Registration Dossier
Registration Dossier
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EC number: 246-690-9 | CAS number: 25167-70-8
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 14.7 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA, 2010; ECETOC, 2003, 2010
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 264.5 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- The rat oral rat NOAEL was converted into a corrected inhalation NOAEC according to ECHA guidance (Chapter R.8: Characterisation of dose [concentration]-response for human health, Figure R. 8-3)
- Justification:
- No toxicologically relevant findings when tested up to a limit dose of 1000 mg/kg bw/d
- Justification:
- Default assessment factor for sub-acute to chronic extrapolation (ECHA guidance, Chapter R. 8)
- Justification:
- Default assessment factor for the inhalation route (ECHA guidance, Chapter R. 8)
- 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).
- Justification:
- There are no data to quantify variability in susceptibility to the effects of exposure to 2,4,4-trimethylpentene 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.
- Justification:
- No issues regarding quality of whole database
- Justification:
- No remaining uncertainties present
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:
- 2.1 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA, 2010; ECETOC, 2003, 2010
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The rat oral rat NOAEL was converted into a corrected dermal NOAEL after correcting for differences in uptake between the two routes of exposure.
- Justification:
- No toxicologically relevant findings when tested up to an oral limit dose of 1000 mg/kg bw/d
- Justification:
- Default assessment factor for sub-acute to chronic extrapolation (ECHA guidance, Chapter R. 8)
- Justification:
- Default assessment factor for allometric scaling in the rat (ECHA guidance, Chapter R. 8)
- 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).
- Justification:
- There are no data to quantify variability in susceptibility to the effects of exposure to 2,4,4-trimethylpentene 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.
- Justification:
- No issues regarding quality of whole database
- Justification:
- No remaining uncertainties present
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
Acute toxicity
ECHA Guidance R.8 (Chapter R.8.1.2.5) indicates that DNELs for acute toxicity are not necessary if no acute toxicity hazard leading to classification has been identified. Animal data for 2,4,4-trimethylpentene demonstrate that the acute oral (HLS, 1996a) and dermal (HLS, 1996b) LD50 values are greater than 2000 mg/kg bw, while the inhalation LC50 (WIL Research Laboratories, 2006a) is in excess of 19,171 mg/m3, the highest vapour concentration tested. No acute DNELs will therefore be derived for these routes of exposure.
Other information suggests that 2,4,4-trimethylpentane may cause transient CNS depression after ingestion, while a low kinematic viscosity (0.611 mm2/s at 40 degrees C) is consistent with a potential to damage the lungs if swallowed, with classification triggered in both instances. Qualitative risk characterisation will be conducted to address these endpoints as neither is suited to derivation of a quantitative DNEL.
Irritation/Sensitisation
2,4,4-Trimethylpentene is not irritating to skin (HLS, 1996c; WIL Research Laboratories, 2005a) or eye (HLS, 1996d; WIL Research Laboratories, 2005b), nor does it induce or elicit sensitisation after skin contact (HLS, 1997a). No quantitative DNELs or qualitative risk characterisation are therefore necessary for these endpoints.
Repeated dose toxicity
Results from oral sub-acute repeated dose toxicity testing of 2,4,4-trimethylpentene according to OECD Guideline 407 demonstrate no adverse systemic effects following gavage administration at 300 mg/kg bw/d for up to 28 days; higher treatments (1000 mg/kg bw/d) were associated with increased liver and kidney weights, however no accompanying histopathological alterations were present (HLS, 1997b). Findings of alpha-2u-globulin nephropathy described in other studies (HLS, 1997c; Swenberg and Schoonhoven, 2004) are not relevant to human risk assessment or to the derivation of long-term DNELs.
Further results from a 90 -day repeated-dose toxicity also indicated that increased liver and kidney weights were present at 300 and 1000 mg/kg bw/d, with corresponding histopathological changes including hepatocellular hypertrophy (liver) and alpha 2u-globulin nephropathy (in males only; confirmed with immunohistochemical staining). As above, these are not relevant to human risk assessment and the derivation of long-term DNELs (CRL 2022a).
