N-(1,3-Dimethylbutyl)-N

OECD SIDS
N-(1,3-DIMETHYLBUTYL)-N´-PHENYL-1,4-PHENYLENEDIAMINE
3 HUMAN HEALTH HAZARDS
3.1 Effects on Human Health
3.1.1 Toxicokinetics, Metabolism and Distribution
There are no studies on the toxicokinetics of 6PPD available.
However, some conclusions can be drawn from toxicity studies with acute and repeated application:
The appearance of systemic toxicity after oral and dermal exposure shows the principal
bioavailability of 6PPD via these routes.
Biomonitoring of workers in the rubber industry detected 6PPD in urine thereby demonstrating that
the substance can be resorbed from the respiratory tract and possibly after dermal contact (Rimatori
and Castellino, 1989).
3.1.2 Acute Toxicity
Inhalation
There are no data available.
Dermal
There are no studies according to the current OECD guideline but there are 2 older studies which
give sufficient information to evaluate this endpoint: No mortality was observed after a 24-hour
semi-occlusive application of 3160, 5010 or 7940 mg 6PPD/kg bw to the clipped intact skin of 2
rabbits/dose (LD 50 > 7940 mg/kg bw). Reduced appetite and activity for 3-7 days were the only
clinical signs, whereas the viscera appeared normal (Randall and Bannister, 1990). In a second
study 6PPD was applied at doses of 798, 1260, 2000, 3160, 5010, 7980 mg/kg bw (1 rabbit/dose)
under a dressing of plastic strips. Doses of 5010 mg/kg bw caused mortality after 10-11 days
accompanied by loss of appetite, lethargy and gradual wasting. Gross autopsy yielded liver
discoloration and pulmonary hyperemia. According to this study the LDL 0 is in the range between
3160 and 5010 mg/kg bw (Younger, 1962).
Conclusion
The dermal LD 50 in rabbits was > 3000 mg/kg bw. Signs of intoxication were reduced food
consumption, hypoactivity and lethargy.
Oral
There is one study according to the OECD TG 401 (Hatano Research Institute, 1999; Ohara et al.,
1999a) and some other study reports with rats which give sufficient information to evaluate this
endpoint (Randall and Bannister, 1990; Younger, 1962).
In the OECD guideline study 5 male and 5 female rats were dosed with 0, 250, 500, 1000 and 2000
mg 6PPD/kg bw in corn oil by gavage. Deaths occurred at day 2 – 4 p.a. at 1000 mg/kg (2/5 males
and 3/5 females) and at 2000 mg/kg (all animals), resulting in LD 50 values between 1000 – 2000
mg/kg for male rats and 500 – 1000 mg/kg for female rats. Signs of intoxication were hypoactivity ,
diarrhea, bradypnea, hypothermia and a prone position in the 1000 mg/kg or higher dosed groups,
abnormal gait in 2000 mg/kg males, and lacrimation and weakness of limbs in 2000 mg/kg females.
Pathological lesions were observed in digestive organs and the respiratory system (Hatano Research
Institute, 1999; Ohara et al., 1999a).
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