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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.31 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Value:
27.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
not applicable, based on 90 day subchronic inhalation study in mouse and rat
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Default for subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route if derived from an inhalation study (R8)
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
3
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However the population exposed in the workplace is highly homogeneous and the health of the work force is typically good (healthy worker effect) while metabolic differences due to genetic polymorphisms do not automatically require an increased assessment factor since compensating mechanisms (including alternative pathways of elimination) are often present (ECETOC, 2003, 2010). Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 3 (i.e. the 90th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within workers.
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:
DNEL (Derived No Effect Level)
Value:
2.31 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
6
Dose descriptor:
NOAEC
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
default for subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not necessary for the inhalation route if derived from an inhalation study (R8)
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
3
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However the population exposed in the workplace is highly homogeneous and the health of the work force is typically good (healthy worker effect) while metabolic differences due to genetic polymorphisms do not automatically require an increased assessment factor since compensating mechanisms (including alternative pathways of elimination) are often present (ECETOC, 2003, 2010). Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 3 (i.e. the 90th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within workers.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
160.23 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
3
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not necessary for the inhalation route if derived from an inhalation study (R8)
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
3
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However the population exposed in the workplace is highly homogeneous and the health of the work force is typically good (healthy worker effect) while metabolic differences due to genetic polymorphisms do not automatically require an increased assessment factor since compensating mechanisms (including alternative pathways of elimination) are often present (ECETOC, 2003, 2010). Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 3 (i.e. the 90th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within workers.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.95 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEL
Value:
5.69 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no study by dermal route available, data derived from a well-conducted subchronic 90 day inhalation study in mouse and rat
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
default for subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not necessary since the DNEL is derived from the 90 day mouse inhalation study NOAEC (27.6 mg/m3) (R8)
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
3
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However the population exposed in the workplace is highly homogeneous and the health of the work force is typically good (healthy worker effect) while metabolic differences due to genetic polymorphisms do not automatically require an increased assessment factor since compensating mechanisms (including alternative pathways of elimination) are often present (ECETOC, 2003, 2010). Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 3 (i.e. the 90th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within workers.
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:
low hazard (no threshold derived)

Additional information - workers

For justifications see CSR Section 5.11.2

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.69 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
27.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
not applicable, based on 90 day subchronic inhalation study in mouse and rat
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
default for subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not necessary for the inhalation route if derived from an inhalation study (R8)
AF for other interspecies differences:
1
Justification:
an analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However an analysis of assessment factors conducted by ECETOC (2003, 2010) showed that metabolic differences due to genetic polymorphisms do not to automatically require an increased assessment factor since alternative pathways of elimination are often present. Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 5 (i.e. the 95th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within the general population.
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:
DNEL (Derived No Effect Level)
Value:
0.69 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
default for subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not necessary for the inhalation route if derived from an inhalation study (R8)
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However an analysis of assessment factors conducted by ECETOC (2003, 2010) showed that metabolic differences due to genetic polymorphisms do not to automatically require an increased assessment factor since alternative pathways of elimination are often present. Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 5 (i.e. the 95th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within the general population.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
143.5 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not necessary for the inhalation route if derived from an inhalation study (R8)
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However an analysis of assessment factors conducted by ECETOC (2003, 2010) showed that metabolic differences due to genetic polymorphisms do not to automatically require an increased assessment factor since alternative pathways of elimination are often present. Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 5 (i.e. the 95th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within the general population.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Value:
2.83 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
data derived from well-conducted subchronic 90 day mouse inhl study
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
default for subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling is not necessary since the DNEL is derived from the 90 day mouse inhalation study NOAEC (27.6 mg/m3) (R8)
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However an analysis of assessment factors conducted by ECETOC (2003, 2010) showed that metabolic differences due to genetic polymorphisms do not to automatically require an increased assessment factor since alternative pathways of elimination are often present. Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 5 (i.e. the 95th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within the general population.
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:
0.03 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not applicable
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However an analysis of assessment factors conducted by ECETOC (2003, 2010) showed that metabolic differences due to genetic polymorphisms do not to automatically require an increased assessment factor since alternative pathways of elimination are often present. Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 5 (i.e. the 95th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within the general population.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25.6 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC, 2003; 2010
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
other: LD50
Value:
512 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not applicable
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
Justification:
An analysis of assessment factors conducted by ECETOC (2003, 2010) showed that a standard approach of applying a default AF for any remaining differences is not appropriate since, in the majority of cases, this is adequately covered by the inherent interdependence of the inter- and intra-species assessment factors and taken into account by allometric scaling (see, for instance, ECETOC analysis of information from Calabrese and Gilbert (1993) Reg. Tox. Pharmacol. 17: 44-51). Furthermore, data available for 3a,4,7,7a-tetrahydro-4,7-methanoindene, together with information available for chemically-related structures , do not raise concern for possible differences in effect within or between species. Overall, no factor for remaining differences will therefore be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify variability in susceptibility to the effects of exposure to 3a,4,7,7a-tetrahydro-4,7-methanoindene in the human population. However an analysis of assessment factors conducted by ECETOC (2003, 2010) showed that metabolic differences due to genetic polymorphisms do not to automatically require an increased assessment factor since alternative pathways of elimination are often present. Following a review of the distribution of variability in toxicokinetic and toxicodynamic parameters for populations of different ages, genders and disease states, ECETOC concluded that human data (Renwick and Lazarus (1998) Reg. Tox. Pharmacol. 27:3-20 ; Hattis et al. (1999) Risk Anal. 19: 421-431) support the use of an assessment factor of 5 (i.e. the 95th percentile of human toxicokinetic and toxicodynamic variability) to account for intra-species variability present within the general population.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

For justifications see CSR Section 5.11.2