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The Sarcosine category contains N-acyl derivatives of N-methylglycine that function as hair-conditioning agents and surfactant-cleansing agents in cosmetic formulations. Other uses in non-cosmetic areas are known and some sarcosines are used in the metal finishing and processing industries as anti-rust agents. Their salts are known generally as N-acyl sarcosinates, fatty acid sarcosinates, or sarcosinates.

Structural similarities of the category substances are reflected in similar physico-chemical properties and mode of action. They have a common structural formula (see attachment), where R may be either hydrogen or sodium; the N-acyl part is a fatty acid chain ranging in length between 12 to 18 carbon atoms (R’ = C11 to C17) and having up to three unsaturations.

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, environmental fate and eco-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)”. Therefore, the available experimental data were collected and evaluated according to Annex XI in regard to:

-      Test duration (only tests which cover the expected exposure duration were regarded as suitable)

-      Key parameters of the test (only tests that cover the key parameter were accepted as suitable)

-      Comparability of the test systems

-      The adequacy of the results for C&L

-      The documentation of the test procedures (only in case of good documentation data)

Only data that were judged to cover the requirements specified above were used as adequate data suitable for the category and its members. In this particular case the similarity of the Sarcosine category members is justified, in accordance with the specifications listed in Regulation (EC) No 1907/2006 Annex XI, 1.5. Grouping of substances and read across, on basis of scope of variability and overlapping of composition, representative molecular structure, physico-chemical properties, toxicological, ecotoxicological profiles and supported by various QSAR methods. There is no convincing evidence that any one of these respective chemicals might lie out of the overall profile of this category. The key points that the members share are:

(i) Common origin: produced from condensation of fatty acids and N-methyl glycine. Typically the fatty acid needs to be activated in the form of chloride.

(ii) Similar structural features: long hydrophobic chain connected to a polar head through an amide bond

(iii) Similar physico-chemical properties: recognizable trends in melting point, boiling point, water solubility and partition coefficient. Similar surface tension activity.

(iv) Common properties for environmental fate & eco-toxicological profile: readily biodegradable, no potential for bioaccumulation, low to moderate adsorption potential, clear trend of increasing toxicity in aquatic organisms correlating with increasing carbon chain length, being the C18 compounds the most toxic substances.

(v) Similar metabolic pathways: the substances within the Sarcosine category have similar toxicokinetic behaviour that consists in no hydrolysis before absorption and absorption of the intact substance followed by a rapid excretion.

(vi) Common levels and mode of human health related effects: the available data on toxicological properties show that the substances of the Sarcosine category have similar toxicokinetic behaviour, no hydrolysis of the ester bond before absorption, absorption of the intact substance followed by a rapid excretion. The substances within the category showed acute toxicity via the inhalation route due to their irritant properties (reflected by their self-warning characteristics), skin irritating effects and severe damaging effects on the eye. Despite these corrosive/irritating effects, the constant pattern in toxicological properties within all substances considered herein consists in a lack of change of potency of properties.Thus, the category members showed no acute oral or dermal toxicity, no skin sensitisation properties, are of low systemic toxicity after repeated oral exposure, are not mutagenic or clastogenic, have shown no indication for reproduction toxicity and have no effect on intrauterine development.

Similar ecotoxicity profile

For the Sarcosine category, short-term fish toxicity studies are available for three category members, short-term toxicity studies conducted with aquatic invertebrates for four category members and toxicity studies conducted with algae and microorganisms for two category members (see experimental data presented in Table 6).

The Sarcosine category shows a clear trend of increasing toxicity in aquatic organisms correlating with increasing carbon chain length, in whichthe C18 compounds are the most toxic substances. The available studies cover all fatty acid chain lengths as well as acids and salts. Thus, the data gaps for the category members can be covered by interpolation or by the corresponding acid or salt. Since dissociation of the sodium salt under environmental conditions yields the same ionic species as dissociation of the acidic form of the substance, it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment.

In accordance with Annex IX, column 2 of Regulation (EC) No 1907/2006, toxicity testing with sediment and terrestrial organisms does not need to be conducted as the Chemical Safety Assessment does not indicate a need for further investigations. The environmental exposure assessment for all category members according to Annex XI, Section 3 of Regulation (EC) No 1907/2006 indicates no risk for the aquatic and terrestrial compartment (all RCR < 1; please refer to Chapter 9 and 10 of the Chemical Safety Report for detailed information).

Aquatic toxicity

Table: Environmental Toxicity (*)

ID No.

