Multigenerational tests

Coupled Daphnia multigeneration test (toxicity of effluent ... 

Reproductive toxicity of acesulfame K was studied in test systems aimed at detecting teratogenicity, oral embiyotoxicity and in a multigeneration study. No teratogenicity, no embryotoxicity, and no effects on reproduction, development of the fetuses and lactation performance were found.7... 

Renwick et al. (2000) have performed an analysis of the need for an additional UF for infants and children. They considered that the proposal to introduce an additional 10-fold factor when exposure of infants and children is anticipated implies either age-related differences between species or differences within humans, which exceed those present in adults. Alternatively, the extra factor could be related to deficiencies of current testing methods or concerns over irreversibility in developing organ systems. They concluded that the available data did not provide a scientific rationale for an extra factor due to inadequacy of inter- and intraspecies UFs. Justification for the factor therefore must relate to the adequacy and sensitivity of current methods or concern about irreversible effects in the developing organism. They also pointed out that when adequate reproduction, multigeneration, or developmental studies are conducted, there will be no need for an additional 10-fold factor. 

The Redbook states that the teratology phase should be incorporated into the rodent multigeneration reproduction study unless justification can be provided for conducting a separate developmental study. A separate study is justified, for instance, if the test substance is believed to have the capacity to alter the rate of its own metabolism through induction of metabolizing enzymes or as a result of damage incurred by the liver. 

The dams are fed the treated diet from GD6. In the case of a combined multigeneration and developmental study, the females will also have been exposed to the test substance prior to implantation. 

There are critical needs with regard to protecting the environment (Medina, 1996). The use of solvents introduces stresses on ecosystems, ultimately on the global level. More testing for acute human toxicity is needed, but increasingly, researchers will strive to include effects on entire ecosystems, and long-term, multigenerational effects on fertility, reproductive quality, and hormonal functions. Any solvent that leads to environmental problems, that can be persistent, toxic, and bioaccumulative, or any combination of these three attributes, needs to be evaluated (Division, 1996). This... 

Mucous membrane tissue lining of nose, mouth, esophagus, stomach, and intestine. Multigeneration Study A toxicity test in which at least three generations of the test organism are exposed to die chemical being assessed. Exposure is usually continuous. 

Multigenerational Study. This approach involves the continuous exposure of a rodent species (usually mice). The parental animals are exposed shortly after weaning (30-40 days of age). At reproductive maturity, the animals are mated. The first generation is produced (Ff. From these an F2 is produced and then subsequently an /) generation. The effects of the test is monitored through each generation. The measured parameters include fertility, litter size, and neonatal viability. This is a time-consuming effort that usually takes about two years to complete. 

Figure 21.3 Abbreviated protocol for a multigeneration reproductive toxicity test.

As a result of lessons learned from DBS, an in utero exposure phase was added to the carcinogenicity testing requirements for food additives, drugs, and pesticides. The results of multigeneration reproduction studies must be considered together with those from carcinogenicity bioassays and conventional developmental toxicity studies in hazard evaluation. 

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