Lead Carbonate Intermediate

Endpoint summary

Description of key information

The main component of the substance “Reaction product of lead chloride or lead sulphate with alkaline solution” is lead (Pb). Pb salts used as source material are waste materials produced by Pb battery recycling process or by-products of the hydrometallurgical upgrading of PGM rich lead bullion. This transported isolated intermediate produced under strictly controlled condition by existing RMMs. It is an inorganic solid UVCB-substance having ~85% of particles smaller than 400 µm. The major and the most hazardous constituent of this intermediate is lead (conc. >50 %) which is determined to be poorly water soluble (section 4.8, EU method A.6).

Studies presented for acute oral toxicity are from available animal testing data from Pb compounds, which were used for read-across purposes. Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects. See IUCLID Section 13 for Analogue approach report.

The classification is based on the composition of “Reaction product of lead chloride or lead suphate with alkaline solution” (see section 4.23), and assessed by using C&L rules for mixtures. All constituents in this intermediate having classification entries in CLP Annex VI were considered.  As a worst-case assumption all relevant compounds are considered leachable i.e. bioavailable.  The 100% distribution means that e.g. when 50 % Pb is present that all of it (100%) is allocated to the form of 'Pb compounds' and not a certain amount as e.g. PbCO3, which could result in a different classification.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sept. 1991-Feb. 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Hypothesis for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects. Rationale for key study selection: the substance “Reaction product of lead chloride or lead sulphate with alkaline solution” consist mainly of Lead carbonate, which has been studied in this robust study summary. Well-documented and corresponded to the requirements of the recommended Annex V test guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Forschungsinstitut fur Versuchstierzucht, A-2325 Himberg
- Age at study initiation: approx. 8 weeks at time of administration
- Weight at study initiation: See Table
- Fasting period before study: Feed was withdrawn the evening before application and was offered again about three hours after application.
- Housing: Single gaging in Makrolon cages type III (39 cm x 23 cm x 15 cm). Wire mesh lids. Bedding material: for laboratory animals, type 4 HV (Finn Tapvei Ky, SF-73600 Kaavi), gamma irradiated with 10 kGy 60Co.
- Diet (e.g. ad libitum): Altromin 1314 ff, gamma irradiated with 10 kGy 60Co, ad libitum. Random samples of the feed are analysed for contaminants by Altromin, D-4937
- Water (e.g. ad libitum): tap water,offered in Makrolon bottles with stainless steel canules, ad libitum.
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22 degrees centigrade
- Humidity (%): average of 70%
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): artificial light from 6AM to 6 PM


IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:


MAXIMUM DOSE VOLUME APPLIED: 10 ml per kg body weight


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

"NAFTOVIN T2" was administered once perorally to 5 male and 5 female Him:OFA rats. The test substance, suspended in Arachis oil, was applied once at a dose of 2000 mg per kg body weight by stomach intubation.

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Behavior, reactions and physical signs of the animals were observed 10, 30 min, 1, 2, 4 and 6 hours after administration (p.a.) and then at least once a day for a total of 2 weeks. Body weight was determined before administration, 7 days p.a. and 14 days p.a.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived until the end of the study.

Clinical signs:

All animals were normal during the whole study. No toxic signs were noted.

Body weight:

Body weight gain of the animals was inconspicuous.

Gross pathology:

9/10 animals were normal at post mortem examination. In one male, white foci on the surface of the liver, large mesenterial lymph nodes and a large caecum were noted.

Other findings:

No sex differences between males and females were noted in the response to the test substance.

Synopsis of Results:

sex	dose (mg/kg)	number of dead/affected/exposed animals
male	2000	0/0/5
female	2000	0/0/5

Post mortem Findings:

System organ, finding	sex	No. of affected animal
Normal	m	11, 12, 13,14
	f	16,17,18,19,20
Alimentary System
Liver, White foci, >5, 1 mm diameter	m	15
Caecum, large	m	15
Haematopoietic System	m	15
Lymph nodes, mesenterial, large	m	15

Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects.

