Chlorphenesin

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.64 mg/m³

Most sensitive endpoint:

repeated dose toxicity

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

Value:

122.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Inhalation is not the preferred route for absorption. Original value is NOAEL 100 mg/kg bw/day, subacute toxicity in rat by oral administration. Allometric scaling from rat to human is 4. The result is multiplied by 70 kg considered as the average weight of a human being (bw) and divided by 10 m^3/person considered as the average volume that is breathed in a 8h exposure. Conclusion [(100 mg/kg bw/d / 4)*70 kg bw]/10 m^3/person= 175 mg/m^3. This value should be multiply by 0.5 (considering the oral absorption 50% in oral-to-inhalation extrapolation) and by 1.4 (considering the correction for differences between human and experimental exposure conditions, i.e. 7 days per week (experimental)/ 5 days per week (worker population)). NAEC is 122.5 mg/ m^3.

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed n ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

1

Justification:

Already considered in NOAEC calculation (Appendix R 8.2).

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

5

Justification:

Default value proposed in ECHA R.8 Guidance for worker (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.467 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

300

Modified dose descriptor starting point:

other: NOAEL ( 100 mg/ kg bw/day) modified considering the differences between human and experimental exposure conditions.

Value:

140 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Original value NOAEL 100 mg/kg bw/day (subacute toxicity in rat by oral administration) was multiplied by 1.4 (considering the correction for differences between human and experimental exposure conditions, i.e. 7 days per week (experimental)/ 5 days per week (worker population)). Starting point = 100 mg/ kg bw/day * 1.4 = 140 mg/ kg bw/day

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed n ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

4

Justification:

Default value proposed in ECHA R.8 guidance ( table R 8.3)

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

5

Justification:

Default value proposed in ECHA R.8 Guidance for worker (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

Chlorphenesin is classified H315 (skin irr. cat.2) and H319 (eye irr.cat.2) according to the CLP Regulation (EC n.1272/2008).

The assessment is done based on repeated dose toxicity studies (NOAEL 28 days rat =100 mg/kg bw/day).

 

The values of DNEL calculated for workers are:

 

INHALATION ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL= 1.64 mg/m^3 (NAEC= 122.5 mg/m^3 and Overall AF= 75)

b) SHORT TERM: No hazard identified

LOCAL EFFECTS: Low hazard identified for LONG and SHORT TERM exposure based on its potential to be irritant for mucous membrane of nasopharyngeal region.

DERMAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 0.467 mg/kg bw/day (Starting point: 100 mg/kg bw/day(NOAEL) *1.4 = 140 mg/kg bw/day and Overall AF= 300)

b) SHORT TERM: No hazard identified

LOCAL EFFECTS: Low hazard identified for LONG AND SHORT TERM based on the substance has been classified irritant to the skin (H315).

 

HAZARD FOR EYE:LOCAL EFFECTS: Low hazard identified based on the substance has been classified irritant to the eyes (H319).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.247 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

150

Modified dose descriptor starting point:

NOAEC

Value:

37.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Inhalation is not the preferred route for absorption. Original value is NOAEL 100 mg/kg bw/day, subacute toxicity in rat by oral administration. Allometric scaling from rat to human is 4. The result is multiplied by 60 kg considered as the average weight of a human being (bw) and divided by 20m^3/person considered as the average volume that is breathed by general population . Conclusion [(100 mg/kg bw/d / 4)*60 kg bw]/20 m^3/person= 75 mg/m^3. This value should be multiply by 0.5 (considering the oral absorption 50% in oral-to-inhalation extrapolation). NAEC is 37.5 mg/ m^3.

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6)

AF for differences in duration of exposure:

6

Justification:

Default value proposed n ECHA R.8 Guidance for sub-acute to chronic (table R 8.6)

AF for interspecies differences (allometric scaling):

1

Justification:

Already considered in NOAEC calculation (Appendix R8.2)

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6)

AF for intraspecies differences:

10

Justification:

Default value proposed in ECHA R.8 Guidance for general population (table R 8.6)

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.167 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

600

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed n ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

4

Justification:

Default value proposed in ECHA R.8 guidance ( table R 8.3).

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

10

Justification:

Default value proposed in ECHA R.8 Guidance for general population (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

A DNEL is not derived as no acute toxicity hazard leading to Classification & Labelling was identified (ECHA guidance document R 8.1.2.5). According to the Commission Regulation (EU) 2016/863 of 31 May 2016 amending Annexes VII and VIII to Regulation (EC) No 1907/2006 testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation). LD 50 oral route for Chlorphenesin is major than 2000 mg/kg bw and no classification is required for acute oral toxicity.

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.167 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

600

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation.

AF for dose response relationship:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for differences in duration of exposure:

6

Justification:

Default value proposed n ECHA R.8 Guidance for sub-acute to chronic (table R 8.6).

AF for interspecies differences (allometric scaling):

4

Justification:

Default value proposed in ECHA R.8 guidance ( table R 8.3).

AF for other interspecies differences:

2.5

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6).

AF for intraspecies differences:

10

Justification:

Default value proposed in ECHA R.8 Guidance for general population (table R 8.6).

AF for the quality of the whole database:

1

Justification:

Default value proposed in ECHA R.8 Guidance (table R 8.6) for database of good quality and reliability.

AF for remaining uncertainties:

1

Justification:

No further uncertainties.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

Chlorphenesin is classified H315 (skin irr. cat.2) and H319 (eye irr.cat.2) according to the CLP Regulation (EC n.1272/2008).

The assessment is done based on repeated dose toxicity studies (NOAEL 28 days rat =100 mg/kg bw/day).

 

The values of DNEL calculated for general population are:

 

INHALATION ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL= 0.247 mg/m^3 (NAEC= 37.5 mg/m^3 and Overall AF= 150)

b) SHORT TERM: No hazard identified

LOCAL EFFECTS: Low hazard identified for LONG AND SHORT TERM based its potential to be irritant for mucous membrane of nasopharyngeal region

DERMAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 0.167 mg/kg bw day (Starting point NOAEL= 100 mg/kg bw/day and Overall AF= 600)

b) SHORT TERM: No hazard identified

LOCAL EFFECTS:  Low hazard identified for LONG AND SHORT TERM based on the substance has been classified irritant to the skin.

 

ORAL ROUTE:

SYSTEMIC EFFECTS:

a) LONG TERM: DNEL = 0.167 mg/kg bw/day (NOAEL= 100 mg/kg bw/ day and Overall AF= 600)

b) SHORT TERM: : No hazard identified  based on the substance is not classified for acute oral toxicity.

 

HAZARD FOR EYE:LOCAL EFFECTS: Low hazard identified based on the substance has been classified irritant to the eyes.