Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral, LD50 > 2,000 mg/kg bw, rat (NTP, 1983)
Oral, LD50 > 1,500 - <3,000 mg/kg bw, mouse (NTP, 1983)
Inhalation, LC50 > 2.6 mg/L, rat (Clark, 1988)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
2 600 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The acute toxicity of eugenol was evaluated in 2 key oral (gavage) studies and a key inhalational study. The oral studies were compared to the OECD Guideline No. 423 while the inhalation study was compared to the OECD Guideline No. 403. None of the studies were compliant with Good Laboratory Practices (GLP).

In one oral (gavage) study, eugenol was administered at dose levels of 180, 375, 750, 1,500, or 3,000 mg/kg/body weight to groups of 5 male and 5 female B6C3F1 mice and in the other study at 150, 250, 500, 1,000, or 2,000 mg/kg body weight to groups of 5 male and 5 female F344/N rats. Animals were observed over a 15-day period (NTP, 1983). In mice, mortality was seen in 1 male in the 750 mg/kg body weight dose group and in 2 males and 5 females in the 3,000 mg/kg body weight dose group. In rats, mortality was seen in 1 female in the 2,000 mg/kg body weight dose group. No other toxicological effects were reported by the authors for either study. The oral median LD50 was reported to be >1,500 mg/kg body weight for male and female mice and >2,000 mg/kg body weight for male and female rats.

 

The acute toxicity of inhaled eugenol was assessed in groups of 5 male and 5 female Sprague-Dawley rats; the animals were exposed to eugenol in a submicron aerosol formulation at concentrations of 0.77, 1.37, or 2.58 mg/L for 4 hours and were observed over a 14-day period (Clark, 1988). Immediately following exposure, all high-dose rats were lethargic and many mid- and high-dose rats had wet snouts and red-brown staining of their fur (actual numbers of animals with these findings were not reported). Low dose rats and control animals were normal in appearance and behaviour. Macroscopic pathological changes included dark red, slightly raised areas in the lungs of 2 animals each in the low- and high-dose groups. The 4-hour inhalation LD50 was reported to be >2.6 mg/L in both male and female rats.

 

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 2000 mg/kg bw.

Acute toxicity via Dermal route:

No data was available. However, the substance is not classified as skin irritating and acuted oral toxicity is greater than 2000 mg/kg bw. Moreover, considering that the skin is a physical barrier for the substance, acute toxicity by dermal is not expected.

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008.

Acute toxicity (Inhalation):

Based on the available data, the substance is not classified according to the Regulation (EC) No. 1272/2008.

 

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

 

Specific target organ toxicity: single exposure (Dermal):

No data was available. However, the registered substance is not a skin irritant that could facilitate the penetration of the substance across the skin. Moreover, no narcotic effects were observed in the acute oral toxicity study and the skin is a physical barrier for the substance. Therefore the criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not expected.

 

Specific target organ toxicity: single exposure (Inhalation):

A rat acute inhalative 4-hour(mist) is available. No respiratory tract irritation or narcotic effect was observed.

No Aspiration hazard symptoms were observed from available studies by oral route. However, as the substance may contain an impurity self-classified with H304, and considering the viscosity of the substance is expected to lie below the threshold of 20.5 mm2/s (measured dynamic viscosity of 8.39 mPa.s at 25°C, corresponding to kinematic viscosity of 7.9 mm2/s for a density of 1.065, and anticipated to be lower at 40°C) the classification is proposed to apply to the quality grade with high impurity content (>10%).

Categories Display