Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
78.39 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: substance specific (see discussion)
Overall assessment factor (AF):
11.2
Modified dose descriptor starting point:
NOAEC
Value:
877.97 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
substance specific (see discussion)
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
2.2
Justification:
substance specific (see discussion)
AF for the quality of the whole database:
1
Justification:
based on high quality data
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
11.31 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: substance specific (see discussion)
Overall assessment factor (AF):
11.2
Modified dose descriptor starting point:
NOAEL
Value:
126.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Reliable subchronic toxicity data via the inhalation route were available.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
substance specific (see discussion)
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
2.2
Justification:
substance specific (see discussion)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
DNEL (Derived No Effect Level)
Value:
1.26 µg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: substance specific (see discussion)
Overall assessment factor (AF):
40.32
Dose descriptor:
other: LOAEL
AF for dose response relationship:
3
Justification:
no NOAEL identified
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
default
AF for other interspecies differences:
1
Justification:
default
AF for intraspecies differences:
2.2
Justification:
substance specific (see worker discussion)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

In the absence of any significant findings relating to reproductive or developmental endpoints in appropriate screening tests, the critical health effect is considered to be repeated-dose toxicity.

There are only limited repeated dose toxicity data available for the dermal route for dimethoxymethylsilane (CAS 16881-77-9). In the available key dermal repeated dose toxicity study (Losco P. E. et al., 1996), which meets generally accepted scientific principles, but was not conducted according to an appropriate OECD TG and without GLP, New Zealand White rabbits of both sexes were exposed to dimethoxymethylsilane (CAS 16881-77-9) under occlusive conditions for 9 doses over a time of 11 days. The animals received the test item at doses of 43, 85, and 171 mg/kg bw. At the end of exposure period the animals were euthanised. 5 animals from high-dose and control group were kept as satellite groups for 2 weeks of recovery. No systemic toxicity was observed up to the high dose of 171 mg/kg bw. However, local dermal effects were seen still seen in the low dose group. Thus, the NOAEL for systemic toxicity was set at 171 mg/kg bw/day, and the LOAEL for local effects was set at 43 mg/kg bw/day, which corresponds to 0.051 mg/cm². Since the study duration is not sufficient for the properly predict risk of systemic toxicity after repeated dermal exposure, only the LOAEL for local effects will be used for DNEL derivation.

There are no repeat dose toxicity studies available for dimethoxymethylsilane (CAS: 16881-77-9) for the oral and inhalation routes, however, reliable data are available for the structural analogue substance trimethoxymethylsilane (CAS: 1185-55-3). Both substances will ultimately hydrolyse to produce the same hydrolysis product, methylsilanetriol. The Si-C bond is stable under physiological conditions; methyl moieties are thus firmly bound to the silanol group. The latter renders both molecules very polar and ready for rapid excretion via urine. It is therefore considered that read-across between the substances is appropriate. The other hydrolysis product is methanol. It is of note that the oral NOAEL in rats for methanol is greater (at least 2000 mg/kgbw/day) than the dose that is expected to be generated from hydrolysis of dimethoxymethylsilane in the stomach under conditions of a limit test. Therefore any effects of dimethoxymethylsilane will not be attributable to methanol.

 

For the oral route, a reliable key OECD 422 combined repeated dose/reproductive and developmental screening study in compliance with GLP is available for trimethoxymethylsilane (CAS 1185-55-3) (Dow Corning Corporation, 2005). This study is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item to male and female rats for at least 28 days. The test item was administered in corn oil as vehicle at dosages of 50, 250, and 1000 mg/kg body weight/day, and controls received the vehicle only. Based on effects seen in the study the NOAEL for systemic toxicity was considered to be 50 mg/kg bw/day (Dow Corning Corporation, 2005).

 

For the inhalation route there is a study according to OECD TG 413 and GLP (Dow Corning Corporation, 2008). The test item (CAS 1185-55-3) was administered to Sprague-Dawley rats (10 per sex and dose) by whole body exposure at concentrations of 25, 100, 400 and 1600 ppm, corresponding to 140, 560, 2200 and 8900 mg/m³ for 6 hours per day, 5 days/week for a total of 90 days followed by a 28 day recovery period for the control and high dose groups. Based on increased incidence of grossly observed urinary bladder calculi along with kidney dilation at the 2200 mg/m³ exposure level, the NOAEC for trimethoxymethylsilane vapour was 100 ppm (corresponding to 560 mg/m³) the LOAEC was 400 ppm (corresponding to 2200 mg/m³) (Dow Corning Corporation, 2008).

