Reaction products of 4-Diazo-3,4-dihydro-7-nitro-3-oxo-1-naphthalenesulfonic acid coupled with 7-Amino-4-hydroxy-2-naphthalenesulfonic acid, subsequently chelated with Chromium(3+) and cobalt(3+), further mixed with reaction products of 2,4,6-Trichloro-1,3,5-triazine and Ethanol, 2-[(4-aminophenyl)sulfonyl]-, 1-(hydrogen sulfate), sodium salts

Endpoint summary

Description of key information

Acute toxicity: via oral route

The LD50 value of Everzol SR98 was 5000 mg/kg B.W. (OECD TG423).

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:

From December 15, 2017 to March 20, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Species:

rat

Strain:

Wistar

Remarks:

Rayttus norvegicus

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Animais de Laboratorio Criacao e Comercio Ltda (ANILAB)
- Age at study initiation: 8-9 weeks old
- Housing: three animals per cage
- Water: ad libitum
- Acclimation period: 5 days
- Temperature (°C): 19.8-23.9 °C
- Humidity (%): 48-70 %
- Photoperiod (hrs dark / hrs light): 12-hrs dark / 12-hrs light cycle

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Purified water

Doses:

300 and 2000 mg/kg B.W.

No. of animals per sex per dose:

Three

Sex:

female

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Table 1.Individual body weight.

Treatment	Dose (mg/kg)	Animal #	Body Weight (g)
			Initial (Day 0)	Day 7	Day 14	Difference between final and initial weight
1^st	300	1	176.79	197.11	206.56	29.77
		2	185.60	211.13	207.02	21.42
		3	170.04	190.67	195.23	25.19
2^nd	300	1	170.38	177.80	186.56	16.18
		2	197.87	202.74	228.86	30.99
		3	188.01	193.91	207.20	19.19
3^rd	2000	1	240.02	243.32	247.20	7.18
		2	233.32	233.09	241.25	7.93
		3	235.54	239.52	247.43	11.89
4^th	2000	1	231.11	241.76	156.10	24.99
		2	208.10	212.56	218.39	10.29
		3	207.68	222.42	229.42	21.74

Table 2. Behavioral and clinical alterations observed during the experimental period.

Treatment	Step	Sex	Animal#	Observation day
				0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
				0:30h	10:00h	11:27h	12:06h
300	1	♀	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Treatment	Step	Sex	Animal#	Observation day
				0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
				0:30h	10:07h	12:00h	14:06h
300	2	♀	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Treatment	Step	Sex	Animal#	Observation day
				0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
				0:30h	11:15h	12:30h	14:10h
2000	3	♀	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Treatment	Step	Sex	Animal#	Observation day
				0				1	2	3	4	5	6	7	8	9	10	11	12	13	14
				0:30h	11:27h	12:35h	14:02h
2000	4	♀	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
			3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 - None visual alterations observed.

 

Table 3. Pathological findings in animals at doses of 300 and 2000 mg/kg of body weight.

Treatment	Dose (mg/kg)	Anomal#	Macroscopic Alterations
			Skin	Brain	Eyes	Lungs	Heart	Liver	Spleen	Urinary system	G.I.T	R.T	Carcass
1^st	300	1	0	0	0	0	0	0	0	0	0	0	0
		2	0	0	0	0	0	0	0	0	0	0	0
		3	0	0	0	0	0	0	0	0	0	0	0
2^nd	300	1	0	0	0	0	0	0	0	0	0	0	0
		2	0	0	0	0	0	0	0	0	0	0	0
		3	0	0	0	0	0	0	0	0	0	0	0
3^rd	2000	1	0	0	0	0	0	0	0	0	0	0	0
		2	0	0	0	0	0	0	0	0	0	0	0
		3	0	0	0	0	0	0	0	0	0	0	0
4^th	2000	1	0	0	0	0	0	0	0	0	0	0	0
		2	0	0	0	0	0	0	0	0	0	0	0
		3	0	0	0	0	0	0	0	0	0	0	0

G.I.T - Gastrointestinal tract

R.T - Reproductive tract

0 – Not observed alteration

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

According to OECD 423 test method, the oral LD50 value of Everzol SR98 was estimated to be 5000 mg/kg B.W. for female rats. Therefore, Everzol SR98 was Category 5 based on GHS criteria.

Executive summary:

This test using the procedures outlined in the BIOAGRI Study Plan for 16264.463.103.17. Twelve females, divided in groups of three animals, were tested in four steps at the dose levels of 300 and 2000 mg/kg B.W.. The test substance was applied diluted using purified water. The volume administered to each animal was calculated according to the body weight determined on the day of treatment. After dosing by gavage, the animals were observed during 14 days to evaluate deaths, and behavioral and clinical alterations. The test substance administered by oral route for female rats did not cause treatment-related deaths in any of the steps at the dose levels of 300 and 2000 mg/kg B.W.. At the clinical examinations, toxicity signs were not observed. The animals were euthanized in the end of the observation period and were submitted to necropsies, where they did not present macroscopic alterations or acute toxic effects caused by test substance. Based on the flow chart with the starting dose of 300 mg/kg B.W., the test substance was classified as category 5, according to the GHS. The acute oral LD50 value of the test substance Everzol SR98 was estimated to be 5000 mg/kg B.W. for female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

Acute toxicity: via oral route

Twelve females, divided in groups of three animals, were tested in four steps at the dose levels of 300 and 2000 mg/kg B.W.. The test substance was applied diluted using purified water. The volume administered to each animal was calculated according to the body weight determined on the day of treatment. After dosing by gavage, the animals were observed during 14 days to evaluate deaths, and behavioral and clinical alterations. The test substance administered by oral route for female rats did not cause treatment-related deaths in any of the steps at the dose levels of 300 and 2000 mg/kg B.W.. At the clinical examinations, toxicity signs were not observed. The animals were euthanized in the end of the observation period and were submitted to necropsies, where they did not present macroscopic alterations or acute toxic effects caused by test substance. Based on the flow chart with the starting dose of 300 mg/kg B.W., the test substance was classified as category 5, according to the GHS. The acute oral LD50 value of the test substance Everzol SR98 was estimated to be 5000 mg/kg B.W. for female rats.