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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.4 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):
25
Value:
170 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
210 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in an oral subchronic repeated dose toxicity study.

To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= NOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h)* (7 days exposure rat/5 days exposure worker)

= 170 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (1/1) * 0.67 m³ * 1.4= 420 mg/m³

In accordance with ECHA Guidance, a factor of two is applied for the extrapolation from oral to inhalation absorption.

420 mg/m³ / 2 = 210 mg/m³

AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
2
Justification:
DNEL is based on 90-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
The DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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:
2.38 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
238 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a subchronic repeated dose oral toxicity study.

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) * (7 days exposure rat/5 days exposure worker) = 170 mg/kg bw/day *(1/1) * 1.4 = 238 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.

AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
2
Justification:
DNEL based on a 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
default
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
data is based on a high-quality study
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
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

Acute / short-term exposure

In acute toxicity studies, bis(isopropyl)naphthalene (DIPN) has been shown to be of low toxicity. According to EU legislation no classification and labelling is required.

 

Long-term exposure

Valid data on long term exposure is only available from one repeated dose toxicity study (6 months study) (Kawai 1973). Other studies investigating long term effects do not provide valid data for the assessment of long term toxicity (see endpoint summaries section 7.5 and 7.7).

Kawai reports a NOAEL of 170 mg/kg bw/day. This value originates from a feeding study in rats over 6 months. The NOAEL derived is based on systemic effect. Local effects were not observed in this study.

Since no information is available covering other exposure routes, DNELs for dermal exposure will be derived by route-to-route extrapolation using the oral NOAEL as dose descriptor starting point.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.48 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):
50
Value:
170 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
74 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in an oral subchronic repeated dose toxicity study.

To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= NOAELoral * (1/1.15 m³/kg bw/day (24h)) * (ABSoral-rat / ABSinh-human)

= 170 mg/kg bw/day * (1/1.15 m³/kg bw/day) * (1/1) = 148 mg/m³

AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
2
Justification:
DNEL is based on 90-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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:
0.85 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):
200
Value:
170 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
170 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a subchronic repeated dose oral toxicity study.

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) * (7 days exposure rat/7 days exposure general population) = 170 mg/kg bw/day *(1/1) *1 = 170 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.

AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
2
Justification:
DNEL based on 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
default
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
Justification:
DNEL based on a high quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
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:
0.85 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
170 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAEL from oral 6 month study; no route-to-route extrapolation required.
AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
2
Justification:
DNEL based on 90-day study
AF for interspecies differences (allometric scaling):
4
Justification:
default
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
Justification:
based on a high quality study
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Acute / short-term exposure

In acute toxicity studies, bis(isopropyl)naphthalene (DIPN) has been shown to be of low toxicity. According to EU legislation no classification and labelling is required.

Long-term exposure

Valid data on long term exposure is only available from one repeated dose toxicity study (6 months study) (Kawai 1973). Other studies investigating long term effects do not provide valid data for the assessment of long term toxicity (see endpoint summaries section 7.5 and 7.7).

Kawai reports a NOAEL of 170 mg/kg bw/day. This value originates from a feeding study in rats over 6 months. The NOAEL derived is based on systemic effect. Local effects were not observed in this study.

Since no information is available covering other exposure routes, DNELs for dermal and inhalation exposure will be derived by route-to-route extrapolation using the oral NOAEL as dose descriptor starting point.

 

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