Fatty acids, C16-18, zinc salts

Endpoint summary

Description of key information

A key study for acute oral toxicity with fatty acids, C16-18, zinc salts is available (OECD 401) indicating a LD50 > 5000 mg/kg bw.

 

A key study for acute inhalation toxicity with fatty acids, C16-18, zinc salts is available indicating a LC50 > 50 mg/L.

 

A key study for acute dermal toxicity with fatty acids, C16-18, zinc salts is available indicating a LD50 > 2000 mg/kg bw.

 

In conclusion, the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral, inhalation and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study report reliable with restrictions. No original document, a translated German summary without signature and raw data, purity of test item is missing. The study was peer-reviewed and rated reliable within the framework of the EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN. Institute for Health and Consumer Protection. ECB - Existing Substances. Final Report, 2004". In accordance with Section 1 (0.5), Annex I of Regulation (EC) No 1907/2006 (REACH), this study was considered reliable with restrictions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

, see "Rationale for reliability"

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: "Nossan" in Correzzana, Milan
- Age at study initiation: young healhty animals
- Weight at study initiation: mean weight 200 +/- 20 g
- Fasting period before study: Overnight fasting; 3 -4 hours after administration food supply is restored.
- Housing: Cages were made from translucent polycarbonate, Model 1290 (425 x 260 x 150 mm) from the firm Techniplast, Gazzada (Varese); The stable has an overpressure opposed to the atmosphere outside.
- Diet: Food pellets (Firm Nossan, Correzzana)
- Water (ad libitum): Filtered water from the municpal water supply; Filtered with Seitz-Filter
- Quarantine period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C +/- 2°C
- Humidity: 55 % +/- 10 %
- Air changes: minimal 8 times per hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

The test substance is administered in its pure form or in a medium. If needed the test substance will be solved in either a suitable medium or in a suspension. Preferably in an aqueous medium, followed by a solution in vegetable oil, solution in other media and lastly a suspension. For nonaqueous mediua toxic characterisitcs should be considered.
The volume administered is either smaller or equal to 10 ml/kg body weight. Exceptionally up to 20 ml/kg body weight can be administered if a aqueous solution is used.
No further information on the oral exposure was stated.

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

Test group: 5 males / 5 females
Control animals: 5 males / 5 females (administered medium or physiological solution)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Careful clinical observations were made several times during the first day and afterwards once daily. For every animal the time of death will be noted. Signs of toxication are among others: weight variations, diarrhoea, general condition, every variation from the norm. Rats were weighed prior to administration and if they survived at the end of observation. The weight will be compared to the control animals.
- Necropsy of survivors performed: Yes
All rats that survive the observation period and all rats that died during the observation period will be subject to autopsy.
No further information on the study design was stated.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No signs of intoxication was observed.

Gross pathology:

no data

Other findings:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

According to the results of the study, zinc stearate has an LD50 (male and female rats) > 5000 mg/kg bw.
According to the Regulation (EC) No. 1272/2008 and its subsequent amendments, the test item is not classified as acute toxic via the oral route.

This conclusion is in accordance with the EU RAR.
Conclusions of EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN. Institute for Health and Consumer Protection. ECB - Existing Substances. Final Report, 2004: "Zinc distearate does not need to be classified on the basis of its acute toxicity according to the EC criteria."

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was peer-reviewed and rated reliable within the framework of the EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN. Institute for Health and Consumer Protection. ECB - Existing Substances. Final Report, 2004. In accordance with Section 1 (0.5), Annex I of Regulation (EC) No 1907/2006 (REACH), this study was considered reliable with restrictions.

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

A single 1-hr exposure of rats to 200 mg/l zinc stearate. The rats were observed for two weeks.

GLP compliance:

no

Test type:

other: not stated

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Albino rats were used.
No further information on the test animals was stated.

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

Rats were exposed to zinc stearate for one hour.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

200 mg/l zinc stearate (Chamber concentration)

No. of animals per sex per dose:

10 rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Examinations performed: moratlity was reported.
No further information on the study design was stated.

Statistics:

not stated

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 200 other: mg/l

Based on:

test mat.

Exp. duration:

1 h

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 50 other: mg/l

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: This LC50 was recalculated from the LC50 (1 hr) by using Haber's law.

Mortality:

1/10 rats died during the 2-week observation period.

Clinical signs:

other: All animals appeared depressed for the first six hours. From 24 hrs. until day 14, they appeared normal.

Body weight:

not stated

Gross pathology:

not stated

Other findings:

not stated

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 (4 h) > 50 mg/l (recalculated from LC50 (1h) by using Haber's law)
According to the Regulation (EC) No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.

