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Description of key information

- Acute oral toxicity studies revealed a LD50 > 2000 mg/ kg bw and no mortality was observed after oral exposure with Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate

(BASF 2003; 10A0636/021054 and supporting study BASF 2000; 10A0408/991123). 

 - The key study for acute inhalative toxicity study revealed a LC0 = 5.22 mg/L and no mortality was observed after 4h of exposure with Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate (BASF SE 2017; 13I0636/02X067)

Based on the absence of acute oral and inhalative toxicity and the low dermal penetration rate, no acute dermal toxicity is to be expected.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

Two acute oral toxicity studies were conducted with Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate. Both studies (BASF 2003; 10A0636/021054 and BASF 2000; 10A0408/991123) were done by an Acute Toxic Class Method in a limit study with a single dose of 2000 mg/kg body weight of test substance (vehicle: olive oil in the key study and 0.5% tylose in bidest water in the additional study). The test substance was administered by gavage to 6 Wistar rats- 3 rats in each step (females in the key study and males and females in the additional study) which were observed for 14 days. The studies were conducted according to OECD 423 and GLP. The test substance of the key study represents the currently manufactured product.

Both studies showed identical results:

No mortality occurred, no clinical toxicity signs were observed. The mean body weights of the animals was not affected throughout the study period and no macroscopic pathologic abnormalities were noted at necroscopy. Thus, Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate was found to be practically non-toxic and the LD50 value was determined as:

Oral LD50 females > 2000 mg/kg bw (key study)

Oral LD50 males, females >2000 mg/kg bw (supporting study)

 

Acute inhalative toxicity

In the chosen key study for acute inhalative toxicity acc. to OECD 403 and GLP, rats were exposed in a single exposure via the inhalation (nose-only exposure) route to a dust aerosol of Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate. After establishing the desired generation procedures during the pre-test trials, 10 healthy rats (5/sex) were exposed to the test atmosphere for 4 hours. Chamber concentration and particle size distributions of the test atmosphere were determined periodically during the exposure period. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days following exposure. Body weights were recorded and necropsies were performed on all animals at terminal sacrifice.

The gravimetric chamber concentration was 5.22 mg/L and the average mass median aerodynamic diameter was estimated to be 2.52 μm with an average geometric standard deviation of 2.34. All animals survived exposure to the test atmosphere and gained body weight during the study. Following exposure, all rats exhibited irregular respiration. However, all animals recovered by Day 2 and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the end of the 14-day observation period.

Under the conditions of this study, the single exposure acute inhalation LC50 of Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate is greater than 5.22 mg/L in male and female rats.

 

Acute dermal toxicity

In light of the accumulated study results on the test substance from acute oral toxicity studies and skin absorption studies, an acute toxicity study via the dermal route is scientifically not required and is not in line with animal welfare requirements. The reasons for the present data waiving is based on the following study results and considerations:   

- Acute oral toxicity studies revealed a LD50 > 2000 mg/ kg bw and no mortality was observed after oral exposure with Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate (BASF 2003; 10A0636/021054 and supporting study BASF 2000; 10A0408/991123). 

 - The key study for acute inhalative toxicity study revealed a LC0 = 5.22 mg/L and no mortality was observed after 4h of exposure with Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate (BASF SE 2017; 13I0636/02X067).

 - Result of the dermal absorption from an in-vivo study in male rats of 3% (key-BASFAG01B0496/046023, in IUCLID section 7.1.2). 

Based on the low bioavailability after dermal application (compared to the oral application) and the absence of mortality after oral or inhalative administration at limit doses, no acute dermal toxicity is to be expected. Therefore, an acute dermal toxicity study in rats is not scientifically required.

Justification for classification or non-classification

The present data on acute oral toxicity do not fulfill the criteria laid down in 67/548/EEC and 1272/2008/EEC, and therefore, a non-classification is warranted.