Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
147 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
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:
42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
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

Where relevant data are available, local and systemic DNELs for worker exposure to TBHP have been developed based on assessment factors recommended by ECETOC (Derivation of Assessment Factors for Human Health Risk Assessment. Technical Report No. 86, pp 86, ECETOC, Brussels, February 2003).

Acute toxicity

A DNEL for acute toxicity should be derived if a hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. The TGD notes that such peaks are normally associated with inhalation exposure but are less common for skin contact and ingestion (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Appendix R.8-8). Results for acute oral and acute dermal toxicity both return LD50 values greater than 2000 mg/kg bwt (i.e. no classification required). With regard to inhalation expsoure, information available for a series of C9-C13 n-alkanes indicates that the acute (4 -hr) inhalation LC50 of NExBTL renewable diesel vapour (comprising predominately i-C16 to i-C18) will exceed 20 mg/l, with exposure to such concentrations unlikely given the low saturated vapour concentration of the components present.

The derivation of DNELs for acute toxicity is therefore not appropriate or necessary for NExBTL renewable diesel.

Irritation

Corrosive and irritant effects on the skin and eye are local, concentration-dependent phenomena. However results from GLP-compliant guideline tests conducted on NExBTL renewable diesel indicate it is not irritating to skin or eye, hence the derivation of DNELs for these endpoints is not appropriate or necessary.

Long-term systemic effects

The potential of NExBTL renewable diesel to cause long-term systemic effects can judged from results of repeated dose (neuro)toxicity and reproductive (2-generation) testing.

For NExBTL renewable diesel, the following NOAELs are presented in the IUCLID dossier:

sub-chronic effects: rat oral NOAEL = 1000 mg/kg bwt/day

reproductive effects: rat oral NOAEL = 1000 mg/kg bwt/day

developmental toxicity: rat oral = 1000 mg/kg bwt/day

Oral

No oral DNEL is required for Workers.

Dermal

Dose descriptor

A rat oral sub-chronic NOAEL of 1000 mg/kg bwt/d will be used with appropriate modification to derive a dermal DNEL for NExBTL renewable diesel.

Modification of dose descriptor

In the absence of information to the contrary it is assumed that oral uptake and dermal uptake are identical (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Section R.8.4.2, Ad2).

For workers, no modification of the NOAEL is required.

Assessment factors and DNELs

DNELworker-dermal = 1000 / 24 = 42 mg/kg bwt/d

Inhalation

Dose descriptor

A rat oral NOAEL of 1000 mg/kg bwt/d will be used with appropriate modification to derive an inhalation DNEL for NExBTL renewable diesel.

Modification of dose descriptor

In the absence of data to the contrary, it has been assumed that the extent of inhalation uptake of NExBTL renewable diesel is double that following oral exposure (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Section R.8.4.2, Ad2).

The corrected inhalatory NOAEC is calculated as follows:

NOAECinhalation = NOAELoral x 1/sRVrat x ABSoral-rat/ABSinh-human x sRVhuman/wRVhuman 1

= 1000 x 1/0.38 x 1/2 x 6.7/10

Corrected inhalation NOAECworker = 881 mg/m3

Assessment factors and DNELs

DNELworker-inhalation = 881 / 6 = 147 mg/m3

Long-term local effects

NExBTL renewable diesel was not irritating to skin or eye, nor were there any signs of gastric irritation following repeated oral (gavage) administration to rats at a dose of 1000 mg/kg bwt/d for 90 days. It is concluded, based on the available information, that NExBTL renewable diesel does not cause local (site of contact) toxicity.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
94 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
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:
18 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
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:
18 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
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

Where relevant data are available, local and systemic DNELs for worker exposure to TBHP have been developed based on assessment factors recommended by ECETOC (Derivation of Assessment Factors for Human Health Risk Assessment. Technical Report No. 86, pp 86, ECETOC, Brussels, February 2003).

