Sodium hypochlorite

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Defciencies: Yes. No data on haematological examinations, results of drinking water intake not reported, no individual animal data.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

(methods comparable)

Deviations:

yes

Principles of method if other than guideline:

haematological results and drinking water intake not reported

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Sodium hypochlorite

EC Number:

231-668-3

EC Name:

Sodium hypochlorite

Cas Number:

7681-52-9

Molecular formula:

ClO.Na

IUPAC Name:

sodium hypochlorite

Details on test material:

Sodium hypochlorite

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

7 weeks old
169-172 g (mean group weights, males)
119-120 g (mean group weights, females)

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

Concentration in vehicle:
0, 0.025, 0.05, 0.1, 0.2 0.4 % (0, 12.5, 25, 50, 100, 200 mg/kg bw/day for males and 14.3, 28.6, 57.2, 114.4, 228.8 mg/kg bw/day for females assuming a water consumption of 25 mL/day for a rat and a body weight of 500 and 350 g)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

ad libitum
Daily (drinking water)

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.025, 0.05, 0.1, 0.2 0.4 % (0, 12.5, 25, 50, 100, 200 mg/kg bw/day for males and 14.3, 28.6, 57.2, 114.4, 228.8 mg/kg bw/day for females assuming a water consumption of 25 mL/day for a rat and a body weight of 500 and 350 g).
Basis:
no data

No. of animals per sex per dose:

number of animals per group: 10 per sex

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

Clinical signs Yes (daily)
Mortality Yes (daily)
Body weight Yes (weekly)
Water consumption Yes (weekly)
Haematology Yes( blood samples were taken at study termination; however, no further information is provided)

Sacrifice and pathology:

Organ Weights
Yes, for all surviving animals
organs: liver, kidneys, adrenals, testes, ovaries, spleen, brain, heart, pituitary gland, salivary glands, lungs.


Gross and histopathology
Yes, for all surviving animals
organs: liver, kidneys, adrenals, testes, ovaries, spleen, brain, heart, pituitary gland, salivary glands, lungs.

Other examinations:

none

Statistics:

The data were subjected to analyses of variance and differences between the means were tested by Student’s t-test.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

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):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

Clinical signs
Emaciation


Mortality
No mortalities at any dose

Body weight gain
Body weight gain was statistically significantly reduced in males of the 0.2 and 0.4 % groups and in females of the 0.4 % group. Please refer to Table.


Haematology
Blood samples were taken at study termination; however, no results of the examination are provided.


Clinical chemistry
Blood samples were taken at study termination; however, no results of the examination are provided.


Urinalysis
Blood samples were taken at study termination; however, no results of the examination are provided.


Organ weights
High-dose males: absolute weights of lung, liver and spleen were significantly lower than controls.
High-dose females: absolute weights of salivary glands, lung, heart and brain were significantly lower than controls.


Gross and histopathology
Biochemical examination showed signs of damage to the liver in the 0.2 and 0.4 % groups of both sexes.

Effect levels

1

Dose descriptor:

LOAEL

Effect level:

100 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: (assuming a water consumption of 25 mL/day for a rat and a body weight of 500 g) based in reduced body weight gain and histopathological liver changes.

2

Dose descriptor:

LOAEL

Effect level:

114.4 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

other: (assuming a water consumption of 25 mL/day for a rat and a body weight of 350 g) based in reduced body weight gain and histopathological liver changes.

3

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: (assuming a water consumption of 25 mL/day for a rat and a body weight of 500 g)

4

Dose descriptor:

NOAEL

Effect level:

57.2 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

other: (assuming a water consumption of 25 mL/day for a rat and a body weight of 350 g)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Mean body weights

Test substance concentration (% NaOCl)	Mean body weights [g]
	Males in week				Females in week
	0	2	13		0	2	13
			[g]	% of control			[g]	% of control
0 (control)	169	228	347	100	119	143	183	100
0.025	172	228	336	97	119	141	180	98
0.05	171	224	336	97	120	139	186	101
0.1	172	213	321	93	119	140	180	98
0.2	168	173	281	81	119	127	177	96
0.4	169	116	185	53	119	92	127	69

Applicant's summary and conclusion

Conclusions:

LO(A)EL: 0.2 %,
corresponding to 100 mg/kg bw/d (males) and 114.4 mg/kg bw/d (females)
(assuming a water consumption of 25 mL/day for a rat and a body weight of 500 and 350g)
based in reduced body weight gain and histopathological liver changes.
NO(A)EL: 0.1 %,
corresponding to 50 mg/kg bw/d (males) and 57.2 mg/kg bw/d (females)
(assuming a water consumption of 25 mL/day for a rat and a body weight of 500 and 350g)

Executive summary:

There were no mortalities throughout the study. Body weight gain was statistically significantly reduced in males of the 0.2 and 04 % groups and in females of the 0.4 % group. At autopsy there were no obvious macroscopic changes in any group, although several animals, particularly in the high dose, appeared emaciated. Absolute weights of the lung, liver and spleen of males and the salivary gland, lung, heart and brain of females were significantly lower in the highest-dose groups than in controls. No histological changes attributable to sodium hypochlorite administration were found in any of the experimental groups, but biochemical examination of the sera showed signs of slight damage to the liver in the two highest dose groups in both sexes.