Lead Carbonate Intermediate

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Trilead bis(carbonate) dihydroxide

EC Number:

215-290-6

EC Name:

Trilead bis(carbonate) dihydroxide

Cas Number:

1319-46-6

Molecular formula:

C2H2O8Pb3

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): Basic Lead Carbonate
- Physical state: white powder
- Analytical purity: Technical grade (min. 99%)
- Impurities (identity and concentrations): traces of lead acetate (<0.3%) and stearic acid- Composition of test material, percentage of components: Lead Content: approx. 79.5%
- Stability under test conditions: stable at room temperature- Storage condition of test material: at room temperature

Test animals

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:

Administration / exposure

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:

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.