Neodecanoic acid, iron salt

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Iron trichloride

Author:

OECD

Year:

2007

Bibliographic source:

OECD HPV Chemical Programme, SIDS Dossier, approved at SIAM 24 (17-20 April 2007)

Report date:

2007

Reference 2

Reference Type:

other: secondary source

Title:

Oral subchronic toxicity studies of ferric chloride in F344 rat.

Author:

Sato H. et al.

Year:

1985

Bibliographic source:

Bulletin of National Institute of Hygienic Sciences (Tokyo) 103, 21-28

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

trichloroiron;hexahydrate

EC Number:

600-047-2

Cas Number:

10025-77-1

Molecular formula:

FeCl3 x 6H2O

IUPAC Name:

trichloroiron;hexahydrate

Specific details on test material used for the study:

- Name of test material (as cited in study report): Ferric chloride hexahydrate
- Physical state: Solid
- Analytical purity: 98.5%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data.

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
Ferric chloride was dissolved in water at concentrations of 0 (control), 0.12, 0.25, 0.5, 1.0 or 2.0 % (w/v)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

98 days

Frequency of treatment:

Continuous

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.12 other: % w/v in water

Remarks:

equivalent to approximately 80 mg/kg bw/day in male rats, 88 mg/kg bw/day in female rats.

Doses / concentrations 2

Dose / conc.:

0.25 other: % w/v in water

Remarks:

equivalent to approximately 154 mg/kg bw/day in male rats, 176 mg/kg bw/day in female rats.

Doses / concentrations 3

Dose / conc.:

0.5 other: % w/v in water

Remarks:

equivalent to approximately 277 mg/kg bw/day in male rats, 314 mg/kg bw/day in female rats.

Doses / concentrations 4

Dose / conc.:

1 other: % w/v in water

Remarks:

equivalent to approximately 550 mg/kg bw/day in male rats, 571 mg/kg bw/day in female rats.

Doses / concentrations 5

Dose / conc.:

2 other: % w/v in water

Remarks:

equivalent to approximately 1231 mg/kg bw/day in male rats, 1034 mg/kg bw/day in female rats.

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

This is a dose-range finding study to determine doses for a two-year carcinogenicity study. No satellite group included.

Examinations

Observations and examinations performed and frequency:

The following test parameters such as biochemical and haematological endpoints, body and organ weights and water consumption were recorded.
- Body weights and water consumption were recorded weekly throughout the test period.
- Biochemical endpoints evaluated were: GOT, GPT, LDH, ALP, TC, TGL, TP, A/G, BUN, CR, UA, Fe (males)
- Haematological endpoints were: RBC, WBC

The dose of feric chloride in mg/kg/day was calculated from the drinking water intake and the final weight of male and female rats.

Sacrifice and pathology:

- Organ weights recorded: Salivary gland, thymus, lung, heart, liver, spleen, adrenal, kidney, gonads, brain, pituitary.
- Histopathological examination was carried out with special staining for iron deposition using Berlin Blue reaction.

Other examinations:

n.a.

Statistics:

Statistical analysis performed, no further information

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Neuropathological findings:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Details on results:

- Mortality: None of the animals in any of the groups died during the 13-week period of the study.
- Body weight: There was a statisitcally significant dose related decrease in male body weight (1% level of significance) at 0.5% and above and a statisitcally significant decrease in female body weight at 2% (1% level) and 1% (5% level). Decreased on body weight for male rats were of the order of 46%, 26% and 10% of controls for the 2%, 1% and 0.5% dose levels, respectively. In females there was a 20% reduction at 2% and a 6% reduction at 1%.
- Water consumption: There was a significant suppression in the intake of drinking water observed in groups given concentrations of 0.5% or more (no further detail).
- Haematology: Males of the treated groups had significantly increased red blood cell counts (no further details).
- Clinical Chemistry: Higher levels of serum iron were observed in males (control: 102 ± 5 g/dl; 0.12%: 107 ± 11 g/dl; 0.25%: 109 ± 8  g/dl; 0.5%: 129 ± 22  g/dl; 1.0%: 139 ± 10  g/dl; 2.0%: 156 g/dl).

Gross pathology:
No findings reported.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

0.5 other: % w/v in drinking water

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Target system / organ toxicity

Key result

Critical effects observed:

no

Any other information on results incl. tables

Table 1_Doses: The dose of feric chloride in mg/kg bw/day was calculated from the drinking water intake and the final weight of male and female rats

Dose of ferric chloride hexahydrate		Final weight (kg)		Final daily water intake (mL/d)		Dose (mg/kg bw/day)
%	mg/L	Males	Females	Males	Females	Males	Females
0	0	0.35	0.195	23.5	15	0	0
0.12	1.2	0.345	0.19	23	14	80	88
0.25	2.5	0.34	0.185	21	13	154	176
0.5	5.0	0.325	0.175	18	11	277	314
1.0	10.0	0.3	0.175	16.5	10	550	571
2.0	20.0	0.195	0.145	12	7.5	1231	1034

Applicant's summary and conclusion

Conclusions:

In conclusions, the NOAEL derived from a 90-day repeated dose toxicity study in rats was 0.5% (equivalent to 277 and 314 mg/kg bw/day in males and females, respectively).

Executive summary:

Iron trichloride hexahydrate (98.5% purity) was administered to Fischer 344 rats (10/sex/dose) in their drinking water for 13 weeks, at concentrations of 0.12, 0.25, 0.5, 1.0 and 2.0 % FeCl3 (equivalent to approximately 80, 154, 277, 550 and 1231 mg/kg bw/day in male rats, 88, 176, 314, 571 and 1034 mg/kg bw/day in female rats). All deaths and clinical signs of toxicity were recorded. Body weights were measured weekly. At the end of the dosing period, all survivors were killed for haematological, clinical chemistry and pathological exminations. All major organs and tissues were examined microscopically. There were no deaths or clinical signs of toxicity. There was a significant reduction in body weight gains at the two highest doses at the end of the treatment period. Treated males had increased levels of serum iron and higher red blood cell counts compared with controls. The NOAEL was 0.5 % (equivalent to 277 and 314 mg/kg bw/day in males and females, respectively) based on the reduced body weight gain.