N,N-dimethyloctanamide

Endpoint summary

Description of key information

Information drawn partly from experiments with a mixture of dimethylamides (mainly C8/C10):
Acute oral toxicity (rat): LD50> 2000 mg/kg bw  (Clariant 1993, Hoffmann) (C8/10)
Acute dermal toxicity (rat): LD50 (male): > 2000 mg/kg bw  (BASF SE 2012) (C8)
Acute inhalation toxicity (rat): >3551 mg/m3 (Bayer 1991; J. Pauluhn) (C8/10)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

3 551 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Valid data is available for the assessment of acute oral, acute dermal and acute inhalation toxicity. Toxicity test were performed with a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide). Due to the fact that a high amount in the mixture was N,N-dimethyloctanamide and the rest of the mixture are homologues with a lower and higher molecular weight which can be assumed to have a similar toxicological behaviour it is concluded that the mixture has nearly an similar toxicological behaviour like pure N,N-dimethyloctanamide.

Acute oral toxicity:

Studies according OECD guidelines:

The acute oral toxicity of a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide in rats was determined according to OECD Guideline 401 under GLP (Clariant 1993, Hoffmann). Therefore 2000mg/kg bw of the test substance was applied via gavage to five male and female wistar rats in a limit test. One female died in the 2000 mg/kg on application day. Additional to unspecific symptoms adverse effects on motion sequence, respiration and reflexes were observed. The animal showed also abdominal and letaral position, lid narrows, epiphora, reduced surface temperature and signs of stupor. On day 7 after application all surviving animals were free of symptoms. The body weight gain was not affected. In result a Dosis letalis media (LD50) above 2000mg/kg bodyweight can be drawn from the experiment. Necropsy of died animal shows liver colouring and lobular pattern and diffuse redness of the gastric mucosa. Necropsy of the survived animals reveals no macroscopic visible alteration.

Studies according to other guidelines

In another study the acute oral toxicity of a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide) was evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act (40 CFR), and the Toxic Substances Control Act (40 CFR) (Stepan 1998, J.J. Kreuzmann). Therefore female and male sprague dawley rats received 5.0 g/kg, 2.5 g/kg, 1.25 g/kg and 0.625 g/kg via gavage (five animals for the highest dosage and two animals per sex for all other dosages). At the dose level of 5.0 g/kg ten deaths occurred between days 0 and 1 of the observation period. At the dose level of 2.5 g/kg three deaths occurred between days 0 and 1 of the observation period. At the dose level of 1.25 g/kg one death occurred on day 2 of the observation period. At the dose level of 0.625 g/kg no deaths occurred during the observation period. The gross necropsy findings in the animals that died during the observation period were those generally seen in agonal animals. The acute oral LD was value was estimated to be 1.77 g/kg in male and female Sprague-Dawley rats.

According to the registrant, the study must be rated less of relevance as there were minor information missing in the report and the study was conducted according to a less suitable protocol , which is not perfect suitable to derive classification. If linear regression is used for calculation of LD50 a LD50 of 1875 -2344mg/kg can be calculated. The revised report calculates a LD 50 of 1770 mg/kg with 95% confidence limits of 1020 – 3080 mg/kg bw. As these calculated values are near to the classification limit and the study was not suitable to distinguish between 1800, 2000mg/kg and a better study is available the Registrant decides to rate this study lower in relevance and to refer to the more suitable conducted study from Clariant (Clariant 1993, Hoffmann).

 

Acute dermal toxicity:

A study for acute dermal toxicity in male and female rats was conducted with a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide) under 24-hour occlusion conditions. The method used complied with the OECD - Guideline No. 402 and was performed under GLP (Bayer 1995, W. Bomann). Five wistar rats / sex received dosages of 50, 200, 2000 and 5000 mg/kg b.w. (male) and 50, 200, 400 and 2000 mg/kg b.w. (female) via dermal application. The results are summarized as follows:

LD50: rat (male): approx. 2000 mg/kg b.w.

rat (female): >400 - <2000 mg/kg b.w.

