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Description of key information

Rat, oral 28 day study: NOAEL (male) = 300 mg/kg bw; NOAEL (female) = 1000 mg/kg bw (GLP, OECD 407, BASF SE, 2010)

Key value for chemical safety assessment

Additional information

There is a reliable study available to assess the repeated dose toxicity after 28days oral administration of the test substance.

The 28 day repeated dose study with rats was performed according to the OECD guideline 407 following GLP requirements (BASF SE, 2010). Oxooel 13 was administered by gavage to groups of 5 male and 5 female Wistar rats at dose levels of 0 mg/kg body weight/day (olive oil as vehicle control), 100 mg/kg bw/d, 300 mg/kg bw/d or 1000 mg/kg bw/d over a period of 4 weeks.

Food consumption and body weights were determined weekly. The rats were examined for signs of toxicity or mortality at least once a day. In addition, the rats were daily examined for any clinically abnormal signs before and within 2 hours as well as within 5 hours after treatment. Moreover, detailed clinical examinations in an open field were conducted prior to the start of the administration period and weekly thereafter. Beside this, a functional observational battery (FOB) as well as measurement of motor activity (MA) was carried out at the end of the administration period.

Clinicochemical and hematological examinations as well as urinalyses were performed towards the end of the administration period. After the administration period all rats were sacrificed and assessed by gross pathology, followed by histopathological examinations.

The following test substance-related, relevant findings were noted:

 

Test group 1000 mg/kg bw/d:

Clinical Examinations

• Salivation after treatment was observed in all male and 4 female animals from day 3 onwards on several days.

Clinical Pathology

• Not significantly decreased total white blood cell counts and absolute lymphocyte counts were measured in male rats.

• Increased relative neutrophil counts were measured in male rats.

Pathology

• Increased liver weights in females that were assessed as adaptive and non-adverse.

• Slightly increased eosinophilic droplets were observed in the cytoplasm of proximal tubules in all males that was assessed as non-adverse.

 

Test group 300 mg/kg bw/d:

Clinical Examinations

• Salivation after treatment was observed in 1 male on study day 27 and in 1 male on study day 28.

• Salivation after treatment was observed in 2 females on study days 5 and 6.

Clinical Pathology

• No treatment-related, adverse findings were observed.

Pathology

• Increased liver weights in females that were assessed as adaptive and non-adverse.

 

Test group 100 mg/kg bw/d:

Clinical Examinations

• Salivation after treatment was observed in 1 male on day 25.

Clinical Pathology

• No treatment-related, adverse findings were observed.

Pathology

• No treatment-related, adverse findings were observed.

 

In conclusion, with regard to hematological parameters the oral administration of Oxooel 13 by gavage over a period of 4 weeks revealed signs of toxicity in male Wistar rats at dose levels of 1000 mg/kg bw/d but none in female Wistar rats. Salivation was considered to be related to either the bad taste of the test substance or local affection of the upper digestive tract. This finding was not considered to be an adverse and toxicologically relevant effect.

Therefore, under the conditions of the present study, the no observed adverse effect level (NOAEL) was 300 mg/kg bw/d for male and 1000 mg/kg bw/d for female Wistar rats.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC):

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for repeated dose toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for repeated dose toxicity

under Regulation (EC) No. 1272/2008.