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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.47 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):
10
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
24.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
1
Justification:
The approach of the DNEL derivation is already conservative (no further assessment factor needed).
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The approach of the DNEL derivation is already conservative (no further assessment factor needed).
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:
0.7 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):
40
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
28 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by the dermal route.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
1
Justification:
The approach of the DNEL derivation is already conservative (no further assessment factor needed).
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The approach of the DNEL derivation is already conservative (no further assessment factor needed).
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:
low hazard (no threshold derived)

Additional information - workers

Long-term exposure - systemic effects

In the absence of an inhalation as well as dermal toxicity study with repeated exposure, the long term DNEL for the inhalative route of exposure concerning systemic effects was derived from the NOAEL obtained in the key subchronic oral repeated dose study in Wistar rats (OECD 408). In this study, female animals were more sensitive compared to male animals and thus, the NOAEL obtained for female animals was taken into account for DNEL derivation. The corrected inhalatory NOAEC was calculated using the default respiratory volume for the rat and a correction for the difference between human respiratory rats under standard conditions and under conditions of light activity.

The corrected dermal NOAEL was calculated using a correction for the differences in exposure duration.

Calculation of the NOAEC

 

- standard dose descriptor (NOAEL): 20 mg/kg bw/d

- 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)/ABSinhal-human): 50/100

- 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

- exposure duration rat/expsoure duration of humans: 7/5 (days per week)

Corrected inhalatory NOAEC for workers:

= NOAEL * (1/sRVrat) * (ABSoral-rat/ABSinhal-human) *(sRVhuman/wRV)

= 20 mg/kg bw/d * (1/0.38 m³/kg bw/d)* (50/100) * (6.7m³/10 m³)

= 24.7 mg/m³

 

Calculation of the NOAEL

 

- standard dose descriptor (NOAEL): 20 mg/kg bw/d

- oral absorption of the rat/dermal absorption of humans (ABSoral-rat)/ABSdermal-human): 1/1

- exposure duration rat/expsoure duration of humans: 7/5 (days per week)

Corrected dermal NOAEL for workers:

= NOAEL * (ABSoral-rat/ABSdermal-human)

= 20 mg/kg bw/d * (7/5) * (1/1)

= 28 mg/kg bw

 

References

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-2012 -G-19 -EN.

 

Qualitative risk assessment

The available data for short as well as long term local and short term systemic effects do not provide quantitative dose-response information; thus, no DNELs have been derived and no quantitative risk assessment was performed. Exposure assessment and risk characterization are performed on a qualitative basis.

The purpose of a qualitative risk characterization is to assess "the likelihood that effects are avoided when implementing the exposure scenario…" (REACH Annex 1, Section 6.5) when there is no basis for setting a DNEL/DMEL.

Implementation of risk management measures (RMMs) and operational conditions (OCs) need to be proportional to the degree of concern for the health hazard presented by the substance. Therefore the substance is categorized by the hazard according to ECHA Guidance on information requirements and chemical safety assessment, Part E; November 2012.

The substance shows the following hazards: acute oral toxicity, cat. 2 and eye irritation, cat. 2

Eye irritation is considered a low hazard while acute oral toxicity (cat. 2) represents a high hazard therefore the substance is categorized to the high hazard group.

RMM should be appropriate for hazard class and operational condition. Therefore, a code of behavior is communicated via the Safety Data Sheet (SDS) containing precaution statements and response phrases and general handling instructions. 

A review of this information on RMM and behavior advice given with the product indicates that, if the user complies to the advice, the risk of exposure for worker and professional user can be considered as adequately controlled.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 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):
80
Dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Most sensitive and reliable study for DNEL calculation

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
1
Justification:
The approach of the DNEL derivation is already conservative (no further assessment factor needed).
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The approach of the DNEL derivation is already conservative (no further assessment factor needed).
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

No consumer uses were identified. The general population does not get in contact with the substance. Therefore, in accordance with the REACH legislation (regulation (EC) No 1907/2006, Annex I, 1.4.1), no DNEL has to be derived for the general population. Although there are no consumer uses for diisopropanol-p-toluidine (CAS 38668-48-3), the systemic long-term oral DNEL for the general population is necessary for our assessment of indirect exposure of humans via the environment (ECHA GD R.16, v 3.0, Feb 2016).

Long-term exposure - systemic effects

The general population long term DNEL for the oral route of exposure concerning systemic toxicity was derived from the NOAEL obtained in the subchronic oral repeated dose study in Wistar rats (OECD 408). In this study, female animals were more sensitive compared to male animals and thus, the NOAEL obtained for female animals was taken into account for DNEL derivation. The corrected oral NOAEL way equal with the oral NOAEL of the repeated dose study, since no difference in absorption rate between rats, humans, and exposure routes and exposure duration was assumed.

Calculation of the oral NOAEL

 

- Standard dose descriptor (NOAEL): 20 mg/kg bw/d

- Oral absorption of the rat/oral absorption of humans (ABSoral-rat)/ABSoral-human): 1/1

Corrected oral NOAEL for the general population:

= NOAEL * (ABSoral-rat/ABSoral-human)

= 20 mg/kg bw/d * (1/1)

= 20 mg/kg bw

References

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-2012 -G-19 -EN.