Components of a controversial pregnancy test used in the 1960s and 1970s can cause deformities in zebrafish embryos, a new study suggests.
Hormone pregnancy tests (HPTs) were given to an estimated 1.5 million women to determine whether or not they were expecting.
The tests, which contained the hormones progestogen and oestrogen, were withdrawn from the market in 1978.
Studies from the late 1960s to early 1970s suggested a link between use of hormone pregnancy tests and a wide range of serious birth defects.
But a recent review into the tests concluded the scientific evidence "does not support a causal association" between the use of HPTs, such as Primodos, and birth defects or miscarriage.
But campaigners called the review by the Commission on Human Medicines a "whitewash", saying the expert working group did not examine all of the available evidence on the use of the drugs.
Now the latest study, published in the journal Scientific Reports,
found that components of the controversial drug caused deformations to fish embryos just hours after they received a dose.
Norethisterone acetate and Ethinyl estradiol, components of the drug, are still used in other medications including treatments for endometriosis and contraceptives.
The study, led by Dr Neil Vargesson from the University of Aberdeen, found these drugs can cause developmental anomalies when directly applied to zebrafish embryos.
Damage was "extremely rapid", within one hour zebrafish embryos showed significantly reduced movement, and, within four hours, "obvious morphological defects".
The authors wrote: "Norethisterone acetate and Ethinyl estradiol cause embryonic damage in a dose and time responsive manner. The damage occurs rapidly after drug exposure, affecting multiple organ systems."
They also found drug components accumulate in the forming zebrafish embryo for at least 24 hours.
Dr Vargesson said: "At the moment the scientific research into whether or not Primodos caused these birth defects is inconclusive.
"What this study highlights is that there is a lot still to be learned about Primodos and more widely its components effects on mammals.
"Our experiments with the zebrafish embryos shows quite clearly the effects the Primodos components have.
"This does not mean it would do the same in humans of course, we are a long way from saying that but we need to carry out more research into these components because they are still in drugs today and in some cases in much higher doses than those found in Primodos.
"The assumption by some previously has been that the doses given to mothers was too low to cause any damage but our study shows that the levels of Primodos' components accumulate in the embryos over time because they don't have a fully functional liver that can break down the drug.
"This, too, is new information and if the same thing happens in mammals, these drugs could build up in the embryo to much higher levels than shown in the mother's blood."
Marie Lyon, chairwoman of the Association for Children Damaged by Hormone Pregnancy Tests, welcomed the latest study, adding that the campaign group had "no confidence" in the Commission on Human Medicines report published last year.
Dr June Raine, director of vigilance and risk management of medicines at the Medicines and Healthcare products Regulatory Agency, said: "Patient safety is our highest priority and the safety and effectiveness of all available medicines is kept under constant review. As new data comes to light, action is taken as appropriate to make sure the benefits of medications outweigh the risks."
She added: "The expert working group of the Commission on Human Medicines conducted a comprehensive independent scientific review of all available evidence including this then-unpublished scientific study and their overall conclusion was that the available scientific evidence, taking all aspects into consideration, did not support a causal association between the use of hormone pregnancy tests such as Primodos during early pregnancy and birth defects or miscarriage.
"The expert working group made a number of future-facing recommendations and our focus is now on implementing these.
"While the review cannot take away from the very real suffering experienced by the families involved, it helps shape the path to further strengthen the scientific evidence which supports safety monitoring of medicines in pregnancy."