hydronium;iron(3+);hexahydroxide;disulfate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June to September 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Valid and conclusive guideline study under GLP; Relevant and adequate for this endpoint

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Commission Regulation (EC) No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Statement of compliance in accordance with Directive 2004/9/EC, Department of Health of the Government of the U.K., 12 September 2014, inspection date 12 to 14 March 2014

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

- Name of test material (as cited in study report): Hydronium Jarosite
- Substance type: Inorganic chemical
- Physical state: Light brown solid
- Analytical purity: > 97 %
- Storage condition of test material: Room temperature in the dark
- Other: CAS Number 97592-90-0

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 8 to 12 weeks.
- Weight at study initiation: Range 145 to 171 g (individual values 145, 145, 147, 155, 167 and 171 - see Table 1 below), the body weight variation did not exceed ±20 % of the body weight of the initially dosed animal.
- Fasting period before study: Overnight
- Housing: On receipt the animals were randomly allocated to cages. They were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. The bedding was routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
- Diet: Ad libitum (with the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK); the diet was routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
- Water: Ad libitum (with the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing); the drinking water was routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12 /12

IN-LIFE DATES:
From: 02 July 2014
To: 30 July 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

400 (CAS 25322-68-3)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 or 200 mg/mL for the 300 and 2000 mg/kg bw dose levels, respectively
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: Polyethylene glycol 400 was used because the test item did not dissolve/suspend in distilled water, arachis oil BP or dimethyl sulphoxide.

MAXIMUM DOSE VOLUME APPLIED: 0.171 kg bw · 10 mL/kg bw = 1.71 mL

DOSAGE PREPARATION: No analysis was carried out to determine the homogeneity, concentration or stability of the test item formulation. The test item was formulated within two hours of it being applied to the test system; it is assumed that the formulation was stable for this duration. This exception is considered not to affect the purpose or integrity of the study.

CLASS METHOD
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.

Doses:

300 and 2000 mg/kg bw in the pre-test
2000 mg/kg bw in the main test

No. of animals per sex per dose:

1 in the pre-test
4 in the main test

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes (all test animals)
- Other examinations performed: clinical signs, body weight (all test animals)

Results and discussion

Preliminary study:

In the absence of data regarding the toxicity of the test item, 300 mg/kg bw was chosen as the starting dose (one female rat). In the absence of toxicity at a dose level of 300 mg/kg, an additional (female) animal was treated with a dose of 2000 mg/kg bw. In the absence of toxicity at this dose level, an additional group of 4 female animals was treated at this level.

Effect levels

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality

Mortality:

There were no unscheduled deaths.

Clinical signs:

Hunched posture was noted 1 hour after dosing in two animals treated at a dose level of 2000 mg/kg. There were no other signs of systemic toxicity noted.

Body weight:

All animals showed expected gains in body weight.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual Body Weights and Body Weight Changes

Dose Level [mg/kg bw]	Animal Number and Sex	Body Weight [g] at Day			Body Weight Gain [g] During Week
		0	7	14	1	2
300	1-0 Female	167	186	199	19	13
2000	2-0 Female	171	186	194	15	8
	3-0 Female	145	161	181	16	20
	3-1 Female	147	173	186	26	13
	3-2 Female	145	161	174	16	13
	3-3 Female	155	179	193	24	14

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information according to CLP (7th ATP of Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU. Criteria used for interpretation of results: EU

Executive summary:

The acute oral toxicity of the test item Hydronium Jarosite (CAS 97592-90-0) was determined in a GLP study using the Fixed Dose Method according to the OECD TG 420 (2001) and EU B.1 bis (Commission Regulation (EC) No 440/2008) protocols. The experiment has to be considered relevant, adequate and conclusive. Therefore it was rated „reliable without restriction“, i.e. “Klimisch 1” according to the scale of Klimisch et al. (1997).

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a suspension in polyethylene glycol 400, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no unscheduled deaths. Hunched posture was noted 1 hour after dosing in two animals treated at a dose level of 2000 mg/kg. There were no other signs of systemic toxicity noted. All animals showed expected gains in body weight. No abnormalities were noted at necropsy.

In conclusion the acute oral toxicity of the test item is > 2000 mg/kg bw (discriminating dose at which no mortality and no signs of systemic toxicity occurred).

• Klimisch HJ, Andreae M, Tillmann U (1997). A Systematic Approach for Evaluating the Quality of Experimental Toxicological and Ecotoxicological Data. DOI 10.1006/rtph.1996.1076 PMID 9056496 Regul Toxicol Pharmacol 25:1-5.