Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
49.5 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):
33
Dose descriptor starting point:
NOAEL
Value:
320 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
1 633.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

The long-term DNEL for systemic effects via the inhalation route is determined based on no systemic toxicity after repeated exposure to concentrations up to 0.62 mg/l, the NOAEC was set at ≥620 mg/m³, which was the highest dose tested (Bio-Research Laboratories, 1980).

Correction for molecular weight of triethoxy(phenyl)silane and trimethoxy(phenyl)silane: 240.38 g/mol / 198.3 g/mol=1.21

Correction for lower human breathing rate: 4

Correction for experimental vs. occupational exposure duration: 6.5 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:

620 mg/m³×4×(6.5/8)×(6.7 /10)×1.21=1633.6 mg/m

AF for dose response relationship:
1
Justification:
study is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
based on a subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
2.2
Justification:
substance-specific, see discussion
AF for the quality of the whole database:
1
Justification:
based on a high-quality study
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:
1.7 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):
33
Dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
56 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data are available for the dermal route. However, reliable data are available for the oral route.

Corrected starting point for the dermal route for workers:

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) * (7 days exposure rat/5 days exposure worker) = 40 mg/kg bw/day *(1/1) * 1.4 = 56 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.

AF for dose response relationship:
1
Justification:
based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
based on a subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
substance-specific (see discussion)
AF for other interspecies differences:
2.5
Justification:
ECHA default
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 study
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:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

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.

 

An OECD 422 combined repeated dose/reproductive and developmental screening study with triethoxy(phenyl)silane by oral route in rats is available (Eurofins, 2019).

Triethoxy(phenyl)silane was administered in corn oil as vehicle at dosages of 40, 120, and 360 mg/kg body weight/day, and controls received the vehicle only. Based on the findings in urinary bladder noted in mid and high dose group, a general NOAEL was set to 40 mg/kg bw/day.

A repeated inhalation toxicity study similar or equivalent to the OECD TG 412, but not in compliance with GLP, is also available on trimethoxy(phenyl)silane. The test item was administered to Sprague-Dawley rats (10 per sex and dose) by whole body exposure at concentrations of 9.5, 52.4, and 76.5 ppm, corresponding to 77, 425, and 620 mg/m³ for 6.5 hours per day, 5 days/week for a total of 28 days. There were no compound related effects in mortality, clinical signs, body weight, food consumption, haematology, clinical chemistry, organ weights, or gross and histologic pathology.

Based on no systemic toxicity after repeated exposure to concentrations up to 620 mg/m³, the NOAEC was set at≥620 mg/m³, which was the highest dose tested (Bio-Research Laboratories, 1980).

No information on repeated dose toxicity via the dermal route is available.

In acute oral and dermal toxicity studies LD50s of 2802 and 3014 mg/kg bw were observed, respectively.

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.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.09 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):
48
Dose descriptor starting point:
NOAEL
Value:
620 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
580.51 mg/m³
Explanation for the modification of the dose descriptor starting point:

The long-term DNEL for systemic effects via the inhalation route is determined based on no systemic toxicity after repeated exposure to concentrations up to 620 mg/m³, the NOAEC was set at ≥ 620 mg/m³, which was the highest dose tested (Bio-Research Laboratories, 1980).

Correction for molecular weight of triethoxy(phenyl)silane and trimethoxy(phenyl)silane: 240.38 g/mol / 198.3 g/mol=1.21
Correction for experimental vs. occupational exposure duration: 6.5 h/24 h

Correction for number of exposures per week: 5 d/7 d

Correction for lower human breathing rate: 4

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

620 mg/m³×1.21×(6.5/24)×(5/7)×4=580.51 mg/m³

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
based on a subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
3.2
Justification:
substance-specific, see discussion
AF for the quality of the whole database:
1
Justification:
base on high-quality study
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:
0.83 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
Dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data are available for the dermal route. However, reliable data are available for the oral route.

Corrected starting point for the dermal route for workers:

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) = 40 mg/kg bw/day *(1/1) = 40 mg/kg bw/day. It is assumed that oral and dermal absorption rates are equal.

AF for dose response relationship:
1
Justification:
based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
based on a subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
substance-specific, see discussion
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
3.2
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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.83 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
Dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
AF for dose response relationship:
1
Justification:
based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
based on a subacute study
AF for interspecies differences (allometric scaling):
1
Justification:
substance-specific, see discussion
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
3.2
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:
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.

 An OECD 422 combined repeated dose/reproductive and developmental screening study with triethoxy(phenyl)silane by oral route in rats is available (Eurofins, 2019).

Triethoxy(phenyl)silane was administered in corn oil as vehicle at dosages of 40, 120, and 360 mg/kg body weight/day, and controls received the vehicle only. Based on the findings in urinary bladder noted in mid and high dose group, a general NOAEL was set to 40 mg/kg bw/day.

 

A repeated inhalation toxicity study similar or equivalent to the OECD TG 412, but not in compliance with GLP, is also available on trimethoxy(phenyl)silane. The test item was administered to Sprague-Dawley rats (10 per sex and dose) by whole body exposure at concentrations of 9.5, 52.4, and 76.5 ppm, corresponding to 77, 425, and 620 mg/m³ for 6.5 hours per day, 5 days/week for a total of 28 days. There were no compound related effects in mortality, clinical signs, body weight, food consumption, haematology, clinical chemistry, organ weights, or gross and histologic pathology.

Based on no systemic toxicity after repeated exposure to concentrations up to 620 mg/m³, the NOAEC was set at≥620 mg/m³, which was the highest dose tested (Bio-Research Laboratories, 1980).

No information on repeated dose toxicity via the dermal route is available.

In acute oral and dermal toxicity studies LD50s of 2802 and 3014 mg/kg bw were observed, respectively.

The main hazard is observed after repeated oral exposure. Therefore, DNELs for long-term exposure are adequate to protect against short-term exposures and no separate short-term DNELs are calculated for general population.