Ferbam

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-11-25 - 1987-12-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

revised Nov. 1984

Deviations:

no

GLP compliance:

yes

Remarks:

according to US FDA (21 CFR 58) and US EPA (40 CFR 160 and 40 CFR 792)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ferbam

EC Number:

238-484-2

EC Name:

Ferbam

Cas Number:

14484-64-1

Molecular formula:

C9H18FeN3S6

IUPAC Name:

iron(3+) tris(dimethyldithiocarbamate)

Test material form:

solid: particulate/powder

Details on test material:

Appearance: Black powder
Bulk density: 0.21 g/mL
Solubility: Water: approximately 1 ppm; acetone: 0.81 g/100mL (20 °C); chloroform: 2 g/100mL (20 °C)
Storage: At ambient temperature in the dark in closed container
Stability: At least 14 days at 55 °C; poor in organic solvents

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Young adult rats of the Wistar strain (8 weeks old at study start, SPF-quality, randomly bred) were supplied by Charles River Wiga GmbH, Sulzfeld, FRG. Upon receipt each animal was identified with an ear tag. At least five days prior to dosing (acclimatization period) the animals were individually housed in polycarbonate cages containing purified sawdust (Woody clean supplied by Broekman Institute, Someren, The Netherlands) as bedding material. The animals had free access to tap-water (via automatic-nozzles) and a standard pelleted laboratory animal diet (RMH-B, Hope Farms, Woerden, The Netherlands). Certificates of analysis for both diet and drinking water are retained in the N0T0X archives.

ENVIRONMENTAL CONDITIONS
The animal room was air-conditioned, with the temperature maintained within the range of 20-22°C and the relative humidity within the range of 55-70% during the study. The artificial light cycle was 12 hours light, 12 hours dark.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

Animals were fasted overnight prior to dosing until 3 hours after administration of the test substance. The test substance was suspended in 1% aqueous methyl cellulose (Boom B.V.. Meppel, The Netherlands) and administered once only by gavage using a stainless steel stomach cannula attached to a disposable plastic syringe. The dose level was 5000 mg/kg body weight. Each time the dose volume was 15 ml/kg body weight. The day of dosing was designated as day 0.

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

Observations
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on the day of dosing (approximately once every two hours) and once daily thereafter for 14 days
- Necropsy of survivors performed: yes

Statistics:

not perfomed

Results and discussion

Preliminary study:

In order to establish an appropriate dose range three groups of animals, each comprising 1 male and 1 female, were dosed with an oral dose of test substance at 3200, 4200 and 5600 mg/kg body weight. No mortality occurred during the 7-day observation period. Signs of toxicity were body weight loss, lethargy, piloerection, bloody eye encrustation and diarrhoea. Based on the absence of mortality and the low toxicity, observed in the pilot study, the test could be performed as a limit test. One group of animals, comprising 5 males and 5 females, was treated with a single oral dose of test substance at 5000 mg/kg body weight.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One female rat died on day 4 of dosing.

Clinical signs:

other: Signs of toxicity were body weight loss for the female rat found dead, lethargy, piloerection, dacryorrhoea, diarrhoea and emaciation.

Gross pathology:

Macroscopic examination of animals at termination did not reveal any abnormalities that were considered test substance related, with the exception of a slightly enlarged liver of the female rat which died on day 4.

Other findings:

none

Any other information on results incl. tables

Table 1: Daily Incidence of Mortality and Clinical Observations fo Male and Female Rats Combined Following Acute Oral Dosing of test material
Dose level (mg/kg)	Signs of reaction	Number showing effects during day of dosing (hours:minutes) or day of observation (day)																	Total mortality
		00:15	02:15	03:35	1	2	3	4	5	6	7	8	9	10	11	12	13	14
5000	No abnomalities	10	0	0	1	3	9	4	3	4	5	8	9	9	9	9	9	9
	Lethargy	0	10	10	0	0	1	5	1	0	0	0	0	0	0	0	0	0
	Emaciation	0	0	0	0	0	0	0	0	2	2	0	0	0	0	0	0	0
	Piloerection	0	6	10	1	7	1	0	6	5	3	1	0	0	0	0	0	0
	Diarrhoea	0	0	0	9	0	0	0	0	0	0	0	0	0	0	0	0	0
	Dacryorrhoea	0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Deads	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1/10

Table 2: Indivudual body weights and dose volumes acute oral toxicity study of test material in the rat
Dose Level (mg/kg)	Animal number	Body Weight (g) on:			Body weight Gain (g) Day 0-14	Dose Volume (mL)
		Day 0*	Day 7	Day 14
5000 (Males)	3306	221	220	304	83	3.3
	3308	216	224	291	75	3.2
	3310	230	221	301	71	3.5
	3312	225	251	313	88	3.4
	3314	227	227	303	76	3.4
	Mean	224	229	302	79
	S.D.	5.4	12.8	7.9	6.8
	N	5	5	5	5
5000 (Females)	3113	169	174	218	49	2.5
	3115	170	178	222	52	2.6
	3117	176	-	-	-	2.6
	3119	174	170	219	45	2.6
	3121	185	185	252	67	2.8
	Mean	175	177	228	53
	S.D.	6.4	6.4	16.3	9.6
	N	5	4	4	4
* Day of dosing

Applicant's summary and conclusion

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

LD50 value for both males and females was noted as exceeding 5000 mg/kg.

Executive summary:

The acute oral toxicity of the test item was evaluated in this single-dose study in rats according to EPA OPP 81 -1 (Acute oral toxicity) and in compliance with GLP ( US FDA 21 CFR 58 and US EPA 40 CFR 160 and 40 CFR 792).

One group of Wistar rats, comprising 5 males and 5 females, was treated with a single oral dose of the test material at 5000 mg/kg body weight. One female rat died on day 4 of dosing. Signs of toxicity were body weight loss for the female found dead, lethargy, piloerection, dacryorrhoea, diarrhoea and emaciation. These signs were considered reversible since as of day 9 no more abnormalities were observed during the 14-day observation period. All animals showed body weight gain during the study period. Macroscopic examination of animals at termination did not reveal any abnormalities that were considered test substance related, with the exception of a slightly enlarged liver of the female which died on day 4. Since only one animal died, the LD50 value for both males and females was noted as exceeding 5000 mg/kg body weight.