Ferbam

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-11-19 - 1987-12-03

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 81-2 (Acute Dermal Toxicity)

Version / remarks:

revised Nov. 1984

Deviations:

no

GLP compliance:

yes

Remarks:

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:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Adult rabbits of the NZW strain (9-10 weeks old at study start, SPF-quality) were supplied by the Broekman Institute, Someren, The Netherlands. 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 metal cages (RUCO, Valkenswaard, The Netherlands). The animals had free access to tap-water (via automatic nozzles) and were held on a restricted diet of a standard laboratory animal feed (LK-01) obtained from Hope Farms, Woerden, The Netherlands. Certificates of analysis for both diet and drinking water are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
The animal room was air-conditioned, with the temperature maintained within the range of 20-21°C and the relative humidity within the range of 55-65% during the study. The artificial light cycle was 12 hours light, 12 hours dark.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

methylcellulose

Details on dermal exposure:

Dosing
On the day of dosing the test substance was suspended in 1% aqueous methyl cellulose (Boom B.V., Meppel , The Netherlands) and was evenly spread on a surgical gauze (6x10 cm) that was fixed to successively micropore and flexible bandage (Coban, 3M, St. Paul, Minn., USA). This patch was applied to the clipped area of each animal and fixed with adhesive tape (Sleek, Smith and Nephew, Hull, U.K.). The dose volume was 7.5 ml/kg body weight. The dose level was 4000 mg/kg body weight. The day of dosing was designated as day 0.

Observations
Cage-side observations were performed on the day of dosing (approximately once every two hours) and once daily thereafter for 14 days. Any signs of toxicity were recorded along with the time of onset and duration. Individual body weights were measured weekly. At the end of the study (day 14) all animals were killed with euthesate and subjected to necropsy. In addition, observations regarding changes of the treated skin surface were performed following bandage removal and on day 4, 7, and 14.

Duration of exposure:

24 hours

Doses:

4000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily (Observations regarding changes of the treated skin surface were performed following bandage removal and on day 4, 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

not reported

Results and discussion

Preliminary study:

Upon request of the sponsor the test could be performed as a limit test. One group of animals, comprising 5 males and 5 females, was treated with a single dermal dose of test substance at 4000 mg/kg body weight.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occurred during the 14-day observation period.

Clinical signs:

other: Six animals showed a closed 3rd eyelid which was red or swollen in some animals (Table 1). The treated skin surface of the animals revealed slight erythema and oedema, which disappeared by the end of the first week (Table 2). In addition the treated surfa

Gross pathology:

Macroscopic abnormalities at necropsy at the end of the observation period included local dark red areas in the lungs, enlarged spleen, accessory spleen tissue in the pancreas, dilated ileum and some petechiae in the dorso-lateral muscles (Table 1).

Other findings:

not reported

Any other information on results incl. tables

Table 1: Individual Animal Observations Acute Dermal Toxicity study in the rabbit - Test item at 4000 mg/kg

Physical/Clinical Parameter

Animal Number/Sex

3202 M

3204 M

3206 M

3208 M

3210 M

3250 F

3252 F

3254 F

3258 F

3260 F

No effects of treatment

DPD

14

14

14

3rd eyelid

- closed

DPD

2-4

2

- closed and swollen

DPD

1

- closed and red

DPD

1

1

Dead

KIL

X

X

X

X

X

X

X

X

X

X

Necropsy findings:

- no gross lesions

X

X

X

X

X

X

X

- Lungs local dark red areas

X

- Enlarged spleen

X

- Accessory spleen tissue in the pancreas

X

- diated ileum

X

- some small petechiae in dorso-lateral muscles

X

X

Glossary of terms for lsit of individuel findings: DPD = Days post dosing KIL = Killed at necropsy KGL = no gross lesions X = positive

Table 2: Group Incidences for irritation of the treated skin surface Acute dermal toxicity study in the rabbit - Test iteml at 4000 mg/kg body weight
Observation	Day of Evaluation
	1*	4	7	14
No abnomalities	0	3	5	10
Sligth erythema	9	0	0	0
Oedema	9	2	0	0
Black discolouration	9	6	5	0
* Following bandage removal

Table 3: Indivudual body weights and dose volumes Acute dermal toxicity study in the rabbit - Test item at 4000 mg/kg body weight
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
4000 (Males)	3202	2196	2343	2536	340	16.5
	3204	2395	2402	2513	118	18.0
	3206	1804	1920	2174	370	13.5
	3208	2065	2237	2358	293	15.5
	3210	1991	2125	2290	299	14.9
	Mean	2090	2205	2347	284
	S.D.	221.6	191.4	152.4	98.0
	N	5	5	5	5
4000 (Females)	3250	2145	2279	2347	202	16.1
	3252	2152	2283	2402	250	16.1
	3254	2277	2352	2470	193	17.1
	3258	2172	2215	2356	184	16.3
	3260	2349	2424	2502	153	17.6
	Mean	2219	2313	2415	196
	S.D.	90.1	83.4	68.7	35.2
	N	5	5	5	5
* Day of dosing

Applicant's summary and conclusion

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

Under the conditions used in this study, the LD50 value for both males and females was noted as exceeding 4000 mg/kg.

Executive summary:

The test material has been assessed in an acute dermal toxicity study in accordance with U.S. EPA FIFRA Guideline 81 -2 and in compliance with GLP. One group of NZW rabbits, comprising 5 males and 5 females, was treated with a single dermal dose of the test item at 4000 mg/kg body weight for 24 hours. No mortalities occurred during the 14-day observation period. A sign of toxicity was a closed and red or swollen 3rd eyelid. The treated skin surface of the animals revealed slight erythema and oedema, which disappeared by the end of the first week. In addition the treated surface was black discoloured due to staining by the test substance. All animals showed body weight gain during the study period. Macroscopic abnormalities noted in animals at necropsy included local dark red areas in the lungs, enlarged spleen, accessory spleen tissue in the pancreas, dilated ileum and petechiae in the dorso-lateral muscles. The LD50 value for both males and females was noted as exceeding 4000 mg/kg body weight.