Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.5 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):

12.5

Modified dose descriptor starting point:

NOAEC

Value:

44.07 mg/m³

Explanation for the modification of the dose descriptor starting point:

Worker Population - NOAEL of 25 mg/kg/d / 0.38 m3/kg = 65.8 * [6.7 m3/ 10 m3] = 44.07 mg/m3

AF for dose response relationship:

1

Justification:

Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.

AF for differences in duration of exposure:

1

Justification:

For duration adjustment no factor is needed.

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

A default factor of 2.5 accounts for additional interspecies differences.

AF for intraspecies differences:

5

Justification:

For intraspecies differences (workers) the default factor is 5.

AF for the quality of the whole database:

1

Justification:

The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.5 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):

50

Modified dose descriptor starting point:

NOAEL

Value:

25 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Dermal risk assessment is based on the oral NOAEL of 25 mg/kg/day from the repeat dose toxicity test. The worst case (100% absorption) was assumed.

AF for dose response relationship:

1

Justification:

Since the DNEL is to be derived from a starting position based on an NOAEL from a good quality study, the dose response assessment factor was the default value, AF = 1.

AF for differences in duration of exposure:

1

Justification:

For duration adjustment no factor is needed.

AF for interspecies differences (allometric scaling):

4

Justification:

The allometric scaling factor for the rat is 4.

AF for other interspecies differences:

2.5

Justification:

A default factor of 2.5 accounts for additional interspecies differences.

AF for intraspecies differences:

5

Justification:

For intraspecies differences (workers) the default factor is 5.

AF for the quality of the whole database:

1

Justification:

The default assessment factor to be applied is AF = 1. Higher factors may be applied based on scientific judgment related to adequacy and consistency. The database is considered relevant to assessment of repeated dose oral toxicity and is considered adequate, robust and reliable.

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

A.- ACUTE TOXICITY:

No acute effects were seen. Therefore no acute DNELs are necessary to be derived.

 

B.-SKIN IRRITATION AND SENSITIZATION. Acute Local effects

The substance is not skin irritant. No DNEL need to be derived.

C.- REPEAT DOSE TOXICITY: Systemic effects

Long term Dermal exposure

Dermal risk assessment is based on the oral NOAEL of 25 mg/kg/day from a chronic toxicity test. The worst case (100% absorption) was assumed.

The following adjustment factors are applied:

(1) for duration adjustment no factor is needed,

(2) the allometric scaling factor for the rat is 4;

(3) a default factor of 2.5 accounts for additional interspecies differences;

(4) for intraspecies differences (workers) the default factor is 5,

 

This gives a reference AF of 50 for workers (4 x 2.5 x 5),

DNEL_{syst.long term}Dermal route is established in 0.5 mg/kg/day (workers)

Long term Oral exposure

Starting point is NOAEL of 25 mg/kg/day from a chronic toxicity rat study. Assuming 100% absorption and the AF described above, critical exposure levels are as follows:

Workers: = 0.5 mg/kg/day

Long term Inhalatory exposure

Same starting point is taken as previous calculations.

 

Worker Population - NOAEL of 25 mg/kg/d /0.38m3/kg * [6.7 m3/ 10 m3] = 44.07 mg/m3.

 

Assessment factors are:

1)     a default factor of 2.5 accounts for additional interspecies differences;

2)     for intraspecies differences (workers) the default factor is 5,

 

 

DNEL inhalation, systemic, chronic worker population = 44.07 / 12.5 = 3.5 mg/m3.

 

C.- REPRODUCTIVE AND DEVELOPMENT TOXICITY

Oral exposure

Starting point is NOAEL_fert.= 25 mg/kg/day from a reproductionstudy on rats.

 

The following adjustment factors are applied:

(1) the allometric scaling factor for the rat is 4;

(2) a default factor of 2.5 accounts for additional interspecies differences;

(3) for intraspecies differences (workers) the default factor is 5, for consumers is 10

 

Overall the reference AF is 50 (4 x 2.5 x 5) .The respective critical oral exposure level at the workplace is identified as:

 

DNEL = 0.5 mg /kg/day for workers and

 

Dermal exposure

Same starting point and same AF were used for deriving DNELs. Worst case of 100% absorption was assumed.

 

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

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