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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:
30 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Please note: All factors derived below are used in mathematically terms as divisors to derive DNEL(s) from an NOAEL.

Derivation of DNELlocal

With the exception of a mild reversible irritation in the rabbit eye no adverse local effects were induced by cis-cyclooctene. Therefore, no DNEL has to be derived for local effects.

Derivation of DNELacute

No adverse effects were noted upon acute exposure in experimental animals upon oral or dermal application. Also no acute adverse effects were noted in repeated dose studies. This means that the DNELlong termis also protective for acute exposures.

Derivation of DNELlong term

General population/ consumers

There will be no exposure for consumers; the substance is used solely as monomer and as transported and on-site isolated intermediate for chemical synthesis.DNELs for the population are not required

WorkersStarting point

No adverse effects were noted in a 28-day oral gavage study with rats the NOAEL was 150 mg/kg bw/d. Reduced body weight gain was noted at 500 mg/kg bw/d. This value is taken as starting point to derive a DNELlong term.

Cis-cyclooctene was not genotoxic and there was no structural alert for carcinogenic activity.

  • Route to route extrapolation

Toxicokinetic studies with experimental animals (rats) indicated that oral absorption was complete. As a worst case consideration dermal absorption is considered as 100%. Absorption via the inhalation route is considered as 100% by default.

  • Exposure duration extrapolation

Oral and dermal route

Considering a NOAEL of 150 mg/kg bw/d with the default exposure duration assessment. A default factor of 6 is chosen for extrapolation from subacute to chronic exposure

Inhalation route

In a read across approach a sub-chronic inhalation toxicity studies with cyclohexene, the C6-analog of cyclooctene, in rats, guinea pigs and rabbits were considered with a daily exposure of 6h on 5 days per week for a period of 6 months. The most sensitive species was the rat with NOAEC of 300 ppm (13.4 mmol/m³) based on reduced body weight gain at 600 ppm while no adverse effects were noted for rabbits and guinea pigs at the highest dose level. This NOAEC corresponds to 1500 mg cis-cyclooctene/m³.

A default factor of 2 is chosen for extrapolation from subchronic to chronic exposure.

Experimental exposure was 6h per day, 5 days per week:

For workers an additional assessment of 1.33 is included accounting for 8h per day. Also for workers a factor of 1.5 is included accounting for a inhalation of 10 m³ during light activity as compared to default of 6.7 m³ per 8h.

 

Interspecies extrapolation

For interspecies extrapolation the default factor of 4 for metabolic differences between rat and humans is considered for both the oral and the dermal exposure route. This factor is by default not considered relevant for inhalation exposure. In addition a further safety factor of 2.5 is used by default for all exposure routes.

Intra-species assessment factors

Default safety factors accounting for intra-species differences in susceptibility (factor 5 for workers) are assumed for all exposure routes.

Additional safety factors

Toxicokinetic information indicated that there is no potential for accumulation.

The starting point for deriving a DNELlong term(inhalation) is derived from a 6 months inhalation study with cyclohexene by read-across. Comparing endpoints of oral repeated dose studies it was evident that while structurally similar the C6 cycloalkene showed more toxic effects than the C8 analog.

Therefore no further assessment factors are considered necessary.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

There will be no exposure for consumers, the substance is used solely as monomer and as transported and on-site isolated intermediate for chemical synthesis. DNELs for the population are not required.