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Description of key information

ZINC

(13 wk) NOAEL 234 mg ZnSO4.7H2O/kg bw rats (approximately 53.5 mg Zn2+/kg bw or 155 mg trizinc dicitrate/kg (bw)*) (Maita et al., 1981; rel 2)

(13 wk) NOAEL = 469 mg ZnSO4.7H2O/kg bw rats (approximately 104 mg Zn2+/kg bw or 302 mg trizinc dicitrate/kg (bw)*). (Maita et al., 1981, rel. 2).

CITRIC ACID

(5 d) NOAEL 4000 mg/kg, rats (Bachtold1976; rel 2)

(10 d) NOAEL (mortality) values of 1000 and 4000 mg/kg, mice and rats respectively (Bachtold 1978, rel. 2)

For DNEL derivation human data (listed under IUCLID chapter 7.10.3) are used with a 10 week NOAEL of approx. 50 mg Zn2 +/person/d based on a depressed copper uptake and an altered lipid profile in humans.

This section contains substantially new data.

Key value for chemical safety assessment

Additional information

Although most of the available test data for citric acid does not match current testing standards (due to short testing duration, or insufficient information, etc), it does indicate low acute toxicity following repeat dose exposure.For example, a reliable five day study in rats gave NAOEL value of 4000 mg/kg (Bachtold, 1976; rel 2); a 10 day study in mice and rats gave NOAEL (mortality) values of 1000 mg/kg and 4000 mg/kg respectively (Bachtold, 1978;rel 2).

 

The effect of trizinc dicitrate is not expected to differ significantly from the effects of the zinc ions and citric acid separately once absorbedtherefore the assessment of this substance will be based on both citric acid and zinc respectively. Since the toxicological effects of citric acid are negligible, the effects of trizinc dicitrate are derived from zinc.

 

Results from a 13 week reliable screening repeat dose/reproduction feeding study in rats with zinc sulphate reported aNOAEL of 234 mg ZnSO4.7H2O/kg bw (approximately 53.5 mg Zn2+/kg bw or 155 mg trizinc dicitrate/kg (bw)*), and in mice a NOAEL of 469 mg ZnSO4.7H2O/kg bw. (Which approximates to 104 mg Zn2+/kg bw or 302 mg trizinc dicitrate/kg (bw)*).  (Maita et al, 1981).

Another study in rats with zinc monoglycerolate reported a NOAEL = 31.52 mg zinc monoglycerolate/kg bw. This correlates to a NOAEL ~ 13.26 mg Zn2+/kg bw or 38.45 mg trizinc dicitrate/kg (bw)*).(Edwards and Buckley, 1995, Zinc chloride RAR 2008).

For DNEL derivation human data (listed under IUCLID chapter 7.10.3) are used with a 10 week NOAEL of approx. 50 mg Zn2 +/person/d based on a depressed copper uptake and an altered lipid profile in humans, which is in line with existing evaluation like EFSA, EU and MAK commission.

This information is considered as substantial new information compared to the study results from animal studies.

Other zinc RAR have been reviewed and the data contained is identical to that which has been detailed here.

*Conversion factor = (MW trizinc dicitrate / (MW Zinc x 3) = 547 / (65x3) = 2.9)

Justification for classification or non-classification