Ammonium N-methyl-N-(1-oxododecyl)glycinate

Endpoint summary

Description of key information

Oral (OECD 420), rat: LD50 > 2000 mg/kg bw

Inhalation: Data waiving as studies for two other routes, i.e. oral and dermal, are provided.

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Sep - 07 Oct 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 4166310

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature

Species:

rat

Strain:

other: Wistar rats (Shoe:WIST)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: DIMED Schönwalde GmbH, Schönwalde, Germany
- Weight at study initiation: 136 - 141 g
- Housing: the rats were kept in transparent polycarbonate cages (Macrolone type III) with two or three in each cage. Bedding was pinewood sawdust “Lignocel-Fasern”.
- Diet: pelleted complete rodent diet Altromin 1314, (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water acidified with hydrochloric acid, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 Sep 2004 To: 07 Oct 2004

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

1 female (sighting study), 4 females (main study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was observed for mortality and clinical signs 30 min, 2, 4 and 6 h after the administration and thereafter daily for a period of 14 consecutive days. Body weights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: All animals showed a hunched posture and piloerection 30 min, 2 and 4 h after the application of the test item. After 6 h piloerection was still observed. From Day 1 to the end of the observation period on Day 14 the animals were free of any abnormalities

Gross pathology:

Necropsy and histopathological examination revealted no substance-related findings.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1) performed with the registered substance, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006 (REACH).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 Feb - 29 Mar 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:WI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld, Germany
- Weight at study initiation: 220 - 282 g
- Housing: The rats were caged in macrolone cages (type 3) individually during the 24 h application and separately according to sex in groups of 2 or 3 during the remaining time. The animals were provided with specific environment material such as hay bricks (Provimi Kliba AG, Kaiseraugust, Switzerland) as well as hiding tunnels of polycarbonate (Plexx, Netherlands). Lignocel-Granulat (Altromin, Lage, Lippe, Germany) served as bedding material.
- Diet: pelleted diet Altromin 1324 (Altromin, Lage, Lippe, Germany), ad libitum
- Water: tap water acidified with hydrochloric acid, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back/flanks (6 x 8 cm)
- Type of wrap if used: The test material was applied onto the shaved skin and covered with 4-layered gauze which was fixed with adhesive tape (Gothaplast) by wrapping the trunk of the animals.

REMOVAL OF TEST SUBSTANCE
- Washing: The bandage and gauze were removed after the exposure time and residual test material was removed using mild soap and lukewarm water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 1 mL/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw (range finding study)
2000 mg/kg bw (main study)

No. of animals per sex per dose:

1 female (range finding study)
5 males and 5 females (main study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was observed for mortality and clinical signs 1, 3 and 6 h after test material application and thereafter daily for a period of 14 consecutive days. Body weights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes

Preliminary study:

The animal showed piloerection one and three hours after test material application of a dose of 2000 mg/kg bw. Six hours after test material application as well as from day 1 to the end of the observation period on day 14, the animal was free of any abnormalities. After termination of the 24 h application on day 1, a slight to well defined erythema (grade 2) was displayed on the treated skin areas, but no edema was observed. On day 2, a very slight erythema (grade 1) was still observed, whereas no skin reactions were recorded on day 3 until the remaining study period.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: very slight to slight erythema and very slight edema were observed up to day 3 after test material application but fully reversible within 4 days

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Both, all female and male animals did not show any abnormalities after the dermal application of a dose of 2000 mg/kg bw during the entire 14-day observation period.

Gross pathology:

All animals did not display any pathological alterations during macroscopically examination.

Other findings:

On day one, a very slight erythema (grade 1) was observed in 2/10 animals, whereas a slight to well defined erythema (grade 2) was observed in 7/10 animals. Additionally, a very slight edema (grade 1) was observed in 2/10 animals. On day 2, very slight erythema (grade 1) were observed in 5/10 animals and a slight to well defined erythema (grade 2) was recorded in 4/10 animals. Very slight erythema (grade 1) were also observed in 3/10 animals on day 3 after test material application. Furthermore, the treated skin areas of 6/10 animals displayed isolated scales (day 3). However, all skin reactions were fully reversible within 4 days after application of the test material until the end of the study period.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 1) studies performed with the registered substance and with analogue substances showing similar structure and intrinsic properties as for the registered substance. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in physico-chemical, ecotoxicological and toxicological properties. Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006 (REACH). Therefore, the available information fulfils the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 (REACH).

Additional information

Acute toxicity: oral

An acute oral toxicity study performed according to OECD TG 420 and in compliance with GLP with Ammonium N-methyl-N-(1-oxododecyl)glycinate (CAS 68003-46-3) is available (Frey-Tox, 2004a). In this limit test five fasted female Wistar rats (Shoe: WIST) were administered a single dose of 2000 mg/kg bw of the test substance via oral gavage. The animals were observed for 14 days after administration. No mortality occurred during the study period and body weight gain was normal. All animals showed a hunched posture and pilo­erection 30 minutes to six hours post administration. From day 1 to the end of the observation period, no further clinical signs of systemic toxicity were observed. Thus, the acute oral LD50 value was considered to be greater than 2000 mg/kg bw. Based on the study results and according to EU classification criteria, the test substance is not to be classified.

 

Acute toxicity: inhalation

No data on acute inhalation toxicity is required as data on two other routes of exposure, i.e. oral and dermal, are provided.

 

Acute toxicity: dermal

With respect to the registered substance, an acute dermal toxicity study was performed with Ammonium N-methyl-N-(1-oxododecyl)glycinate (CAS 68003-46-3) according to OECD TG 402 and in compliance with GLP (Frey-Tox, 2016). In this limit test five Wistar rats of each sex were exposed to a single dose of 2000 mg/kg bw of the neat test substance for 24 h via semi-occlusive dressing and observed for 14 days post-application. No mortalities occurred and no systemic clinical signs of toxicity related to the administration of the test item were observed up to the end of the 14-day observation period. Furthermore, no effect on body weight development was recorded during the study period. Macroscopic examination at the end of the study revealed no treatment-related changes. On day 1, very slight erythema formation (grade 1) was observed in 2/10 animals, whereas slight to well defined erythema (grade 2) were observed in 7/10 animals. Additionally, very slight edema formation (grade 1) was observed in 2/10 animals. On day 2, very slight erythema (grade 1) were observed in 5/10 animals and slight to well defined erythema (grade 2) were recorded in 4/10 animals. Very slight erythema (grade 1) were also observed in 3/10 animals on day 3 after test material application. Furthermore, the treated skin areas of 6/10 animals displayed isolated scales (day 3). However, all skin reactions were fully reversible within 4 days after application of the test material until the end of the study period. Thus, the acute dermal LD50 value was considered to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

The available data on the registered substance Ammonium N-methyl-N-(1-oxododecyl)glycinate (CAS 68003-46-3) for both acute oral and acute dermal toxicity do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP). Data are therefore conclusive but not sufficient for classification. No data are, however, available regarding acute inhalation toxicity.