Registration Dossier

Administrative data

Description of key information

In a well conducted study (Biodynamics Inc., 1985), doses of 2000, 2500, 3200 and 4000 mg/kg bw HEDP-4Na (as 31% active salt) were administered to rats (5/sex) by oral gavage. Animals were observed for 14 days. Ataxia and/or tremors, oral and nasal discharge, hypoactivity, soft stool and fecal and/or urinary staining were observed at all doses. The majority of surviving animals showed some weight loss during the 1st week after dosing, but all animals then gained weight between days 7 and 14. Macroscopic abnormalities observed at necropsy were primarily changes suggestive of irritation: lungs (discolouration)  and gastrointestinal  tract  (red  or  black  walls,  or  red  or black fluid  present).  Most of the animals in the 2500, 3200 and 4000 mg/kg dose groups had enlarged kidneys at necropsy, and one animal in the 4000 mg/kg bw group had unilateral renal pallor, dilated renal pelvis and red fluid surrounding the kidney. The LD50was calculated to be 2850 mg/kg bw (equivalent to 940 mg/kg/day bw active salt, which is equivalent to 659 mg/kg bw/day active acid).

 

In an acute dermal toxicity limit test (Biodynamics Inc., 1985) 5000 mg/kg bw of HEDP-4Na (as 31% active salt) was applied to the skin of rabbits (5/sex, occlusive dressing, 24 hours). Animals were then observed for 14 days. One female died on Day 13 (not test-related). Most animals had severe dermal effects at the dose site (necrosis followed by eschar formation and/or exfoliation of the eschar tissue), which persisted throughout the observation period. The LD50 was determined to be >5000 mg/kg bw as test material (subsequently calculated to be equivalent to >3500 mg active acid/kg bw). 

 

The test substance was tested at pH 11.5. The above local irritation effects in the oral study and severe dermal effects in the dermal study may not be directly comparable to the registration substance. The deaths possibly are actually secondary to the local effects and therefore using this study as read-across is conservative or worst-case approach.

There are no acute inhalation data.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
940 mg/kg bw
Quality of whole database:
(Active acid)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 500 mg/kg bw
Quality of whole database:
(Active acid)

Additional information

The most recent reliable study was selected as the key studies.

Justification for classification or non-classification

Based on the available data, it is proposed that the sodium salts of HEDP (based on active acid) be classified as Acute Oral Cat. 4 H302: Harmful if swallowed' according to Regulation (EC) No 1272/2008. There is no proposal to classify HEDP salts for acute dermal toxicity.