5,7-di-tert-butyl-3-[4-(2-hydroxyethoxy)phenyl]-1-heteropolycycl-2(3H)-one

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.12 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):

750

Modified dose descriptor starting point:

LOAEC

Value:

88.1 mg/m³

Explanation for the modification of the dose descriptor starting point:

LOAELoral 100 mg/kg/d x (1/0.38 m3.kg-1.d-1) x (50% rat oral / 100% human inhal) x (6.7 m3 / 10 m3) = LOAECinhal 88.1 mg/m3

AF for dose response relationship:

10

Justification:

Extrapolation from LOAEL to NAEL (NOAEL). See below for a justification of the AF used

AF for differences in duration of exposure:

6

Justification:

Default factor extrapolation from subchronic to chronic duration

AF for interspecies differences (allometric scaling):

1

Justification:

Not required for oral to inhalation conversion of starting point

AF for other interspecies differences:

2.5

Justification:

Default factor for remaining differences

AF for intraspecies differences:

5

Justification:

Default factor for worker exposures

AF for the quality of the whole database:

1

Justification:

Data appropriate for manufacturing intermediate

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

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)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.033 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):

3 000

Modified dose descriptor starting point:

LOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

LOAELoral 100 mg/kg/d x (50% rat oral / 50% derm abs human)  = LOAELdermal 100 mg/kg/d

AF for dose response relationship:

10

Justification:

Extrapolation from LOAEL to NAEL (NOAEL). See below for a justification of the AF used

AF for differences in duration of exposure:

6

Justification:

Default factor extrapolation from subchronic to chronic duration

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling factor from rats to man

AF for other interspecies differences:

2.5

Justification:

Default factor for remaining differences

AF for intraspecies differences:

5

Justification:

Default factor for worker exposures

AF for the quality of the whole database:

1

Justification:

Data appropriate for manufacturing intermediate

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high 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:

medium hazard (no threshold derived)

Additional information - workers

The material has been adequately tested for a production intermediate. Acute toxicity data does not indicate requirement for classification via the dermal or oral route. No acute inhalation toxicity data has been generated. The material was irritating to eyes and was a skin sensitiser. In an OECD 422 combined repeat dose toxicity and reproductive screening study, the LOAEL (100 mg/kg bw/d) was established on multiple effects, the most severe of these being accumulation of macrophages in the lungs of females and hepatotoxicity in males, effects on male reproductive organs male pituitary glands, adrenal glands and thyroids were noted, although there were no effects on reproduction. In accordance with ECHA guidance document R8 (2012), an attempt was made to estimate the NOAEL using the BMD and associated methodologies outlined in R.8 (2012). These indicated that the NOAEL might be established at around 11 mg/kg bw/day for this study, or alternatively than an assessment factor with respect to the dose response relationship, might be established as 10. See the attached document. The material was not genotoxic in a battery of in vitro genotoxicity tests.

Long term DNELs were established on the basis of the LOAEL, in the usual way, with an additional AF of 10 for dose response (notionally extrapolating from a LOAEL to NOAEL) justified using techniques specified in the ECHA guidance. Local effects (inhalation and dermal) are considered likely hazards. For acute DNELs, these were not set, because controls preventing exceedance of the long term DNELs will also protect against acute/short term hazards. The material was considered hazardous for respiratory and skin local effects, but as controlled production intermediate no exposure should normally occur, and further data to establish precise DNELs for local effects is considered unnecessary.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

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:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

Given this is a production intermediate and is consumed in the production of other materials, no exposure of the public is anticipated and general population DNELs are not required.