Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.26 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
881.57 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEC = 1000 x 1/0.38 x 6.7/10 x 0.5 = 793 mg/m3. A correction factor of 0.5 is applied according to the R8 guidance when there are no data on oral and inhalation absorption.
AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
OECD 408 ( Butterworth, 1978), 3 months exposure
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation.
AF for other interspecies differences:
2.5
Justification:
AF by default
AF for intraspecies differences:
5
Justification:
AF by default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
no other factor is applied
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
10 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
As no information is available on dermal absorption, dermal absorption is considered to be equal to the oral absorption.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Butterworth, 1978 is the key study with a 3 months exposure duration
AF for interspecies differences (allometric scaling):
4
Justification:
An allometric scaling factor of 4 must be applied because the key study was performed on rats.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for worker DNELs
AF for the quality of the whole database:
1
Justification:
The key study is considered as a reliable study with a klimisch score of 1.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is applied.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

WORKERS

1. Acute / short term exposure - systemic effects

Dermal route : Based on the available data, no acute dermal DNEL is deemed necessay because of the LD50>2000 mg/kg

Inhalation route : Due to the absence of mortality at the maximum saturated concentration, no DNEL is derived.

2. Acute / short term exposure - local effects

No information on local effects (dermal and inhalation routes) are available.

1/ Inhalation DNEL (long term, systemic effect)- WORKERS

The oral subchronic toxicity study (Butterworth, 1978) was considered as a key study for the derivation of the DNEL. In this study, the limit dose of 1000 mg/kg/day was used as the high dose-levels and was considered to be the NOAEL of this study.

 

Step 1: Selection of the relevant dose descriptor:

Oral NOAEL = 1000 mg/kg/day

 

Step 2: Modification of the starting point:

- Conversion into an inhalatory rat NOAEC by dividing by 0.38 m3/kg (8-hour respiratory volume in the rat)

-Correction for absorption difference between inhalation and oral absorption:

The oral absorption is estimated to 50%. According to ECHA Guidance – Chapter R8 (p25), the inhalation absorption is 100% : “if data on the starting route (oral) are available these should be used, but for the end route (inhalation), the worst case inhalation absorption should be assumed (i.e. factor 1)”. Therefore the correction factor is 0.5 (50/100 ).

- Correction for activity driven differences in respiratory volume in workers compared to individuals at rest (6.7 m3/10 m3)

NOAEC (worker, 8 h) = 1000 x 1/0.38 x 6.7/10 x 0.5 = 881.57 mg/m3

 

Step 3: Assessment factors:

- Interspecies differences: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed. However, a factor of 2.5 to correct for differences other than differences in metabolic rate is applied.

- Intraspecies differences: the default assessment factor of 5 is applied.

- Differences in exposure duration: 2

- Dose-response relationship: a factor of 1 is applied due to the use of a NOAEL as dose descriptor and the low toxicity of the test substance.

- Quality of whole database: 1

Global assessment factor: 2.5 x 5 x 2 x 1 x 1 = 25

 

Step 4: DNEL derivation:

Worker inhalation DNEL (long term, systemic effects) = 881.57 / 25= 35.26 mg/m3

 

 

2/ Dermal DNEL (long term, systemic effect)- WORKERS

The oral subchronic toxicity study (Butterworth, 1978) was considered as a key study for the derivation of the DNEL. In this study, the limit dose of 1000 mg/kg/day was used as the high dose-levels and was considered to be the NOAEL of this study.

 

Step 1: Selection of the relevant dose descriptor:

Oral NOAEL = 1000 mg/kg/day

 

Step 2: Modification of the starting point:

-Correction for absorption difference between rat and human:

No difference in dermal and oral absorption are expected between rats and humans.

-Correction for absorption difference between dermal and oral absorption:

No data on absorption is available on heptanol or heptanoic acid.

Dermal NOAEL = 1000 mg/kg bw

 

Step 3: Assessment factors:

- Interspecies differences: an allometric scaling factor of 4 (standard for rats) is applied because no route-to-route extrapolation is performed. A factor of 2.5 to correct for differences other than differences in metabolic rate is also applied.

- Intraspecies differences: the default assessment factor of 5 is applied.

- Differences in exposure duration: 2

- Dose-response relationship: a factor of 1 is applied due to the use of a NOAEL as dose descriptor and the low toxicity of the test substance.

- Quality of whole database: 1

Global assessment factor: 4 x 2.5 x 5x 2 x 1 = 100

 

Step 4: DNEL derivation:

Worker dermal DNEL (long term, systemic effects) = 1000 / 100 = 10 mg/kg bw/day

 

 

 

 

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:
hazard unknown (no further information necessary)
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