Hatcol 1760

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

30

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:

17 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

48

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

Basis for calculation of long-term DNEL for dermal exposure: systemic effects

Rationale for selection of dose descriptor: The test material did produce some reversible ffects (increased liver weights, thymus lymphoid atrophy) at the highest level (1,000 mg/kg bw/day), but not at the lower tested levels. Renal effects at lower dose levels were observed in male rats but were associated with hydrocarbon-induced alpha-2 -microglobulin dependent male rat nephropathy, which is not relevant for humans.

Modification of starting factor: The starting factor needs to be adjusted from seven times per week to five times a week. the tthe test material is expected to be poorly absorbed through skin and dermal penetration through human skin is expected to be considerably less than through rat skin. A modification factor of 2.3 is applied to account for this difference. (CONCAWE DNEL guidance, 2009). Extrapolation from oral to dermal exposure is inherently extremely conservative for the test material.

250 mg/kg * 7d/w / 5d/w * 2.3 = 805 mg/kg

Assessment factors:

Intraspecies = 3 (CONCAWE DNEL guidance 2009)

Interspecies = 4 (CONCAWE DNEL guidance 2009)

Duration = 4 (Subchronic to chronic (R.8, page 35) (90 day is a factor of 2, 28 day is a factor of 6, so assign a 54 day study a factor of 4)

Total = 48 (3)(4)(4) = 48

Basis for calculation of long-term DNEL for inhalationl exposure: systemic effects

Rationale for selection of dose descriptor: the test material did produce some reversible effects (increased liver weights, thymus lymphoid atrophy) at the highest level (1,000 mg/kg bw/day), but not at the lower tested levels. Renal effects at lower dose levels were observed in male rats but were associated with hydrocarbon-induced alpha-2 -microglobulin dependent male rat nephropathy, which is not relevant for humans.

Modification of starting factor: The starting factor needs to be adjusted from seven times per week to five times per week. Additionally the dose needs to be allometrically scaled from rat to human (divide by 0.38 for rat), and adjusted for worker ventilation rate (6.7 m3/ 10 m3).

(250 mg/kg) * (7 days/week/ 5 days/week) * (1/0.38m3/kg) * (6.7m3/10 m3) = 617 mg /m3

Assessment factors:

Intraspecies = 3 (CONCAWE DNEL guidance 2009)

Interspecies = 2.5 (CONCAWE DNEL guidance 2009)

Duration = 4 (Subchronic to chronic (R.8, page 35)90

dats is a factor of 2, 28 day is a factor of 6, so asisgn a 54 day study a factor of 4).

Total = 30 (3)(2.5)(4) = 30

Calculation of DNEL: 617 mg/m3 / 15 = 21 mg/m3

Within industry an occupational exposure limit of 5 mg/m3 os generally applied for aerosols of mineral oils since at this concentration the oil is a rather thick fog which may moisten floors and equipment and pose a safety hazard. It is advised to keep the same limit value for the test material.

Reference:

CONCAW DNEL Guidance (2009)

R.8 - ECHA Guidance on information requirements and chemical safety assessment - chapter R.8 - May 2008

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

General population is considered for indirect exposure via the environment only.

Long-term DNEL for general population, oral route, systemic effects: 40 mg/kg/day

Dose descriptor: NOAEL 250 mg/kg/ bw

Basis for dose descriptor: Based on an oral repeate dose study (OECD 422) with Hatcol 1760 in the rat, a NOAEL of 250 mg/kg bw/day was set.

Rationale for selection of dose descriptor:

the test material did produce some reversible effects (increased liver weights, thymus lymphoid atrophy) at the highest level (1,000 mg/kg bw/day), but not at the lower tested levels. Renal effects at lower dose levels were observed in male rats but were associated with hydrocarbon-induced alpha-2 -microglobulin dependent male rat nephropathy, which is not relevant for humans.

Dose descriptor was not a NOAEL at the highest dose tested and was not ≥ limit dose.

Modification of starting factor: It is assumed that dietary exposure is constant throughout the day therefore no time scaling is required.

Assessment factors

Intraspecies = 5 (DNEL guidance Version 3.4)

Interspecies = 4 (DNEL guidance Version 3.4)

Duration = 4 (Subchronic to chronic (R.8, page 35) (90 day is a factor of 2, 28 day is a factor of 6, so assign a 54 day study a factor of 4))

total = 80 (5)(4)(4) = 80

Calculation of DNEL: 250 mg/kg/day / 80 = 3 mg/kg

Reference:

R.8 - ECHA Guidance on information requirements and chemical safety assessment - chapter R.8 - May 2008