Octanoic acid, zinc salt, basic

Endpoint summary

Description of key information

Acute oral toxicity (OECD 423; GLP): LD50 > 2000mg/kg

 

No acute dermal or inhalation toxicity studies with Octanoic acid, zinc salt, basic are available, thus the acute dermal and inhalation toxicity will be addressed with existing data on the dissociation products zinc and octanoic acid and with existing data on structurally similar zinc salts of fatty acids.

Signs of acute dermal toxicity are not expected for Octanoic acid, zinc salt, basic, since the acute dermal toxicity for the moiety zinc can be considered low in view of the poor absorption by this route and the moiety zinc has not shown signs of acute dermal toxicity in experimental testing and in peer-reviewed publicly available assessment reports there were no toxicological findings reported for the moiety octanoic acid.

 

A study for acute toxicity via inhalation was not conducted with Octanoic acid, zinc salt, basic, since it is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance.

 

The calculated oral and dermal LD50 for Octanoic acid, zinc salt, basic is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral 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

Study period:

2012-01-13 to 2012-02-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 2001-12-17

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 2008-05-30

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2009-11-12

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Source: Charles River Laboratories, Research Models and Services, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 167 - 182 g
- Fasting period before study: feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Housing: during the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages.
- Diet (ad libitum): commercial diet, ssniff R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS:
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Air changes: 12 to 18- fold air change per hour
- - Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 0.8% aqueous hydroxypropylmethylcellulose

Details on oral exposure:

VEHICLE
- Methocel; batch no. 11 A 27-N27, Fagron GmbH & Co., 22885 Barsbüttel, Germany

MAXIMUM DOSE VOLUME APPLIED: the administration volume was 10 mL/kg bw.

DOSAGE PREPARATION: the test substance was diluted to the appropriate concentration in the vehicle.

Doses:

2000 mg/ kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed befroe and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days.
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on deaths were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes
At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. Autopsy and macroscopic inspection of animals which died prematurely would have been carried out as soon as possible after exitus.
Histopathology was not carried out as no macroscopical findings were noted at autopsy.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: mortality: 0/6, no signs of toxicity

Mortality:

No death was recorded within the test period.

Clinical signs:

other: Under the present test conditions, a single oral administration of 2000 mg octanoic acid, zinc salt, basic/kg bw to female rats did not reveal any signs of toxicity.

Gross pathology:

No pathological changes were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (female rats) > 2000 mg/kg b.w.
According to the EC-Regulation 1272/2008, the test item is not classified as acute toxic via the oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

adequate relevant and reliable GLP guideline study RL1

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Octanoic acid, zinc salt, basic

Octanoic acid, zinc salt, basic is a zinc salt of a short-chained fatty acid containing 8 C-atoms. Thus, read-across of data available for zinc salts of shorter-chained (C12) and longer-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 Octanoic acid, zinc salt, basic (C8).

 

Acute oral toxicity

Acute toxicity is addressed with substance-specific information (OECD 423, LD50 > 2000 mg/kg) and supporting data on structurally similar zinc salts of fatty acids (zinc salts of shorter-chained (C12) and longer-chained (C16 -18) fatty acids), including (i) zinc dilaurate, (ii) zinc bis[12 -hydroxy-octadecanoate, and (iii) Fatty acids, C16-18, zinc salts, as well as existing informationon the moiety zinc.

  

Acute inhalation toxicity

According to the data requirements as laid down in regulation (EC) 1907/2006, Annex VIII, Section 8.5.2, “testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.”

According to the testing requirements as laid down in regulation (EC) 1272/2008, Article 8 (6) “Tests that are carried out for the purposes of this Regulation shall be carried out on the substance or on the mixture in the form(s) or physical state(s) in which the substance or mixture is placed on the market and in which it can reasonably be expected to be used. ”

