Sodium dihydrogen citrate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

other: non-standard (see below)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonably well documented study meeting generally accepted scientific principles but not conducted in compliance with GLP. Study acceptable for assessment. This result was obtained by valid read-across.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Principles of method if other than guideline:

In a non-standard study, unspecified groups of rats were treated by gavage for 10 successive days with a further 10 days observation. Body weights were recorded prior to treatment and following the 5th and 10th administrations.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Citric acid

EC Number:

201-069-1

EC Name:

Citric acid

Cas Number:

77-92-9

IUPAC Name:

citric acid

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
No details given.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: unclear, possibly in "traganth suspension"

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
No details

VEHICLE
no details

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No details.

Duration of treatment / exposure:

administration on 10 successive days.

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
2, 4, 8, 16 g/kg bw/day
Basis:
no data

No. of animals per sex per dose:

Not clear (based on data presented it is likely that dose groups comprised 10 animals).

Control animals:

other: control animals were given 80 ml/kg bw traganth suspension (presumably per day). It is possible that his material was used as the vehicle. No further details are given.

Details on study design:

- Dose selection rationale: no details given
- Post-exposure recovery period in satellite groups: observation for 10 days following exposure

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: observations reported as brief descriptions without reference to individual animals . No tabulated data presented.

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: prior to treatment and 24 h following the 5th and 10th daily administration

FOOD EFFICIENCY:
- Body weight gain:: Yes ; given as the increase after 5 and 10 days treatment. Pretreatment weights not given.

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: No data
HISTOPATHOLOGY: No data

Other examinations:

None reported.

Statistics:

No details given.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

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 examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
8 g/kg bw/day: sedation within 2 h of 1st administration and death of all animals by 3rd administration.
4 g/kg bw/day: slight sedation within 2 h of 1st administration but no deaths following 10 days administration and 10 days observation.
2 g/kg bw/day: No findings reported.

BODY WEIGHT AND WEIGHT GAIN
No clear effect on body weight (recorded at 5 and 10 days treatment, and following 10 days observation) was evident in comparisons of the 2 and 4 g/kg bw/day groups and the control group (80 ml/kg/day traganth suspension). No statistics are given. See table 2.

OPHTHALMOSCOPIC EXAMINATION
Not applicable.


HAEMATOLOGY
Not applicable.

CLINICAL CHEMISTRY
Not applicable.

URINALYSIS
Not applicable.

NEUROBEHAVIOUR
Not applicable.

ORGAN WEIGHTS
Not applicable.

GROSS PATHOLOGY
Not applicable.

HISTOPATHOLOGY: NON-NEOPLASTIC
Not applicable.

HISTORICAL CONTROL DATA (if applicable)
None given

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

4 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: overall effects clinical signs; mortality; body weight

2

Dose descriptor:

LOAEL

Effect level:

8 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: overall effects clinical signs; mortality; body weight

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Study design - Animal assignment

Test Group	Dose to Animal (mg/kg bw/day)
Control	80 ml/kg bw/day traganth suspension
1	2000
2	4000
3	8000
4	16000

 

Table 2: Mortality and body weight gains during 10 days of treatment and 10 days of observation

Dose rate (g/kg bw/day)	Mortality% (treatment day)										Mortality% (observation days)	Total Weight Gain (g)
	1	2	3	4	5	6	7	8	9	10	1-10	Treatment day 5	Treatment day 10	Observation day 10
0	0	0	0	0	0	0	0	0	0	0	0	23.4	44.1	72.1
2	0	0	0	0	0	0	0	0	0	0	0	24.2	45.7	75.9
4	0	0	0	0	0	0	0	0	0	0	0	20.8	42.1	79.1
8	10	80	100	100	100	100	100	100	100	100	100	-	-	-
16	100	100	100	100	100	100	100	100	100	100	100	-	-	-

 

Applicant's summary and conclusion

Conclusions:

A fairly limited report of an unspecified study without guideline or GLP compliance, identified 10-day NOAEL and LOAEL values in the rat of 4 and 8 g/kg bw/day respectively. The 10-day LD50 was given as 5.66 (+/- 0.44) g/kg bw/day.