Two-Generation Reproduction Toxicity Study

RTI. 1992. Research Triangle Institute. Two-generation reproductive toxicity study of tributyl phosphate administered in the feed to CD (Sprague-Dawley) rats. RTI Project No. 60C-4652. 

OECD, Organization for Economic Cooperation and Development, Guideline 416, Two Generation Reproduction Toxicity Study, 2001b. 

Ema M (2008) Two generation reproductive toxicity study of the flame retardant HBCD in rats. Reprod Toxicol 25 335-351... 

Tyl RW, Gerhart JM, Myers CB, et al Two generation reproductive toxicity study of dietary tributyl phosphate in CD rats. Eundam Appl Toxicol 40(1) 90-100, 1997... 

CMA. 1996. Chemical Manufacturers Association. Sodium chlorite drinking water rat two-generation reproductive toxicity study. Quintiles Report Ref CMA/17/96. 

OECD (2001) Test Guideline 416. OECD Guideline for Testing of Chemicals. Two-generation reproduction toxicity study. 

OECD Guideline 416 two-generation reproductive toxicity study January 2001... 

The two-generation reproductive toxicity study (OECD416) and the prenatal developmental toxicity study (OECD414) have served us relatively well for three decades. No major calamities have been observed with registered compounds during that time. Nevertheless, novel aspects of reproductive toxicity and considerations of animal use and economy have prompted innovations... 

Janer G, Hakkert BC, Piersma AH et al (2007) A retrospective analysis of the added value of the rat two-generation reproductive toxicity study versus the rat subchronic toxicity study. Reprod Toxicol 24(1) 103-113... 

Two-generation reproductive toxicity study (e.g., OECD Test Guideline No. 416)... 

REACH as an alternative for the two-generation reproductive toxicity study. The EOGRTS was recently (28 July 2011) adopted as new OECD test guideline 443 (18). 

In a two-generation reproductive toxicity study in rats, no adverse effect was observed on feed consumption, survival, reproductive parameters, pup weight, sex distribution, survival, gross lesions or microscopic anatomy after oral doses of 15-150 mg/kg bw per day (Blacker et al., 1993). 

Two-generation reproductive toxicity study Ecotoxicological information... 

Aoyama H, Hojo H, Takahashi KL et al (2005) A two-generation reproductive toxicity study of 2, 4- dichlorophenol in rats. Toxicol Sci 30 59-78... 

OECD Guideline for Testing of Chemicals Proposal for updating Guideline 416 Two-Generation Reproduction Toxicity Study (January 22, 2001b)... 

Typically, the demonstration of no adverse effect requires a larger set of evidence than does the demonstration of an adverse effect. To support a conclusion that a given exposure does not cause developmental toxicity, the available studies must be conducted in at least two mammalian species and must test for a wide variety of pre- and postnatal outcomes (EPA 1991). A minimum data set for a conclusion of no reproductive toxicity would normally consist of at least one two-generation reproductive toxicity study. 

The Army s interim RfD of 7 x 10 mg/kg per day for sulfur mustard was based on an oral two-generation reproductive toxicity study in rats, in which thickening of the forestomach epithelium was observed. The subcommittee agrees that this study is the best available one from which to derive the RfD for sulfur mustard and concludes that the interim RfD for sulfur mustard is scientifically valid. However, the subcommittee recommends adjustments in two of the uncertainty factors used to derive that RfD. Although the adjustments do not change the RfD for sulfur mustard, the subcommittee believes that they are scientifically justified and should be reflected in the Army s supporting documentation for the RfD. 

Tyl RW, Myers CB, Mart MC, et al. (2003) Two-generation reproductive toxicity study of inhaled tertiary amyl methyl ether (TAME) vapor in CD rats. Journal of Applied Toxicology 23 397—410. 

As with most organophosphorus insecticides, acute toxicity is predominant. However tolerance to repeated exposures can occur. The no-observed-adverse-effect level (NOAEL) established from a rabbit developmental toxicity study was 50 mg kg day based on maternal toxicity (i.e., reduced body weight gain). Developmental toxicity studies were negative in rats and rabbits. A two-generation reproductive toxicity study in rats showed no increased sensitivity in pups compared to dams. Repeated exposure to malathion does not cause delayed neurotoxicity. The NOAEL of 2.4 mg kg day was established based on plasma cholinesterase inhibition in a long-term dosing study in rats. 

A two-generation reproductive toxicity study was used to evaluate fertility in adult rats and viability/ toxicity in their offspring. Reproductive parameters were tested over two generations of drinking water exposure to perchlorate. The reproductive NOAEL is... 

In a two generation reproductive toxicity study, piperazine dihydrochloride was administered in the diet of rats at doses of 250, 600, or 1250 mg kg day A dose-response effect for decreased litter size was seen in the 600 and 1250 mg kg groups suggesting that piperazine exposure at these dose levels can impair fertility. 

Bevan C, Neeper-Bradley TL, Tyl RW, Fisher LC, Panson RD, Kneiss JJ, Andrews LS (1997a) Two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) in rats. J Appl Toxicol 17(1) 13-19... 

---