Soybean oil, epoxidised, reaction products with methanol and water

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

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:

0.14 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

300

Modified dose descriptor starting point:

LOAEL

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.83 mg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

200

Dose descriptor:

other: LOAEL

Additional information - workers

Correction of dose descriptors if needed (for example route-to-route extrapolation), application of assessment factors and derivation of the endpoint specific DN(M)EL

Correction of dose descriptors may be needed for the following situations:

1. If for a given human exposure route there is a dose descriptor for the same route in experimental animals but for that particular exposure route there is a difference in bioavailability between experimental animals and humans at the relevant level of exposure.

2. If for a given human exposure route there is not a dose descriptor for the same route (in experimental animals or humans).

3. Differences in human and experimental exposure conditions.

4. Differences in respiratory volumes between experimental animals (at rest) and humans (light activity).

In case of Cargill BP-A, no difference in bioavailability is expected for the oral and the dermal route. For the relevant route of human exposure, which would be the dermal route, limited data is available (acute dermal toxicity on surrogate chemical ESBO and skin irritation on Cargill BP-A). These data do not indicate a difference in effects between both exposure routes, therefore the data on oral toxicity testing can be used to assess dermal DNELs.

Human exposure to Cargill BP-A is considered to be negligible, as the substance is a monomer and incorporated in a polymer-matrix. Workers might be exposed during filling. During the polymerization process (done in a closed systems exposure is expected to be very low. Exposure of the general population/consumers is not expected, therefore only worker exposure will be taken into account.

The respiratory route is considered irrelevant for Cargill BP-A based on molecular weight and the very low vapour pressure.

Based on these considerations, it is concluded that correction of dose descriptors is not necessary to do route-to route extrapolation from the oral to the dermal route. In derivation of the DNELs, uncertainties in the extrapolation of experimental data to the human exposure situation (variability and uncertainty) will be taken into account.

In order to correct for the different units used to express the oral and dermal DNELS, the following approach is taken:

Based on an average bodyweight of 70 kg and an exposed area during filling (worst case approach) of 420 cm2 (one side of the hands), the DNEL will be corrected.

For acute toxicity no DNELs are derived based on the absence of hazards found in the acute toxicity tests and absence of high peak-exposures to Cargill BP-A. Based on the data it is expected that the long-term DNELs are sufficient to protect workers.

In order to derive the DNELs for long-term exposure in workers (long-term dermal DNEL) based on the 2-year feeding study in rats with ESBO, the following assessment factors are applied:

3          for extrapolation from LOAEL to NOAEL
4          for differences in metabolic rates
2.5       for other interspecies differences
5          for intraspecies differences (rat versus human worker)
1          for differences in exposure duration
1          for uncertainties in the dose-response relation
2          for uncertainty of the data-base

All factors are default assessment factors. Only for the confidence in the data-base a worst case factor of 2 was chosen, because actual starting hazard data were not on Cargill BP-A, but on the surrogate compound ESBO. Based on the bridging studies available, no reason is available to expect that this factor should be higher.

The overall assessment factor is 300. This will lead to a DNEL of 0.83 mg/kg bw.

When a long-term dermal or oral DNEL is derived based on the developmental/fertility studies in the rat with ESBO, the following assessment factors are applied:

4          for differences in metabolic rates
2.5       for other interspecies differences
10        for intraspecies differences (rat versus human)
1          for differences in exposure duration
1          for uncertainties in the dose-response relation
2          for uncertainty of the data-base

All factors are default assessment factors. In a worst case approach the assessment factor for intra-species differences is set at 10, because the working population, due to age, might be more sensitive for any effects on the reproductive system. In addition, again for the confidence in the data-base a worst case factor of 2 was chosen, because actual starting hazard data were not on Cargill BP-A, but on the surrogate compound ESBO. Based on the bridging studies available, no reason is available to expect that this factor should be higher.

The overall assessment factor is 200. This will lead to a DNEL of 50 mg/kg bw.

Conclusion

In a worst case approach, the long-term dermal DNEL is based on the 2 year study in rats

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

Additional information - General Population

See "Discussion" under workers