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Description of key information

Oral (OECD 401), rat (m/f): LD50 > 5000 mg/kg bw (limit test), based on read-across
Inhalation (OECD 403), rat (m/f): LC50 = 1.37 mg/L, based on read-across
Dermal (OECD 402), rat (m/f): LD50 > 2000 mg/kg bw (limit test), based on read-across

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
11 Dec - 23 Dec 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Lack on test material details.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
lack of test material details
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 154 ± 6.8 g (males), 163 ± 10.5 g (females)
- Fasting period before study: animals were fasted overnight prior to administration.
- Diet: rat food (NAFAG, Gossau SG), ad libitum
- Housing: animals were housed in groups of 5 in Macrolon III cages
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 10/10

Route of administration:
oral: gavage
Vehicle:
other: 2% carboxymethylcellulose + 0.1% Tween 80
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Animals showed slight signs of dyspnoea from 1 h to 6 days after treatment. Animals had slight exophthalmos until 5 h after administration. Animals showed slight to moderate ruffled fur until Day 4. Slight to moderate diarrhoea was observed until Day 2 and a slightly curved body position until Day 5. All animals recovered within 7 days.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 2) studies from a structurally related category member. aken 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. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Lack of details on test method.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
lack of details on test method
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: WIGA, Sulzfeld, Germany
- Weight at study initiation: 187 g (males), 204 g (females)
- Diet: Herilan MRH (Eggersmann KG, Rinteln/Weser, Germany), ad libitum
- Water: tap water, ad libitum
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic head-nose apparatus (BUNDSCHUH, Griesheim, Germany) and constant infusion apperatus (UNITA I, BRAUN, Melsungen, Germany)
- Rate of air: 1000 L/h

TEST ATMOSPHERE
- Brief description of analytical method used: for the quantitative analysis an indirect indicator method was used. Therefore, the substance was mixed with 0.06 and 0.19% Oil Res 0 C.J. 26125. The samples were measured spectroscopically at 525 nm and the concentration of the test substance was evaluated using a calibration line.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.3, 0.6, 2.2 and 3.7 mg/L (analytical concentration)
0.95, 1.67, 11.4 and 22.7 mg/L (nominal concentration)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed daily for mortality and individual body weights were determined before start of the study and thereafter weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The statistical analysis was performed according to the "Probitanalyse" (D.J. Finney, 1971, Syndics of the Cambridge University Press, London, UK).
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1.37 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
1.8 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
1.05 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
0.6 mg/L: 3 males and 1 female animal died
2.2 mg/L: 10 males and 4 females died
3.7 mg/L: 8 males and 10 females died
Clinical signs:
other: 0.3 mg/L: flight attempts and gasping breathing 0.6 mg/L: additional to the signs of the low dose group and noisy breathing and slight staggering. One female showed lateral position. 2.2 mg/L: additional to the signs of the 0.6 mg/L dose group and bloody
Body weight:
2.2 mg/L (females): weight loss (mean 8 g) from Day 7-14
3.7 mg/L (males): weight loss (mean 4 g) from the Day of exposure to Day 7
Gross pathology:
Animals that died during the study period:
0.6 mg/L: heart: acute dilatation, acute hyperemia; lung: oedema with emphysema at the edges, pulmonary lobes were wet and fleshy and excess of blood were observed
2.2 mg/L: acute dilatation, acute hyperemia; lung: severe exhalation especially at the peripheral areas, severe oedema formation, single areas wet and fleshy. One animal with slight hydrothorax
3.7 mg/L: acute dilatation, acute hyperemia; lung: laminar bleedings, slight exhalation

Surviving animals:
Organs showed no signs of toxicity.

Table 1. Table for acute inhalation toxicity.

Target concentration
[mg/L air]

Toxicological results*

Duration of clinical signs

Mortality (%)

Males

0.3

0/10/10

Day 2-7

0

0.6

3/10/10

Day 2-7

30

2.2

10/10/10

Day 2-7

100

3.7

8/10/10

Day 2-7

80

Females

0.3

0/10/10

Day 2-7

0

0.6

1/10/10

Day 2-7

10

2.2

4/10/10

Day 2-7

40

3.7

10/10/10

Day 2-7

100

LC50 = 1.37 (1.01-1.85) mg/L air

* first number = number of dead animals

 second number = number of animals with clinical signs

 third number = number of animals used

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Acute Inhal 4, H332
DSD: Xn, R20
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 370 mg/m³
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 2, due to read across) studies from a structurally related category member. The available study is sufficient 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.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The Department of Health of the Government of the United Kingdom
Test type:
standard acute method
Species:
rat
Strain:
other: RCCHan:WIST
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 240-370 g (males) and 207-228 g (females)
- Housing: animals were housed individually during the exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet: 2014C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
other: arachis oil BP
Details on dermal exposure:
TEST SITE
- Area of exposure: backs and flanks
- % coverage: approximately 10%
- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: the treated skin and surrounding hair were wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24 h


Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs at 30 min, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. Individual body weights were determined on Day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, evaluation of dermal reactions using the Draize scoring system.
Sex:
male/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:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
The test animals showed expected body weight gains during the study period with the exception of one female which showed bodyweight loss during the first week but expected weight gain during the second week.
Gross pathology:
Necropsy revealed no substance-related findings.
Other findings:
- Other observations: very slight erythema (Draize scoring value: 1) was noted at the test sites of 7/10 animals being fully reversible within 5 days. No edema formation was observed in any animal. Crust formation was also noted at the test site of one female being reversible within 9 days. There were no signs of dermal irritation noted at the test sites of the remaining animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. The available study is sufficient 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.

Additional information

There is no sufficient data available on the acute toxicity of Reaction products of oleoyl sarcosine with sodium hydroxide. 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.

Discussion

Acute oral toxicity

No studies are available investigating the acute oral toxicity of Reaction products of oleoyl sarcosine with sodium hydroxide. In order to fulfil the standard information requirements set out in Annex VII, 8.5. and in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across to the structurally related category member Sodium N-lauroylsarcosinate (CAS 137-16-6) and (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) was conducted.

The acute toxicity via the oral route of Sodium N-lauroylsarcosinate (CAS 137-16-6) has been investigated in rats in accordance with OECD guideline 401 under GLP conditions (Haynes, 1987).

A group of 10 Sprague Dawley rats (5 males and 5 females) was treated with the limit dose of 5000 mg/kg bw of the test substance by gavage. The observation period following administration was 14 days. During the study period, one female animal died at Day 2. No clinical signs of toxicity were observed in the surviving animals. All surviving animals showed normal body weight gain. The female animal found dead had been cannibalised and autolysed. Thus, no detailed post-mortem examination was possible. In surviving animals no abnormalities were noted at necropsy.

Thus, the oral LD50 for male and female rats is greater than 5000 mg/kg bw.

Two studies investigating the acute toxicity via the oral route of (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) are available (Sarasin, 1980; BASF, 1979).

One study was performed in Sprague-Dawley rats similar to OECD guideline 401 (Sarasin, 1980). A group of 10 rats (5 males and 5 females) was dosed with 5000 mg/kg bw of the test substance by gavage. The animals were observed for a period of 14 days following administration.

During the study period, no mortality occurred in any animal. Observed clinical signs included slight dyspnoea, slight exophthalmos and slight to moderate ruffled fur and slight to moderate diarrhoea and a slightly curved body position. All animals recovered within 7 days. No effects on body weight were noted and necropsy revealed no substance-related findings. Thus, the oral LD50 for male and female rats was considered to be greater than 5000 mg/kg bw.

In a further study with limited data given, (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) was tested for acute oral toxicity similar to OECD guideline 401 (BASF, 1979). Rats were given the test material per oral administration. No further study details were provided. The authors determined the oral LD50 for rats to be greater than 9200 mg/kg bw.

In summary, the oral LD50 of (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine is considered to be greater than 5000 mg/kg bw.

Acute inhalation toxicity

No studies are available investigating the acute toxicity via the inhalation route of Reaction products of oleoyl sarcosine with sodium hydroxide. In order to fulfil the standard information requirements set out in Annex VIII, 8.5.2. and in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from the structurally related category member (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) was conducted.

 

The acute inhalation toxicity of (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) was evaluated in two studies similar to OECD guideline 403 (BASF, 1979 a,b). In the key study, groups of 10 Sprague-Dawley rats were exposed nose / head only to 0.3, 0.6, 2.2 and 3.7 mg/L air for 4 h. The animals were observed for a period of 14 days following administration.

Mortality occurred in male animals in the 0.6, 2.2 and 3.7 mg/L air groups (30, 100 and 80% mortality). In female animals, mortality was observed in the 0.6, 2.2 and 3.7 mg/L air groups (10, 40 and 100% mortality), as well. Clinical signs of toxicity were observed in all surviving animals including flight attempts, gasping and noisy breathing, slight staggering, bloody nose area, low motility, hair loss in the head area and salivation in varying degrees.