Substance

CAS No.

Chain length

Short term toxicity to fish

Long term toxicity to fish

 

Short term toxicity to aquatic invertebrates

Long term toxicity to aquatic invertebrates

Toxicity to aquatic algae

Toxicity to microorganisms

# 1

N-lauroylsarcosine

97-78-9

C12 acid

RA from Sodium N-lauroylsarcosinate (CAS 137-16-6)

Waiving based on CSA

RA from Sodium N-lauroylsarcosinate (CAS 137-16-6)

Waiving based on CSA

RA from Sodium N-lauroylsarcosinate (CAS 137-16-6)

RA from Sodium N-lauroylsarcosinate (CAS 137-16-6)

# 2

Sodium N-lauroylsarcosinate

137-16-6

C12 salt

LC50 (96h) = 107 mg/L

Waiving based on CSA

EC50 (48h) = 29.7 mg/L

Waiving based on CSA

EC50 (72h) = 79 mg/L

NOEC (72h) = 9.2 mg/L

EC50 (3h) > 1000 mg/L

# 3

N-(1-oxotetradecyl) sarcosine

52558-73-3

C14 acid

RA fromReaction products of oleoyl sarcosine with sodium hydroxide

Waiving based on CSA

RA from Sodium N-methyl-N-(1-oxotetradecyl)aminoacetate (CAS 30364-51-3)

Waiving based on CSA

RA from (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

RA from (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

# 4

Sodium N-methyl-N-(1-oxotetradecyl)aminoacetate

30364-51-3

C14 salt

RA fromReaction products of oleoyl sarcosine with sodium hydroxide

Waiving based on CSA

EC50 (48h) = 4.1 mg/L

Waiving based on CSA

RA from (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

RA from (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

# 5

(Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine

110-25-8

C18 acid

LC50 (96h) = 9.3 mg/L

Waiving based on CSA

EC50 (48h) = 0.43 mg/L

Waiving based on CSA

EC50 (72h) = 6.3 mg/L

NOEC (72h) = 0.91 mg/L

EC50 (3h) = 1300 mg/L

NOEC (3h) = 10 mg/L

# 6

Reaction products of oleoyl sarcosine with sodium hydroxide

--

C18 salt

LC50 (96 h) = 0.37 mg/L

 

Waiving based on CSA

EC50 (48h) = 1.4 mg/L

Waiving based on CSA

RA from (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

RA from (Z)-N-methyl-N-(1-oxo-9-octadecenyl)glycine (CAS 110-25-8)

(*) substances marked in bold are registered under REACH Regulation EC 1907/2006 in 2013, the remaining substances were registered in 2010 or will be registered later.

Short-term fish toxicity

Short-term fish toxicity studies are available for three category members, one study for the salt with the shortest fatty acid chain length (C12, Sodium N-lauroylsarcosinate, CAS 137-16-6), one study for the salt with the longest fatty acid chain length in the category (C18, Reaction products of oleoyl sarcosine with sodium hydroxide) and two studies for the acid with the longest fatty acid chain length (C18, (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8).

The Sarcosine category shows a clear trend of increasing toxicity in aquatic organisms correlating with increasing carbon chain length, in which the C18 compounds are the most toxic substances, with Reaction products of oleoyl sarcosine with sodium hydroxide as worst-case for short-term fish toxicity. The available studies cover the shortest (C12) and the longest fatty acid chain length (C18) as well as acids and salts. Thus, the data gaps for the category members can be covered by interpolation, including read across from the worst-case C18 salt. Since dissociation of the sodium salt under environmental conditions yields the same ionic species as dissociation of the acidic form of the substance, it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment. This read across approach is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. Grouping of substances and read across approach as is explained within the category justification in IUCLID section 13.

The short-term fish study conducted with the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6) resulted in a LC50 (96 h) = 107 mg/L (nominal) for Danio rerio. Following the trend of increasing toxicity at longer chain lengths, the key study performed with the C18 acid ((Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8) showed a LC50 (96 h) of 9.3 mg/L (nominal) for Leuciscus idus whereas the supporting study resulted in a LC50 (96 h) > 0.43 mg/L (nominal) for Danio rerio. The highest toxicity to fish species was observed for Reaction products of oleoyl sarcosine with sodium hydroxide (C18 salt) with a LC50 (96 h) of 0.37 mg/L (nominal).

The data gap for the C12 acid (N-lauroylsarcosine, CAS 97-78-9) is covered with the short-term fish study of the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6), as it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment.

