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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on generations indicated in Effect levels (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Triacetoxyethylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and citric acid are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and citric acid in the same category ). Therefore, citric acid has comparable values with acetic acid and the target substance triacetoxyethylsilane.
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
other: read-across
Title:
Unnamed
Year:
2011

Materials and methods

Principles of method if other than guideline:
Read-across approach from published experimental data on fertility and one-generation study on the supporting substance Citric acid.
GLP compliance:
no
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Citric acid
- Molecular formula (if other than submission substance): C6H8O7
- Molecular weight (if other than submission substance): 192.12
- Smiles notation (if other than submission substance): OC(=O)CC(O)(CC(O)=O)C(=O)O
- InChl (if other than submission substance): InChI=1/C6H8O7/c7-3(8)1-6(13,5(11)12)2-4(9)10/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
- Structural formula attached as image file (if other than submission substance): see Fig. in attached report

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
not examined
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
not examined
Reproductive performance:
not examined

Details on results (P0)

Based on the experimental results obtained with the supporting substance Citric acid (NOAEL >= 2500 mg/kg bw/day (basis for effect: number of pregnancies) in rats daily treated by feed before, during, and after mating), the read-across approach was applied and the NOAEL with the substance triacetoxyethylsilane is calculated to be equal or greater than 3048.62 mg/kg bw/day.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
>= 3 048.62 mg/kg bw/day
Sex:
female
Basis for effect level:
other: (Read-across approach from citric acid effect level based on test material and basis for effect: number of pregnancies)

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

Based on the experimental results obtained with the analogue Citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance triacetoxyethylsilane is calculated to be equal or greater than 3048.62 mg/kg bw/day.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 3 048.62 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: (Read-across approach from citric acid effect level based on test material and basis for effect: number of young born, or survival of young animals)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” version 2.1.2. Presented results show that both substances have common (eco)toxicological behavior (attachment).

Table 1: Data Matrix, Analogue Approach:

CAS Number

 

Source chemical

77-92-9

Target chemical

17689-77-9

CHEMICAL NAME

Citric acid

Triacetoxyethylsilane

PHYSICO-CHEMICAL DATA

Melting Point

Measured data:

153 ºC

Measured data:

-17.7 ºC (Freezing point)

Boiling Point

Decomposes

 

Measured data:

180.8 ºC at 102.1 kPa

Density

Measured data:

1.665 g/cm3 at 20 ºC

Measured data:

1.144 at 20 ºC (relative density)

Vapour Pressure

Estimated data:

5.6E-09 mm Hg

Measured data:

2.67 Pa at 20 ºC.

Partition Coefficient (log Kow)

Measured data:

-1.72

Calculated (EPI-Suite, US EPA v4.1):

0.74

Water solubility

 

Measured data:

1330 g/L

Not applicable:

Hydrolytically unstable.

ENVIRONMENTAL FATE and PATHWAY

Hydrolysis as a function of pH

 

Key study:

Read-across from experimental results on analogue propyltriacetoxysilane:

An abiotic degradation study was performed on propyltriacetoxysilane according to OECD Guideline 111 (GLP study). The half-life at pH 1.2, 4, 7 and 9 of propyltriacetoxysilane was determined to be < 37.5 seconds since the test item was completely hydrolysed at 150 seconds after the initial contact of the test item with water and four completed half life cycles could be estimated in a reaction time of 150 seconds. The stated mechanism of hydrolysis of propyltriacetoxysilane was free acetic acid as the main hydrolysis product and the fast kinetic polycondensation reaction of the forming silanols (trihydroxypropylsilane). Based on these results, the read-across approach was applied and triacetoxethylsilane was determined to rapidly hydrolysed into acetic acid and corresponding silanols in contact with water, resulting on a very low half-life time, regardless of pH.

Aerobic Biodegradation

 

Readily biodegradable

Key study:

Read-across from experimental results on analogue methylsilanetriyl triacetate:

Readily biodegradable.