The main clinical signs observed were as following: piloerection, decreased motility, decreased reactivity, poor resp. no reflexes, spastic gait and labored breathing. The clinical signs occurred 30 minutes after administration and were reversible within the post-treatment observation period. A dose of 200 mg/kg b.w. was a no-effect level for the systemic effects.

The following main local effects were observed: reddening, dark color, incrustation, squamation and formation of scab. The skin effects lasted from day 2 until the end of the study. A dose of 50 mg/kg b.w. resp. 0.6 mg/cm2 was a threshold level for the local effects. Linear regression between 400 and 2000 mg/kg bw of female results points to a LD 50 near to 800 mg/kg bw (important for GHS label)

In the lethal dose range in males resp. at all doses in females transient reductions of body weights were observed, which were reversible until the end of the study. In animals which died during the observation period, a brownish- red content in the urinary bladder and discoloration of the liver was observed. At the end of the observation period no treatment-related gross findings were evident.Accordingly, the test substance was of moderate toxicity to female rats and of low toxicity to male rats following acute dermal application.

In a more adequate acute dermal toxicity study (Limit Test), according to OECD guideline 402, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of Octanamide, N,N-dimethyl- to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.The following test item-related clinical observations were recorded during the course of the study:

No mortality occurred, Impaired general state in seven animals, Poor general state in one animals,

Dyspnoea in six animals, Piloerection in six animals, Exsiccosis in two animals,Exophthalmos in one animal, Lacrimation in one animal, Lateral position in one animal and Diarrhea in one animal.

The following test item-related local effects were recorded during the course of the study: Slight to well-defined erythema (grade 1 to 2)

The mean body weights of the male and female animals increased as expected in four animals in each group but distinctly decreased in one male and female animal during the observation period. Macroscopic pathological findings in the animals examined on the last day of observation (findings in the male and female animal, which showed weight reduction):

o  Dark red discoloration of the liver

o  No content in stomach

o  Red discoloration of the glandular stomach

o  Red discoloration of the small intestine and its content

 There were no macroscopic pathological findings in the other 4 males and females. Accordingly, the acute dermal median lethal dose (LD₅₀) was determined to be LD₅₀, dermal, rat > 2000 mg/kg bw.

Additonally the acute dermal toxicity of N,N-dimethyldecanamid in rats was determined according OECD Guideline No. 402.The study was performed as a limit test with 10 Wistar rats (five males and five females). The rats were exposed to a single dermal dose of 5000 mg/kg bw for 24 hours followed by an observation period of 14 days. During the study clinical signs of reaction to the treatment were recorded daily. Body weight was recorded once a week. After the two week observation period the animals were killed and subjected to a gross necropsy examination. All animals in the main study survived the treatment and showed very slight signs of toxicity. Some females show stagnation in body weight increase all other rats had normal body weight gain. Clinical signs were only piloerections and post mortem inspection revealed no abnormalities. The dermal LD50 of N,N-dimethyldecanamidin rats was found to be above 5000 mg/kg bw.

As dosages in male and female rats were different in the Bayer study (Bayer 1995, W. Bomann)

and linear regression with less datapoints were done, the result of the Bayer study is found to be discussable. In connection with the low oral toxcity the result received with female rats is not understandable. Furthermore the Bayer study was conducted with a C8/10 mixture containing also small amounts of C6 and C12 which may also explain the the difference to results of pure C8 and pure C10 (both are acute dermal not classified, please refer to already registred document for CAS 14433-76-2). Nevertheless in a recent performed study dimethyloctaneamid did not show acute dermal toxicity (BASF SE 2012). Therefore the study from Bayer was rated as less relevant for judiging these endpoint for C8 FADMA and the BASF study is rated as more adequat and therefore used for assessment and classification.

