Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.38 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
15
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:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: VCI inhalation DNEL for corrosive substances
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
other: VCI inhalation DNEL for corrosive substances

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

PFA category members are primary alkylamines and as such belong to a group of substances which share essential chemical key aspects andexhibit a closely related effect spectrum. On that background a group approach by applying read-across principles is justified and universal DNELs are derived for the whole category of primary alkylamines. A comparable grouping for assessment purposes was also considered appropriate during the EU risk assessment on primary alkylamines.

Exposed population are workers which are expected to have infrequent and short-term exposures. However, for DNEL calculation chronic exposure conditions were assumed as worst-case scenario.

The following DNELs have been identified (justifications see below):

1) DNEL inhalation, systemic, long term

2) DNEL inhalation, local, long term

3) DNEL, inhalation, local, acute

1) Since no route-specific repeated inhalation data is available neither for C12 -18 -(even numbered)-alkylamines nor for the other primary alkylamines considered a category, route-to-route extrapolation was performed using the NOAEL from the 28 -day oral toxicity test with C16 -18 -(even numbered, saturated and unsaturated)-alkylamines (common name: (Z)-octadec-9 -enylamine; CAS-No.112 -90 -3) which was identified as key study. No modification of the dose descriptor was performed based on pulmonary physiological and clearance dynamics considerations which do not indicate significant differences in the absorption rates between both exposure routes. Based on the overall toxicity profile, a treshold mechanism in form of primary local effects with implications for secondary systemic toxicity apply. With regard to interspecies differences, allometric scaling concerning oral-to-inhalation extrapolation is not appropriate and no assessment factor was applied. The adjustment for "remaining differences" is not considered scientifically justified. Analysis of various data sets have revealed that for workers a factor of 3 may be appropriate and that potential residual interspecies differences is largely accounted for already in the assessment factor for intraspecies variability. However, taking into account the general toxicity profile of primary alkylamines, a somewhat more conservative approach is taken and a combined inter-/intraspecies AF of 5 is considered. Since the assessment is based on the outcome of a 28 -day repeated dose toxicity study, time extrapolation to chronic exposure conditions generally have to be considered. However, because "local cytotoxicity" as concentration dependent effect is dominating in the overall toxicity profile, the full set of default assessment factors for duration extrapolation is not appropriate. This was also recognised during the EU risk assessment on primary alkylamines where duration adjustment was modified and an assessment factor of 3 was used. Likewise the same AF of 3 is applied here. With regard to dose-response considerations as well as the overall quality of the database no indication of any conspicuous behaviour exist. Since C12 -18 -(even numbered)-alkylamines are considered within a generic category approach comparable to the existing EU risk assessment, the database for some endpoints becomes rather small, but is considered to be still adequate for assessment purposes.

2) and 3)  Worker DNEL: Long-term/acute for inhalation route, local effects

The German VCI ("Verband der chemischen Industrie") established an inhalation DNEL for local effects for corrosive substances of 1 mg/m3 that should be applied for long- and short-term exposure equally. The derivation of this value is fully described in Messinger (2014). Briefly, the DNEL is a generic cut-off value based on an extensive analysis of the German occupational exposure limit (OEL) values as published in TRGS 900 (“Technnische Regeln für Gefahrstoffe”) for substances that are legally classified as corrosive. Overall, the applicability domain of the DNEL of 1 mg/m3 for corrosive substances is defined as follows (Messinger, 2014):

- The substance is not a CMR substance, not a heavy metal derivative, not a sensitiser and does not hydrolyse to strong acids/bases

- The substance is not very toxic by ingestion, dermal contact or inhalation.

The submission substance fulfils these criteria and the DNEL of 1 mg/m3 can be applied.

  

Reference 

Messinger, H. (2014): An approach for the delineation of a generic cut-off value for local respiratory tract irritation by irritating or corrosive substances as a pragmatic tool to fulfill REACH requirements, Regulatory Toxicology and Pharmacology, 3, 317-324

The substance is classified for human health as corrosive to the skin (and assumed corrosive to the eye). The hazard statement H314: Causes severe skin burns and eye damage, is applicable.

No DNEL for systemic effects is derived since the corrosive properties of the substance determine the hazard and risk profile. Otherwise, dermal systemic exposure would have to be calculated, which would then assume (even if gloves are worn) some dermal exposure to the substance. This cannot reflect the real situation since the skin would suffer from the corrosive effects. Rather than calculating some dermal exposure potentially leading to systemic effects and discounting these results afterwards on the basis of the corrosive effects, it is more appropriate to base the dermal assessment entirely on the qualitative risk characterisation for a corrosive substance. Based on the classification and the hazard statement a moderate hazard band for the qualitative assessment is assumed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.035 mg/m³
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No consumer uses are identified for PFA category members. However, DNELs for the general population are required for the assessment of human exposure via the environment. While EUSES software does not require an inhalation DNEL (since total exposure is calculated as a dose), CHESAR requires both an oral and an inhalation DNEL for long-term systemic effects for the general population. Therefore, the inhalation DNEL for the general population is calculated here from the inhalation DNEL for workers (long-term, systemic effects) by considering continuous rather than workplace exposure and by applying an additional assessment factor of 2:

DNEL inhalation general population = DNEL inhalation workers x 8 h/24 h x 5 d/7d x 40 w/52 w / 2

DNEL inhalation general population = 0.38 mg/m3 x 8 h/24 h x 5 d/7d x 40 w/52 w / 2

DNEL inhalation general population = 0.035 mg/m3

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:
no hazard identified
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:
40 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
84
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:
medium hazard (no threshold derived)

Additional information - General Population

PFA category members are not used in the consumer sector. DNEL derivations for the general population is therefore not necessary and not required. However, although no consumer uses were identified, an oral DNEL long-term (systemic) and an inhalation DNEL long-term (systemic) was derived to consider indirect exposures via the environment.