Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08-10-1996 to 25-10-1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar (HsdCpb:WU/SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, 33176 Borchen, Germany.
- Age at study initiation: Young adult animals
- Fasting period before study: Animals were fasted prior to substance administration for a period of about 16 hours. 3 hours after application food was offered ad libitum
- Housing: Makrolon type III cages, grouped caged per sex, each cage containing maximum of five rats. The bedding used was soft wood type HW 300/500W, produced by JELU-WERK, Ludwigsmühle, 73494 Rosenberg.
- Diet :Ssniff R 10 diet pellet form (laboratory standard rat diet) produced by Ssniff Spezialfutter GmbH, 69494 Soest. Food was offered ad libitum.
- Water :The animals received tap water ad libitum, (Fa. Gelsenwasser, Wasserwerk, 45271 Haltern).
- Acclimation period: Animals were acclimatised for at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light):Artificial light, from 7.00 a.m. to 7.00 p.m.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:2.03 cm³/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: Rats were checked at least twice daily for any mortality. Animals were observed for clincial signs soon after dosing and at frequent intervals for the remainder of Day 0 (a period of approximately six hours). On subsequent days animals were observed once a day. All animals were observed for 14 days after dosing. Individual body weights were recorded on Days 0 (prior to dosing), 7 and 14. The bodyweight was also recorded on the day of death.
- Necropsy of survivors performed: yes. All surviving animals were killed on Day 14 by carbon dioxide inhalation and subjected to a macroscopic examination after opening the abdominal and thoracic cavities
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, macroscopic appearance of all examined tissues was recorded for each animal.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg bw: 2/5 males died
Clinical signs:
In the first six hours after treatment with the test substance all animals showed severe clinical symptoms. Symptoms like padding movements, gait abnormality, decreased activity and squatting position were recorded. 24 and 48 hours after treatment most of the animals showed still the described clinical signs. Only one male and one female showed these signs 72 hours after treatment with the test substance. Milder clinical signs like piloerection were observed until day 7. After 7 days until the end of the observation period there were no more signs of systemic reaction to treatment.
Body weight:
In the first week after application of the test substance only minimal body weight gains were noticed in male and female animals. In the second week after treatment with the test substance the rats achieved satisfactory body weight gains.
Gross pathology:
The macroscopic examination of the two perished animals showed the most severe lesions in the stomach and the intestine. The mucosa of these tissues showed hyperaemia and haemorrhages. No macroscopic abnormalities were observed in animals killed on day 14.

Any other information on results incl. tables

Table 1. Mortality.

Dose (mg/kg bw)(1)

Number of animals m/f(2)

Mortality

Male

Female

total

Rel (%)(3)

total

Rel (%)

2000

5/5

2

40

0

0

(1) bw = body weight.

(2) m/f = male/female.

(3) rel (%) = relative mortality in percent.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this study performed in rats according to OECD 401 and GLP, the LD50 of (3-Chloropropyl)diethoxymethylsilane was found to be > 2000 mg/kg bw.