ENVIRONMENTAL TOXICITY

Acute Toxicity to Fish

Experimental data:

(96 h) LC 50 = 1516 mg/L

Weight of evidence:

Read-across from experimental results with acetic acid:

In the first study, Wallen et. al., 1957 (reliability 2), an acute toxicity test was performed according to OECD Guideline 302. The LC50 (based on mortality) of test material, acetic acid, inGambusia affinisfor 96h exposure period was 251 mg/L. Based on this experimental result, read-across approach was applied and LC50 (96h, based on mortality) for triacetoxyethylsilane was calculated to be 326.42 mg/L.

In the study of Juhnke et. al, 1978 (reliability 2), an acute toxicity test was performed according to German Standard Method for Waste Water and Sludge of 1976 with test material acetic acid. The LC50 for 48h toxicity on the golden orfe (Leuscicus idul melanotus) was 410 mg/L (basis for effect: mortality). Based on this result, read-across approach was applied and LC50 (48h, based on mortality) for triacetoxyethylsilane was calculated to be 533.19 mg/L.

In the study of Mattson et. al., 1976 (reliability 2), Fathead minnow (Pimephales promelas) were exposed under static conditions to a series of concentrations of acetic acid. The 96 h LC50 was 79-88 mg/L (basis for effect: mortality). Based on this experimental result obtained with the supporting substance acetic acid, read-across approach was applied and the LC50 (96h) for triacetoxyethylsilane was calculated to be 102.74 -114.44 mg/L (bassis for effect: mortality).

 

Supporting studies:

Read-across from experimental results with sodium acetate:

There are two supporting studies from DeYoung et. al., 1996 and Terhaar et. al., 1972, both with reliability 2 performed for the supporting substance sodium acetate. In the first one and based on the experimental results (120h LC50 = 13330 mg/L forPimephales promelas), read-across approach was applied and the 120h LC50 for triacetoxyethylsilane was calculated to be 12690 mg/L. In the second study and based on the experimental results (96h LC50 = 10000 mg/L forPimephales promelas), the read-across approach was applied and the 96h LC50 for triacetoxyethylsilane was calculated to be 9520 mg/L.

Acute Toxicity to Aquatic Invertebrates

Experimental data:

(48 h) EC 50 = 1535 mg/L

Weight of evidence:

Read-across from experimental results with acetic acid:

In the first study, Janssen et. al., 1993 (reliability 2), an acute immobilisation test with acetic acid was performed according to an equivalent method to OECD Guideline 202. The EC50 inDaphnia magnafor 48h exposure period was 65 mg/L (basis for effect: mobility). Based on this experimental result, read-across approach from the supporting substance acetic acid was applied and EC50 (48h) for triacetoxyethylsilane was calculated to be 84.53 mg/L (based on mobility and with no pH adjustment).

In the study by Bringmann et. al, 1982 (reliability 2), a largely standardized procedure of water toxicology for testing the potential toxic action of water pollutants measured by the immobilization ofDaphnia magnaaccording to DIN 38412, Part II guideline (Daphnia short-time test) was performed. The EC50 (48h, basis for effect: mobility) for acetic acid was 95 mg/L with no pH adjustment and 6000 mg/L with pH adjustment. Based on this result, read-across approach from supporting substance acetic acid was applied and EC50 (48h, basis for effect: mobility) for triacetoxyethylsilane was calculated to be 123.54 mg/L with no pH adjustment and 7802.83 with pH adjustment.

In the study by Dowden et. al., 1965 (reliability 4), the EC50 of 86 chemicals was determined using a standardised method. The 24h EC50 of acetic acid forDaphnia magnawas determined to be 47 mg/L (basis for effect: mobility). Based on this result obtained with the supporting substance acetic acid, read-across approach was applied and the EC50 (48h, based on mobility) for triacetoxyethylsilane was calculated to be 61.12 mg/L.

In the published study by Saha et. al., 2006 (reliability 4), an acute toxicity test was performed withMoina micrurain a renewal system. Based on the experimental results obtained with the supporting substance acetic acid forMoina micrura(96h LC50 = 163.72 mg/L, basis for effect: mortality), the read-across approach was applied and the 96h LC50 for triacetoxyethylsilane was calculated to be 212.91 mg/L.

