3-methylbut-2-en-1-ol

Endpoint summary

Description of key information

Repeated dose toxicity – oral:  subchronic study; rat, drinking water; OECD TG 408, GLP (BASF52C0274/00099): 
NOAEL (male) = 65.4 mg/kg bw; 
NOAEL (female) = 82.1 mg/kg bw 

Additional information

Oral administration

As key study, a subchronic oral toxicity study with 3-methylbut-2-en-1-ol was conducted under GLP conditions and according to OECD Guideline 408 (BASF52C0274/00099). The scope of examinations was extended to cover also effects on reproductive organs (see also IUCLID chapter 7.8.1). 3-methylbut-2-en-1-ol was administered to groups of 10 male and 10 female Wistar rats in the drinking water at concentrations of 0, 200, 1000 and 5000 ppm for three months. These concentrations corresponded to dosages of 14.4 and 21.0 mg/kg bw/day, 65.4 and 82.1 mg/kg bw/day or 243.8 and 307.2 mg/kg bw/day for males and females.

Food consumption, water consumption and body weights were determined weekly. The animals were examined for clinical signs of toxicity or mortality at least once a day. Detailed clinical examinations in an open field were conducted prior to the start of the administration period and weekly thereafter. A functional observational battery (FOB) and measurement of motor activity was carried out towards the end of the administration period. Ophthalmological examinations were carried out prior to the start and towards the end of the administration period. Clinical-chemical and hematological examinations as well as urinalyses and investigation of sperm parameters were carried out towards the end of the administration period. All animals were assessed by gross pathology, followed by histopathological examinations.

Substance related effects were seen in animals of the high and mid dose group. Food consumption was significantly decreased in both sexes of the high dose group (up to 18.2 % below control in males and 21 % in females) and in males of the mid dose group (up to 9.4 % below control). Water consumption was significantly reduced in both sexes of the high dose group during the entire study (up to 49.9 % (males) and 47.8 % (females) below control) and the mid dose group (up to 25.1 (males) and 28.9 % (females) below control) which can be most likely be explained by the intensive taste and odor of the test substance solutions. Body weight was significantly impaired at the high dose (12.2 % (males) and 8.8 % (females) below control) on day 91. A significantly decreased body weight change was seen in the same dose group (20.4 % (males) and 19.2 % (females) below control) on day 91.

There were no treatment related significant changes in clinical examinations, opthalmoscopy, functional observational battery, clinical chemistry and hematology.

 

Urinalysis revealed decreased amounts of urine with increased specific gravity in the high dose males and females. These findings are assessed as being compound-related and are mainly caused by the reduced water consumption. Changes of mean organ weight parameters observed, were regarded to be the consequence of the significantly decreased body weights rather than a specific treatment-related effect . Pathology findings did not indicate treatment-related gross lesions or microscopic findings in any of the organs investigated.

As reduction in food and water consumption resulted in significant decrease of body weight only at the high dose level, the no observed adverse effect level (NOAEL) was assessed to be 1000 ppm (65.4 mg/kg bw/day in males, 82.1 mg/kg bw/day in females). The lowest observed adverse effect level (LOAEL) was 5000 ppm (243.8 and 307.2 mg/kg bw/day for males and females). No effects on reproductive organs or sperm parameters were observed.

 

As supportive evidence, subacute range-finding studies were performed with rats administrating the test substance to 3 rats per sex and group dor 14 days either via drinking water or via gavage (BASF12S0274/00063, BASF12S0274/00028). In the drinking water studies, comparable patterns of effects were observed as described in the subchronic key study. In the subacute gavage study with a limited set of endpoints assessed, no effects were observed in doses up to 750 mg/kg bw, indicating that the adverse effects described above might depend on the type of application.

 

Dermal administration

There are no data available.

 

Inhalation

There are no data available.

 

 

Conclusion

There was no substance-specific organotoxicity detectable after 90 day repeated oral administration of 3-methylbut-2-en-1-ol to rats. As treatment-related findings, reduction in food and water consumption were observed which was accompanied by a decrease in body weight and body weight gain. A NOAEL has been set at 65.4 mg/kg bw/day for males and 82.1 mg/kg bw/day for females.

Justification for classification or non-classification

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