Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl acrylate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH guidance R.8, 2012 and ECETOC, 2010

Overall assessment factor (AF):

20.4

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

88.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

Default correction for breathing volume, activity and route-to-route extrapolation according to ECHA R.8, 2012

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

6

Justification:

Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Acrylates are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF for remaining differences is justified.

AF for intraspecies differences:

3

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 3 is sufficiently conservative. (ECETOC, 2010)

AF for the quality of the whole database:

1

Justification:

The key studies were of high quality, being rated K1 or K2. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.

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:

1.39 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH guidance R.8, 2012 and ECETOC, 2010

Overall assessment factor (AF):

72

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Default oral to dermal extrapolation with a factor of 1 (ECHA R.8, 2012), in line with consideration on physico-chemical properities and related adsorption potential according to according to ECHA R.7c (2017).

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required

AF for differences in duration of exposure:

6

Justification:

Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012) )

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling factor rat to humans (ECHA 2012).

AF for other interspecies differences:

1

Justification:

Acrylates are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.

AF for intraspecies differences:

3

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 3 is sufficiently conservative. (ECETOC, 2010)

AF for the quality of the whole database:

1

Justification:

The key studies were of high quality, being rated K1 or K2. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Sytemic effects, long term

Calculation from the oral repeated dose/ repro screening study (OECD 422) study with IBOA in rats

 

DNEL inhal worker long-term

Description	Value/ factor	Remark
Step 1) Relevant dose-descriptor	NOAEL:100 mg/kg bw/d	NOAEL for urinalysis and reprotoxicity in rats given IBOA by oral gavage in OECD 422 protocol
Step 2) Modification of starting point	0.38 m³/kg   6.7 m^3/10 m^3	Correction for rat standard breathing volume, 8 hrs (ECHA R.8, 2012) -Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (10 m^3/6.7 m^3;ECHA R.8, 2012)
Route-to-Route extrapolation	2	Oral to inhalation extrapolation (ECHA R.8, 2012) This is considered as very conservative approach as the low vapour pressure indicates a comparably low absorption potential when compared to oral administration (according to ECHA R.7c, 2017)
NAEC worker	88.2 mg/m^3
Step 3) Assessment factors
Interspecies	1	No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)
Intraspecies	3	Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 3 is sufficiently conservative. (ECETOC, 2010)
Exposure duration	6	Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)
Dose response	1	The NOAEL is reliable. No adjustment is required.
Quality of database	1	The key studies were of high quality, being rated K1 or K2. No adjustment is required.
Remaining uncertainties	1	No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.
DNEL
Based upon a NOAEL of 100 mg/kg bw/d for rats in an OECD 422 screening study after oral administration	4,90 mg/m^3		Using a total factor (POD modifier and AF) of 20.4 (/ 0.38 x 10/6.7 m³ x 2 x 1 x 3 x 6 x 1 x 1 x 1) a DNELlong-term, inhal, workerof 4.90 mg/m³ is derived.

 

 

 

 

DNEL dermal worker long-term

Description	Value/ factor	Remark
Step 1) Relevant dose-descriptor	NOAEL: 100 mg/kg bw/d	NOAEL for urinalysis and reprotoxicity in rats given IBOA by oral gavage in OECD 422 protocol
Step 2) Modification of starting point	1	Default oral to dermal extrapolation (ECHA R.8, 2012), in line with consideration on physico-chemical properities and related adsorption potential according to according to ECHA R.7c (2017).
NAEL worker	100 mg/kg bw/d
Step 3) Assessment factors
Interspecies	4	Allometric scaling rat to humans (ECHA R.8, 2012)
Intraspecies	3	Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 3 is sufficiently conservative. (ECETOC, 2010)
Exposure duration	6	Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)
Dose response	1	The NOAEL is reliable. No adjustment is required.
Quality of database	1	The key studies were of high quality, being rated K1 or K2. No adjustment is required.
Remaining uncertainties	1	No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.
DNEL
Based upon a NOAEL of 100 mg/kg bw/d for rats in an OECD 422 screening study after oral administration	1.39 mg/kg bw/d		Using a total factor (POD modifier and AF) of 72 (1 x 4 x 3 x 6 x 1 x 1) a DNELlong-term, dermal, workerof 1.39 mg/kg bw/d is derived.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.45 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH guidance R.8, 2012 and ECETOC, 2010

Overall assessment factor (AF):

69

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

43.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Default correction for breathing volume and route-to-route extrapolation according to ECHA R.8, 2012

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required.

AF for differences in duration of exposure:

5

Justification:

Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Acrylates are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF for remaining differences is justified.

AF for intraspecies differences:

5

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)

AF for the quality of the whole database:

1

Justification:

The key studies were of high quality, being rated K1 or K2. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.

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:

0.83 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH guidance R.8, 2012 and ECETOC, 2010

Overall assessment factor (AF):

120

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Default oral to dermal extrapolation with a factor of 1 (ECHA R.8, 2012), in line with consideration on physico-chemical properities and related adsorption potential according to according to ECHA R.7c (2017).

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required

AF for differences in duration of exposure:

6

Justification:

Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling rat to humans (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Acrylates are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.

