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Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

In accordance with Annex 11, Section 1 of REACH, this endpoint has been waived on the basis of readily available data:

 

(1) Reproduction:  Screening data from a 90 week feeding study using citric acid indicate a lack of treatment related effects on the reproductive organs. Based on this it is concluded that trisodium citrate is not expected to impair fertility.

Developmental effects: Read across data from a reliable citric acid feeding study in rats, mice, rabbits and hamsters did not report any treatment related developmental effects at the highest doses tested. 

 

(2) A long history of human exposure to citric acid and its derived salts.

 

 

Information available in the public domain on tests carried out on other salts of this metal indicates that the sodium ions are not expected to contribute to the toxicity of the substance. Additionally, the substance will dissociate when in solution, so test organisms exposure will be to the citrate and the metal ions separately.

Therefore, the hazard assessment for tri sodium citrate canbe based on the properties of citric acid. All of which are sufficient to fulfil the requirements for this endpoint.


Short description of key information:
Read across data from a 90 week 1.2 % (about 600 mg/kg/bw/day) dietary supplement feeding study with citric acid reported no effects on either the number of young born to mice and rats or their subsequent survival up to the point of weaning. (Bonting et al 1956) This would correspond to 800 mg/kg* (bw) expressed as tri sodium citrate.

*The value is derived by using by using a conversion factor of 1.34 (MW(tri sodium citrate)/MW(citric acid) = 258.1/192.9 = 1.34)

In addition, read across data from a reliable study by the Food & Drug Research Laboratories (1973) reported no citric acid related teratogenic effects in any of the species tested. For mice - NAOEL > 241 mg/kg, equivalent to NOAEL > 315 mg/kg tri sodium citrate); rats (NAOEL > 295 mg/kg, equivalent NOAEL > 395 mg/kg tri sodium citrate); rabbits (NAOEL > 425 mg/kg, equivalent to NOAEL > 570 mg/kg tri sodium citrate) and hamsters (NAOEL > 272 mg/kg, equivalent to NOAEL > 365 mg/kg tri sodium citrate)

Toxicity to reproduction: other studies

Additional information

In accordance with Annex 11, Section 1 of REACH, further testing on toxicity to reproduction is not considered necessary based on the following information:

 

(1) Reproduction:  Screening data from a 90 week feeding study using citric acid indicate a lack of treatment related effects on the reproductive organs. Based on this it is concluded that trisodium citrate is not expected to impair fertility.

Developmental effects: Read across data from a reliable citric acid feeding study in rats, mice, rabbits and hamsters did not report any treatment related developmental effects at the highest doses tested. 

 

(2) A long history of human exposure to citric acid and its derived salts.

 

 

Information available in the public domain on tests carried out on other salts of this metal indicates that the sodium ions are not expected to contribute to the toxicity of the substance. Additionally, the substance will dissociate when in solution, so test organisms exposure will be to the citrate and the metal ions separately.

Therefore, the hazard assessment fortri sodium citrate canbe based on the properties of citric acid. All of which are sufficient to fulfil the requirements for this endpoint.

Justification for classification or non-classification