Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - 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
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Additional information - workers

No DNELs for acute dermal and inhalation exposure have been derived for TPnB-highers as this substance is not classified for acute toxicity by the dermal and inhalation route. TPnB-highers did not show any adverse effects regarding sensitisation, mutagenicity or reproductive toxicity. Therefore, no DNELs have been derived for these endpoints. No DNELs have been derived for local effects as no quantitative assessment is possible due to the lack of dose-response data for skin and eye irritation.

Worker-DNEL long-term for the inhalation route

TPnB-highers has a very low vapour pressure (< 0.01 mbar at 20°C) and has a boiling point of 306°C. Therefore, it is highly unlikely that exposure of workers occurs via the inhalation route. Aerosol formation could be possible under conditions of elevated temperature. No vapour or aerosol inhalation toxicity studies have been conducted with TPnB-highers. Therefore, the NOAEL of 100 mg/kg bw/day from the OECD 422 oral gavage study in rats has been used as the critical dose descriptor to derive the DNEL for inhalation exposure. The systemic NOAEL has been converted into an inhalation concentration of 88.2 mg/m3. A total assessment factor of 30, based on theintra-species factor of 5 and a factor of 6 to correct for the duration of the study (according to the ECHA Guidance Document, Chapter R.8), has been applied to derive a DNEL long-term for the inhalation route of exposure of 2.9 mg/m3. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorfet al 2010) which indicates that no additional factor for remaining differences is justified.

Worker-DNEL long-term for the dermal route

No repeated dose toxicity study for the dermal route is available for TPnB-highers. An OECD 422 study in rats with oral gavage administration of the test material is available.The dose levels used are 20, 100 and 500 mg/kg/day.Treatment-related effects were observed in males and females in the 500 mg/kg/day dose group including transient clinical observations, higher liver weights, and liver and thyroid gland hypertrophy. There was no treatment-related toxicity in the 100 and 20 mg/kg/day dose groups and no indication of neurological toxicity at any dose level. Based upon these results, the no-observed-effect level (NOEL) for general toxicity was 100 mg/kg/day. A total assessment factor of 120, based on the allometric factor of 4, the intra-species factor of 5 and a factor of 6 to correct for exposure duration (according to the ECHA Guidance Document, Chapter R.8), has been applied to derive a DNEL long-term for the dermal route of exposure of 0.83 mg/kg bw/day. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorf et al 2010) which indicates that no additional factor for remaining differences is justified.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Additional information - General Population

No DNELs for acute dermal and inhalation exposure have been derived for TPnB-highers as this substance is not classified for acute toxicity by the dermal and inhalation route. TPnB-highers did not show any adverse effects regarding sensitisation, mutagenicity or reproductive toxicity. Therefore, no DNELs have been derived for these endpoints. No DNELs have been derived for local effects as no quantitative assessment is possible due to the lack of dose-response data for skin and eye irritation.

General population-DNEL short-term for oral route

The only endpoint assessed in the acute oral toxicity study is mortality and only limited information on sub-lethal effects can be retrieved from that study. The relevant dose descriptor via the oral route is the NOAEL of 100 mg/kg bw/day from the OECD 422 oral gavage study in rats. A total assessment factor of 40, based on the allometric factor of 4 and the intra-species factor of 10 (according to the ECHA Guidance Document, Chapter R.8), has been applied to derive a DNEL short-term for the oral route of exposure of 2.5 mg/kg bw/day. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorf et al 2010) which indicates that no additional factor for remaining differences is justified.

General population-DNEL long-term for inhalation route

TPnB-highers has a very low vapour pressure (< 0.01 mbar at 20°C) and has a boiling point of 306°C. Therefore, it is highly unlikely that exposure of consumers occurs via the inhalation route. Aerosol formation could be possible under conditions of elevated temperature. However, no uses of TPnB-highers under these conditions are known to us. No vapour or aerosol inhalation toxicity studies have been conducted with TPnB-highers and no DNEL for the inhalation route has been derived as inhalation exposure to TPnB-highers is unlikely.

General population-DNEL long-term for dermal route

No repeated dose toxicity study for the dermal route is available for TPnB-highers. An OECD 422 study in rats with oral gavage administration of the test material is available.The dose levels used are 20, 100 and 500 mg/kg/day.Treatment-related effects were observed in males and females in the 500 mg/kg/day dose group including transient clinical observations, higher liver weights, and liver and thyroid gland hypertrophy. There was no treatment-related toxicity in the 100 and 20 mg/kg/day dose groups and no indication of neurological toxicity at any dose level. Based upon these results, the no-observed-effect level (NOEL) for general toxicity was 100 mg/kg/day. A total assessment factor of 240, based on the allometric factor of 4, the intra-species factor of 10 and a factor of 6 to correct for exposure duration (according to the ECHA Guidance Document, Chapter R.8), has been applied to derive a DNEL long-term for the dermal route of exposure of 0.42 mg/kg bw/day. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorf et al 2010) which indicates that no additional factor for remaining differences is justified.

General population-DNEL long-term for oral route

The relevant dose descriptor for long-term exposure via the oral route is the NOAEL of 100 mg/kg bw/day from the OECD 422 oral gavage study in rats.A total assessment factor of 240, based on the allometric factor of 4, the intra-species factor of 10 and a factor of 6 to correct for exposure duration (according to the ECHA Guidance Document, Chapter R.8), has been applied to derive a DNEL long-term for the oral route of exposure of 0.42 mg/kg bw/day. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorf et al 2010) which indicates that no additional factor for remaining differences is justified.