Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.235 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
DNEL value:
17.63 mg/m³
Explanation for the modification of the dose descriptor starting point:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
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:
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:
low hazard (no threshold derived)

Additional information - workers

Worker:

Based on the available data, Ethanone, 1-(2-hydroxy-5-nonylphenyl)-, oxime, branched, has to be considered as irritating to skin and eyes (Skin and Eye Cat. 2 [only R38 according to DSD-DPD but not R36]), sensitizing to the skin (R43/Cat.1) and toxic to reproduction (R60/61; Cat. 1B, FD) respectively.

The primary routes of anticipated industrial and professional exposure are via inhalation and skin contact. In industrial settings, ingestion is not an anticipated route of exposure, but has to be considered for the general population (see below).

Inhalation long-term exposure – systemic effects:

The LOAEL from an oral OECD Guideline 421 study (Reproduction / Developmental Toxicity Screening Test) (BASF, 2014) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The LOAEL for toxicity to reproduction was at 30 mg/kg bw/day.

This point of departure was modified to get the corrected starting point for DNEL derivation.

An additional safety factor of 3 was applied in order to convert this LOAEL to a NOAEL of 10 mg/kg bw/day (standard factor as outlined in REACh Guidance document R.8). 

Then, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 1/0.38 m³/kg/d x 6.7 m³/10 m³). The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 17.63 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 1

Besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that 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 have to be taken into account.

- Remaining differences: 2.5

Standard factor as outlined in REACh Guidance document R.8  

 - Intraspecies factor: 5

Standard factor as outlined in REACh Guidance document R.8  

- Exposure duration: 6

Standard factor as outlined in REACh Guidance document R.8  

- Dose-response: 1

Total AF = 1 x 2.5 x 5 x 6 x 1 = 75

Based on this calculation the resulting DNEL is 0.235 mg/m³.

No additional safety factor to compensate for the read across is necessary as the range-finding study with Ethanone, 1-(2-hydroxy-5-nonylphenyl)-, oxime, branched showed that the effects on the seminal vesicles observed in this range-finder at 150 mg/kg (the lowest dose tested) are comparable to the effects on the seminal vesicles observed at 30 mg/kg in the OECD 421 study with the read across substance. The read across substance seems to represent the worst case and thus no further safety factor is applied.

Dermal short-term and long-term exposure – local and systemic effects:

The substance is irritating to the skin and causes skin sensitization in experimental animals.

For these effects, a qualitative assessment was conducted:

Though sensitization reactions and irritation of the skin are generally regarded as threshold effects, deriving a threshold and setting a DNEL is not possible in this case. No sufficient dose-response data of the tested substance are on-hand, which would support a quantitative determination of a local DNEL.

Therefore the use of gloves and the use of stringent risk management measures as outlined in ECHA guidance document Part E: Risk Characterization (Table E. 3-1, page 28-32) is required in order to prevent any skin contact with the test substance and thus the occurrence of skin sensitization and skin irritation.

 

The use of gloves and of stringent risk management measures will also protect the worker from any systemic dermal effects, short-term and long-term. The derivation of a DNEL for systemic dermal exposure in this case is not possible as the toxicokinetic assessment revealed a low dermal absorption potential and thus a route-to-route extrapolation from the available oral studies is not feasible as it would lead to considerable error and potentially to a DNEL that could be either too high or too low and thus might not be protective enough for the local effects (skin sensitization and skin irritation).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Consumer

The general population is not exposed to the registered substance since it is exclusively used in very restrictive industrial and professional settings (mining, closed batch conditions). There is no relevant environmental release that results in an exposure above the TTC for Cramer Class III substances (high risk) and therefore also no relevant indirect exposure to the general population occurs.