N-nitro-N-(3-methyl-3,6-dihydro-2H-1,3,5-oxadiazin-4-yl)amine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

NOAEL

150 mg/kg bw/day

Additional information

In a dose range finding feeding study (Syngenta 2001; 0, 50, 500, 2000, and 4000 ppm), toxicity was observed in parental animals at 2000 and 4000 ppm. Effects in offspring (viability, body weight gain) were seen only at levels where maternal toxicity was observed.

In a subsequent one generation reproductive toxicity study (RCC, 2002; OECD 415; 0, 50, 200, 600, and 2000 ppm) no effects on the reproductive performance were seen. General toxicity was reported for parents and offspring at 2000 ppm (reduced body weight gain). Since no effects in offspring were seen at levels below maternal toxicity and since no reproductive effects were seen in F0 animals below the LOAEL for general toxicity, the substance is not considered toxic to reproduction. However, German Competent Authority criticized that the maternal effects occurred only during (pre)mating and gestation and not during lactation, while the effects in pups occurred during lactation, only (BAuA, 27.05.2003; reference number: 99 04 1142 00). This was interpreted as a potential indication of an adverse developmental effect. In addition the food consumption in both studies led to different doses. For clarification the German Competent Authority requested an additional study and suggested application by gavage.

The requested one generation reproduction toxicity study (OECD 415, Harlan, 2009) was conducted by gavage (0, 50, 150, and 500 mg/kg bw/d). The LOAEL in F0 was 150 mg/kg bw/d based on general toxicity. Reproductive effects occur at 500 mg/kg bw/d (lower number of implantations, litter size and post-natal loss). Pups weight in the 150 mg/kg bw/d group was reduced. This effect was attributed to maternal toxicity. Hence there is no indication of toxicity to reproduction under conditions of a one generation (OECD 415) study.

In accordance with the request from the German Competent Authority (BAuA, 27.05.2003; reference number: 99 04 1142 00) no additional studies (OECD 416 and/or OECD 414) need to be conducted as the result of the OECD 415-study does not indicate effects on fertility.

Short description of key information:
Initially a dose range finding study (Syngenta, 2001) and a subsequent one generation feeding study (OECD 415; RCC, 2002) have been conducted. On request of the German competent authority (BAuA, 27.05.2003; reference number: 99 04 1142 00) a second one-generation study (OECD 415; gavage; Harlan, 2009) was conducted. Effects on development and fertility occur at 150 and 500 mg/kg bw/d, respectively, and have been attributed to maternal toxicity.

Effects on developmental toxicity

Description of key information

see above (fertility)

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

50 mg/kg bw/day

Additional information

see above (fertility)

Justification for classification or non-classification

Effects on development and fertility occur at 150 and 500 mg/kg/d, respectively, and have been attributed to maternal toxicity. Hence, no classification for reproductive effects is warranted.