1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs.

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.4 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):

75

Dose descriptor starting point:

NOAEL

Value:

60 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

106 mg/m³

Explanation for the modification of the dose descriptor starting point:

The dose starting point was the NOAEL result of 60 mg/kg bw/day for systemic toxicity, obtained from the OECD 422 Oral (Gavage) Combined Repeat Dose Toxicity Study With Reproduction / Developmental Toxicity Screening Test in the Rat.

Route to route extrapolation based on 100% absorption via the oral route and 100% via the inhalation route (inhalation exposure is unlikely, but when the substance would reach the alveoli, absorption can be expected). NOAEC= 60 mg/kg bw*1/ 0.38 m3 /kg bw= 157 mg/m3. This value is corrected for the inhalation volumes in 8 hours under the respective conditions (6.7 m3 for base level, 10 m3 for light activity) --> 106 mg/m3.

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

Study duration extrapolation from sub-acute to chronic studies

AF for interspecies differences (allometric scaling):

1

Justification:

Not applied, because this factor is already included in the derivation of the inhalation NOAEC

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

Default for workers

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

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.2 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):

300

Dose descriptor starting point:

NOAEL

Value:

60 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

60 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation based on 100% absorption via both the oral and the dermal route

The DNEL derived is based on the NOEL result of 60 mg/kg bw/day for systemic toxicity, obtained from the OECD 422 Oral (Gavage) Combined Repeat Dose Toxicity Study With Reproduction / Developmental Toxicity Screening Test in the Rat. It is considered that dermal absorption will not be higher than oral absorption, therefore no default factor (i.e. factor 1) should be introduced when performing oral-to dermal extrapolation. Further default assessment factors were introduced for allometric scaling for interspecies variability’s (4 for rats), remaining interspecies variability’s (default factor 2.5), intraspecies variability’s (default factor of 5 for workers) and study duration extrapolation (6 for subacute to chronic studies). This gave an overall assessment factor of 300.

AF for differences in duration of exposure:

6

Justification:

Study duration extrapolation from sub-acute to chronic studies

AF for interspecies differences (allometric scaling):

4

Justification:

Default for rats

AF for other interspecies differences:

2.5

Justification:

Default

AF for intraspecies differences:

5

Justification:

Default for workers

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

The substance is classified for human health as corrosive to the skin (and assumed corrosive to the eye).

 

The hazard statement H314: Causes severe skin burns and eye damage, is applicable.

 

Short-term systemic effects

A DNEL for short-term systemic effects was not derived for the dermal route, as an acute dermal toxicity study showed the substance to have a LD50 > 2000 mg/kg and not be classified for dermal toxicity. It is considered that dermal effects will be characterised by local tissue damage rather than by systemic effects.

A DNEL for short-term system effects was not derived for the inhalation route, as no acute inhalation study has been conducted as the substance is corrosive and inhalation is not considered to be a significant route of exposure. Exposure to aerosols containing inhalatory or respiratory droplets during use of the substance is not anticipated.

Short-term local effects

 

A DNEL for short-term local dermal effects was not derived as the skin irritation study which showed corrosion and acute dermal toxicity study which showed severe dermal effects, do not give suitable dose-response information required to derive a DNEL. For corrosive substances, appropriate PPE should be used by all workers. As a result, direct dermal contact occurs only infrequently/accidentally.

 

A DNEL for short-term local inhalation systemic effects was not derived as no acute toxicity testing has been conducted via the inhalation route. The substance has a low measured vapour pressure of 5.1 x 10^-4 Pa at 25°C and is not considered to be volatile. Inhalation is not considered to be a significant route of exposure.

Exposure to aerosols containing inhalatory or respiratory droplets during use of the substance is not anticipated

 

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:

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

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 (no further information necessary)

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

DNELs have not been derived for the general public as there will be no exposure to the general public/consumers.

The substance will only be used by industry and not by the public. Due to minimal release of the substance from industrial use, exposure to the general public is not anticipated.