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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
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:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
25
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:
medium hazard (no threshold derived)

Additional information - workers

Acute/short-term exposure:

N-Vinylformamide is harmful by ingestion (DSD: R22, EU GHS: Acute oral toxicity Cat. 4). However, this is not a relevant exposure route for workers and a DNEL has therefore not been derived.

Dermal - local and systemic effects: Not quantifiable, since no acute hazard has been identified for this route (data available).

Inhalation - local and systemic effects: Not quantifiable, since no acute hazard has been identified for this route (data available).

N-Vinylformamide may cause severe damage to the eye. However, this is no threshold effect and a DNEL is therefore not quantifiable. The wearing of tightly fitting safety goggles which is a highly accepted risk management measure is considered sufficient to ensure the safety of workers.

Long-term exposure:

Inhalation - local and systemic effects:

The DNEL for long-term exposure following vapour inhalation was derived based on the NOAEC value from a subchronic repeated dose inhalation study with rats (BASF AG, 1995). The respective NOAEC for local and systemic effects was 50 mg/m³ (= 17 ppm). Local effects at the next dose level of 250 mg/m³ (86 ppm) were some clinical irritation of the upper respiratory tract with mild changes in the nasal cavity as histopathological correlate. Regarding systemic effects at 250 mg/m³, the liver was identified as the main target organ (increased liver weights including histopathologically detectable liver changes), and the kidney also represented a target organ (increased urinary volume, decreased specific gravity of urine as well as decreased blood levels of sodium and chloride, increased absolute kidney weights in females, although without histopathological correlate).

 

The NOAEC of 50 mg/m³ which was taken as relevant dose descriptor for long-term toxicity had to be modified in order to get the correct starting point for DNEL derivation:

According to the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-2, p. 27), the inhalatory rat NOAEC was converted into the NAEC corrected for human worker exposure conditions (8h exposure per day, respiratory volume adapted for a worker with light activity) by multiplying with the corresponding factors (x 0.75, x 0.67). The resulting corrected NAEC for local and systemic effects is equal to 25.1 mg/m³ (= 8.5 ppm).

Interspecies variation:

Concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans are to be taken into account (e.g. in case of effects at the olfactory epithelium, see Frederick et al. 1998, Harkema 1991). Furthermore, there is no evidence for differences in the general mode of action or kinetics of N-Vinylformamide in humans compared to rats. Thus, no allometric assessment factors were applied and the interspecies factor for remaining differences was set to be 2.5.

 

Intraspecies variation:

The intraspecies variation among human workers was recognised by an assessment factor of 5 by default.

 

Exposure duration:

An assessment factor of 2 was used for extrapolation of exposure duration from sub-chronic (90-day inhalation study) to chronic by default.

Dose-response:

An assessment factor of 1 was used by default.

Quality of whole database:

An assessment factor of 1 was used by default.

Accordingly, an overall assessment factor of 25 was calculated based on the recommendations given in the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-6, p. 38) and based on the above mentioned arguments. Thus, the DNEL for long-term exposure was calculated as follows:

DNEL long-term exposure local and systemic = NAEC corrected / Overall AF = 25.1 mg/m³ / 25 = 1 mg/m³ (= 0.34 ppm).

Dermal - systemic effects:

The DNEL for systemic effects after long-term dermal exposure was derived based on the NOAEL value from a subchronic repeated dose inhalation study with rats (BASF AG, 1995). The respective NOAEL for local and systemic effects was 50 mg/m³ (= 17 ppm). Local effects at the next dose level of 250 mg/m³ (86 ppm) were some clinical irritation of the upper respiratory tract with mild changes in the nasal cavity as histopathological correlate. Regarding systemic effects at 250 mg/m³, the liver was identified as the main target organ (increased liver weights including histopathologically detectable liver changes), and the kidney also represented a target organ (increased urinary volume, decreased specific gravity of urine as well as decreased blood levels of sodium and chloride, increased absolute kidney weights in females, although without histopathological correlate).