Acute toxicity

A DNEL for acute toxicity should be derived if a hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. The TGD notes that such peaks are normally associated with inhalation exposure but are less common for skin contact and ingestion (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Appendix R.8-8). Results for acute oral and acute dermal toxicity both return LD50 values greater than 2000 mg/kg bwt (i.e. no classification required). With regard to inhalation expsoure, information available for a series of C9-C13 n-alkanes indicates that the acute (4 -hr) inhalation LC50 of NExBTL renewable diesel vapour (comprising predominately i-C16 to i-C18) will exceed 20 mg/l, with exposure to such concentrations unlikely given the low saturated vapour concentration of the components present.

Irritation

Corrosive and irritant effects on the skin and eye are local, concentration-dependent phenomena. However results from GLP-compliant guideline tests conducted on NExBTL renewable diesel indicate it is not irritating to skin or eye, hence the derivation of DNELs for these endpoints is not appropriate or necessary.

Long-term systemic effects

The potential of NExBTL renewable diesel to cause long-term systemic effects can judged from results of repeated dose (neuro)toxicity and reproductive (2-generation) testing.

For NExBTL renewable diesel, the following NOAELs are presented in the IUCLID dossier:

sub-chronic effects: rat oral NOAEL = 1000 mg/kg bwt/day

reproductive effects: rat oral NOAEL = 1000 mg/kg bwt/day

developmental toxicity: rat oral = 1000 mg/kg bwt/day

Oral

Dose descriptor

A rat oral NOAEL of 1000 mg/kg bwt/d will be used.

Modification of dose descriptor

In the absence of information to the contrary it is assumed that oral absorption of NExBTL renewable diesel by humans is identical to that in the rat and, therefore, no modification of the dose descriptor is required. However the dose descriptor will be adjusted to take into account a 7 d/wk exposure versus the 5 d/week treatment regime used in the sub-chronic toxicity test.

The modified dose descriptor is therefore 1000 x (5/7) = 714 mg/kg bwt/d

Assessment factors and DNELs

DNELgeneral population-oral = 714 / 40 = 18 mg/kg bwt/d

Dermal

Dose descriptor

A rat oral sub-chronic NOAEL of 1000 mg/kg bwt/d will be used with appropriate modification to derive a dermal DNEL for NExBTL renewable diesel.

Modification of dose descriptor

In the absence of information to the contrary it is assumed that oral uptake and dermal uptake are identical (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Section R.8.4.2, Ad2). However the dose descriptor must be adjusted to take into account a 7 d/wk exposure versus the 5 d/week treatment regime used in the sub-chronic toxicity test.

The modified dose descriptor for the general population is therefore:

1000 x (5/7) = 714 mg/kg bwt/d

Assessment factors and DNELs

DNELgeneral population-dermal = 714 / 40 = 18 mg/kg bwt/d

Inhalation

Dose descriptor

A rat oral NOAEL of 1000 mg/kg bwt/d will be used with appropriate modification to derive an inhalation DNEL for NExBTL renewable diesel.

Modification of dose descriptor

In the absence of data to the contrary, it has been assumed that the extent of inhalation uptake of NExBTL renewable diesel is double that following oral exposure (ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. Section R.8.4.2, Ad2).

The corrected inhalatory NOAEC is calculated as follows:

NOAECinhalation = NOAELoral x 1/sRVrat x ABSoral-rat/ABSinh-human

= 1000 x 1/0.38 x 1/2

Corrected inhalation NOAECgeneral population = 1316 mg/m3

The value is further modified for duration of exposure : 1316 x (5/7) = 940 mg/m3

Assessment factors and DNELs

DNELgeneral population-inhalation = 940 / 10 = 94 mg/m3

Long-term local effects

NExBTL renewable diesel was not irritating to skin or eye, nor were there any signs of gastric irritation following repeated oral (gavage) administration to rats at a dose of 1000 mg/kg bwt/d for 90 days. It is concluded, based on the available information, that NExBTL renewable diesel does not cause local (site of contact) toxicity.