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Description of key information

Nose-only exposure of rats to DEA aerosols for 3 months (OECD TG 413) resulted in a systemic NOAEC of 15 mg/m³ and the NOAEC for local respiratory tract effects was 3 mg/m³.
Repeated unoccluded dermal application of ethanolic DEA solutions in subchronic (13 weeks, protocol similar to OECD TG 411) a NOAEL for systemic effects or local skin irritation could not be achieved (LOAEL 32 mg/kg bw in rats; 80 mg/kg bw in mice). The 2 year dermal studies (NTP, 1999, protocol similar to OECD TG 451) with rats and mice also showed non-carcinogenic effects. Critical effects appear to be kidney (nephropathy) and liver toxicity, anaemia and dermal hyperkeratosis/acanthosis. The overall dermal LOAEL based on the 13 week and 2 years study is concluded to be 8 mg/kg bw/day.
In rats, subchronic oral treatment via the drinking water (protocol similar to OECD TG 408) resulted in a LOAEL of 25/14 mg/kg bw (equal to 320/160 ppm) in males/females. In the subchronic oral study in mice a LOAEL of 104/142 mg/kg bw (equal to 630/630 ppm) was noted in males/females.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEL
14 mg/kg bw/day

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
3 mg/m³

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEL
8 mg/kg bw/day

Additional information

Nose-only exposure of rats to DEA aerosols for 3 months (BASF AG, 1996 and 2002a, OECD TG 413) resulted in systemic and local effects:

- kidney effects (increased incidences of mild hematuria in both sexes, some increase in renal tubular cells and granular casts in male animals, slight increases in kidney weights, minimal or slight tubular hyperplasia in some female animals and intratubular lithiasis slightly more pronounced than in controls in some male animals);

- adaptive liver effects (mild increases of liver weights and serum alkaline phosphatase serum levels without histopathological findings);

- a mild normochromic microcytic anaemia and some influence on the male reproductive system consisting of diffuse testicular atrophy and minimal to slight atrophy of the prostate was present at the high concentration only.

Furthermore, local effects (respiratory tract irritation, squamous metaplasia of the laryngeal epithelium, inflammatory response) were observed. No functional or morphological evidence of neurotoxicity was observed. The NOAEC for systemic effects was 15 mg/m³ and the NOAEC for local respiratory tract effects was 3 mg/m³.

 

Repeated unoccluded dermal application of ethanolic DEA solutions in subacute (14 days) and subchronic (13 weeks, protocol similar to OECD TG 411) (NTP, 1992) studies with rats and mice led to mortality at high dose levels (≥500 mg/kg bw in rats; ≥1000 mg/kg bw in mice). In rats, systemic signs of toxicity consisted predominantly of anaemia and nephropathy. In addition, liver weights were increased without a histopathological correlate. In mice, systemic effects occurred mainly in the form of liver and kidney damage. In both species, local skin irritation was observed. A NOAEL for systemic effects or local skin irritation could not be achieved (LOAEL 32 mg/kg bw in rats; 80 mg/kg bw in mice).

The 2 year studies (NTP, 1999, protocol similar to OECD TG 451, see section 7.7) with rats and mice also showed non-carcinogenic effects (see section on carcinogenicity) from the lowest tested dermal dose (8 mg/kg bw/day). Critical effects appear to be kidney (nephropathy) and liver toxicity, anaemia and dermal hyperkeratosis/acanthosis. Besides anaemia, nephropathy was observed at the lowest tested dose in the 13 week dermal toxicity study (32 mg/kg bw/day) in female rats. After 13 weeks effects on the kidneys are not yet masked by ageing and appear a treatment related adverse effect. Therefore, the observation of nephropathy in female rats at the lowest tested dermal dose of 8 mg/kg bw/day in the 2 year study, which was somewhat masked by ageing, is also considered adverse. In males this effect was completely masked by the ageing process after 2 years of exposure. In conclusion, the overall dermal LOAEL based on the 13 week and 2 year studies is concluded to be 8 mg/kg bw/day.

 

In rats, subchronic oral treatment via the drinking water (NTP, 1992, protocol similar to OECD TG 408) caused mortality at the high dose in males (5000 ppm). Impaired body weight gains were observed at concentrations equal to or higher than 320 ppm in females and 630 ppm in males. Systemic effects consisted of anaemia, nephrotoxicity, cortical vacuolization of adrenal glands and demyelinization of brain/spinal cord without any neurofunctional finding. In males, damage of reproductive organs in the form of testicular degeneration and associated weight changes and impaired spermatology was observed. Based on anaemia observed, a LOAEL of 25/14 mg/kg bw (equal to 320/160 ppm) was achieved in males/females.

In the subchronic oral study in mice (NTP, 1992, protocol similar to OECD TG 408), mortality was observed in males at ≥5000 ppm and in females at ≥2500 ppm. Body weight gain was decreased in both species at concentrations of 1250 ppm (females) or 2500 ppm (males) and higher. Systemic effects consisted of hepato- and nephrotoxicity and myocardial degeneration. The most sensitive effect was necrotic liver damage at all concentrations. A LOAEL of 104/142 mg/kg bw (equal to 630/630 ppm) was noted in males/females.

 


Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: other; urogenital: kidneys; nervous system

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: larynx

Repeated dose toxicity: dermal - systemic effects (target organ) cardiovascular / hematological: other; digestive: liver; urogenital: kidneys; other: skin

Justification for classification or non-classification

DEA is listed on Annex I of Directive 67/548/EEC and classified for repeated dose toxicity after oral exposure (Xn, R48/22). This results in the following classification under the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008: STOT RE 2; H373.