Fatty acids, tallow, zinc salts

Endpoint summary

Description of key information

Hazard assessment is conducted by means of read-across from structural analogues.

The slightly soluble and insoluble zinc compounds (i.e., zinc oxide, zinc hydroxide, zinc phosphate, zinc carbonate, zinc metal, zinc sulphide as well as Fatty acids, C16-18, zinc salts ) are of low acute, dermal and inhalation toxicity not requiring a classification for acute toxicity according to the EC criteria.

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 from supporting substance (structural analogue or surrogate)

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:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the results of the study, zinc stearate has an LD50 (male and female rats) > 5000 mg/kg bw.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the oral route.
According to the Regulation (EC) No. 1272/2008 and subsequent regulations, 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

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on chemical structure and common physiological active moieties (refer to endpoint discussion for further details).
The selected study is thus 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 from supporting substance (structural analogue or surrogate)

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:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LC50 (4 h) > 50 mg/l (recalculated from LC50 (1h) by using Haber's law)
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.
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

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on chemical structure and common physiological active moieties (refer to endpoint discussion for further details). The selected study is thus 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 from supporting substance (structural analogue or surrogate)

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:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 for 10 % zinc stearate in eye shadow form (formulation) is > 2000 mg/kg bw for rabbits.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified.
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

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on chemical structure and common physiological active moieties (refer to endpoint discussion for further details).
The selected study is thus 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

No studies are available on acute toxicity of fatty acids, tallow, zinc salts. In accordance to Regulation (EC) No 1907/2006 Annex XI, 1.5, a read across to the structural analogue fatty acids, C16-18, zinc salts (CAS No. 91051-01-3) was conducted. Based on similar structure, physico-chemical properties (i.e. water solubility) and zinc content, the toxicological profile of the two substances is expected to be comparable. Further justification is given within the CSR chapter 5 and the read-across justification. The data available for fatty acids, C16-18, zinc salts and the supporting data available for inorganic zinc salts are discussed below.

Fatty acids, zinc salts

Oral

Acute oral toxicity was tested in a limit test performed according to OECD Guideline 401 (Biffi, 1990). Groups of 5 male and 5 female Wistar rats received a single oral application of 5000 mg/kg bw fatty acids, C16-18, zinc salts. Since no clinical signs and no mortality was observed within the 14 day observation period, the LD50 was found to be >5000 mg/kg bw. Another acute oral toxicity study with zinc bis[12-hydroxyoctadecanoate] revealed an LD50 value > 2000 mg/kg bw in rats (Buecher, 2002).

 

Inhalation

Acute inhalation toxicity was evaluated in a study where 10 albino rats were exposed to 200 mg/L fatty acids, C16-18, zinc salts to the whole body for 1 h (Penick, 1977). While all animals appeared depressed for the first six hours, they appeared normal from 24 h until the end of the 14 day observation period. Although one animal died during the observation period, an LC50 value of 200 mg/L could be determined after 1 h exposure, which corresponds to an LC50 value of 50 mg/L after 4 h exposure (calculated according to Haber’s Law). This LC50 value for fatty acids, C16-18, zinc salts being 50 mg/L is about 3 magnitudes higher than the value reported for metal fume fever. However, metal fume fever is not relevant for fatty acids, C16-18, zinc salts.

 

Additionally three studies with dogs and rats examined the effect of fatty acids, C16-18, zinc salts after intratracheal application (Heiman and Aschner, 1922; Ueda et al., 1984; Harding, 1958). Moreover, intratracheal administration of zinc caprylate to rats was performed. However, due to the application route the studies can be regarded as not relevant for assessment.

 

Dermal

A LD50 of >2000 mg/kg bw was found in a study with 10 rabbits, which received dermal application of 10% fatty acids, C16-18, zinc salts in an eyeshadow formulation (CTFA, 1976).

