Copper diformate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2020-06-11 to 2020-07-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

2008

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau

Version / remarks:

2000

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Copper diformate

EC Number:

208-865-8

EC Name:

Copper diformate

Cas Number:

544-19-4

Molecular formula:

CH2O2.1/2Cu

IUPAC Name:

copper diformate

Test material form:

solid: particulate/powder

Details on test material:

blue in color

Test animals

Species:

rat

Strain:

other: RccHan™:WIST albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Ltd
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately eight to twelve weeks
- Weight at study initiation: 156 to 176 g
- Fasting period before study: overnight prior to and approximately four hours after dosing
- Housing: in groups of one or four rats. Cages were solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved softwood bark-free fiber bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals. Each cage of animals was provided with Aspen chew blocks or balls for environmental enrichment. Chew blocks or balls were provided throughout the study and were replaced when necessary. Each cage of animals was provided with a plastic shelter for environmental enrichment, which was replaced at the same time as the cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days
- Method of randomisation in assigning animals to test and control groups : The animals were allocated without conscious bias to cages within the treatment groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours continuous dark

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

formulation was administered at a volume of 10 mL/kg body weight

Doses:

5, 30 and 200 mg/mL (50, 300, 2000 mg/kg)

No. of animals per sex per dose:

Sighting investigations: 1 female per dose (2000, 50 and 300 mg/kg)
Main study: 4 females per dose (50 and 300 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality: at least twice daily
- Necropsy of survivors performed: Yes. All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of the brain, cecum, duodenum, heart, kidneys, small and large intestine, liver, lungs and bronchi, spleen, stomach, subcutaneous tissue and urinary bladder was recorded.
- Clinical signs including body weight: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, surviving animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). Additional observations were performed as necessary when evident toxicity was observed. The nature and severity, where appropriate, of any clinical signs and the time were recorded at each observation. The weight of each rat was recorded on Days -1 (not reported), 1 (prior to dosing), 8 and 15 or at death. Individual weekly body weight changes and group mean body weights were calculated.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Preliminary study:

2000 mg/kg: The sighting study animal dosed at 2000 mg/kg died approximately two hours after dosing.
300 mg/kg: Clinical signs observed for female 21 in the sighting study dosed at 300 mg/kg comprised piloerection, abnormal colored urine (red or brown), pallor of whole body, abnormal colored feces (black) and both eyes dull. These signs were first noted from approximately 3 hours after dosing. Recovery as judged by external app earance and behavior, was complete by Day 9.
50 mg/kg: No clinical signs were observed for animals dosed at 50 mg/kg in the sighting study or main study.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

female 22 (2000 mg/kg sighting study): The female (animal number 22) dosed at 2000 mg/kg in the sighting study died approximately two hours after dosing.
female 24 (300 mg/kg): female (animal number 24) dosed at 300 mg/kg in the main study also died approximately 3 hours after dosing
females 23, 25, 26(300 mg/kg): females (animal numbers 23, 25 and 26) dosed at 300 mg/kg in the main study were killed for welfare reasons approximately 4 hours after dosing.

Clinical signs:

other: female 22 (2000 mg/kg): Clinical signs prior to death for female 22 (dosed at 2000 mg/kg) comprised chin rubbing, salivation, flattened posture, irregular breathing, piloerection, reduced body tone and both eyelids partially closed. These signs were obser

Gross pathology:

female 22 (2000 mg/kg): Macroscopic examination of this animal revealed a congestion (darkened tissue/organ) of the subcutaneous tissue, stomach, duodenum and small intestines. There were also fluid contents (blue liquid) present in the stomach, duodenum and small intestines.
females 23, 24, 25 and 26 (300 mg/kg): Macroscopic examination of these animals revealed congestion (darkened tissue/organ) of the subcutaneous tissue, liver, spleen, large intestines and cecum of all females, brain and kidneys of three females and heart of one female. Pallor of tissues/organs was observed on the kidneys of female 26 and lungs and bronchi of all females. There were also fluid contents (blue liquid) present in the stomach, duodenum and small intestines of all females and large intestines of two females. Gaseous distention was observed in the stomach of all females and lastly, a small cecum was observed in one female.
Macroscopic examination of the surviving animals at study termination on Day 15 did not reveal any abnormalities.

Any other information on results incl. tables

Mortality data:

Dose (mg/kg)	No. of deaths	Day*
		1			2 to 15
		2h	3h	4h	a	b
Sighting study
300	0/1F	0	0	-	0	0
2000	1/1F	1	-	-	-	-
Main study
300	4/4F	0	1	3	-	-
Sighting study
50	0/1F	0	0	-	0	0
Main study
50	0/4F	0	0	-	0	0

* The day/time indicated is the time that the animal was found dead/killed for humane reasons

F Female

h Hour

a First observation

b Second observation

- Not applicable

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute median lethal oral dose (LD50) to rats of Copper Diformate was demonstrated to be between 50 and 300 mg/kg body weight.

Executive summary:

The study was performed to assess the acute oral toxicity of Copper Diformate to the rat. Fasted female rats received a single oral gavage dose of the test item, formulated in corn oil,at the following dose levels:

Sighting investigations 1 and 2: 300 and 2000 mg/kg body weight respectively. Main study: Based on the results of the sighting investigations a further four fasted females were similarly dosed at 300 mg/kg body weight. Third sighting study: Due to the number of deaths in the main study at 300 mg/kg body weight, a further female in a third sighting study was dosed at 50 mg/kg body weight. Second main study: Based on the results of the third sighting study a further four fasted females were similarly dosed at 50 mg/kg body weight to complete the study.

No clinical signs were observed for animals dosed at 50 mg/kg in the sighting study or main study.

The acute median lethal oral dose (LD50) to rats of Copper Diformate was demonstrated to be between 50 and 300 mg/kg body weight. Copper Diformate is included in Category 3, according to the Globally Harmonised System

(GHS)