2,5-Diaminotoluene Dihydrochloride

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

/LABORATORY ANIMALS: Acute Exposure/ The aim of the study was to evaluate the skin sensitizing potency of p-toluenediamine 2HCl (PTD), p-phenylenediamine (PPD), p-aminophenol (PAP), p-aminobenzene (PAB) and Sudan III, and to study cross-reactivity. Induction was performed according to the guinea pig maximization test protocol by injections on day 0, and topical application on day 7 for 48 hours. Modifications included that the highest possible elicitation concentrations were not chosen, and that challenge was performed by open application and not closed. Challenge on day 21 by open application for 24 hours. Readings were made at 24, 48 and 72 hours after challenge application. Only results related to PTD are reviewed here. 100% of the animals induced with PTD (6/6) reacted at challenge with PTD, showing that the test substance was an extremely potent skin sensitizer. Positive reactions were recorded in the animals induced with PTD at challenge also with PPD (5/6), PAP (3/6), PAB (5/6) and Sudan III (1/6), indicating cross-reactivity to these substances in animals induced with PTD. 100% of the animals induced with PPD (6/6) reacted at challenge with PTD, but not in animals induced with PAP or PAB. The results indicate cross-reactivity to PTD in animals induced with PPD.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The teratogenic potential of toluene-2,5-diamine was studied in pregnant JCL:ddN mice. A 50-mg/kg dose of toluene-2,5-diamine dihydrochloride dissolved in distilled water was injected subcutaneously into 8 groups of 10 or 11 mice on one of days 7 to 14 of gestation. The mice were terminated on day 18 of gestation, and the uteri and fetuses were examined for abnormalities. The greatest teratogenic effects were observed in the mice dosed on day 8; 18% of the fetuses had craniofacial malformations. These mice also had a greater incidence of fused or distorted thoracic vertebrae associated with absent or fused ribs. No fused or distorted vertebrae were observed in the control mice and did not occur at all or occurred to a much lesser extent in mice treated on the other 7 days. All of the mice survived to termination, and no significant differences in the incidence of intrauterine deaths were found between groups and the untreated controls. Based on these results, a more detailed analysis of the teratogenicity of toluene-2,5-diamine was carried out on an additional 2 groups of mice. On day 8 of gestation, a larger dose of toluene-2,5-diamine dihydrochloride (75 mg/kg) was administered subcutaneously to a group 10 mice, and 50 mg/kg was administered intraperitoneally to a group of 12 mice. Six dams from the subcutaneously treated group and 4 dams from the intraperitoneal group died before termination. Nearly half of the fetuses in both groups were either dead or reabsorbed. Thirty-five percent of the fetuses from the subcutaneously treated mice and 45% of those from the intraperitoneally treated mice had craniofacial and skeletal malformations.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pregnant mice were injected with 2,5-diaminotoluene dihydrochloride, a hair-dye constituent, in a single SC dose of 50 mg/kg body weight and the fetuses examined for abnormalities on day 18 of pregnancy. A low incidence of exencephaly and a high incidence of skeletal malformations were found in the group treated on day 8. Similar malformations were also detected in 2 additional groups treated with a higher SC dose (75 mg/kg) or with an ip dose of 50 mg/kg on day 8 of pregnancy. No such malformations were found in the untreated control group or in groups treated on days 10-14 of pregnancy, and only a very low incidence of vertebral and rib anomalies followed treatment on day 7 or 9.

/GENOTOXICITY/ Toluene-2,5-diamine dihydrochloride in corn oil was applied topically to the shaved dorsal surface at doses of 1.5, 15, 150 mg/kg bw for 5 consecutive days to male mice. A weekly mating sequence with 2 females per week was started 2 days after the last application and was continued for 7 weeks. No attempt was made to prevent ingestion of the test substance during the treatment period. Fourteen days after the midweek of being caged with the male, the females were sacrificed. The final evaluation revealed no indication of dominant lethality. The positive control triethylenemelamine induced a significant dominant lethal response demonstrating the validity of the test system.

/GENOTOXICITY/ 2,5-diaminotoluene dihydrochloride has been investigated for the induction of somatic mutations in the mouse spot test. Female C57B1/6J mice were mated with C57B1/10J or T stock males. On days 9, 10, and 11 post fertilization 2,5-diaminotoluene dihydrochloride was administered dermally to a shaved patch on the dorsal side of the animal. At 12 and 24 days after birth the offspring was scored for coat color spots. Benz(a)pyrene was used as positive control. No toxic effects in the treated animals and no effect on fertility or litter size were observed. There was no significant increase in treated animals with recessive spots as compared to the concurrent controls. 2,5-Diaminotoluene dihydrochloride exposure did not induce an increase in the percentage "white mid-ventral spots" either, which are thought to be related to toxicity of treatment. Under the conditions of this test, 2,5-diaminotoluene dihydrochloride did not induce somatic mutations in this mouse spot test and consequently, 2,5-diaminotoluene dihydrochloride is not genotoxic (mutagenic) in mice.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Organic bases/Amines and related compounds/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patent can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . Cover skin burns with dry sterile dressings after decontamination ... . /Organic bases/Amines and related compounds/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. If patient is unresponsive to these measures, vasopressors may be helpful. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Organic bases/Amines and related compounds/

0.0003

SCREEN Current

0.003

PPRTV Current

Toluene-2,5-diamine dihydrochloride

PDF Document

Suggestive evidence of carcinogenic potential

2013

1.90e+01

2.50e+02

6.00e+00

4.00e+01

3.60e-03

3.00e-04

5.70e+01

7.40e+02

1.80e+01

4.00e+01

3.00e-04

Volatile

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,4-Benzenediamine, 2-methyl-, dihydrochloride- is included on this list. Effective date: 4/29/83; Sunset date: 4/29/93.