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Description of key information

A substance specific key study for acute oral toxicity with naphthenic acids, zinc salts, basic is available indicating no signs of acute oral toxicity with a LD50 for female rats greater than 2000 mg/kg bw. In a supporting study for acute oral toxicity, naphthenic acids, zinc salts did not show signs of acute toxicity as well, with a LD50 for male and female rats greater than 5000 mg/kg bw.

A key study for acute inhalation toxicity with naphthenic acids, zinc salts is available, indicating a LC50 greater than 420 mg/m3 (analytical concentration; test was conducted at the maximum attainable concentration).

A key study for acute dermal toxicity with naphthenic acids, zinc salts is available indicating an LD50 greater than 2000 mg/kg bw.

Overall, Naphthenic acids, zinc salts, basic is not expected to show acute toxic effects via oral, inhalation and dermal route.

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:
experimental group: 14-08-2006 to 30-08-2006; control group: 26-07-2006 to 09-08-2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001-12-17
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
dated 2005-12-13
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle - France)
- Age at study initiation: treatment group: 9 weeks old; control group: approx. 8 to 12 weeks old
- Weight at study initiation: treatment group: 225 - 242 g; control group: 205 - 225
- Fasting period before study: animals are deprived of food but not water overnight prior to treatment, starting on the previous day. Food was distributed again 4 hours after the product is administered.
- Housing: three animals are kept in each Makrolon cage, dimensions 47 cm x 31 cm x 19 cm, and the bottom is lined with dust-free wood shavings.
- Diet (ad libitum)
- Water (ad libitum): public water supply
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: between 20 and 21°C
- Relative humidity: between 43% and 64%
- Air renewal: at least 10 cycles per hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: the test item VP 112/18 was diluted in dimethyl sulfoxyde and administered by force-feeding using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 female rats
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: systematic examinations are carried out to identify any behavioural or toxic effects on the major physiological functions 30 minutes, 1 hour, 3 hours, 4 hours, 24 hours and 48 hours after administration of the product and continued on the following day. Observations and mortality check are carried out every day during 14 days.
The animals are weighed on day D0 (just before administering the product) then on D2, D7, and D14. Weight changes should be calculated and recorded.
- Necropsy of survivors performed: yes
Necropsies are carried out on animals which died during the test. Macroscopic observations are entered on individual autopsy sheets
On D14, the animals are anaesthetised with sodium pentobarbital and administration continued to fatal levels.
Only those organs likely to be modified in cases of acute toxicity are examined.
Statistics:
not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off value: 2500 mg/kg bw
Mortality:
It was noted the death of 1 treated rat, 48 hours following the test item administration, due to a gavage injury. No mortality attributable to the test item administration was noted.

Clinical signs:
No clinical signs related to the administration of the test item were observed.

Body weight:
The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.
Gross pathology:
The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
LD50 (female rats) > 2000 mg/kg bw (LD50 cut-off value (female rats): 2500 mg/kg bw)
According to the EC-Regulation 1272/2008 and its subsequent amendments, the test item is not classified as acute toxic via the oral route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980-09-24 to 1980-10-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981-05-12
Deviations:
yes
Remarks:
information on strain of rats, equilibration period, and on time period of observations were missing; rats were not weighed weekly
Principles of method if other than guideline:
It has to be mentioned that no OECD guideline was available at the time of conduct.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS - albino rats
- Housing: the animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3.
- Weight at study initiation: average initial body weight: 210 g (males) and 205 g (females)
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: mineral spirits and clean air
Details on inhalation exposure:
PREPARATION OF TEST MATERIAL
The material was used as a 50% w/v suspension in mineral spirits

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the animals were exposed to the test material inside a 260 liter plexiglass exposure chamber.

- System of generating particulates/aerosols: the material was administered as an aerosol which was generated by a six jet Collision nebulizer (BGI Incorporated, Waltham, Mass.). The air was passed through a desicant prior to being passed through the test material. The rate of flow through the chamber was 20 liters per minute (except during particle size measurement) at a temperature of 72°F (22.2°C).