Genetic toxicity
Adequate information exists to characterise the genetic toxicity of 2,4,4-trimethylpentene. Results of bacterial mutation assays (HLS, 1996e; BioReliance, 2005) demonstrate an absence of mutagenic potential towards strains of Salmonella typhimurium when tested in the absence or presence of exogenous metabolic activation, while no evidence of clastogenicity was found in vitro after treatment of human lymphocytes (HLS, 1997d) or CHO cells (BioReliance, 2006) in the absence and in the presence of S9 fraction. No increase in micronucleated polychromatic erythrocytes was found in rats following a single 4-hr exposure to 19,171 mg/m3 2,4,4-trimethylpentene (WIL Research Laboratories, 2006a) ).
Reproductive / developmental toxicity
Results from an OECD 421 screening study, and from OECD 414 prenatal developmental toxicity studies in both rats and rabbits, showed no adverse effects on reproductive or developmental performance (HLS, 1997c; CRL 2022b, CRL 2022c).
Mode of Action Considerations
For studies relevant to the setting of DNELs, a threshold mode of action was assumed.
Modification of Relevant Dose Descriptors to the Correct Starting Point
Relevant dose descriptors were developed for the different routes of exposure (see Guidance Document, Chapter R.8, Appendix R.8-2). In the absence of information on the extent of absorption of 2,4,4-trimethylpentene, uptake by the oral, dermal and inhalation routes has been assumed to be 50%, 100% and 100%, respectively (see Guidance Document, Chapter R.8, R.8.4.2b). The values are provided below.
Dermal route:
The corrected dermal NOAEL is:
dermal NOAEL = oral NOAEL * (ABSoral-rat/ABSderm-human)
dermal NOAEL = 300 * (50/100)
dermal NOAEL = 150 mg/kg/d
Thus, the corrected dose descriptor for dermal route is 150 mg/kg/day.
Inhalation route:
To convert oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3for an 8-h exposure period).
The corrected inhalation NOAEC for workers is:
inhalatory NOAEC = oral NOAEL * (1/ sRV rat 8h) * (ABS oral / ABS inh) * (sRV human / wRV)
inhalatory NOAEC= 300 * (1/0.38) * (50/100) * (6.7 / 10)
inhalatory NOAEC = 264.5 mg/m3
Thus, the corrected dose descriptor for inhalation is 264.5 mg/m3 for workers.
Application of Assessment Factors to the Corrected Dose Descriptors
Endpoint-specific DNEL values were derived from the corrected dose descriptors after application of assessment factors (AF). The AFs were based on the procedures described by the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC 2003; 2010).
ECETOC (2003). Derivation of Assessment Factors for Human Health Risk Assessment, Technical Report 86, Brussels, February 2003.
ECETOC (2010). Guidance on assessment factors to derive a DNEL. Technical report No. 110, ECETOC, Brussels, October 2010
Long-term DNEL Assessment Factors (Dermal) |
||
Assessment Factor |
Worker |
|
Differences in metabolic rate per b. w. (allometric scaling) |
4 (rat) |
|
Interspecies remaining differences (toxicodynamic and toxicokinetic) |
1 |
|
Intraspecies differences |
3 |
|
Duration extrapolation (sub-acute/sub-chronic/chronic) |
6 (sub-chronic) |
|
Issues related to dose-response |
1 |
|
Quality of whole database |
1 |
|
Overall AF |
72 |
|
Long-term DNEL Assessment Factors (Inhalation) |
||
Assessment Factor |
Worker |
|
Differences in metabolic rate per b. w. (allometric scaling) |
- |
|
Interspecies remaining differences (toxicodynamic and toxicokinetic) |
1 |
|
Intraspecies differences |
3 |
|
Duration extrapolation (sub-acute/sub-chronic/chronic) |
6 (sub-chronic) |
|
Issues related to dose-response |
1 |
|
Quality of whole database |
1 |
|
Overall AF |
18 |
|
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.4 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA, 2010; ECETOC, 2003, 2010
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 130.4 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- The rat oral rat NOAEL was converted into a corrected inhalation NOAEC according to ECHA guidance (Chapter R.8: Characterisation of dose [concentration]-response for human health, Figure R. 8-3)
- Justification:
- No toxicologically relevant findings when tested up to a limit dose of 1000 mg/kg bw/d
- Justification:
- Default assessment factor for sub-acute to chronic extrapolation (ECHA guidance, Chapter R. 8)
- Justification:
- Default assessment factor for the inhalation route (ECHA guidance, Chapter R. 8)
- 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).
