Fatty acids, C18-24, zinc salts

Endpoint summary

Description of key information

No acute toxicity studies with substance Fatty acids, C18-24, zinc salts are available, thus the acute toxicity will be addressed with existing data on the structural analog substances fatty acid(s), C8, C12, C18OH and C16-18 zinc salt(s) and the dissociation products zinc and fatty acids, C18-24. Signs of acute toxicity are not expected for substance Fatty acids, C18-24, zinc salts, since the structurally related fatty acid(s) zinc salts, as well as the moieties zinc and fatty acids, C18-24 are of low toxicity with dose descriptors (LD(C)50) above the guideline limits, respectively no adverse effect expected based on other information.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that key and supporting source substance(s) and target substance have similar acute toxicity based on their structural similarity.

2. SOURCE AND TARGET CHEMICALS COMPOSITION
Source(s) and target are all fatty acid(s) zinc salts. They have a very close structural similarity only varying in their fatty acids chain length distribution and consequential minor variations in their relative zinc content.

2.1. Composition of key source substance Fatty Acids, C16-18, zinc salts / 91051-01-3 / 293-049-4:
- Fatty Acids, - zinc dipalmitate / zinc dihexadecanoate / 4991-47-3 / 225-652-5: >=20.0 - <=65.0% (w/w)
- zinc distearate / zinc dioctadecanoate / 557-05-1 / 209-151-9: >=35.0 - <=80.0% (w/w)
- Fatty Acids, >C18, zinc salts: <= 6.0% (w/w)
- Fatty acids, C16-18 / Fatty acids, C16-18 / 67701-03-5 / 266-928-5: <= 3.0% (w/w)
- water / dihydrogen oxide / 7732-18-5 / 231-791-2: <= 2.0% (w/w)
Only components which do not affect the classification may be present in the source substance.

2.2. Composition of supporting source substances

2.2.1. Composition of supporting source substance zinc bis[12-hydroxyoctadecanoate] / 35674-68-1 / 252-669-5:
- zinc bis[12-hydroxyoctadecanoate] / 35674-68-1 / 252-669-5: >=80.0 - <=100.0% (w/w)
- zinc distearate / zinc dioctadecanoate / 557-05-1 / 209-151-9: <=15.0% (w/w)
- zinc dipalmitate / zinc dihexadecanoate / 4991-47-3 / 225-652-5: <=4.0% (w/w)
- zinc dioleate / zinc dioctadec-9-enoate / 557-07-3 / 209-154-5: <=3.0% (w/w)
- zinc diricinoleate / zinc bis(12-hydroxyoctadec-9-enoate) / 13040-19-2 / 235-911-4: <=3.0% (w/w)
- zinc didocosanoate / zinc didocosanoate / 16529-65-0 / 240-597-7: <=1.0% (w/w)
- 12-hydroxystearic acid / 12-hydroxyoctadecanoic acid / 106-14-9 / 203-366-1: <=4.0% (w/w)
- stearic acid / stearic acid / 57-11-4 / 200-313-4: <=1.0% (w/w)
- water / dihydrogen oxide / 7732-18-5 / 231-791-2: <=1.0% (w/w)

2.2.2. Composition of supporting source substance Octanoic acid, zinc salt, basic / 90480-58-3 /291-793-4:
- Octanoic acid, zinc salt, basic / 90480-58-3 /291-793-4: >=80.0 - <=100.0% (w/w)
Only components which do not affect the classification may be present in the target substance.

2.3. Composition of target substance Fatty acids, C18-24, zinc salts / 84776-57-8 / 283-985-1:
- zinc distearate / zinc dioctadecanoate / 557-05-1 / 209-151-9: >=30.0 - <=45.0% (w/w)
- zinc diicosanoate / zinc diicosanoate / 7278-04-8 / 230-693-7: >=5.0 - <=15.0% (w/w)
- zinc didocosanoate / zinc didocosanoate / 16529-65-0 / 240-597-7: >=40.0 - <=55.0% (w/w)
- Zinc salts of fatty acids C24: <= 10.0% (w/w)
- Fatty acids, C18-24 / 98106-57-1 / 308-578-9: <= 5.0% (w/w)
- water / dihydrogen oxide / 7732-18-5 / 231-791-2: <= 2.0% (w/w)
Only components which do not affect the classification may be present in the target substance.

