N,N'-di-sec-butyl-p-phenylenediamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study. No internationally accepted protocol followed, but study well documented and acceptable protocol. However, no confidence limits could be calculated for male rats. Apparently the study did not include any control animals.

Justification for type of information:

Key study, GLP, Klimisch score 2.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Santoflex 44 was administered to fasted albino rats of both sexes as a 392 mg/mL solution in corn oil by oral intubation. The volume administered was adjusted according to body weight and dosage to be given. Following dosing, each rat was individually housed and clinical observations were made twice daily until sacrifice at day 15. Body weights were recorded weekly and necropsies were performed on all animals.

GLP compliance:

yes

Test type:

other: not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-di-sec-butyl-p-phenylenediamine

EC Number:

202-992-2

EC Name:

N,N'-di-sec-butyl-p-phenylenediamine

Cas Number:

101-96-2

Molecular formula:

C14H24N2

IUPAC Name:

N,N'-di-sec-butyl-p-phenylenediamine

Details on test material:

- Physical state: dark red/brown liquid
- Analytical purity: 96.09%
- Lot/batch No.: S
- Stability under test conditions: the test material was stated to react with strong oxidizing agents. According to the study report, it was exposed to no such materials, with the exceptions of those potenially present in the testing environment.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sasco Inc., O'Fallon, MO
- Age at study initiation: approx. 8 weeks (young adults)
- Weight at study initiation: 225-247 g (males); 166-182 g (females)
- Fasting period before study: overnight
- Housing: individually, stainless steel cages or polycarbonate cages with stainless steel mesh bottom
- Diet (e.g. ad libitum): Purina Laboratory Rodent Chow, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: quarantine, at least 5 days

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 392 mg/mL
- Amount of vehicle (if gavage): depends on body weight and dosing

ADMINISTRATION
- Rats are dose by gavage using a hypodermic syringe and ball tipped, stainless steel needle.

Doses:

200, 313, 490, 767, 1200 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3 time/d during first 8 hours, twice daily after that
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

271 mg/kg bw

Based on:

test mat.

95% CL:

146 - 366

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

281 mg/kg bw

Based on:

test mat.

95% CL:

0

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

265 mg/kg bw

Based on:

test mat.

95% CL:

108 - 383

Mortality:

In many cases, mortality followed after the observation of other clinical abnormalities.

Clinical signs:

other: Lethargy was observed in 32 rats. The following observations were also made in animals that suffered from lethargy: ptosis (21 of 32 animals), ataxa (15 of 32 animals), prostration and lacrimation (5 of 32 animals). These effects were observed only in ani

Gross pathology:

Necropsy findings indicated that toxicity to the gastrointestinal tissue may have contributed to lethality in all but one of the 36 decedents. Signs of gastrointestinal inflammation were observed in 30 animals, in 15 rats irritation was sufficiently severe to result in hemorrhage. Each of five other animals had gelatinous red material, a red fluid filled mass, or a red/green fluid filled mass in the stomach. Gastrointestinal tracts of 14 animals were distended. Eleven rats had green fluid in the urinary bladder or green urinary staining of fur. Eight animals had red/brown fluid in the urinary bladder or fur stained with urine of a similar coloration.

Applicant's summary and conclusion

Conclusions:

The LD50 of the test material is 271 mg/kg bw with 95% confidence limts 146-366 mg/kg bw

Executive summary:

Santoflex 44 antioxidant was administered to fasted albino rats of both sexes through oral gavage of a 392 mg/ml solution in corn oil. The administered volume was adapted to the animal's body weight and the target dose. The rats were observed for clinical signs and mortality for 14 days. After day 15 the surviving animals were sacrificed. Necropsies were performed on all animals.

The acute oral LD50 was calculated to be 271 mg/kg bw, with 95% confidence limits of 146 and 366 mg/kg. Commonly observed clinical abnormalities included lethargy, ataxia, ptosis and abnormal urinary coloration (green and/or red/brown). Necropsy findings including gastrointestinal inflammation (in many cases reaching the severity of hemorrhage), gastrointestinal distension, and red, fluid filled gastric masses indicated that toxicity to gastrointestinal tissue may have contributed to lethality in virtually all of the rats that died on the test.