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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19.6 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):
18
Modified dose descriptor starting point:
NOAEC
DNEL value:
353 mg/m³
Explanation for the modification of the dose descriptor starting point:
No experimental data on repeated exposure by inhalation available. Recommended approach using oral data and assuming the same absorption for inhalation and oral route.
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). This is considered as a worst case approach.
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:
1
Justification:
There is no evidence for species differences in the general mode of actions or kinetics.
AF for intraspecies differences:
3
Justification:
The (ECETOC) 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:
2.8 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):
72
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Recommended approach using oral data and assuming the same absorption for dermal and oral route.
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). This is considered as a worst case approach.
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:
1
Justification:
There is no evidence for species differences in the general mode of actions or kinetics.
AF for intraspecies differences:
3
Justification:
The (ECETOC) 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
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Long-term exposure – systemic effects

 

Inhalation exposure – calculation of the NOAECcorr:

In order to derive the worker DNEL long-term for inhalation route systemic, the NOAEL of 200 mg/kg bw/day from the subacute oral toxicity study (GAF, 1990) is considered to represent the most conservative dose descriptor for systemic effects related to long-term inhalation exposure.

In order to derive a worker DNEL and under the assumption of a daily exposure period of 8 hours, the oral NOAEL is converted into an inhalation NOAECcorr according to the following formula:

inhalation NOAECcorr

= oral NOAEL × 1/sRV(rat) × ABSoral(rat)/ABSinhalation(human) × sRV(human)/wRV(human)

= 200 mg/kg bw/d × 1/0.38 m³/kg bw/d × 1 × 6.7 m³ / 10 m³ = 353 mg/m³

with:

oral NOAEL: 200 mg/kg bw/day

sRV(rat): 0.38 m³/kg bw (8 hours) [standard respiratory volume of the rat]

ABSoral(rat)/ABSinhalation(human): 1 [ratio of oral absorption in the rat to inhalative absorption in the human]

sRV(human)/wRV(human): 6.7 m³/10 m³ (8 hours) [ratio of human standard respiratory volume to worker respiratory volume]

Accordingly, the oral NOAEL of 200 mg/kg bw/day is transformed in an inhalation NOAECcorr of 353 mg/m³.

This NOAECcorr serves as dose descriptor starting point to derive the corresponding DNEL value.

 

Dermal exposure - calculation of the NOAELcorr:

In order to derive a worker DNEL, the oral NOAEL of 200 mg/kg bw/day (GAF, 1990) is converted into a dermal NOAEL according to the following formula:

dermal NOAEL

= oral NOAEL × ABSoral(rat) / ABSdermal(human)

= 200 mg/kg bw/d × 1

= 200 mg/kg bw/d

with:

oral NOAEL: 200 mg/kg bw/day

ABSoral(rat)/ABSdermal(human): 1 [ratio of oral absorption in the rat to dermal absorption in the human]

Accordingly, the oral NOAEL of 200 mg/kg bw/day is transformed in a dermal NOAEL of 200 mg/kg bw/day. This NOAELcorr serves as dose descriptor starting point to derive the corresponding DNEL value.

 

References 

ECETOC technical report no. 110, 2010 "Guidance on assessment factors to derive a DNEL"; ECETOC technical report no. 86, 2003 “Derivation of assessment factors for human health risk assessment” and ECHA “Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health”, Version: 2.1 (2012),

VCI position paper, 2010: (VCI (Verband der Chemischen Industrie e.V.) (2010). VCI document "Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität". Published 21.01.2010, www.vci.de).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

1,4 -bis[(vinyloxy)methyl]cyclohexane is exclusively handled by industrial and professional workers. Based on the available data, the derivation of general population DNEL (long-term oral exposure) is not triggered in order to enable quantitative risk assessment related to potential exposure of the general population via secondary poisoning. Exposure of the general population is considered to be negligible. Thus, no DNELs were derived for the general population.