 

Inorganic zinc salts

Oral

With LD50 values consistently exceeding 2000 mg/kg bw, slightly soluble or insoluble zinc compounds such as zinc oxide (LD50 ranges between 5000 and 15000mg/kg bw), zinc phosphate (LD50 >5000mg/kg bw), zinc metal (LD50 >2000mg/kg bw) or zinc sulphide (LD50 >15000mg/kg bw), show a low level of acute oral toxicity (Loeser, 1972 and 1977; Klein and Glaser, 1989; Prinsen, 1996; Sachtleben Chemie GmbH, 2000).

 

Inhalation

In an acute inhalation toxicity limit test similar to OECD 403, 10 animals per sex were exposed to zinc oxide aerosol (head and nose only) for 4 h (Klimisch et al., 1982). Aerosol concentration was 5.7 mg/L and the particle size distribution had a mass median aerodynamic diameter of 4mm ± 2.9 (GSD). All animals survived up to 14 days post exposure. Apart from a dusty fur on the head the day after the exposure, no effects were noted. Body weights developed normally and no abnormalities were observed at pathological examination. Thus, the LC50 was considered to be > 5.7 mg/L.

Zinc metal was further shown to be of low acute inhalation toxicity (i.e. LC50 values of > 5.41 mg/L/4h) (Arts, 1996). Given the common characteristics shared via their solubility characteristics, the remaining slightly soluble zinc compounds are also considered to be of low acute inhalation toxicity.

Of significance for humans from an acute toxicity standpoint is the occurrence of metal fume fever following exposure to ultrafine particles of special grades of zinc oxide in context of very specific operations. According to the response from 11 zinc companies to a questionnaire, there have been no observations of zinc metal fume fever over the last decade and in recent occupational practice. However in light of responsible care and since no studies are available that allow the establishment of a NOAEC for metal fume fever with a reasonable degree of certainty, a LOAEC (5 mg ZnO/m³) for 2 hours (showed the typical metal fume fever symptoms beginning 4 to 8 hours after exposure and disappearing within 24 hours) can be used for metal fume fever based on the study by Gordon et al. (1992).

Dermal

In an acute dermal toxicity study according to OECD guideline 402 zinc sulphate heptahydrate was administered to the skin of five Wistar rats of each sex at 2000 mg/kg bw for 24 hours, followed by an 15-day observation period (van Huygevoort, 1999). The LD50 was determined to be > 2000 mg/kg bw.

 

In conclusion, applying read-across, fatty acids, tallow, zinc salts does not need to be classified on the basis of its acute toxicity.

This conclusion is in line with the conclusion for the structural analogue (i.e. Fatty acids, C16 -18, zinc salts) from EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN: "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 fatty acids, tallow, zinc salts.

 

 

References:

Arts, MHE (1996). Acute (4-hour) inhalation toxicity study with Zinc powder in rats. EU risk assessment zinc metal, 2004. Testing laboratory: TNO, Zeist, The Netherlands. Report no.: TNO-report V96.734.

Klein and Glaser (1989). EU risk assessment report for zinc phosphate 2004.

Prinsen MK (1996). Acute oral toxicity study (limit study) with zinc powder in rats. EU Risk Assessment Zinc metal 2004. Testing laboratory: TNO, Zeist, The Netherlands. Report no.: TNO-report V96.515.

Sachtleben Chemie GmbH (2000). Acute oral toxicity in rat.IUCLID 2000 ECB.

Van Huygevoort AHBM (1999c). Assessment of Acute Dermal Toxicity with Zinc Sulphate Heptahydrate in the Rat. Project 254385. NOTOX B V., ‘s-Hertogenbosch, The Netherlands.

Justification for selection of acute toxicity – oral endpoint

Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint

Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint

Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to endpoint discussion for further details).

Justification for classification or non-classification

The slightly soluble and insoluble zinc compounds (i.e., zinc oxide, zinc hydroxide, zinc phosphate, zinc carbonate, zinc metal, zinc sulphide as well as fatty acids, C16-18, zinc salts) are of low acute, dermal and inhalation toxicity.

Based on read-across from the structurally similar substances, the available data on oral, inhalation and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.