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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.15 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):
10
Modified dose descriptor starting point:
NOAEC
Value:
11.53 mg/m³
Explanation for the modification of the dose descriptor starting point:
Corrected NOAEC = Oral NOAEL * (1/sRV rat 8h) * (ABS oral-rat / ABS inh-human) * (sRV human 8h / wRV 8h) with oral NOAEL = 6.54 mg/kg bw/d; sRV rat 8h = 0.38 m3/kg bw; ABS oral rat = 100% **; ABS inh-human=100% ; sRV human 8h = 6.7 m3/person; wRV 8h = 10 m3/person. Corrected NOAEC = 11.53 mg/m3
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used in derivation of inhalation DNEL
AF for other interspecies differences:
1
Justification:
Standard factor used for interspecies remaining differences is 2.5. Hepatotoxicity was observed in three species (rat, mouse and dog) treated with THPX substances in sub-acute, sub-chronic and chronic studies by oral route. Therefore, This AF is considered = 1. (See Table 1)
AF for intraspecies differences:
5
Justification:
Default factor used for worker
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.635 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
65.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal NOAEL = oral NOAEL * (ABS oral / ABS dermal) with Oral NOAEL = 6.54 mg/kg bw/d; ABS oral = 100%; ABS dermal = 10% (Supported by experimental data from other THP+salts and known reactivity of THPC-urea for amine moeity, see guidance R.7). Dermal NOAEL = 65.4 mg/kg bw/day.
AF for dose response relationship:
1
Justification:
NOAEL is used as the starting point
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor for interspecies differences Rat vs Human
AF for other interspecies differences:
1
Justification:
Hepatotoxicity was observed in three species (rat, mouse and dog) treated with THPX substances in sub-acute, sub-chronic and chronic studies by oral route. Therefore, This AF is considered = 1. (See Table 1)
AF for intraspecies differences:
5
Justification:
Default factor used for worker
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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:
high hazard (no threshold derived)

Additional information - workers

Hepatotoxicity was observed in three species (rat, mouse and dog) treated with THPX substances in sub-acute, sub-chronic and chronic studies by oral route. Therefore, The AF for other interspecies differences is considered = 1 instead of 2.5. (See Table 1).

Table 1:Database on repeated-dose NOAEL/LOAEL (gavage) on THPX substances characterising the lowest observed effect: hepatotoxicity.Doses mg/kg bw/day expressed as active ingredient content.

   

 

 

 

 

 

 

 

 

 

Hepatotoxicity

THPC-Urea (Cas N° :27104-30-9)

THPS (CAS N° : 55566-30-8)

THPC (CAS N° : 124-64-1)

Perform ST/STI (CAS N° : 359406-89-6)

 

 

 

 

 

 

 

 

 

 

28 days – Oral (mg AI/kg bw/day)

NOAEL

Not achieved

No histopathology

No study

5

 

 

LOAEL

52

15

 

 

 

 

 

 

 

 

 

 

90 days - oral – rat (mg AI/kg bw/day)

NOAEL

6.54

13.1

0.75

No study

2.5

5

 

 

LOAEL

3.75

 

 

90 days - oral - rat
NTP (mg AI/kg bw/day)

NOAEL

No study

5

3.75

No study

 

 

LOAEL

10

7.5

 

 

90 days - oral - mouse
NTP (mg AI/kg bw/day)

NOAEL

No study

10

4.5

No study

 

 

LOAEL

20

15

 

 

90-days - oral – dog (mg AI/kg bw/day)

NOAEL

No study

0.75

No study

No study

 

 

LOAEL

4.75

 

 

 

 

 

 

 

 

 

 

2 years - oral – rat (mg AI/kg bw/day)

NOAEL

No study

Not achieved

Not achieved

No study

 

 

LOAEL

5 (other doses: 10 mg/kg bw/day)

3.75 (other dose: 7.5 mg/kg bw/day)

 

 

2 years - oral – mouse (mg AI/kg bw/day)

NOAEL

No study

Not achieved

Not achieved

No study

 

 

LOAEL

5 (other doses: 10 mg/kg bw/day)

7.5 (other dose: 15 mg/kg bw/day)

 

 

 

 

 

 

 

 

 

 

 

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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

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