Multigeneration reproduction

Reproductive Toxicity. No studies were foimd regarding reproductive toxicity of 3,3 -dichloro-benzidine. Should data suggesting that reproductive organs are affected in a 90-day study become available, multigenerational reproductive studies in animals may be warranted. 

Wolfe GW, Layton KA (2003) Multigeneration reproduction toxicity study in rats (unaudited draft) diethylhexylphthaiate muitigenerational reproductive assessment when administered to Sprague-Dawley rats in the diet. The Immune Research Corporation (Gaithersburg, Maryland), TRC Study no 7244-200... 

In multigeneration reproduction study in rats decreased pup weights occurred in the Fi and F2 generation at the 7000-ppm exposure level. ... 

Kreckmann KH, Roberts LG, Staab RJ Inhalation multigeneration reproduction study with cyclohexane in rats. Toxicologist 42(1-S) 105-106, 1998... 

Short RD, Johannsen FR, Levinskas GJ et al Teratology and multigeneration reproduction studies with maleic anhydride in rats. Fundam Appl Toxicol A59-366, 1986... 

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. 

Recent historical control data for multigeneration reproduction studies is available from an industry survey conducted by the... 

The first phase of ToxCast profiled a 309-chemical library consisting mostly of pesticidal actives as well as several other compounds of high interest. The acceptance criteria for chemical selection for inclusion in Phase I were as follows (a) availability of in vivo data from bioassays on chronic/cancer, multigenerational reproductive, and/or prenatal developmental toxicity (95% Phase I chemicals met this criteria) (b) solubility in DMSO (the vehicle for HTS assays) with a log of the octanol/water partition coefficient (logP) between -1 and +6 (97.5% met this criteria) (c) molecular weight in the range of 250-1,000 (90% met this criteria) and (d) commercially available at a purity >90% (98% met this criteria) (16). Current information about the Phase I (and Phase II) chemical library can be found at the NCCT website address http //www. epa.gov/ncct/toxcast/chemicals.html. 

Chemical-induced reproductive toxicity consists of effects on reproductive performance (e.g., fertility and fecundity), the reproductive tract, and/or sexual development. Reproductive toxicity has been routinely assessed, using laboratory animal studies, in the chemical risk assessment process for over 40 years. For environmental chemicals, the multigeneration reproduction and fertility study in rats has been the primary tool for assessing reproductive toxicity potential in humans. Unfortunately, these expensive and animal-intensive studies have only been conducted on a fraction of environmentally... 

Multigenerational reproductive study (rat) No effects seen Decreased reproductive fitness, decreased offspring survival (80mgkg I per day), kidney degeneration (20 mg kg-1 per day)... 

Reproductive Effects. The existing evidence does not point to a strong effect of silver on reproduction. However, no multigeneration reproductive studies were located, and therefore a firm conclusion regarding reproductive toxicity can not be made. 

Figure 21.3 Abbreviated protocol for a multigeneration reproductive toxicity test.

Multigeneration reproduction feeding study in a rodent, carried to a minimum of two generations, with a teratology phase, and... 

In a multigeneration reproductive assessment by continuous breeding study of BALB/c mice were fed a diet containing potassium dichromate(VI). Males and females were exposed to chromium for 7 days and then 20 pairs (F0) in each dose group were allowed to continuously mate for 85 days (NTP 1997). The... 

Two types of studies specifically designed to assess developmental toxicity are discussed in this section the prenatal developmental toxicity study and the developmental neurotoxicity study. Several other types of studies, although not solely designed to assess developmental toxicity, can be used for that purpose. They include single- and multigeneration reproduction studies, reproductive assessment by continuous-breeding studies, and serial mating (dominant lethal) studies discussed in later sections. 

Several authorities have published guidelines on multigeneration reproductive assays (OECD 2000b FDA 2000 EPA 1998b). For a... 

As noted by ORNL, the most significant deficiency in the data base on GB is a multigeneration reproductive study. However, because two developmental toxicity studies on GB (Denk 1975 La Borde and Bates 1986) and a multigeneration reproductive study on VX (Goldman et al. 1988) indicate that reproductive effects are unlikely, the subcommittee agrees with ORNL that a factor of 3 for the uncertainty factor for database adequacy (UFd) is appropriate. 

Multigeneration reproductive studies in rats (Sasser et al, 1989b) and teratology studies in rats and rabbits (Hackett et al, 1987) given lewisite by gastric intubation were negative or compromised by concurrent maternal toxicity. 

Waalkens-Berendsen DH, Koeter HB, Sinkeldam EJ. Multigeneration reproduction study of isomalt in rats. Food Chem Toxicol 1990 28(1) 11-19. 

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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