 

Supporting studies:

Read-across from experimental results with acetic acid and sodium acetate:

There are two supporting studies from Anderson, 1944 (reliability 4) and Bringmann et. al., 1977, (reliability 3) performed for the supporting substances acetic acid and sodium acetate respectively. In the first one and based on the experimental results with supporting substance acetic acid (16h NOAEC = 150 mg/L forDaphnia magnaand basis for effect: mobility), read-across approach was applied and the 16h NOAEC for triacetoxyethylsilane was calculated to be 195.07 mg/L. In the second study and based on the experimental results with supporting substance sodium acetate (24h LC50 = 7170 mg/L forDaphnia magnaand basis for effect: mobility), the read-across approach was applied and the 24h LC50 for triacetoxyethylsilane was calculated to be 6825.91 mg/L.

Toxicity to Aquatic Plants

 

Experimental data:

(72 h) EC 50 = 640 mg/L

Key study:

Read-across from experimental results on analogue propyltriacetoxysilane:

An Algae Growth Inhibition Test was performed according to OECD Guideline 201 (GLP study) on test item Propyltriacetoxysilane. The EC50 value (based on growth) rate for Pseudokirchenriella subpicata at 72 hour exposure period was 24.42 mg/L without pH adjustment and > 1562.50 mg/L with pH adjustment. The NOEC (72h and based on growth rate) was determined to be 18 mg/L without pH adjustment and 40 mg/L with pH adjustment. Based on microscopic observations performed at test termination in all test concentrations no differences in size and shape of algal cells were reported as compared to the algae cells in the control. Based on these results, the read-across approach was applied and the EC50 (72h) for triacetoxyethylsilane was calculated to be 23.03 mg/L without pH adjustment and > 1474.22 mg/L with pH adjustment, and NOEC (72) was 16.98 mg/L without pH adjustment and 37.74 mg/L with pH adjustment.

 

Supporting studies:

Read-across from experimental results on acetic acid and sodium acetate:

In the study by Bringmann and Kühn 1980 (klimisch 3) performed with acetic acid, the 8 days Toxicity Threshold for Scenedermus quadricauda was determined to be 4000 mg/L based on growth rate. Based on this result, the read-across approach was applied and the 8 days Toxicity Threshold for triacetoxyethylsilane was calculated to be 5201.89 mg/L.

In the study by Krebs, 1991 (klimisch 2) conducted on acetic acid, the EC50 at 24 hours of green algae exposure was 156 mg/L based on growth inhibition. The read-across was applied and EC50 (24h) for triacetoxyethylsilane was calculated to be 202.87 mg/L.

Based on the experimental results obtained by Bringmann and Kühn 1978 (klimisch 3) with acetic acid for Microcystis aeruginosa (8d Toxicity threshold = 90 mg/L, basis for effect: cell multiplication), the read-across approach was applied and the 8 days Toxicity Thershold for triacetoxyethylsilane was calculated to be 117.04 mg/L.

In the publication by Hoare et al., 1967 (klimisch 3) the EC50 at 60 hours of Anacystis nidularis (blue-green algae exposure) was determined to be 1640 mg/L based on growth inhibition. Taking into account this result, the read-across approach was applied and EC50 (60h, basis for effect: growth inhibition) for triacetoxyethylsilane was calculated to be 1561.30 mg/L.

Toxicity to microorganisms

 

No data

Key study:

Read-across from experimental results on analogue methylsilanetriyl triacetate:

In the ready biodegradability test was performed according to OECD Guideline 301 F on analogue methyltriacetoxysilane the 28 day-NOEC was determined to be 100 mg/L since the substance degraded well and did not inhibit the degradation of the toxicity test. Based on these results, the read-across approach was applied and 28 day-NOEC for triacetoxyethylsilane was calculated to be 106.37 mg/L under test conditions.

MAMMALIAN TOXICITY

Acute Toxicity: Oral

Experimental data:

LD 50 = 5790 – 7100 mg/kg bw (mice)

LD 50 = 11700 mg/kg bw (rats)

Data waiving (Column 2 of REACH Annex VIII):

The substance is corrosive.

Acute Toxicity: Inhalation

No data

Data waiving (Column 2 of REACH Annex VIII):

The substance is corrosive.