This conclusion is in accordance with the conclusion of the EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN. Institute for Health and Consumer Protection. ECB - Existing Substances. Final Report, 2004:
"Zinc distearate does not need to be classified on the basis of its acute toxicity according to the EC criteria."

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

50 000 mg/m³ air

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was peer-reviewed and rated reliable within the framework of the EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN. Institute for Health and Consumer Protection. ECB - Existing Substances. Final Report, 2004". In accordance with Section 1 (0.5), Annex I of Regulation (EC) No 1907/2006 (REACH), this study was considered reliable with restrictions.

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

10 % zinc stearate in eyeshadow form was applied dermally to rabbits.

GLP compliance:

not specified

Test type:

other: in vivo

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Rabbits were used.
No further information on the test animals was stated.

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 % zinc stearate in eyeshadow form was applied dermally to rabbits.
No further information on dermal exposure was stated.

Duration of exposure:

Not stated

Doses:

Not stated

No. of animals per sex per dose:

10 rabbits

Control animals:

not specified

Details on study design:

No information on the study design was stated.

Statistics:

Not stated.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality was reported.

Clinical signs:

other: Not stated

Gross pathology:

Not stated

Other findings:

Not stated

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for 10 % zinc stearate in eye shadow form (formulation) is > 2000 mg/kg bw for rabbits.
According to the Regulation (EC) No 1272/2008 and subsequent regulations, the test item is not classified.

This conclusion is in accordance with the EU RAR.
Conclusions of EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN. Institute for Health and Consumer Protection. ECB - Existing Substances. Final Report, 2004: "Zinc distearate does not need to be classified on the basis of its acute toxicity according to the EC criteria."

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity is addressed with substance-specific information and data on structurally similar substances (zinc salts of shorter-chained (C8, C12) and similar chained (C18) fatty acids) as well as supporting information from the assessment entities zinc and fatty acids, C16-18.

Fatty acids, C16-18, zinc salts

A key study for acute oral toxicity with Fatty acids, C16-18, zinc salts is available (OECD 401) indicating a LD50 > 5000 mg/kg bw.

 

A key study for acute inhalation toxicity with Fatty acids, C16.18, zinc salts is available indicating a LC50 > 50 mg/L.

 

A key study for acute dermal toxicity with Fatty acids, C16-18, zinc salts is available indicating a LD50 > 2000 mg/kg bw.

 

Further, following the HERAG guidance for metals and metal salts (see section 7.1.2 of the technical dossier: dermal absorption), negligible percutaneous uptake based on minimal penetration, i.e. a dermal absorption rate in the range of maximally 0.1 - 1.0 %, can be anticipated. Dermal absorption in this order of magnitude is not considered to be "significant".

In conclusion, the substance is not to be classified according to regulation (EC) 1272/2008 and its subsequent amendments for acute oral, inhalation and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

This conclusion is in line with the EU risk assessment carried out on 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."

Additionally, information from structurally similar zinc salts of fatty acids, as well as for the moieties liberated upon dissolution, zinc and fatty acids, C16-18, were taken into account in order to substantiate the conclusion above. Signs of acute oral, inhalation and dermal toxicity are also not expected for Fatty acids, C16-18, zinc salts based on data on structurally similar zinc salts of fatty acids and data on the moieties zinc and fatty acids C16-18, since the moiety zinc has not shown signs of acute oral and inhalation toxicity in experimental testing and the acute dermal toxicity for the moiety zinc can be considered low in view of the poor absorption by this route. For the moiety fatty acids, C16-18 there were no toxicological findings reported in peer-reviewed publicly available assessment reports, neither by the oral nor by the dermal route. Fatty acids as C16-18 obtained from natural sources 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)). And acute toxicity values determined for structurally similar fatty acid zinc salts are above the cut values triggering a classification.

Structuarally similar fatty acids, zinc salts

Acute oral toxicity

Fatty acids, C16-18, zinc salts is a zinc salt of a fatty acid containing 16 -18 C atoms. Thus, data for the substance under consideration as well as read-across of data available for zinc salts of shorter-chained (C8,12) and similar chained (C18) 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, C16-18, zinc salts.

Regarding acute oral toxicity, read-across data from different reliable studies conducted with (i) Zinc 12-hydroxystearate; and (ii) octanoic acid, zinc salt, basic is available. The LD50 for these structurally related fatty acid zinc salts is greater than 2000 mg/kg bw.

