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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:
28 April 2000 to 6 June 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, 59 NouSan No. 4200
Version / remarks:
1985
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Iodomethane
EC Number:
200-819-5
EC Name:
Iodomethane
Cas Number:
74-88-4
Molecular formula:
CH3I
IUPAC Name:
iodomethane
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Iodomethane
- Physical state: liquid
- Analytical purity: 99.7%
- Impurities (identity and concentrations): 0.2 % water and <0.1 % methanol
- Composition of test material, percentage of components: not stated
- Isomers composition: not stated

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: range-finder: males and females-11 weeks, main study: males-10 to 13 weeks and females-10 to 12 weeks
- Weight at study initiation: range-finder: males-306 to 358 g and females- 205 to 216 g, main study: males-283 to 399 g and females- 208 to 270 g
- Fasting period before study: overnight before dosing
- Housing: The animals were housed individually in suspended stainless steel cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: a minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 22 °C
- Humidity: 37 to 59 %
- Air changes: room ventilation was set to produce 10-15 air changes/hour.
- Photoperiod: Light timers were set to maintain a 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
DOSAGE PREPARATION:
- The test material was administered as received or mixed with corn oil to produce a 10 % w/v concentration and dispensed fresh on the day of dosing. The preparations were stirred continuously during dosing.
- The density of the test material was determined twice to confirm the volatile nature of the test material. The average of the two density measurements resulted in 2.22 g/mL. The density of the test material (bulk) was determined to be 2.22 g/mL.
- For the range finding study the test material was dosed as supplied for all concentrations. The maximum volume applied was 2.25 mL/kg
- For the main LC50 study at 50 and 75 mg/kg the test material was dosed from the 10 % w/v dilution prepared in corn oil. For all other dose groups the test material was dosed as supplied (100 %).

- Rationale for the selection of the starting dose: The range-finding data indicated that the test material produced mortality at the 500 mg/kg level in males and in females. Delayed mortality (day 5) was observed at the lowest dose level tested (100 mg/kg) in males, but no mortality occurred in the females.
Doses:
Range finding study: 100, 500, 1250, 2500 and 5000 mg/kg bw
Main LC50 study: 50, 75, 85, 100, 150, 250, 350 mg/kg bw
No. of animals per sex per dose:
- Range finding study: 1 animal per sex per dose
- Main LC50 study:
50 mg/kg: 5 animals per sex per dose
75 mg/kg: 5 males
85 mg/kg: 5 males
100 mg/kg: 5 animals per sex per dose
150 mg/kg: 5 females
250 mg/kg: 5 animals per sex per dose
350 mg/kg: 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical abnormalities a minimum of two times on study day 0 (post-dose) and daily thereafter (days 1-14). A general
health/mortality check was performed twice daily (in the morning and in the afternoon).
- Individual body weights were obtained for the 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, all study animals which died spontaneously during the study or were euthanised by carbon dioxide inhalation at study termination (day 14) were necropsied. Body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined. All gross lesions were collected and retained in 10 % neutral buffered formalin for possible future histological evaluation.
Statistics:
The LD50 and 95 % confidence intervals were calculated separately for each sex using a computer adaptation of the method of Litchfield and Wilcoxon.

Results and discussion

Preliminary study:
The range-finding data indicated that the test material produced mortality at the 500 mg/kg level in males and in females. Delayed mortality (day 5) was observed at the lowest dose level tested (100 mg/kg) in males, but no mortality occurred in the females.
Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
79.84 mg/kg bw
Based on:
test mat.
95% CL:
>= 77.25 - <= 82.55
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
131.98 mg/kg bw
Based on:
test mat.
95% CL:
>= 95.35 - <= 182.7
Mortality:
- All male rats died at the 85 mg/kg dose. No males died at the 75 mg/kg dose.
- For females, all rats died at the 350 mg/kg high dose but none at the 50 mg/kg low dose. Partial deaths were observed at the intermediate doses.
- All mortality occurred by study day 2.
- A summary is shown in Table 1.
Clinical signs:
other: - The most notable clinical abnormalities observed during the study included breathing abnormalities, prostration, tremors, soft stools/few faeces, faecal stain, dilated pupils, skin pale in colour, ocular discharge, salivation, decreased activity, wobbly
Gross pathology:
- The most notable gross internal findings were observed in the animals that died and included abnormal content of the digestive tract, foci/thickening of the stomach, mottled and/or dark red lung lobes, foci on the thymus and blackish-purple lobes of the liver. No significant gross internal findings were observed at necropsy on study day 14 .

Any other information on results incl. tables

Table 1: Summary of mortalities

Dose level (mg/kg)

Sex

No. of animals

Study day

Mortality

0

1

2

3 to 14

50

Male

5

0

0

0

0

0/5

75

5

0

0

0

0

0/5

85

5

4

1

-

-

5/5

100

5

4

0

1

-

5/5

250

5

5

-

-

-

5/5

50

Female

5

0

0

0

0

0/5

100

5

1

0

0

0

1/5

150

5

3

0

1

0

4/5

250

5

4

0

0

0

4/5

350

5

5

-

-

-

5/5

Applicant's summary and conclusion

Interpretation of results:
other: Category 3 according to EU criteria.
Conclusions:
Under the conditions of this study, the acute oral LD50 was determined to be 79.84 mg/kg and 131.98 mg/kg in male and female rats respectively. 
Executive summary:

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines EPA OPPTS 870.1100 and JMAFF 59 NohSan No. 3850, under GLP conditions.

The single-dose oral toxicity of the test material was evaluated in Sprague-Dawley rats. An LD50 study was performed in which 5 groups of five male and five female rats received a single oral administration of the test material 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 male rats died at the 85 mg/kg dose. No males died at the 75 mg/kg dose. For females, all rats died at the 350 mg/kg high dose but none at the 50 mg/kg low dose. Partial deaths were observed at the intermediate doses. All mortality occurred by study day 2. The most notable clinical abnormalities observed during the study included breathing abnormalities, prostration, tremors, soft stools/few faeces, faecal stain, dilated pupils, skin pale in colour, ocular discharge, salivation, wobbly gait, decreased activity, eyelids partially closed, and dark material around the facial area. Body weight gain/maintenance was noted for all surviving animals during the test period. The most notable gross internal findings were observed in the animals that died and included abnormal content of the digestive tract, foci/thickening of the stomach, mottled and/or dark red lung lobes, foci on the thymus and blackish-purple lobes of the liver. No significant gross internal findings were observed at necropsy on study day 14.

Under the conditions of this study, the acute oral LD50 was determined to be 79.84 mg/kg and 131.98 mg/kg in male and female rats respectively.