Acute Toxicity: Dermal

Experimental data:

A 4-hour skin irritation study in rabbits exposed to a solution containing 60% citric acid caused erythema and edema. This study did not assess a lethal dose value. TheLD50 was not provided.

Data waiving (Column 2 of REACH Annex VIII):

The substance is corrosive.

Repeated Dose Toxicity

Repeated dose toxicity: oral:

Experimental results:

In a 150-day study with male New Zealand White rabbits daily treated by feed, theNOAEL was 1500 mg/kg bw/day(based on no effects observed at the only dose tested).

In a 6-week study with male Sprague-Dawley rats daily treated by feed, theNOAEL was 4800 mg/kg bw/day(based on no effects observed at the highest dose tested).

Repeated dose toxicity: Oral: Weight of evidence:

Read-across from experimental results with acetic acid and sodium acetate:

In the first study, Alexandrov et. al., 1989 (reliability 2), an 8 month test with 60 mg/kg bw acetic acid (3 times per week, by intubation into the esophagus) in male rats was performed. The NOAEL (chronic) in male rats for acetic acid was 60 mg/kg bw. (basis for effect: mobility). Based on this experimental result, read-across approach from the supporting substance acetic acid was applied and NOAEL for triacetoxyethylsilane was calculated to be 78.03 mg/kg bw.

In the study by Cory Slechta, 1986 (reliability 3), male rats were chronically treated via drinking water with sodium acetate from weaning. No effects were mentioned on survival, reinforcement behaviour or body weight gain. Based on the experimental results obtained with the supporting substance sodium acetate (NOAEL in male rats >= 0.05 mg/kg bw/day, based on no effects observed at the highest dose tested.), the read-across approach was applied and NOAEL for triacetoxyethylsilane was calculated to be >= 0.05 mg/kg bw/day.

In the study by Dryden et. al., 1965 (reliability 2), male rats were daily treated by feed with sodium acetate during four weeks. No effects on growth or survival were observed at ca. 3600 mg/kg bw/day (the only dose tested). Based on the experimental results obtained with the supporting substance sodium acetate (NOAEL in male rats >= 3600 mg/kg bw/day), the read-across approach was applied and NOAEL for triacetoxyethylsilane was calculated to be >= 3417.23 mg/kg bw/day.

In the study by Goldman, 1981 (reliability 3), male rats received a daily dose of sodium acetate in the diet during 3 months. Indications of altered thyroid function and decreased growth were reported at the only dose tested. However, only males were exposed to the substance, a small number of animals were used and only the body weights and several indices of thyroid function were studied. The reported effects cannot be considered as being clearly adverse. The study is considered to be of limited use in evaluating the toxicity of the substance. Based on these results from supporting substance sodium acetate (NOAEL in male rats >= 21 mg/kg bw/day, based on no evidence of clearly adverse effects at the only dose tested), read across approach was performed and NOAEL for triacetoxyethylsilane was calculated to be >= 19.99 mg/kg bw/day.

In the study by Massaro et. al., 1987 (reliability 3) complex maze learning was investigated in male adult rats using a latent learning task. The adult subjects were exposed to sodium acetate in drinking water for 112 days beginning at weaning. No evidence of impairment of simple task performance was observed. The study is considered to be of limited use in evaluating the toxicity of the substance. Based on these results from supporting substance sodium acetate (NOAEL in male rats >= 0.01 mg/kg bw/day, based on no effects observed at the only dose tested), read-across approach was performed and NOAEL for triacetoxyethylsilane was calculated to be >= 0.01 mg/kg bw/day.

Genetic Toxicity in vitro

Gene mutation in bacteria

Experimental data:

In a bacterial reverse mutation assays usingS. typhimurium(TA97, TA98, TA100 and TA104) in the presence and absence of metabolic activation and up to 2000 μg/plate, citric acid was not mutagenic.

 

Weight of evidence:

Read-across from experimental results with acetic acid and sodium acetate:

In the study by Zeiger et. al., 1992 (reliability 1), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 and with GLP compliance was performed. A standard Ames test was carried out with acetic acid usingSalmonella typhimuriumstrains TA 98, TA 100, TA 1535, and TA 97, with and without metabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these experimental results, read-across approach was applied and triacetoxyethylsilane was also considered as no mutagenic under test conditions.