3. ANALOGUE APPROACH JUSTIFICATION
Source(s) and target have a very close structural similarity only varying in their fatty acids chain length distribution and consequential minor variations in their relative zinc content. They are produced by the oleochemistry sector, starting from natural fatty materials and consist of natural fatty acids and zinc. In the body, fatty acids zinc salts will partly dissociate into the zinc cation and the fatty acids anions, especially in an acidic environment like the stomach (c.f. EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1). As zinc is an essential trace element and fatty acids are major nutrients, both moieties are effectively processed and regulated in the body. A minor variation in the fatty acid composition and the zinc amount of source(s) and target is not expected to substantially impact the systemic activity. This assumption is supported by the available data. For the key source substance Fatty acids, C16-18, zinc salts an oral LD50 > 5000 mg/kg bw was reported. Also non systemic acute oral toxicity (LD 50 > 2000 mg/kg bw) was observed in different supporting tests with Zinc bis[12-hydroxyoctadecanoate], i.e. a zinc salt of a C18 fatty acid with an additional hydroxyl group, as well as octanoic acid, zinc salt, basic, i.e. a zinc salt of a shorter-chained (C8) fatty acid and substantially higher relative zinc amount. The missing of a systemic acute oral toxicity is also supported by existing data on the entities formed upon dissolution of substance Fatty acids, C18-24, zinc salts, namely zinc and fatty acids, C18-24 (see respective assessment entities).
Thus, read-across of data available for zinc salts of shorter-chained (C8) and similar chained (C18, C16-18) fatty acids based on structural similarity, water solubility and zinc content in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of Fatty acids, C18-24, zinc salts.
Therefore, read-across from the existing acute oral toxicity study(ies) on the source substance(s) is considered as an appropriate adaptation to the standard information requirements of Annex VII, 8.5.1 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Key result

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

other: read-across data on structural analogue Fatty acids, C16-18, zinc salts

Interpretation of results:

GHS criteria not met

Executive summary:

Read-across from the existing acute oral toxicity study(ies) on the source substance(s) is considered as an appropriate adaptation to the standard information requirements of Annex VII, 8.5.1 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

Source(s) and target have a very close structural similarity only varying in their chain lengths. They are produced by the oleochemistry sector, starting from natural fatty materials and consist of natural fatty acids and zinc. In the body, fatty acids zinc salts will partly dissociate into the zinc cation and the fatty acids anions, especially in an acidic environment like the stomach (c.f. EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1). As zinc is an essential trace element and fatty acids are major nutrients, both moieties are effectively processed and regulated in the body. A minor variation in the fatty acid composition and the zinc amount of sourc(es) and target is not expected to substantially impact the systemic activity.

Read-across of data available for zinc salts of shorter-chained (C8) and similar chained (C18, C16 -18) fatty acids based on structural similarity, water solubility and zinc content in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of Fatty acids, C18-24, zinc salts.

For the key source substance Fatty acids, C16-18, zinc salts an oral LD50 > 5000 mg/kg bw was reported. Also non systemic acute oral toxicity (LD 50 > 2000 mg/kg bw) was observed in different supporting tests with Zinc bis[12-hydroxyoctadecanoate], i.e. a zinc salt of a C18 fatty acid with an additional hydroxy group, as well as octanoic acid, zinc salt, basic, i.e. a zinc salt of a shorter-chained (C8) fatty acid and substantially higher relative zinc amount. The missing of a systemic acute oral toxicity is also supported by existing data on the entities formed upon dissolution of substance Fatty acids, C18-24, zinc salts, namely zinc and fatty acids, C18-24 (see respective assessment entities). Based on these data the LD oral for substance Fatty acids, C18-24, zinc salts can safely be assumed to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that key and supporting source substance(s) and target substance have similar acute toxicity based on their structural similarity.

2. SOURCE AND TARGET CHEMICALS COMPOSITION
Source(s) and target are all fatty acid(s) zinc salts. They have a very close structural similarity only varying in their fatty acids chain length distribution and consequential minor variations in their relative zinc content.

