Tributylmethylammonium chloride

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

48.98 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

18

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

881.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite. Conversion of an oral NOAEL into a corrected NOAEC: For workers (8h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human * sRVhuman/wRV = 1000 * 1/0.38 m³/kg/8h * ABSoral-rat /ABSinhal-human * 6.7 m³ (8h)/10 m3 (8h) = 1000 * 1/0.38 m³/kg/8h * 0.5 * 6.7 m³ (8h)/10 m³ (8h) = 1000 /0.38 * 0.5* (6.7/10) = 881.6 mg/m³.

With ABS: Absorption, sRV: Standard Respiratory Volume; wRV: Worker Respiratory Volume; ABSoral-rat /ABSinhal-human= 50/100= 0.5, assuming no differences in inhalation absorption between rats and humans.

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to
chronic exposure worker

AF for interspecies differences (allometric scaling):

1

Justification:

No correction for caloric demand for inhalation; is included in dose descriptor starting point.

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

3

Justification:

Difference in sensitivity among workers

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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:

6.9 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

72

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite. Correction dermal NOAEL: 1000 x 50/100^a = 500 mg/kg bw/day (^a % oral/dermal absorption)

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure worker

AF for interspecies differences (allometric scaling):

4

Justification:

Correction for caloric demand from rat to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

3

Justification:

Difference in sensitivity among workers

AF for the quality of the whole database:

1

Justification:

re;liable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

83.3 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

12

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not relevant, route of original study = dermal exposure.

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for interspecies differences (allometric scaling):

4

Justification:

Correction for caloric demand from rat to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

3

Justification:

Difference in sensitivity among workers

AF for the quality of the whole database:

1

Justification:

reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties, dose-related response observed

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.17 mg/cm²

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

21.6

Dose descriptor:

other: LOAEL (3.68 mg/cm2)

AF for dose response relationship:

3

Justification:

Value is LOAEL

AF for differences in duration of exposure:

1

Justification:

Local effects are not dependent on exposure duration.

AF for interspecies differences (allometric scaling):

2.4

Justification:

Correction for caloric demand from rabbit to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

3

Justification:

Difference in sensitivity among workers

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.17 mg/cm²

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

12

Dose descriptor starting point:

other: LOAEL (3.68 mg/cm2)

AF for dose response relationship:

3

Justification:

Value is LOAEL

AF for interspecies differences (allometric scaling):

2.4

Justification:

Correction for caloric demand from rabbit to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

3

Justification:

Difference in sensitivity among workers

AF for the quality of the whole database:

1

Justification:

Reliable study used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.35 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

30

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

130.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite. For the general population (24h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human = 300 * 1/1.15 m³/kg * ABSoral-rat /ABSinhal-human = 300 * 1/1.15 m³/kg * 0.5 = 130.5 mg/m³ With ABS: Absorption, sRV: Standard Respiratory Volume; ABSoral-rat /ABSinhal-human= 50/100= 0.5, assuming no differences in inhalation absorption between rats and humans.

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

No correction for caloric demand for inhalation; is included in dose descriptor starting point.

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

5

Justification:

Difference in sensitivity among general public

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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:

DNEL (Derived No Effect Level)

Value:

4.2 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

120

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

500 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Correction NOAEL: 1000 mg/ kg bw x 50/100^a = 500 mg/kg bw/day (^a % oral/dermal absorption)

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

Correction for caloric demand from rat to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

5

Justification:

Difference in sensitivity among general population.

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

50 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

20

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for interspecies differences (allometric scaling):

4

Justification:

Correction for caloric demand from rat to human

AF for other interspecies differences:

1

Justification:

Not relevant

AF for intraspecies differences:

5

Justification:

Difference in sensitivity within population

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.1 mg/cm²

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

36

Dose descriptor:

other: LOAEL (3.68 mg/cm2)

AF for dose response relationship:

3

Justification:

Value is LOAEL

AF for differences in duration of exposure:

1

Justification:

Local effects are not dependent on exposure duration

AF for interspecies differences (allometric scaling):

2.4

Justification:

Correction for caloric demand from rabbit to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

5

Justification:

Difference in sensitivity within population

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.1 mg/cm²

Most sensitive endpoint:

acute toxicity

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010)

Overall assessment factor (AF):

20

Dose descriptor starting point:

other: LOAEL (3.68 mg/cm2)

AF for dose response relationship:

3

Justification:

Value is LOAEL

AF for interspecies differences (allometric scaling):

2.4

Justification:

Correction for caloric demand from rabbit to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

5

Justification:

Difference in sensitivity within population

AF for the quality of the whole database:

1

Justification:

Reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining differences

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC guidance (Technical Report No. 110, October 2010

Overall assessment factor (AF):

120

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Value is NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from subacute study to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

Correction for caloric demand from rat to human

AF for other interspecies differences:

1

Justification:

No remaining differences

AF for intraspecies differences:

5

Justification:

Difference in sensitivity among general population

AF for the quality of the whole database:

1

Justification:

reliable studies used

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)