3-hydroxy-2,2-dimethylpropyl 3-hydroxy-2,2-dimethylpropionate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.45 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):

25

Modified dose descriptor starting point:

NOAEC

Value:

261.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

oral NOAEL / [sRV * time] *ABS(oral)/ABS(inhal) * no/light work = 300 mg/kg bw/d / [0.8 L/min/kg bw rat * 8*60 min] * 50%/100% * 6.7m3/10m3 = 300 /0.384 *1/2 *0.67 mg/m3

AF for dose response relationship:

1

Justification:

NOAEL of a GLP, OECD408 study with 3 doses

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

see route to route extrapolation

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

default for worker

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

6 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):

100

Modified dose descriptor starting point:

NOAEL

Value:

600 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

oral NOAEL * 1/1 *ABS(oral)/ABS(derm) = 300 mg/kg bw/d *1 *100%/50% = 300 *1 *2 mg/kg bw/d

AF for dose response relationship:

1

Justification:

NOAEL of a GLP, OECD408 study with 3 doses

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Extrapolation systemic effects rat to human

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

default worker

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Acute exposure - systemic effects

It is not necessary to derive a DNEL for acute effects based on the available data. In an acute oral study (BASF AG, 1974) the LD50 (rat) was 8000 mg/kg bw. There is no relevant risk to be expected from inhalative exposure since the inhalation hazard toxicity test (BASF 1974) showed no effects.

Acute exposure - local effects

HPN is classified as "Risk of serious damage to eyes" (R41). A test was performed (as the guideline prescribes) with undiluted test substance. Therefore, this test does not provide dose-response data that could be used for the derivation of a DNEL.

It is not possible to derive a DNEL based on the available data. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent eye exposure.

Long-term exposure - systemic effects

The DNELs for inhalation and dermal long term exposure are derived from the subchronic oral NOAEL, which was obtained from an OECD 408 study (BASF SE, 2013). At 1000 mg/kg bw/day transient, treatment-related adverse findings were observed: head shaking, unsteady gate, semiclosed or closed eyes, poor general condition, adominal position, twitching, atonia splayed limbs, labored and intermitted respiration; therefore the NOAEL is 300 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.61 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):

50

Modified dose descriptor starting point:

NOAEC

Value:

130.4 mg/m³

Explanation for the modification of the dose descriptor starting point:

oral NOAEL / [sRV * time] *ABS(oral)/ABS(inhal) = 300 mg/kg bw/d / [0.8 L/min/kg bw rat * 24*60 min] * 50%/100% = 300 /1.15 /2 mg/m3

AF for dose response relationship:

1

Justification:

NOAEL of a GLP, OECD408 study with 3 doses

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

No interspecies extrapolation for inhalation, see route to route

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

default for general population

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

DNEL (Derived No Effect Level)

Value:

3 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):

200

Modified dose descriptor starting point:

NOAEL

Value:

600 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

oral NOAEL * 1/1 *ABS(oral)/ABS(derm) = 300 mg/kg bw/d *1 *100%/50% = 300 *1 *2 mg/kg bw/d

AF for dose response relationship:

1

Justification:

NOAEL of a GLP, OECD408 study with 3 doses

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat to human

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

default general population

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.5 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):

200

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no extrapolation

AF for dose response relationship:

1

Justification:

NOAEL of a GLP, OECD408 study with 3 doses

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Rat to human

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

default general population

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

Acute exposure - systemic effects

Same considerations as for the worker.

Acute exposure - local effects

Same considerations as for the worker.

Long term exposure - systemic effects

The DNELs for inhalation and dermal long term exposure are derived from the subchronic oral NOAEL, which was obtained from a OECD 408 study (BASF SE; 2013). At 1000 mg/kg bw/day transient, treatment-related adverse findings were observed: head shaking, unsteady gate, semiclosed or closed eyes, poor general condition, abdominal position, twitching, atonia splayed limbs, labored and intermitted respiration; therefore the NOAEL is 300 mg/kg bw/day.