Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.3 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
DNEL value:
175 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
308 mg/m³
Explanation for the modification of the dose descriptor starting point:

A long-term systemic inhalation DNEL is derived from the oral NOAEL of 175 mg/kg bw/day (OECD 414) using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 10%, equal to that of the inhalation rate (i.e. oral and inhalation absorption values both 10% are assumed). The corrected inhalation NOAEC for workers is derived as: oral NOAEL x (1/0.38 m3/kg/day) x (6.7 m3/10m3 (8 h)) x (% oral absorption/ % inhalation absorption) = 175 mg/kg bw/day x (1/0.38) x 0.67 x (10/10) = 308 mg/m3. The following assessment factors have been used in accordance with REACH guidance: Interspecies: a default value of 2.5 (remaining differences) is proposed (the application of a factor for allometric scaling is not required for the inhalation route); Intraspecies: a default value of 5 is proposed for workers; Exposure duration: a default value of 2 is proposed for extrapolation from a sub-chronic study to chronic exposure (this represents a conservative approach); Dose-response: a default value of 1 is proposed as, based on the available data, the substance is of low toxicity; Quality of the data base: a default factor of 1 is proposed; Remaining uncertainties: a default factor of 1 is proposed to account for any associated uncertainties and use of read-across study. An overall assessment factor of for long-term inhalational effects is therefore calculated for workers.

Applying the assessment factor of 25 to the corrected inhalation NOAEC of 308 mg/m3 gives an inhalation DNEL value of 12.3 mg/m3 for long-term systemic effects.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore a DNEL for acute systemic effects following inhalation exposures is not proposed.

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.75 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
DNEL value:
175 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
175 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A long-term systemic dermal DNEL is derived from the oral NOAEL of 175 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 10% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 175 mg/kg bw/day x (10/10) = 175 mg/kg bw/day.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore a DNEL for acute systemic effects is not proposed. The substance is irritating and sensitising to the skin following dermal contact and is not expected to pass easily through the skin. Effects following dermal exposure will be characterised by dermal irritation and possible sensitising effects that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal uptake. Considering the relative low systemic toxicity via the oral route, any relevant exposure leading to systemic effects can be expected to be preceded by local dermal effects first.

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

According to REACH "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10t/y, the establishement of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, acute DNELs should default the long-term systemic DNELs.

For local effects, a DNEL was not quantifiable; However, as the substance is known to be a skin sensitizer, local effects must be assessed qualitatively and risk management measures applied as necessary. The potential for respiratory sensitization is unknown; however, given its skin sensitization potential, this endpoint should also be assessed qualitatively.

The dose descriptor starting point for DNEL calculation used was a NOAEL: 175 mg/kg bw (determined during an OECD 414 pre-natal developmental study in rats performed in 2016 -2017).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not intended to be marketed for consumer use.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not intended to be marketed for consumer use.

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The substance is not intended to be marketed for consumer use.

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:
no hazard identified
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

The substance is not intended to be marketed for consumer use.