Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 January 1993 - 12 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Principles of method if other than guideline:
The temperature and relative humidity of the animal room (66-72 °F and 30-60 %, respectively) exceeded the range specified in the protocol (61-70°F and 40-60%, respectively) during this study. The final body weight and method of euthanasia was not recorded for animal #6636/M and #6640/M, respectively. These occurrences are considered to have had no adverse effect on the outcome of this study.
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:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mohican Valley Rabbitry, Loudonville, OH.
- Age at study initiation: NDA
- Weight at study initiation: Male: 2.662 - 2.893 kg. Female: 2.436 - 2.601 kg
- Housing: The animals were housed individually in suspended stainless steel cages.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow #5322 ad libitum
- Water (e.g. ad libitum): Municipal tap water treated by reverse osmosis or deionization (back-up system) ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66 - 72
- Humidity (%): 30 - 60 %
- Air changes (per hr): 10 - 12
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 2nd March 1993 To: 12th April 1993

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Not specified, but covered with 4" x 8" gauze dressing.
- % coverage: ≥ 10%
- Type of wrap if used: plastic

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed using gauze moistened with distilled water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): NDA
- Concentration (if solution): 100%
Duration of exposure:
ca. 24 hours
Doses:
200, 400 and 750 mg/kg bw
No. of animals per sex per dose:
5 males, 5 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed daily. Bodyweights recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs, gross necropsy
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 LD50 level administered.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
404 mg/kg bw
Based on:
test mat.
95% CL:
287 - 568
Mortality:
200 mg/kg: 0/5 males, 0/5 females
400 mg/kg: 4/5 males, 2/5 females
750 mg/kg: 4/5 males, 5/5 females
Clinical signs:
Clinical abnormalities were observed during the LD50 study in the animals that died during the study were sacrificed moribund and in animals surviving to study termination. In the animals that died or were sacrificed moribund during the study, clinical abnormalities included slight to severe dermal irritation at the site of the test material application, urine/fecal stain, soft stool/diarrhea, decreased food consumption, decreased activity, pale eyes, decreased defecation, tremors, wobbly gait, respiratory abnormalities, mucoid stools, reddened iris, prostration, partial immobility of the hindlimbs, dark material and swelling around the facial area, convulsions, dehydration, emaciation, red ocular discharge, apparent hypothermia, raised area on the abdominal region and grinding of teeth. Clinical abnormalities noted in the animals surviving to study termination included slight to severe dermal irritation at the site of test material application, decreased defecation, decreased activity, pale eyes, dark material around the facial area, partial immobility of the hindlimbs, tremors, wobbly gait, soft stool, mucoid stools, fecal stain, reddened iris, apparent decreased food consumption and raised area on the abdominal region.
Body weight:
Although, body weight loss was noted during the day 0-7 interval for 1 male and 1 female in the 400 mg/kg dose level and for the one surviving male in the 750 mg/kg dose level, these animals did gain weight during the day 7-14 interval. Body weight gain was noted for the remaining surviving animals during the test period.
Gross pathology:
The most notable gross internal findings were observed in the animals that died and included reddened mucosa in the digestive tract, petechial hemorrhages, abnormally coloured fluid/mucoid contents in the digestive tract, dark red foci on the mucosa of the stomach, mottled and/or dark red thymus, mottled and/or firm, consolidated lungs, clear amber or red fluid contents in the thoracic cavity and light red foamy contents in the trachea. Cysts on the oviducts were noted in two female rabbits surviving to study termination. However, this observation was not considered significant since it is commonly observed in this strain of rabbit.

Applicant's summary and conclusion

Interpretation of results:
other: Acute tox. 3
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, the acute dermal LD50 of [Di/Mono] Methyltin Chlorides Solution in the male rabbit was determined to be 380 mg/kg. In the female rabbit, the dermal LD50 was determined to be 413 mg/kg. In the sexes combined, the dermal LD50 was determined to be 404 mg/kg.
Executive summary:

The single-dose dermal toxicity of (Di/Mono] Methyltin Chlorides Solution (84.8 % DMTC in mixture with MMTC) was evaluated in New Zealand White rabbits. The study was initiated with a range-finding test at levels ranging from 100 to 2000 mg/kg bw. Following the range-finding test, an LD50 study was performed in which three groups of male and female rabbits received a single dermal administration of the test material at graded dosage levels. Following dosing, the LD50 study rabbits were observed daily and weighed weekly. A gross necropsy examination was performed on all LD50 study animals at the time of death, moribund euthanasia, or scheduled euthanasia (day 14).

Mortality during the LD50 study occurred as follows:

Dose Level

(mg/kg)

Incidence of Mortality

Males

Females

Combined

200

0/5

0/5

0/10

400

4/5

2/5

6/10

750

4/5

5/5

9/10

Clinical abnormalities were observed during the LD50 study in the animals that died during the study were sacrificed moribund and in animals surviving to study termination. In the animals that died or were sacrificed moribund during the study, clinical abnormalities included slight to severe dermal irritation at the site of test article application, urine/fecal stain, soft stool/diarrhea, decreased food consumption, decreased activity, pale eyes, decreased defecation, tremors, wobbly gait, respiratory abnormalities, mucoid stools, reddened iris, prostration, partial immobility of the hindlimbs, dark material and swelling around the facial area, convulsions, dehydration, emaciation, red ocular discharge, apparent hypothermia, raised area on the abdominal region and grinding of teeth. Clinical abnormalities noted in the animals surviving to study termination included slight to severe dermal irritation at the site of test article application, decreased defecation, decreased activity, pale eyes, dark material around the facial area, partial immobility of the hindlimbs, tremors, wobbly gait, soft stool, mucoid stools, fecal stain, reddened iris, apparent decreased food consumption and raised area on the abdominal region. Weight loss was noted during the day 0-7 interval for 1 male and 1 female in the 400 mg/kg dose level and for the one surviving male in the 750 mg/kg dose level; however, these animals did gain weight during the day 7-14 interval. Body weight gain was noted for the remaining surviving animals during the test period. The most notable gross internal findings were observed in the animals that died and included reddened mucosa in the digestive tract, petechial hemorrhages, abnormally coloured fluid/mucoid contents in the digestive tract, dark red foci on the mucosa of the stomach, mottled and/or dark red thymus, mottled and/or firm, consolidated lungs, clear amber or red fluid contents in the thoracic cavity and light red foamy contents in the trachea. Cysts on the oviducts were noted in two of the female rabbits surviving to study termination. However, this observation was not considered significant since it is commonly observed in this strain of rabbit.

Under the conditions of this test, the acute dermal LD50 of [Di/Mono] Methyltin Chlorides Solution in the male rabbit was determined to be 380 mg/kg. In the female rabbit, the dermal LD50 was determined to be 413 mg/kg. In the sexes combined, the dermal LD50 was determined to be 404 mg/kg.