Dimethoxydiphenylsilane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethoxydiphenylsilane

EC Number:

229-929-1

EC Name:

Dimethoxydiphenylsilane

Cas Number:

6843-66-9

Molecular formula:

C14H16O2Si

IUPAC Name:

dimethoxydiphenylsilane

Test animals

Species:

rat

Strain:

other: Hsd/Cpb:WU (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, 33176 Borchen, Gartenstraße 27
- Age at study initiation: jung adults
- Weight at study initiation: males 134-149 g, females 121-135 g
- Fasting period before study: 16 h prior to application and 3 h after application
- Housing: conventional, max. 5 animals per sex per cage (Makrolon Typ III, bedded with softwood fibre Type HW 300/500 W, JELU-Werk, Ludwigsmuehle, 73494 Rosenberg, certificate of contaminant analysis regularly provided by the producer)
- Diet: Ssniff R 10 (Ssniff, Spezialfuttermittel GmbH, 59494 Soest, analyses regularly conducted by producer), ad libitum
- Water: tap water (Gelsenwasser, Wasserwerk, 45721 Haltern, samples of tap water quaterly analysed), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.85 ml/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: after 0.5, 1, 2, 3, 4, 5, and 6 h, and on the following days once daily
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology of livers and kidneys of animals that were found dead

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Males: 2 out of 5 animals died (40%) (the first male 48 hours after test material application, the second after 72 hours)
Females: 1 out of 5 animals died (20%) (sacrifice 30 hours after test material application)

Clinical signs:

other: - decreased motility, abnormal tread, staggering, tremor, ataxia, hunched posture, prone position, lateral position - ruffled fur, salivation, haemorrhagic rhinorrhoea, prolaps penis, reddened extremities and mucosae - slight sedation, anesthesia-like sta

Gross pathology:

Gross pathology of the animals which died during the study revealed similar results. One male showed autolysis in general and cannibalism at the mouth. One male and the female animal showed emaciation, adherence of the eyes baused by secret formation, prolaps penis, blotchy and cirrhosis-like altered liver, and oesophagus and stomach filled with nutrition mash. Additionally a partly reddened and with secretion covered gastric squamous epithelium and a glandular stomach with isolated bleedings were recorded. In males the latter was white coloured and swollen, whereas the mucosa came off. In males the kidneys were dot-shaped and structured, and showed a slight pelvic extension. The cranial vault presented haematomas. In the other males haemorrhagic fluids were found in the thoracic cavity. In all animals adrenals were darkly coloured, the pancreas was white and bloodless, and the caecum content was hard and solid. The urinary bladder was bulging, and in males the genitals were decreased. In the lungs of both males a strong hyperaemia was noted. The spleen of the female animal was of a slight rose colour.
None of the surviving animals showed test material related gross pathological changes.

Other findings:

Histopathology (non-neoplastic):
Livers and kidneys of all three animals which died within 72 hours after test material application were microscopically examined. The specific substance related findings were degeneration of the kindney cortex and non-degenerative steatosis of the liver.

Any other information on results incl. tables

Clinical signs:

Signs of toxicity were first observed in males 2 hours and in females 3 hours after application. Symptoms were decreased motility and ruffled fur. After 3 hours males showed abnormal tread, staggering, salivation, haemorrhagic rhinorrhoea, and prolaps penis. 4 hours after application abnormal tread, decrease in motility, staggering, and ruffled fur was noted for both males and females. Males showed furthermore hunched posture, slight sedation, gasping, salivation and haemorrhagic rhinorrhoea, as well as prolaps penis, breath sounds, and anesthesia-like state. Additionally stronger salivation, and stronger ruffled fur, as well as prone position, tremor, and increased respiratory frequency were observed 5 and 6 hours after test material application. At this time females showed additionally slight sedation, ataxia, and stronger ruffled fur. Two females regenerated within 5 and 6 hours. After 24 hours for both males and females abnormal tread, hunched posture, lateral position, slight to moderate sedation, staggering, gasping, ruffled fur, moderate to strong hypothermia, reduced body weight, and anesthesia-like state were noted. Whereas one male did not show any signs of toxicity, other males were in a moribund condition with haemorrhagic rhinorrhoea and prolaps penis. Females showed clinical signs such as tremor, Straub phenomenon, salivation, emaciation and delayed body weight gain, and reddened extremities and mucosae. One female was in such a moribund condition that it was sacrificed in the mean of animal welfare 30 hours after test material application. At this time one male and female each were free of clinical signs. For the other males and females abnormal tread, staggering, ruffled fur, and delayed body weight gain were recorded. Males additionally showed lateral position, moribund condition, slight to moderate loss of body weight, prolaps penis, and anesthesia-like state. Females showed at this time additionally emaciation. 72 hours post application one female was free of clinical signs, while the remaining males and females showed hunched posture and ruffled fur. For males additionally hypothermia, delayed body weight gain, and prolaps penis were recorded, whereas females showed additionally abnormal tread, reduced body weight, and emaciation. 96 hours postapplication two males and three females were free of clinical signs, one male still showed ruffled fur and prolaps penis, and femals showed hunched posture and ruffled fur. Five days after test material application the one male and the one female animal still showed ruffled fur and the male animal additionally delayed body weight gain and prolaps penis. After six to eight days only in one male prolaps penis was recorded. Later this animal was also free of clinical signs.

Histopathology:

Livers and kidneys of all three animals which died within 72 hours after test material application were microscopically examined. One male showed slight to moderate signs of autolysis. The livers showed slight to moderate activation of Kupffer cells, slight congestion, and slight to moderate centrolobular to diffuse steatosis without degeneration. Nephrons of the exterior renal cortex showed a moderate expanded lumen without epithelial alterations. In the interior renal cortex the epitheliums of the proximal tubulus were slight to moderately swollen and the lumen was filled with eosinophilic cylinders. No alterations were found in the collecting tubules. Only poor swelling of the epithelium and granulated cylinders in the collecting tubules were observed in the animal, which showed autolysis.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

The test item was tested for acute oral toxicity according to the OECD TG 401 and in compliance with GLP. The LD 50 was found to be > 2000 mg/kg bw for both males and females. Hence, classification for acute oral toxicity according to 67/584/EEC and EC/1272/2008 is not warranted.