Dipotassium hydrogen citrate

Endpoint summary

Description of key information

A study conducted according to a protocol that was similar to OECD 401, but limited in some respects and without GLP status, identified an acute oral LD50 value of 5.4 g/kg bw for citric acid for male and female mice.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 4 March 1981 to 3 April 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Study was conducted equivalent to the not longer valid Guideline OECD 401.

Principles of method if other than guideline:

Groups of 5 mice of each sex were given a single gavage dose with observation for mortality for 10 days. Clinical observations were made at 2 h and 24 h after treatment; body weights
were only recorded prior to dosing. The observation period was 10 days instead of 14 recommended by guideline.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: Füllinsdorf Albino (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoffmann-La Roche & Co. Ltd, Company breeding farm: Tierfarm Füllinsdorf. (no further details)
- Age at study initiation: not stated
- Weight at study initiation: 20 g
- Fasting period before study: not stated
- Housing: 5/Macrolon type III cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: not stated
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 50 +/- 10
- Air changes (per hr): 20-25
- Photoperiod (hrs dark / hrs light): 12 h/12 h
IN-LIFE DATES: (main study) From: 1981-03-24 To:1981-04-03

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Concentration in vehicle: (main study) 150-600 mg/ml
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw

Doses:

0, 3, 4.2, 6, 8.5, 13 g/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: clinical observations at 2 h and 24 h following treatment; observation for mortality daily for 10 days; body weights recorded only prior to
treatment
- Necropsy of survivors performed: no
- Other examinations performed: none

Statistics:

probit analysis

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 400 mg/kg bw

Based on:

test mat.

95% CL:

>= 4 500 - <= 6 400

Remarks on result:

other: observation limited to 10 days

Mortality:

No deaths at 3 g/kg bw, death of all exposed within 24 h at 8.5 g/kg bw, and above. See table 1.

Clinical signs:

other: Clinical observations were limited to 2 h and 24 h after treatment; the descriptions given are very limited. See table 1.

Gross pathology:

Not examined.

Other findings:

None.

Table 1: Number of animals dead and with evident toxicity and time range within which mortality occurred

Dose	Mortality (dead/total)	Time of death (within)	Overt toxicity
(g/kg bw)	Combined (5 male, 5 female)*		2 h	24 h
0 (control)	0/10	-	none	none
3.0	0/10	-	none	none
4.2	2/10	24 h	none	none
6.0	7/10	24 h	slight relaxation	none
8.5	10/10	24 h	death	-
12.0	10/10	24 h	death	-

* Separate data for each sex not given

Interpretation of results:

GHS criteria not met

Conclusions:

A study conducted according to a protocol that was similar to OECD 401, but limited in some respects and without GLP status, identified an acute oral LD50 value of 5.4 g/kg bw for male and female mice.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

from 4 March 1981 to 3 April 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Potassium citrate salts are known to show a very high solubility in water and dissociate rapidly.
Potassium in known to be non-toxic. The toxicity is determined by the citrate moiety of the substance.
Because of that a read-across to citric acid is suitable for the determination of the toxicity.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

Study was conducted equivalent to the not longer valid Guideline OECD 401.

Principles of method if other than guideline:

Groups of 5 mice of each sex were given a single gavage dose with observation for mortality for 10 days. Clinical observations were made at 2 h and 24 h after treatment; body weights
were only recorded prior to dosing. The observation period was 10 days instead of 14 recommended by guideline.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: Füllinsdorf Albino (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoffmann-La Roche & Co. Ltd, Company breeding farm: Tierfarm Füllinsdorf. (no further details)
- Age at study initiation: not stated
- Weight at study initiation: 20 g
- Fasting period before study: not stated
- Housing: 5/Macrolon type III cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: not stated
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 50 +/- 10
- Air changes (per hr): 20-25
- Photoperiod (hrs dark / hrs light): 12 h/12 h
IN-LIFE DATES: (main study) From: 1981-03-24 To:1981-04-03

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Concentration in vehicle: (main study) 150-600 mg/ml
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw

Doses:

0, 3, 4.2, 6, 8.5, 13 g/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: clinical observations at 2 h and 24 h following treatment; observation for mortality daily for 10 days; body weights recorded only prior to
treatment
- Necropsy of survivors performed: no
- Other examinations performed: none

Statistics:

probit analysis

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 400 mg/kg bw

Based on:

test mat.

95% CL:

>= 4 500 - <= 6 400

Remarks on result:

other: observation limited to 10 days

Mortality:

No deaths at 3 g/kg bw, death of all exposed within 24 h at 8.5 g/kg bw, and above. See table 1.

Clinical signs:

other: Clinical observations were limited to 2 h and 24 h after treatment; the descriptions given are very limited. See table 1.

Gross pathology:

Not examined.

Other findings:

None.

Table 1: Number of animals dead and with evident toxicity and time range within which mortality occurred

Dose	Mortality (dead/total)	Time of death (within)	Overt toxicity
(g/kg bw)	Combined (5 male, 5 female)*		2 h	24 h
0 (control)	0/10	-	none	none
3.0	0/10	-	none	none
4.2	2/10	24 h	none	none
6.0	7/10	24 h	slight relaxation	none
8.5	10/10	24 h	death	-
12.0	10/10	24 h	death	-

* Separate data for each sex not given

Interpretation of results:

GHS criteria not met

Conclusions:

A study conducted according to a protocol that was similar to OECD 401, but limited in some respects and without GLP status, identified an acute oral LD50 value of 5.4 g/kg bw for male and female mice.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 400 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available