Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
147 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
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:
21 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

[3-(2,3-epoxypropoxy)propyl]trimethoxysilane(GLYMO) is a volatile liquid which hydrolyses (half-life 6.5 hours at pH 7) in moist air and in contact with tissues to form methanol and [3-(2,3-epoxypropoxy)propyl]silanetriol.

 

Following repeated oral exposure to GLYMO with gavage doses of 1000 mg/kg bw/day for 28 days, no adverse effects were observed in rats (DCC, 1981). No suitable data are available for the dermal or inhalation routes.

In a subchronic toxicity study with rats according to OECD Guideline 408theNOAELfor the related substancebeta-(3,4-epoxycyclohexyl)ethyltriethoxysilanewas found to be 1000 mg/kg bw/day.

In a good quality oral one-generation reproductive toxicity study (Beckeret al., 2004) conducted to OECD 415 and GLP, the parental and reproductive NOAELs for GLYMO were 500 and ≥ 1000 (the highest dose tested) mg/kg bw/d, in rats. Treatment with the test substance resulted in signs of discomfort after dosing (noted for P females from early / mid gestation onwards), decreased body weight gain of males, and increased absolute and relative liver and kidney weights in P males and females. Histopathology revealed effects on livers and kidneys of males. Test animals were dosed for 90 day, 5 days per week.

In a well conducted oral study (BRRC, 1993), using a protocol similar to OECD 414 and GLP, the NOAELs for maternal toxicity and developmental toxicity were 200 and ≥400 (the highest dose tested) mg/kg bw/day, respectively, in rabbits. No developmental effects were observed at the highest dose, in the presence of maternal toxicity.

For the purposes of calculating DNELs for general systemic toxicity, the parental NOAEL of 500 mg/kg/day (males) from the one-generation reproduction study is selected as the most appropriate starting point. Although the examinations did not conform fully to the guidelines for repeated-dose toxicity, the duration of exposure was longer than the available repeated-dose study, in which no effects were observed (90 days versus 28 days). No DNELs for reproductive or developmental toxicity are calculated in the absence of effects. No significant effects on fertility or developmental endpoints were observed up to the maximum dose tested in an OECD 414 and 415 developmental and one-generation reproductive toxicity tests in rats, up to the maximum dose levels of 400 and 1000 mg/kg/day, respectively. It is therefore not possible to quantify DNELs for reproductive or developmental endpoints.

The available carcinogencity study indicates that GLYMO is not carcinogenic, therefore no DMEL for carcinogenicity can be calculated.

A further in vivo genetic toxicity study is proposed; it is not possible to come to a conclusion about genetic toxicity until the results of the proposed testing are known.

 

No quantitative DN(M)ELs could be derived for:

Acute toxicity – local effects

Long-term toxicity – local effects

Reproductive/developmental toxicity (no effects)

Mutagenicity (further testing proposed)

Carcinogenicity (not carcinogenic)

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. GLYMO is not currently classified as mutagenic, carcinogenic or sensitising. Mutagenicity will need to be reassessed in the light of results of proposed further testing.

The DNELs used for risk characterisation (workers) are therefore:

DNEL (long-term, inhalation): 147 mg/m3

DNEL (long-term, dermal): 21 mg/kg/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Value:
43.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

DNELs for the general population are based on the data discussed above for the DNELs for workers.

The DNELs used for risk characterisation (consumers/general population) are:

DNEL (long-term, inhalation): 43.5 mg/m3

DNEL (long-term, dermal): 12.5 mg/kg/day

DNEL (long-term, oral): 12.5 mg/kg/day