Surviving animals were free of symptoms from Day 2-8 after treatment and the organs showed no signs of toxicity at necropsy. Body weight loss was observed in females of the 2.2 mg/L and in males of the high-dose group. In animals that died during the study period, clinical signs of toxicity were acute dilatation, acute hyperaemia, oedema and hyperaemia of the lungs, severe exhalation especially at the peripheral areas, severe oedema formation and laminar bleedings of the lungs (high-dose group).

Thus, the LC50 is calculated to be 1.8 mg/L air for females and 1.05 mg/L air for males. The combined LC50 value for males and females is considered to be 1.37 mg/L air after 4 h exposure to the test material.

In the second study, similarly performed as described above, 10 Sprague-Dawley rats were exposed nose / head only to 0.17, 1.35, 1.84, 1.85, 3.28 and 4.96 mg/L air (analytical concentration) for 1 h. Within the first 3 days after exposure, mortality occurred in male animals in the 1.35, 1.84, 1.85, 3.28 and 4.96 mg/L air groups (10, 60, 70, 80 and 100% mortality) and in female animals in the 1.35, 1.85, 3.28 and 4.96 mg/L air groups (30, 30, 30 and 90% mortality). Except in the lowest dose group, the animals of all other groups had eye and nose exudate, eyelid closure, dyspnoea, staggering, cowering position and scrubby substance-clotted fur. Male animals of the 3.28 mg/L and females of the 1.84 mg/L dose groups showed reduced body weight gain at the beginning of the study period being comparable to the control within 14 days. At gross pathology in animals that died during the study period, acute dilatation of the heart and acute hyperemia of the lung were observed. In surviving animals, no signs of toxicity were observed at gross pathology.

Thus, the LC50 for male and female animals is calculated to be > 1.01 – 1.85 mg/L air after 1 h exposure.

Acute dermal toxicity

No studies are available investigating the acute toxicity via the dermal route of Reaction products of oleoyl sarcosine with sodium hydroxide. In order to fulfil the standard information requirements set out in Annex VIII, 8.5.3. and in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from the structurally related category member Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3) was conducted.

The acute dermal toxicity of Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate (CAS 30364-51-3) was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Bradshaw, 2013).

Groups of 10 rats (5 males and 5 females) were treated with the test substance moistened with arachis oil BP at the limit dose of 2000 mg/kg bw under semi-occlusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. No substance-related findings during necropsy were observed in any animal. No effects on body weight gain were observed with the exception of one female which showed bodyweight loss during the first week but expected weight gain during the second week. Evaluation of the dermal skin reactions showed very slight erythema (Draize scoring value: 1) at the test sites of 7/10 animals being fully reversible within at the most 5 days. No edema formation was observed in any animal. Crust formation was noted at the test site of one female being reversible within 9 days.

Thus, the dermal LD50 for male and female rats was considered to be greater than the tested limit dose 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties among category members and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties among category members and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties among category members and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on the acute oral toxicity of substances structurally related to Reaction products of oleoyl sarcosine with sodium hydroxide according to Regulation (EC) No 1907/2006, Annex XI, 1.5. do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC; therefore, Reaction products of oleoyl sarcosine with sodium hydroxide is not expected to exert acute toxicity, either, and the data are thus conclusive but not sufficient for classification.

 

The available data on the acute inhalation toxicity of substances structurally related to Reaction products of oleoyl sarcosine with sodium hydroxide according to Regulation (EC) No 1907/2006, Annex XI, 1.5. meet the criteria for classification for Acute toxicity - inhalation category 4 (H332) according to Regulation (EC) No 1272/2008 and as Harmful by inhalation (Xn; R20) according to Directive 67/548/EEC; therefore, Reaction products of oleoyl sarcosine with sodium hydroxide is expected to exert comparable acute toxicity, either, and is therefore classified accordingly.

The available data on the acute dermal toxicity of the a substance structurally related to Reaction products of oleoyl sarcosine with sodium hydroxide according to Regulation (EC) No 1907/2006, Annex XI, 1.5. do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC; therefore, Reaction products of oleoyl sarcosine with sodium hydroxide is not expected to exert acute toxicity, either, and the data are thus conclusive but not sufficient for classification.

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