- Method of particle size determination: particle size of the aerosol was determined using an Andersen Sampler cascade impactor. The Andersen Sampler was run for 5 minutes midway through the exposure. During sampling, air from the breathing zone of the animals was drawn through the cascade impactor at the rate of 1 cubic foot per minute (28.3 liters per minute).
The amount of aerosol impacting on each plate of the Andersen Sampler was determined by differential weighing. From these values the mass median diameter of the aerosol was calculated to be 0.54u and the concentration was calculated to be 0.42 mg/liter.

TEST ATMOSPHERE
The average concentration of the aerosol over the four hour exposure period was calculated to be 11.6 mg/liter by differential weighing of the flask from which the aerosol was generated.

Analytical verification of test atmosphere concentrations:
yes
Remarks:
please refer to "details on inhalation exposure" above
Duration of exposure:
4 h
Concentrations:
Actual concentration: 0.42 mg/liter (maximum concentration which could be attained)
Nominal concentration: 11.6 mg/liter
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Examinations performed: Signs of toxicity and mortalities (daily) were noted. The average initial body weight and the average final body weight were determined.
Statistics:
not stated
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 420 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: the maximum concentration which could be attained
Mortality:
No mortality occurred during the study.
Clinical signs:
other: No untoward symptoms were observed during the four hour exposure period. Within 18 - 24 hours the animals appeared depressed and ruffled. They were essentially normal after 48 hours.
Body weight:
The average body weight of the rats increased during the study.
Gross pathology:
Gross pathological examination revealed nothing remarkable.
Interpretation of results:
not classified
Conclusions:
LC50 (male and female rats, 4h) > 0.42 mg/liter (analytical); test was conducted at the maximum attainable concentration.
According to the EC-Regulation 1272/2008 and its subsequent Amendments, the test item is not classified as acute toxic via the inhalation route.
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:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because they hydrolyse to common products.

This prediction is supported by toxicological data on the substances themselves and on the dissolution products of the substances.
Target and source substances are mono-constituent substances. Both substances differ only in the production process, resulting in (i) an neutral product and (ii) a basic product.

The target substance is the basic product containing a slightly higher zinc content. The dissolution product, namely the zinc cation, is not the driver for toxic effects.
Consequently, the target substance is identical to the source substance and share a structural similarity with common functional groups, carboxylic acid, alkyl side chains.

Therefore, read-across from the existing acute inhalation toxicity study on the source substance is considered as an appropriate adaption to the standard information requirements of Annex VII and VIII, 8.5 and 8.5.2 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

The justification of the proposed read-across approach is elaborated in the next chapters. Please find this information in the attachements as well.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
a) Target substance
The target substance naphthenic acids, zinc salts, basic is a mono-constituent substance (EC: 282-762-6, CAS: 84418-50-8).
b) Source substance
The source substance naphthenic acids, zinc salts is a mono-constituent substance (EC: 234-409-2, CAS: 12001-85-3).
c) Purity and impurities
The source substance is derived from the same educts in the production process. Consequently, the hazard profile of the target substance is intrinsically covered.


3. ANALOGUE APPROACH JUSTIFICATION
a) Structural similarity and functional groups
The structure of the target and source substances are the same, namely a naphthenic acids, zinc salt. The target substance is the basic product containing a slightly higher zinc content compared to the neutral product. The dissolution product, namely the zinc cation, is not the driver for toxic effects with regard to Human Health and especially to local effects.

b) Common breakdown products
The common characteristic of the target substance and the source substance is that both liberate the same moiety upon dissolution in aqueous media. Zinc cations and naphthenate anions are formed upon dissolution under toxicological relevant conditions such as body fluids and in the environment.


4. DATA MATRIX
A comparison of the experimental toxicological data between the source and target substance is not applicable in the applied approach, since the overall ecotoxicity/systemic toxicity of the target substance is assessed by taking the (eco-)toxicological profile of the zinc cation and the acid anion (naphthenic acid) into account. An endpoint-specific description is provided in the respective endpoint summaries of both assessment entities.
The structural similarities between the source and the target substances and the similarities in their breakdown products presented above support the read-across hypothesis. Adequate, reliable and available scientific information indicates that the source and target substances and their subsequent degradation product have similar toxicity profiles.

