11-aminoundecanoic acid

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.86 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):

75

Dose descriptor starting point:

NOAEL

Value:

79 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

139 mg/m³

Explanation for the modification of the dose descriptor starting point:

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

*No correction for inhalatory and oral absorption rates (considered to be 100 % because 11-aminoundecanoic acid is well       absorbed by both routes)

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

*Corrected dose descriptor:NOAEC (worker, 8 h)= 79 x 1/0.38 x 6.7/10 = 139 mg/m³

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

AF for interspecies differences (allometric scaling):

2.5

AF for other interspecies differences:

1

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:

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

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

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

Acute/short term exposure

Hazard assessment conclusion:

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

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.26 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):

300

Dose descriptor starting point:

NOAEL

Value:

79 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

0.26 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

DNEL Value based on NOAEL OECD 421 :

79 x 1 x 1/(2.5 x 4 x 5 x 6 x 1 x 1) = 0.26 mg/kg bw

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

AF for interspecies differences (allometric scaling):

2.5

AF for other interspecies differences:

4

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:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

For acute effects, no significant effects that would justify DNEL derivation were observed in the corresponding toxicity studies.

For systemic effects, DNEL derivation was performed following the method proposed in the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8.

 

1. Long term exposure-systemic toxicity

1.1 Inhalation DNEL(workers)

 Occupational exposure to 11 -aminoundecanoic acid may occur mainly by inhalation of particles, therefore we consider the inhalation route as the most relevant for DNEL derivation.

Of all repeated dose toxicity studies in rats, the OECD TG 421 (reproductive/developmental screening) study (CIT, 2008) is selected for DNEL derivation as it is the study where the lowest NOAEL was observed among the repeated dose toxicity studies data set with 11-aminoundecanoic acid, and because effects on kidneys, considered as the critical effect with a threshold mode of action, were also observed in this study.

 

• Step 1: Selection of the relevant dose descriptor:

*NOAEL (parental toxicity) = 1250 ppm, equivalent to79 mg/kg/day

*No reproductive effects but renal effects were observed in the parents (histopathological findings).

• 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)

*No correction for inhalatory and oral absorption rates (considered to be 100 % because 11-aminoundecanoic acid is well       absorbed by both routes)

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

*Corrected dose descriptor:NOAEC (worker, 8 h)= 79 x 1/0.38 x 6.7/10 = 139 mg/m³

• Step 3: Assessment factors:

*Interspecies : 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 : the default assessment factor of 5 is applied.

* Differences in exposure duration: as the exposure in rats was 54 days, a factor of 6 for subacute-to-chronic extrapolation is applied.

*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: a factor of 1 is applied based on the good quality of the whole database.

*Global assessment factor: 2.5 x 5 x 6 x 1 x 1 = 75

 

• Step 4: DNEL derivation:

 Worker DNEL (long term, systemic effects)= 79 x 1/0.38 x 6.7/10 x 1/75 = 1.86 mg/m³

 

2. Dermal DNEL (workers)

Occupational exposure to 11 -aminoundecanoic 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 Oral NOAEL selected for the derivation of the inhalation DNEL.

 

Step 1) Relevant dose-descriptor          

* NOAEL, rats= (parental toxicity) =1250 ppm, equivalent to79 mg/kg/day

 

Step 2)Modification of starting point:

* Correction for oral to dermal absorption :

11 -aminoundecanoic acid has a low octanol partition coefficient (log Kow=0.16) which predicts a low dermal absorption. However as no dermal penetration study is available we consider 100% absorbsion as a worst case (=1).

 

No difference in dermal absorption is expected between rats and humans, no correction factor will be applied.

Step 3) Assessment factors

* Interspecies: 2.5 x 4

* Intraspecies : 5

* Exposure duration : 6 (as the exposure in rats was 54 days, a factor of 6 for subacute-to-chronic extrapolation is applied).

* Dose response:1

* Quality of database:1

 

DNEL Value based on NOAEL OECD 421 :

79 x 1 x 1/(2.5 x 4 x 5 x 6 x 1 x 1) = 0.26 mg/kg bw

 

Oral route

 

The oral route of exposure is not relevant to workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.45 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):

150

Dose descriptor starting point:

NOAEL

Value:

79 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

67.94 mg/m³

Explanation for the modification of the dose descriptor starting point:

see discussion below

 

79 mg/kg/day x1/1.15=67.94 mg/m3

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

AF for interspecies differences (allometric scaling):

2.5

AF for other interspecies differences:

4

AF for intraspecies differences:

10

AF for remaining uncertainties:

1

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:

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

Acute/short term exposure

Hazard assessment conclusion:

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

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.13 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):

600

Dose descriptor starting point:

NOAEL

Value:

79 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

79 mg/kg bw/day

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

AF for interspecies differences (allometric scaling):

2.5

AF for other interspecies differences:

4

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:

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

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:

0.13 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):

600

Dose descriptor starting point:

NOAEL

Value:

79 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

79 mg/kg bw/day

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

AF for interspecies differences (allometric scaling):

2.5

AF for other interspecies differences:

4

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

Occupational exposure to 11 -aminoundecanoic acid is the most relevant potential safety concern under the conditions of use of the substance. There is no direct consumer use of 11 -aminoundecanoic acid, Food contact materials made of polyamide 11 contain low residual levels of 11-aminoundecanoic acid (<100 ppm) and are subject to very strict regulations, therefore no DNEL derivation for general population was deemed necessary.