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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
7.64 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
Dose descriptor starting point:
NOAEL
Value:
650 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
573.03 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. For details on calculations please refer to discussion.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not used for inhalation. Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
2.17 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
Dose descriptor starting point:
NOAEL
Value:
650 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
650 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. The recommended approach using oral data and assuming the same absorption for dermal and oral route is used. For details, please refer to the discussion.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
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:
no hazard identified

Additional information - workers

According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

Long term, systemic DNEL

Occupational exposure to the test substance occurs mainly by inhalation and dermal route. Therefore two long-term DNELs are calculated for workers. In view of the data used for evaluation, the "quality of whole database factor", "dose-response factor" and remaining “uncertainties” and are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

Exposure by inhalation

Step 1: Selection of the relevant dose descriptor (starting point):

No repeated dose inhalation toxicity studies are available for tert-butylbenzene. Therefore the DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

The Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test according to OECD 422 is selected for DNEL derivation. This study is the relevant repeated dose study performed using tert-butylbenzene in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 650 mg/kg bw/day.

Step 2: Modification into a correct starting point:

Using a conservative approach, a worker DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation than oral absorption.

Relevant dose descriptor (NOAEL): 650 mg/kg bw/day

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat 50 %/ ABSinh-human 100 %): 0.5

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

Corrected inhalatory NOAEC for workers

= 650 mg/kg bw/day * 0.5 * (1 / 0.38 m³/kg bw/day) * (6.7 m³/10 m³)

= 573.03 mg/m³

Step 3: Use of assessment factors: 75

Interspecies: Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 6

In conclusion, long term systemic inhalation DNEL, workers = 7.64 mg/m³

Dermal exposure

Step 1: Selection of the relevant dose descriptor (starting point):

No repeated dose dermal toxicity studies are available for tert-butylbenzene. Therefore the DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

The Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test according to OECD 422 is selected for DNEL derivation. This study is the relevant repeated dose study performed using tert-butylbenzene in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 650 mg/kg bw/day.

Step 2: Modification of the starting point:

A worker DNEL (long-term dermal exposure) is derived.

Factor for dermal NOAEL= 100 % oral / 100 % dermal= 1

oral NOAEL 650 mg/kg bw/day * 1 = 650 mg/kg bw/day dermal NOAEL

Step 3: Use of assessment factors: 300

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 6

In conclusion, long term systemic dermal DNEL, workers = 2.17 mg/kg bw/day

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1 ECHA-2010-G-19 –EN.

- ECHA (2012) Practical Guide 14: How to prepare toxicological summaries in IUCLID and how to derive DNELs

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.88 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
Dose descriptor starting point:
NOAEL
Value:
650 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
282.61 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. For details on calculations please refer to discussion.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
1.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
650 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
650 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. The recommended approach using oral data and assuming the same absorption for dermal and oral route is used. For details, please refer to the discussion.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
1.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
650 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
650 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
10
Justification:
The default value for the relatively homogenous group "general population" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
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

According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

Long term, systemic DNEL

Occupational exposure to the test substance occurs mainly by inhalation and dermal route. Therefore two long-term DNELs are calculated for general Population. In view of the data used for evaluation, the "quality of whole database factor", "dose-response factor" and remaining “uncertainties” and are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

Exposure by inhalation

Step 1: Selection of the relevant dose descriptor (starting point):

No repeated dose inhalation toxicity studies are available for tert-butylbenzene. Therefore the DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

The Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test according to OECD 422 is selected for DNEL derivation. This study is the relevant repeated dose study performed using tert-butylbenzene in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 650 mg/kg bw/day.

Step 2: Modification into a correct starting point:

Using a conservative approach, a worker DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation than oral absorption.

Relevant dose descriptor (NOAEL): 650 mg/kg bw/day

Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance (R.8.4.2): 1.15 m3/kg bw

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat 50 %/ ABSinh-human 100 %): 0.5

Corrected inhalatory NOAEC for general population

= 650 mg/kg bw/day * 0.5 * (1 / 1.15 m3/kg bw)

= 282.61 mg/m³

Step 3: Use of assessment factors: 150

Interspecies: Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 6

In conclusion, long term systemic inhalation DNEL, general population = 1.88 mg/m³

Dermal exposure

Step 1: Selection of the relevant dose descriptor (starting point):

No repeated dose dermal toxicity studies are available for tert-butylbenzene. Therefore the DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

The Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test according to OECD 422 is selected for DNEL derivation. This study is the relevant repeated dose study performed using tert-butylbenzene in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 650 mg/kg bw/day.

Step 2: Modification of the starting point:

A general population DNEL (long-term dermal exposure) is derived.

Factor for dermal NOAEL= 100 % oral / 100 % dermal= 1

oral NOAEL 650 mg/kg bw/day * 1 = 650 mg/kg bw/day dermal NOAEL

Step 3: Use of assessment factors: 300

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 6

In conclusion, long term systemic dermal DNEL, general population = 1.08 mg/kg bw/day

Oral exposure

Step 1: Selection of the relevant dose descriptor (starting point):

No repeated dose dermal toxicity studies are available for tert-butylbenzene. Therefore the DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

The Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test according to OECD 422 is selected for DNEL derivation. This study is the relevant repeated dose study performed using tert-butylbenzene in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 650 mg/kg bw/day.

Step 2: Modification of the starting point:

A general population DNEL (long-term oral exposure) is derived.

oral NOAEL 650 mg/kg bw/day = 650 mg/kg bw/day oral NOAEL

Step 3: Use of assessment factors: 300

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 6

In conclusion, long term systemic oral DNEL, general population = 1.08 mg/kg bw/day