Copper dibromide

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

review article or handbook

Title:

EU RISK ASSESSMENT - [COPPER, COPPER II SULPHATE PENTAHYDRATE, COPPER(I)OXIDE, COPPER(II)OXIDE, DICOPPER CHLORIDE TRIHYDROXIDE] CAS [7440-50-8, 7758-99-8, 1317-39-1, 1317–38–0, 1332-65-6] CHAPTER 4.1.2. HUMAN HEALTH - EFFECTS ASSESSMENT

Author:

RAPPORTEUR: ITALY

Year:

2007

Bibliographic source:

European Copper Institute

Materials and methods

Test material

Test material information

1

Reference substance name:

Copper

EC Number:

231-159-6

EC Name:

Copper

Cas Number:

7440-50-8

Molecular formula:

Cu

IUPAC Name:

copper

Applicant's summary and conclusion

Conclusions:

Results of a two-generation reproduction toxicity test in rats, conducted in accordance with Annex V and OECD guidelines, showed no treatment-related effects on reproductive parameters in either the parental generation or offspring associated with a diet containing copper sulphate. The NOAEL for reproductive toxicity in this study was 1500 ppm dietary copper sulphate pentahydrate (equivalent to 381 ppm copper), the highest concentration tested.
It is noted that the NOAEL of 250 ppm Cu for reduced spleen weight is consistent with the NOAEL for repeated dose toxicity reported by Hébert et al (1993) (see Section 4.1.2.6.1).
Additional useful data on fertility have been provided by a repeated exposure dietary study (Hébert 1993). This study showed that consumption of copper, as copper sulphate, at up to and including 68 mg Cu/kgBW/day in rats and 536 mg Cu/kgBW/day in mice for 13 weeks had no effect on male reproductive organ weights, spermatid or spematozoal measurements, oestrous cycle length or proportion of oestrous cycle spent in each stage. Effects on other reproductive parameters were not examined in this study.
Several animal studies have been published which have investigated developmental toxicity of copper compounds. Only one of these studies, conducted by Munley (2003a), conforms to recommended test methods (Annex V Test Guideline B.31; OECD Tets Guideline 414) and currently this provides the most reliable data on the developmental toxicity of copper. The findings of this study showed that developmental effects in rabbits, namely increased occurrence of a common skeletal abnormality, were only apparent at doses of copper hydroxide which caused maternal toxicity as indicated by initial weight loss and inappetance. There were no indications of fetal abnormalities associated with treatment at up to maternally toxic levels. The NOAEL for maternal toxicity and developmental effects in rabbits in this test was 6 mg Cu/kgBW/day. Effects on the fetus were considered to be secondary to maternal toxicity and thus not a specific effect of copper on reproduction. Maternal toxicity in this study was considered to be a local effect on the stomach resulting from gavage administration and consequently provides no basis for deriving a NOAEL for repeat-dosing toxicity.
Other studies investigating developmental effects in animals have significant deficiencies in methodology and/or reporting. In some of the studies which showed developmental effects, there was clear evidence of maternal toxicity; in other studies, maternal toxicity could not be ruled out. Consequently, these studies provide little useful information concerning the developmental effects of copper compounds which are relevant to human risk assessment.
Investigations of the effects of copper-containing IUDs on foetal development and other reproductive parameters in animals have failed to demonstrate any effects which could be associated with exposure to copper.
The available data concerning reproductive effects of copper in humans are sparse. Of the four human studies which have been reviewed here, two have major deficiencies which make the reliability of their findings uncertain. The remaining two studies, both drinking water studies, failed to demonstrate any association between copper levels in drinking water and adverse pregnancy outcome.