Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.6 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
9
Modified dose descriptor starting point:
LOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.6 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
9
Dose descriptor starting point:
LOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Acute Dermal (Systemic)

No acute toxicity hazard (leading to C&L) via the dermal route has been identified. DNEL is not quantifiable -Single dose study with no deaths or remarkable findings at 200 mg/kg.  LC50 >200 mg/kg. An oral LD50 value of 856 mg/kg bw, combined with an estimated dermal absorption rate 2.3 mg/cm2 over a 24-hour period (estimated by U.S. EPA DermWin v1.43), suggests that acute systemic toxicity via the dermal route is unlikely to occur under ordinary handling and use.

 

Acute inhalation (Local & Systemic)

The DNEL is valid for up to 15-minutes of exposure andwas derived on the basis of systemic toxicity. Since no short-term local effects (leading to C&L) via the inhalation route have been identified, this DNEL is assumed to be protective of both systemic toxicity and local effects. Itwas derived from a starting point of 24 mg/m3 (8-hour LOAEC, rat). This concentration was at or near the saturated vapour concentration and no mortality and no clinical signs or gross pathology findings were observed at this concentration. Consistent with Chapter R.8 (May 2008) of the REACH guidance and with ECETOC Technical Report No. 86 (February 2003), a factor of 0.67 was used to modify the starting point to light work and the following assessment factors were applied:1 for exposure duration, 1 for interspecies, 3 for intraspecies, 3 for LOAEC to NOAEC, and 1 for quality of the database. The DNEL was then adjusted to 15-minutes using Haber's Law.

 

Long-term dermal (systemic)

The DNEL is valid for typical worker exposures and assumes 100% absorption of external dose. It was derived using a NOAEL of 20 mg/kg bw/day as the starting point, which was the low dose from an OECD 422 (rat, oral gavage, 28-day male and 50-day female). At the mid dose of 60 mg/kg bw/day, liver enzyme induction was evoked in both genders and storage of alpha 2µ protein in males and mild anemia in females was observed. At 200 mg/kg body weight/day, distinct systemic toxicity such as salivation, markedly reduced food consumption and retarded body weight development, and mild impairment of motor activity in the males was observed.Consistent with Chapter R.8 (May 2008) of the REACH guidance and with ECETOC Technical Report No. 86 (February 2003), no modification of the starting point was necessary as it is assumed (conservatively) that 100% of the substance in contact with the skin will be absorbed. The following assessment factors were applied: 6 for exposure duration, 4 for interspecies, 3 for intraspecies, and 1 for quality of the database.

 

Long-term inhalation (Local & Systemic)

The DNEL is valid for typical worker exposures on the basis of systemic toxicity. Since no long-term local effects (leading to C&L) via the inhalation route have been identified, this DNEL is assumed to be protective of both systemic toxicity and local effects. It was derived using a NOAEL of 20 mg/kg bw/day as the starting point, which was the low dose from an OECD 422 (rat, oral gavage, 28-day male and 50-day female). At the mid dose of 60 mg/kg bw/day, liver enzyme induction was evoked in both genders and storage of alpha 2µ protein in males and mild anemia in females was observed. At 200 mg/kg body weight/day, distinct systemic toxicity such as salivation, markedly reduced food consumption and retarded body weight development, and mild impairment of motor activity in the males was observed. Consistent with Chapter R.8 (May 2008) of the REACH guidance and with ECETOC Technical Report No. 86 (February 2003), afactor of 1 was used to modify the starting point for absorption from oral to inhalation, 2.6 was used to modify the starting point from oral to 8hr inhalation exposure, 0.67 was used to modify the starting point to light work, and an overall assessment factor of 18 was used and derived as follows: 6 for exposure duration, 1 for interspecies, 3 for intraspecies, and 1 for quality of the database.

 

General Population - Hazard via inhalation route

Systemic 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

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

General Population - Hazard via dermal route

Systemic 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

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

General Population - Hazard via oral route

Systemic 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

No consumer uses expected for this substance.