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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
127 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC technical report No. 86
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Derivation of DNEL-workers

 

Hazard via inhalation route

Hazard assessment of titanium tetrabutanolate is based on the most hazardous degradation product, n-butanol, since the target substance reacts in use applications and no reliable study is available from the substance itself.

 

NOAEC from rat subchronic inhalation study of n-butyl acetate, metabolic precursor of n-butanol, is used to derive DNEL.

 

Relevant dose descriptor for the endpoint

NOAEC = 1 520 mg/m3for n-butyl acetate; subchronic, inhalation, rat by David, R.M. (2001).

 

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 1.

Route of exposure (inhalation vs inhalation); bioavailability is assumed to be 100% in humans and in experimental animals

Corrected inhalatory NOAEC = inhalatory NOAEC * exp. time rat / exp. time worker * ABS rat / ABS human * sRVhuman 8h / wRV

ABS - absorption

sRVhuman - respiratory volume under standard conditions

wRV - respiratory volume light activity for worker

 

Corrected inhalatory NOAEC= 1 520 mg/m3* (6h/d / 8h/d) * (100/100) * (6,7m3/10m3) =764 mg/m3

Assessment factors – Based on ECETOC technical report No. 86

Intraspecies differences for workers                                    3

Exposure duration - subchronic to chronic                         2

Overall AF                                                                        3*2 = 6 

DNEL worker systemic effects by inhalation= 764 mg/m3 / 6 = 127 mg/

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
152 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC technical report No. 86
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
37.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report No. 86
Explanation for the modification of the dose descriptor starting point:
NOAEL from rat subchronic oral study of n-butanol is used to derive DNEL since no dermal study is available from the substance.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
3.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report No. 86
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Derivation of DNEL-general population

 

Hazard via inhalation route

Hazard assessment of titanium tetrabutanolate is based on the most hazardous degradation product, n-butanol, since the target substance reacts in use applications and no reliable study is available from the substance itself.

 

NOAEC from rat subchronic inhalation study of n-butyl acetate, metabolic precursor of n-butanol, is used to derive DNEL.

 

Relevant dose descriptor for the endpoint

NOAEC = 1 520 mg/m3for n-butyl acetate; subchronic, inhalation, rat by David, R.M. (2001).

 

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 1.

Route of exposure (inhalation vs inhalation); bioavailability is assumed to be 100% in humans and in experimental animals and exposure time 6 hours/day for rats and for general population.

Corrected inhalatory NOAEC= inhalatory NOAEC * exp. timerat/ exp. timegeneral population* ABSrat/ ABShuman

ABS - absorption

 

Corrected inhalatory NOAEC= 1 520 mg/m3* (6 h/d / 6 h/d) * (100 / 100) = 1 520 mg/m3

Assessment factors – Based on ECETOC technical report No. 86

Intraspecies differences – general population = 5

Exposure duration - subchronic to chronic = 2

Overall AF = 5*2 = 10 

 

DNEL general population systemic effects by inhalation= 1 520 mg/m3/ 10 = 152 mg/m3

Hazard via oral route

Hazard assessment of titanium tetrabutanolate is based on the most hazardous degradation product, n-butanol, since the target substance reacts in use applications and no reliable study is available from the substance itself.

NOAEL from rat subchronic oral study of n-butanol is used to derive DNEL.

Relevant dose descriptor for the endpoint

NOAEL = 150 mg/kg bw/day for n-butanol; subchronic, oral gavage, rat by Tompkins, C.E. (1995).

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012) Example B. 2.

100% oral absorption regardless of species

Corrected oral NOAEL = oral NOAEL * (ABSrat / ABShuman)

Corrected oral NOAEL = 150 * (100/100)

Corrected oral NOAEL = 150 mg/kg bw/day

Assessment factors – Based on ECETOC technical report No. 86

Allometric scaling - rat                                    4

Intraspecies differences - general population   5

Exposure duration - subchronic to chronic       2

Overall AF                                 4 * 5 * 2 = 40

DNEL general population by oral route = 150 mg/kg bw/day / 40 = 3.75 mg/kg bw/day

Hazard via dermal route

Hazard assessment of titanium tetrabutanolate is based on the most hazardous degradation product, n-butanol, since the target substance reacts in the use applications and no dermal study is available from the substance itself.

NOAEL from rat subchronic oral study of n-butanol is used to derive DNEL.

 

Relevant dose descriptor for the endpoint

NOAEL = 150 mg/kg bw/day for n-butanol; subchronic, oral gavage, rat by Tompkins, C.E. (1995).

Modification of the dose descriptor according to ECHA Guidance R.8 (November 2012). Example B. 5

100% oral absorption regardless of species

10% dermal absorption regardless of species

 

Corrected dermal NOAEL = oral NOAEL * (ABSoral-rat / ABSdermal-human)

Corrected dermal NOAEL = 150 mg/kg bw/day * (100/10)

Corrected dermal NOAEL = 1 500 mg/kg bw/day

 

Assessment factors – Based on ECETOC technical report No. 86

Allometric scaling -rat                                       4

Intraspecies differences - general population    5

Exposure duration - subchronic to chronic        2

Overall AF                                    4 * 5 * 2 = 40 

 

DNEL general population by dermal route = 1 500 mg/kg bw/day / 40 = 37.5 mg/kg bw/day