Acute inhalation toxicity (mixture of dimethylamides):

Acute inhalation toxicity:

A study for acute inhalation toxicity was conducted with a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide) in accordance with OECD Guideline No. 403 (Bayer 1991, J. Pauluhn). Therefore 5 SPF-bred Wistar rats were exposed (head/nose only) to 118.5; 586.4; 2007.6 and 3550.7 mg/m3 (analytical determined).Rats subjected to a concentration of 119 mg/m3 air tolerated the exposure without signs occurring. Rats exposed to 586 mg/m3 air exhibited a transient reddening of the nose on the day of exposure and reduced motility. Rats subjected to the max. tested concentration (3551 mg/m3 air; nebulisation of the undiluted test article) exhibited persistent signs causally linked to an irritation of the respiratory tract (slower breathing, serous nasal discharge, dyspnea, stridor, hypothermia). 3551 mg/m3 air was the range at which mortality started for male rats (1 of 5 died). The results of this study show that the respirable test article aerosol had a relatively low acute inhalation toxicity in the rat. The acute potential hazard of the respiratory tract is attributed to the potency of the test substance aerosol to act as a mucosa irritant.LC50 inhalation (aerosol) Rat (exposure: 4 h) > 3551 mg/m3 air.

It must also be noted that such a high concentration of 3551 mg/m3 (analytically determined) is created by a nominal concentration of 50000 mg/m3

 

 

Key study assignment:

 

As there is only one reliable and relevant study available for inhalation toxicity, these studies has been used as key study.

For acute oral toxicity there are two studies available with a comparable mixture. 

According to the registrant, the study from Stepan (Stepan 1998, J.J. Kreuzmann) must be rated less of relevance as there were minor information missing in the report and the study was conducted according to a less suitable protocol, which is not perfect suitable to derive classification. Linear regression results vary if the LD50 is calculated based on results of this studies depending on the calculation method and confidence limits used. In result an LD 50 near to the classification limit could be derived and as the study was not suitable to distinguish between 1800, 2000mg/kg and a better study is available the Registrant decides to rate this study lower in relevance and to refer to the more suitable conducted study (Clariant 1993, Hoffmann) to decide about acute oral toxicity.

For acute dermal toxicity there is one study available conducted with the pure N,N-Dimethyloctaneamide. As this study represents morelikely the registred substance this study is rated as key study.

Justification for selection of acute toxicity – oral endpoint
Most adequat reliable result, see discussion.

Justification for selection of acute toxicity – inhalation endpoint
Most adequat reliable result, see discussion.

Justification for selection of acute toxicity – dermal endpoint
Most adequat reliable result, see discussion.

Justification for classification or non-classification

The available data for mixtures containing large amounts of N,N-dimethyldecanamide as well as shorter and longer homologues indicate a low potential for acute toxicity.

The available study indicates an oral LD50> 2000 mg/kg bw (Clariant 1993, Hoffmann) for male and female rats. Therefore the mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide has not classified for acute oral toxicity according to GHS (Regulation (EU) 1272/2008) and also not classified according to EU-criteria DSD (67/548/EEC).

As the LD50 (rat) for acute dermal toxicity of N,N-dimethyloctaneamide was found to be above 2000 mg/kg bw for male rats and female rats (BASF 2012), the substance has not to be classified as acute dermal toxic according to GHS (Regulation (EU)

As an acute inhalation toxicity test with a mixture of dimethylamides (main components N,N-dimethyloctanamide, N,N-dimethyldecanamide) reveals only one death in the highest administered concentration of 3551 mg/m³air, which reflexes the maximum attainable concentration (due to physical properties; nominal concentration 50000 mg/m3), the mixture has to not to be classified for acute inhalation toxicity according to GHS (Regulation (EU) 1272/2008) and EU-criteria DSD (67/548/EEC).

Based on the fact that a high amount in the mixture was N,N-dimethyloctanamide and the rest of the mixture are homologues with a lower and higher molecular weight which can be assumed to have a similar toxicological behaviour it is concluded that the mixture has nearly an similar toxicological behaviour like pure N,N-dimethyloctanamide. In result N,N-dimethyloctanamide is also identically labeled.

Derived labelling for acute oral, dermal toxicity and inhalation toxicity (N,N-dimethyloctanamide):

GHS: no classification

DSD: no classification