Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
37 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
375 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
925 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL: 375 mg/kg bw/day in rats, subacute exposure duration.

NOAEC human (8h worker) = oral NOAEL rat x correction respiratory volume (worker) x correction for light activity (worker) x Abs oral-rat/ Abs inh-human x correction exposure conditions animal/huma

NOAEC human (8h worker) = 375 mg/kg bw/day x (1/0,38) x (6,7/10) x 100/100 x 7/5 = 925 mg/m3

Same absorption for oral and inhalation, thus 100%/100%.

AF for dose response relationship:
1
Justification:
no increased AF justified
AF for differences in duration of exposure:
2
Justification:
data from subchronic exposure duration
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling already used when converting dose metric
AF for other interspecies differences:
2.5
Justification:
deafault factor for remaining intraspecies difference other than allometric scaling
AF for intraspecies differences:
5
Justification:
defaultfactor for workers
AF for the quality of the whole database:
1
Justification:
no increased factor justified
AF for remaining uncertainties:
1
Justification:
no increased AF justified
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:
10.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
375 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 050 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Assuming 50% absorption from dermal exposure compared to 100% absorption from oral exposure (ABS oral-rat / ABS derm-human) and difference between human and experimental exposure conditions (7/5):

NOAEL = 375 x 100/50 x 7/5 =1050 mg/kg

DNEL = 1050 / 100 = 10.5 mg/kg

AF for dose response relationship:
1
Justification:
no increased AF justified
AF for differences in duration of exposure:
2
Justification:
default factor from subchronic to chronic exposure duration
AF for interspecies differences (allometric scaling):
4
Justification:
default for rats
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value
AF for the quality of the whole database:
1
Justification:
no increased AF justified
AF for remaining uncertainties:
1
Justification:
no increased AF justified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Skin sensitisation DNELs (”acute / short term exposure local effects” and “long-term exposure local effects”): 

It is difficult to derive a quantitative sensitisation DNELs based on the available test systems, as most of these tests, as well as the human patch test, were not designed to derive a threshold for sensitisation. This was also addressed in the guidance document Chapter R.8: Characterisation of dose [concentration]-response for human health May 2008.APPENDIX R. 8-10] concluding that GMPT and the Buehler test data are only allowing a qualitative assessment and that LLNA and human data may be only allowing (in some case) the derivation in a more quantitative manner. 

 

A few LLNA studies conducted with TMPeoTA (different batches) show skin sensitisation. But only two of the studies determined a threshold for sensitisation. These two studies were conducted according to the protocol for the non-radioactive version of the LLNA (BASF, 2002, Gamer A.O. (a) and BASF, 2004, Gamer A.O. (d)). 

 

Therefore, based on the data available, no quantitative derivation of a local DNEL can be calculated due to the following uncertainties: 

 

 -The LLNA method used was modified to avoid use of radioactive material. This modified method does not allow a judgement on the potency of the sensitizer. No EC3 value can be derived.  

 

 -Dermal penetration is a prerequisite step for sensitization. Based on calculations made using the OECD toolbox (DermWin), penetration is expected to be low also taking into consideration the molecular weight of TMPeoTA.

 

Thus, the first step of the general approach given in APPENDIX R. 8-10 is followed and a qualitative approach (by using potency categorisation) to define the risk management measures (RMMs) (see section qualitative approach for sensitisation) is performed. The second step of the approach cannot be fulfilled as it is not possible to derive reliable DNELs for sensitisation. 

 

Instead, based on the qualitative information that the substance is a skin sensitiser, adequate risk management measures are implemented.  

  

 

Qualitative approach for sensitisation: 

A qualitative assessment based on information available on skin sensitisation is given below: 

 

 - Based on a Buehler test (BASF, 2004, Gamer A.O.) according to Table R. 8-25 the substance is a moderate sensitizer. 

 

 - Based on results obtained when using the non-radioactive LLNA(BASF, 2002, Gamer A.O. (a) and BASF, 2004, Gamer A.O. (d)) no categorisation based on potency according to Table R. 8-23 is possible. Nevertheless, the test result obtained indicates that the substance has a sensitising potential (Skin Sens 1B). 

 

Based on all the integrated information there is the concern that TMPeoTA is a skin sensitiser (Skin Sens 1B). Therefore, risk management measure controlling the local dermal exposure is implemented (seeRisk management measure addressing the classification of the substance).    

 

Risk management measure addressing the classification of the substance: 

The substance is classified as irritant to eye and skin sensitiser therefore working with this substance requires a stringent use of appropriate chemical resistant gloves, protective clothing and suitable eye protection if any skin/eye contact is foreseen. Workers should receive a task specific training on how to use the protective equipment and the correct use of it needs to be supervised. Besides that, workers should be warned to avoid skin and eye contact, to wash off any skin contamination immediately and to report skin/eye problems that may develop. Taking these measures into account, the intensity of exposure is considered to be very low. 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

Since the substance is used at industrial and professional domains, no exposure of the general population to is expected. Therefore, no DNELs for the general population were calculated.