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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:
24 February 1993 - 15 April 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solution
Details on test material:
- Physical state: liquid
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Age at study initiation: Young adult
- Weight at study initiation: Males: 229 - 261 g Females: 231 - 273 g
- Fasting period before study: Overnight
- Housing: The animals were housed individually in suspended stainless steel cages
- Diet (e.g. ad libitum): Municipal tap water treated by reverse osmosis or deionization (back-up system) was available to the animals ad libitum throughout the study.
- Water (e.g. ad libitum): Purina Certified Rodent Chow #5002 was provided ad libitum to the animals throughout the study (except during fasting).
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 64-79°F
- Humidity (%): 35 - 58
- Photoperiod): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 24 February 1993 To: 15 April 1993

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSING
On day -1, the animals chosen for the LD50 study were weighed and fasted overnight. On day 0, the test material was administered orally as a single dose using a ball tipped stainless steel gavage needle attached to a syringe. Individual doses were calculated based on the animal's fasted (day 0) body weight. Animals were returned to ad libitum feeding after dosing.

CLINICAL OBSERVATIONS
LD50 study animals were observed for clinical abnormalities a minimum of two times on study day 0 (postdose) and daily thereafter (days 1-14). A mortality check was performed twice daily, in the morning and afternoon.

BODY WEIGHTS
Individual body weights were obtained for the LD50 study animals prior to fasting (day -1), prior to dosing on day 0 and for all surviving animals on days 7 and 14.

GROSS NECROPSY
All LD50 study animals which died spontaneously during the study or were euthanized (carbon dioxide inhalation) at study termination (day 14) were necropsied. Body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined. No tissues were retained.
Doses:
Preliminary Study: 100, 300, 500, 1000, 2000, 3000, 5000 mg/kg

Main study: 200, 300 and 500 mg/kg.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were obtained for the LD50 study animals prior to fasting (day -1), prior to dosing on day 0 and for all surviving animals on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical observations were made a minimum of two times on study day 0 (postdose) and daily thereafter (days 1-14). A mortality check was performed twice daily, in the morning and afternoon.
Statistics:
The LD50 and 95% confidence intervals were calculated separately for males, females and the combined sexes (when possible) using a computer adaption of the method of Litchfield and Wilcoxon. Body weight means and standard deviations were calculated separately for males and females for each dose level administered.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
273 mg/kg bw
Based on:
other: 85% Dimethyltin dichloride: 15% monomethyltin dichloride
95% CL:
141 - 528.5
Sex:
female
Dose descriptor:
LD50
Effect level:
164 mg/kg bw
Based on:
other: 85% Dimethyltin dichloride: 15% monomethyltin dichloride
95% CL:
104.5 - 258
Sex:
male/female
Dose descriptor:
LD50
Effect level:
204.5 mg/kg bw
Based on:
other: 85% Dimethyltin dichloride: 15% monomethyltin dichloride
95% CL:
152.5 - 273.5
Mortality:
No animals in the 200 mg/kg bw group died.
1 male and 3 females in the 300 mg/kg bw group died.
2 male and 4 females in the 500 mg/kg bw group died.

All mortality occurred by study day 4.
Clinical signs:
The most notable clinical abnormalities observed included decreased activity, salivation, rough haircoat, mucoid/soft stools, fecal/urine stain, hunched posture, dehydration, dark material around the facial area, decreased defecation and food consumption, gasping and rales.
Body weight:
Body weight gain was noted for the majority of surviving animals during the test period.
Gross pathology:
The most notable gross internal findings were observed in the animals that died and included dark red medulla of the kidney, dark red foci on the thymus, mottled lungs, abnormal coloured mucoid/fluid contents and eroded area(s), reddened mucosa and dark red linear striations on the stomach.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, the acute oral LD50 of [Di/Mono] Methyltin Chlorides Solution in the male rat was determined to be 546 mg/kg. In the female rat, the oral LD50 was determined to be 328 mg/kg. In the sexes combined, the oral LD50 was determined to be 409 mg/kg. The [Di/Mono] Methyltin Chlorides Solution is a 50% organotin solution in an unspecified solvent and therefore the LD50 value achieved should be halved. The LD50 of 84.79 % pure Dimethyltin dichloride would therefore be 273 mg/kg for male rats 164 mg/kg for female rats, with the combined LD50 being 204.5 mg/kg bw.
Executive summary:

The single-dose oral toxicity of [Di/Mono] Methyltin Chlorides Solution was evaluated in Sprague-Dawley rats. The study was initiated with a range-finding test at levels ranging from 100 to 5000 mg/kg body weight. Following the range-finding test, an LD50 study was performed in which three groups of male and female rats received a single oral administration of the test article at graded dosage levels. Following dosing, the LD50 study rats were observed daily and weighed weekly. A gross necropsy examination was performed on all LD50 study animals at the time of death or scheduled euthanasia (day 14).

All mortality occurred by study day 4. The most notable clinical abnormalities observed during the LD50 study included decreased activity, salivation, rough haircoat, mucoid/soft stools, fecal/urine stain, hunched posture, dehydration, dark material around the facial area, decreased defecation and food consumption, gasping and rales. Body weight gain was noted for the majority of surviving animals during the test period. The most notable gross internal findings were observed in the animals that died and included dark red medulla of the kidney, dark red foci on the thymus, mottled lungs, abnormal colored mucoid/fluid contents and eroded area(s), reddened mucosa and dark red linear striations on the stomach.

Under the conditions of this test, the acute oral LD50 of [Di/Mono] Methyltin Chlorides Solution in the male rat was determined to be 546 mg/kg. In the female rat, the oral LD50 was determined to be 328 mg/kg. In the sexes combined, the oral LD50 was determined to be 409 mg/kg. The [Di/Mono] Methyltin Chlorides Solution is a 50% organotin solution in an unspecified solvent and therefore the LD50 value achieved should be halved. The LD50 of 84.79 % pure Dimethyltin dichloride would therefore be 273 mg/kg for male rats 164 mg/kg for female rats, with the combined LD50 being 204.5 mg/kg bw.