Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1
Dose descriptor starting point:
NOAEC
Value:
6.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

RAC is of the opinion (ECHA/RAC/RES-O-0000006695-63-01/F) that a human NOAEC can be set based on the NOAEC of 6.2 mg/m³ reported in the Kilo et al. study (2016) for hepatic effects in humans, resulting in a DNEL of 6 mg/m³. RAC further notes that DMF is a well-known reproductive toxicant and thus supports the inhalation DNEL for developmental toxicity in rabbits calculated to 6 mg/m³ in the restriction proposal, based on a NOAEC of 150 mg/m³ for malformations in a rabbit developmental toxicity study (Hellwiget al., 1991; Key_BASFAG1989.Developmental toxicity / teratogenicity).

Overall, RAC proposes a systemic long term DNEL of 6 mg/m³ for the inhalation route based on a combination of human data and rabbit developmental toxicity data.

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:
1.1 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
90
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

RAC decided in its opinion (ECHA/RAC/RES-O-0000006695-63-01/F) to use the LOAEL from the dermal developmental toxicity study (i.e. 100 mg/kg/day) (Key_BASFAG1984.Developmental toxicity / teratogenicity) as dose-descriptor starting point.

AF for dose response relationship:
3
Justification:
default (LOAEL)
AF for interspecies differences (allometric scaling):
2.4
Justification:
default for rabbit
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default for workers
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:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
2
Dose descriptor starting point:
NOAEC
Value:
6.2 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
2.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Although no consumer uses are relevant the inhalation systemic long-term DNEL for the general population is derived for the assessment of man via environment.

RAC is of the opinion (ECHA/RAC/RES-O-0000006695-63-01/F) that a human NOAEC can be set based on the NOAEC of 6.2 mg/m³ reported in the Kilo et al. study (2016) for hepatic effects in humans. As this NOAEC was obtained for workers, it needs to be modified for the general population by correction for exposure duration (5 d/week vs. 7 d/week and 8 h/d vs. 24 h/d) and for increased respiratory volume of workers under light activity (10m³/8h / 6.7 m³/8h = 1.5).

Modified dose descriptor starting point: 6.2 mg/m³ x 5 d/7 d x 8 h/24 h x 1.5 = 2.2 mg/m³

AF for intraspecies differences:
2
Justification:
as the dose descriptor starting point was derived from an epidemiological study in a mixed group of workers, an AF of 2 is needed to account for more sensitive sub-groups in the general population
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:
low 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:
DNEL (Derived No Effect Level)
Value:
0.16 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
2
Dose descriptor starting point:
other: NOAEC of 6.2 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
0.31 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Although no consumer uses are relevant the oral systemic long-term DNEL for the general population is derived for the assessment of man via environment.

RAC is of the opinion (ECHA/RAC/RES-O-0000006695-63-01/F) that a human NOAEC can be set based on the NOAEC of 6.2 mg/m³ reported in the Kilo et al. study (2016) for hepatic effects in humans. This NOAEC was obtained for workers. It needs to be modified for the general population by correction for exposure duration (5 d/week vs. 7 d/week and 8 h/d vs. 24 h/d) and for the increased respiratory volume of workers under light activity (10 m³/8h / 6.7 m³/8h = 1.5).

In addition it is extrapolated from the inhalation to the oral route by using the sRV for workers for 8 h of 10 m³/person (10 m³ / 70 kg = 0.14 m³ / kg bw)

Modified dose descriptor starting point:

6.2 mg/m³ x 0.14 m³/kg bw/8 h = 0.868 mg/kg bw/8 h

0.868 mg/kg bw/8 h x 5 d/7 d x 8 h/24 h x 1.5 = 0.31 mg/kg bw/d

AF for intraspecies differences:
2
Justification:
as the dose descriptor starting point was derived from an epidemiological study in a mixed group of workers, an AF of 2 is needed to account for more sensitive sub-groups in the general population
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population