Copper, .beta.-resorcylate salicylate lead complexes

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 May 2010 - 30 June 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant to GLP and testing guideline; adequate coherence between data, comments and conclusions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Copper Lead Resorcylate Salicylate Complex

EC Number:

614-455-3

Cas Number:

68411-07-4

Molecular formula:

C7H5O4-, C7H5O3- Cu , Pb

IUPAC Name:

Copper Lead Resorcylate Salicylate Complex

Details on test material:

- Name of test material (as cited in study report): Lead-Cooper-Resorcylate-Salicylate (LC 12-15)
- Substance type: multicontituent
- Physical state: slightly pale green powder
- Composition of test material, percentage of components: copper: 11.9%, lead: 35.7%, resorcylate: 14.1%, salicylate: 35.7%
- Lot/batch No.: 09/201
- Expiration date of the lot/batch: 04 November 2011
- Storage conditions of test material: at room temperature.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder: Janvier, Saint-Genest-Saint-Isle, France
- Age at study initiation: on the day of treatment, the animals were approximately 8 weeks old
- Weight at study initiation: mean body weight ± standard deviation of 207 ± 12 g
- Fasting period before study: approximately 18 hours
- Housing: cages with stainless steel lid (43 cm x 22 cm x 20 cm)
- Diet (e.g. ad libitum): free access to SSNIFF R/M-H pelleted diet
- Water (e.g. ad libitum): free access to bottles containing tap water (filtered with a 0.22 µm filter)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): 12 cycles/hour
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 02 June 2010 To: 30 June 2010.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: standard vehicle used for specific routes of administration

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Taking into account information on the test item, the starting dose-level of 300 mg/kg was chosen.

Doses:

300 and 2000 mg/kg.

No. of animals per sex per dose:

3 females per group and per dose.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: a period of up to 14 days
- Frequency of observations and weighing: Each animal was observed after dosing at least once during the first 30 minutes, periodically during
the first 24 hours for detection of possible treatment-related clinical signs and then at least once a day for 14 day.
The body weight of each animal was recorded just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of all animals performed: yes.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled mortality were observed during the study.

Clinical signs:

other: No clinical signs were observed during the study.

Gross pathology:

Macroscopic post-mortem examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 of the test item, Lead Copper Resorcylate-Salicylate (LC 12-15), was higher than 2000 mg/kg in rats.
According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labeling of dangerous substances, concerning the potential toxicity by oral route, the test item, Lead-Copper-Resorcylate-Salicylate (LC 12-15), should not be classified.

Executive summary:

The objective of this study was to evaluate the toxicity of the test item, Lead‑Copper‑Resorcylate‑Salicylate (LC 12-15), following a single oral administration in rats according to OECD (No. 423, 17th December 2001) and Commission Regulation (EC) (No. 440/2008, B.1tris, 30 May 2008)guidelines.

The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

 

Methods

The test item, Lead-Copper-Resorcylate-Salicylate (LC 12-15), was administered by oral route (gavage) to groups of three fasted female Sprague-Dawley rats at dose-levels of 300 and 2000 mg/kg under a dosage-volume of 10 mL/kg. The test item was prepared in 0.5% methylcellulose.

 

The study design was as follows:

 

Dose-level (mg/kg)	Volume (mL/kg)	Female
300	10	3
2000	10	3
2000	10	3

 

Each animal was observed at least once a day for mortality and clinical signs for a period of up to 14 days following the single administration. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed then subjected to a macroscopic post-mortem examination.

 

The interpretation of results was based on the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations).

 

Results

No unscheduled mortality and noclinical signs were observed during the study.

When compared to CIT historical control data, a lower body weight gain was noted between day 8 and day 15 in 1/3 females treated at the dose-level of 300 mg/kg (vs.15 ± in control data base) and between day 1 and day 8 in 4/6 females treated at the dose-level of 2000 mg/kg (24 to 31 g vs.41 ± 9 g in control data base). The body weight gain returned to normal thereafter.

At necropsy, no apparent abnormalities were observed in any animal.

Conclusion

Under the experimental conditions of this study, the oral LD₅₀ of the test item, Lead‑Copper‑Resorcylate-Salicylate (LC 12-15), was higher than 2000 mg/kg in rats.

According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), concerning the potential toxicity by oral route, the test item should not be classified.