Based on the considerations above, it can be concluded that the results of the acute inhalation toxicity study conducted with the source substance is likely to predict the properties of the target substance and are considered as adequate to fulfil the information requirements of Annex VII and VIII, 8.5 and 8.5.2
Since the source substance is not classified for acute inhalation toxicity, the target substance naphthenic acids, zinc salts, basic will not be classified as well. Thus, the information requirements of Annex VII and VIII, 8.5 and 8.5.2. are fulfilled by the source and target substance.
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981-05-12
Deviations:
yes
Remarks:
information on strain of rats, equilibration period, and on time period of observations were missing; rats were not weighed weekly
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 420 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: the maximum concentration which could be attained
Mortality:
No mortality occurred during the study.
Clinical signs:
other: No untoward symptoms were observed during the four hour exposure period. Within 18 - 24 hours the animals appeared depressed and ruffled. They were essentially normal after 48 hours.
Body weight:
The average body weight of the rats increased during the study.
Gross pathology:
Gross pathological examination revealed nothing remarkable.
Interpretation of results:
not classified
Conclusions:
LC50 (male and female rats, 4h) > 0.42 mg/liter (analytical); test was conducted at the maximum attainable concentration.
According to the EC-Regulation 1272/2008 and its subsequent Amendments, the test item is not classified as acute toxic via the inhalation route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
420 mg/m³

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980-09-11 to 1980-09-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 1981-05-12
Deviations:
yes
Remarks:
substance was tested on abraded skin; removal of substance was not described; area covered by test substance was not exactly stated; body weight was not determined weekly; information on strain of rabbit was missing
Principles of method if other than guideline:
It has to be mentioned that no OECD guideline was available at the time of conduct.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS - albino rabbits
- Weight at study initiation: between 2.0 and 3.0 kg; average initial weight: 2.33 kg (males) and 2.27 kg (females)
- Housing: the animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure and type of wrap used: all animals had their backs clipped free of hair 24 hours prior to testing. All of the animals had their backs abraded prior to dosing.
All rabbits were weighed and the correct amount of experimental material was applied to the back of each animal. These treated areas were covered with large gauze patches and an impervious material was wrapped snugly around the trunk of each animal.

REMOVAL OF TEST SUBSTANCE
- Washing: the dressing was removed after the exposure period and any excess material was removed and the approximate amount remaining was noted.
- Time after start of exposure: 24 hours after application of the test material


Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for a 14 day period for signs of toxicity and for mortalities.
- Necropsy of survivors performed: yes
Gross autopsies were performed on all animals which died during the 14 day observation period and also on all survivors of the 14 day observation period.
Statistics:
not stated
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
Except for very substantial skin irritation lasting throughout the course of the observation period, no other untoward symptoms were observed.
Body weight:
The average body weight of the rabbits increased during the study.
Gross pathology:
Gross pathologic examination revealed nothing remarkable.
Interpretation of results:
not classified
Conclusions:
LD50 (male and female rabbits; abraded skin) > 2000 mg/kg
According to the EC-Regulation 1272/2008 and its subsequent amendments, the test item is not classified as acute toxic via the dermal route.
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because they hydrolyse to common products.

This prediction is supported by toxicological data on the substances themselves and on the dissolution products of the substances.
Target and source substances are mono-constituent substances. Both substances differ only in the production process, resulting in (i) an neutral product and (ii) a basic product.

The target substance is the basic product containing a slightly higher zinc content. The dissolution product, namely the zinc cation, is not the driver for toxic effects.
Consequently, the target substance is identical to the source substance and share a structural similarity with common functional groups, carboxylic acid, alkyl side chains.

Therefore, read-across from the existing acute dermal toxicity study on the source substance is considered as an appropriate adaption to the standard information requirements of Annex VII and VIII, 8.5 and 8.5.3 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

The justification of the proposed read-across approach is elaborated in the next chapters. Please find this information in the attachements as well.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
a) Target substance
The target substance naphthenic acids, zinc salts, basic is a mono-constituent substance (EC: 282-762-6, CAS: 84418-50-8).
b) Source substance
The source substance naphthenic acids, zinc salts is a mono-constituent substance (EC: 234-409-2, CAS: 12001-85-3).
c) Purity and impurities
The source substance is derived from the same educts in the production process. Consequently, the hazard profile of the target substance is intrinsically covered.