See IUCLID Section 13 for Analogue approach report.

Interpretation of results:

GHS criteria not met

Conclusions:

The observations in life revealed no toxic signs. 9/10 animals were normal at post mortem examination. Alterations of the 10th rat are not attributed to the action of the test substance, as similar changes are known to occur spontaneously with a low incidence in untreated rats of the strain used, and due to the single occurence in this study.

No differences between the sexes were noted in the response to the test substance.

All animals survived until termination.

Therefore, LD50 (oral) for both male and female rats is higher than 2000 mg "NAFTOVIN T2" per kg body weight.

Executive summary:

It was the aim of this study to reveal acute toxic effects of "NAFTOVIN T2" after a single oral administration. The study was conducted considering OECD Guideline 401 (Limit-Test).

"NAFTOVIN T2" was administered once perorally to 5 male amd female Him:OFA rats. The test substance, suspended in Arachis oil, was applied once at a dose of 2000 mg per kg body weight by stomach intubation.

Results:

Mortality: All animals survived until 14 days p.a.

Observations in life: All animals were normal during the whole study. No toxic signs were observed.

Body Weight: Body weight gain was inconspicuous in all animals.

Post mortem findings: 9/10 animals were normal at terminal necropsy. Different alterations, observed in one male, are not regarded as test substance related.

Sex differences: No differences between the sexes were observed in the response to the test substance.

Due to the results obtained in this study LD50 (oral) of "NAFTOVIN T2" is beyond 2000 mg per kg body weight in both female and male rats. No toxic effects of the test substance were noted.

Reference 2

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:

Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects.
See IUCLID Section 13 for Analogue approach report.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other:

Remarks:

This conclusion is based on the results of the in vivo study performed wtih CAS 1319-46-6

Interpretation of results:

GHS criteria not met

Additional information

The substance “Reaction product of lead chloride or lead sulphate with alkaline solution” consists mainly of lead and therefore read-across is based on properties of lead.

Although lead can exert toxic effects upon multiple organ systems and body functions, this toxicity manifests under conditions of sub-chronic to chronic exposure that can range from months to years in duration. Acute toxicity is not observed in animals after oral exposures up to the limit values of acute toxicity testing. For oral exposures, data demonstrating lack of toxicity are available for doses of 2000 mg/kg/bw or higher.

Similarly, toxicity in humans after true acute exposures is limited and, when documented, is generally under conditions that yield sub-chronic or chronic exposures (section 7.10, supportive information). This finding is not unexpected given the pharmacokinetics of lead uptake into the body. Lead uptake is generally quite low and heavily reliant upon easily saturable active transport mechanisms. Once saturation of these uptake mechanisms has occurred, uptake proceeds by inefficient passive diffusion. The uptake of lead is thus highly non-linear as a function of dose with uptake efficiency declining with the amount of lead administered to a test animal or an exposed human. Although toxic under chronic exposure situations, the acute toxicity of lead and inorganic lead compounds appears to be quite low via all exposure routes.

However self-classification of this UVCB-substance requires information on the constituents and their classification entries. Calculated classification was performed from all constituents in this intermediate having classification entries in CLP Annex VI (using mixture toxicity rules) with MeClas-tool. For acute toxicity lead compounds were the major drivers. Composition and mineralogy of the material (see IUCLID section 4.23) were taken into account.

Justification for classification or non-classification

The derived classification result for the UVC substance “Reaction product of lead chloride or lead sulphate with alkaline solution”

is when calculated with MeClas-tool following C&L mixture rules:

CLP:

Acute toxicity, oral: Cat 4; H302 (ATE: 300 -2000 mg/kg bw)

Acute toxicity, dermal: not classified

Acute toxicity, inhalation: Cat 4; H332 (ATE: 2000 -25000 mg/kg bw)