AF for intraspecies differences:

5

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)

AF for the quality of the whole database:

1

Justification:

The key studies were of high quality, being rated K1 or K2. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.83 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH guidance R.8, 2012 and ECETOC, 2010

Overall assessment factor (AF):

120

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

oral study; no adjustment is necessary

AF for dose response relationship:

1

Justification:

The NOAEL is reliable. No adjustment is required

AF for differences in duration of exposure:

6

Justification:

Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling rat to humans (ECHA R.8, 2012)

AF for other interspecies differences:

1

Justification:

Acrylates are metabolised via general metabolic pathways that are common and very similar to rodents and humans and the absence of any specific target organs indicating a specific MOA at high concentrations there is no reason to believe that an additional AF of 2.5 for remaining differences is justified.

AF for intraspecies differences:

5

Justification:

Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)

AF for the quality of the whole database:

1

Justification:

The key studies were of high quality, being rated K1 or K2. No adjustment is required.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.

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

Sytemic effects, long term

Calculation from the oral repeated dose/ repro screening study (OECD 422) study with IBOA in rats

DNEL inhal gen pop long-term

Description	Value/ factor	Remark
Step 1) Relevant dose-descriptor	NOAEL:100 mg/kg bw/d	NOAEL for urinalysis and reprotoxicity in rats given IBOA by oral gavage in OECD 422 protocol
Step 2) Modification of starting point	1.15 m³/kg	Correction for rat standard breathing volume, 24 hrs (ECHA R.8, 2012)
Route-to-Route extrapolation	2	Oral to inhalation extrapolation (ECHA R.8, 2012) This is considered as very conservative approach as the low vapour pressure indicates a comparably low absorption potential when compared to oral administration (according to ECHA R.7c, 2017)
NAEC general population	43.5 mg/m^3
Step 3) Assessment factors
Interspecies	1	No allometric scaling rat to humans as intraspecies adjustment is accounted for in relative breathing volumes (ECHA R.8, 2012)
Intraspecies	5	Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)
Exposure duration	6	Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)
Dose response	1	The NOAEL is reliable. No adjustment is required.
Quality of database	1	The key studies were of high quality, being rated K1 or K2. No adjustment is required.
Remaining uncertainties	1	No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.
DNEL
Based upon a NOAEL of 100 mg/kg bw/d for rats in an OECD 422 screening study after oral administration	1.45 mg/m^3		Using a total factor (POD modifier and AF) of 69 (/ 1.15 m³ x 2 x 1 x 5 x 6 x 1 x 1 x 1) a DNELlong-term,inhal, gen. pop.of 1.45 mg/m³ is derived.

 

                               

 

 

DNEL dermal general population long-term

Description	Value/ factor	Remark
Step 1) Relevant dose-descriptor	NOAEL:100 mg/kg bw/d	NOAEL for urinalysis and reprotoxicity in rats given IBOA by oral gavage in OECD 422 protocol
Step 2) Modification of starting point	1	Default oral to dermal extrapolation (ECHA R.8, 2012), in line with consideration on physico-chemical properities and related adsorption potential according to according to ECHA R.7c (2017).
NAEL general population	100 mg/kg bw/d
Step 3) Assessment factors
Interspecies	4	Allometric scaling rat to humans (ECHA R.8, 2012)
Intraspecies	5	Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)
Exposure duration	6	Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)
Dose response	1	The NOAEL is reliable. No adjustment is required.
Quality of database	1	The key studies were of high quality, being rated K1 or K2. No adjustment is required.
Remaining uncertainties	1	No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.
DNEL
Based upon a NOAEL of 100 mg/kg bw/d for rats in an OECD 422 screening study after oral administration	0.83 mg/kg bw/d		Using a total factor (POD modifier and AF) of 120 (1 x 4 x 5 x 6 x 1 x 1) a DNELlong-term,dermal, gen.pop.of 0.83 mg/kg bw/d is derived.

 

DNEL oral general population long-term

Description	Value/ factor	Remark
Step 1) Relevant dose-descriptor	NOAEL:100 mg/kg bw/d	NOAEL for urinalysis and reprotoxicity in rats given IBOA by oral gavage in OECD 422 protocol
Step 2) Modification of starting point	1	No route-to-route extrapolation required.
NAEL general population	100 mg/kg bw/d
Step 3) Assessment factors
Interspecies	4	Allometric scaling rat to humans (ECHA R.8, 2012)
Intraspecies	5	Known mode of action involving ubiquitous and non-specific enzyme systems (carboxylesterases) makes a lower variability likely, hence the AF of 5 is sufficiently conservative. (ECETOC, 2010)
Exposure duration	6	Default AF 6 for extrapolation from sub-acute to chronic (ECHA 2012)
Dose response	1	The NOAEL is reliable. No adjustment is required.
Quality of database	1	The key studies were of high quality, being rated K1 or K2. No adjustment is required.
Remaining uncertainties	1	No remaining uncertainities. Long-term toxicity data from the metabolites and metabolite donors substances support the conclusion on this hazard level which is based on a screening study.
DNEL
Based upon a NOAEL of 100 mg/kg bw/d for rats in an OECD 422 screening study after oral administration	0.83 mg/kg bw/d		Using a total factor (POD modifier and AF) of 120 (1 x 4 x 5 x 6 x 1 x 1) a DNELlong-term,dermal, gen.pop.of 0.83 mg/kg bw/d is derived.