 

The typical pattern of worker exposure to dimethoxymethylsilane is low levels of exposure on a repeated basis. Short-term high exposures are considered unlikely given the high levels of control in place at sites producing and using the substance. DNELs for long-term exposure are therefore adequate to protect against short-term exposures and no separate short-term DNELs are calculated for workers. No oral exposure will occur during occupational handling and use therefore DNELs via the oral route are not calculated for workers.

 

The long-term DNEL for systemic effects via the dermal route is determined on the basis of route-to-route extrapolation from the NOAEC for the structural analogue substance trimethoxymethylsilane (560 mg/m³) from a 90-day inhalation study in rats (exposure duration: 6 h/d, 5 d/week).

The molecular weight difference between target and source chemical is 106 g/mol/136.22 g/mol = 0.78; the NOAEC for the target chemical is therefore 560 mg/m³ x 0.78 = 436.8 mg/m³

The following corrections were made to the NOAEC:

Correction for respiratory volume: 0.29 m³/kg bw/day (rat, 6 h)

Correction for route to route extrapolation (relative absorption inhalation vs. dermal): 1

The corrected NOAEL (dermal) is therefore:

436.8 mg/m³ x 0.29 m³/kg bw/day x 1 = 126.7 mg/kg bw/day

 

The following assessment factors were applied to the corrected NOAEL:

Exposure duration (sub-chronic to chronic): 2 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Interspecies differences (toxicokinetics, rat/human): 1 (substance specific, see below)

Intraspecies differences (toxicodynamics, worker): 2.24 (√5) (substance specific, see below)

Intraspecies differences (toxicokinetics, worker): 1 (substance specific, see below)

Overall Assessment Factor: 11.2

 

The overall DNEL (repeated-dose – systemic – dermal - worker) is therefore:

126.67 mg/kg bw/day/11.2 = 11.31 mg/kg bw/day.

  

The long-term DNEL for local effects via the dermal route is determined on the basis of the LOAEL deduced from the repeated dermal toxicity study with the submission substance. No further corrections were made to the LOAEL of 0.051 mg/cm².

 

The following assessment factors were applied to the LOAEL:

Dose response relationship (LOAEL/NOAEL extrapolation): 3 (no NOAEL identified)

Exposure duration (sub-acute to chronic): 6 (default)

Interspecies differences: 1 (default)

Intraspecies differences (toxicodynamics, worker): 2.24 (√5) (substance specific, see below)

Intraspecies differences (toxicokinetics, worker): 1 (substance specific, see below)

Overall Assessment Factor: 40.32

 

The overall DNEL (repeated-dose – local – dermal - worker) is therefore:

0.051 mg/cm²/40.32 = 0.00126 mg/cm² = 1.26 µg/cm²/day

The long-term DNEL for systemic effects via the inhalation route is determined on the basis of the 90-day inhalation NOAEC for the structural analogue substance trimethoxymethylsilane (560 mg/m³, exposure duration: 6 h/d, 5 days/week).

The molecular weight difference between target and source chemical is 106 g/mol/136.22 g/mol = 0.78; the NOAEC for the target chemical is therefore 560 mg/m³ x 0.78 = 436.8 mg/m³

 

The following corrections were made:

Correction for lower human breathing rate: 4

Correction for experimental vs. occupational exposure duration: 6 h/8 h

Correction for respiratory volume (worker, light physical activity): 6.7 m³/10 m³

Therefore the corrected NOAEC for long-term systemic effects via the inhalation route is:

436.8 mg/m³ x 4 x (6 h/8 h) x (6.7 m³/10 m³) = 877.97 mg/m³

 

The following assessment factors were applied to the corrected NOAEC:

Exposure duration (sub-chronic to chronic): 2 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Interspecies differences (toxicokinetics, rat/human): 1 (substance specific, see below)

Intraspecies differences (toxicodynamics, worker): 2.24 (√5) (substance specific, see below)

Intraspecies differences (toxicokinetics, worker): 1 (substance specific, see below)

Overall Assessment Factor: 11.2

 

The overall DNEL (repeated-dose – systemic – inhalation - worker) is therefore:

877.97 mg/m³ /11.2 =78.39 mg/m³.

