N-(1,3-Dimethylbutyl)-N

OECD SIDS
N-(1,3-DIMETHYLBUTYL)-N´-PHENYL-1,4-PHENYLENEDIAMINE
In contrast studies from 1962 and 1973 reported oral LD 50 values in the range of 3340 - 3580 mg/kg
bw. Groups of 5 rats were fed undiluted 6PPD by stomach tube in dosages of 2510, 3160, 3980 (3
females and 2 males each) and 5010 mg/kg bw (4 males and 1 female). Deaths occurred within 2-5
days p.a.. Number of deaths for the 4 dose groups were 1/3 females, 1/3 females and 1/2 males, 3/3
females as well as 5/5 in the highest dose group (Younger, 1962). Gavage application of 6PPD (no
data on substance preparation) in doses of 2510, 3160, 3980, 5010 and 6310 mg/kg bw resulted in
death of 1, 2, 3, 3 or 4 of the 5 rats/dose (males and females mixed) (Randall and Bannister, 1990).
Signs of intoxication were severe diarrhea, loss of appetite, salivation, ocular discharge, reduced
activity, increasing weakness, dyspnea and collapse within 15 - 30 minutes after application, which
in some cases was followed by recovery after several hours. At necropsy acute gastrointestinal
inflammation, liver discoloration (jaundice), renal and liver congestion and haemorrhagic lungs
were observed (Randall and Bannister, 1990; Younger, 1962). The inconsistent range of oral LD 50
values can be explained by the substance preparation which influences the bioavailability after oral
application. According to the OECD guideline in the study of Ohara (Hatano Research Institute
1999; Ohara et al., 1999a) 6PPD as a lipophilic substance was dissolved in corn oil as a suitable
vehicle whereas other studies either applied undissolved 6PPD (Younger, 1962) or the use of a
vehicle is not described (Randall and Bannister, 1990).
Conclusion
The oral LD 50 in rats ranged between 500-1000 mg/kg bw for females and between 1000-2000
mg/kg bw for males. Signs of intoxication were hypoactivity, diarrhea, bradypnea, hypothermia and
a prone position accompanied by pathological lesions in digestive organs and respiratory system.
3.1.3 Irritation
Skin Irritation
There are no studies according to the current OECD guideline, however, there are study reports
which give sufficient information to evaluate this endpoint:
In an older study undiluted 6PPD (amount not given) was applied to the clipped, intact skin of 3
rabbits for 24 hours under a dressing of plastic strips. The compound was removed with soap and
water. Within 4 hours 2/3 rabbits developed barely perceptible redness (average score 0.6/8
according to the method of Draize). At the 24 hour-reading slight to well defined erythema were
reported as the maximal reaction (score 1.6) returning to barely perceptible redness within 72 hours
(score 1.0) and complete reversibility within 120 hours (score 0.0). The compound was evaluated as
a slight irritant (Younger, 1962).
Another study reported no irritant reaction at all (score 0.0/8.0 in accordance with the Federal
Hazardous Substance Act, 21 CFR, § 191.11, 1964) when 0.5 ml undiluted 6PPD were applied to
the clipped intact or abraded skin of 6 rabbits under a semi-occlusive dressing for 24 hours followed
by an observation period of 7 days (Randall and Bannister, 1990).
Groups of 6 rabbits were exposed to preparations of 6PPD in vaseline (0.5 g with 2.5 or 25 % 6PPD
corresponding to 0.0125 and 0.125 g 6PPD) or olive oil (0.025 g 6PPD in 0.5 ml oil) according to
the method of Draize (no information on occlusion). Exposure of the scarified or unscarified skin
was for 24 hours, further readings were after 48 and 72 hours. Neither individual nor average scores
for erythema / oedema or the time course of the reaction and the reversibility of effects were
documented in the available publication. Test results were presented as primary cutaneous irritation
indexes (PCII) of 0.6 and 1.0 calculated for the low and high concentration vaseline preparation of
6PPD, leading for both to a classification of low irritant potential (criteria not documented). In
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