  

Acute inhalation toxicity

Regarding acute inhalative toxicity, a reliable study conducted with the structurally similar substance zinc dilaurate is available. Based on the lack of an acute inhalative toxicity potential of this shorter-chained (C12) fatty acid zinc salt, for which a LC50 of greater than 5.08 mg/L (actual concentration) was determined, the lack of acute inhalative toxicity considered for Fatty acids, C16-18, zinc salts is supported.

 

Moieties liberated upon dissolution, zinc and fatty acids, C16 -18

Please refer to the respective assessment entity section for data on the moieties zinc and fatty acids C16 -18. In brief:

Zinc

 

Acute oral toxicity

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

Acute inhalation toxicity

- Key study carried out according to OECD guideline no 403 indicating for micro zinc oxide LC50 > 5.7 mg/L/4hrs.

Metal fume fever is not relevant for Fatty acids, C16-18, zinc salts. The LC50 for Fatty acids, C16-18, zinc salts is greater than 50 mg/L and is thus magnitudes higher than the value reported for metal fume fever. A similar conclusion can be drawn for the structural analogue zinc dilaurate for which a LC50 of greater than 5.08 mg/L (actual concentration) was determined.

Acute dermal toxicity

- There are no available data on which to evaluate acute dermal toxicity for ZnO micromaterial. However, acute dermal toxicity can be considered to be low taking into account the poor percutaneous absorption of zinc oxide or the zinc cation.

Fatty acids, C16-18

 

Acute oral toxicity

Fatty acids, C16 -18 is a mixture of palmitic (C16) and stearic (C18) acid. Palmitic and stearic acid are naturally produced by a wide range of plants and organisms. They are naturally present in butter, cheese, milk and meat. Thus, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

According to a very recent ECHA report, non-branched aliphatic fatty acids (C5-C24) “are expected to be of low toxicity by their nature (similar to high purity fatty acids of natural origin which do not need to be registered as included in Annex V to REACH). […] From a human health perspective, substances in this group are considered to have a low systemic toxicity profile with no specific target organ toxicity or CMR properties. Some have irritant and/or corrosive properties that are reflected in the classification and labelling. Risk from these properties can be avoided by implementing risk management measures in supply chains based on the correct classification and labelling products. Therefore, there is no need for further action on the substances belonging to the group of aliphatic fatty acids non-branched (C5-C24)” (ECHA, 2020: Integrated Regulatory Strategy Annual Report May 2020).

 

Further, 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 (HERA 2002 and references therein; Clayton & Clayton, 1982; CIR, 1987). The available data for the fatty acid salts also indicate that these are of low acute toxicity. For example, an acute oral LD50value of >5,000 mg/kg (highest dose tested) has been reported for sodium soap. This test was done according to GLP and OECD Guideline 401 (HERA 2002 and references therein), while in another study also done to GLP and according to Directive 84/449/EEC, B.1, an LD50value of >2,000 mg/kg (highest dose tested) was reported for fatty acids, C16-18 and C18-unstad., sodium salts” (HERA, 2002 and references therein).

Based on in vivo data it was reported that “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).

“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 NDA Panel, 2017).

“Any toxic effects, such as excessive salivation, diarrhoea, central nervous system depression, loss of reflex actions or coma, shown at higher doses, decrease in severity with an increase in the chain length of the fatty acid (Pi-Sunyer et al., 1969). These reported effects are a result of the high doses administered and the fact that unlike humans rats don’t have a vomiting reflex. Therefore, these high dose effects are not considered relevant for human exposure” (HERA, 2002 and references therein).

  

Acute dermal toxicity

Fatty acids, C16 -18 is a mixture of palmitic (C16) and stearic (C18) acid. Palmitic and stearic acid are naturally produced by a wide range of plants and organisms. They are naturally present in butter, cheese, milk and meat. Thus, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

The HERA document on fatty acids salts concluded that “the available acute dermal toxicity data for the fatty acids (and their salts) provide a clear picture of low acute toxicity for this group of chemicals. All dermal LD50values were greater than >2,000 mg/kg (BIBRA, 1996; HERA 2002 and references therein; Clayton & Clayton, 1982; CIR, 1982, 1987).

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 and references therein).

Additionally, fatty acids as C16-18 obtained from natural sources 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)).

Justification for classification or non-classification

The oral and dermal LD50 for Fatty acids, C16-18, zinc salts is > 2000mg/kg and the inhalation LD50 is > 50 mg/L, hence the substance is not to be classified according to regulation (EC) 1272/2008 and its subsequent amendments for acute oral, inhalation and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).