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Administrative data

Description of key information

Oral: The acute oral LD50 was determined to be 400 - 1600 mg/kg bw in rats (handbook information)

Dermal: The acute dermal LD50 was determined to be > 2000 mg/kg bw in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
400 mg/kg bw
Quality of whole database:
Handbook information, for further information please refer to discussion.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP and guideline study, whole database factor: 1.

Additional information

Acute toxicity oral: In accordance with column 2 of REACH Annex VIII, the acute toxicity oral does not need to be conducted as the substance is classified as corrosive to the skin. According to the criteria in CLP Annex 1, the dose range for acute oral toxicity category 4 is defined as >300 but <=2000 mg/kg bw. The acute oral LD50 of DEO in rats is described with a dose range of 400 - 1600 mg/kg bw (Patty, 1963). Massive renal oxalate deposits were observed following treatment with 400 mg/kg bw or higher in rats. In a 14-day oral gavage dose range finding study (summarized in Research Institute for Organic Syntheses Inc., 2011b) all rats dosed at 600 mg/kg bw/d (5m/5f) died between application day 5 and 14, whereas no death occurred at 300 mg/kg bw/d. This demonstrates that the acute oral LD50 is >300 mg/kg bw/d. Therefore, the classification as Category 4, H302: Harmful if swallowed for the acute oral toxicity is justified.

 

Acute toxicity dermal: The test substance applied at a dose of 2000 mg/kg bw did not result in death of the treated animals. No clinical signs of intoxication were observed. Macroscopic changes in kidneys (increase in size, changes of colour, granular or rough surface) were diagnosed during gross pathological examinations in four of five male and all female animals. On the basis of these findings, a histopathological examination of the kidneys was performed in one male and female animal. Urolithiasis and interstitial inflamation were observed. According to the results of this study, the LD50 (dermal) of the test substance, Diethyl oxalate, for rats of both sexes is higher than 2000 mg/kg bw. Concurrently the test substance caused severe damage of kidneys at a dose level of 2000 mg/kg bw, detected by gross pathological and histopathological examinations.

 

Acute toxicity inhalation: In accordance with column 2 of REACH Annex VIII, the acute toxicity inhalation study does not need to be conducted as Diethyl oxalate is classified as corrosive to skin.

Justification for classification or non-classification

Diethyl oxalate is harmful after oral administration (acute oral Cat. 4, H302: Harmful if swallowed) according to the criteria of Regulation (EC) No 1272/2008.

 

Classification for acute dermal or inhalation toxicity is not warranted according to the criteria of Regulation (EC) No 1272/2008.

The ECHA Guidance on the Application of the CLP Criteria (ECHA 2008) acknowledges that acute toxicity refers to lethality and STOT-SE to non lethal effects. Care should be taken not to assign both classes for the same toxic effect, essentially giving a “double classification”, even where the criteria for both classes are fulfilled. In such case the most appropriate class should be assigned.

DEO caused lethality, and in the absence of lethality adverse effects in the kidney after acute single exposure. As kidney effects were also observed after repeated exposure, classification as STOT RE cat. 2 (kidney) in addition to acute oral cat. 4 sufficiently classifies the health effects of DEO. STOT-SE does not need to be further assigned in accordance to Regulation (EC) No. 1272/2008, in order to prevent “double classification”.