Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.31 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
LOAEL
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

Read-across from other, structurally closely related ZDDPs is justified because of structural similarity and analogy of properties and effects.

1. Relevant Toxicology Data, exposure pattern and route

The dermal repeat dose toxicity of this substance was evaluated with rats at doses as high as 350 mg/kg/day for up to 28 consecutive days. This study is considered to be the relevant dose descriptor for the dermal route of exposure for workers. A LOAEL of 70mg/kg bw/day was established.

For inhalation, the oral toxicity study (OECD 422) carried out on a structurally similar material was considered to be the appropriate hazard information, from which appropriate corrected descriptors could be derived.

2. Mode of action

No non-threshold mode of action is associated with this substance, in particular, the test substance has no genotoxic potential.

 

3. Correction of dose descriptor

Dermal: The calculation of the DNEL is based on the results of repeated dose dermal toxicity study in rats. LOAEL = 70 mg/kg/d.

Inhalation: DNEL calculation was based on the results of an OECD 422 toxicity study in rats. NOAEL (oral) = 160 mg/kg/d. Test material purity is 91% and it was taken into account when calculating DNEL.

 

4. Application of assessment factors

Dermal route: Based on REACH guidance, chapter r8, default values to correct for differences in metabolic rate (allometric scaling, rat to human) of 4 was used; regarding the additional factor for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate and toxicodynamic differences, the default factor for remaining uncertainties of 2.5 could be reduced to 1 for the effects on the skin (REACH, chapter r8, page 33). The assessment factor for duration extrapolation was 6. The assessment factor of 5 was adopted for intraspecies differences. DNEL (Derived No Effect Level) = 0.58 mg/kg bw/day.

Inhalation route: The inhalation route was extrapolated by oral route information in the absence of data for this administration route. The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m3/kg for 8 hours exposure of workers, see Table R. 8-2 in Section R.8.4.2, REACH guidance, chapter r8). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m3 for base level, 10 m3 for light activity). NOAEL (corrected) = NOAEL (oral) ÷0.38 m3/kg*(ABS rat-oral ÷ ABS human-inhalation) x 6.7 ÷ 10.3 = 273.9 m3/kg Assessment Factors: Based on REACH guidance, chapter r8, default values to correct for differences in metabolic rate (allometric scaling, rat to human) of 1 was used; The assessment factor for duration extrapolation was 6. The assessment factor of 5 was adopted for intraspecies differences. DNEL (inhalation): NOAEL (inhalation) / Sum of assessment factors applicable = 273.9 m3/kg / 30 = 9.12 mg/ m3/d Purity taken into account: DNEL = 9.12 * 91% = 8.31mg/ m3/d

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.11 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
LOAEL
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:
0.24 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
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

1. Relevant Toxicology Data, exposure pattern and route

The dermal repeat dose toxicity of this substance was evaluated with rats at doses as high as 350 mg/kg/day for up to 28 consecutive days. This study is considered to be the relevant dose descriptor for the dermal route of exposure for the general population. A LOAEL of 70mg/kg bw/day was established.

For inhalation, the oral toxicity study (OECD 422) carried out on a structurally similar material was considered to be the appropriate hazard information, from which appropriate corrected descriptors could be derived.

For the oral route of exposure, the abovementioned OECD 422 on a structurally similar material was considered to be the appropriate hazard information from which to derive suitable DNELS for the general population.

2. Mode of action

No non-threshold mode of action is associated with this substance, in particular, the test substance has no genotoxic potential.

 3. Correction of dose descriptor

Dermal route: DNEL was calculated based on the results of a repeated dose dermal toxicity study in rats. LOAEL = 70 mg/kg/d.

Oral route: DNEL was calculated based on the results of an OECD 422 toxicity study in rats. NOAEL (oral) = 160 mg/kg/d.

Inhalation route: DNEL was calculated based on the results of an OECD 422 toxicity study in rats. NOAEL (oral) = 160 mg/kg/d. Test material purity is 91%. The inhalation route was extrapolated by oral route information in the absence of data for this administration route. The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure of general public, see Table R. 8-2 in Section R.8.4.2, REACH guidance, chapter r8). NOAEL (corrected) = NOAEL (oral) ÷1.15 = 139.1 m3/kg

 4. Application of assessment factors

Dermal route: Based on REACH guidance, chapter r8, default values to correct for differences in metabolic rate (allometric scaling, rat to human) of 4 was used; Regarding the additional factor for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate and toxicodynamic differences, the default factor for remaining uncertainties of 2.5 could be reduced to 1 for the effects on the skin (REACH, chapter r8, page 33). The assessment factor for duration extrapolation was 6. The assessment factor of 10 was adopted for intraspecies differences.

Oral route: Based on REACH guidance, chapter r8, default values to correct for differences in metabolic rate (allometric scaling 4) and an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part) was used. The assessment factor for duration extrapolation was 6. The assessment factor of 10 was adopted for intraspecies differences. NOAEL (dermal): NOAEL (oral) / Sum of assessment factors applicable = 160kg bw / 600 = 0.27 mg/kg/d Taken purity into account: 0.27 mg/kg * 91% = 0.24 mg/kg/d

Inhalation route: Based on REACH guidance, chapter r8, default values to correct for differences in metabolic rate (allometric scaling, rat to human) of 1 was used; The assessment factor for duration extrapolation was 6. The assessment factor of 10 was adopted for intraspecies differences. DNEL (inhalation): NOAEL (inhalation) / Sum of assessment factors applicable =139.1 m3/kg / 60 = 2.32 mg/ m3/d Taken purity into account: DNEL = 2.32 * 91% = 2.11 mg/ m3/d