For both category members with C14 fatty acid chain length (acid and salt) read across is done from all other category members with available short-term fish results, using the worst case result from the C18 salt (Reaction products of oleoyl sarcosine with sodium hydroxide) as key study. The two studies for the C18 acid ((Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8) and the study for the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6) are used in addition as read across to show by interpolation that comparable short-term effects on fish are expected for the C14 salt and acid as for the other category members, all of them characterized by a comparable structure.

Long-term fish toxicity

In accordance with Annex IX, column 2 of Regulation (EC) No 1907/2006, long-term toxicity testing to fish does not need to be conducted as the Chemical Safety Assessment does not indicate a need for further investigations. The environmental exposure assessment for all category members according to Annex XI, Section 3 of Regulation (EC) No 1907/2006 indicates no risk for the aquatic compartment (all RCR < 1; please refer to Chapter 9 and 10 of the Chemical Safety Report for detailed information). Thus, a long-term test with fish is not deemed necessary.

Short-term toxicity to aquatic invertebrates

Short-term toxicity studies conducted with aquatic invertebrates are available for four category members covering all three fatty acid chain lengths (C12, C14 and C18) in the category as well as acids and salts. One study is available for the salt with the shortest chain length (C12, Sodium N-lauroylsarcosinate, CAS 137-16-6), one study for the salt with C14 chain length (Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate, CAS 30364-51-3), one study for the salt with the longest fatty acid chain length in the category (C18, Reaction products of oleoyl sarcosine with sodium hydroxide) and two studies for the acid with the longest fatty acid chain length (C18, (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8).

The Sarcosine category shows a clear trend of increasing toxicity in aquatic organisms correlating with increasing carbon chain length, in which the C18 compounds are the most toxic substances, with (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine (CAS 110-25-8) as worst-case for short-term aquatic invertebrates. As studies for all three fatty acid chain lengths are available, all data gaps for the other category members can be covered. Since dissociation of the sodium salt under environmental conditions yields the same ionic species as dissociation of the acidic form of the substance, it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment. This read across approach is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. Grouping of substances and read across approach as is explained within the category justification in IUCLID section 13.

The short-term aquatic invertebrates study conducted with the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6) resulted in an EC50 (48 h) of 29.7 mg/L (nominal) for Daphnia magna. Following the trend of increasing toxicity at longer chain length, an EC50 (48 h) of 4.1 mg/L (measured geom. mean) was observed for the C14 salt (Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate, CAS 30364-51-3) for Daphnia magna. For both category members with C18 fatty acid chain length (acid and salt), the highest toxicity was observed for aquatic invertebrates, with EC50 values (48 h) of 0.43 mg/L, measured geom. mean, (C18 acid, CAS 110-25-8) and 1.4 mg/L, nominal, (C18 salt, Reaction products of oleoyl sarcosine with sodium hydroxide).

The data gap for the C12 acid (N-lauroylsarcosine, CAS 97-78-9) is covered with the corresponding salt, and the data gap for the C14 salt (Sodium N-methyl-N-(1-oxotetradecyl) aminoacetate, CAS 30364-51-3) with the corresponding acid, as it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment.

Long-term toxicity to aquatic invertebrates

In accordance with Annex IX, column 2 of Regulation (EC) No 1907/2006, long-term toxicity testing to aquatic invertebrates does not need to be conducted as the Chemical Safety Assessment does not indicate a need for further investigations. The environmental exposure assessment for all category members according to Annex XI, Section 3 of Regulation (EC) No 1907/2006 indicates no risk for the aquatic compartment (all RCR < 1; please refer to Chapter 9 and 10 of the Chemical Safety Report for detailed information). Thus, a long-term test with aquatic invertebrates is not deemed necessary.

Toxicity to aquatic algae

Toxicity studies conducted with aquatic algae are available for two category members, one study for the salt with the shortest fatty acid chain length (C12, Sodium N-lauroylsarcosinate, CAS 137-16-6) and two studies for the acid with the longest fatty acid chain length (C18, (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8).

The Sarcosine category shows a clear trend of increasing toxicity in aquatic organisms correlating with increasing carbon chain length, in which the C18 compounds are the most toxic substances. The available studies cover the shortest and the longest fatty acid chain length as well as acids and salts. Thus, the data gaps for the other category members can be covered by interpolation, including read across from the worst-case C18 acid. Since dissociation of the sodium salt under environmental conditions yields the same ionic species as dissociation of the acidic form of the substance, it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment. This read across approach is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. Grouping of substances and read across approach as is explained within the category justification in IUCLID section 13.

