Effects of nickel chloride on lactating rats and their suckling pups, and the transfer of nickel through rat milk.
The excretion of nickel into rat milk following subcutaneous (sc) doses of nickel chloride (NiCl2) and the effects on the lactating rat and her suckling pups were determined. Plasma and milk Ni concentrations increased in a dose-dependent manner 4 hr after single doses of 0, 10, 50, or 100 mumol NiCl2/kg to lactating rats, giving milk/plasma Ni ratios of 0.02. Peak plasma Ni concentrations were reached 4 hr after injection, while milk Ni increased until 12 hr and remained elevated at 24 hr. Dosing for 4 days at 50 or 100 mumol NiCl2/kg/day led to higher milk/plasma Ni ratios of 0.10. These doses of NiCl2 had no effect on body weight but caused decreased food consumption, thymic atrophy, and a small increase in hepatic lipid peroxidation in the dams. Significant alterations in milk composition, which were not due to decreased food consumption as determined in pair-fed rats, included increased milk solids (42%) and lipid (110%), and decreased milk protein (29%) and lactose (61%). NiCl2 treatment also caused significant decreases in mammary RNA content and the RNA/DNA ratio compared to both ad libitum-fed and pair-fed rats, indicating that milk synthetic activity was reduced by NiCl2. Pups suckling the NiCl2-treated dams had plasma Ni concentrations of 24 and 48 micrograms/liter in the 50 and 100 mumol/kg dose groups, respectively, and had decreased liver weight but no changes in hepatic lipid peroxidation or thymus weight. The results indicate that high doses of NiCl2 led to the excretion of Ni into rat milk and changes in milk quality and production. Reductions in liver weight in the suckling pups were also observed which may have been due to nickel exposure or to changes in milk composition.
Dostal
L A
LA
Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Hopfer
S M
SM
Lin
S M
SM
Sunderman
F W
FW
D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism; D001692:Biological Transport; D001835:Body Weight / Q000187:drug effects; D004247:DNA / Q000032:analysis; D005260:Female; D007774:Lactation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000096:biosynthesis; D008321:Mammary Glands, Animal / Q000032:analysis / Q000378:metabolism; D008892:Milk / Q000032:analysis / Q000378:metabolism*; D009532:Nickel / Q000493:pharmacokinetics / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D012313:RNA; C022838:nickel chloride; D009532:Nickel; D004247:DNA