Potassium dicyanoaurate

Endpoint summary

Description of key information

Acute oral toxicity study in rats by the procedure according to OECD401 guideline.
Acute dermal toxicity study in rats, limit dose procedure according to OECD402 guideline.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 5th - Novermber 21st 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, follows standard guidelines. Available as an unpublished report, acceptable without restrictions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Bor: WISW (SPFCpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchtierzucht GmbH & Co. KG., D-4799 Borchen
- Age at study initiation: Males: 8 weeks; Females: 9 weeks
- Weight at study initiation: Males: 138 - 168 g; Females: 137 - 148 g
- Fasting period before study: Approx. 16 hours
- Housing: 1 animal per cage. Macrolon cages (type II).
- Diet (e.g. ad libitum): ssniff R, Special diet for rats. ad libitum.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: ≥5 days under test conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 23°C
- Humidity (%): 40 - 60%
- Photoperiod (hrs dark / hrs light): 6 a.m.- 6 p.m. CET artififical lighting, 6 p.m. - 6 a.m. CET natural light-dark-rhythm.

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

desalted water

Details on oral exposure:

VEHICLE
Test item in aqueous solution.

MAXIMUM DOSE VOLUME APPLIED: 2.5 ml/kg b.w.

Doses:

10.0, 21.5, 46.4 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for mortalities: 0.5, 1, 2, 4, 6, 24 hours, daily thereafter; Weighing: days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

LD50 values calculated by Probit analysis

Sex:

male

Dose descriptor:

LD50

Effect level:

36.1 mg/kg bw

Based on:

test mat.

95% CL:

14.6 - 66.9

Remarks on result:

other: Slope of dose response curve: 7.76

Sex:

female

Dose descriptor:

LD50

Effect level:

24.4 mg/kg bw

Based on:

test mat.

95% CL:

12.6 - 50.8

Remarks on result:

other: Slope of dose response curve: 4.56

Sex:

male/female

Dose descriptor:

LD50

Effect level:

29.2 mg/kg bw

Based on:

test mat.

95% CL:

21.7 - 39.8

Remarks on result:

other: Slope of dose response curve: 6.45

Mortality:

At the 21.5 mg/kg treatment level 2 females were found dead at 24 hours.
At the 46.4 mg/kg treatment level 1 male was found dead at 4 hours. 3 further males and 5 females were found dead at 24 hours.

Clinical signs:

other: No clinical signs were observed in the 10.0 mg/kg b.w. treatment group. At higher doses rats of both sexes showed slight to moderate hypokinesia, restrained gait, piloerection, clonic convulsions and sunken sides. One male in the 46.4 mg/kg group addition

Gross pathology:

No macroscopic changes were observed in animals surviving at 14 days.
Of those that had died earlier male animals showed reddened small intestine and glandular stomach whilst females showed severely bloated stomach and hemorrages were found in the glandular stomach. Male and females exhibited stomachs that were tightly filled with liquid.

Table 1 - Body weights of the individual animals.

Dose (mg/kg)	Animal No.	Day 0	Day 7	Day 14
Males
10	1	153	197	222
	2	156	201	239
	3	155	204	235
	4	160	204	233
	5	157	206	237
21.5	11	167	200	246
	12	156	192	233
	13	158	183	213
	14	159	195	234
	15	168	215	260
46.4	21	160	189	221
	22	164
	23	164
	24	158
	25	138
Females
10	6	137	153	158
	7	148	178	193
	8	145	155	158
	9	141	166	173
	10	142	165	170
21.5	16	141	152	166
	17	144	156	165
	18	145
	19	140
	20	143	159	167
46.4	26	145
	27	148
	28	146
	29	145
	30	140

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

In a 14 day acute toxicity test on male and female rats the LD50 of potassium dicyanoaurate was found to be 29.2 mg/kg.

Executive summary:

In a 14 day acute toxicity test on male and female rats the LD50 of potassium dicyanoaurate was found to be 29.2 mg/kg. The female rats in the study were found to be more sensitive than the males.

The study was conducted to GLP standards and in accordance with standard guidelines.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

29.2 mg/kg bw

Quality of whole database:

One GLP-compliant study is available, performed according to OECD guideline and produced quality and reliable data.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, follows standard guidelines. Available as an unpublished report, acceptable without restrictions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CD / Crl: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 258 - 268 g (males), 222 - 252 g (females)
- Fasting period before study: Yes, feeding discontinued approx. 16 hours before administration of test item.
- Housing: During the 14-day observation period the animals were kept singly in MAKROLON cages (type III plus) with granulated textured wood (Granulat A2, J. Brandenburg, Germany) as bedding material.
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany) ad libitum with exception of 16 h fasting period before administration of test item.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 55% ± 15%
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light (about 150 lux at approx. 1.5 m room height)

IN-LIFE DATES: From: 17 July 2014 To: 24 July 2014

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

Aqua ad iniectabilia

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 6 cm
- % coverage: 10 %
- Type of wrap if used: 8 layers gauze covered with a plastic sheet and secured with adhesive plaster.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No, residues of test item were not removed.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.7255 mL/kg b.w. preparation based on volume. 10 g Potassium dicyanoaurate mixed with 5 g water resulting in suspension with the density of 1.7386 g/mL.
- Concentration (if solution): 2000 mg/kg b.w.
- Constant volume or concentration used: no
- For solids, paste formed: no, suspension with a density of 1.7386 g/mL was used.

