2-(2,4-diaminophenoxy)ethanol dihydrochloride

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

17.63 mg/m³

Explanation for the modification of the dose descriptor starting point:

The test substance 2,4-diaminophenoxyethanol dihydrochloride was administered daily by gavage to Sprague-Dawley rats at the dose level of 4, 20 or 100 mg/kg bw/day for 13 weeks. At 4 and 20 mg/kg bw/day the test item was well tolerated. A 100 mg/kg bw/day, ptyalism was observed in both males and females and lower body weight gains were noted for males. Presence of urinary bilirubin, nitrites, glucose and coloured urine in both males and females was observed at the end of the treatment period. After a

4 week treatment-free period, all the above-mentioned changes were no longer noted. Deposition of brownish pigment in the thyroids and an augmented degree of spleen hemosiderosis were also observed for most animals given 100 mg/kg bw/day on completion of treatment and treatment-free periods. Under the experimental conditions of the study, the NOEL is established to be 20 mg/kg bw/day.The Relevant dose descriptor: NOAEL: 20 mg/kg/bw  Route to route extrapolation:  NOAEC = NOAEL x (1/sRV(rat))  x  (sRVhuman/wRV)  x  (ABSoral/ABSinhal.)      

NOAEC = 20 mg/kg/day  x  (1/0.38 m3/kg/bw)  x  (6.7 m3/10 m3) x (50%*/100%) =  17.63 mg/m3

*oral bioavailability unknown and  by default supposed to be 50%, inhalation bioavailability is supposed to be 100%.

The relevant dose descriptor: long term NOAEC = 17.63mg/m3

The Assessment factor = 1 x 2.5 x 5 x 2 x 1 x 1 = 25

Worker-DNEL long term inhalation systemic=   0.7 mg/m3

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

2

Justification:

default value for extrapolation subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Extrapolation from oral to inhalation route (example B3 of guidance R8)

AF for other interspecies differences:

2.5

Justification:

R8 ECHA guidance

AF for intraspecies differences:

5

Justification:

default value for workers

AF for the quality of the whole database:

1

Justification:

reliability 2

AF for remaining uncertainties:

1

Justification:

default value

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23.81 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

595.24 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The test substance 2,4-diaminophenoxyethanol dihydrochloride was administered daily by gavage to Sprague-Dawley rats at the dose level of 4, 20 or 100 mg/kg bw/day for 13 weeks. At 4 and 20 mg/kg bw/day the test item was well tolerated. A 100 mg/kg bw/day, ptyalism was observed in both males and females and lower body weight gains were noted for males. Presence of urinary bilirubin, nitrites, glucose and coloured urine in both males and females was observed at the end of the treatment period. After a 4 week treatment-free period, all the above-mentioned changes were no longer noted. Deposition of brownish pigment in the thyroids and an augmented degree of spleen hemosiderosis were also observed for most animals given 100 mg/kg bw/day on completion of treatment and treatment-free periods. Under the experimental conditions of the study, the NOEL is established to be 20 mg/kg bw/day.

The Relevant dose descriptor: NOAEL: 20 mg/kg/bw  Route to route extrapolation:  NOAEL = NOAEL x  (ABSoral/ABSdermal)      

NOAEL = 20 mg/kg/day  x  (50%*/1.68%) =  595.24 mg/kg bw/d

*oral bioavailability unknown and  by default supposed to be 50%, dermal bioavailability is determined to be 1.68%.

The relevant dose descriptor: long term NOAEL = 595.24 mg/kg bw/d

The Assessment factor = 1 x 2 x 4x 2.5 x 5 x 1 x 1 = 100

Worker-DNEL long term dermal systemic=   23.81 mg/m3

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

2

Justification:

for extrapolation subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

allometric value (Rat)

AF for other interspecies differences:

2.5

Justification:

default value systemic effect or for effects on skin, eye and GI tract via local metabolism, for effects on respiratory tract

AF for intraspecies differences:

5

Justification:

default value worker

AF for the quality of the whole database:

1

Justification:

reliability 2

AF for remaining uncertainties:

1

Justification:

not concerned

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

53.33 µg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

15

Dose descriptor:

other: EC3

AF for dose response relationship:

3

Justification:

from LOAEL to NOAEL minimum/majority case

AF for differences in duration of exposure:

1

Justification:

default value

AF for interspecies differences (allometric scaling):

1

Justification:

default value systemic effect

AF for other interspecies differences:

1

Justification:

default value local effect or for effects on skin, eye and GI tract via simple destruction of membranes

AF for intraspecies differences:

5

Justification:

default value worker

AF for the quality of the whole database:

1

Justification:

reliability 2

AF for remaining uncertainties:

1

Justification:

not concerned

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

53.33 µg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

15

Dose descriptor starting point:

other: EC3

AF for dose response relationship:

3

Justification:

from LOAEL to NOAEL minimum/majority case

AF for interspecies differences (allometric scaling):

1

Justification:

default value systemic effect

AF for other interspecies differences:

1

Justification:

default value local effect or for effects on skin, eye and GI tract via simple destruction of membranes

AF for intraspecies differences:

5

Justification:

default value worker

AF for the quality of the whole database:

1

Justification:

reliability 2

AF for remaining uncertainties:

1

Justification:

not concerned

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

The CSR need not include consideration of the risks to human health from the end use of cosmetic products within the scope of Regulation EC 1223/2009.