Well I haven't flown that particular trip but I've flown the EWR-GRU trip many times and it's very similar in terms of flight time and rest. Although it's a hard trip, it's very productive. Basically you're away from base for about 36 hours and you get 20 hours of flight time (Pay!). You fly the trip four times and you're done for the month. In other words you're at work for six days and you get 80 hours of pay.
Is it safe? It's certainly legal and if you do one of these trips a week, you get plenty of time for rest both prior to and after the trip. Plus you sleep really well for the eight to ten hours between legs. And you get some rest during each leg.
Incidentally, this trip goes very senior because of the time off aspect!
Flame away!