Duration of exposure:

Exposure time was 24 hours.

Doses:

One dose level of 2000 mg/kg b.w. was examined.

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before and immediately, and 5, 15, 30, 60 min, as well as 3, 6, and 24 hours after application of test item.
- Necropsy of survivors performed: yes
- Other examinations performed: changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central nervous system and somatomotor activity as well as behaviour pattern, were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Observations on mortality were made at least once daily. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded. The skin was observed for the development of erythema and oedema. At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities observed during the test.

Clinical signs:

other: No clinical signs observed.

Gross pathology:

No macroscopic findings observed at necropsy.

Table 1. Summary of effects

Symptoms/Criteria	Potassium dicyanoaurate 2000 mg/kg b.w. (n=5)
	males	females
Clinical signs	None	None
Skin reactions	None	None
Mortality 6 h	0	0
24 h	0	0
7 d	0	0
14 d	0	0
Mean body weight gain (g) Start	264.6	237.2
After 7 d	297.6 (+12.5)	238.8 (+0.7)
After 14 d	351.6 (+32.9)	256.8 (+8.3)
Inhibition of bodyweight gain	None	None
Necropsy findings	None	None

Interpretation of results:

GHS criteria not met

Conclusions:

According to the EC-Commission directive 67/548/EEC and its subsequent amendments Potassium dicyanoaurate requires no labelling.
The test material is not classified for acute dermal toxicity according to the EC Regulation 1272/2008 and subsequent regulations and according to the Globally Harmonized Classification System (GHS).

Executive summary:

Acute dermal toxicity study of Potassium dicyanoaurate was according to OECD guideline 402 and EC method B.3 in rats. The test was conducted according to GLP.

The test item Potassium dicyanoaurate was applied dermally, on the shaved intact dorsal skin to rats once for 24 hours. This treatment was followed by an observation period of 2 weeks.

Under the test conditions, a single dermal administration of 2000 mg Potassium dicyanoaurate/kg b.w. did not reveal any signs of toxicity. No animal died prematurely. All animals gained the expected weight throughout the whole experimental period. The LD50 was determined to be >2000 mg/kg b.w. According to the EC-Commission directive 67/548/EEC and its subsequent amendments Potassium dicyanoaurate requires no labelling. The test material is not classified for acute dermal toxicity according to the EC Regulation 1272/2008 and subsequent regulations and according to the Globally Harmonized Classification System (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One GLP-compliant study is available, performed according to OECD and EU guidelines and produced quality and reliable data.

Additional information

The acute oral toxicity of potassium dicyanoaurate was tested in rats following OECD guideline 401 and EU method B.1. Rats were orally gavaged with a single dose of potassium dicyanoaurate solution in desalted water at nominal concentrations of 10.0, 21.5 and 46.4 mg/kg, followed by a 14-day observation period. The LD50 was calculated to be 24.4 mg/kg bw for females and 36.1 mg/kg bw for males, giving an overall LD50 of 29.2 mg/kg bw. Signs of clinical toxicity were observed at 21.5 mg/kg bodyweight and higher (Berthold 1992).

In a limit test for acute dermal toxicity following OECD guideline 402 and EU method B.3, a single application of 2000 mg/kg bw potassium dicyanoaurate solution was applied occlusive on rats for 24 hours. No premature deaths or signs of toxicity were observed (Leuschner 2014). Potassium dicyanoaurate is not classified for acute dermal toxicity according to GHS and EC regulation 1272/2008.

Justification for selection of acute toxicity – oral endpoint
Only one study covering the endpoint but it is a Guideline study (OECD401) conducted to GLP standards.

Justification for selection of acute toxicity – dermal endpoint
Only one study covering the endpoint but it is a Guideline study (OECD402) conducted to GLP standards. No acute dermal toxicity or signs of clinical toxicity were observed at the limit dose of 2000 mg/kg bw silver cyanide.

Justification for classification or non-classification

According to GHS and EC regulation 1272/2008, potassium dicyanoaurate is classified as category 2 for acute oral toxicity based on a LD50 of 29.2 mg/kg bw. No classification for acute dermal toxicity is required as no toxicity effects were observed in a limit test at 2000 mg/kg bw.