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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.6 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
7.5
Modified dose descriptor starting point:
NOAEC
Value:
11.85 mg/m³
Explanation for the modification of the dose descriptor starting point:

After oral or inhalative exposure only sytemic but no local effects were observed.

AF for dose response relationship:
1
Justification:
ECHA Guidance - NOAEL
AF for differences in duration of exposure:
1
Justification:
ECHA Guidance - long-term study
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA Guidance - inhalation route
AF for other interspecies differences:
2.5
Justification:
ECHA Guidance
AF for intraspecies differences:
3
Justification:
EU Risk Asseessment Report, see REACH Annex 1, 0.5
AF for the quality of the whole database:
1
Justification:
ECHA Guidance
AF for remaining uncertainties:
1
Justification:
ECHA Guidance
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.4 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEL
Value:
100.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

After oral and dermal exposure especially sytemic toxicity was observed.

AF for dose response relationship:
1
Justification:
ECHA Guidance - NOAEL
AF for differences in duration of exposure:
1
Justification:
ECHA Guidance - long-term study
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA Guidance
AF for intraspecies differences:
3
Justification:
EU Risk Asseessment Report, see REACH Annex 1, 0.5
AF for the quality of the whole database:
1
Justification:
ECHA Guidance
AF for remaining uncertainties:
1
Justification:
ECHA Guidance
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

 Long –term – inhalation, systemic toxicity

NOAEL of 4.8 mg/kg bw/d for reproductive and developmental effects observed in 3-generation oral study in rats (Wolfe and Layton, 2004).

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 4.8 mg/kg bw/day

NOAEL from 3-Generation study in rats

Step 2) Modification of starting point

0.38 m3/kg bw



75/75


6.7 m3/10 m3

7/5

- Conversion into inhalation NAEC (in mg/m3) by using an 8-hour respiratory volume for the rat.

- Correction for 75% bioavailability for inhalation in humans and 75% for oral absorption in adult rats

- Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

- Correction for use of NOAEL from feeding study with 7d exposure/week compared to worker's exposure 5 d/week

Step 3) Assessment factors

Interspecies

2.5

Only a factor 2.5 is used, and no allometric scaling factors is used

Intraspecies

3

In the EU RA of DEHP anassessment factors of 3 is used for potential intraspecies differences for the worker (see also see REACH Annex 1, 0.5 for justification).

Exposure duration

1

The NOAEL is based on a 3-Generation study

Dose response

1

Quality of database

1

DNEL

Value

based on NOAELrat

1.6 mg/m3

= 4.8 x 1/0.38 x 75/75 x 6.7/10 x 7/5 x1/(2.5 x 3 x 1 x 1 x 1)

This DNEL of 1.6 mg/m3 corresponds to an oral intake of 230 µg/kg bw/day (assuming equal absorption rates of 75% for oral and inhalation exposure, 70 kg body weight, respiratory volume 10 m3 /work day: 1.6 mg/m3 x 10 m3/day x 1/70 kg bw).

Long –term – dermal, systemic toxicity

NOAEL of 4.8 mg/kg bw/d for reproductive and developmental effects observed in 3-generation oral study in rats (Wolfe and Layton, 2004).

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 4.8 mg/kg bw/day

NOAEL from 3-Generation study in rats

Step 2) Modification of starting point

75/5

7/5

- Correction for 5%bioavailability for dermal exposure in human and 75% for oral absorption in adults rats 

- Correction for use of NOAEL from feeding study with 7d exposure/week compared to worker's exposure 5 d/week

Step 3) Assessment factors

Interspecies

2.5 x 4

Intraspecies

3

In the EU RA of DEHP anassessment factors of 3 is used for potential intraspecies differences for the worker (see also see REACH Annex 1, 0.5 for justification).

Exposure duration

1

The NOAEL is based on a 2-year study

Dose response

1

Quality of database

1

DNEL

Value

based on NOAELrats

3.4 mg/kg bw/day

= 4.8 x 75/5 x 7/5 x 1/(10 x 3 x 1 x 1 x 1)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.13 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
4.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

After oral or inhalative exposure only sytemic but no local effects were observed.

