Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Modified dose descriptor starting point:
NOAEC
Value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral to inhalation; readily oral bioavailability is assumed; daily respiration volume for a worker of 10 mg/m3.
AF for dose response relationship:
1
Justification:
the starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default assessment factor; from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
prediction of inhalation exposure from data of oral experimental; the allometric scaling is already considered in the calculation of starting point.
AF for other interspecies differences:
2.5
Justification:
default assessment factor; no substance-specific data are available
AF for intraspecies differences:
2.5
Justification:
the NOAEL comprises the susceptibility of females already
AF for the quality of the whole database:
1
Justification:
all data are klimish 1 or 2
AF for remaining uncertainties:
1
Justification:
the experimental obtained data is considered to be sufficiently conservative
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.3 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
DNEL related information
DNEL derivation method:
other: According to the VCI recommendation; based on Messinger (2013)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
DNEL related information
DNEL derivation method:
other: According to the VCI recommendation; based on Messinger (2013)

Workers - Hazard via dermal route

Systemic effects

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

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

For the risk assessment in the chapter 10, the lowest DNEL (Worker) of 1 mg/m3 will be used comprising systemic and local effect for inhalation routes.

Long-term inhalatory systemic DNEL (Worker)

The NOAEL of 50 mg/kg bw/day regarding to systemic toxic effects from a 28-day oral toxicity study in rats was used for the derivation of the `DNEL long-term inhalation, systemic`. The registered substance is assumed to be readily bioavailable based on the molecular size. No difference of absorption was assumed between oral and inhalation routes According to the ECHA REACH Guidance, the dose descriptor starting point NOAEC was calculated:

Starting point NOAEC(inhal.)     = NOEL(oral, rat) x 1/sRVrat xABS(oral-rat)/ABS(inh-human) x sRVhuman/wRV

               = 50 mg/kg bw/d x 1/0.38 m3/kg/d x 1/1 x 6.7 m3/10 m3
             = 88 mg/m3

with sRV: standard respiratory volume;ABS: Absorption; wRV: worker respiratory volume

According to the ECHA REACH Guidance, the DNEL was then obtained by applying assessment factors to the starting point:

- dose-response relationship:

There is no reason to consider special concern, because the starting point for the DNEL calculation is a NOAEL

- differences in duration of exposure:

A default assessment factor of 6 was applied base on the extrapolation from subacute to chronic

- interspecies differences (allometric scalling):

No allometric scalling is considered here, because the allometric scaling is already considered in the calculation of starting point.

- other interspecies differences:

A default assessment factor of 2 was applied; no substance-specific data are available

- intraspecies differences:

The default factor of 5 was modified to be 2.5 because the used NOAEL comprises the susceptibility of females already

- the quality of the whole database:

The available data have been evaluated with regard to their reliability, relevance and completeness. All data are Klimish 1 or 2. Based hereupon no indications exist to assume limited reliability and/or relevance of the data base used.

- remaining uncertainties:

The experimental obtained data is considered to be sufficiently conservative.

Considering the available data, an overall assessment factor of 37.5 was applied. The DNEL of system effects for worker via inhalation route was calculated to be 2.3 mg/m3.

Short-term inhalatory systemic DNEL (Worker)

The short term exposure is controlled by the conditions for long-term. The DNEL of 2.3 mg/m3 (acute and long-term) should be used.

Inhalatory local effects (long-term and short-term; Worker)

The most critical effect of the registration substance is identified as the local irritation effect. It is irritating to skin (R38) and severly irritating to eyes (R41). With respect to the observed effect on eyes together with the surfactant property of the substance, it is justified to consider the substance as potentially corrosive to respiratory tract.

The German VCI ("Verband der chemischen Industrie") established an inhalation DNEL for local effects for corrosive substances of 1 mg/m3that should be applied for long- and short-term exposure equally. The derivation of this value is fully described in Messinger (2013). 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. Substances identified as corrosive in self-classifications only were not considered, since they lack a peer review of the classification assigned. After exclusion of some (groups of) substances, such as CMR substances, the evaluation retrieved 40 corrosive substances with OEL values effective in Germany. In addition to the dermal effects, corrosive substances often display pronounced acute toxicity when administered by other pathways, especially via inhalation. When all very toxic (R26 or R27 or R28) and all sensitising (R42 or R43) substances were removed from the set of 40 corrosive substances, only 2/24 (8%) substances had an OEL below 1 mg/m3. The two substances are 1) sulfuric acid, a very strong acid vigorously reacting with water and b) barium hydroxide, for which the low OEL was derived on the basis of systemic effects (Messinger, 2013).

Overall, the applicability domain of the DNEL of 1 mg/m3for corrosive substances is defined as follows (Messinger, 2013):

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

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

The registration substance is a skin sensitizer and therefore, does not fully fulfills the criteria set by Messinger, 2013. Therefore, the derived value is considered as to valid to avoid the potentially local damage effect on respiratory tract. Due to the observed skin sensitization property, any dermal exposure to airborne substances by deposition should be avoided.

In conclusion, the DNEL of 1 mg/m3can be applied. With this DNEL for local effects, any potential systemic effects are covered as well.

Dermal systemic and local effects (long-term and short-term; worker)

The registered substance is considered to be a skin sensitizer. No dermal exposure is allowed.

Local effects of eyes (worker)

The registered substance may cause serious eye damage. No eye exposure is allowed.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

No consumer use and no use associated with general population exposure will be supported by the registrant.