Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.61 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):
12
Dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
AF for differences in duration of exposure:
0.75
Justification:
0.75 is used to convert from 6 hr to 8 hr daily exposure and 0.67 for respiration for light work.
AF for interspecies differences (allometric scaling):
4
Justification:
ECETOC value
AF for intraspecies differences:
3
Justification:
ECETOC value
Justification:
subchronic to chronic dosing
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:
7.03 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
AF for other interspecies differences:
4
AF for intraspecies differences:
3
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Value:
35 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
9
Modified dose descriptor starting point:
other:

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:
low hazard (no threshold derived)

Additional information - workers

Workers

Acute oral exposure

Chapter 8 of the reach TGD (Appendix R.8 -8) indicates that acute exposure DNEL values are not normally required. However, acute oral toxicity studies in mice indicated that while the LD50 was estimated at 1800 mg/kg, a NOEL was established at 316 mg/kg. Using and adjustment factor of 3 for interspecies differences and an adjustment factor of 3 for intraspecies differences, a DNEL of 35 mg/kg was calculated. It is assumed also that there will be limited acute or long-term oral exposures to TMPD in worker populations. Additionally, the lack of dermal toxicity would indicate that TMPD is non-hazardous under acute exposure scenarios. Eye and respiratory irritation thresholds are assumed to exceed thresholds for chronic systemic effects.                            

Long-term inhalation, systemic

A 90-day repeat dose oral toxicity study gave a NOAEL of 120 mg/kg. The NOEL first must be converted to mg/m3 by dividing by a factor of 0.38, and then corrected for oral bioavailability (50%) by multiplying by a factor of 0.5. Further corrections are then necessary to convert from the 6 hour daily exposure to an 8 hour per day exposure (0.75), and to adjusted for respiration for light work (0.67). ECETOC Assessment factors were applied, for intraspecies (3), for interspecies (4), for a total of 12.     

- Converting mg/kg to mg/m3 = 120/0.38 = 315.78 mg/m3

- Correcting for oral bioavailability = 315.78*0.5 = 157.89 mg/m3

- Correcting for 7-day experimental exposure to 5-day work week, and light work= 157.89 mg/m3* (0.75) *(0.67) = 79.34 mg/m3

- Application of adjustment factors: 79.33 mg/m3/12= 6.61 mg/m3

Long-term dermal, systemic

A 90 -day repeat dose oral toxicity study gave a NOAEL of 120 mg/kg. The NOAEL first must be corrected to convert from the 6 hour daily exposure to an 8 hour per day exposure (0.75), and correction for 7-day experimental exposure to 5-day work week (1.4) and to adjusted for respiration for light work (0.67). ECETOC Assessment factors were applied, which consisted for intraspecies (3), for interspecies (4), for a total of 12.

- Correcting for 7-day experimental exposure to 5-day work week, and light work = 120 mg/kg*(1.4)*(0.67)*(0.75) = 84.42 mg/kg

- Application of adjustment factors: 84.42 mg/kg/12 = 7.03 mg/kg

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
AF for other interspecies differences:
4
AF for intraspecies differences:
5
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL extrapolated from long term DNEL

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:
6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
AF for other interspecies differences:
5
AF for intraspecies differences:
4
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:
6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Value:
120 mg/kg bw/day
AF for interspecies differences (allometric scaling):
4
AF for intraspecies differences:
5
Acute/short 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):
18
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

General Population

Acute oral exposure

Chapter 8 of the reach TGD (Appendix R.8 -8) indicates that acute exposure DNEL values are not normally required. However, acute oral toxicity studies in mice indicated that while the LD50 was estimated at 1800 mg/kg, a NOEL was established at 316 mg/kg. Using and adjustment factor of 3 for interspecies differences and an adjustment factor of 3 for intraspecies differences and a factor of 2 for the general population, a DNEL of 18 mg/kg was calculated. It is assumed also that there will be limited acute or long-term oral exposures to TMPD in the general populations. Additionally, the lack of dermal toxicity would indicate that TMPD is non-hazardous under acute exposure scenarios. Eye and respiratory irritation thresholds are assumed to exceed thresholds for chronic systemic effcts.

Long-term inhalation, systemic

A 90 day repeat dose oral toxicity study gave a NOAEL of 120 mg/kg.  The NOAEL first must be converted to mg/m3by dividing by a factor of 1.15, and then corrected for oral bioavailability (50%) by multiplying by a factor of 0.5. ECETOC Assessment factors were applied, which consisted for intraspecies (5), for interspecies (4), for a total of 20.   

 - Converting mg/kg to mg/m3= 120/1.15 = 104.34 mg/m3

- Correcting for oral bioavailability = 120 *0.5 = 52.17 mg/m3

- Application of adjustment factors – 52.17 mg/m3/20 = 2 .6 mg/m3

Long-term dermal, systemic

A 90-day repeat dose oral toxicity study gave a NOAEL of 120 mg/kg.  ECETOC Assessment factors were applied, which consisted for intraspecies (5), for interspecies (4), for a total of 20.

- Application of adjustment factors: 120 mg/kg/20 = 6.0 mg/kg

Long-term oral, systemic

A 90-day repeat dose oral toxicity study gave a NOAEL of 120 mg/kg. ECETOC Assessment factors were applied, which consisted for intraspecies (5), for interspecies (4), for a total of 20.

- Application of adjustment factors: 120 mg/kg/20 = 6.0 mg/kg