2.1. Composition of key source substance Fatty Acids, C16-18, zinc salts / 2452-01-9 / 293-049-4:
- Fatty Acids, - zinc dipalmitate / zinc dihexadecanoate / 4991-47-3 / 225-652-5: >=20.0 - <=65.0% (w/w)
- zinc distearate / zinc dioctadecanoate / 557-05-1 / 209-151-9: >=35.0 - <=80.0% (w/w)
- Fatty Acids, >C18, zinc salts: <= 6.0% (w/w)
- Fatty acids, C16-18 / Fatty acids, C16-18 / 67701-03-5 / 266-928-5: <= 3.0% (w/w)
- water / dihydrogen oxide / 7732-18-5 / 231-791-2: <= 2.0% (w/w)
Only components which do not affect the classification may be present in the source substance.

2.2. Composition of supporting source substance zinc didodecanoate / 35674-68-1 / 219-518-5:
- zinc dilaurate / zinc didodecanoate / 2452-01-9 / 219-518-5: >=95.0 - <=100.0% (w/w)
- fatty acids, - fatty acids, >C12, zinc salts / fatty acids, >C12, zinc salts: <=5.0% (w/w)
- lauric acid / lauric acid / 143-07-7 / 205-582-1: <=2.0% (w/w)
- water / dihydrogen oxide / 7732-18-5 / 231-791-2: <=1.0% (w/w)
Only components which do not affect the classification may be present in the target substance.

2.3. Composition of target substance Fatty acids, C18-24, zinc salts / 84776-57-8 / 283-985-1:
- zinc distearate / zinc dioctadecanoate / 557-05-1 / 209-151-9: >=30.0 - <=45.0% (w/w)
- zinc diicosanoate / zinc diicosanoate / 7278-04-8 / 230-693-7: >=5.0 - <=15.0% (w/w)
- zinc didocosanoate / zinc didocosanoate / 16529-65-0 / 240-597-7: >=40.0 - <=55.0% (w/w)
- Zinc salts of fatty acids C24: <= 10.0% (w/w)
- Fatty acids, C18-24 / 98106-57-1 / 308-578-9: <= 5.0% (w/w)
- water / dihydrogen oxide / 7732-18-5 / 231-791-2: <= 2.0% (w/w)
Only components which do not affect the classification may be present in the target substance.

3. ANALOGUE APPROACH JUSTIFICATION
Source(s) and target have a very close structural similarity only varying in their fatty acids chain length distribution and consequential minor variations in their relative zinc content. They are produced by the oleochemistry sector, starting from natural fatty materials and consist of natural fatty acids and zinc. In the body, fatty acids zinc salts will partly dissociate into the zinc cation and the fatty acids anions. As zinc is an essential trace element and fatty acids are major nutrients, both moieties are effectively processed and regulated in the body. A minor variation in the fatty acid composition and the zinc amount of source(s) and target is not expected to substantially impact the systemic activity. This assumption is supported by the available data. For the key source substance Fatty acids, C16-18, zinc salts a 1h inhalative LC50 > 200 mg/L (4h LC > 50 mg/L by applying Haber´s law) was reported. Also non systemic acute inhalative toxicity (4h LC50 > 5.08 mg/L) was observed in a supporting test with zinc didodecanoate, i.e. a zinc salt of a shorter-chained (C12) fatty acid and thus higher relative zinc amount. The missing of a systemic acute inhalative toxicity is also supported by existing data on the entities formed upon dissolution of substance Fatty acids, C18-24, zinc salts, namely zinc and fatty acids, C18-24 (see respective assessment entities).
Thus, read-across of data available for zinc salts of shorter-chained (C12) and similar chained (C16-18) fatty acids based on structural similarity, water solubility and zinc content in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of Fatty acids, C18-24, zinc salts.
Therefore, read-across from the existing acute inhalative toxicity study(ies) on the source substance(s) is considered as an appropriate adaptation to the standard information requirements of Annex VII, 8.5.1 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 200 mg/L air

Based on:

other: read-across data on structural analogue Fatty acids, C16-18, zinc salts

Exp. duration:

