Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.44 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:
4.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected inhalatory NOAEC = Oral NOAELx(Abs oral rat/Abs inh human) x (1/sRVrat8h) x (sRVhuman8h/wRVhuman8h) = 2.5 mg/kg x (1/0.38) x (6.7/10) = 4.4 mg/m3; ABS oral rat = 100% (Hepatotoxicity effects indicate total absorption of the substance), ABS inh human = 100%= 100%

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 scalling used in derivation of inhalation DNEL
AF for other interspecies differences:
1
Justification:
Standard factor used for interspecies remaining differences is 2.5. However, 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 but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.63 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:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL = oral NOAEL x (ABS oral/ABS dermal) with oral NOAEL = 2.5 mg AI/kg bw/day; ABS oral = 100%; ABS dermal = 10% (based on physicochemical properties & worst case THPS absorption 4.80%). Dermal NOAEL = 25 mg AI/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:
Standard factor used for interspecies remaining differences is 2.5. However, 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.
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:
high hazard (no threshold derived)
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

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.

 

Hepatotoxycity

THPC-Urea

THPS

THPC

Perform ST/ STi

CAS#27104-30-9

CAS#55566-30-8

CAS#124-64-1

CAS#359406-89-1

28 days – Oral

(mg AI/kg bw/day)

NOAEL

Not achieved

No histopathology

No study

5

LOAEL

52

15

 

90 days – Oral – rats

(mg AI/kg bw/day)

NOAEL

6.54

0.75

No study

2.5

LOAEL

13.1

3.75

5

90 days – Oral – rats

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

3.75

(other dose: 7.5 mg/kg bw day)

No study

LOAEL

5

(other dose: 10 mg/kg bw day)

2 years – Oral – mouse

(mg AI/kg bw/day)

NOAEL

No study

Not achieved

Not achieved

7.5

(other dose: 15 mg/kg bw day)

No study

LOAEL

5

(other dose: 10 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:
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

Exposure of general population is not foreseen. The life cycle of THPC-urea-amine is short and restricted to industrial uses. It covers three steps:

1-Manufacturing in chemical production plant with high level of safety

2-Formulation on industrial sites licensed to use THPC-urea-amine only in accordance with a user manual setting the safety requirements.

3- Fabric treatment to impart flame retardant properties on the same licensed industrial sites.

Specific steps in the technical process lead to the complete reaction and/or destruction of the remaining THPC-urea-amine during the treatment of the fabric and the aqueous liquors. The THPC-urea-amine monomer is polymerised within the treated fabrics and therefore is not present in the textiles. In addition, following chemical or UV degradation the polymer in the treated fabric does not breakdown to release THPC-urea-amine monomer.

Therefore, no DNELs for general population are defined.