Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
394.25 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 516 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC

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:
54.27 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
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

Workers

The oral route was not considered As the acute dermal toxicity of MAK was > 2 g/kg BW, the acute dermal route was not calculated. 

               Acute Inhalation

A 10-month repeat dose inhalation study gave a NOEC of 1025 ppm (4750 mg/m3, the highest dose tested). The NOEC was converted from the 6 hour exposure time in the study to a 15 minute STEL (short-term exposure limit) using Haber’s law. The corrected value was further adjusted for light work (from 6.7 M3to 10 m3per 8 hours). ECETOC assessment factors of 3 for intraspecies and 2 for subchronic to chronic were applied.

- Converting ppm to mg/m3= (FW*ppm)/24.45 = (114.19*1025)/24.45 = 4750 mg/m3

- Converting to a 15 minute STEL with Habers law = cube root of ((4787 mg/m3)3 *6 hr)/0.25hr = 13701 mg/m3

- Converting for light work = 13808mg/m3* (0.67) = 9097 mg/m3

- Application of adjustment factors – 9251.3 mg/m3/6 =1516 mg/m3

               Long-term inhalation

A 10-month repeat dose inhalation study gave an NOEC of 1025 ppm (4787 mg/m3, the highest dose tested). The NOEC was converted from the 6 hour daily exposure to an 8 hour per day exposure (0.75), and was then adjusted for respiration for light work (0.67). ECETOC assessment factors were applied, which consisted of subchronic to chronic studies (2) and for intraspecies (3) for a total of 6.

- Converting ppm to mg/m3= (FW*ppm)/24.45 = (114.19*1025)/24.45 = 4750 mg/m3

- Converting for 6 hour exposure to 8 hour day and light work= 4750 mg/m3* (0.75) *(0.67) = 2365.50 mg/m3

- Application of adjustment factors – 2405.4 mg/m3/6 =394.25 mg/m3

 

               Long-term dermal

The dermal DNEL was found by correcting the inhalation DNEL for route and allometric scaling and removing light work.

- Correct for inhalation to dermal = inhalation DNEL * sRV (0.38 m3/kg/ 8 hr) = 394.25 * 0.38 = 149.81 mg/kg bw/day

- Application of additional adjustment factor of 4 for rat/human allometric scaling = 50.7/4 = 54.27 mg/kg BW/ day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
84.31 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL extrapolated from long term DNEL

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.32 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.32 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
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

General population

               Acute inhalation

A 10-month repeat dose inhalation study gave a NOEC of 1025 ppm (4750 mg/m3, the highest dose tested). The NOEC was converted from the 6 hour exposure time in the study to a 15 minute STEL (short-term exposure limit) using Haber’s law. ECETOC assessment factors of 5 for intraspecies and 2 for subchronic to chronic were applied.

- Converting ppm to mg/m3= (FW*ppm)/24.45 = (114.19*1025)/24.45 = 4750 mg/m3

- Converting to a 15 minute STEL with Habers law = cube root of ((4787 mg/m3)3 *6 hr)/0.25hr = 13701 mg/m3

- Application of adjustment factors – 13701 mg/m3/10 =1370.1 mg/m3

               Long-term inhalation

A 10-month repeat dose inhalation study gave an NOEC of 1025 ppm (4787 mg/m3, the highest dose tested). The NOEC was converted from the 6 hour daily exposure to 24 hours per day (.25) and from 5 days/week to 7 days per week (.71). ECETOC assessment factors were applied, which consisted of subchronic to chronic studies (2) and for intraspecies (5) for a total of 10.

- Converting ppm to mg/m3= (FW*ppm)/24.45 = (114.19*1025)/24.45 = 4750 mg/m3

- Converting from 6 to 24 hours day = 4750* 0.25 = 1187.5 mg/m3

Converting from 5 to 7 days per week exposure – 1187.5 * 0.71 = 843.13 mg/m3

- Application of adjustment factors – 843.13/10 =84.3 mg/m3

 

Long term dermal

The dermal DNEL was found by correcting the inhalation DNEL for route and allometric scaling and removing light work.

- Correct for inhalation to dermal = inhalation DNEL * sRV (1.15 m3/kg/ 8 hr) = 84.3 * 1.15 = 96.9 mg/kg bw/day

- Application of additional adjustment factor of 4 for rat/human allometric scaling = 45.7/4 = 23.32 mg/kg BW/ day

 

Long term oral

The oral DNEL was found by correcting the inhalation DNEL for route and allometric scaling and removing light work.

- Correct for inhalation to dermal = inhalation DNEL * sRV (1.15 m3/kg/ 8 hr) = 84.3 * 1.15 = 96.9 mg/kg bw/day

- Application of additional adjustment factor of 4 for rat/human allometric scaling = 45.7/4 = 23.32 mg/kg BW/ day