Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
12.006 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):
105
Modified dose descriptor starting point:
NOAEC
Value:
1 260.658 mg/m³
AF for interspecies differences (allometric scaling):
7
Justification:
mouse default
AF for intraspecies differences:
5
Justification:
worker default
AF for the quality of the whole database:
1
Justification:
data on substance
AF for remaining uncertainties:
1
Justification:
none known
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:
DNEL (Derived No Effect Level)
Value:
6.81 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
105
Modified dose descriptor starting point:
NOAEL
Value:
715 mg/kg bw/day
AF for interspecies differences (allometric scaling):
7
Justification:
mouse default
AF for intraspecies differences:
5
Justification:
worker default
AF for the quality of the whole database:
1
Justification:
data on substance
AF for remaining uncertainties:
1
Justification:
none known
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - workers

Toxicokinetics

Absorption:Acetaminophen is rapidly and almost completely absorbed from the GI tract following oral administration.Food may delay slightly absorption of extended-release tablets of acetaminophen

Distribution:Acetaminophen is rapidly and uniformly distributed into most body tissues About 25% of acetaminophen in blood is bound to plasma proteins Following oral administration of immediate- or extended-release acetaminophen preparations, peak plasma concentrations are attained within 10-60 or 60-120 minutes, respectively. Following oral administration of a single 500-mg conventional tablet or a single 650-mg extended-release tablet, average plasma acetaminophen concentrations of 2.1 or 1.8 ug/mL, respectively, occur at 6 or 8 hours, respectively.

Metabolism:About 80-85% of the acetaminophen in the body undergoes conjugation principally with glucuronic acid and to a lesser extent with sulfuric acid. Acetaminophen also is metabolized by microsomal enzyme systems in the liver.

Excretion:Acetaminophen is excreted in urine principally as acetaminophen glucuronide with small amounts of acetaminophen sulfate and mercaptate and unchanged drug. Approximately 85% of a dose of acetaminophen is excreted in urine as free and conjugated acetaminophen within 24 hours after ingestion.Administration of acetaminophen to patients with moderate to severe renal impairment may result in accumulation of acetaminophen conjugates.

 

Acute toxicity

Paracetamol is non acute toxicity to dermal and inhalation routes investigated, the acute oral LD50 of the substance was found to be > 2000 mg/kg/bw and so will qualify for category 4 in acute oral condition. 

 

Irritation / corrosion

In vivo studies of the substance show that the substance is irritating to skin and eyes, and so the substance is classified as skin irri 2 & eye irri 2 for skin and eye as per the regulation.

 

Sensitisation

Skin sensitisation of Paracetamol was tested on humans. Positive responses were recorded and so the substance was found to be sensitizing to the skin.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.961 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):
210
Modified dose descriptor starting point:
NOAEC
Value:
621.739 mg/m³
AF for interspecies differences (allometric scaling):
7
Justification:
mouse default
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
1
Justification:
data on substance
AF for remaining uncertainties:
1
Justification:
none known
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.405 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
210
Modified dose descriptor starting point:
NOAEL
Value:
715 mg/kg bw/day
AF for interspecies differences (allometric scaling):
7
Justification:
mouse default
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
1
Justification:
data on substance
AF for remaining uncertainties:
1
Justification:
none known
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.702 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
210
Modified dose descriptor starting point:
NOAEL
Value:
357.5 mg/kg bw/day
AF for interspecies differences (allometric scaling):
7
Justification:
mouse default
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
1
Justification:
data on substance
AF for remaining uncertainties:
1
Justification:
none known
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - General Population

DNEL derivation

 

Paracetamolis non acute toxic to dermal and inhalation but is slightly toxic to oral route, do show irritation effect to skin and eye, is not genotoxic and is not a developmental or reproductive toxin.

 

In the absence of local effects following short-term or long-term exposure, no dose-response data are available and a quantitative dose descriptor is not derived. DNEL values for local exposure are therefore not calculated.

 

In the absence of acute systemic toxicity, no dose-response data are available and a quantitative dose descriptor is not derived. DNEL values for acute systemic effects are therefore not calculated.

 

A standard approach to deriving DNEL values would be to use the reproductive toxicity dataset and apply assessment factors as described in ECHA guidance documents. The critical endpoint is considered to be the NOAEL of 1430 mg/kd bw/d in oral category.