Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.411 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
Dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
30.86 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no adequate experimental data on the inhalation route available. Therefore, the worker-DNEL long-term for inhalation route - systemic is derived from the oral NOAEL of 25 mg/kg bw/day, obtained in the key "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in Wistar Rats Oral Administration (Gavage)" (OECD TG 422). The NOAECcorr. is calculated as follows:

- standard respiratory volume rat = 0.38 m³/kg/8h

- standard respiratory volume human = 6.7 m³/8h

- worker respiratory volume = 10 m³/8h

- absorption (oral, rat) = 50 % (default)

- absorption (inhalative, human) = 100 % (default).As worst case, inhalative absorption is assumed to be two times more than oral absorption which allows for a modification of the starting point by factor 2.

- exposure animal = 7 days / week

- exposure human = 5 days / week

--> modified dose descriptor (corrected inhalatory NOAEC) = 25 mg/kg bw/day * (1/0.38 m³/kg/d) * (6.7 m³ (8h)/10 m³ (8h)) * (50%/100%) * (7 day exposure animal / 5 day worker) = 30.86 mg/m³

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance: starting point for the DNEL calculation is a NOAEL, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
ECHA REACH Guidance: The recommended AF for the extrapolation from sub-acute to chronic exposure is applied.
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance: no additional factor needed for extrapolation from oral to inhalation route
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance: The recommended AF for the interspecies differences is applied.
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance: The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance: The quality of the whole data base is considered to be sufficient.
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance: default factor. The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
medium hazard (no threshold derived)

Additional information - workers

Worker:

Based on the available data, Benzaldehyde, 2-hydroxy-5-nonyl-, oxime, branched, has to be considered as irritating to the skin (R38/Cat. 2), poses the risk of serious eye damage (R41/Cat.1 ), is sensitizing to the skin (R43/Cat.1), may cause damage to organs through prolonged or repeated exposure (R48/22, STOT RE Cat. 2) and is 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 NOAEL from an oral OECD Guideline 422 study (BASF, 2020) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for toxicity to reproduction was at 25 mg/kg bw/day.

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

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, for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, exposure duration and potential absorption differences, by multiplying with the corresponding factors.

The NOAECcorr. is calculated as follows:

- standard respiratory volume rat = 0.38 m³/kg/8h

- standard respiratory volume human = 6.7 m³/8h

- worker respiratory volume = 10 m³/8h

- absorption (oral, rat) = 50 % (default)

- absorption (inhalative, human) = 100 % (default).As worst case, inhalative absorption is assumed to be two times more than oral absorption which allows for a modification of the starting point by factor 2.

- exposure animal = 7 days / week

- exposure human = 5 days / week

--> modified dose descriptor (corrected inhalatory NOAEC) = 25 mg/kg bw/day * (1/0.38 m³/kg/d) * (6.7 m³ (8h)/10 m³ (8h)) * (50%/100%) * (7 day exposure animal / 5 day worker) = 30.86 mg/m³

The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 30.86 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 0.411 mg/m³.

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 32 -36) 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:
medium 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.

For assessment of exposure "man via the environment" a DNEL(oral, systemic long-term) of 0.0416 mg/kg bw/day is assumed based on the NOAEL of 25 mg/kg of the OECD 422 study and an overall assessment factor of 600.