Registration Dossier

Administrative data

Description of key information

ACUTE TOXICITY ORAL
Korte jr., D.W.:
Acute oral toxicity - rat: Diethyleneglycol dinitrate is a slightly toxic compound that produces signs of neurotoxicity in addition to standard symptoms of nitrate ester poisoning. Calculated MLD values were 990.4 ± 30.0 mg/kg in male Sprague-Dawley rats and 753.1 ± 35.9 mg/kg in female Sprague-Dawley rats.
Acute oral toxicity - mice: DEGDN is a slightly toxic compound that appears to produce primarily behavioral and reflexive clinical signs. The calculated MLD and standard error for DEGDN are 1395 ± 59 mg/kg in male and 1321 ± 74 mg/kg in female ICR mice.
Krasovsky, G.N.:
The oral LD50 of DEGDN in white mice was 1250 mg/kg; in white rats 1180 mg/kg; and in guinea pigs 1250 mg/kg. In all species, acute poisoning was characterized by cyanosis (blockage of cellular respiration by massive formation of methemoglobin) and by symptoms of damage to the central nervous system.
The clinical signs observed in all studies reported for DEGDN are similiar with the exception that cyanosis was not observed in study in ICR Mice (Korte jr.). Krasovsky have reported that cyanosis was observed in rats and mice following acute oral administration of DEGDN. The failure to observe cyanosis in the animals in study in ICR Mice most probably reflects the difficulty in detecting cyanotic changes in mice under the artifical (fluorescent) light conditions of the animal facility and/or in coordinating the scheduled observation periods with the kinetics in the mouse of methemoglobin formation and reduction following DEGDN administration.
ACUTE TOXICITY DERMAL
Korte jr., D.W.: A limit dose of 2 g/kg of neat diethyleneglycol dinitrate (DEGDN) was not toxic to rabbits following a 24-hr dermal exposure. DEGDN possesses a minimal potential for acute dermal toxicity.
ACUTE TOXICITY INHALATION
No data available.
HARMONIZED CLASSIFICATION according to Regulation (EC) No.1272/2008:
Acute Tox. 2*, H300
Acute Tox. 1*, H310
Acute Tox. 2*, H330

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
50 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
0.002 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
50 mg/kg bw

Additional information

ACUTE TOXICITY ORAL

The preferred rodent species is the rat and normally females are used for acute toxicity study by oral route.

The LD50 (oral) of DEGDN has been found to be similar in several species. LD50 (rat-female)=753.1 ± 35.9 mg/kg.

DEGDN produces signs of neurotoxicity in addition to standard symptoms of nitrate ester poisoning. The duration of clinical signs was acute. Most animals were exhibiting signs by 2 hours after dosing and had either died or cleared by 72 hours after dosing.

DEGDN has classification harmonized in Annex VI of CLP as Acute Tox. 2* by oral route. The criteria for classification of substances for acute toxicity category 2 by oral route are based on following lethal dose data: 5 < LD50 50 mg/kg bw. The source data for harmonized classification are not available.

 

Based on LD50 values the results of studies are in slight conflict with harmonized classification. However, the clinical signs were observed and LD50 = 50 mg/kg (based on classification criteria for harmonized classification) should be selected as effect level for acute toxicity – oral.

 

ACUTE TOXICITY DERMAL

Korte jr., D.W.: No systemic signs clearly attributable to the compound were observed in any of the animals during the two-week observation period, that could be directly attributed to administration of the DEGDN. No gross or microscopic findings are consistent with the observation that significant quantities of test compound remained on the back after the 24-hr exposure. This observation is also consistent with hydrophilic character of the substance.

A limit dose of 2 g/kg of neat diethyleneglycol dinitrate (DEGDN) was not toxic to rabbits following a 24-hr dermal exposure. DEGDN possesses a minimal potential for acute dermal toxicity.

 

DEGDN has classification harmonized in Annex VI of CLP as Acute Tox. 1* by dermal route. The criteria for classification of substances for acute toxicity category 1 by dermal route are based on following lethal dose data: 0 < LD50 50 mg/kg bw.

 

LD50 = 50 mg/kg (based on classification criteria for harmonized classification) should be selected as effect level for acute toxicity – dermal. However, the results of study (LD50 value, no clinical signs and no gross and microscopical findings) are in conflict with harmonized classification. The source data for harmonized classification are not available.

 

ACUTE TOXICITY INHALATION

Experimental data are not available.

 

DEGDN has classification harmonized in Annex VI of CLP as Acute Tox. 2* by inhalation. The criteria for classification of substances for acute toxicity category 2 by inhalation are based on following lethal dose data: 0,5 < LC50 ≤ 2 mg/l (vapour).

 

LC50 = 2 mg/l (based on classification criteria for harmonized classification) should be selected as effect level for acute toxicity – inhalation. The source data for harmonized classification are not available.

Justification for classification or non-classification

HARMONIZED CLASSIFICATION of DEGDN according to Regulation (EC) No.1272/2008 for Acute Toxicity by oral, dermal route and by inhalation:

Acute Tox. 2*, H300

Acute Tox. 1*, H310

Acute Tox. 2*, H330

The classificationindicated by the reference *in Annex VI in the columnClassificationin Table 3.1 shall be considered as a minimum classification.This classification shall be applied if none of the conditions stated in Annex VI (1.2.1) are fulfilled.

These conditions are not fulfilled for classification DEGDN.