Ametryn

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

96.5 mg/kg bw/day

Additional information

The effect of Ametryn technical on reproductive parameters was evaluated in a 2-generation reproductive toxicity study in rats (Ganiger, 1999).  This GLP study was conducted according to OECD test guideline 416. Ametryn technical was administered in the diet at nominal concentrations of 0, 75, 300, or 1200 ppm to Wistar rats. There were no test article-related effects on pup survival parameters or fertility reported for any dose level. Therefore the NOAEL for reproductive toxicity in rats was 1200 ppm, the highest dose level tested. Decreased body weight gain, body weights, and food consumption was noted starting at the 300 ppm dose level at different phases of the study. Based on this information, the overall NOEL of Ametryn technical in Wistar rats was considered to be 75 ppm for two successive generations. This level is considered equivalent to 5.9 and 6.0 mg/kg bw/day for male rats and 7.9 and 8.3 mg/kg bw/day for female rats for the P and F1 generations, respectively.

Supportive information on the effect of Ametryn technical on fertility was provided by a GLP, two-generation reproductive toxicity study in rats, involving dietary administration of Ametryn technical. This study was similar to OECD test guideline 416. There were no test article-related effects reported on reproductive and pup survival parameters at Ametryn technical dietary concentrations of up to and including 2000 ppm. A NOEL of 20 ppm was reported on the basis of decreased body weights, body weight gain, and food consumption observed at higher dose levels of 200 and 1200 ppm.

Short description of key information:
A GLP, dietary, two-generation reproduction toxicity study in rats conducted according to OECD test guideline 416 reported a NOEL for Ametryn technical of 75 ppm (equivalent to 5.9 and 6.0 mg/kg bw/day for male rats and 7.9 and 8.3 mg/kg bw/day in female rats, of the P and F1 generations, respectively) for overall toxicity (Ganiger, 1999). As no effects on reproductive or pup survival parameters were observed, the NOAEL for reproductive toxicity in rats was considered to be 1200 ppm (equivalent to 96.5 and 98.5 mg/kg bw/day for male rats and 120.6 and 123.9 mg/kg bw/day for female rats, of the P and F1 generations, respectively). Supportive information comes from another two-generation reproduction toxicity study in rats (similar to OECD test guideline 416) that did not report on any effects on reproductive parameters at any dietary concentration up to 2000 ppm Ametryn technical (the highest dose tested). There were no adverse effects on reproductive or pup survival parameters reported in these studies, even at the highest dose levels evaluated.

Effects on developmental toxicity

Description of key information

GLP, oral gavage, prenatal developmental toxicity studies on Ametryn technical in rats and rabbits conducted according to OECD test guideline 414 reported embryo and fetal toxicity NOAELs of 60 mg/kg bw/day in rats and 300 mg/kg bw/day in rabbits.  These were the highest dose levels evaluated.  NOELs for maternal toxicity were reported to be 30 and 100 mg/kg bw/day in rabbits and rats, respectively.  Two supportive GLP-compliant prenatal developmental toxicity studies did not identify any significant teratogenic or embryotoxic effects following oral administration of Ametryn technical  to rats or rabbits.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

60 mg/kg bw/day

Additional information

The effects of Ametryn technical on developmental toxicity parameters was evaluated in two GLP-compliant prenatal development toxicity studies, both conducted according to OECD test guideline 414. In the first study, Ametryn technical was administered by oral gavage at dose levels of 0, 30, 100, or 300 mg/kg bw/day in carboxy methylcellulose to timed-pregnant Wistar rats (Veena, 1998). A reduction in body weight gain and food intake was noted in the high-dose females. There were no significant embryotoxic or teratogenic effects reported, although a trend (not statistically significant) towards an increase in early and late resorptions, pre- and post-implantation loss, as well as a reduction in mean fetal weight, in the high-dose litters was reported. On the basis of these findings, the NOAEL for maternal toxicity was considered to be 100 mg/kg bw/day, and the NOAEL for developmental toxicity was considered to be 300 mg/kg bw/day.

 

In the second study, Ametryn technical was administered at dose levels of 0, 10, 30, or 60 mg/kg bw/day to time-pregnant New Zealand White rabbits (Ponnana, 1999). A reduction in maternal body weight and body weight gain during the treatment period in high-dose does was reported. There were no significant embryo- or fetotoxic or teratogenic effects reported. On the basis of these findings, the NOAEL for maternal toxicity was 30 mg/kg bw/day and the NOAEL for developmental toxicity was considered to be 60 mg/kg bw/day.

 

Supportive evidence on the effects of Ametryn technical on developmental parameters is provided by two additional GLP compliant prenatal development toxicity studies that are similar in design to OECD test guideline 414. In these studies, oral gavage administration of Ametryn technical was not associated with embryotoxic or teratogenic effects in rats and rabbits. A minor skeletal variation of unossified forepaw metacarpals was observed at Ametryn technical dose levels of 50 and 250 mg/kg bw/day in rats; however, this was accompanied by moderate to severe maternal toxicity. Maternal toxicity also was observed in rabbits at a dose of 60 mg/kg bw/day. The reported NOELs for developmental toxicity in these studies were 5 mg/kg bw/day in rats and 60 mg/kg bw/day in rabbits (the highest dose levels evaluated). The NOELs for maternal toxicity were 5 mg/kg bw/day in rats and 10 mg/kg bw/day in rabbits.