Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC Technical Report No. 110_Page 62
Overall assessment factor (AF):
160
Modified dose descriptor starting point:
LOAEC
DNEL value:
42 mg/m³
Explanation for the modification of the dose descriptor starting point:
Comparable resorption for oral and inhalation routes; Human body weight of 70kg/person; Daily respration volume of 10 m³ for a worker for 8 hours.
AF for dose response relationship:
2
Justification:
No NOAEL could be established and the LOAEL is used as the base for the DNEL derivation. The effect at LOAEL was lmited to reduced spleen weight of fetuses, therefore the use of 2 as additional factor is considered to be appropriate
AF for differences in duration of exposure:
1
Justification:
The exposure duration covered the entire second and the third term of the pregnancy;
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor of rat is given as 4 in ECHA REACH Guidance
AF for other interspecies differences:
10
Justification:
According to the ECETOC Technical Report No. 110_Page 62
AF for intraspecies differences:
1
Justification:
According to the ECETOC Technical Report No. 110_Page 62
AF for the quality of the whole database:
1
Justification:
All data are Klinish 1 or 2.
AF for remaining uncertainties:
2
Justification:
The assessment is based on the read-across.
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.3 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.3 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.3 mg/m³
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC Technical Report No. 110_Page 62
Overall assessment factor (AF):
160
Modified dose descriptor starting point:
LOAEL
DNEL value:
6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Comparable resorption for oral and dermal routes; Human body weight of 70kg/person;
AF for dose response relationship:
2
Justification:
No NOAEL could be established and the LOAEL is used as the base for the DNEL derivation. The effect at LOAEL was lmited to reduced spleen weight of fetuses, therefore the use of 2 as additional factor is considered to be appropriate.
AF for differences in duration of exposure:
1
Justification:
The exposure duration covered the entire second and the third term of the pregnancy;
AF for interspecies differences (allometric scaling):
4
Justification:
The allometric scaling factor of rat is given as 4 in ECHA REACH Guidance
AF for other interspecies differences:
10
Justification:
According to the ECETOC Technical Report No. 110_Page 62
AF for intraspecies differences:
1
Justification:
According to the ECETOC Technical Report No. 110_Page 62
AF for the quality of the whole database:
1
Justification:
All data are Klinish 1 or 2.
AF for remaining uncertainties:
2
Justification:
The assessment is based on the read-across.
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
0.04 mg/kg bw/day
DNEL related information

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:
no hazard identified

Additional information - workers

Correction of the obtained NOAEL/LOAEL of the read-across supporting substance

The registration substance is a weak acid and the read-across supporting substance is the corresponding weak base. When dissolved in water the read-across supporting substance will be converted to the registration substance

Since the conversion from salt to acid form is likely to occur already in the gastro-intestinal tract when given orally to the animals, there should be no bioavailability difference based on the molar dose. The obtained NOAEL of the read-across supporting substance should be therefore corrected, considering the molecular mass difference (420 g/mol vs ca. 530 g/mol). In the presented key study, the applied doses were 8, 40, 200 mg/kg bw, corresponding to 6, 30 and 160 mg/kg bw for the registration substance. For the DNEL derivation the dose levels of 6 mg/kg bw as LOAEL will be used.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
high 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:
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:
high 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:
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:
other toxicological threshold
Value:
1.5 µg/kg bw/day
DNEL related information
Explanation for the modification of the dose descriptor starting point:

TTC for Cramer II/III (EFSA Journal 2012; 10(7):2750) is to be applied for the general population for oral routes.

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