of the starting point

 

 

 

6h/8h

to 8h exposure

 

6.7 m³/10 m³

to light work

Step 3) Assessment factors

 

 

Exposure duration

6

subacute to chronic

Interspecies

1

no interspecies extrapolation for inhalation

Intraspecies

3

worker

DNEL

Value

For workers

40 mg/m3x 0.75 x 0.67 / (6 x 1 x 3) = 1.12 mg/m³

Factor 36

 

Long term worker (local effects, inhalation)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 4 mg/m3(OECD 422; inhalative; rat)

Local effects in larynx

Step 2) modification of the starting point

 

 

 

6h/8h

to 8h exposure

 

6.7 m³/10 m³

to light work

Step 3) Assessment factors

 

 

Exposure duration

1

Irritation threshold, no time extrapolation

Interspecies

1

no interspecies extrapolation for inhalation

Intraspecies

3

worker

DNEL

Value

For workers

4 mg/m3x 0.75 x 0.67 / (1 x 1 x 3) = 0.67 mg/m³

Factor 6

 

 

Dermal

The DNELs for dermal long term exposure of workers are derived from the NOAELs obtained in a subchronic dermal study following OECD test guideline 411 (Huntsman, 2002). Application of the test substance to an intact cutaneous site for approximately 6 hours, once daily for 90 consecutive days resulted in ulceration, epidermal hyperplasia, fibrosis and inflammation at doses of 87 and 175 mg/kg bw/d. These changes represent local irritation following topical administration. Based on the results of the study, the NOAEL for local effects was at least 17 mg/kg bw/d while the systemic NOAEL was at least 175 mg/kg bw/d (highest dose tested).

 

Long term worker (systemic effects, dermal)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 175 mg/kg bw/d (OECD 411; dermal; rat)

 

Step 2) modification of the starting point

 

 

Step 3) Assessment factors

 

 

Exposure duration

2

subchronic to chronic

Interspecies

4

extrapolation systemic effects rat to human

Intraspecies

3

worker

DNEL

Value

For workers

175 mg/kg bw/d/ (2 x 4 x 3) = 7.3 mg/kg bw/d

Factor 24

 

Long term worker (local effects, dermal)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 17 mg/kg bw/d (OECD 411; dermal; rat)

Local irritation

Step 2) modification of the starting point

 

 

Step 3) Assessment factors

 

 

Exposure duration

1

Irritation threshold, no time extrapolation

Interspecies

1

no interspecies extrapolation for local effects

Intraspecies

3

worker

DNEL

Value

For workers

17 mg/kg bw/d/ (1 x 1 x 3) = 5.7 mg/kg bw/d (19 µg/cm2)

Factor 3

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
121
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19 µg/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:
high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Short term exposure general population (local and systemic effects)

 

Same considerations as for the worker.

 

Long term exposure general population (local and systemic effects)

Inhalatory

The DNELs for inhalatory long term exposure of the general population are derived from the NOAEL obtained in an inhalative combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; BASF SE 2010).2-(2-Aminoethoxy)ethanol was administered via inhalation (aerosol) to groups of 10 male and 10 female Wistar rats (F0 animals) at concentrations of 4, 16, and 40 mg/m³. Regarding clinical examinations, no signs of general systemic toxicity were observed in male and female parental animals at any dose level during the entire study period. Fertility indices for male and female animals were not impaired by test-substance administration even at a dose level of 40 mg/m³. In addition, live birth and viability indices of pups in all test groups were not influenced. Concerning clinical pathology no treatment-related, adverse effects were observed up to a dose level of 40 mg/m3. With regard to pathology, treatment-related microscopic changes were observed in larynx (level 1) and consisted of increased squamous metaplasia of the respiratory epithelium and chronic (active) inflammation at level 1 of the larynx only to a marginal or slight degree. This was observed in both sexes. Histopathological examination of the mid- and low-dose groups of the larynx at this level 1 revealed that these treatment-related findings (squamous metaplasia and chronic [active] inflammation) were also observed in the mid-dose group (16 mg/m³), however, to a lesser severity degree compared to the high-dose groups (40 mg/m³). Other macroscopic and/or microscopic changes observed were either non-dose related and/or considered to be normal background changes. No treatment-related changes were observed in both sexes at a concentration of 4 mg/m³. Thus, the no observed adverse effect concentration (NOAEC) for general systemic toxicity as well as reproductive performance, fertility and developmental toxicity was 40 mg/m³. The NOAEC for local effects was 4 mg/m³.

 

Long term general population (systemic effects, inhalation)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 40 mg/m3(OECD 422; inhalative; rat)

 

Step 2) modification of the starting point

 

 

 

6h/24h

to 24h exposure

Step 3) Assessment factors

 

 

Exposure duration

6

subacute to chronic

Interspecies

1

no interspecies extrapolation for inhalation

Intraspecies

5

general population

DNEL

Value

For general population

40 mg/m3x 0.25 / (6 x 1 x 5) = 0.33 mg/m³

Factor 121

 

Long term general population (local effects, inhalation)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 4 mg/m3(OECD 422; inhalative; rat)

Local effects in larynx

Step 2) modification of the starting point

 

 

 

6h/24h

to 24h exposure

Step 3) Assessment factors

 

 

Exposure duration

1

Irritation threshold, no time extrapolation

Interspecies

1

no interspecies extrapolation for inhalation

Intraspecies

5

general population

DNEL

Value

For general population

4 mg/m3x 0.25 / (1 x 1 x 5) = 0.2 mg/m³

Factor 20

 

 

Dermal and oral

 

The DNELs for dermal and oral long term exposure of the general population are derived from the NOAELs obtained in a subchronic dermal study following OECD test guideline 411 (Huntsman, 2002). Application of the test substance to an intact cutaneous site for approximately 6 hours, once daily for 90 consecutive days resulted in ulceration, epidermal hyperplasia, fibrosis and inflammation at doses of 87 and 175 mg/kg bw/d. These changes represent local irritation following topical administration. Based on the results of the study, the NOAEL for local effects was at least 17 mg/kg bw/d while the systemic NOAEL was at least 175 mg/kg bw/d (highest dose tested).

 

Long term general population (systemic effects, dermal)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 175 mg/kg bw/d (OECD 411; dermal; rat)

 

Step 2) modification of the starting point

 

 

Step 3) Assessment factors

 

 

Exposure duration

2

subchronic to chronic

Interspecies

4

extrapolation systemic effects rat to human

Intraspecies

5

general population

DNEL

Value

For general population

175 mg/kg bw/d/ (2 x 4 x 5) = 4.4 mg/kg bw/d

Factor 40

 

Long term general population (local effects, dermal)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 17 mg/kg bw/d (OECD 411; dermal; rat)

Local irritation

Step 2) modification of the starting point

 

 

Step 3) Assessment factors

 

 

Exposure duration

1

Irritation threshold, no time extrapolation

Interspecies

1

no interspecies extrapolation for local effects

Intraspecies

5

general population

DNEL

Value

For general population

17 mg/kg bw/d/ (1 x 1 x 5) = 3.4 mg/kg bw/d (19 µg/cm2 )

Factor 5

 

Long term general population (systemic effects, oral)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 175 mg/kg bw/d (OECD 411; dermal; rat)

 

Step 2) modification of the starting point

 

 

 

1

route to route (dermal to oral)

Step 3) Assessment factors

 

 

Exposure duration

2

subchronic to chronic

Interspecies

4

extrapolation systemic effects rat to human

Intraspecies

5

general population

DNEL

Value

For general population

175 mg/kg bw/d x 1/ (2 x 4 x 5) = 4.4 mg/kg bw/d

Factor 40