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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:
4.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
105 mg/m³
Explanation for the modification of the dose descriptor starting point:
Not necessary; repeated dose toxicity study by inhalation is available.
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Default AF for time extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling was already considered when calculating the starting point (NOAEC)
AF for other interspecies differences:
2.5
Justification:
Default AF for other interspecies differences
AF for intraspecies differences:
5
Justification:
Default AF for exposure group "worker"
AF for the quality of the whole database:
1
Justification:
Quality of whole data base is considered to be sufficient and uncritical
AF for remaining uncertainties:
1
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
1
Justification:
Not applicable in case of local effects
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling was already considered when calculating the starting point (NOAEC)
AF for other interspecies differences:
2.5
Justification:
Default AF for other interspecies differences
AF for intraspecies differences:
5
Justification:
Default AF for exposure group "worker"
AF for the quality of the whole database:
1
Justification:
Quality of whole data base is considered to be sufficient and uncritical
AF for remaining uncertainties:
1
Justification:
Default value
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:
2.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEL
DNEL value:
60.3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No repeated dose toxicity study with dermal application is available. Therefore an inhalation-to-dermal extrapolation is done.

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Default value for time extrapolation from sub-chronic to chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling was already considered due to the starting point (NOAEC)
AF for other interspecies differences:
2.5
Justification:
Default AF for other interspecies differences
AF for intraspecies differences:
5
Justification:
Default AF for exposure group "worker"
AF for the quality of the whole database:
1
Justification:
Quality of whole data base is considered to be sufficient and uncritical
AF for remaining uncertainties:
1
Justification:
Default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Derivation of worker DNELs for isobutyl vinyl ether (IBVE)

General remarks

A category aproach (OECD SIDS 2006) is available for vinyl ethers (report included in IUCLID chapter 13): methyl vinyl ether (MVE; CAS 107-25-5), ethyl vinyl ether (EVE, CAS 109-92-2), and isobutyl vinyl ether (IBVE, CAS 109-53-5).

The oral LD50 of IBVE in rats was 13100 mg/kg bw. The dermal LD50 in rabbits was 15400 mg/kg bw. In acute inhalation studies in rats the LC50 (4 h) was > 21000 mg/m³.

IBVE was a skin irritant in rabbits after 2 or 24 hours of occlusive treatment. Undiluted IBVE was only slightly irritant to the rabbit eye.

After subchronic inhalation exposure to IBVE in rats local effects in the nasal cavity were found as well as adapative effects in liver and kidney (increased metabolism of the test substance; no histopathological effects) at a concentration of >= 500 ppm (2080 mg/m³); the NOAEC was 50 ppm (208 mg/m³).

No mutagenic activity was found in in vitro studies with bacterial or mammalian cells as well as no clastogenic or aneugenic activity in mammalian cells. Data on genotoxicity in vivo or carcinogenic activity are not available.

Reproductive toxicity (reduced live birth index in F1 rats) after inhalation exposure to IBVE was reported in a Guideline study according to OECD TG422 at 2000 ppm (8300 mg/m³) in the presence of maternal toxicity like clinical signs and reduced body weight; the NOAEC for reproductive toxicity is 500 ppm (2080 mg/m³).

DNEL acute toxicity

IBVE is not classified for acute toxicity. Thus, no DNELs for acute toxicity were considered.

Worker-DNEL long-term for inhalation route-systemic

Relevant dose-descriptor for the endpoint concerned: NOAEC systemic 208 mg/m³, sub-chronic inhalation study in rats with IBVE (BASF 2004).

Correction of starting point

No difference in bioavailability between humans and rats assumed.

Same route of exposure.

Differences in exposure conditions (6 h/day in rat inhalation study versus occupational exposure 8 h/day): factor 6/8 = 0.75

Differences in respiratory volumes between experimental animals (at rest) and humans (light activity): respiratory volume in humans during 8 h at rest is 6.7 m³ versus 10 m³ for 8 h at light activity for workers; factor 6.7/10 =  0.67

NOAEC x 0.75 x 0.67 = 208 mg/m³ x 0.5025 = 105 mg/m³

Assessment factors relating to the extrapolation procedure

Interspecies differences: default factor of 2.5.

