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Description of key information

Acute oral toxicity: RA to N,N-dimethyldecanamide (CAS 14433-76-2)  LD50> 2000 mg/kg bw  (Cognis 1997; M. Hoyer) underlined by RA to Mixture of dimethylamides (CAS 67359-57-3) LD50> 2000 mg/kg bw  (Clariant 1993, Hoffmann)
Acute dermal toxicity (rat): RA to N,N-dimethyldecanamide (CAS 14433-76-2) LD50>5000 mg/kg bw (C10, Cognis 1997; M. Hoyer) underlined by LD50 (male): > 2000 mg/kg bw (BASF SE 2012) (C8)
Acute inhalation toxicity: RA to Mixture of dimethylamides (CAS 67359-57-3), rat LC50 >3551 mg/m3 (Bayer 1991; J. Pauluhn) (C8/10)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no 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
Quality of whole database:
highest technical attainable concentration tested

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Additional information

Justification for grouping of substances and read-across

There are no reliable data available for the acute toxicity N,N-Dimethyldodecan-amide (CAS 3007-53-2). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substance listed below are selected as reference substances for hazard assessment.

 

Overview of acute toxicity

 

Target Substance

Source Substance 1

Source Substance 2

Source Substance 3

 

N,N-Dimethyldodecan-amide

N,N-Dimethyldecan-amide

N,N-Dimethyloctanamide

Mixture of N,N-Dimethyloctanamide and N,N-Dimethyldecanamide

CAS

3007-53-2

14433-76-2

1118-92-9

67359-57-3

Acute oral toxicity

RA to 14433-76-2

OECD 420: LD50 > 2000 mg/kg bw, rat, some effects observed in sighting study at 5000 mg/kg

(BASF, 1997)

RA to 67359-57-3

OECD 401, rat LD50>2000mg/kg bw, one animal died, (Clariant 1993)

40 CFR, rat, LD50=1770 mg/kg bw (Stepan 1998)

Acute inhalation toxicity

RA to 67359-57-3

RA to 67359-57-3

RA to 67359-57-3

OECD 403, LC50 > 3550.7 mg/l/4h (max attainable conc.), respiratory irritation observed at highest dose (Bayer, 1991)

Acute dermal toxicity

RA to 14433-76-2

OECD 402, LD50 > 5000 mg/kg bw (BASF, 1997)

OECD 402, rat, LD50 > 2000 mg/kg bw, systemic and local effects at highest dose observed (BASF 2012)

OECD 402, rat, LD50 > 400 < 2000 mg/kg bw (females), > 2000 mg/kg (males) (Bayer 1995)

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for N,N-Dimethyldodecan-amide (CAS 3007-53-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Acute oral toxicity:

N,N-dimethyldecanamide (CAS 14433-76-2)

The acute oral toxicity in rats was determined according to OECD Guideline No. 420 (Cognis 1997; M. Hoyer).The study was initiated with a sighting study, in which one female rat was given N,N-Dimethyldecan-1 -amide in a 2000 mg/kg bw dose. Slight signs of toxicity were observed in this rat, therefore another female rat was given N,N-Dimethyldecan-1-amide in a 5000 mg/kg bw dose. This animal died under severe signs of toxicity on day 2.On the basis of the results from the sighting study it was decided to carry out the main study with one group consisting of five male and five female rats given a dose of 2000 mg/kg bw.All animals in the main study survived the treatment and showed slight signs of toxicity (clinical signs: pinched abdomen, piloerection). Gross necropsy revealed a gas filled intestine for three animals, distended vessel of testes in one animal, light margin of liver in two animals.

The oral LD50 of N,N-Dimethyldecan-1-amide in rats was found to be above 2000 mg/kg bw.

 

Mixture of dimethylamides (CAS 67359-57-3)

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.

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 rate the clariant study as more reliable.

 

Acute inhalation toxicity

Mixture of dimethylamides (CAS 67359-57-3)

A study for acute inhalation toxicity was conducted with "confidential substance name" 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

 

Acute dermal toxicity:

N,N-dimethyldecanamide (CAS 14433-76-2) 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. Mixture of dimethylamides (CAS 67359-57-3) 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.

 

Additional the acute dermal toxicity a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide 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.

 

N,N-Dimethyloctanamide (CAS 3007-53-2)

In a 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.

 

In summary, the available data indicate a decrease in toxicity towards longer chain length. Therefore, the short chain length or chain length mixture can be assumed to represent a worst-case assumption for the toxicological behavior of the target substance and an overestimation concerning toxicity can be anticipated, when transferring results from source to target substance. However, as this is not in conflict with a precaution principle and may follow a trend with increase molecular mass, the read across is confirmed via acute toxicity data.

If valid information from the close homologue N,N-dimethyldecanamide is available this is assumed to be most adequate represent the behavior of N,N-Dimethyldodecan-amide and is therefore used to describe the toxicological behavior of the target substance. If no valid information from this close homologue (N,N-dimethyldecanamide) is available the Mixture of dimethylamides (CAS 67359-57-3) is used as information source followed by the pure N,N-dimethyloctanamid.

Hence, taking reliability, adequacy and availability into account the following information on acute toxicity is used for assessment:

Acute oral toxicity: RA to N,N-dimethyldecanamide (CAS 14433-76-2) LD50> 2000 mg/kg bw (Cognis 1997; M. Hoyer) underlined by RA toMixture of dimethylamides (CAS 67359-57-3) LD50> 2000 mg/kg bw (Clariant 1993, Hoffmann)

Acute dermal toxicity (rat): RA to N,N-dimethyldecanamide (CAS 14433-76-2)LD50>5000 mg/kg bw (C10, Cognis 1997; M. Hoyer) underlined by LD50 (male): > 2000 mg/kg bw (BASF SE 2012) (C8)

and

Acute inhalation toxicity:RA toMixture of dimethylamides (CAS 67359-57-3), rat LC50 >3551 mg/m3 (Bayer 1991; J. Pauluhn) (C8/10)

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 therefore N,N-Dimethyldodecan-amide 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-dimethyldecanamide was found to be above 5000 or 2000 mg/kg bw following 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).

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

GHS: no classification

DSD: no classification