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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:
147 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
42 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The subject chemical is currently not listed as a harmful substance in the Annex I of the EU Dangerous Substance Directive 67/548/EEC or in Annex VI to EC Regulation 1272/2008. It is not a Category 1 or 2 mutagen, carcinogen, or reproductive hazard; thus, DNEL/DMEL values for these endpoints were not derived. There is no published IOEL (Indicative Occupational Exposure Limit) value or other relevant exposure limit value available for this material.

Toxicology Summary

Acute toxicity

The acute oral and dermal toxicities of the surrogate chemical, undecenyl methoxycrylene, were low with LD50 values >2000 mg/kg bw.

Irritation

The subject chemical was not a skin irritant in humans at concentrations of up to 20% in an HRIPT study. The surrogate material, undecenyl methoxycrylene, was negative for skin sensitization when tested in vitro in the Episkin reconstituted human epidermis study. The subject chemical failed to produce an irritant response in vitro in the HET-CAM test utilizing hen's egg chorioallantoic membranes. The surrogate material, undecenyl methoxycrylene, was negative when tested in the SkinEthic in vitro test with reconstituted human corneal epithelial cells. The surrogate material produced a maximum group mean score of 11.0 in rabbits based on the Kay and Colandra classification scheme indicating minimal eye irritation potential.

Sensitization

The subject chemical was negative when tested in 56 human subjects in a HRIPT study. The surrogate chemical, undecenyl methoxycrylene, was negative when tested in the mouse local lymph node assay. The respiratory tract sensitization potential of the subject chemical is presumed to be low.

Repeated dose toxicity

The surrogate chemical, undecenyl methoxycrylene, was administered by oral gavage for a period of 42 -days for male rats and up to eight weeks for female rats at dose levels of 0, 100, 300 or 1000 mg/kg bw/day. Only minimal effects were observed in the liver and thyroid glands and were considered adaptive in nature and not to represent a significant systemic toxicity. The NOAEL in this study was reported as 1000 mg/kg bw/day. This latter value was used to derive long-term systemic DNEL values.

Genetic toxicity

The subject chemical was negative in two Ames bacterial mutagenicity assays at maximum plate incorporation levels of 5000 micrograms/plate. It was also negative for mutagenicity in an in vitro L5178Y T/K +- Mouse Lymphoma assay and an in vitro chromosomal aberration study using cultured human lymphocytes. The in vivo genetic toxicity of the subject chemical has not been determined.

Reproductive and developmental toxicity

The surrogate chemical, undecenyl methoxycrylene, failed to produce any reproductive or developmental toxicity when administered to rats by gavage at dose levels up to 1000 mg/kg bw/day. The NOAEL for reproductive effects was 1000 mg/kg bw/day.

DNEL Derivations

Mode of action considerations

For the critical study selected, a threshold mode of action was assumed.

Modification of the relevant dose descriptors to the correct starting point

In the case of worker exposures, the oral route of exposure was not considered. For potential dermal and inhalation exposures, route-to-route extrapolations from the oral NOAEL value were performed (see Guidance Document, Chapter R.8, Appendix R.8 -2). A first-pass effect was discounted for the purposes of these calculations.

Dermal:

Due to a lack of dermal absorption data for the subject chemical, complete absorption of the test material by both the oral and dermal routes was assumed. Thus, dermal exposure to the same amount of the test material would produce an equivalent internal dose. Differences in metabolism, distribution and elimination were not considered and thus no further corrections were applied (see Guidance Document, Section R.8.4.2, page 25). Thus the corrected dose descriptor for the worker is 1000 mg/kg bw/day.

Inhalation:

In the case of worker exposures, a 50% absorption of the test material by the oral versus the inhalation route was assumed (see Guidance Document, Chapter R.8, Appendix R.8.4.2, page 25). The rat repeated-dose oral NOAEL value was divided by 0.38 m3/kg bw to yield an equivalent air concentration for an 8 -hour exposure (see Guidance Document, Chapter R.8, Example R.8 -2, page 65). This value was further corrected to account for increased metabolic rate (and inhalation volume) in the case of light work versus basal metabolism (multiplicative factor of 6.7 m3/10 m3, or 0.67).

(NOAELoralX 0.50) / 0.38 m3/kg bwt = 1316 mg/m3

1316 mg/m3X 0.67 = 882 mg/m3= NOAELinh, corr

Application of assessment factors

Dermal:

An AF of 4 was applied to the corrected dose descriptor for dermal long-term (repeated dose) systemic effects in workers (interspecies differences, allometric scaling). In addition, an AF of 2 (subchronic to chronic) and an intraspecies (sensitive worker) AF of 3 were applied. The overall AF obtained was 24.

Inhalation:

Allometric scaling was already performed in the previous step (corrected dose descriptor) and no further factors were applied. In the case of worker exposure, an AF of 2 (subchronic to chronic) and an AF value of 3 (intraspecies, sensitive worker) was assigned to give an overall AF of 6.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
43.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

DNEL Derivations / Long-Term Systemic

Mode of action considerations

For the critical study selected, a threshold mode of action was assumed.

Modification of the relevant dose descriptors to the correct starting point

In the case of exposures of the general population, route-to-route extrapolations from the oral NOAEL value were performed for oral, dermal and inhalation (see Guidance Document, Chapter R.8, Appendix R.8 -2). A first-pass effect was discounted for the purposes of these calculations.

Oral:

Complete absorption of the subject chemical by the oral route was assumed. The corrected dose descriptor for the general population is 1000 mg/kg bw/day.

Dermal:

Due to a lack of dermal absorption data for the subject chemical, complete absorption of the test material by the dermal route was assumed. Differences in metabolism, distribution and elimination were not considered and thus no further corrections were applied (see Guidance Document, Section R.8.4.2, page 25). Thus the corrected dose descriptor for the general population is 1000 mg/kg bw/day.

Inhalation:

In the case of exposures of the general population, a 50% absorption of the test material by the oral versus the inhalation route was assumed (see Guidance Document, Chapter R.8, Appendix R.8.4.2, page 25). The rat repeated-dose oral NOAEL value was divided by 1.15 m3/kg bw to yield an equivalent air concentration for a continuous exposure (see Guidance Document, Chapter R.8, Example R.8 -2, page 64). This value was not further corrected.

(NOAELoralX 0.50) / 1.15 m3/kg bwt = 435 mg/m3

= NOAELinh, corr

Application of assessment factors

Oral:

An AF of 4 was applied to the corrected dose descriptor for oral long-term (repeated dose) systemic effects in the general population (interspecies differences, allometric scaling). In addition, an AF of 2 (subchronic to chronic) and an intraspecies (sensitive worker) AF of 5 were applied. The overall AF obtained was 40.

Dermal:

An AF of 4 was applied to the corrected dose descriptor for oral long-term (repeated dose) systemic effects in the general population (interspecies differences, allometric scaling). In addition, an AF of 2 (subchronic to chronic) and an intraspecies (sensitive person) AF of 5 were applied. The overall AF obtained was 40.

Inhalation:

Allometric scaling was already performed in the previous step (corrected dose descriptor) and no further factors were applied. In the case of worker exposure, an AF of 2 (subchronic to chronic) and an AF value of 5 (intraspecies, sensitive person) was assigned to give an overall AF of 10.