The substance is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are no likely to occur during manufacture and handling of that substance. The pure substance is exclusively formulated in solution for which no uses are described in which droplets in an inhalable size are generated (e. g. spray applications). Furthermore, there is no reason of concern for toxicity with respect to acute inhalation, because high exposure levels which are not covered by the long-term DNEL are not expected. Testing for acute toxicity by inhalation is therefore not applicable.   Additionally, the material was subjected to a test to determine the potential of the dust to be airborne (modified Heubach procedure (DIN 55992-1:2006)), yielding an MMAD of 32.58 µm with a GSD of 1.52. On the basis of results of this dustiness test (modified Heubach method), MPPD modelling was performed and shows that the substance does not penetrate to the deep lung tissues (tracheobronchial: <0.05%; pulmonary: <0.05%), whereas the inhaled material (Head: 40%) is cleared to the GI tract (by swallowing), where oral bioavailability will determine its uptake.   Furthermore, different reliable, relevant and adequate studies conducted with different zinc compounds are read-across as supporting information, including (i) zinc oxide; (ii) Fatty acids, C16-C18, zinc salts; and (iii) zinc dilaurate. It is assumed that after intake Octanoic acid, zinc salt, basic is changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities. The toxic potential of the fatty acid chain, i.e. octanoate, is assumed to be negligible. 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)). Available inhalation toxicity data of structural analogues indicate a lack of a toxic potential via the inhalation route. Based on the assumption that zinc compounds with similar water solubility characteristics can be read across, it can be concluded that other slightly soluble and insoluble zinc compounds are also not expected to be acutely toxic via the inhalation route. This conclusion is applied to Octanoic acid, zinc salt, basic. In conclusion, testing for acute toxicity of Octanoic acid, zinc salt, basic via the inhalation route is not required according the criteria laid down in Regulation (EC) 1907/2006 Annex VIII, 8.5, column 2.   

 

Acute dermal toxicity

Signs of acute dermal toxicity are not expected for Octanoic acid, zinc salt, basic, since the acute dermal toxicity for the moiety zinc can be considered low in view of the poor absorption by this route and the moiety zinc has not shown signs of acute dermal toxicity in experimental testing and in peer-reviewed publicly available assessment reports there were no toxicological findings reported for the moiety octanoic acid.

Furthermore, the LD50 of Fatty acids, C16-18, zinc salts has been estimated to be greater than 2000 mg/kg bw. Based on the assumption that zinc compounds with similar solubility characteristics can be read-across, it is concluded that other slightly soluble and insoluble zinc compounds are also expected to be not acutely toxic.

Further testing is not required.

The calculated oral and dermal LD50 for Octanoic acid, zinc salt, basic is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral 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 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 Octanoic acid, zinc salt, basic.

 

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

Zinc

Acute oral toxicity

With LD50values consistently exceeding 2,000 mg/kg bw, zinc oxide (LD50ranges 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

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.

Octanoic acid

Acute oral toxicity

Octanoic acid is a naturally occurring saturated C8- fatty acid, which is present in milk of various mammals and also in coconut oil and palm kernel oil. 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 LD50values 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).

Based on in vivo data it was reported that “in an OECD TG 401 study, a group of five rats/sex was administered octanoic acid at a dose of 2000 mg/kg bw. There were no deaths, clinical signs, or findings at gross necropsy. The LD50was > 2000 mg/kg bw”(OECD SIDS, 2014).

“Smyth et al. (1962) studied the acute oral toxicity of undiluted caprylic- or capric acid (mixed isomers tested) in groups of five non-fasted male Carworth–Wistar rats. Based upon mortalities during the 14-day observation period, the authors reported median lethal dose (LD50) values of 1,300 mg/kg bw for caprylic acid and 3,300 mg/kg bw for capric acid (no further details available). Jenner et al. (1964) administered, by gavage, increasing doses of octanoic acid to groups of five male and five female fasted Osborn–Mendel rats (dose range 8,190–12,370 mg/kg bw). The treated rats showed depression and diarrhoea during the 2-week observation period. The rats died between 4 h and 9 days after application. The authors calculated a LD50of 10,080 mg/kg bw for male and female rats (no further details given)” (EFSA ANS Panel, 2017).

The EFSA ANS Panel concluded that octanoic acid has a low acute oral toxicity.

Acute dermal toxicity

The substance subjected to registration is a naturally occurring saturated C8- fatty acid, which is present in milk of various mammals and also in coconut oil and palm kernel oil. Based on this, 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; IUCLID, 2000e; Clayton & Clayton, 1982; CIR, 1982, 1987).

In a series of studies performed by the British Industrial Biological Research Association (BIBRA, UK), the acute dermal toxicity of octanoic acid was evaluated in rats. In these studies, octanoic acid was found to have a very low acute dermal toxicity in rats. The established LD50 was higher than 5,000 mg/kg bw (BIBRA, 1996).

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).

Justification for classification or non-classification

The calculated oral and dermal LD50 for Octanoic acid, zinc salt, basic is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).