In the study by McMahon et. al., 1979 (reliability 2), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 (with deviations) was performed. A bacterial mutagen screening technique was carried out with acetic acid usingSalmonella typhimuriumstrains TA 1535, TA 1537, TA 98 and TA 100, with and without metabolic activation. Acetic acid did not show any mutagenic effect under test conditions. Based on these experimental results, read-across approach was applied and triacetoxyethylsilane was also considered as no mutagenic under test conditions.

In the study by Ishidate et. al., 1984 (reliability 2), bacterial reverse mutation assay (Ames test) according to OECD Guideline 471 (with deviations) was performed. The study was carried out with sodium acetate and usingSalmonella typhimuriumstrains TA92, TA1535, TA100, TA1537, TA94, only with metabolic activation. No significant increases in the numbers of revertant colonies were detected at the maximum dose tested. Based on these experimental results, read-across approach was applied and triacetoxyethylsilane was also considered as no mutagenic under test conditions.

 

Chromosomal aberration

No data.

Weight of evidence:

Read-across from experimental results with acetic acid and sodium acetate:

In the study by Morita et. al., 1990 (reliability 2), a cytogenetic assay was carried out with acetic acid using Chinese hamster ovary K1 cells. Acetic acid was not clastogenic at concentrations close to those showing cytotoxicity, both with and without metabolic activation. Low pH did induce some artificial chromosome aberrations, but these were eliminated by neutralization of the test medium. Based on these experimental results and applying the read-across approach, the substance triacetoxyethylsilane is also considered as not clastogenic under test conditions.

In the study by Ishidate et. al., 1983 (reliability 2), a chromosomal aberrations tests were carried out with sodium acetate using a Chinese hamster fibroblast cell line. In the studies, no metabolic activation systems were applied. The maximum dose of each sample was selected by a preliminary test in which the dose needed for 50% cell-growth inhibition was estimated using a cell densiometer. The incidence of cells with aberrations (including gaps) was 0%. Based on these experimental results, the read-across approach was applied and triacetoxyethylsilane was also considered as no mutagenic under test conditions.

Mammalian gene mutation

No data.

Key study:

Read-across from experimental results on analogue propyltriacetoxysilane:

A mammalian cell gene mutation assay was performed with mouse lymphoma L5178Y cells on analogue Propyltriacetoxysilane according to OECD Guideline 476. No biologically relevant increase of mutants was found after treatment with test item in both experiments, I (up to 10.0 mM with metabolic activation for 4h exposure and up to 5.5 mM without metabolic activation for 4h exposure) and II (up to 8.5 mM with metabolic activation for 4h exposure and up to 5.0 mM without metabolic activation for 24h exposure). Based on these results, the read-across approach was applied and the substance triacetoxyethylsilane was considered to be non-mutagenic on mouse lymphoma L5178Y cells with and without metabolic activation under test conditions.

Genetic Toxicity in vivo

 

Experimental data:

In a Dominant Lethal assay using male/female rats dosed at 3 g/kg for 5 days, citric acid did not induced germ cell genotoxicity.

Key study:

Read-across from experimental results with supporting substance sodium acetate:

In the study by Seiler, 1981 (reliability 2), the Testicular DNA-synthesis inhibition test (DSI test) was performed on male mice with Sodium Acetate (single oral dose by gavage). No inhibitory effect on DNA-replication was detectable in animals treated with Sodium Acetate. Based on these results, read-across approach was applied and triacetoxyethylsilane is also considered no genotoxic in animals (based on no effects on DNA-replication).

Carcinogenicity

No data.

No data.

Reproductive Toxicity

Toxicity to reproduction

Experimental data:

In a one-generation oral reproductive toxicity study, female rats and mice were daily treated with citric acid before, during, and after mating. The NOAEL was equal or greater than 2500 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young).

In a fertility study, female rats were exposed to citric acid in their daily diet for several months. TheNOAEL (reproductive toxicity) was 600 mg/kg bw/day(based on no effects observed at the only dose tested).