1 h

Key result

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 50 mg/L air

Based on:

other: read-across data on structural analogue Fatty acids, C16-18, zinc salts

Exp. duration:

4 h

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

Supporting information to waiver:
Study on acute dermal toxicity of substance Fatty acids, C18-24, zinc salts has been waived, as by read-across to the structural analogue substance Fatty acids, C16-18, zinc salts, substance Fatty acids, C18-24, zinc salts does neither meet the criteria for classification for acute toxicity nor for STOT SE. Systemic toxicity by dermal exposure is not expected, as such effects are also not known for the structural analogue substance Fatty acids, C16-18, zinc salts which is used in in cosmetical skin products and was applied in in vivo studies with dermal exposure (skin irritation studies). Thus waiving of an acute dermal toxicity study in accordance with Annex VIII, 8.5.3 column 2 is justified.
As supporting information, a study on dermal LD50 of an Fatty acids, C16-18, zinc salts containig cosmetic product is given.

Reason / purpose for cross-reference:

read-across: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

FATTY ACIDS, C18-24, ZINC SALTS:

No acute toxicity studies with substance Fatty acids, C18-24, zinc salts are available, thus the acute toxicity will be addressed with existing data on the structural analog substances Fatty acid(s), C8, C12, C18OH and C16-18 zinc salts and the dissociation products zinc and fatty acids.

Acute toxicity is not expected for substance Fatty acids, C18-24, zinc salts, since the structurally related fatty acid(s) zinc salts, as well as the moieties zinc and fatty acids are of low toxicity with dose descriptors (LD(C)50) above the guideline limits, respectively no adverse effect expected based on other information.

This conclusion is in line with the conclusion of an EU risk assessment carried out on the structural analogue substance Fatty acids, C16-18, zinc salts (i.e. zinc stearate) within the framework of EU Existing Chemicals Regulation 793/93 (EU RAR Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1): "Zinc distearate does not need to be classified on the basis of its acute toxicity according to the EC criteria." A similar lack of acute toxicity is considered for substance Fatty acids, C18-24, zinc salts.

 

Conclusion: Based on read-across, Fatty acids, C18-24, zinc salts does not need to be classified on the basis of its acute toxicity.

Please refer to the section for the respective assessment entity for data on the moieties. In brief:

 

ZINC:

Acute oral toxicity

- With LD50 values consistently exceeding 2,000 mg/kg bw, zinc oxide (LD50 ranges between 5,000 and 15,000 mg/kg bw), shows very low level of acute oral toxicity.

 

FATTY ACIDS, C18-24:

- Toxicity via the oral route:

Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)).

The linear, saturated, even numbered C18-24 fatty acids are present in breast milk and body fat and in natural fats from vegetal as well as animal origin used as human and animal nutrients or for technical applications (Gunstone 2004, Kingsbury et al., 1961, Krist et al., 2008, Much et al., 2013, Yuhas et al., 2006). Based on this, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

According to the HERA document on fatty acid salts (2002) “the available data for fatty acids provide a clear picture of low acute toxicity for this class of chemicals. All oral LD50 values were greater than 2,000 mg/kg, with little mortality being observed even at the highest doses tested in the studies IUCLID, 2000c, 2000e, 2000f, 2000g; Clayton & Clayton, 1982; CIR, 1987)”(HERA, 2002).

Additionally, based on animal data reported in the HERA document on fatty acid salts (2002), fatty acids with chain lengths of C18 to C22 showed no toxicity after oral administration to rats. The LD50 was set above 5000 mg/kg bw. (HERA, 2002).  “In an OECD TG 401 study, a group of five rats/sex was administered docosanoic acid (C22) at a dose of 2000 mg/kg bw. There were no clinical signs, deaths, or findings at necropsy. The LD50 was > 2000 mg/kg bw.”(OECD SIDS, 2001, 2014). “International-BioResearch (1974, as referred to by CIR, 1987) determined the acute oral toxicity in groups of five male albino rats. Animals were administered by gavage lauric-, myristic-, palmitic- or stearic acid with increasing doses of up to 10,000 mg/kg bw and oleic acid up to 20,000 mg/kg bw. It was observed that for all these fatty acids the LD50 value was above the maximum level tested. No mortality was observed in five albino rats gavaged with 5 g/kg bw oleic acid (commercially supplied); clinical signs were not reported during the 7-day post-exposure period (CTFA, 1978, as referred to in CIR, 1987)”(EFSA ANS Panel, 2017). “In an OECD TG 401 study, a group of five rats/sex was administered octadecanoic acid (as a 50% suspension in DMSO) at a dose of 5000 mg/kg bw. There was one death. Animals exhibited transient piloerection, excessive salivation, and diminished activity. At necropsy, the male animal that died exhibited a stomach full of test substance; surviving animals showed remnants of test substance in the stomach with swelling of the mucous membrane. The LD50 was > 5000 mg/kg bw” (OECD SIDS, 2014).