- Justification:
- There are no data to quantify variability in susceptibility to the effects of exposure to 2,4,4-trimethylpentene 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.
- Justification:
- No issues regarding quality of whole database
- Justification:
- No remaining uncertainties present
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:
- 1.2 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA, 2010; ECETOC, 2003, 2010
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 150 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- The rat oral rat NOAEL was converted into a corrected dermal NOAEL after correcting for differences in uptake between the two routes of exposure
- Justification:
- No toxicologically relevant findings when tested up to a limit dose of 1000 mg/kg bw/d
- Justification:
- Default assessment factor for sub-acute to chronic extrapolation (ECHA guidance, Chapter R. 8)
- Justification:
- Default assessment factor for allometric scaling in the rat (ECHA guidance, Chapter R. 8)
- 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).
- Justification:
- There are no data to quantify variability in susceptibility to the effects of exposure to 2,4,4-trimethylpentene 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.
- Justification:
- No issues regarding quality of whole database
- Justification:
- No remaining uncertainties present
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:
- 2.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA, 2010; ECETOC, 2003, 2010
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- None applied
- Justification:
- No toxicologically relevant findings when tested up to a limit dose of 1000 mg/kg bw/d
- Justification:
- Default assessment factor for sub-acute to chronic extrapolation (ECHA guidance, Chapter R. 8)
- Justification:
- Default assessment factor for allometric scaling in the rat (ECHA guidance, Chapter R. 8)
- 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).
- Justification:
- There are no data to quantify variability in susceptibility to the effects of exposure to 2,4,4-trimethylpentene 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.
- Justification:
- No issues regarding quality of whole database
- Justification:
- No remaining uncertainties present
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
Acute toxicity
ECHA Guidance R.8 (Chapter R.8.1.2.5) indicates that DNELs for acute toxicity are not necessary if no acute toxicity hazard leading to classification has been identified. Animal data for 2,4,4-trimethylpentene demonstrate that the acute oral (HLS, 1996a) and dermal (HLS, 1996b) LD50 values are greater than 2000 mg/kg bw, while the inhalation LC50 (WIL Research Laboratories, 2006a) is in excess of 19,171 mg/m3, the highest vapour concentration tested. No acute DNELs will therefore be derived for these routes of exposure.
Other information suggests that 2,4,4-trimethylpentane may cause transient CNS depression after ingestion, while a low kinematic viscosity (0.611 mm2/s at 40 degrees C) is consistent with a potential to damage the lungs if swallowed, with classification triggered in both instances. Qualitative risk characterisation will be conducted to address these endpoints as neither is suited to derivation of a quantitative DNEL.
Irritation/Sensitisation
2,4,4-Trimethylpentene is not irritating to skin (HLS, 1996c; WIL Research Laboratories, 2005a) or eye (HLS, 1996d; WIL Research Laboratories, 2005b), nor does it induce or elicit sensitisation after skin contact (HLS, 1997a). No quantitative DNELs or qualitative risk characterisation are therefore necessary for these endpoints.
Repeated dose toxicity
Results from oral sub-acute repeated dose toxicity testing of 2,4,4-trimethylpentene according to OECD Guideline 407 demonstrate no adverse systemic effects following gavage administration at 300 mg/kg bw/d for up to 28 days; higher treatments (1000 mg/kg bw/d) were associated with increased liver and kidney weights, however no accompanying histopathological alterations were present (HLS, 1997b). Findings of alpha-2u-globulin nephropathy described in other studies (HLS, 1997c; Swenberg and Schoonhoven, 2004) are not relevant to human risk assessment or to the derivation of long-term DNELs.
Further results from a 90 -day repeated-dose toxicity also indicated that increased liver and kidney weights were present at 300 and 1000 mg/kg bw/d, with corresponding histopathological changes including hepatocellular hypertrophy (liver) and alpha 2u-globulin nephropathy (in males only; confirmed with immunohistochemical staining). As above, these are not relevant to human risk assessment and the derivation of long-term DNELs (CRL 2022a).