 

Allometric scaling factor (Toxicokinetics)

The allometric scaling factor accounts for metabolic differences between the test species and humans. This factor is not considered to be relevant for dimethoxymethylsilane on the following grounds:

 

1.  The silanol hydrolysis product of the substance (and many other related substances) shows no biodegradation in a ready biodegradation test other than can be accounted for by degradation of non-silanol hydrolysis products (see Section 5); this suggests that the substance and its silanol hydrolysis product are not recognised by biological systems containing all the mammalian enzymes and metabolic systems (see Section 5.1.2).

 

2. Toxicokinetic arguments show that the silanol hydrolysis product has low log Kow and hence low uptake, rapid excretion via urine, which would be true in all mammals, with minimal interspecies differences. 

 

3. Higher enzyme expression levels, stronger inducibility, higher substrate affinities and co-factor levels are factors that are potentially in favour of a more rapid xenobiotic metabolism, including elimination, by rodents compared to humans. Enzymes are not involved in the abiotic hydrolysis of the alkoxysilanes, and the silanols are rapidly excreted as such without prior enzymatic conjugation. This knowledge eliminates a great deal of the uncertainty on toxicokinetic interspecies differences.Since the metabolism of dimethoxymethylsilane by humans and rats does not involve enzymes, the toxicokinetic differences (both inter- and intraspecies) are reduced from 4.0 to 1.0. Only the toxicodynamic differences remain to be considered.

 

Intraspecies differences

The intraspecies assessment factor takes account for the variability in sensitivity between individuals. The human population is far more diverse than experimental animals that are bred to be as similar as possible, and unhealthy animals are not allowed to start the study. This AF also covers differences between ethnic groups and age groups. The default intraspecies factors are typically broken down into equal factors accounting for toxicodynamic and toxicokinetic differences, respectively. Accordingly, an interspecies factor of 10 is composed of two identical factors of √10 = 3.2.

Likewise, the default for workers (AF = 5) can be split into AFs of √5 = 2.24. As discussed above, the conversion of siloxanes to silanols and their excretion proceeds without enzymatic involvement. Individual genetic dispositions and other are therefore without effect on these processes. As a result, the toxicokinetic components (3.2 and 2.24 for general population and workers, respectively) can be eliminated from the intraspecies AF for substances that hydrolyse fast into the ultimate excretion product.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: substance specific (see discussion)
Overall assessment factor (AF):
16
Modified dose descriptor starting point:
NOAEC
Value:
312 mg/m³
Explanation for the modification of the dose descriptor starting point:
Reliable subchronic toxicity data via the inhalation route were available.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
substance specific (see worker discussion)
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
3.2
Justification:
substance specific (see worker discussion)
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:
no hazard identified
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:
5.66 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: substance specific (see discussion)
Overall assessment factor (AF):
16
Modified dose descriptor starting point:
NOAEL
Value:
90.48 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Reliable subchronic toxicity data via the inhalation route were available.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
substance specific (see worker discussion)
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
3.2
Justification:
substance specific (see worker discussion)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
DNEL (Derived No Effect Level)
Value:
0.89 µg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: substance specific (see discussion)
Overall assessment factor (AF):
57.6
Dose descriptor:
other: LOAEL
AF for dose response relationship:
3
Justification:
no NOAEL identified
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
default
AF for other interspecies differences:
1
Justification:
default
AF for intraspecies differences:
3.2
Justification:
substance specific (see worker discussion)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
0.81 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: substance specific (see discussion)
Overall assessment factor (AF):
48
Modified dose descriptor starting point:
NOAEL
Value:
39 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
substance specific (see worker discussion)
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
3.2
Justification:
substance specific (see worker discussion)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
no hazard identified

Additional information - General Population

In the absence of any significant findings relating to reproductive or developmental endpoints in appropriate screening tests, the critical health effect is considered to be repeated-dose toxicity.