Intraspecies differences: default assessment factor of 5 for workers.

Differences in duration of exposure: sub-chronic data used, assessment factor 2.

Issues related to dose-response: the starting point for the DNEL calculation is a NOAEC; therefore a default assessment factor of 1 is used.

Quality of whole database: sufficient; no additional assessment factor.

Overall assessment factor: 2.5 x 5 x 2= 25
DNEL worker chronic inhalation systemic = 105 mg/m³ : 25 = 4.2 mg/m³

Worker-DNEL long-term for inhalation route-local

Relevant dose-descriptor for the endpoint concerned:
NOAEC = 208 mg/m³ for local effects in the upper respiratory tract of rats after sub-chronic inhalation exposure to IBVE (BASF 2004).

Correction of starting point

No difference in bioavailability between humans and rats assumed.

Same route of exposure in rats and humans; no correction necessary.

Correction of exposure conditions (occupational exposure duration 8 h/day versus 6 h/day in the rat study and differences in respiratory volume in 8 h at rest [6.7 m³) and at light work [10 m³]). Factor 6/8 = 0.75 (exposure duration) and factor 6.7/10 = 0.67 (respiratory volume).

NOAEC 208 mg/m³ x 0.75 x 0.67 = 105 mg/m³ (corrected starting point)

Assessment factors relating to the extrapolation procedure

Interspecies differences: human versus rat; additional factor of 2.5 for ‘remaining differences’ between rat and humans.

Intraspecies differences: default assessment factor of 5 for workers.

Differences in duration of exposure: not applicable for local effects.

Issues related to dose-response: the starting point for the DNEL calculation is a NOAEC; therefore an assessment factor of 1 is used.

Quality of whole database: sufficient; assessment factor 1.

Overall assessment factor: 2.5 x 5 = 12.5
DNEL worker chronic inhalation local = 105 mg/m³ : 12.5 = 8.4 mg/m³

Worker-DNEL long-term for dermal route-systemic

Relevant dose-descriptor for the endpoint concerned: NOAEC systemic 208 mg/m³, sub-chronic inhalation study in rats with IBVE (BASF 2004).

 

This point of departure was modified to get the corrected starting point for DNEL derivation based on a route-to-route (inhal. to dermal) extrapolation. A corrected dermal NOAEL (NOAELcorr) was calculated using the default respiratory volume reflecting the daily exposure period of the rats during the study (6 hours):

NOAEL (dermal-rat) =NOAEC x (sRVrat) x (ABSinhal-rat/ABSdermal-human)=208 mg/m³ x (0.29 m³/kg bw/d) x (1/1) = 60.3 mg/kg bw/d

- Standard dose descriptor (NOAEC): 208 mg/m³

- Standard respiratory volume of the rat (sRVrat) for 6 hours: 0.29 m³/kg bw/d

- Inhalation absorption of the rat/dermal absorption of humans (ABSinhal-rat)/ABSdermal-human): 1/1

 

Use of assessment factors: 25

Interspecies AF: 1 (allometric scaling already considered due to starting point (NOAEC))

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 2 (sub-chronic to chronic study)

Remaining uncertainties AF: 1

 

In conclusion, long-term systemic dermal DNEL, workers was calculated to be 2.4 mg/kg bw/d.

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

Derivation of consumer DNELs for isobutyl vinyl ether (IBVE)

General remarks:

IBVE is practically exclusively used as an intermediate in the manufacture of vinyl ether polymers and co-polymers. Further to its use as industrial intermediate in the manufacture of pharmaceuticals and dyes, IBVE is also used as intermediate in the manufacture of polymers and co-polymers for use as food packaging materials and adhesives. Hence, consumer exposure to residual IBVE may occur through the use of these products. However, this exposure is considered to be negligible, since most of the marketed vinyl ether copolymers are heat-treated and potentially existing residual vinyl ethers are expected to evaporate during this process. Since IBVE is also not added intentionally into consumer products (no consumer uses), corresponding consumer DNELs were not considered.