Chinomethionate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3rd April 1990 to 25th April 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF, Guideline on Toxicology Study Data for Application of Agricultural Chemical Registration, 59 Nohsan No. 4200, January 1985.

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chinomethionate

EC Number:

219-455-3

EC Name:

Chinomethionate

Cas Number:

2439-01-2

Molecular formula:

C10H6N2OS2

IUPAC Name:

6-methyl-2H-[1,3]dithiolo[4,5-b]quinoxalin-2-one

Test material form:

solid: particulate/powder

Remarks:

Yellow powder

Specific details on test material used for the study:

TEST SUBSTANCE INFORMATION:
- Identification in report: Technical grade MORESTAN
- Chemical name: 6-Methyl-1,3-dithiolo[4,5-b]quinoxalin-2-one
-CAS Registry No.: 2439-01-2
- Physical apprearnce: Yellow granules

SOURCE OF TEST MATERIAL
- Source of test material: Mobay Corporation, Agricultural Chemicals Division, Box 4913, Hawthorn Road, Kansas City, Missouri 64120-0013
- Lot No. of test material: 203930103
- Expiration date of the lot: Not reported
- Purity: 94.2% (purity test date not reported)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Freezer
- Stability under test conditions: Unknown at room temperature
- Solubility and stability of the test substance in the vehicle: Not testsed as all doses were prepared just prior to administration, assumed stable for the duration of the test
- Reactivity of the test substance with the vehicle: None

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None, all doses prepared on the day of administration
- Final dilution of a dissolved solid, stock liquid or gel: Test concentrations: 1630, 2520 and 3680 mg/kg in males and 968, 1630, 2520 and 3680 mg/kg in females


FORM AS APPLIED IN THE TEST (if different from that of starting material) Test substance applied as a solution in 2%(v/v) Cremophor EL in deionised water (10ml/kg)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sasco, Inc., Houston, Texas
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 223-281g (20 males), 187-218g (15 males). All bodyweigt ranges on day 0 were within 20% of the mean bodyweights for each sex.
- Fasting period before study: Fasted overnight prior to dosing
- Housing: Individually in stainless steel cages suspended over a deotized animal cage board (DACB) bedding. Bedding changed a minimum of three times a week with new cages every three weeks. Room disinfected at least once every three weeks.
- Diet available ad libitum
- Water availabale ad libitum
- Acclimation period: At least six days prior to study initiation

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%): 40-70
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: To: From: 3rd April 1990 (Release of animal shipment for study use) to 25th April 1990 (Terminal sacrifice date)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 2% (v/v) Cremophor EL in deionized water (10 ml/kg)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Analytically confirmed doses of 1630, 2520 and 3680 mg/kg in males and 968, 1630, 2520 and 3680 mg/kg in females
- Amount of vehicle (if gavage): Administered at 10 ml/kg by gavage
- Justification for choice of vehicle: Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

Nominal doses of 1500, 2250 and 3375 mg/kg in males and 1000, 1500, 2250 and 3375 mg/kg in females. Analytically confirmed as doses of 1630, 2520 and 3680 mg/kg in males and 968, 1630, 2520 and 3680 mg/kg in females.

No. of animals per sex per dose:

Five animals per sex/dose. 35 Animals in total for study use.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Five (young adult) Sprague-Dawley rats per sex/dose were observed for 14-days post dose for mortality and clinical signs with observations performed twice daily (once at weekends). Bodyweight were recorded on Day 0, 7 and 14. Observations were performed twice daily (once at weekends).
- Gross necropsy of survivors performed: yes
- Other examinations performed: Gross pathological examination was performed on all animals as soon as practicable after death. Suirviving animals after 14-days were asphixiated by CO2 before gross pathological examination was performed.

Statistics:

LD50 values, 95% confidence intervals and the slope of the dose mortality curve were calculated by modified probit analysis computer program (1982: Stephen, C.E.)

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

2 541 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 095 mg/kg bw

Based on:

test mat.

Mortality:

The incidence of mortality increased with dose for males and females with all deaths 1-4 days post dose for both sexes.

Males: 1/5 at 1630 mg/kg /bw
1/5 at 2520 mg/kg /bw
5/5 at 3680 mg/kg /bw

Females: 2/5 at 968 mg/kg /bw
4/5 at 1630 mg/kg /bw
5/5 at 2520 mg/kg /bw
5/5 at 3680 mg/kg /bw

Clinical signs:

Clinical signs presented in table below.

Body weight:

Surviving males bodyweight gain decreased from days 0-7 in a dose related manner, recovery was evident from days 7-14.
Body weight gain was not effected in surviving females

Gross pathology:

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Other findings:

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Any other information on results incl. tables

Clinical signs	Male: dose (mg/kg)			Female: dose (mg/kg)
	1630	2520	3680	968	1630	2520	3680
Decreased motor activity	2		2	2	4	4	2
Tremors					2	2	1
Red nasal stain	4	4	5	4	5	4	1
Hunched posture	1	1	4			4	2
Yellow perianal stain	2	2	5	1	2	4	3
Yellow urine stain	2		2	2	3	2	2
Red stain on both forepaws		1	2	2	2	3	1
Red lacrimal stain	1	1		1	2	1	1
Red stain on forehead			1	1	2	1	1
Yellow oral stain	1		2				1
Alopecia on ventrum	2
Alopecia with red spots on both forepaws		1
Alopecia on both forepaws		1

Non-dose related signs included Diarrhea (1 male at 3680 mg/kg bw) and clear lacrimation (2 females at 3680 mg/kg/ bw)     

	Males
Dose (mg/kg)	1630		2520		3680
	4/5 Sacrificed	1/5 Found dead	4/5 Sacrificed	1/5 Found dead	5/5 Found dead
No gross lesions	2		3
Nasal stain					4
salivation		1			3
Ventrum/anal/perineal stain		1			3
Duodenum ulcers/dark zones	1	1		1	5
Discolouration/ ulcers/ zones Stomach, glandular mucosa				1	4
Abdominal fluid/exudate		1			1
Alopecia	2		1

 

	Females
Dose (mg/kg)	968		1630		2520	3680
	3/5 Sacrificed	2/5 Found dead	1/5 Sacrificed	4/5 Found dead	5/5 Found dead	5/5 Found dead
No gross lesions	2		1
Nasal stain		2			3	1
Anal/perineal stain		2		2	4
Ocular stain/discharge		1			1	2
Duodenal ulcers/depressed/ dark zones/mesentery	1	2		4	5	5
Discolouration/ulcers/zones Stomach, glandular mucosa		2		1	2	5
Abdominal fluid/exudate				1
Salivation					1	1
Fluid-filled small intestines		1
Ruptured vessel by adrenal				1

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral toxicity of MORESTAN in young adult Sprague-Dawley rats was tested using analytically-confirmed doses of 1630, 2520 and 3680 mg/kg in males and 968, 1630, 2520 and 3680 mg/kg in females (5 animals/sex/dose). Treatment related signs of toxicity were observed (and with the exception of Alopecia) were resolved in surviving animals by day 7. For all surviving males a dose-dependent reduction in body weight gain was observed from day 0-7 which recovery between days 7-14. This effect was not observed in surviving females. Evidence of treatment-related gross lesions were observed in animals found dead, with one low dose male and female showing gross lesions which survided to day 14.

The acute oral LD50 (with 95% confidence limits) was 2541 mg/kg (1592 to 4070 mg/kg) for males. For females the acute oral LD50 was 1095 mg/kg.
The no-observed-effect level for MORESTAN was <1630 mg/kg for males and <968 mg/kg for females.