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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.53 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Modified dose descriptor starting point:
NOAEC
Value:
13.13 mg/m³
Explanation for the modification of the dose descriptor starting point:
According to ECHA-guidance R.8.
AF for dose response relationship:
2
Justification:
According to ECHA-guidance R.8.
AF for differences in duration of exposure:
2
Justification:
According to ECHA-guidance R.8.
AF for interspecies differences (allometric scaling):
1.6
Justification:
According to ECHA-guidance R.8.
AF for other interspecies differences:
2.5
Justification:
According to ECHA-guidance R.8.
AF for intraspecies differences:
5
Justification:
According to ECHA-guidance R.8.
AF for the quality of the whole database:
1
Justification:
According to ECHA-guidance R.8.
AF for remaining uncertainties:
1
Justification:
According to ECHA-guidance R.8.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.59 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:
According to ECHA-guidance R.8.

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:
DNEL (Derived No Effect Level)
Value:
0.15 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Modified dose descriptor starting point:
NOAEL
Value:
3.75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to ECHA-guidance R.8.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1.6
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
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

Allometric scaling factor

Based on the body weight given in the study report of the oral sub-chronic repeated dose study and according ECHA Guidance R.8, p.24, the allometric scaling factor is calculated to be 1.6.

Long-term exposure: Systemic Effects

a) Inhalation DNEL

One oral sub-chronic repeated dose study was available. This study was used for calculation of a dermal DNEL for long-term systemic effects. Before applying appropriate assessment factors the NOAEL from the repeated dose study needs to be corrected according to ECHA Guidance R.8.

Data regarding absorption of phenothiazine from the gastrointestinal tract after oral application indicate that in best case 50% of orally administered phenothiazine are actually absorbed. Therefore it is prudent to apply an additional safety factor of 2 to correct for oral and dermal absorption (according to ECHA Guidance R.8, p.19). Respiratory volumes and exposure duration need to be taken into account according to ECHA Guidance R.8, p. 20 and 59).

The corrected NOAEC for workers is calculated to be: 13.13 mg/m3. All further assessment factors according to ECHA Guidance R.8 are applied to this corrected dose descriptor.

b) Dermal DNEL

The same oral sub-chronic repeated dose study as mentioned for "Inhalation DNEL" was used to derive a dermal DNEL.

No reliable data on dermal absorption was available. However, in the study for acute dermal toxicity no signs of systemic toxicity were found. Following ECHA Guidance R.8, p19 ("On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation.") no additional factor was introduced. No further correction of the NOAEL resulting from the oral sub-chronic repeated dose study was necessary, i.e. the same value as for oral application was taken for calculation of the dermal DNEL.

Qualitative approach for short-term exposure and long-term exposure: Local effects

Phenothiazine is not classified as either irritating to skin or to the eye. Following the results of a guinea pig maximisation test on skin sensitising properties, phenothiazine has a weak skin sensitising potential. However, there is no dose-response information available, hence making calculation of an appropriate DNEL not possible. Therefore, a qualitative approach (acc. ECHA Guidance) is followed.

Risk management measures (RMM) and operational conditions (OC) may be chosen in relation to the potency of the sensitizer (see ECHA Guidance R.8, p120). Based on the respective guidance and the present study result, a moderate incidence of sensitization can be assumed for phenothiazine. A qualitative approach for choosing appropriate RMMs and OCs is described in ECHA Guidance Part E - Risk Characterisation, p15ff. There it is proposed that moderate R43 skin sensitizers (such as phenothiazine) are allocated to the moderate hazard category on the basis that exposure to these moderate skin sensitizing substances should be well controlled. RMMs proposed for moderate hazards (according to ECHA Guidance - Part E, Table E.3 -1) inter alia comprise: good standard of general ventilation, minimizing number of staff exposed and containment as appropriate should be considered/applied. Before any risk measurement measures are selected, a risk characterisation should take place, to relate exposure and the hazard categories.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.13 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Modified dose descriptor starting point:
NOAEC
Value:
6.56 mg/m³
Explanation for the modification of the dose descriptor starting point:
According to ECHA-guidance R.8.
AF for dose response relationship:
2
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1.6
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.39 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:
According to ECHA-guidance R.8.

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:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Modified dose descriptor starting point:
NOAEL
Value:
3.75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to ECHA-guidance R.8.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1.6
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Modified dose descriptor starting point:
NOAEL
Value:
3.75 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1.6
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.24 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Allometric scaling factor

See discussion above (worker section).

Long-term exposure: Systemic Effects

a) Inhalation DNEL

See discussion above (worker section).

b) Dermal DNEL

See discussion above (worker section).

Qualitative approach for short-term exposure and long-term exposure: Local effects

See discussion above (worker section).

It is acknowledged in ECHA Guidance - Part E that RMMs for consumer preparations are limited. Since the actual implementation of technical controls and personal protective equipment (PPE) is usually difficult to achieve in practice, product-integrated measures (such as the maximum volume of the bottle, diluted preparations, etc.) are often the only appropriate RMMs.