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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 Feb 1987 to 12 March 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP. The restrictions were that no data on purity or stability of the test item were provided and the females were tested at 2 doses, whereas at least 3 are recommended to permit an "acceptable determination of the LD50".

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No GLP. No data on purity or stability. The females were tested at 2 doses, whereas at least 3 are recommended to permit an "acceptable determination of the LD50".
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar Bor:WISW (SPFTNO)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co., Borchen, GERMANY
- Age at study initiation: 57 days (males), 71-72 days (females)
- Weight at study initiation: 172-197 g (males), 146-164 g (females)
- Fasting period before study: 16 h
- Housing: Macrolon cages type II
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): 55 +/-15
- Photoperiod (hrs dark / hrs light): 12 /12

IN-LIFE DATES: From: 25 February 1988 To: 12 March 1988

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.62 ml/kg bw

Doses:
5170 mg/kg bw (males)
2401 or 5170 mg/kg bw (females)
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: observation for mortality twice daily (once daily on weekends and holidays); clinical observations after treatment continuously for 4-6 h then daily; bodyweights on days 0, 7, 14.
- Necropsy of survivors performed: yes, macroscopic examination included external appearance, body orifices, body cavities (thoracic and abdominal), and their contents.
Statistics:
None given. LD50 value for males is derived from a limit test (1 dose). The LD50 value for females (based on 2 doses) is described as an estimate.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 170 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 5 170 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Estimate
Mortality:
Two females died at 5170 mg/kg bw (3-4 hours after exposure). There were no deaths in males at this dose or in females at 2401 mg/kg bw.
Clinical signs:
Various overt signs of toxicity in both sexes at both doses (see Table 1 for details). Most common were: reduced locomotion; impaired co-ordination; loss of muscle tone; loss of righting reflex. Initial symptoms of intoxication occurred seven minutes after administration of the substance and lasted two days.

Body weight:
No clear treatment-related effect.
Gross pathology:
The stomach and intestines of the two females that died were filled with liquid and the mucosa of the proventricular was red.

Any other information on results incl. tables

Table 1: Number of animals dead and with evident toxicity, and time range within which mortality occurred

 

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity(#/total)

Male

Female

Combined

Male

Female

Combined

2401

-

0/5

0/5

n/a

Reduced locomotion

Impaired co-ordination

Loss of muscle tone

Loss of righting reflex - lateral

Loss of righting reflex - supine

Loss ofpinna, pain or corneal reflexes

Clonic spasms

Excitation-like twitching

Ptosis (drooping eyelid)

Lacrymation

Mydriasis (dilated pupils)

Hypersialosis (excessive salivation)

Laboured breathing

Reduced body temperature

Abnormal gait

Sunken flanks

cyanosis

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

4/5

4/5

2/5

1/5

1/5

0/5

1/5

0/5

0/5

1/5

0/5

0/5

0/5

1/5

1/5

2/5

0/5

4/5

4/5

2/5

1/5

1/5

0/5

1/5

0/5

0/5

1/5

0/5

0/5

0/5

1/5

1/5

2/5

0/5

5170

0/5

2/5

2/10

4 h

Reduced locomotion

Impaired co-ordination

Loss of muscle tone

Loss of righting reflex - lateral

Loss of righting reflex - supine

Loss ofpinna, pain, corneal reflexes

Clonic spasms

Excitation-like twitching

Ptosis (drooping eyelid)

Lacrymation

Mydriasis (dilated pupils)

Hypersialosis (excessive salivation)

Laboured breathing

Reduced body temperature

Abnormal gait

Sunken flanks

cyanosis

5/5

5/5

4/5

2/5

2/5

0/5

1/5

0/5

0/5

0/5

0/5

0/5

4/5

0/5

0/5

1/5

0/5

4/5

4/5

3/5

3/5

3/5

2,2,2/5

0/5

1/5

2/5

0/5

2/5

4/5

4/5

2/5

1/5

3/5

2/5

9/10

9/10

7/10

5/10

5/10

2?/10

1/10

1/10

2/10

0/10

2/10

4/10

8/10

2/10

1/10

4/10

2/10

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study conducted in compliance with the now deleted OECD 401, but not to GLP (reliability score 2), the LD50 values for trimethoxy(propyl)silane were ≥ 5170 mg/kg bw, for male and female rats, respectively. These values would indicate low acute toxicity by the oral route. The most common signs of toxicity were reduced locomotion, impaired co-ordination, loss of muscle tone and loss of righting reflex.