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Effects on fertility

Description of key information
No info
Additional information

Oral administration of NTAN to Sprague-Dawley rats at doses of 1, 10 and 45 mg/kg/day resulted in overt signs of parental toxicity at the 45 mg/kg/day dose including death, clinical signs of toxicity (including convulsions, labored breathing, etc.), decreased food consumption, body weight, body weight gain, and motor activity changes (see also the 28-day repeated dose study). Overall mating, pregnancy, offspring survival and pup body weights were not notably affected by treatment with NTAN. Based on the results of this study, the no-observed-adverse-effect level (NOAEL) for parental systemic toxicity of NTAN was 10 mg/kg/day and the NOAEL for reproductive/developmental toxicity was at least 45 mg/kg/day.


Short description of key information:
A combined oral repeated dose (subacute) and reproductive/developmental toxicity screening study was available.

Effects on developmental toxicity

Description of key information
In the combined oral repeated dose (subacute) and reproductive/developmental toxicity screening study, it was noted (see above) that offspring survical and pup body weights were not notably affected by treatment with NTAN.  Gross external observations, following parturition on lactation day 0, were low in incidence and were noted in 4-6 fetuses in each treatment group, including the vehicle control group. All gross external morphology observations were common observations likely associated with delivery and consisted mainly of bruising, pale skin and a lesion/scab on the neck.  None of the gross external observations were attributed to NTAN treatment.
Visceral examinations were performed on dead pups, when feasible. No visible abnormalities were noted during the visceral examinations.
Additional information

Although not a full-blown developmental toxicity study was available, the information described above indicates that NTAN did not induce developmental toxicity at a dose level up to 45 mg/kg bw when given during 2 weeks prior to mating, during mating and during the complete pregnancy period.

Justification for classification or non-classification

NTAN did not show reproduction/developmental toxicity at a level up to 45 mg/kg bw, although this level resulted in severe parental toxicity, including death. As such no classification for reproduction toxicity is warranted.

Additional information

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