Disodium tartrate

Endpoint summary

Description of key information

Oral (no guideline followed), rat: LD50 > 3100 mg/kg bw

RA from source substance Monosodium L(+) tartrate (CAS 526 -94 -3)

Inhalation: no data available

Dermal: no data available

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: 2-year dietary feeding study (Repeated Dose Toxicity, oral)
- Short description of test conditions: Groups of 35 male and female Sprague-Dawley rats were subjected to a 2-year dietary feeding study, where they received daily doses of the test substance via the food (commercial diet) at dose levels of 25600, 42240, 60160, 76800 ppm. Mortality was assessed daily.
- Parameters analysed / observed: clinical signs, macroscopic pathology, tumorigenic response

GLP compliance:

not specified

Test type:

other: 2-year dietary feeding study

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CFY rats, hysterectomy-derived strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Anglia Laboratory Animals, Huntingdon, England
- Housing: 5 animals per cage in cages with wire mesh floors
- Diet: commercial diet (Spratt's Laboratory Animal Diet No. 2), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 50 ± 5
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSAGE PREPARATION (if unusual): Diet containing different concentrations of test substance.

Doses:

25600, 42240, 60160 or 76800 ppm
which corresponds for males: 890, 1620, 2200 or 3100 mg/kg bw /day
which corresponds for females: 1190, 2050, 3030 or 4100 mg/kg bw /day

No. of animals per sex per dose:

35 males and 35 females per dose group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 2 years
- Frequency of observations and weighing: animals were observed daily and individual body weights were determined weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: food intake and tumorigenic response

Statistics:

Student's t-test assessing the significance of intergroup differences, mortality was analysed using Fisher's Exact Probability test used as a 'one-tailed' test

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 3 100 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 4 100 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period relevant for acute oral toxicity (14 days)

Clinical signs:

No clinical signs of toxicity were observed during the study period relevant for acute oral toxicity (14 days)

Body weight:

A dosage-related reduction in bodyweight gain compared to control animals could be observed in all treatment groups during the study period relevant for acute oral toxicity (14 days)

Gross pathology:

Necropsy and histopathological examination revealed no substance-related findings.

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 3 100 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 4 100 mg/kg bw

Based on:

test mat.

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

In a 2-year repeated dose toxity study with the source substance Sodium hydrogen tartrate (CAS 526-94-3) used for the assessment of acute toxicity following the oral route, no acute oral toxicity was observed. As explained in the analogue justification, this result is considered to be valid also for the target substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 100 mg/kg bw

Quality of whole database:

The available information comprises an adequate, reliable (Klimisch score 2) study (Repeated dose toxicity: oral) from a reference substance with similar structure and similar properties. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details).
Taken together, the information from these independent source is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No. 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, of Regulation (EC) No. 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity

 

Justification for read-across

There are no data for acute toxicity available for disodium tartrate (CAS 868 -18 -8). To fulfil the standard data requirements defined in Regulation (EC) No. 1907/2006, Annex VII, 8.5, read-across from an appropriate substance is conducted in accordance with Regulation (EC) No. 1907/2006, Annex XI.

According to Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across) “to avoid the need to test every substance for every endpoint”.

 

For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read across, with regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substances are the basis of read-across. A detailed justification for the analogue read- across approach is provided in the technical dossier (see IUCLID Section 13).

As no experimental/measured data are available on acute toxicity of disodium tartrate (CAS 868 -18 -8) following the oral route, read-across to reliable data on the analogue substance sodium hydrogen tartrate (CAS 526 -94 -3) was conducted.

Oral

A repeated dose toxicity study (oral) (2-year study) was performed in rats without following any OECD Guideline and was used for assesing the acute oral toxicity (Hunter et al., 1977). The substance was administered via the diet, which contained different concentrations of the test substance. In this repeated dose toxicity study (oral) LD50 values >3100 mg/kg bw and >4100 mg/kg bw were estimated as these were the highest doses for males and females, respectively, and no mortality occured. These LD50 values are higher than the threshold of 2000 mg/kg bw and thus it can be concluded that the test substance does not show acute toxicity via the oral route.

Justification for classification or non-classification

Based on the analogue read-across approach, the available data on acute oral toxicity of the test substance do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.