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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.23 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
105.8 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The susbtance is not classified for acute Hazard.  No hazard has been identified due to lack of data for thisendpoint/effect in thedataset in compliance toREACH Annexes datarequirements.Thus it is impossible to propose a hazard assessment 

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:
0.6 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:
60 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

1 -Workers

Undecylenic acid can be present as a solid or a liquid, considering the melting point of 21°C. The dustiness is low.

During unloading, unpacking and charging, dermal and/or inhalation contact is possible with:

-       solid substance

-       airborne dust.

Dermal and/or inhalation contact is possible during breaching of the system with

-       liquid substance

-       evaporated substance.

That is the reason why we consider the inhalation and dermal route as relevant exposure, and corresponding long term DNEL will therefore be derived

 

1.1             Short term, inhalation or dermal, local toxicity

Regarding acute toxicity, the DNELacuteonly needs to be derived in case the substance is labelled for an acute toxicity hazard and when peak exposures substantially higher than the DNELlong-termare possible. As both criteria do not apply for undecylenic acid, the derivation of a DNELacuteis not necessary.

Regarding local toxicity, although undecylenic acid is classified irritant to the skin and eyes, no substantially high peak exposure are expected in the plant. Furthermore, the workers are therefore obliged to wear safety goggles, protective work clothes, gloves when handling the substance and respiratory protection if handling high concentrations.

 

1.2             Long-term, inhalation, systemic toxicity

Occupational exposure to undecylenic acid may occur mainly by inhalation of particles or dust. Although it is a solid or a liquid at 21°C with a low vapour pressure, we consider the inhalation route as one of the relevant route for DNEL derivation.

In a 90-day repeated toxicity study performed in rats with undecylenic acid sodium salt (Fabreguettes, 1999), the oral NOAEL for systemic toxicity was 60 mg/kg bw/day.: Cardiomyopathy was recorded at 180 mg/kg bw/d, myocardial degeneration / monocellular aggregation which was reversible during the treatment free period.

 

Step 1) Relevant dose-descriptor:NOAELrat= 60 mg/kg bw/d

Step 2) Modification of starting point

-Conversion into inhalation NOAEC (in mg/m3) by using an 8-hour respiratory volume for the rat: 0.38 m3/kg bw

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

-Correcting for inhalation to oral absorption: no factor is add. Justification: A low inhalation absorption is expected because undecylenic acid has a low volatility (boiling point above 150°C, vapour pressure of less than 0.5 kPa).

-No difference in oral and inhalation absorption is expected between rats and humans.

NOAEC corrected = 105.8 mg/m3

 

Step 3) Assessment factors

-Interspecies = 2.5 (data on rat)

-Intraspecies = 5 (workers)

-Exposure duration = 2 (subchronic study)

-Dose response = 1 (dose descriptor = NOAEL)

-Quality of database = 1

Global assessment factor = 25

 

Step 4) DNEL calculation

DNEL Value (long term inhalation, systemic)= 105.8 / 25 = 4.23 mg/m3

 

 

1.3 Long-term, dermal, systemic toxicity

 

Occupational exposure to undecylenic acid may also occur by dermal exposure. Although no dermal repeated dose toxicity studies is available as well as no information on dermal absorption, we derived a dermal DNEL based on the same Oral NOAEL selected for the derivation of the inhalation DNEL.

 

Step 1) Relevant dose-descriptor:NOAELrat= 60 mg/kg bw/d

Step 2) Modification of starting point

Correcting for dermal to oral absorption: Factor of 1 is used.

Justification: Undecylenic acid has a high octanol/water partition coefficient (log Kow=4) which predicts a high dermal absorption. However, the water solubility is low therefore, no significant dermal absorption would be expected. As no dermal penetration study is available we will consider 100% absorption as a worst case.

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

 

Step 3) Assessment factors

-Interspecies = 2.5 x 4 (data on rat)

-Intraspecies = 5 (workers)

-Exposure duration = 2 (subchronic study)

-Dose response = 1 (dose descriptor = NOAEL)

-Quality of database = 1

Global assessment factor = 100

 

Step 4) DNEL calculation

DNEL Value (long term dermal, systemic)= 60 / 100 = 0.6 mg/m3

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:
DNEL (Derived No Effect Level)
Value:
0.3 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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
60 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Correcting for dermal to oral absorption: Factor of 1 is used.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.3 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):
200
Modified dose descriptor starting point:
NOAEL
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

2. General population

Exposure with undecylenic acid is expected to be low as it is used as an intermediate. Undecylenic acidis an organic unsaturated fatty acid derived from natural castor oil.It is used as an intermediate in the manufacturing of food aroma and in the manufacture of musk fragrances for perfumes.Undecylenic acid is a natural fungicide and is used as an intermediate in the manufacturing of anti fungus products for pharmaceutical and cosmetic use. It is further used as an intermediate in the synthesis of fine chemicals and the manufacture of polymers of salts for anti-corrosive additives and of products that enter the formulation of anti-dandruff shampoo.

If there is exposure, it will be minor and mainly occur via dermal and oral route.

2.1 DNEL long term dermal, systemic effect

In a 90-day repeated toxicity study performed in rats with undecylenic acid (Fabreguettes, 1999), the oral NOAEL for systemic toxicity was 60 mg/kg bw/day.: Cardiomyopathy was recorded at 180 mg/kg bw/d, myocardial degeneration / monocellular aggregation which was reversible during the treatment free period.

 

Step 1) Relevant dose-descriptor:NOAELrat= 60 mg/kg bw/d

Step 2) Modification of starting point

Correcting for dermal to oral absorption: Factor of 1 is used.

Justification: Undecylenic acid has a high octanol/water partition coefficient (log Kow=4) which predicts a high dermal absorption. However, the water solubility is low therefore, no significant dermal absorption would be expected. As no dermal penetration study is available we will consider 100% absorption as a worst case.

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

 

Step 3) Assessment factors

-Interspecies = 2.5 x 4 (data on rat)

-Intraspecies = 10 (general population)

-Exposure duration = 2 (subchronic study)

-Dose response = 1 (dose descriptor = NOAEL)

-Quality of database = 1

Global assessment factor = 200

 

Step 4) DNEL calculation

DNEL Value (long term dermal, systemic)= 60 / 200 = 0.3 mg/kg/day

 

2.2 DNEL long term oral, systemic effect

In a 90-day repeated toxicity study performed in rats with undecylenic acid (Fabreguettes, 1999), the oral NOAEL for systemic toxicity was 60 mg/kg bw/day.: Cardiomyopathy was recorded at 180 mg/kg bw/d, myocardial degeneration / monocellular aggregation which was reversible during the treatment free period.

 

Step 1) Relevant dose-descriptor:NOAELrat= 60 mg/kg bw/d

Step 2) Modification of starting point

No difference in oral absorption is expected between rats and humans.

 

Step 3) Assessment factors

-Interspecies = 2.5 x 4 (data on rat)

-Intraspecies = 10 (general population)

-Exposure duration = 2 (subchronic study)

-Dose response = 1 (dose descriptor = NOAEL)

-Quality of database = 1

Global assessment factor = 200

 

Step 4) DNEL calculation

DNEL Value (long term dermal, systemic)= 60 / 200 = 0.3 mg/kg/day