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Description of key information

Oral: LD50 (rat) > 5000 mg/kg bw
Dermal: LD50 (rat) > 2000 mg/kg bw

Key value for chemical safety assessment

Additional information

Within the Vinasses category, data on acute toxicity are only available for one subgroup of Vinasses, e. g. Vinasses, residue of fermentation. However, all Vinasses subgroups share a common origin and are therefore constituted of the same components determining their toxicological properties. Thus, read-across is performed based on a category approach (a detailed justification is attached in IUCLID section 13).

 

Oral

The acute toxicity of Vinasses, residue of fermentation after oral administration to Wistar rats was investigated in a limit test according to OECD guideline 401 under GLP conditions (Daamen, 1992). A group of 10 Wistar rats (5 per sex) were given the undiluted test material by gavage at 5000 mg/kg bw (3.817 mL/kg bw) and observed for a period of 14 days post-administration. The dose level was selected based on the results of a pilot study with pairs of male and female animals given the test material at 1000, 2000 and 5000 mg/bw, in which no abnormalities had been noted during the 7-day observation period.

No mortalities occurred during the study period. Signs of ill health or behavioural changes included piloerection, observed in 3 males and 3 females approximately 2 h after dosing. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Macroscopic post-mortem examination of the surviving animals at termination did not reveal any abnormalities. Therefore, the oral LD50 for male and female rats was considered to be greater than 5000 mg/kg bw.

Three further reliable studies are available, in which the acute oral toxicity of Vinasses, residue of fermentation was studied in rats administered the test material by gavage at 5000 mg/kg bw (Clouzeau, 1992; Lheritier, 1990; van Eeken and Aboulwafa-van Velthoven, 1983). Since no mortalities occurred in any of the three studies. the oral LD50 for male and female rats was determined to be greater than 5000 mg/kg bw. Moreover, no clinical signs and no abnormalities in body weight (gain) were observed during the 14-day observation period and macroscopic examinations at termination revealed no treatment-related changes (Clouzeau, 1992; Lheritier, 1990).

In an earlier study, the oral LD50 was reported to be greater than 40000 mg/kg bw in rats administered three different types of Vinasses, residue of fermentation (van Eeken, 1974).

 

Inhalation

This information is not available.

 

Dermal

The acute dermal toxicity of Vinasses, residue of fermentation was tested in accordance with OECD guideline 402 and in compliance with GLP (van Otterdijk, 2010a). The study was performed as a limit test in two groups of Wistar rats (5 males and 5 females) at a dose of 2000 mg/kg bw (1.05 mL/kg bw). The test substance was applied unchanged on the shaved skin of the test animals for 24 h under occlusive conditions. The test animals were observed for 14 days after application, and sacrificed thereafter for gross pathological examinations. No mortalities occurred. Slight clinical signs were observed in 9/10 animals on days 1 and/or 2 and included lethargy, hunched posture, shallow respiration, piloerection, ptosis and/or chromodacryorrhoea. No abnormal changes in body weight (gain) were observed. No abnormalities were found at macroscopic post mortem examination of the animals. According to the results of this study, the dermal LD50 value for male and female rats was greater than 2000 mg/kg bw.

 

Other routes

An acute toxicity study was conducted in rats administered Vinasses, residue of fermentation by intravenous injection (Prinsen, 1994). The study was carried out with three dose levels (500, 750 and 1000 mg/kg bw) using five female albino rats for each dose level and five males for the two high dose levels.

Two males and one female showed dyspnoea and coma, immediately after dosing (750 mg/kg bw) and needed reanimation to survive. Immediately after dosing (1000 mg/kg bw) two males showed dyspnoea and coma and needed reanimation. Within ten minutes after dosing, despite reanimation, one male died. At the same doses of 1000 mg/kg bw four females showed dyspnoea and coma, immediately after dosing and needed reanimation to survive.

At 4 h after dosing 500 mg/kg bw, sluggishness was observed in all females, while a swollen nose was observed at 1 and 4 hours after dosing. At 750 mg/kg bw, immediately after dosing and until 4 h thereafter, sluggishness was observed in all males and females. A swollen nose was observed in males at 1 h after dosing and in females at 1-4 h after dosing. In addition, the males showed swollen legs at 1-4 h after dosing and females piloerection at 1 or 4 h after dosing. Two males and one female showed dyspnoea and coma. At 1000 mg/kg bw, two males showed dyspnoea and coma immediately after dosing. Immediately after dosing and until 4 h thereafter, sluggishness, swollen legs and nose were observed in all males (except one). In addition, the males showed a blue discolouration at 1 h after dosing. One male showed vocalization at 4 h after dosing. In females, sluggishness (at 1 h after dosing), swollen nose (at 1-4 h after dosing) and piloerection (at 4 h after dosing) were observed. One female showed endogenous blue discolouration. Four females showed dyspnoea and coma immediately after dosing (and needed reanimation to survive). During the remainder of the 14-day observation period, no clinical symptoms were observed at any dose.

Generally, all surviving animals gained weight during the 14-day observation period. One male and one female both treated with the 750 mg/kg bw dose level showed a very minor dip in body weight. Macroscopic examination of the animals did not reveal any treatment-related gross alterations at the end of the observation period. The one male that died also did not reveal treatment-related gross alterations.

Based on the study results, the LD50 (i.v.) was determined to be around 1000 mg/kg bw.

In another study, three types of Vinasses, residue of fermentation, were tested for acute toxicity in rats after intraperitoneal injection (van Eeken, 1974). Five days after dosing, the LD50 (i.p.) values were determined to be 7070, 10000 and 11800 mg/kg bw for each of the tested samples, respectively.

Justification for classification or non-classification

The available data on the acute toxicity of the substance are conclusive but not sufficient for classification according to the DSD (67/548/EEC) and CLP (1272/2008/EC) criteria.