Genetic toxicity
Adequate information exists to characterise the genetic toxicity of 2,4,4-trimethylpentene. Results of bacterial mutation assays (HLS, 1996e; BioReliance, 2005) demonstrate an absence of mutagenic potential towards strains of Salmonella typhimurium when tested in the absence or presence of exogenous metabolic activation, while no evidence of clastogenicity was found in vitro after treatment of human lymphocytes (HLS, 1997d) or CHO cells (BioReliance, 2006) in the absence and in the presence of S9 fraction. No increase in micronucleated polychromatic erythrocytes was found in rats following a single 4-hr exposure to 19,171 mg/m3 2,4,4-trimethylpentene (WIL Research Laboratories, 2006a) ).
Reproductive / developmental toxicity
Results from an OECD 421 screening study, and from OECD 414 prenatal developmental toxicity studies in both rats and rabbits, showed no adverse effects on reproductive or developmental performance (HLS, 1997c; CRL 2022b, CRL 2022c).
Mode of Action Considerations
For studies relevant to the setting of DNELs, a threshold mode of action was assumed.
Modification of Relevant Dose Descriptors to the Correct Starting Point
Relevant dose descriptors were developed for the different routes of exposure (see Guidance Document, Chapter R.8, Appendix R.8-2). In the absence of information on the extent of absorption of 2,4,4-trimethylpentene, uptake by the oral, dermal and inhalation routes has been assumed to be 50%, 100% and 100%, respectively (see Guidance Document, Chapter R.8, R.8.4.2b). The values are provided below.
Dermal route:
The corrected dermal NOAEL is:
dermal NOAEL = oral NOAEL * (ABSoral-rat/ABSderm-human)
dermal NOAEL = 300 * (50/100)
dermal NOAEL = 150 mg/kg/d
Thus, the corrected dose descriptor for dermal route is 150 mg/kg/day.
Inhalation route:
To convert oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24 h). The corrected inhalation NOAEC for general population is:
inhalatory NOAEC = oral NOAEL * (1/ sRV rat 24h) * (ABS oral / ABS inh)
inhalatory NOAEC= 300 * (1/1.15) * (50/100)
inhalatory NOAEC = 130.4 mg/m3
Thus, the corrected dose descriptor for inhalation is 130.4 mg/m3 for general population.
Application of Assessment Factors to the Corrected Dose Descriptors
Endpoint-specific DNEL values were derived from the corrected dose descriptors after application of assessment factors (AF). The AFs were based on the procedures described by the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC 2003; 2010).
ECETOC (2003). Derivation of Assessment Factors for Human Health Risk Assessment, Technical Report 86, Brussels, February 2003.
ECETOC (2010). Guidance on assessment factors to derive a DNEL. Technical report No. 110, ECETOC, Brussels, October 2010.
Long-term DNEL Assessment Factors (Oral) |
||
Assessment Factor |
General Population |
|
Differences in metabolic rate per b. w. (allometric scaling) |
4 (rat) |
|
Interspecies remaining differences (toxicodynamic and toxicokinetic) |
1 |
|
Intraspecies differences |
5 |
|
Duration extrapolation (sub-acute/sub-chronic/chronic) |
6 (sub-chronic) |
|
Issues related to dose-response |
1 |
|
Quality of whole database |
1 |
|
Overall AF |
120 |
|
Long-term DNEL Assessment Factors (Dermal) |
||
Assessment Factor |
General Population |
|
Differences in metabolic rate per b. w. (allometric scaling) |
4 (rat) |
|
Interspecies remaining differences (toxicodynamic and toxicokinetic) |
1 |
|
Intraspecies differences |
5 |
|
Duration extrapolation (sub-acute/sub-chronic/chronic) |
6 (sub-chronic) |
|
Issues related to dose-response |
1 |
|
Quality of whole database |
1 |
|
Overall AF |
120 |
|
Long-term DNEL Assessment Factors (Inhalation) |
||
Assessment Factor |
General Population |
|
Differences in metabolic rate per b. w. (allometric scaling) |
- |
|
Interspecies remaining differences (toxicodynamic and toxicokinetic) |
1 |
|
Intraspecies differences |
5 |
|
Duration extrapolation (sub-acute/sub-chronic/chronic) |
6 (sub-chronic) |
|
Issues related to dose-response |
1 |
|
Quality of whole database |
1 |
|
Overall AF |
30 |
|
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