In conclusion, the conduct of any further toxicity studies with acute exposure in animals would not contribute any new additional information and is therefore not considered to be required.

- Toxicity via the inhalative route

The conduct of an acute inhalation toxicity study is unjustified as inhalation of the substance is considered negligible, based on the low vapour pressure of long chain fatty acids. The conduct of an acute inhalation toxicity study is therefore waived in accordance with the criteria in Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006.

- Toxicity via the dermal route:

The available acute dermal toxicity data for fatty acids (and their salts) provide a clear picture of low acute toxicity for this group of chemicals. All dermal LD50 values were greater than >2,000 mg/kg (BIBRA, 1996; IUCLID, 2000e; Clayton & Clayton, 1982; CIR, 1982, 1987)” (HERA, 2002).

“In a subchronic study, no adverse effects were produced from topical application of myristic acid (C14) to rabbit skin. One-half ml of a 30% preparation of myristic acid in ether and propylene glycol (solvents at a 1:1 ratio in concentration) was massaged into the depilated skin of the flanks of 5 rabbits daily for 30 days. The opposite flank of the rabbits was depilated and treated with solvent only. No significant macroscopic changes were observed. Microscopic lesions included thinning of collagen fibres in the superficial layer of the dermis after 10 days and a loose dermal infiltrate of lymphomononuclear cells and histocytes after 20 and 30 days (CIR, 1987)” (HERA, 2002).

No dermal toxicity was reported for similar substances such as sodium stearate. “In a dermal study in which concentrations of sodium stearate (C18) ranged between 10-25% in a 20% bath soap detergent form, the LD50was >3000 mg/kg (highest dose tested) (CIR, 1982). In a dermal study in guinea pigs, application of commercial grade oleic acid (3,000 mg/kg) produced no deaths and no signs of toxicity. The number of applications was not stated (CIR, 1987)” (HERA, 2002).

As the available data for fatty acids provide a clear picture of low acute toxicity for this class of chemicals, oral LD50 values were greater than 2,000 mg/kg, low acute toxicity is also anticipated for the dermal route. The low systemic toxicity is corroborated by the wide use of fats and fatty acid in cosmetic preparations, e.g. body oils and their natural occurrence in epidermal surface lipids (CIR, 1987, Apostolos, 2009, Nicolaides, 1974).

The conduct of any further toxicity studies with acute exposure in animals would not contribute any new additional information and is therefore not considered to be required and waived in accordance with Annex XI, Section 1.2.

Justification for classification or non-classification

By read-across to structural analog substances Fatty acid(s), C8, C12, C18OH and C16-18 zinc salts and the dissociation products zinc and fatty acids, C18-24, acute toxicity is not expected for substance Fatty acids, C18-24, zinc salts, since the structurally related fatty acid(s) zinc salts, as well as the moieties zinc and fatty acids, C18-24 are of low toxicity with dose descriptors (LD(C)50) above the guideline limits, respectively no adverse effect expected based on other information.

 

According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations, substance Fatty acids, C18-24, zinc salts does not have to be classified for acute oral, dermal or inhalative toxicity or specific target toxicity, single exposure (STOT SE).

According to the criteria of REGULATION (EC) No 1272/2008, substance Fatty acids, C18-24, zinc salts does not have to be classified and has no obligatory labelling requirement for acute oral, dermal or inhalative toxicity or specific target toxicity, single exposure (STOT SE).