AF for dose response relationship:
1
Justification:
ECHA Guidance - NOAEL
AF for differences in duration of exposure:
1
Justification:
ECHA Guidance - long-term study
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA Guidance - inhalation route
AF for other interspecies differences:
2.5
Justification:
ECHA Guidance
AF for intraspecies differences:
10
Justification:
ECHA Guidance
AF for the quality of the whole database:
1
Justification:
ECHA Guidance
AF for remaining uncertainties:
1
Justification:
ECHA Guidance
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:
DNEL (Derived No Effect Level)
Value:
0.72 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
72 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

After oral and dermal exposure especially sytemic toxicity was observed.

AF for dose response relationship:
1
Justification:
ECHA Guidance - NOAEL
AF for differences in duration of exposure:
1
Justification:
ECHA Guidance - long-term study
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA Guidance
AF for intraspecies differences:
10
Justification:
ECHA Guidance
AF for the quality of the whole database:
1
Justification:
ECHA Guidance
AF for remaining uncertainties:
1
Justification:
ECHA Guidance
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:
DNEL (Derived No Effect Level)
Value:
0.036 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
3.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no route to route extrapolation

AF for dose response relationship:
1
Justification:
ECHA Guidance - NOAEL
AF for differences in duration of exposure:
1
Justification:
ECHA Guidance - long-term study
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA Guidance
AF for intraspecies differences:
10
Justification:
ECHA Guidance
AF for the quality of the whole database:
1
Justification:
ECHA Guidance
AF for remaining uncertainties:
1
Justification:
ECHA Guidance
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

Long –term – inhalation, systemic toxicity

NOAEL of 4.8 mg/kg bw/d for reproductive and developmental effects observed in 3-generation oral study in rats (Wolfe and Layton, 2004).

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 4.8 mg/kg bw/day

NOAEL from 3-Generation study in rats

Step 2) Modification of starting point

1.15 m3/kg bw



75/75 (adults)

75/100 (children)

- Conversion into inhalation NAEC (in mg/m3) by using a 24-hour respiratory volume for the rat. 

- no difference in inhalative bioavailability assumed: 75% bioavailability for inhalative exposure in adult humans and 75% for oral absorption in adult rats

- correction factor 75/100 for children

Step 3) Assessment factors

Interspecies

2.5

Only a factor 2.5 is used, and no allometric scaling factors is used

Intraspecies

10

Exposure duration

1

The NOAEL is based on a 3-Generation study

Dose response

1

Quality of database

1

DNEL

Value

based on NOAELrats

0.17 mg/m3(0.04 ppm) for adults

= 4.8 x 1/1.15 x 75/75 x 1/(2.5 x 10 x 1 x 1 x 1) 

0.13 mg/m3(0.04 ppm) for children

= 4.8 x 1/1.15 x 75/100 x 1/(2.5 x 10 x 1 x 1 x 1)

Long –term – oral, systemic toxicity

NOAEL of 4.8 mg/kg bw/d for reproductive and developmental effects observed in 3-generation oral study in rats (Wolfe and Layton, 2004).

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 4.8 mg/kg bw/day

NOAEL from 3 -Generation study in rats

Step 2) Modification of starting point

75/75 (adults)

75/100 (children)

- no difference in oral bioavailability assumed: 75% bioavailability for oral exposure in adult humans and 75% for oral absorption in adult rats

- correction factor 75/100 for children

Step 3) Assessment factors

Interspecies

2.5 x 4

Intraspecies

10

Exposure duration

1

The NOAEL is based on a 3 -Generation study

Dose response

1

Quality of database

1

DNEL

Value

based on NOAELrats

0.048 mg/kg bw/d for adults 

= 4.8 x 75/75 x 1/(10 x 10 x 1 x 1 x 1)

0.036 mg/kg bw/d for children

= 4.8 x 75/100 x 1/(10 x 10 x 1 x 1 x 1)

 Long –term – dermal, systemic toxicity

NOAEL of 4.8 mg/kg bw/d for reproductive and developmental effects observed in 3-generation oral study in rats (Wolfe and Layton, 2004).

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 4.8 mg/kg bw/day

NOAEL from 3-Generation study in rats

Step 2) Modification of starting point

75/5

Correction for 5%bioavailability for dermal exposure in humans and 75% for oral absorption in adult rats

Step 3) Assessment factors

Interspecies

2.5 x 4

Intraspecies

10

Exposure duration

1

The NOAEL is based on 3-Generation study

Dose response

1

Quality of database

1

DNEL

Value

based on NOAELrats

0.72 mg/kg bw/d

= 4.8 x 75/5 x 1/(10 x 10 x 1 x 1 x 1)