There are only limited repeat dose toxicity data available for the dermal route for dimethoxymethylsilane (CAS 16881-77-9).In the available key dermal repeated dose toxicity study (Losco P. E. et al., 1996), which meets generally accepted scientific principles, but was not conducted according to an appropriate OECD TG and without GLP, New Zealand White rabbits of both sexes were exposed to dimethoxymethylsilane (CAS 16881-77-9) under occlusive conditions for 9 doses over a time of 11 days. The animals received the test item at doses of 43, 85, and 171 mg/kg bw. At the end of exposure period the animals were euthanised. 5 animals from high-dose and control group were kept as satellite groups for 2 weeks of recovery. No systemic toxicity was observed up to the high dose of 171 mg/kg bw. However, local dermal effects were seen still seen in the low dose group. Thus, the NOAEL for systemic toxicity was set at 171 mg/kg bw/day, and the LOAEL for local effects was set at 43 mg/kg bw/day, which corresponds to 0.051 mg/cm². Since the study duration is not sufficient for the properly predict risk of systemic toxicity after repeated dermal exposure, only the LOAEL for local effects will be used for DNEL derivation.

There are no repeat dose toxicity studies available for dimethoxymethylsilane (CAS: 16881-77-9) for the oral and inhalation routes, however, reliable data are available for the structural analogue substance trimethoxymethylsilane (CAS: 1185-55-3). Both substances will ultimately hydrolyse to produce the same hydrolysis product, methylsilanetriol. The Si-C bond is stable under physiological conditions; methyl moieties are thus firmly bound to the silanol group. The latter renders both molecules very polar and ready for rapid excretion via urine. It is therefore considered that read-across between the substances is appropriate. The other hydrolysis product is methanol. It is of note that the oral NOAEL in rats for methanol is greater (at least 2000 mg/kgbw/day) than the dose that is expected to be generated from hydrolysis of dimethoxymethylsilane in the stomach under conditions of a limit test. Therefore any effects of dimethoxymethylsilane will not be attributable to methanol.

 

For the oral route, a reliable key OECD 422 combined repeated dose/reproductive and developmental screening study in compliance with GLP is available for trimethoxy(methyl)silane (CAS 1185-55-3) (Dow Corning Corporation, 2005). This study is a valid investigation of the toxicological effects resulting from repeated oral-gavage administration of the test item to male and female rats for at least 28 days. The test item was administered in corn oil as vehicle at dosages of 50, 250, and 1000 mg/kg body weight/day, and controls received the vehicle only. Based on effects seen in the study the NOAEL for systemic toxicity was considered to be 50 mg/kg bw/day (Dow Corning Corporation, 2005).

 

For the inhalation route there is a study according to OECD TG 413 and GLP (Dow Corning Corporation, 2008). The test item (CAS 1185-55-3) was administered to Sprague-Dawley rats (10 per sex and dose) by whole body exposure at concentrations of 25, 100, 400 and 1600 ppm, corresponding to 140, 560, 2200 and 8900 mg/m³ for 6 hours per day, 5 days/week for a total of 90 days followed by a 28 day recovery period for the control and high dose groups. Based on increased incidence of grossly observed urinary bladder calculi along with kidney dilation at the 2200 mg/m³ exposure level, the NOAEC for trimethoxy(methyl)silane vapour was 100 ppm (corresponding to 560 mg/m³) the LOAEC was 400 ppm ( corresponding to 2200 mg/m³) (Dow Corning Corporation, 2008).

The long-term DNEL for systemic effects via the oral route is determined from the OECD 422 oral study on trimethoxy(methyl)silane, which identified a NOAEL of 50 mg/kg bw/day.

The molecular weight difference between target and source chemical is 106 g/mol/136.22 g/mol = 0.78. The NOAEL (oral) for the target chemical is therefore: 50 mg/kg bw x 0.78=39 mg/kg bw/day

No further corrections were made to the NOAEL.

 

The following assessment factors were applied to the corrected NOAEL:

Exposure duration (sub-acute to chronic): 6 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Interspecies differences (toxicokinetics, rat/human): 1 (substance-specific, see worker)

Intraspecies differences (toxicodynamics, gen. pop.): 3.2 (i. e. √10) (substance-specific, see worker)

Intraspecies differences (toxicokinetics, gen. pop.): 1 (substance-specific, see worker)

Overall Assessment Factor: 48

 

The overall DNEL (long-term – systemic – oral – general population) is therefore:

39 mg/kg bw/day/48 = 0.81 mg/kg bw/day.

