p-phenylenediamine

Endpoint summary

Description of key information

Oral Minimum Lethal Dose (rat gavage) = 75 mg/kg
Dermal Weight of Evidence indicates that the test substance did not produce mortality in experimental animals (guinea pigs and rabbits)
Inhalation 4-hour LC50 (rats) = -0.92 mg/L

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

discriminating dose

Value:

75 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

920 mg/m³ air

Additional information

Acute Oral Toxicity: The test substance has an acute oral minimum lethal dose in rats of 75 mg/kg. After administration to 50 mg/kg and above, acute toxicity was associated with central nervous system effects, observed as unsteady gait, loss of balance, lateral decubitus, piloerection, and/or tremors. In addition, rhabdomyolysis was observed in mice and humans at an oral dose level around or below 80 m/kg.

 

Acute Inhalation Toxicity: The test substance is moderately toxic via the inhalation route with a 4-hour LC₅₀ of 0.92 mg/L (920 mg/m³).  After inhalation to the substance at ≥0.94 mg/L (≥940 mg/m³), acute toxicity was associated with central nervous system effects observed as no righting reflex and tremors.

 

Acute Dermal Toxicity: The test substance was applied to New Zealand Albino rabbits as a 40% aqueous solution suspension for a period of 24 hours at doses of 5010 and 7940 mg/kg. All animals dosed (one female in the 5010 mg/kg group and one male and female in the 7940 mg/kg group) survived the 14 day observation period.  Weight loss was observed 2-4 days following dosing. The LD₅₀ was > 7940 mg/kg (Y-78-192- Monsanto). A 10% concentration of test substance was applied to shaved, intact skin of 3 rabbits (sex not reported). Under the conditions of this study, the test substance in dry form or 10% alcohol applied to the shaved, intact skin of rabbits produced no systemic toxicity. Moderate erythema was observed with the 10% alcoholic solution. No mortality was observed (Hanzlik, 1923). Guinea pigs were treated dermally with the test substance (99% purity) for 15 or 30 days. The amount applied was 0.1 mL with a concentration of 3% solution in 25% ethanol. After 15 days of treatment, 5 animals of the control and 5 animals of the test group were sacrificed. After 30 days of treatment, the same process was repeated. No mortality was reported (Mathur et al., 1992).    Guinea pigs were exposed dermally (2 x 2 cm clipped area) to the test substance for 30 days.  The animals were treated (12 animals each in treatment and control groups) with 4 mg/kg of 1% solution of the test substance in 25% ethanol. No morality was reported (Mathur et al., 2005).   While each of the studies described alone would be insufficient to completely describe the potential dermal toxicity of the test substance, they each demonstrate that dermal application of test substance did not produce mortality in experimental animals (guinea pigs and rabbits). In addition, although the number of animals used is low (n=3) as reported in the Y-78-192 study, the doses of test material were not trivial (> 5000 mg/kg). The weight of evidence indicates that test substance is not considered toxic via the dermal route of exposure.

Justification for classification or non-classification

Based on the acute minimum lethal dose in the rat (75 mg/kg) and the 4-hour inhalation LC₅₀  in the rat (920 mg/m³), the substance should classified as T; R 23/25: Toxic, Toxic by inhalation and if swallowed for acute toxicity according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. While each of the dermal studies described alone would be insufficient to completely describe the potential dermal toxicity of the test substance, they each demonstrate that dermal application of test substance did not produce mortality in experimental animals (guinea pigs and rabbits). In addition, although the number of animals used is low (n=3) as reported in the Y-78-192 study, the dose of test material were not trivial (> 5000 mg/kg). The weight of evidence indicates that test substance is not considered toxic via the dermal route of exposure. Although the current information in this IUCLID on the substance would indicate a minor deviation from the harmonised classification (R24), the harmonised classification will be adhered as it is stricter. Therefore, the test substance will be classified as R23/24/25, Toxic; by inhalation, in contact with skin and if swallowed according the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.