The algae study conducted with the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6) resulted in an EC50 (72 h) of 79 mg/L (meas. geom. mean) and a NOEC (72 h) of 9.2 mg/L (meas. geom. mean) for Desmodesmus subspicatus. Following the trend of increasing toxicity at longer chain length, the C18 acid ((Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8) showed an EC50 (72 h) of 6.3 mg/L (meas. initial) and a NOEC (72 h) of 0.91 mg/L (meas. initial) for Desmodesmus subcapitatus in the key study and a lower EC50 value in the supporting study (EC50 (72 h) = 5.1 mg/L, nominal) for Desmodesmus subcapitatus.

The data gap for the C12 acid (N-lauroylsarcosine, CAS 97-78-9) is covered with the algae study of the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6), as it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment.

For both category members with C14 fatty acid chain length (acid and salt) read across is done from all other category members with available algae results, using the worst case result from the C18 acid ((Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8) as key study. The study for the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6) is used in addition as read across to show by interpolation that comparable effects for algae are expected for the C14 salt and acid as for the other category members, all of them characterized by a comparable structure.

The data gap for the C18 salt (Reaction products of oleoyl sarcosine with sodium hydroxide) is covered with the algae studies of the C18 acid ((Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8), as it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment.

Toxicity to microorganisms

Toxicity studies conducted with microorganisms are available for two category members, one study for the salt with the shortest fatty acid chain length (C12, Sodium N-lauroylsarcosinate, CAS 137-16-6) and two studies for the acid with the longest fatty acid chain length (C18, (Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8).

The available studies cover the shortest and the longest fatty acid chain length as well as acids and salts. Thus, the data gaps for the other category members can be covered by interpolation. Since dissociation of the sodium salt under environmental conditions yields the same ionic species as dissociation of the acidic form of the substance, it is not relevant which form of sarcosinate molecule is used as source substance for the aquatic toxicity assessment. This read across approach is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. Grouping of substances and read across approach as is explained within the category justification in IUCLID section 13.

The microorganism study (OECD 209) conducted with the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6) resulted in an EC50 (3 h) > 1000 mg/L (nominal). In the microorganism study (OECD 209) performed with the C18 acid ((Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8) an EC50 (3 h) of 1300 mg/L (nominal) and a NOEC (3 h) of 10 mg/L (nominal) were reported in the key study.

The data gap for the C12 acid (N-lauroylsarcosine, CAS 97-78-9) is covered with the microorganism study of the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6), as the anions formed by dissociation of both the source and target substance have identical chemical structures.

For both category members with C14 fatty acid chain length (acid and salt) read across is done from all other category members with available microorganism results, using the C18 acid ((Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8) as key study, as this chain length is known to show the highest toxicity to aquatic organisms. The study for the C12 salt (Sodium N-lauroylsarcosinate, CAS 137-16-6) is used in addition as read across to show by interpolation that comparable effects for microorganisms are expected for the C14 salt and acid as for the other category members, all of them characterized by a comparable structure.

The data gap for the C18 salt (Reaction products of oleoyl sarcosine with sodium hydroxide) is covered with the microorganism studies of the C18 acid ((Z)-N-methyl-N-(1-oxo-9-octadecenyl) glycine, CAS 110-25-8), as the anions formed by dissociation of both the source and target substance have identical chemical structures.

Sediment Toxicity

In accordance with Annex IX, column 2 of Regulation (EC) No 1907/2006, toxicity testing with sediment organisms does not need to be conducted as the Chemical Safety Assessment does not indicate a need for further investigations. The environmental exposure assessment for all category members according to Annex XI, Section 3 of Regulation (EC) No 1907/2006 indicates no risk for the aquatic compartment (all RCR < 1; please refer to Chapter 9 and 10 of the Chemical Safety Report for detailed information). Thus, toxicity studies with sediment organisms are not deemed necessary.

Terrestrial toxicity

In accordance with Annex IX, column 2 of Regulation (EC) No 1907/2006, toxicity testing to terrestrial organisms does not need to be conducted as the Chemical Safety Assessment does not indicate a need for further investigations. The environmental exposure assessment for all category members according to Annex XI, Section 3 of Regulation (EC) No 1907/2006 indicates no risk for the terrestrial compartment (all RCR < 1; please refer to Chapter 9 and 10 of the Chemical Safety Report for detailed information). Thus, toxicity studies with terrestrial organisms are not deemed necessary.

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