 

The long-term DNEL (repeated-dose – systemic – dermal) for the general population is required for assessment of man exposed via the environment. It is determined on the basis of route-to-route extrapolation from the NOAEC for the structural analogue substance trimethoxy(methyl)silane (560 mg/m³) from a 90-day inhalation study in rats (exposure duration: 6 h/d, 5d/week).

The molecular weight difference between target and source chemical is 106 g/mol/136.22 g/mol = 0.78; the NOAEC for the target chemical is therefore 560 mg/m³ x 0.78 = 436.8 mg/m³

 

The following corrections were made:

Correction for respiratory volume: 0.29 m³/kg bw/day (rat, 6 hour)

Correction for route to route extrapolation (relative absorption inhalation vs. dermal): 1

Correction for number of exposures per week (5 days/week to 7 days/week): 5/7

The corrected NOAEL (dermal) is therefore:

436.8 mg/m³ x 0.29 m³/kg bw/day x (6/24) x (5/7) = 90.48 mg/kg bw/day

 

The following assessment factors were applied to the corrected NOAEL:

Exposure duration (sub-chronic to chronic): 2 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Interspecies differences (toxicokinetics, rat/human): 1 (substance-specific, see worker)

Intraspecies differences (toxicodynamics, gen. pop.): 3.2 (i. e. √10) (substance-specific, see worker)

Intraspecies differences (toxicokinetics, gen. pop.): 1 (substance-specific, see worker)

Overall Assessment Factor: 16

 

The overall DNEL (repeated-dose – systemic – dermal – general population) is therefore:

90.48 mg/kg bw/day/16 = 5.66 mg/kg bw/day

The long-term DNEL for local effects via the dermal route is determined on the basis of the LOAEL deduced from the repeated dermal toxicity study with the submission substance. No further corrections were made to the LOAEL of 0.051 mg/cm².

 

The following assessment factors were applied to the LOAEL:

Dose response relationship (LOAEL/NOAEL extrapolation): 3 (no NOAEL identified)

Exposure duration (sub-acute to chronic): 6 (default)

Interspecies differences: 1 (default)

Intraspecies differences (toxicodynamics, gen. pop.): 3.2 (√10) (substance specific, see below)

Intraspecies differences (toxicokinetics, gen. pop.): 1 (substance specific, see below)

Overall Assessment Factor: 57.6

 

The overall DNEL (repeated-dose – local – dermal – general population) is therefore:

0.051 mg/cm²/57.6 = 0.00089 mg/cm² = 0.89 µg/cm²/day

The long-term DNEL for systemic effects via the inhalation route is determined on the basis of the 90-day inhalation NOAEC for the structural analogue substance trimethoxy(methyl) silane (560 mg/m³, exposure duration: 6 h/d, 5 days/week).

The molecular weight difference between target and source chemical is 106 g/mol/136.22 g/mol = 0.78; the NOAEC for the target chemical is therefore 560 mg/m³ x 0.78 = 436.8 mg/m³

 

The following corrections were made:

Correction for lower human breathing rate: 4

Correction for experimental exposure duration (6 h/day to 24 h/day): 6/24

Correction for number of exposures per week (5 days/week to 7 days/week): 5/7

Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is:

436.8 mg/m³ x 4 x (6/24) x (5/7) = 312 mg/m³

 

The assessment factors were selected on the following basis:

Exposure duration (sub-chronic to chronic): 2 (default)

Interspecies differences (toxicodynamics): 2.5 (default)

Interspecies differences (toxicokinetics, rat/human): 1 (substance-specific, see worker)

Intraspecies differences (toxicodynamics, gen. pop.): 3.2 (i. e. √10) (substance-specific, see worker)

Intraspecies differences (toxicokinetics, gen. pop.): 1 (substance-specific, see worker)

Overall Assessment Factor: 16

 

The overall DNEL (long-term – systemic – inhalation – general population) is therefore:

312 mg/m³/16 = 19.5 mg/m³