Bis(2-ethylhexyl) phthalate

Endpoint summary

Description of key information

In experimental animals, DEHP exhibits low  acute oral, dermal and inhalation toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

20 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

10 620 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

19 800 mg/kg bw

Additional information

Acute oral toxicity

In rats:

Acute oral toxicity of DEHP in the rat has been estimated as a prerequisite to a carcinogenicity study by NTP (1982). Doses from 800 to 20,000 mg/kg of DEHP (99.5% pure) were administered in a single dose by gavage to groups consisting of 5 males and 5 females. The vehicle was corn oil. No deaths were observed during a 14-day observation period, giving an LD0 in excess of 20,000 mg/kg. No individual animal data are given.

Berman (1995) evaluated the acute oral toxicity of DEHP (>99% pure) in rats according to a protocol similar to the OECD N°425 guideline. Groups of 7-15 female Fischer 344 rats were given a single oral dose of DEHP at doses of 0, 150, 500, 1500, 5000 mg/kg and were then observed daily for 7 days. No mortality at the highest dose tested (5000 mg/kg). The oral LD0 of DEHP is higher than 5000 mg/kg in female Fischer 344 rats.

Groups of six male Sprague Dawley rats were administered single oral doses of Diethylhexylphthalate (DEHP) at 2000 mg/kg in 2% gum acacia and were observed clinically for seven days (Chu et al., 1981). No mortality and clinical signs were observed. Body weight and food consumption were not affected by treatment. The liver weight increased in the treated group. Hepatic microsomal aniline oxidase activity was not altered by treatment. The acute oral LD0 is higher than 2000 mg/kg in rats.

In mice:

Acute oral toxicity of DEHP in mice has also been estimated as a prerequisite to a carcinogenicity study by NTP (1982). Doses from 800 to 20,000 mg/kg of DEHP (99.5% pure) were administered as a single dose by gavage to groups consisting of 5 males and 5 females. The vehicle was corn oil. No deaths were observed during a 14-day observation period, thereby giving an LD0 value higher than 20,000 mg/kg. No individual animal data are given in the report.

Acute inhalation toxicity

In a study performed according to GLP principles, groups of 5 male and 5 female rats were exposed for 4 hours to clean air (control group) or DEHP (purity not specified) in concentrations of either 3.39, 6.82, or 10.62 mg/litre (3,390, 6,280, or 10,620 mg/m3) (Greenough, 1981). The highest dose was considered the technical limit of aerosol generation for the test material. The control group and the lowest dose group were exposed on the same day. The mid-dose group and the highest dose group were exposed on different days. The exposure was nose-only. The rats were observed for clinical signs throughout the exposure period and for the first 4 hours after dosing. During the subsequent 14-day observation period the rats were inspected twice daily. Body weights were measured before exposure and with regular intervals during the observation period. A detailed macroscopic examination was performed on all animals at sacrifice at the end of the observation period. No animals died during or after the exposure. All treated animals showed a slightly unkempt appearance for 1-2 days after exposure, those in the highest dose group had a yellowish staining on their fur. This group also had a reduced body weight gain on the second day after exposure, which subsequently returned to the normal pattern. In all groups, dark red foci and patches were observed in the lungs at post mortem inspection. These findings were more frequent in the treated animals. In conclusion, the LC0 of DEHP via inhalation was in this study found to be in excess of 10,620 mg/m3 for 4 hours.

Acute dermal toxicity

The acute dermal toxicity of DEHP has not been investigated in a study of guideline quality. In an older study, rabbits were exposed dermally for 24 hours with doses up to 20 ml/kg (Shaffer et al., 1945). That amount killed 2 of 6 rabbits. The LD50 by skin absorption is ca. 20 ml/kg (19800 mg/kg bw). However, details of the experimental design and original results are not presented in the report.

Justification for classification or non-classification

According to the criteria edicted in REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008, no classification is warranted for the acute toxicity.