Registration Dossier

Administrative data

Description of key information

Oral:
Dog subchronic (13 weeks; gavage; mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide) NOAEL (systemic) = 200mg/kg bw/d; NOEL (local) = 40mg/kg bw/d
Dermal:
No data available
Inhaltive:
No reliable relevant studies available.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subchronic
Species:
dog

Additional information

Studies investigating the toxic potential of a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide) are available. Due to the fact that a high amount in the mixture was N,N-dimethyl-decanamide and the rest of the mixture are homologues with a lower and higher molecular weight which can be assumed to have an similar toxicological behaviour it is concluded that also pure N,N-dimethyldecanamide has an similar behaviour than the mixture.

In conclusion there are valid data available to assess the subacute/subchronic toxicity of N,N-dimethyldecaneamide.

Oral:

To assess the subchronic toxicity of a N,N-dimethylamide mixture a subchronic dog study according to OECD Guideline No. 409 was performed (Bayer 2000, J. Ruf). Therefore Groups of 4 male and 4 female beagle dogs per dosage were treated once daily by gavage over a period of 13 weeks with following daily oral doses: 0 mg/kg bw; Group I : 40 mg/kg bw; Group II : 200 mg/kg bw; Group III : 1000 mg/kg bw From the second day of the study onwards, 1000 mg/kg were reduced to 800 mg/kg, and from the 4th day of the study onwards, 800 mg/kg were reduced to 500 mg/kg due to a markedly reduced health status of some group III-animals. The following result was given in the official report: “Tests of the reflexes, body temperatures, pulse rates, blood pressure, and heart rates showed no changes up to and including group III. The same holds true for the electrocardiograms . The nutritional state, feed intake, and body weight gain also yielded no adverse effects up to and including group III. Clinical observations evidenced repeated vomiting and salivation from group II upwards. Additional effects in group III consisted of uncoordinated movements, nasal discharge, lateral/prone position, and trembling. All these effects from group II upwards are considered to be due to treatment with the test compound. Animal no. B 915/group III had to be sacrificed on day 3 of the study showing lateral position, flat breathing, and bloody faeces before sacrificing, and animal no. B 944/group III died in week 7 of the study exhibiting lateral position, bloody nasal and oral discharge before death. Due to the lung findings observed in the histopathological investigations, these two events might be associated with an unintentional intratracheal application. Ophthalmoscopy showed a lens cataract in one animal of group III. This effect is seen to be treatment-related. Haematology and Differential blood counting showed no changes up to and including group III. Clinical chemistry evidenced a substance-related elevation of APh-values in group III. Increased N-Demethylase values from group II upwards and increased Cytochrome P450-values in group III are seen as treatment-related effects giving evidence for an increased metabolic activity in the liver. In this context the increased liver weights in males of group III are also considered to be treatment-related. Urinalyses showed no changes up to and including group III. Necropsy and histopathological examination did not reveal toxicologically relevant effects up to and including group III. Besides increased liver weights in males of group III (see above), no changes in organ weights were detected up to and including group III.” The author followed that based on the reported effects it can be concluded that 40 mg/kg test substance administered orally by gavages to beagle dogs daily over a period of 13 weeks were tolerated without adverse effects.

In contrast to this conclusion the applicant assessed the effects observed as follow: The NOEL at 40 mg/kg bw/d (0.4%) reported is based on local effects caused by oral application of the test substance at irritating concentrations (≥2%). At 200 mg/kg bw/d clinical chemistry revealed only slightly increased N-DEM values in the absence of any other finding. The increase of this parameter is an indication for a minimal liver enzyme induction but not for an adverse effect. Therefore the NOAEL (systemic) is established at 200 mg/kg bw/d.

Dermal:

No data available.

Inhalative:

No relevant reliable data available.

Key study assignment:

Oral:

There is one 13 weeks studies available which was assessed to be relevant and reliable. Therefore this study is used as key study (Bayer 2000, J. Ruf).

Dermal:

No valid studies are available.

Inhalation:

No relevant reliable study is available.

 

 

 

 

 

 

 

 

Justification for classification or non-classification

There are currently no data available leading to a classification of N,N-dimethyldecanamide for its repeated oral or inhalation toxicity.

According to GHS (Regulation (EU) 1272/2008) the following criteria must be fullfilled:"3.9.2.1. Substances are classified as specific target organ toxicants...... 3.9.2.9.6. Thus classification in Category 1 is applicable, when significant toxic effects observed in a 90-day repeated dose study conducted in experimental animals are seen to occur at or below the guidance values (C).....

Category 1 classification: oral: C ≤ 10 mg/kg body weight/day

Category 2 classification: oral: 10 < C ≤ 100 mg/kg body weight/day

According to EU-criteria DSD (67/548/EEC) the following criteria must be fulfilled for the classification R48 Danger of serious damage to health by prolonged exposure “... Substances and preparations are classified at least as harmful when these effects are observed at levels of the order of (guide values): oral, rat ≤ 50 mg/kg body weight/day..."

As the lowest determined oral NOAEL (systemic) was higher than 100mg/kg body weight/day and lower values only led to local effect the substance has not to be classified derived for the oral repeated dose studies.

Labelling repeated dose toxicity:

GHS: no classification

DSD: no classification