Registration Dossier

Administrative data

Description of key information

Acute oral toxicity was assessed in two studies similar to OECD test guideline 401, resulting in a LD50 of 1920 mg/kg body weight in rats and an LD50 between 1940 and 4850 mg/kg body weight in mice.
In the key study for acute inhalative toxicity according to OECD test guideline 403 in rats, the LD50 was determined to be > 6.1 mg/l after a treatment period of 4 hours.
Acute dermal toxicity was assessed in a study similar to OECD test guideline 402, resulting in a LD50 > 4850 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
1 920 mg/kg bw

Additional information

Acute oral toxicity.

In the key study, similar to OECD test guideline 401, acute oral toxicity of 4-methylanisole was assessed in six groups of 5 Sprague-Dawley rats. Rats were treated with a single oral dose in corn oil via gavage at dose levels ranging from 1000-6810 mg/kg body weight (not further specified). Under the conditions of this study, LD50 was found to be 1920 mg/kg body weight for rats (RIFM1971).

In the supportive study, similar to OECD test guideline 401, 10 fasted mice were treated with a single oral dose of unchanged 4-methylanisole via gavage at dose levels of 2 ml/kg bw (2 animals), 5 ml/kg bw (6 animals), 10 ml/kg bw (2 animals) and observed over a period of 7 days for signs of toxicity. Under the conditions of this study, LD50 was defined to be between 2 and 5 ml/kg bw for mice, representing 1940 and 4850 mg/kg bw respectively, (Givaundan MT1971).

Acute inhalative toxicity.

In the key study for acute inhalative toxicity according to OECD test guideline 403, 5 Wistar rats per sex were treated in a whole-body inhalation system using 4-methylanisole at the maximum technically achievable concentration (6.1 mg/l) for 4 hours followed by an observation period of 14 days (BASF13I0143/897023). No mortality occurred during the study period. Accelerated, irregular or intermittent respiration, eyelid closure, salivation, abdominal position, squatting posture, ruffled fur and tremor was observed during treatment, followed by additional findings, i.e. reddish nasal discharge and urine-contaminated fur. A retardation of the body weight gain was detected after the second week of the observation period in comparison to historical control data. No pathologic findings were noted. The LC50 was determined to be > 6.1 mg/l air after a 4 hour exposure.

In the supportive study, an inhalation hazard test similar to OECD test guideline 403, 3 Wistar rats per sex were exposed whole body with a 4-methylanisole vapour saturated atmosphere (6.71 mg/l nominal concentration, not verified analytically) for 7 hours followed by an observation period for 14 days (BASF10I0143/897007). No mortality was observed during the observation period. During exposure, irregular or accelerated respiration and nasal discharge was observed, whereas no abnormalities became evident after the exposure period. No pathologic findings during necropsy were observed. The LC50 was determined to be > 6.71 mg/l air after a 7 hour exposure.

Acute dermal toxicity.

In the key study addressing acute dermal toxicity similar to OECD test guideline 402, 6 New Zealand White rabbits were treated dermally (under occlusion) with 5 ml/kg bw (4850 mg/kg bw respectitvely) 4-methylanisole and followed by an observation period of 14 days (RIFM 1971). No mortality was observed, resulting in an LD50 > 5 ml/kg bw.

Justification for classification or non-classification

Based on the available data, 4-methylanisole is to be classified as harmful if swallowed (R22) and as acute toxic / oral (Category 4) according to the criteria laid down under 67/548/EEC and regulation (EU) 1272/2008.

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