3. ANALOGUE APPROACH JUSTIFICATION
a) Structural similarity and functional groups
The structure of the target and source substances are the same, namely a naphthenic acids, zinc salt. The target substance is the basic product containing a slightly higher zinc content compared to the neutral product. The dissolution product, namely the zinc cation, is not the driver for toxic effects with regard to Human Health and especially to local effects.

b) Common breakdown products
The common characteristic of the target substance and the source substance is that both liberate the same moiety upon dissolution in aqueous media. Zinc cations and naphthenate anions are formed upon dissolution under toxicological relevant conditions such as body fluids and in the environment.


4. DATA MATRIX
A comparison of the experimental toxicological data between the source and target substance is not applicable in the applied approach, since the overall ecotoxicity/systemic toxicity of the target substance is assessed by taking the (eco-)toxicological profile of the zinc cation and the acid anion (naphthenic acid) into account. An endpoint-specific description is provided in the respective endpoint summaries of both assessment entities.
The structural similarities between the source and the target substances and the similarities in their breakdown products presented above support the read-across hypothesis. Adequate, reliable and available scientific information indicates that the source and target substances and their subsequent degradation product have similar toxicity profiles.

Based on the considerations above, it can be concluded that the results of the acute dermal toxicity study conducted with the source substance is likely to predict the properties of the target substance and are considered as adequate to fulfil the information requirements of Annex VII and VIII, 8.5 and 8.5.3
Since the source substance is not classified for acute dermal toxicity, the target substance naphthenic acids, zinc salts, basic will not be classified as well. Thus, the information requirements of Annex VII and VIII, 8.5 and 8.5.3. are fulfilled by the source and target substance.
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 1981-05-12
Deviations:
yes
Remarks:
substance was tested on abraded skin; removal of substance was not described; area covered by test substance was not exactly stated; body weight was not determined weekly; information on strain of rabbit was missing
Statistics:
not stated
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
Except for very substantial skin irritation lasting throughout the course of the observation period, no other untoward symptoms were observed.
Body weight:
The average body weight of the rabbits increased during the study.
Gross pathology:
Gross pathologic examination revealed nothing remarkable.
Interpretation of results:
not classified
Conclusions:
LD50 (male and female rabbits; abraded skin) > 2000 mg/kg
According to the EC-Regulation 1272/2008 and its subsequent amendments, the test item is not classified as acute toxic via the dermal route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

One key study by Richeux (2006; OECD 423 (2001); GLP compliant) and one supporting study by Anonymous (1980; OECD 401 (1981); GLP compliant), conducted with naphthenic acids, zinc salts, basic and naphthenic acids, zinc salts, respectively, are used to address this endpoint. No signs of acute oral toxicity could be observed in any of the studies. The LD50 was determined to be greater than 2000 mg/kg bw for naphthenic acids, zinc salts, basic (female rats) and greater than 5000 mg/kg bw for naphthenic acids, zinc salts (male and female rats).

Acute inhalation toxicity

One reliable study by Anonymous (1980; OECD 403 (1981); GLP compliant), conducted with naphthenic acids, zinc salts, is used to address this endpoint. No signs of acute toxicity could be observed. The LC50 was determined to be greater the 420 mg/m3 (analytical; maximum attainable concentration).

Unlimited read-across from naphthenic acids, zinc salts to naphthenic acids, zinc salts, basic is justified, since the overbased naphthenic acids, zinc salts, basic only contains a surplus of zinc, which is, however, known not to be the driver for toxic effects with regard to Human Health.

Acute dermal toxicity

One reliable study by Anonymous (1980; OECD 402 (1981); GLP compliant), conducted with naphthenic acids, zinc salts, is used to address this endpoint. No signs of acute dermal toxicity could be observed. The LD50 was determined to be greater than 2000 mg/kg bw.

Unlimited read-across from naphthenic acids, zinc salts to naphthenic acids, zinc salts, basic is justified, since the overbased naphthenic acids, zinc salts, basic only contains a surplus of zinc, which is, however, known not to be the driver for toxic effects with regard to Human Health.

Justification for classification or non-classification

The oral and dermal LD50 for naphthenic acids, zinc salts and naphthenic acids, zinc salts, basic is greater than 2000 mg/kg bw. In addition, the LC50 for naphthenic acids, zinc salts in an acute inhalation toxicity study is greater than 420 mg/m3 air (analytical).

Thus, naphthenic acids, zinc salts, basic 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 organ toxicity, single exposure (STOT SE).