 

The NOAEL of 50 mg/m³ which was taken as relevant dose descriptor for long-term toxicity had to be modified in order to get the correct starting point for DNEL derivation:

According to the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-2, p. 27), the inhalatory NOAEL was converted into the dermal NOAEL by route-to-route extrapolation assuming a 100% absorption of the test substance by inhalation in rats compared to a 50% absorption of the test substance by dermal contact in humans, and a standard respiratory volume (sRV) of the rat corresponding to the daily exposure of workers (8 h/day) of 0.38 m³/kg bodyweight. The resulting corrected dermal NOAEL for systemic effects is equal to 38 mg/kg bodyweight/day.

Interspecies variation:

There is no evidence for differences in the general mode of action or kinetics of N-Vinylformamide in humans compared to rats. Thus, no allometric assessment factors were applied and the interspecies factor for remaining differences was set to be 2.5.

 

Intraspecies variation:

The intraspecies variation among human workers was recognised by an assessment factor of 5 by default.

 

Exposure duration:

An assessment factor of 2 was used for extrapolation of exposure duration from sub-chronic (90-day inhalation study) to chronic by default.

Dose-response:

An assessment factor of 1 was used by default.

Quality of whole database:

An assessment factor of 1 was used by default.

Accordingly, an overall assessment factor of 25 was calculated based on the recommendations given in the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-6, p. 38) and based on the above mentioned arguments. Thus, the DNEL for long-term exposure was calculated as follows:

DNEL long-term exposure local and systemic = NOAEC corrected / Overall AF = 38 mg/kg bw/day / 25 = 1.52 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.178 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.178 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Dose descriptor:
NOAEC
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:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

N-Vinylformamide is manufactured and used as a monomer in the manufacture of polymers in industrial settings only. Resulting polymer products are marketed to industrial customers only. Therefore, consumer exposure is likely to be very low (if any exposure occurs at all, consumers are exposed to trace levels of the monomer N-Vinylformamide only).

The DNEL for long-term exposure following vapour inhalation was derived based on the NOAEC value from a subchronic repeated dose study with rats (BASF AG, 1995). The respective NOAEC for local and systemic effects was 50 mg/m³ (= 17 ppm). Local effects at the next dose level of 250 mg/m³ (86 ppm) were some clinical irritation of the upper respiratory tract with mild changes in the nasal cavity as histopathological correlate. Regarding systemic effects at 250 mg/m³, the liver was identified as the main target organ (increased liver weights including histopathologically detectable liver changes), and the kidney also represented a target organ (increased urinary volume, decreased specific gravity of urine as well as decreased blood levels of sodium and chloride, increased absolute kidney weights in females, although without histopathological correlate).

 

The NOAEC of 50 mg/m³ which was taken as relevant dose descriptor for long-term toxicity had to be modified in order to get the correct starting point for DNEL derivation:

According to the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-2, p. 27), the inhalatory rat NOAEC was converted into the NAEC assuming the default consumer exposure conditions of 24 hours/day, 7 days/week instead of the exposure duration in the study (6 hours/day, 5 days/week) by multiplying with the corresponding factors (x 0.25, x 0.71). The resulting corrected NAEC for local and systemic effects was equal to 8.9 mg/m³ (= 3.0 ppm).

 

Interspecies variation:

Concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat’s ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans are to be taken into account (e.g. in case of effects at the olfactory epithelium, see Frederick et al. 1998, Harkema 1991). Furthermore, there is no evidence for differences in the general mode of action or kinetics of N-Vinylformamide in humans compared to rats. Thus, no allometric assessment factors were applied and the interspecies factor for remaining differences was set to be 2.5.

 

Intraspecies variation:

The intraspecies variation among the general population was recognised by an assessment factor of 10 by default.

 

Exposure duration:

An assessment factor of 2 was used for extrapolation of exposure duration from sub-chronic (90-day inhalation study) to chronic by default.

 

Accordingly, an overall assessment factor of 20 was calculated based on the recommendations given in the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008, Figure R.8-6, p. 38) and based on the above mentioned arguments:

Assessment Factor for

Local effects

Interspecies

2.5

Intraspecies

10

Exposure duration

(sub-chronic to chronic)

2 (default)

Dose-response

1 (default)

Quality of whole database

1 (default)

Overall AF

50

Thus, the DNEL for long-term exposure was calculated as follows:

DNEL long-term exposure local and systemic = NAEC corrected / Overall AF = 8.9 mg/m³ / 50 = 0.178 mg/m³ (= 0.06 ppm).