Weight of evidence:

Read-across from experimental results with citric acid and citric acid, sodium salt:

In the study by Bonting et. al., 1956 (reliability 2), a fertility test was carried out with citric acid on female rats (daily treated by feed for several months). No reproductive effects were observed. Based on the experimental results obtained with the supporting substance citric acid (NOAEL for reproductive effects = 600 mg/kg bw/day; LOAEL > 600 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for triacetoxyethylsilane was calculated to be 731.67 mg/kg bw/day, and LOAEL > 687.88 mg/kg bw/day for reproductive effects.

In the study performed by Wright et. al., 1976 (reliability 2), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats was carried out. Based on the experimental results obtained with the supporting substance citric acid (NOAEL P, F1 >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL for triacetoxyethylsilane was calculated to ≥ than 3048.62 mg/kg bw/day for studied effects.

In the same study performed by Bonting et. al. 1956 (reliability 2), a fertility test was carried out but with citric acid, sodium salt on female rats (daily treated by feed for several months). No reproductive effects were detected. Based on the experimental results obtained with the supporting substance citric acid, sodium salt (NOAEL for reproductive effects = 50 mg/kg bw/day; LOAEL > 50 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for triacetoxyethylsilane was calculated to be 54.71 mg/kg bw/day, and LOAEL > than 54.71 mg/kg bw/day for reproductive effects.

Developmental toxicity

Experimental results:

In a one-generation oral reproductive toxicity study, female rats and mice were daily treated with citric acid before, during, and after mating. The NOAEL was equal or greater than 2500 mg/kg bw/day (basis for effect: number of pregnancies, number of young born, or survival of young).

Weight of evidence:

Read-across from experimental results with acetic acid, sodium acetate, calcium formate and citric acid:

In the study by Food and Drug Research Laboratories, 1974 (reliability 2), following mating, adult female mice, rats and rabbits were dosed daily for 17 days by oral intubation with acetic acid. No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls. Based on the experimental results with supporting substance acetic acid (NOAEL >= 1600 mg/kg bw/day for maternal and developmental toxicity), the read-across approach was applied and the NOAEL of triacetoxyethylsilane for maternal and developmental toxicity was calculated to be >= 2080.75 mg/kg bw/day.

In the study by Kavlock et. al., 1987 (reliability 2), pregnant mice were generally treated by oral gavage during gestation at a dose level predicted from a preliminary range finding study to induce a slight degree of maternal toxicity. No maternal toxicity and no neonatal effects (mortality and body weight) were observed at the treatment dose level of 1000 mg/kg bw/day. Based on the experimental results obtained with supporting substance sodium acetate (NOAEL >= 1000 mg/kg bw/day) for maternal and neonatal toxicity), read-across approach was applied and the NOAEL for triacetoxyethylsilane was calculated to by >= 895.00 mg/kg bw/day.

In the study by Malorny, 1969 (reliability 2) a three-generation drinking water study with calcium formate in the drinking water was performed in Wistar rats during ca. 3 years. No effects on fertility were observed. Number, weight and length of offspring did not differ in treated animals from controls. No statistical differences in organ or bone abnormalities were found. The growth of treated offspring was similar to controls. Based on experimental results on supporting substance calcium formate (NOAEL for maternal and developmental toxicity >= 200 mg/kg bw/day), the read-across approach was applied and the NOAEL for triacetoxyethylsilane was calculated to be >= 240.08 mg/kg bw/day for maternal and developmental toxicity.

In the study by Wright et. al. 1976 (reliability 4), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the mice and rats was carried out. No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats, compared to controls. Based on the experimental results from supporting substance citric acid (NOAEL >= 2500 mg/kg bw/day, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL for triacetoxyethylsilane was calculated to be >= 3048.62 mg/kg bw/day for studied effects.

Applicant's summary and conclusion

Conclusions:
Based on the experimental results obtained with the analogue Citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance triacetoxyethylsilane is calculated to be equal or greater than 3048.62 mg/kg bw/day for studied effects.
Executive summary:

Based on the experimental results obtained with the analogue Citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance triacetoxyethylsilane is calculated to be equal or greater than 3048.62 mg/kg bw/day for studied effects.